Omega-3 Essential Fatty Acids

Essential Fatty Acids (EFAs) are necessary fats that humans cannot synthesize and therefore must obtain from dietary sources. Essential Fatty Acids are necessary for the cardiovascular, reproductive, immune, and nervous systems and to manufacture and repair cell membranes. The best known dietary sources of omega-3 EFA's are fish and flax and their oils.

+General Information

+What are Essential Fatty Acids

What are Essential Fatty Acids?

Essential Fatty Acids (EFAs) are necessary fats that humans cannot synthesize and therefore must obtain from dietary sources. EFAs are long-chain polyunsaturated fatty acids derived from linolenic, linoleic, and oleic acids. There are two families of EFAs: omega-3 and omega-6. Omega-9 is necessary yet "non-essential" because the body can manufacture a modest amount on its own, provided essential EFAs are present. The number following "omega-" represents the position of the first double bond, counting from the terminal methyl group on the molecule. Omega-3 fatty acids are derived from Linolenic Acid, omega-6 from Linoleic Acid, and omega-9 from Oleic Acid.

The parent fatty acid of the omega-6 series is linoleic acid (LA) and the parent fatty acid of the omega-3 series is alpha-linolenic acid (ALA). Humans can synthesize long-chain (20 carbons or more) omega-6 fatty acids, such as dihomo-gamma-linolenic acid (DGLA) and arachidonic acid (AA) from LA and long-chain omega-3 fatty acids, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) from ALA.

Metabolism and Bioavailability

Prior to absorption in the small intestine, fatty acids must be hydrolyzed from dietary fats (triglycerides, phospholipids and cholesterol) by pancreatic enzymes. Bile salts must also be present in the small intestine to allow for the incorporation of fatty acids and other fat digestion products into mixed micelles. Fat absorption from mixed micelles occurs throughout the small intestine, and is 85-95% efficient under normal conditions.

Humans can synthesize longer omega-6 and omega-3 fatty acids from the essential fatty acids LA and ALA, respectively, through a series of desaturation (addition of a double bond) and elongation (addition of two carbon atoms) reactions. LA and ALA compete for the same elongase and desaturase enzymes in the synthesis of longer polyunsaturated fatty acids, such as AA and EPA. Although ALA is the preferred substrate of the delta-6 desaturase enzyme, the excess of dietary LA compared to ALA results in greater net formation of AA than EPA.

The capacity for conversion of ALA to DHA is higher in women than men. Studies of ALA metabolism indicate that approximately 8% of dietary ALA is converted to EPA and 0-4% is converted to DHA in healthy young men. In healthy young women, approximately 21% of dietary ALA is converted to EPA and 9% is converted to DHA. The better conversion efficiency of young women compared to men appears to be related to the effects of estrogen. Although ALA is considered the essential omega-3 fatty acid because it cannot be synthesized by humans, evidence that human conversion of EPA and, particularly, DHA is relatively inefficient suggests that EPA and DHA may also be essential under some conditions.

+Role of Essential Fatty Acids

What Do Essential Fatty Acids Do?

Essential Fatty Acids support the cardiovascular, reproductive, immune, and nervous systems. The human body needs EFAs to manufacture and repair cell membranes, enabling the cells to obtain optimum nutrition and expel harmful waste products. A primary function of EFAs is the production of prostaglandins, which regulate body functions such as heart rate, blood pressure, blood clotting, fertility, conception, and play a role in immune function by regulating inflammation and encouraging the body to fight infection. Essential Fatty Acids are also needed for proper growth in children, particularly for neural development and maturation of sensory systems, with male children having higher needs than females. Fetuses and breast-fed infants also require an adequate supply of EFAs through the mother's dietary intake.

+Omega-3 Essential Fatty Acids

Omega-3 Essential Fatty Acids

In omega-3 fatty acids, the first double bond is located on the third carbon from the methyl end of the hydrocarbon chain. For omega-6 fatty acids, the first double bond is located at the sixth carbon.

The short chain omega-3 fatty acid is alpha-linolenic acid (ALA 18:3n-3). The longer chain of omega-3 fatty acids are commonly known as Eicosapentaenoic acid (EPA, 20:5n-3), Docosapentaenoic acid (DPA, 22:5n-3) and Docosahexaenoic acid (DHA 22:6n-3). In recent medical research, all of these components have been proven to be vitally important in human health, growth and development. Generally speaking, their functions in our body include:

Cellular Membrane Components. The outer membrane of the human cell acts as a gateway allowing raw materials in and the processed material out. This outer membrane requires a constant turnover of PUFAs to remain functional. Omega-3 fatty acids are an essential part of this replenishment. A shortage of omega-3 reduces the ability of cells to efficiently perform their function, leading to nutrient starvation and chronic illnesses. Production of Eicosanoids. Omega-3 is also converted into another class of chemical called Eicosanoids, the most critical of which are prostaglandins. Prostaglandins are important for the regulation of inflammation, pain, swelling, blood pressure, heart function, gastrointestinal function and secretions, kidney function and fluid balance, blood clotting and platelet aggression, allergic response, and nerve transmission, steroid production and hormone synthesis. If the diet is inadequate in omega-3, the prostaglandins produced are either lacking or unbalanced, leading to dysfunction of these vital activities. Each of the omega-3 fatty acids is important in its own way. As many have pointed out, most of the research has been done using fish oil, which contains only two of the three omega-3 fatty acids. In his book, Dr. Donald Rudin finds this disappointing, as he has had better results with flaxseed oil in his own studies. This may be because flaxseed oil starts with the plant form of linolenic acid, ALA, whereas fish oil contains the animal form, DHA. The body can make its own DHA and EPA from ALA. Although some claim that the amount of DHA made is small, the body doesn't need much DHA. Most DHA is contained in cell membranes, and is held there with little replacement. In contrast, ALA and compounds made from it are also needed in the body for a number of essential functions. ALA is not found in fish oil and therefore the consumer does not get the full complement of omega-3 fatty acids by just supplementing with fish oil.

ALA

ALA or Alpha-linolenic acid is the short chain omega-3 fatty acid found in plant sources. According to Dr. Frank Sacks, Professor of Cardiovascular Disease Prevention, Department of Nutrition, Harvard School of Public Health

…the body partially converts ALA to EPA and DHA; it is not known if ALA has substantial health benefits as is, or whether it must be converted to EPA and DHA to produce most of the benefits. My current interpretation of the science is that ALA has direct health benefits, through its role in reducing inflammation and protecting the heart against arrhythmias, and it also has indirect health benefits, through its conversion to EPA and DHA.

DHA

DHA or Docosahexaenoic acid, which comes from marine sources, has been identified as an essential building block of the brain, nerve and eye tissue. It is especially important to the development of visual acuity and motor skills in infants. DHA is supplied naturally through breast milk and more recently through DHA supplemented formula.

EPA

EPA or Ecosapentenoic acid, found most commonly in fish and marine oils, reduces inflammation and blood clots within the cardiovascular system. In addition, clinical tests have shown people with diets rich in EPA are less prone to inflamed joints (Rheumatoid Arthritis), Inflammation of the intestines (Crohn’s Disease) Lupus , Asthma, Multiple Sclerosis and Skin Disease.

DPA

DPA or Docosapentaenoic acid, which is only found in significant amounts in seal oil and breast milk, is almost as important as either the EPA or DHA. About one third of the long chain omega-3 fatty acids circulation in human blood is attributed to DPA as the effective agent. It seems that in the blood vessel walls, EPA may actually be converted to DPA as the effective agent.

Man Cannot Live on Supplementation Alone

Research indicates that omega-3 fatty acids may be better absorbed from food than supplements. Norwegian researchers compared 71 volunteers' absorption of omega-3 fatty acids (EPA and DHA) from salmon, smoked salmon, cod (14 ounces of fish per week) or cod liver oil (3 teaspoons per day). Cooked salmon provided 1.2 grams of omega-3 fatty acids daily, while cod liver oil provided more than twice as much: 3 grams of omega-3 fatty acids per day.

Despite the fact that the salmon group got less than half the amount of omega-3 fatty acids as the cod liver oil group, blood levels of omega-3 fatty acids increased quite a bit more in those eating salmon than those taking cod liver oil. After 8 weeks, EPA levels had risen 129% and DHA rose 45% in those eating cooked salmon compared to 106% and 25%, respectively, in those taking cod liver oil.

In the group eating smoked salmon, blood levels of omega-3 fatty acids rose about one-third less than in the salmon group. In those eating cod, the rise in omega-3 fatty acids was very small.

Concurrent with the rise in omega-3 fatty acids in those eating salmon, a drop was seen in blood levels of a number of pro-inflammatory chemicals (TNFalpha, IL-8, leukotriene B4, and thromboxane B2). Researchers think omega-3 fatty acids may be better absorbed from fish because fish contains these fats in the form of triglycerides, while the omega-3 fatty acids in almost all refined fish oils are in the ethyl ester form. Once absorbed, omega-3 fatty acids are converted by the body from their triglyceride to ester forms as needed. (Lipids. 2006 Dec;41(12):1109-14).

Once again, the research is done using fish oil as the source for omega-3 fatty acids. There is evidence that ALA omega-3 fatty acid is also vital for important body functions. Consequently, one could extrapolate from the above research that natural food sources (such as flax and walnuts) of ALA will be more effective than ALA supplementation.

+Omega-3 Chemistry

Omega-3 Chemistry: A Brief Overview

Omega-3 fatty acids are long-chain polyunsaturated fatty acids (18-22 carbon atoms in chain length) with the first of double bonds beginning with the third carbon atom. They are called “polyunsaturated” because their molecules have two or more of the so-called “double bonds” between carbon atoms. Their designation as “long-chain” fatty acids has to do with the fact that they consist of at least 18 carbon atoms.

The picture below illustrates the molecular structure of alpha-linolenic acid (ALA, omega-3 family) as compared to linoleic acid (LA, omega-6 family). Both consist of 18 carbon atoms and are classified as polyunsaturated, but ALA has three double bonds, the first of which is located in the third position from the “end” of the molecule, whereas LA has just two double bonds, starting with the sixth position. These differences may seem very minor, but they are of paramount importance in terms of the physiological action of ALA and LA, making them perform totally different roles in the human body.

The omega-3 family of fatty acids includes alpha-linolenic acid (ALA, 18 carbon atoms, 3 double bonds), eicosapentaenoic acid (EPA, 20 carbon atoms, 5 double bonds), and docosahexaenoic acid (DHA, 22 carbon atoms, 6 double bonds). ALA is a "base" omega-3 fatty acid, which must be converted to EPA and DHA in the body through a series of enzymatic reactions called "elongation" (the molecule becomes longer by incorporating new carbon atoms) and "desaturation" (new double bonds are created). In nature, ALA is primarily found in certain plant seeds (e.g., flax, hemp, camelina) and their oils, and in most green leafy vegetables (especially purslane), whereas EPA and DHA mostly occur in the tissues of cold-water fish (such as salmon, sardines, and mackerel) and in some (mostly marine) plants.

Omega-3 fatty acids are not just “good fats.” They are truly essential for health and vitality. After the advent of the so-called “lipid hypothesis,” which linked the consumption of dietary fat with increased risk of heart disease and other health problems, fats were so heavily demonized by the official medical establishment that many people started thinking that the best answer to the "fat problem" is to stay away from it altogether. Big food processing companies were quick to realize the enormous profit potential of this trend, and soon the market became flooded with "low fat" and "fat-free" products, promising to put an end to obesity and heart disease.

However, not all fats are created equal. While the consumption of some types of fat may indeed be a risk factor for certain health problems (synthetic trans-fats, so dearly loved by the food-processing industry, rather than natural fats, seem to be the primary culprit here), some other fats, including alpha-liniolenic acid (ALA) from the omega-3 family, are so important for health that they have been termed "essential fatty acids" (EFAs). The essential nature of these fatty acids stems from the fact that our bodies need them to perform vital functions, but are unable to manufacture them. Therefore, we must get them from outside sources (such as food or dietary supplements). That is why any attempt to indiscriminately reduce or eliminate all fats from the diet inevitably leads to an EFA deficit, which may be very detrimental to health.

Essential fatty acids were first discovered back in 1929 by a husband-and-wife research team, George and Mildred Burr. While doing animal research, they have noticed that a lack of essential fatty acids caused the animals to develop some serious health problems, including scaling and swelling of the skin, as well as damage to internal organs. If the EFA deficit was left unattended, the animals eventually died.

In 1956, Hugh Sinclair, one of the world's greatest researchers in the field of human nutrition, suggested that an upsurge in the so-called "diseases of civilization" - namely, coronary heart disease, thrombosis, strokes, diabetes, chronic inflammation, and cancer - was caused by abnormalities in fat metabolism. According to his writings, the main reason for such abnormalities was the fact that modern-day diets are full of processed foods rich in trans-fatty acids, while being extremely poor in essential fatty acids. According to Hugh Sinclair, this EFA deficit was the main reason behind his striking observation: in spite of improvements in medicine and standard of living, the life expectancy of a 50-year-old man had not changed since the middle of the 19th century.

Although Sinclair's opinions were not supported by his peers at the time, and he was even ridiculed by some of them for his bold hypothesis, later research has convincingly shown that he was, indeed, correct. In fact, he is now universally recognized and praised for insights that were far ahead of his time.

Some information courtesy of www.goldofpleasure.com

+It's All About the Balance

It’s all About the Balance: Omega-6 to Omega-3

Degenerative diseases that involve fats prematurely kill over two thirds of the people currently living in affluent, industrialized nations. Three conditions involving fatty degeneration cause 68% of the deaths: cardiovascular disease (43.8%), cancer (22.4%) and diabetes (1.8%). These deaths are the result of eating habits based on ignorance and misconceptions. Since we are natural biological organisms, we must attain, maintain and regain good health through natural approaches – through foods and lifestyles in keeping with the biological needs that nature genetically built into us. If we get the right kind of fats in the right amounts and balances, and prepare them using the right methods, they build our health and keep us healthy.

Historical balance

Throughout human history mankind has ingested an approximate equal proportion (1:1 ratio) of omega-6 to omega-3 fatty acids. Omega-6 and omega-3 are two of the 49 known essential nutrients. As essential nutrients, they cannot be synthesized by the body, but must be ingested directly in foods or in the form of dietary supplements. The relationship of equivalence between these two omega fatty acids is critical because they self-check each other in a delicate balance to regulate thousands of metabolic functions through prostaglandin pathways. Nearly every biologic function is somehow interconnected with the delicate balance between omega-6 and omega-3. Omega-3 fatty acids are intimately involved in the control of inflammation, cardiovascular health, myelin sheath development, allergic reactivity, immune response, hormone modulation, IQ, and behavior. A seemingly minor, yet major change in the balance between omega-6 and omega-3, dictated by dietary ingestion, has absolute deleterious health effects. The rapid change in dietary fat ingestion within only the last 50-100 years has bewildered human biophysiology, which was created to function optimally on equal proportions of dietary omega fatty acids.

Good fat, bad fat

Diets that provide omega-6 oils at the expense of omega-3 stimulate pro-inflammatory pathways in the body. On the other hand, omega-3 fatty acids stimulate anti-inflammatory pathways. As a result, omega-6 has been coined as “bad” and omega-3 as “good”. In fact both are essential for human health and it is the balance of the two in relation to each other that is important. Dominant omega-6 in the body can create a situation that promotes chronic inflammation, propagation of cancer, heart disease, stroke, diabetes, arthritis, and autoimmune disorders. The body’s inflammatory response is intimately regulated by omega-3 fatty acids. The inflammatory response was created to respond to acute injury or microbial attack. However, if the inflammatory response is needlessly provoked, damage to tissue and organs of the body occurs. The reduction of omega-3 in the diet of the industrialized nations has created a situation of chronic inflammation. In this case, the symptom of inflammation precedes the disease. However, as inflammation leads to disease, a vicious, continuous circle of inflammation and disease is formed.

How important is the balance between omega-3 and omega-6?

A deficiency of omega-3 fatty acids has been positively correlated with over 50 diseases and illnesses including cancer, heart disease, diabetes, stroke, and arthritis. The so-called western degenerative diseases have risen in a near perfect linear fashion with the elimination of omega-3 and the over-provision of omega-6 in the food chain. In many regards, saturated fats may have been ruled guilty by association because the genesis of cardiovascular disease now appears to be more closely related to a rise in vegetable oil ingestion than it does to saturated fat. Perhaps it should come as no surprise that supplemental ingestion of omega-3 greatly improves all of the 50 known omega-3 deficiency conditions.

What happened?

In modern society, cereals — mainly wheat, corn and rice — predominate, leading to a relative deficiency of omega-3 fats compared with omega-6 fats. This imbalance is worsened by the consumption of meat from intensively raised, grain-fed animals. Grains are rich in omega-6 fats, thus the meat from grain-fed animals is also high in omega-6. Animals fed on grass and wild plants with a high omega-3 fat content have meat that is either higher in omega-3 fatty acids or in better balance with omega-6. Farmed fish are also fed on grain and therefore, contain lower amounts of omega-3 than those living wild.

With the onset of the industrial revolution, saturated fatty acids in the diet rose dramatically with the increased availability of red meat, dairy products and hydrogenation of polyunsaturated fats, largely from margarine. According to Professor Artemis Simpoulos in his article, Omega-3 Fatty Acids and Antioxidants in Edible Wild Plants,

“the current Western diet is very high in omega-6 fatty acids (the ratio of omega-6 to omega-3 fatty acids is 10-20:1) because of the indiscriminate recommendation to substitute omega-6 fatty acids for saturated fats to lower serum cholesterol concentrations.” Evidence

Simopoulos (in Prostaglandins Leukotrienes & Ess. Fatty Acids, 1999; 60: 421-9) argues that Paleolithic people consumed a higher intake of omega-3 fats due to their diet of green plants, fruits, nuts, berries, fish and lean meat and a lower intake of omega-6 because of their low intake of cereals and refined oils. Some communities probably also had a high intake of monounsaturated fat from simply pressing the oil out of certain fruits such as olives. People living on the island of Crete in the 1960s at the time of a 7 country study and who ate a traditional Mediterranean diet are believed to have consumed diets high in omega-3 and low in omega-6 fats, similar to that of Paleolithic people.

Since human genes have changed little, if at all, in the past 10,000 or indeed 40,000 years, then it follows that most people today now eat foods for which they are not genetically programmed. The result, Simopoulos (1999) suggests, is chronic disease (diabetes, cancer, obesity, cardiovascular disease). He also believes the omega-6 to omega-3 imbalance also explains why, although CHD deaths have dropped due to better treatment and secondary prevention, a reduction in recognized risk factors has failed to have an impact on the incidence of myocardial infarction.

In a landmark study, Japanese researchers have discovered the leading cause of westernized degenerative diseases in Japan, if not in the world. Their work has gone far to confirm the landslide of emerging scientific research which is beginning to reveal that the genesis of degenerative diseases is owed to a drastic reduction in the ingestion of omega-3 in relation to increased ingestion of omega-6. Their findings came after an exhaustive review of over 500 peer-reviewed studies and after accounting for all known and suspected causes for degenerative illnesses. Perhaps having the most impact are the words of the Japanese researchers themselves from the study summary:

"We summarize the evidence that increased dietary linoleic acid (omega-6) and relative omega-3 deficiencies are major risk factors for western type cancers, cardiovascular and cerebrovascular diseases and also for allergic hyper-reactivity. We also raise the possibility that a relative omega-3 deficiency may be affecting the behavioral patterns of a proportion of the young generation in the industrialized countries.

“It is proposed that dietary intervention with omega-3 supplementation and the reduction of omega-6 in the diet could successfully reverse rising trend toward westernized degenerative diseases in Japan, and the world. The dietary transition to a westernized diet in Japan occurring in the last fifty years and the subsequent rise in degenerative disease is merely a microcosm of the transition, which occurred in the United States beginning with the Industrial Revolution.

“A modern dietary shift unprecedented in human history favoring the ingestion of omega-6 at the expense of omega-3 is being owed as a primary, if not the leading, cause of westernized degenerative diseases. In light of this information it is highly advisable to make conscious dietary choices to reduce the amount of extraneous omega-6 in the diet and to ingest omega-3 fatty acids in an effort to return the body to balance.”

Further evidence

The preferred ratio of omega-6 to omega-3 (<5:1) has been based on the ratio that currently exists in our cell membranes and the evidence regarding food habits of Paleolithic people. However, there has been some further evidence from metabolic and epidemiological studies. Chan et al (Lipids 1993; 28:811-7) fed three different ratios of omega-6 linoleic to omega-3 linolenic at 27:1, <7:1 and 3:1 in humans. Platelet enrichment with omega-3 eicosapentaenoic acid (EPA) only occurred on the 3:1 ratio. They also compared two diets, one with double the amount of linolenic, but with the same omega-6 to omega-3 ratio, proving that the ratio not the total quantity is important. In the Lyon Diet Heart Study, the benefits of reducing omega-6 fats and increasing omega-3 fats (ratio 4:1) was shown quite convincingly: after 4 years both heart disease and cancer deaths were halved (De Lorgeril et al. Arch Inter Med 1998; 158: 1181-7).

What now?

Medical advice to eat a low-fat high carbohydrate diet can be misleading. The aim instead should be for a diet that, regardless of its fat content, contains an increased amount of omega-3 fatty acids (a reduced amount of saturated fat) and to prefer carbohydrate containing foods with a low-medium glycaemic index.

More evidence is needed on the ideal omega-6: omega-3 ratio. Nevertheless, in the face of this evidence, it would seem prudent to increase in the intake of foods high in omega-3 fats.

+Essential Fatty Acid Balance and Prostaglandin Production

How Omega-3 Fatty Acids Work: An Introduction to Prostaglandins

It is obvious that an adequate daily intake of omega-3 fatty acids can play a vital role in the prevention and treatment of a great number of serious and widespread diseases affecting modern societies. The ability of omega-3 fatty acids to achieve these health-promoting effects is primarily due to their role as the precursors of prostaglandins – localized tissue hormones that seem to be fundamental in regulating molecules in most forms of life. They do not travel in the blood like hormones, but are created in the cells to serve as catalysts for a large number of processes including the movement of calcium and other substances into and out of cells, dilation and contraction, inhibition and promotion of clotting, regulation of secretions, including digestive juices and hormones, and control of fertility, cell division and growth.

This unique significance of omega-3 fatty acids and prostaglandins for major life-supporting processes in the human body led Dr. Mary Enig, a leading lipid researcher and nutritional scientist of our times, and Sally Fallon, President of Weston A. Price Foundation, to making the following statement:

"Research into prostaglandins holds enormous promise for the treatment of disease with various drugs that selectively inhibit or stimulate the production of specific prostaglandins. Such drugs might be likened to police officers used to direct traffic or called on to help at the scene of an accident. For most of us, however, the best way to ensure adequate prostaglandin production along with proper balance between the various series and their subsets is to follow a diet that provides precursors to eicosanoid production, and keeps the pathways free from blocks and potholes, a diet that provides fuel for our prostaglandin cars and keeps the highways clear." (Tripping Lightly down the Prostaglandin Pathways, Sally Fallon and Mary Enig, PhD, 1996).

In the same article, the authors go on to explain the specific mechanisms behind the formation and major actions of EFA-derived prostaglandins and other eicosanoids (20-carbon hormone-like tissue substances which are similar to prostaglandins):

"Prostaglandins are produced in the cells by the action of enzymes on essential fatty acids. There are two prostaglandin pathways, one that begins with double-unsaturated omega-6 linoleic acid and one that begins with triple-unsaturated omega-3 alpha-linolenic acid. Both pathways essentially involve elongation of the 18-carbon EFA's to the 20-carbon root used in each of the three eicosanoid types, plus further desaturation.

On the omega-6 pathway, the Series 1 prostaglandins are produced from a 20-carbon, triple unsaturated fatty acid called dihomo-y-linolenic acid (DGLA) that is found in liver and other organ meats. The Series 2 prostaglandins are produced from a 20-carbon quadruple unsaturated fatty acid called arachidonic acid (AA) found in butter, animal fats, especially pork, organ meats, eggs and seaweed. On the omega-3 pathway, the Series 3 prostaglandins are produced from a 20-carbon quintuple unsaturated fatty acid called eicosapentaenoic acid (EPA)...."

A fundamental shift in the omega-6: omega-3 ratio created a major prostaglandin imbalance, giving rise to "diseases of modern civilization."

"Early research focused on the interplay between the Series 1 and Series 2 prostaglandins. In the most simple terms, the Series 2 prostaglandins seem to be involved in swelling, inflammation, clotting and dilation, while those of the Series 1 group have the opposite effect. This has led some writers, notably Barry Sears in his popular book The Zone, to call the Series 2 family the "bad" eicosanoids and to warn readers against eating liver and butter, sources of arachidonic acid, the Series 2 precursor. Sears also asserts that perfect balance of the various prostaglandin series can be achieved by following a diet in which protein, carbohydrate and fat are maintained in certain strict proportions. This is a highly simplistic view of the complex interactions on the prostaglandin pathway, one which does not take into account individual requirements for macro and micro nutrients, nor of imbalances that may be caused by nutritional deficiencies, environmental stress or genetic defects. Like all systems in the body, the many eicosanoids work together in an array of loops and feedback mechanisms of infinite complexity....

“The Series 2 prostaglandins do indeed play a role in swelling and inflammation at sites of injury. This is not at all a "bad" effect, but an important protective mechanism - the body's way of immobilizing the affected site to prevent further injury and facilitate healing. Series 2 prostaglandins also seem to play a role in inducing birth, in regulating temperature, in lowering blood pressure, and in the regulation of platelet aggregation and clotting.

“Later investigators have focused on the balance between Series 2 and Series 3 prostaglandins. The Series 2 group is involved in intense actions, often in response to some emergency such as injury or stress; the Series 3 group has a modulating effect. Series 2 eicosanoids might be likened to the "fast lane" in that they are often associated "with an explosive, but transient burst of synthesis. . . if the rate of synthesis is too slow, there will be insufficient active eicosanoids to occupy receptors. If the rate is synthesis is too fast, excess active eicosanoids can cause pathophysiology." The Series 3 prostaglandins are formed at a slower rate and work to attenuate excessive Series 2 production. Their response is "less vigorous." The omega-3 pathway might therefore be likened to the "slow lane." Adequate production of the Series 3 prostaglandins seems to protect against heart attack and stroke as well as certain inflammatory diseases like arthritis, lupus and asthma." (Op. Cit.)

The table below illustrates the opposing effects of different-series prostaglandins on human physiology:

Series 3 Prostaglandins (omega-3)	Series 2 Prostaglandins (omega-6)
Decreased platelet aggregation (blood clotting)	Increased platelet aggregation (blood clotting)
Vasodilation (widening of blood vessels)	Vasoconstriction (narrowing of vessels)
Anti-inflammatory effect	Pro-inflammatory effect
Immune system enhancement	Immune system suppression
Increased oxygen flow	Decreased oxygen flow
Decreased cell proliferation	Increased cell proliferation
Decreased pain	Increased pain
Widening of respiratory passages	Narrowing of respiratory passages
Increased endurance	Lowered endurance

It may seem from this table that the effects of series 3 prostaglandins derived from omega-3 fatty acids (PGE3) are mostly “positive”, making them “good prostaglandins”, whereas series 2 prostaglandins derived from omega-6 fatty acids (PGE2) are “bad prostaglandins”. However, as was explained above, this view is too simplistic. The fact is that both groups of prostaglandins perform vitally important functions and supplement each other through complex and multi-faceted interactions. There is only one crucial condition that must be fulfilled if the entire system is to work well and promote health, rather than disease. This condition is BALANCE. For the prostaglandin pathways to run smoothly, the intake of omega-3 and omega-6 fatty acids must be well-balanced, as was the case during 99% of human history – before the global switch to industrial agriculture and processed foods. For many centuries, the ratio between omega-6 and omega-3 fatty acids was within the 1:1 to 4:1 range believed by most scientists to be acceptable for optimal metabolism of fats and proportionate production of different prostaglandins.

Therefore, for the complex system of essential fat metabolism to function properly, the maximum allowable daily intake of omega-6 fatty acids should be no more than four times greater than the corresponding omega-3 intake. If the intake of omega-6 fats exceeds this maximum allowable level, the body starts producing too many series 2 (omega-6) prostaglandins, and too few series 3 (omega-3) prostaglandins, causing the delicate system of metabolic “checks and balances” to malfunction. Hugh Sinclair was right: the advent of processed foods abundant in “bad fats” (trans-fatty acids and excessive omega-6 linoleic acid) and deficient in “good fats” (omega-3 fatty acids) caused a fundamental abnormality in fat metabolism. The omega-6: omega-3 ratio went completely out of control. In fact, the current average omega-6: omega-3 ratio in the American diet is not 2:1 or even 4:1, but potentially as high as 20 or 30:1.

Thus, the effects of omega-6-derived prostaglandins, which are beneficial under certain circumstances, but can be harmful if the system goes out of balance, begin to overwhelm the body and cause serious health problems. Their thrombogenic (blood-clotting), pro-inflammatory action, when not attenuated by thrombolytic (blood-thinning and anti-clotting), anti-inflammatory properties of omega-3 prostaglandins, leads to the formation of potentially dangerous blood clots and throws the body into the state of chronic inflammation, giving rise to a whole array of clot- and inflammation-related chronic diseases, including thrombosis, arthritis, diabetes, and asthma. The tendency of PGE2 to narrow the blood vessels and promote blood platelet aggregation is conducive to atherosclerosis and coronary heart disease (CHD). In addition, their ability to stimulate cell proliferation may play a role in the development of malignant tumors.

courtesy of www.goldofpleasure.com

+Dietary Intake

Dietary Intake: How Much Omega-3 Do We Need?

The evidence seems to be showing that by adding a certain amount of omega-3 EFAs to the diet it is possible to restore the vitally important prostaglandin balance, avoiding or reversing the negative health consequences of the omega-6 overload. This begs the question:

“What is the recommended daily intake of omega-3 fatty acids?”

Scientists have not yet developed a universal answer with regard to how much omega-3 EFAs are needed daily. Perhaps the most detailed and authoritative recommendations in this regard were made by the participants of the Workshop on the Essentiality of and Recommended Dietary Intakes for Omega-6 and Omega-3 Fatty Acids, held in Bethesda, Maryland, under the auspices of the International Society for the Study of Fatty Acids and Lipids (ISSFAL).

The Workshop participants consisted of investigators of the role of essential fatty acids in nutrition, cardiovascular disease, and mental health. It was truly international in nature bringing together scientists from academia, government, international organizations, and industry from Australia, Canada, Denmark, France, Italy, Japan, Norway, Switzerland, United Kingdom, and the United States.

The Workshop participants came to the following conclusion:

“After much discussion, consensus was reached on the importance of reducing the omega-6 polyunsaturated fatty acids (PUFAs) even as the omega-3 PUFAs are increased in the diet of adults and newborns for optimal brain and cardiovascular health and function. This is necessary to reduce adverse effects of excesses of arachidonic acid (AA) and its eicosanoid products. Such excesses can occur when too much linoleic acid (LA) and AA are present in the diet and an adequate supply of dietary omega-3 fatty acids is not available. The adverse effects of too much AA and its eicosanoids can be avoided by two interdependent dietary changes. First, the amount of plant oils rich in LA, the parent compound of the omega-6 class, which is converted to AA, needs to be reduced. Second, simultaneously the omega-3 PUFAs need to be increased in the diet. LA can be converted to AA and the enzyme, delta-6 desaturase, necessary to desaturate it, is the same one necessary to desaturate alpha-linolenic acid (ALA), the parent compound of the omega-3 class; each competes with the other for this desaturase. The presence of ALA in the diet can inhibit the conversion of the large amounts of LA in the diets of Western industrialized countries which contain too much dietary plant oils rich in omega-6 PUFAs (e.g. corn, safflower, and soybean oils). The increase of ALA, together with EPA and DHA, and reduction of vegetable oils with high LA content, are necessary to achieve a healthier diet in these countries.” (Artemis P. Simopoulos, MD, The Center for Genetics, Nutrition and Health, Washington, DC, U.S.A.; Alexander Leaf, MD, Massachusetts General Hospital, Charlestown, MA, U.S.A.; Norman Salem, Jr. PhD, National Institute of Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, MD, U.S.A. Final Statement by the Participants of the Workshop on the Essentiality of and Recommended Dietary Intakes for Omega-6 and Omega-3 Fatty Acids. Bethesda, MD 1999)

With regard to the recommended dosages of omega-6 and omega-3 fatty acids, the Workshop agreed upon the following guidelines:

Linoleic acid (LA): an adequate intake (AI)* was set at 4.44 grams per day, with an upper limit of 6.67 grams per day (2% and 3% of daily caloric intake, respectively, based on a 2000-calorie diet);
Alpha-linolenic acid (ALA): an adequate intake (AI)* was set at 2.22 grams per day (1% of daily caloric intake), with no upper limit.
*If sufficient scientific evidence is not available to calculate an Estimated Average Requirement, a reference intake called an Adequate Intake (AI) is used instead of a Recommended Dietary Allowance. The AI is a value based on experimentally derived intake levels or approximations of observed mean nutrient intakes by a group (or groups) of healthy people. The AI is expected to meet or exceed the amount needed to maintain a defined nutritional state or criterion of adequacy in essentially all members of a specific healthy population.

Therefore, based on the recommendations of the Workshop, we need at least 2.22 grams of ALA per day. This translates into approximately one teaspoon (5 ml) of flax oil. However, it is important to realize that it is very difficult not to exceed the upper limit for LA consumption (6.67 grams daily) without making a consistent effort to replace processed foods with natural, healthier alternatives present in traditional diets. A single serving of corn, soybean or almost any other "supermarket" vegetable oil supplies 7-8 grams of LA, which exceeds the upper daily limit on LA consumption.

Moreover, highly processed (refined, deodorized or hydrogenated) omega-6 vegetable oils are one of the “cornerstone” ingredients of processed foods, along with refined sugar and white flour. Consequently, by eating processed foods we consume sizable amounts of omega-6 linoleic acid without even paying attention to it. Foods such as cakes, cookies, crackers, potato chips, popcorn, and other popular snacks and foods are usually loaded with omega-6 fats, often in their most dangerous hydrogenated (trans-fat) form. If the consumption of such foods is not curtailed, the daily upper limit for omega-6 fatty acid intake may easily be exceeded many times over.

Additionally, the rate of enzymatic conversion of alpha-linolenic acid into longer-chain precursors of prostaglandins is not uniform, and may be negatively affected by such widespread factors as aging, vitamin and mineral deficiencies, consumption of trans-fatty acids and alcohol, low thyroid function, smoking, and stress. For instance, achieving a maximum rate of ALA-to-EPA conversion requires an adequate daily intake of vitamins C, B6, B3, zinc and magnesium, preferably from natural sources, which are not always available.

Because of this and the fact that maintaining a healthy ratio of omega-6: omega-3 is more critical than the amount of either one, it may be advisable to increase omega-3 supplementation to a level higher than 2.22 grams of ALA daily. Also considering that, as opposed to the case with omega-6 fatty acids, the experts did not impose an upper limit on omega-3 EFA consumption, this would ensure an extra degree of protection against disease-causing abnormalities in fat metabolism. Therefore, many nutritionists recommend a daily dose of one tablespoon (15 ml) of an ALA-rich oil (such as flax oil), supplying about 6 to 8 grams of ALA. This amount of daily omega-3 supplementation will compensate for a probable excess of omega-6 fatty acids in the diet, as well as for a possibility of an impaired ALA-to-EPA conversion.

Recommendations by the Institute of Medicine

Adequate Intake (AI) for Omega-3 Fatty Acids
Life Stage	Age	Source	Males (g/day)	Females (g/day)
Infants	0-6 months	ALA, EPA, DHA*	0.5	0.5
Infants	7-12 months	ALA, EPA, DHA	0.5	0.5
Children	1-3 years	ALA	0.7	0.7
Children	4-8 years	ALA	0.9	0.9
Children	9-13 years	ALA	1.2	1.0
Adolescents	14-18 years	ALA	1.6	1.1
Adults	19-50 years	ALA	1.6	1.1
Pregnancy	All ages	ALA	-	1.4
Lactation	All ages	ALA	-	1.3

All omega-3 polyunsaturated fatty acids present in human milk can contribute to the AI for infants. Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids. Washington, D. C.: National Academies Press; 2002 International Recommendations

The European Commission recommends an omega-6 fatty acid intake of 4-8% of energy and an omega-3 fatty acid intake of 2 g/day of ALA and 200 mg/day of long-chain omega-3 fatty acids (EPA and DHA). The World Health Organization recommends an omega-6 fatty acid intake of 5-8% of energy and an omega-3 fatty acid intake of 1-2% of energy. However, the Japan Society for Lipid Nutrition has recommended that LA intake be reduced to 3-4% of energy in Japanese people whose omega-3 fatty acid intakes average 2.6 g/day, including about 1 g/day of EPA and DHA.

American Heart Association

The American Heart Association recommends that people without documented CHD eat a variety of fish (preferably oily) at least twice weekly, in addition to consuming oils and foods rich in ALA. People with documented CHD are advised to consume approximately 1 g/day of EPA and DHA preferably from oily fish, or to consider EPA and DHA supplements in consultation with a physician. Patients who need to lower serum triglycerides may take 2-4 g/day of EPA and DHA supplements under a physician’s care.

Toxicity Symptoms

In its 2002 guidelines for omega-3 fatty acid intake, the Institute of Medicine at the National Academy of Sciences declined to establish a Tolerable Upper Intake Level (UL) for omega-3 fatty acids. However, research was cited showing increased risk of bleeding and hemorrhagic stroke in a few studies following supplementation with omega-3 fatty acids. Individuals who have disorders involving bleeding, who bruise very easily, or who are taking blood thinners should consult with a medical practitioner before taking supplemental omega-3 fatty acids.

Courtesy of www.goldofpleasure.com and the Linus Pauling Institute of Oregon State University.

+Dietary Sources of Essential Fatty Acids

Where to Get Omega-3 Essential Fatty Acids

As mentioned before, essential fatty acids are so named because the body must have them to perform essential functions, but cannot produce them itself. They must be provided in the diet. So where do you get them?

ALA omega-3 fatty acids are found in certain oilseeds and plants. DHA and EPA are most often found in certain fatty fishes and marine plants. As most of the research on omega-3 fatty acids comes from fish oil supplementation, this is routinely touted as the best choice. However, fish oil cannot provide ALA, which has been shown to have its own essential health benefits. The body can convert ALA to both DHA and EPA, but the rate at which this occurs is under some debate, ranging anywhere from 5-30%.

All sources of omega-3 fatty acids have their pros and cons. Wild fish sources (as listed in table 1) are good sources of DHA and EPA, but there is a risk of heavy metal contamination and depletion of oceanic resources. Farmed fish are not good sources of omega-3 fatty acids because they are fed grain-based feeds and do not have access to the plankton and krill which provide them with omega-3 fatty acids. Fish oil capsules must be properly prepared to ensure no heavy metal contamination and sometimes have a “fishy” aftertaste. Canola oil must be unrefined to provide significant amounts of omega-3 fatty acids, a form which may be difficult to find in the average grocery store. Flaxseed oil and walnuts can easily provide high amounts of ALA, but the efficiency of the body to convert that to DHA and EPA is under some debate.

Additional sources also include eggs from chicken fed an omega-3 enriched diet (typically by including flax as part of their feed) and grass-fed beef (contains a better balance of omega-6: omega-3 fatty acids).

Table 1 Sources of Omega-3 Essential Fatty Acids
	Omega-3 EFAs milligrams
ALA
Walnuts, English, 14 halves (28 g)	2,575
Flaxseed oil, 1 tsp. (5 ml)	2,416
Soybeans, ½ cup (125 ml)	514
Canola oil, 1 tsp. (5 ml)	419
DHA and EPA
Atlantic salmon, cooked, 3 oz. (90 g)	1,825
Rainbow trout, cooked, 3 oz. (90 g)	981
White tuna, skipjack, 3 oz. (90 g)	733
Fish oil capsule, 1000 milligrams	300

As the old adage goes, it is best not to put all your eggs in one basket (even omega-3 eggs)! Each source of omega-3 fatty acids has additional healthful features, making it beneficial to get your omega-3 fatty acids from several sources every day. Additionally, one must consider the importance of a balanced ratio of omega-6: omega-3 fatty acids. To truly see the effects of added omega-3 fatty acids in the diet, one must also reduce intake of omega-6 fatty acids, which are abundant in the current western diet.

+Essential Omega-3

+Omega-3 EFAs: Brain and Behavior

+Alzheimer's Disease

Alzheimer's Disease

Docosahexaenoic acid (DHA), a major component of fish and seal oil, is the most important fatty acid in the brain and retina and makes up more than 30% of the structural lipid (fat) in neurons. There is ample evidence that a deficiency of DHA is associated with depression, attention deficit hyperactivity disorder and dementia. Clinical studies have shown that an increased intake of DHA may benefit patients with dyslexia and Alzheimer's disease.

Researchers at Boston University and Tufts University School of Medicine now report that they have found a clear association between low blood levels (in the phosphatidylcholine fraction of serum) of DHA and the risk of developing Alzheimer's disease. Their study involved 1188 elderly Americans (mean age of 75 years) who had blood samples drawn and analyzed for DHA in 1985. Sixteen of the participants had clinically diagnosed Alzheimer's at the time of blood sampling. The researchers noted that 11 of the 16 (69%) had lower DHA levels. The remaining 1172 participants were followed for 10 years. Again the researchers noted that participants with DHA levels in the lower half of the distribution had a 67% greater risk of developing Alzheimer's disease. The researchers suggest that maintaining adequate levels of DHA may be particularly important for the elderly.

+Attention Deficit Hyperactive Disorder

Attention Deficit Hyperactivity Disorder

It is estimated that 3-5% of the school-age population in the United States suffers from attention-deficit hyperactivity disorder (ADHD). Prominent symptoms of this disorder are a poor attention span, inability to complete tasks, hyperactivity, and a tendency to interrupt others. Almost one quarter of children with ADHD also suffer from one or more specific learning disabilities in math, spelling or reading.

A study first reported in 1995-linked ADHD to a deficiency of certain long-chain fatty acids. These acids (arachidonic, eicosapentaenoic, and docosahexaenoic acids) are all metabolites of the two essential fatty acids, linoleic acid (omega-6) and alpha-linolenic acid (omega-3). Researchers at Purdue University are now leaning towards the conclusion that a sub clinical deficiency in docosahexaenoic acid (DHA) is responsible for the abnormal behavior of children with ADHD.

They point out that supplementation with a long-chain omega-6 fatty acid (evening primrose oil) has been unsuccessful in ameliorating ADHD and believe this is because ADHD-children need more omega-3 acids rather than more omega-6 acids. The researchers also found that children with ADHD were breast fed less often as infants than were children without ADHD. Breast milk is an excellent source of DHA. A study is now underway to investigate the effect of oral supplementation with DHA on the behavior of ADHD children.

In a study of nearly 100 boys, those with lower levels of omega-3 fatty acids demonstrated more learning and behavioral problems (such as temper tantrums and sleep disturbances) than boys with normal omega-3 fatty acid levels. In animal studies, low levels of omega-3 fatty acids have been shown to lower the concentration of certain brain chemicals (such as dopamine and serotonin) related to attention and motivation.

Studies that examine the ability of omega-3 supplements to improve symptoms of ADHD are still needed. At this point in time, eating foods high in omega-3 fatty acids is a reasonable approach for someone with ADHD.

+Autism

Autism

Previous studies link alteration in omega-3 PUFA levels to psychiatric diseases, such as depression schizophrenia and attention deficit hyperactivity disorder (ADHD). Indeed, patients with schizophrenia or ADHA share poor communication skills and other behaviors with autism. For example polydipsia (excessive thirst) is a hallmark of autism, ADHD and essential fatty acid deficiency. On the other hand, omega-3 PUFA levels differed markedly between autism and mentally retarded children. Levels of alpha-linolenic acid, the precursor for omega-3 PUFA, were not statistically different. However, DHA and total omega-3 PUFA levels were 23% and 20% lower, respectively, in autistic children compared to mentally retarded children. Moreover the omega-6: omega-3 ratio increased by 25% among autistic children. Nevertheless, the study offers the first evidence that children with autism show lipid abnormalities.

Cure Autism Now and Lipomics Collaborate on New Biomarker Study
Courtesy of www.autismspeaks.org

Cure Autism Now has partnered with Lipomics Technologies, a company that specializes in metabolite analysis and interpretation, for a new biomarker study of children with autism. This study may offer clues about the causes of autism and may lead to better therapies for autism and other neurodevelopmental disorders.

Results from preliminary research indicate a decrease in levels of an omega-3 fatty acid--docosahexaenoic acid, or DHA--in plasma of autistic individuals, confirming previous findings. In this new study, Lipomics will explore more extensive lipid profiling to see whether metabolic signatures of the disorder, such as DHA levels, are present in male children with autism, as compared with their typical male siblings and unrelated typical children in the same age group.

Lipomics will analyze DNA samples collected by the Autism Genetic Resource Exchange (AGRE) to generate lipomic profiles for each of the samples using its TrueMass lipid analysis. This service can measure the levels of hundreds of lipid metabolites from each small sample.

"Deficiencies of lipid metabolism could be related to some of the physiological symptoms found in autism," said Clara Lajonchere, Ph.D., AGRE Program Director. "The data generated by Lipomics will contribute important new biological information to the growing body of research available to scientists worldwide through AGRE. The results may offer promising clues to understanding the causes of autism. Cure Autism Now hopes to replicate and extend its initial findings by using the expertise that Lipomics provides."

"We are pleased to be working with Cure Autism Now and its AGRE resource to profile the metabolic signatures of autism that we hope will lead to new, more effective therapeutics that can be used in the treatment of this rapidly increasing disorder," said Dr. Tom Anderson, president and CEO of Lipomics Technologies.

+Bipolar Disorder

Bipolar Disorder (Manic Depression)

In a study of 30 people with bipolar disorder, those who were treated with EPA and DHA (in combination with their usual mood stabilizing medications) for four months experienced fewer mood swings and recurrence of either depression or mania than those who received placebo. A similar but larger study is currently underway at the University of California Los Angeles, School of Medicine.

Researchers at Massachusetts General Hospital have reported that omega-3 fatty acid is highly effective in treating children with ADD, ADHD and bipolar disorder. The study was reported in the journal European Neuropsychopharmacology in February 2007.

"Results from this prospective, open study of monotherapy with omega-3 fatty acids … suggest that manic symptoms can be rapidly reduced in youths with BPD with a safe and well-tolerated nutritional supplement," wrote lead researcher Dr. Janet Wozniak.

A high-EPA supplement of was tested for effectiveness and safety on 20 boys and girls with bipolar disorder, ages 6 to 17 years old, over an eight-week period. Half of the participants experienced a rapid 30 percent reduction in symptoms with no side effects.

"This is great news for parents," said Dr. Carol Locke. "Parents are always struggling with how best to help their children. It is incredibly gratifying to develop a product that offers a safe mood stabilizer and natural anti-depressant."

The study demonstrated that supplements reduced the participating children's Young Mania Rating Scale scores (YMRS) -- the standard rating scale for children with bipolar disorder -- by 30 percent. The same research team conducted a similar study with risperidone or olanzapine, the two most commonly prescribed drugs for the disorder. The pharmaceuticals treated the children's disorders but led to side effects including diabetes.

Other commonly prescribed drugs such as lithium, divalproex and carbamazepine are only minimally effective or fraught with adverse effects, the researchers noted.

"EPA and DHA are essential fatty acids that the body cannot make so we must obtain them in our diet…," said Locke. "An imbalance of omega-6 and omega-3 can result in an overall inflammatory response and related disorders such as depression, cardiac disease, cancer, dementia, asthma and rheumatoid arthritis."

Locke concluded, "Over the next five years, we will see Omega-3 fatty acids become a foundation of health."

+Depression

Depression

People who do not get enough omega-3 fatty acids or do not maintain a healthy balance of omega-6 to omega-3 fatty acids in their diet may be at an increased risk for depression. Researchers at the National Institute of Alcohol Abuse and Alcoholism believe that the increasing rates of depression seen in North America over the last 100 years are due to a significant shift in the ratio of omega-6 (arachidonic acid, linoleic acid) to omega-3 (docosahexaenoic acid, linolenic acid) fatty acids in the diet.

The omega-3 fatty acids are important components of nerve cell membranes. They help nerve cells communicate with each other, which is an essential step in maintaining good mental health. Levels of omega-3 fatty acids were found to be measurably low and the ratio of omega-6 to omega-3 fatty acids was particularly high in a study of patients hospitalized for depression.

The human race evolved on a diet having a ratio of about 1:1 of these acids; it is now estimated to be between 10:1 and 25:1. Docosahexaenoic acid (DHA) is a main component of the synaptic membranes and a lack of it has been linked to depression. Fish oils are a rich source of DHA and it can also be biosynthesized in the body from alpha-linolenic acid (ALA) and linoleic acid (LA).

The researchers speculate that the depressions which often accompany alcoholism, multiple sclerosis, and childbirth (postpartum depression) are all due to a lack of DHA and can be corrected by increasing the dietary intake of DHA, ALA or LA. They also point out that depression and coronary heart disease are strongly associated and that a low intake of omega-3 fatty acids has been linked to both.

In a study of people with depression, those who ate a healthy diet consisting of fatty fish two to three times per week for 5 years experienced a significant reduction in feelings of depression and hostility.

Serotonin and Dopamine

Over the last decade, neuroscientists have been examining the consequences of omega-3 deficiencies in the central nervous system. Alterations in serotonin and dopamine levels, as well as the functioning of these two important neurotransmitters is evident in an omega-3 deficiency. The changes observed in omega-3 deficiency in animals is strikingly similar to that found in autopsy studies of human depression (Logan, AC. New Findings About Omega-3 Fatty Acids and Depression).

Antidepressant Activity

Omega-3 deficiency also causes a 35% reduction in brain phosphatidylserine levels. This is also of relevance when considering that phosphatidylserine has documented antidepressant activity in humans (Logan, AC. New Findings About Omega-3 Fatty Acids and Depression).

Mechanisms of EPA/DHA Regulation of Mood

DHA is found in high levels in the cells of the central nervous system (neurons). Here it acts as a form of scaffolding for structural support. When omega-3 intake is inadequate, the nerve cell becomes stiff as cholesterol and omega-6 fatty acids are substituted for omega-3. When a nerve cell becomes rigid, proper neurotransmission from cell to cell and within cells will be compromised.

While DHA provides structure and helps to ensure normal neurotransmission, EPA [an omega-3 fatty acid] may be more important in the signaling within nerve cells. Normalizing communications within nerve cells has been suggested to be an important factor in alleviating depressive symptoms (Logan, AC. New Findings About Omega-3 Fatty Acids and Depression).

In addition, EPA can lower the levels of two important immune chemicals: tumour necrosis factor alpha (TNFa) and interleukin 1 beta (IL-1ß), as well as prostaglandin E2. All three of these chemicals are elevated in depression. In fact, higher levels of TNFa and IL-1ß are associated with severity of depression (Logan, AC. New Findings About Omega-3 Fatty Acids and Depression).

Finally, EPA has been hypothesized to increase brain-derived neurotropic factor (BDNF), which is known to be lower in depressed patients. BDNF is neuroprotective, enhances neurotransmission, has antidepressant activity and supports normal brain structure. BDNF may prevent the death of nerve cells in depression.

+Dyslexia

Dyslexia

Dyslexia is a fairly common condition which involves difficulties in learning to read and write, mirror reversals of letters and words and poor short-term memory. Dyslexia is closely related to dysphasia (problems with coordination and muscle control) and attention-deficit hyperactivity disorder. It is estimated that about 10% of the populations of the United States and the United Kingdom suffer from dyslexia and 4% are severely affected. There was a 3-fold increase in the prevalence of learning disorders in the USA over the period 1976 to 1993 and 80% of the new cases involved dyslexia.

Dr. Jacqueline Stordy of the University of Surrey believes that dyslexia, dyspraxia, and attention-deficit hyperactivity disorder have one common denominator – a deficiency of long-chain fatty acids. She points to a study which found improved dark adaptation (a problem among dyslexics) after supplementation with 480 mg/day of docosahexaenoic acid (a main constituent of fish oil) for a month. Another study involving 15 dysphasic children found that supplementation with a proprietary mixture of tuna oil, evening primrose oil, thyme oil, and vitamin E for 4 months markedly improved their motor skills. The mixture provided 480 mg of docosahexaenoic acid, 35 mg of arachidonic acid, 96 mg of alpha-linolenic acid, 80 mg of vitamin E, and 24 mg of thyme oil daily.

Dr. Stordy concludes that long-chain polyunsaturated fatty acid supplements may benefit children with dyslexia, dyspraxia, and attention-deficit hyperactivity disorder and notes that large, double-blind, placebo-controlled studies are already underway to verify this hypothesis.

Another study entitled “Membrane fatty acids, reading and spelling in dyslexic and non-dyslexic adults” asked 32 dyslexics and 20 controls to complete standardized tests of reading and spelling. The participants gave venous blood samples for analysis of the polar lipid fatty acid composition of red blood cell (RBC) membranes. Relationships between literacy skills and omega-6: omega-3 concentrations were examined using rank-order correlations. The researchers concluded that better word reading was associated with higher total omega-3 concentrations in both dyslexic and control groups. In dyslexic subjects only, reading performance was negatively associated with the ratio of arachidonic acid: eicosapentaenoic acid (ARA: EPA) and with total omega-6 concentrations. There were no significant differences in membrane fatty acid levels between the dyslexic and control subjects.

However, the researchers concluded that because omega-3 status was directly related to reading performance irrespective of dyslexia supports a dimensional view of this condition, and the results also suggest that it is the omega-6: omega-3 balance that is particularly relevant to dyslexia.

References

· Cyhlarova E, Bell J, Dick J, et al. Membrane fatty acids, reading and spelling in dyslexic and non-dyslexic adults. Eur Neuropsychopharmacol 2007;17:116-121.

+Hyperactivity and Aggression

Hyperactivity and Aggression

Children suffering from attention-deficit hyperactivity disorder (ADHD) are inattentive, impulsive, and hyperactive. Researchers at Purdue University now report that hyperactive children have lower levels of key fatty acids in their blood than do normal children. Their experiment involved 53 boys aged 6 to 12 years of age who suffered from ADHD, but were otherwise healthy and 43 matched controls.

Analyses showed that the boys with ADHD had significantly lower levels of arachidonic, eicosapentaenoic and docosahexaenoic acids in their blood. The hyperactive children suffered more from symptoms associated with essential fatty acid deficiency (thirst, frequent urination, and dry hair and skin) and were also much more likely to have asthma and to have had many ear infections.

The researchers concluded that ADHD may be linked to a low intake of omega-3 fatty acids (linolenic, eicosapentaenoic, and docosahexaenoic acids) or a poorer ability to convert 18-carbon fatty acids to longer more highly unsaturated acids. The researchers conclude that supplementation with the missing fatty acids may be a useful treatment for hyperactivity.

Additionally, a new study of teenagers has found that the consumption of omega-3 essential fatty acids relates to lower hostility rates in teenagers. Hostility has been shown to play a role in the development and manifestation of heart disease.

+Schizophrenia

Schizophrenia

There is evidence that schizophrenia is associated with an abnormal metabolism of unsaturated fatty acids in both blood plasma and red blood cells. This abnormality, in turn, is associated with extraordinary low levels of long-chain unsaturated fatty acids such as EPA (eicosapentaenoic acid), DHA (docosahexaenoic acid), and AA (arachidonic acid) in cell membranes.

Researchers at the Imperial College School of Medicine now report that fatty acid levels can be restored to normal and schizophrenia symptoms eliminated or at least vastly diminished by oral supplementation with EPA, the major component of fish oils. Their experiment involved a 30-year-old man who had suffered from schizophrenia for over 10 years. He had frequent (at least daily) hallucinations and also suffered from persecutory delusions and thought disorder. The patient was put on 2 grams/day of EPA and was evaluated for schizophrenia symptoms and blood plasma and red blood cell membrane levels of fatty acids at monthly intervals for 6 months. The results were spectacular. After 6 months the overall score for schizophrenia symptoms had dropped by a factor of 6 (an 85% reduction in severity). Episodes of delusions were completely eliminated and there was an 88% reduction in the number of hallucinatory episodes.

The remarkable clinical improvement in symptoms was associated with substantial increases in the levels of EPA, DHA and AA in red blood cell membranes and with significant increases in EPA and DHA levels in blood plasma. The researchers conclude that EPA supplementation is able to reverse the abnormal fatty acid profiles found in schizophrenics and that this reversal is associated with, and is likely to be the cause of, the clinical improvement.

+Stroke

Stroke

Stroke is the third leading cause of death in this country. A stroke occurs when the oxygen supply to the brain is shut off, causing the death of vital nerve cells.

Ischemic Stroke

Ischemic stroke occurs when blood flow is blocked and not enough oxygen is getting to the brain. The events leading up to this type of stroke is similar to those in heart attacks. Ischemic stroke accounts for two thirds of all strokes.

Hemorrhagic Stroke

Hemorrhagic stroke occurs when the artery supplying blood and oxygen to the brain bursts because of weakness in the vessel wall, usually caused by high blood pressure. The nerve cells that are normally supplied by the burst artery are deprived of oxygen and begin to die. Consequently, reducing elevated blood pressure has become the first line of defense to avoid a hemorrhagic stroke.

Omega-3 fatty acids have been shown to reduce blood pressure and also reduce blood clot formation (thrombosis) by preventing platelets (thrombocytes) from sticking together and forming blood clots. Blood clots, which may result in stroke, heart attack or pulmonary embolism, are the #1 cause of death in the Western world. Most of them are preventable by including omega-3 fatty acids and other anti-clotting foods and supplements into the diet.

+Omega-3 EFAs: Cancer Related Conditions and Diseases

+Cancer

Cancer

Several major epidemiologic studies have found a clear association between a high dietary fat intake and the risk of developing breast and colon cancer. The correlation is particularly strong in the case of animal fats. One study found that a high fish or fish oil consumption is protective against later stage colon cancer in men, but has no effect on mortality from breast cancer. British medical researchers now report that fish and fish oils not only protect against colon cancer in men, but also against colon and breast cancer in women. This protective effect, however, is only apparent in countries where the intake of animal fats is high. In other words, a high intake of fish or fish oils counteracts the detrimental effects of a high animal fat consumption.

The study compared cancer mortality rates in 24 European countries, Canada and the USA with fish consumption and the intake of animal fats. In countries where the animal fat intake was high the researchers found a clear inverse correlation between the ratio of fish fat to animal fat and the risk of developing breast cancer in women and colon cancer in both men and women. A similar correlation was found between cancer risk and the ratio of fish fat to total fat intake.

The researchers conclude that a 15% decrease in animal fat intake combined with a 3-fold increase in fish oil intake could possibly reduce male colon cancer risk by as much as 30% in countries with a high animal fat intake. A 3-fold increase in fish oil intake could be achieved by eating fish three times a week or by taking two standard fish oil capsules daily.

Studies indicate the following:

· Feeding omega-3 has slowed the growth of the tumor and made it less likely that the cancer would spread. (Galli, Claudia, Butrum, Simopoulos et al, eds 1991, Karger, Basel, p462-476)
· A study of 12,866 American men determined that those eating high amounts of omega-3 and low amounts of omega-6 had a 33% lower risk of dying from cancer. (Dolecek, There and Grandits, World Review Nutr. Diet, Karger, 1991, 66: 205-216)
· Tissues taken from 100 skin cancer patients were compared with skin from 100 healthy individuals and it was found that the more omega-6 found in a person’s tissues, the more likely they were to have cancer. (MacKie, MacKie and Bourne, Nutr and Cancer, 1987 9, 205-216)
· A comparison of cancerous brain tumors with healthy tissue revealed that omega-6 was four times more prevalent in the cancerous tissues. (Martin, Robbins and Hussy, Lipids, 1996, 31: 1238-1288)
· Incidence of breast cancer increased as Greenland and Icelandic women abandoned their traditional diets of marine life (mainly seal which is very high in omega-3). (Bjarnason, Int. J., Cancer, 1974, 13: 689-696)
· In a 8-year study of 846 men, those given a diet high in omega-6 were twice as likely to die of cancer as those eating a diet low in omega-6. (Pearce and Dayton, The Lancet, 1971, 464-467.)
· For breast cancer, omega-6 fatty acids appear to have the greater cancer promoting effects and omega-3 fatty acids are the most protective. (C.L. Williams, M., Bollella, Laura Boccia and Arlene Spark, “Dietary Fat and Children” Nutrition today, vol 33, no 4: July/Aug 1998)
· In animal experiments, dietary corn oil very high in omega-6 has been shown to stimulate lung cancer of the adenocarcinoma type. (Okuyama, Kobayashi and Watanabe. p.415)
· How does Omega-3 Work to Reduce the Risk of Cancer?

Research indicates the following:

· Consuming more omega-3 makes the omega-6 linolenic acid that promotes tumor growth less available.
· Omega-3 fatty acids make the cancer cells more vulnerable to free-radical attack by rendering the membranes less saturated.
· Omega-3 fatty acids seem to promote the self-destruction of cancer cells thereby slowing tumor growth.

+Breast Cancer

Breast Cancer

Breast cancer rates differ greatly between countries. Reported rates in the United States are 5 times higher than in Japan. They are twice as high in France as in Spain. Differences in overall fat consumption in these countries have been extensively studied, but no link to breast cancer incidence has yet been detected.

A large team of researchers from the Netherlands, Ireland, Spain, Finland, Switzerland, Germany and the United States now report that, while overall fat consumption may not be significant, the make-up of the fats could be. As part of the large EURAMIC Study, the researchers investigated the link between the content of polyunsaturated fats in adipose (fat) tissue of postmenopausal women and breast cancer incidence. A total of 291 women with breast cancer and 351 controls were included in the study which involved 5 European medical centers. The women all had samples of adipose tissue taken (from the buttocks) and analyzed to determine the concentration of the main polyunsaturated fatty acids: omega-3 fatty acids (alpha-linolenic acid [ALA], eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA]) and omega-6 fatty acids (linoleic acid [LA] and its metabolite arachidonic acid [AA]).

The study found no significant correlation between omega-3 fatty acid levels and breast cancer incidence, but did find a trend to increasing incidence with increasing levels of omega-6 fatty acids in the adipose tissue samples. The researchers also found a significant association between the ratio of LA (omega-6) and EPA and DHA (omega-3) levels and breast cancer incidence in 4 out of 5 of the medical centers involved in the study. Pooling all results showed that women with the highest ratio had a 35% higher breast cancer incidence than women with the lowest ratio. In other words, women with a relatively low level of LA and its metabolites and a relatively high adipose tissue level of EPA and DHA had a lower breast cancer risk. The researchers note that LA (linoleic acid) is the precursor of certain eicosanoids which may promote tumor growth. EPA and DHA inhibit the production of these harmful compounds and may also, on their own, inhibit tumor growth. The researchers also point out that several epidemiological studies have found an inverse correlation between fish consumption and breast cancer incidence and urge further studies to determine the relationship between the dietary intake of specific fatty acids and breast cancer risk.

Although not all experts agree, women who regularly consume foods rich in omega-3 fatty acids over many years may be less likely to develop breast cancer. In addition, the risk of dying from breast cancer may be significantly less for those who eat large quantities of omega-3 from fish and brown kelp seaweed (common in Japan). This is particularly true among women who substitute fish for meat. The balance between omega-6 and omega-3 fatty acids appears to play an important role in the development and growth of breast cancer. Further research is still needed to understand the effect that omega-3 fatty acids may have on the prevention or treatment of breast cancer. For example, several researchers speculate that omega-3 fatty acids in combination with other nutrients (namely, vitamin C, vitamin E, beta-carotene, selenium, and coenzyme Q10) may prove particularly valuable for preventing and treating breast cancer.

+Colon Cancer

Colon Cancer

Consuming significant amounts of foods rich in omega-3 fatty acids appears to reduce the risk of colorectal cancer. For example, Eskimos, who tend to follow a high fat diet but eat significant amounts of fish rich in omega-3 fatty acids, have a low rate of colorectal cancer. Animal studies and laboratory studies have found that omega-3 fatty acids prevent worsening of colon cancer while omega-6 fatty acids promote the growth of colon tumors. Daily consumption of EPA and DHA also appeared to slow or even reverse the progression of colon cancer in people with early stages of the disease.

Several factors put people at risk for colon cancer—lack of dietary fiber and calcium, a build up of toxins in the colon, continued constipation and/or diarrhea, polyps and a high-fat diet.

Obtaining omega-3 fatty acids from flaxseed has the added benefit of also providing flax hull lignans in the diet. Since the plant lignan SDG is converted into the mammalian lignans enterolactone and enterodiol directly within the colon, SDG appears to be particularly effective in combating cancer of the colon.

One study showed that SDG lignan over the short term decreases some early markers of colon cancer risk. Additional studies at the University of Toronto, Department of Nutritional Medicine, were conducted and demonstrated that over the long term, flaxseed lignan still exerts a colon cancer protective effect. Six groups of rats were fed for 100 days either a regular diet or one supplemented with 2.5 or 5% defatted flaxseed. All rats were injected with a single dose of azoxymethane one week prior to commencing the dietary treatments to induce colon cancer. The rats which were fed the defatted flax diet had significantly reduced number of aberrant crypts in the colon compared to the control group. It was concluded that flaxseed has a colon cancer protective effect that is due, in part, to the lignan SDG; and that the protective effect of flaxseed and SDG is associated with increased beta-glucuronidase activity.

Additional research was performed involving the mammalian lignans enterolactone (EL) and enterodiol (ED), derived from SDG. In this research four human colon tumor cell lines were incubated with various levels of EL, ED, or 17 beta-estradiol for 8-10 days. At 100 microM concentration, both lignans significantly reduced cell proliferation of all cell lines. EL was more than twice as effective as ED at this concentration. The growth was not affected by the presence of 17 beta-estradiol, implying that these cells are not estrogen sensitive. The conclusion was that lignans are growth inhibitors of colon tumor cells and may act through mechanism(s) other than antiestrogenic activity.

References

· Jenab, M., & Thompson, L. "Influence of Flaxseed and Lignans on Colon Carcinogenesis' Carcinogenesis, 1996; 17(6): 1343-1348.
· Sung. M.K., Lautens, M., Thompson, L. "Mammalian Lignans Inhibit the Growth of Estrogen-Independent Human Colon Tumor Cells," Anticancer Res., 1998, May-Jun; 18(3A): 1405-08.

+Prostate Cancer

Prostate Cancer

Laboratory and animal studies indicate that omega-3 fatty acids may inhibit the growth of prostate cancer. Similarly, population based studies of groups of men suggest that a low-fat diet with the addition of omega-3 fatty acids help prevent the development of prostate cancer. Like breast cancer, the balance of omega-6 to omega-3 fatty acids appears to be particularly important for reducing the risk of this condition.

Several studies have shown an inverse relationship between blood levels of omega-3 fatty acids (eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA]) and the risk of prostate cancer. A study just completed by medical researchers at the Karolinska Institute confirms this association.

The Swedish study involved 3136 pairs of male twins born between 1886 and 1925. The participants completed food frequency questionnaires in 1961 and 1967 and were then followed up for 30 years. By December 31, 1997 the researchers had recorded 466 diagnoses of prostate cancer (340 fatal ones). The average age of diagnosis was 76.7 years.

After adjusting for other known risk factors the researchers conclude that men who never eat fish have a two- to three-fold higher risk of prostate cancer than do men who eat moderate to high amounts. The researchers emphasize that only fatty fish such as salmon, herring and mackerel, which contain high amounts of omega-3 fatty acids (EPA and DHA), would be expected to be beneficial.

Flaxseed (particularly the lignans found in the hull) has also been shown to be very effective in men with prostate cancer. Flaxseed ingestion produces large amounts of mammalian lignans with weak estrogenic/anti-estrogenic properties. In tests these properties reduced adult relative prostate weight and cell proliferation, suggesting potential protection against prostatic disease, without affecting hormone levels.

Researchers from the University of Wales, College of Medicine, Cardiff, United Kingdom, determined the concentration of lignans in prostate fluid from Portuguese, Chinese and British men. The mean concentration of enterolactone and other plant estrogens were very high among Portuguese and Asian men, respectively. The research team concluded that the levels of lignans and related plant estrogens may be responsible, in part, for lower incidences of prostate cancer in men from Mediterranean countries.

A very recent study involved twenty-five patients with prostate cancer, who were given a lignan-rich flaxseed supplementation. The results show a favorable affect on prostate cancer biology and associated biomarkers.

References

· Tou, J., et al Jour. Toxicol Environ. Health, 1999, 56(8):55.
· Morton, M.S., et al. "Lignans and Isoflavonoids in Plasma and Prostatic fluid in men: samples from Portugal, Hong Kong, and the United Kingdom." Prostrate, 1997: 32(2):122-8.
· Demark-Wahnefried, W., et al., Urology, Jul., 2001, 58(l):47-52.

+Omega-3 EFAs: Gastrointestinal Related Conditions and Diseases

+Crohn's Disease

Crohn’s Disease

Crohn's disease is an inflammatory disease involving intestinal pain, diarrhea, and malabsorption of nutrients. The disease is characterized by periods of active disease interspersed with periods of remission. Conventional treatment with prednisone and salycylates has been only marginally successful in extending the periods of remission.

Elemental diet (ED) therapy is the preferred treatment in Japan. The ED therapy involves tube feeding (enteral nutrition) a mixture of free amino acids, short-chain maltodextrins, and low levels of fat in the form of soybean oil. Compliance with this diet is poor resulting in shorter periods of remission.

Researchers at the University of Bologna report that fish oils prevent relapses. Their experiment involved 78 patients with Crohn's disease who had been classified as having a high risk of relapse. Half the patients were randomized to receive nine fish oil capsules daily, the other half received nine placebo capsules daily. The fish oil capsules contained 500mg of a marine lipid concentrate each (40% eicosapentaenoic acid and 20% docosahexaenoic acid) and provided a total of 2.7 grams of omega-3 fatty acids per day. The capsules were enteric-coated so as to ensure that they dissolved in the small intestine instead of in the stomach and to minimize unpleasant side effects such as flatulence, heartburn, belching, and diarrhea.

The results of the fish oil therapy were spectacular. While 69% of the patients in the control group had a relapse during the one-year study period, only 28% in the therapy group did. At the end of the one-year period, 59% of the patients in the fish oil group were still in remission as compared to only 26% in the placebo group. The researchers concluded that fish oil therapy (with enteric-coated capsules) is effective in preventing relapses in patients with Crohn's disease in remission.

+Inflammatory Bowel Disease

Inflammatory Bowel Disease (IBD)

When added to medication, such as sulfasalazine (a standard medication for IBD), omega-3 fatty acids may reduce symptoms of Crohn's disease and ulcerative colitis -- the two types of IBD. More studies to investigate this preliminary finding are under way. In animals, it appears that ALA (found in flax and other plant sources) works better at decreasing bowel inflammation than EPA and DHA (found mainly in certain fish and marine plants). Plus, fish oil supplements can cause side effects that are similar to symptoms of IBD (such as flatulence and diarrhea). Time-release preparations may help reduce these unwanted effects.

+Ulcerative Colitis

Ulcerative Colitis

Ulcerative colitis, a common form of inflammatory bowel disease, is accompanied by an increased level of leukotriene B4 in the lining of the colon. Fish oils are known to inhibit the synthesis of leukotrienes and it has therefore been postulated that they might be beneficial in the treatment of ulcerative colitis. Researchers at the Veterans Affairs Medical Center have just released the results of a study aimed at testing this hypothesis.

The study involved 11 male patients aged 31 to 74 years who had been diagnosed with ulcerative colitis. The patients were randomized into two groups with one group receiving 15 fish oil capsules (providing 2.7 grams of eicosapentaenoic acid (EPA) and 1.8 grams of docosahexaenoic acid (DHA) daily); the other group received placebo capsules (olive oil). After 3 months on the supplements all participants underwent a 2-month wash-out period and were then assigned to the opposite treatment to what they had received during the first stage for another 3 months. Clinical evaluations of all patients were performed at the start of the study and every month thereafter.

Evaluation of the patients' clinical data at the end of the treatment periods showed a significant beneficial effect of fish oil supplementation. The mean disease severity score for the patients on fish oil declined by 56% as compared to 4% for the placebo group. Eight of the 11 patients (72%) were able to markedly reduce or totally eliminate their use of anti-inflammatory medication and steroids while taking the fish oils.

The researchers conclude that fish oil supplementation results in a marked clinical improvement of active mild to moderate ulcerative colitis.

+Omega-3 EFAs: Heart Related Conditions and Diseases

+Angina

Angina

A team of British and Greek medical researchers report that fish oil supplementation is highly beneficial for angina patients. Their study involved 39 patients (37 men and 2 women) with stable angina pectoris who had experienced at least 6 angina attacks in the 2 weeks prior to the start of the trial. The patients were randomly assigned to receive either 10 grams of fish oil (providing 1.8 g eicosapentaenoic acid and 1.2 g docosahexaenoic acid) or 10 grams of olive oil daily. The daily supplements were supplied in the form of 5 identical looking capsules. The trial lasted for a total of 12 weeks and the patients were evaluated at baseline and after 8 and 12 weeks of supplementation.

By the end of the 12 weeks the number of weekly angina attacks had decreased by 41% in the fish oil group with no change observed in the olive oil group. The use of nitroglycerin (glyceryl trinitrate) tablets decreased by 38% in the fish oil group and also decreased slightly (not statistically significant) in the olive oil group. Exercise tolerance, as measured on a treadmill, increased by 22.6% in the fish oil group, but no change was observed in the olive oil group. The blood level (fasting) of triglycerides decreased by 22% eight weeks into the test in the fish oil group, but then tended to approach pre-trial levels again by the 12th week. No statistically significant changes in blood coagulation parameters were observed in either group. The researchers conclude that low-dose fish oil supplementation may benefit patients with coronary artery disease.

+Atherosclerosis

Atherosclerosis

Dr. Garth Mulvad and Dr. Henning Pederson of the Department of Medicine, Dronning Ingrids Hospital in Norway recently wrote:

"...the International Atherosclerosis Project... is a project supervised by experts at the Louisiana State University of New Orleans, USA. Among other things, they ... studied the coronary arteries of the hearts of 23,000 deceased persons from 16 different countries. It is in the coronary arteries that the fatal blood clots form. The provisional results show that atherosclerosis is far less widespread among the Inuit than elsewhere in the world ... a seventy year old who has lived on the traditional diet of seal and whale has coronary arteries that are just as elastic as a twenty year old Dane."

+Cardiovascular Disorder and Irregular Heartbeat

Cardiovascular Disorders

The International Atherosclerosis Project (1992)

Since 1990, researchers from the Louisiana State University have analyzed the coronary arteries of 23,000 deceased persons from 16 countries. The interim results reveal that the Greenlanders have the lowest rate of atherosclerosis among all those tested. Some of the fascinating early results are as follows:

· The Inuit who ate a modern diet had the same rate of this disease as ordinary Europeans and therefore the results were not based on heredity.
· The Inuit who lived on a traditional diet of marine mammals (mainly seal) had, at the age of seventy, the same coronary artery elasticity as a 20 year old European.
· Some European countries may eat more fish than is found in the traditional Greenland diet, but have a far higher incidence of atherosclerosis and, in general, higher levels of cholesterol.
· At the National Hospital in Nuuk, a person with very high cholesterol was given various diets and medicines without major impact. When he was placed on a traditional Greenland diet (mostly of seal), his cholesterol level fell dramatically in one month.

Irregular Heartbeat

Omega-3 essential fatty acids have been shown to lower heartbeat rates and prevent arrhythmias (disturbances of the normal rhythm in the heart's beating), thus decreasing the chances of a sudden death from a heart attack.

+Heart Disease

Heart Disease

Heart disease remains the leading cause of death in western society. For men, the risk of heart attack begins very young and remains fairly constant throughout life while the female incidence of heart disease begins to equal and surpass that of men as women reach menopause.

Studies indicate that omega-3 fatty acids can reduce the chance of a primary cardiac arrest by 70% and a second arrest by 30%. This results primarily from the fact that omega-3 facilitates the maintenance of the walls of the blood vessels, making them smoother and more elastic, thus reducing vessel blockages which are often the cause of heart problems.

Omega-3 fatty acids also tend to retard the rate of the blood clotting, by reducing the "stickiness" of platelets. Heart muscle damage may still take place from a temporary stoppage of an artery and omega-3 PUFA’s prevent this damage from interfering with heartbeats.

Studies further indicate that omega-3 fatty acids help reduce blood pressure, which is becoming a chronic problem in an aging population.

The Orsoq Study

Dr. E. Jorgenson of the Center of Arctic Environmental Medicine in Denmark recently presented the initial results of the Orsoq Seal Research Project, a pilot study on the effect of seal oil on human health. These preliminary findings indicate that the general population of Denmark, fed on a modern diet, was ten times more likely to develop cardiovascular and inflammatory diseases than Greenlanders on their traditional diet of seal, a food high in omega-3 fatty acids. ("Inuit Whaling", Inuit Circumpolar Conference, June 1992, special issue. Gerth Mulved and Henning Sloth Pederson, Doctors of Medicine Dronning Ingrids Hospital.)

Additional Research

Numerous studies show that increased long term intake of marine oils, rich in EPA and DHA, reduces the morbidity and mortality associated with cardiovascular disorders in middle-aged men. Conflicting data exist as to whether it is EPA or DHA or the combination which is responsible for the various beneficial effects. In any event, it is known that there may be limits to the elongation and desaturation of EPA to DHA, whereas the retroconversion of DHA to EPA occurs. (Harris et al., Grimsgaard et al., 1995)

It is generally agreed that omega-3 fatty acids moderate hyperlipidemia, particularly hypertriglyceridemia, very rapidly in a dose dependent manner. Omega-3 fatty acids reduce the triglyceride levels in the blood by reducing synthesis and secretion of VLDL particles from the liver and enhancing the in vivo liposysis of the VLDL-particles. An improved balance between LDL-cholesterol and HDL-cholesterol is also normally found, whereas the effect on total cholesterol is marginal. A large number of studies report such findings.

Omega-3 fatty acids influence on platelet aggregability at rather low doses (50-350mg), whereas significant effects on blood lipids and blood pressure can be achieved at higher doses (2 g/day). (Christensen et al, 1995)

Recent data (from a parallel group study) show that 3g pure DHA (95% DHA, ethyl ester) produce a 30-40% greater reduction in triglyceride levels in plasma than a corresponding amount of EPA (90% EPA, ethyl ester). DHA also seems to have a more marked effect on increasing HDL-cholesterol, whereas EPA was found to slightly decrease both total cholesterol and APO-1 in normal subjects (Grimsgaard et al, 1995).

This study suggests that DHA might be more beneficial than EPA in terms of effects on blood lipids. Others have reported that DHA-rich oils (4 g/day, 42% DHA) are less active than EPA-rich oils and fish diet on both fasting and postpprandial triglyceride levels. (Agren, 1995)

A positive correlation has been observed between supplementation with EPA and DHA (85% ethyl ester) and improvements in blood pressure and heart rate in subjects suffering from mild hypertension. Recently published studies showed that DHA (EE), not EPA (EE), lowered the heart rate in healthy humans. (Bönaa el al, 1995)

Even short time supplementation with large amounts (19g/day) of a combination of EPA and DHA (as ethyl esters) has shown to have long-lasting effects on the human platelet aggregation, an effect suggested by inhibition on TXA2/PGH2 receptor by EPA- and/or DHA-sensitive mechanisms. (Di Minno et al, 1995)

Studies on cardiac arrhythmias do not give any clear evidence on the efficacy of omega-3 fatty acids. However, a trend towards reduction in ventricular extracystoles in patients with ventricular tachyarrhythmia has been observed after supplementation with omega-3 fatty acids (Christiansen et al, 1995). Animal studies show that DHA may inhibit ventricular tachyarrhythmia more significantly than EPA (Leaf, 1995) and also increases the cardiac contractibility. (Grynberg et al, 1995)

Recent data also show that DHA has more pronounced inhibitory effect on the expression of cytokines in endothelial cells, which clearly down-regulate the inflammatory process and may inhibit the progression of atherosclerosis. (DeCaterina & Libby, 1995)

Epidemiological and clinical research have shown that omega-3 fatty acids intervene in the atherosclerotic process at all steps, and that there probably are synergistic effects of EPA and DHA at many levels. (Argen,1995)

One of the best ways to help prevent and treat heart disease is to eat a low-fat diet and to replace foods rich in saturated and trans-fat with those that are rich in monounsaturated and polyunsaturated fats (including omega-3 fatty acids). Evidence suggests that EPA and DHA help reduce risk factors for heart disease including high cholesterol and high blood pressure. There is also strong evidence that these substances can help prevent and treat atherosclerosis by inhibiting the development of plaque and blood clots, each of which tends to clog arteries. Studies of heart attack survivors have found that daily omega-3 fatty acid supplements dramatically reduce the risk of death, subsequent heart attacks, and stroke. Similarly, people who eat an ALA-rich diet are less likely to suffer a fatal heart attack.

+High Cholesterol

High Cholesterol

People who follow a Mediterranean-style diet tend to have higher HDL ("good") cholesterol levels. Similar to those who follow a Mediterranean diet, Inuit Eskimos, who consume high amounts of omega-3 fatty acids from fatty fish, also tend to have increased HDL cholesterol and decreased triglycerides (fatty material that circulates in the blood). In addition, fish oil supplements containing EPA and DHA have been shown to reduce LDL ("bad") cholesterol and triglycerides. Finally, walnuts and flax, which are both rich in ALA have been shown to lower total cholesterol and triglycerides in people with high cholesterol.

+Omega-3 EFAs: Immune System Related Conditions and Diseases

+AIDS

AIDS

AIDS or acquired immune deficiency syndrome results from a shutdown of the immune system. Note that the name indicates that the condition is not genetic but acquired – due to non-genetic (environmental) causes. Hence it should respond to environmental interventions that include changes in both nutrition and lifestyle. The consumption of omega-3 fatty acids in addition to a complete program of essential nutrient supplementation appears to be helpful in prolonging survival.

+Autoimmune Disease

Autoimmune Disease

Autoimmune disorders, in which the immune system attacks the body as if it were a foreign invader, can also be alleviated with omega-3 fatty acid supplementation.

Multiple Sclerosis is one autoimmune disorder that can be positively affected by high-dose marine oil. Lupus, a life threatening autoimmune disorder that causes kidney failure, has also been shown to be positively affected by high dose marine oil. In animal studies using rats that were bred to develop lupus, significant increases in their life spans are observed if their standard diet is supplemented by high dose marine oil.

IgA nephropathy is another inflammatory condition that attacks the kidneys. The disease, which is a major cause of kidney failure, has been found to be alleviated with marine oil. Long-term studies with marine oil indicate a dramatic reduction in the development of kidney failure in these patients compared with those taking placebo. Here, high-dose marine oil is acting not only as a modulator of eicosanoids but also probably as an inhibitor of the release of various inflammatory cytokines.

+Lupus

Lupus

Lupus is an immune disorder that can ravage the body, attacking organs from kidneys to brain. Supplements of omega-3 fatty acids have reduced inflammation, kidney problems and mortality. In one study, patients with active lupus showed significant improvements on supplements of omega-3 fatty acids. While it may be unlikely that most patients with lupus could replace their conventional anti-inflammatory drugs with omega-3 fatty acids there may be a place for using the omega-3 fatty acids as adjuncts.

+Omega-3 EFAs: Joint Inflammation

+Arthritis

Arthritis

Long before it emerged as a possible remedy for heart disease, fish oil was used to treat arthritis. Maurice Stansby, veteran fish-oil researcher and scientific consultant to the National Marine Fisheries Service in Seattle, uncovered documents indicating that, in the late 1700's, personnel from a hospital in Manchester, England, routinely dosed arthritis patients with cod liver oil supplements to help their "squeaky joints." Stansby surmises that the fish oil tradition was lost to history because it was so unpalatable – the only time patients would take their tonic was when it was forced upon them by attendants.

Interest in treating arthritis patients with fish oil was rekindled by the finding that manipulating fatty acids in the diets of arthritic animals was beneficial. A link with fish oil was also suspected because of evidence that leukotrienes and thromboxane (a product of prostaglandins) are involved in the kinds of inflammatory reactions causing the painful symptoms of arthritis. Accordingly, Harvard researchers decided to test out the effects of fish oil in people who have rheumatoid arthritis, a form of arthritis that can be severely disabling. Dr. Richard Sperling and his coworkers found a lowering of inflammatory biochemical, along with a decrease in joint pain and tenderness, in rheumatoid arthritis patients who took fish oil supplements. Although the results are considered preliminary since no control group was involved, Dr. Sperling thinks that fish oils have the potential to act as anti-inflammatory drugs.

Support for Dr. Sperling's hunch comes from research conducted at Albany Medical College in New York. Dr. Joel Kremer found "modest" improvements in some symptoms of rheumatoid arthritis patients who were on fish oil capsules compared to a group of similar patients who did not take the supplements. The problem with this study is that the patients who took the capsules were also on a special diet, making it difficult to know whether fish oil or something about the diet was responsible. In a more recent study, Dr. Kremer placed people with rheumatoid arthritis on fish oil supplements, but no special diet. Compared to a period of time in which they took a placebo, those participants taking fish oil suffered significantly less joint tenderness and reported less fatigue. It is important to note that, although there appeared to be overall improvement in other symptoms of arthritis such as duration of morning stiffness and joint swelling, the effects of fish oil supplements were not as definite.

Thus, fish oil cannot be viewed as any sort of a panacea for arthritis sufferers. Furthermore, the small amount of research that has been conducted in this area has involved large amounts of fish oil. Dr. Dreamer's patients, for example, took 10 to 15 fish oil capsules a day – surely a pharmaceutical dose. He issues words of caution when it comes to taking fish oil supplements. But he does recommend that people who have arthritis eat more fish. At the very least a fish-rich diet can help keep weight down – an important move to minimize stress on weight-bearing arthritic joints.

+Rheumatoid Arthritis

Rheumatoid Arthritis

Most clinical studies investigating the use of omega-3 fatty acid supplements for inflammatory joint conditions have focused almost entirely on rheumatoid arthritis (RA). Several articles reviewing the research in this area conclude that omega-3 fatty acid supplements reduce tenderness in joints, decrease morning stiffness and allow for a reduction in the amount of medication needed for people with rheumatoid arthritis. In addition, laboratory studies suggest that diets rich in omega-3 fatty acids (and low in omega-6 fatty acids) may benefit people with other inflammatory disorders, such as osteoarthritis. In fact, several test tube studies of cartilage-containing cells have found that omega-3 fatty acids decrease inflammation and reduce the activity of enzymes that destroy cartilage. Similarly, it has been shown to reduce joint stiffness and pain, increase grip strength, and enhance walking pace in a small group of people with osteoarthritis.

Several studies have shown that supplementation with omega-3 polyunsaturated fatty acids (omega-3 PUFAs) found in fish oils is beneficial for RA patients. Spanish medical researchers now report that RA patients tend to have decreased levels of omega-3 PUFAs in their blood and synovial (joint) fluid. Their study involved 24 female and 15 male RA patients (median age of 64 years). Blood and joint fluid samples were collected from the patients and from a control group consisting of 28 healthy volunteers (17 male and 11 female with a median age of 61 years). All samples were analyzed to determine their fatty acid profile.

RA patients were found to have significantly lower levels of eicosapentaenoic acid (the main component of fish tissue oil) in both their blood plasma and synovial fluid. The level of alpha-linolenic acid (found in flaxseed) was lower in the synovial fluid of RA patients, but not in their blood plasma. The level of docosahexaenoic acid (a major component of fish tissue oil) also tended to be lower in synovial fluids of RA patients, but not in their blood plasma.

The researchers conclude that RA patients have an abnormal fatty acid profile and a significant deficiency in certain essential fatty acids. They believe this finding may explain why supplements such as fish oils and gamma-linolenic acid (from evening primrose and borage) have been found to be beneficial in the treatment of rheumatoid arthritis.

+Omega-3 EFAs: Other Conditions and Diseases

+Allergies

Allergies

Allergies are the body’s abnormal sensitivities to certain substances. A person can be allergic to just about anything (e.g. dust, food, and medications etc). When our bodies are nutrient deficient, we need to replenish our bodies with a balance of omega-3 and omega-6 fatty acids.

According to Dr. Alan Greene, concerning pregnant women,

… some food choices can influence the odds that your baby will later develop allergies. New research suggests that the balance between omega-3 fatty acids and omega-6 fatty acids can also tilt these odds. Researchers at the Leipzig Allergy Risk Children’s Study Group analyzed the fats in the colostrum from mothers of children at high risk for allergies. The results were published in the April 2004 Allergy. Those with relatively high levels of omega-6 fatty acids were the most likely to develop cow’s milk allergies. Those with the lowest levels of omega-3 fatty acids were most likely to develop allergies overall. Both omega-3 and omega-6 fatty acids are essential in the diet – but in balance. Unfortunately, many Western diets tend to be too heavy on omega-6 at the expense of omega-3.

+Diabetes

Diabetes

Diabetes is a disorder characterized by high blood levels of glucose in the blood. Diabetes can damage the large blood vessels increasing the risk of stroke and heart attack, and can lead to gangrene in the limbs. Many studies now suggest that omega-3 fatty acids are invaluable in combating circulation problems associated with diabetes by rendering the walls of the veins and arteries smoother and more elastic.

People with diabetes tend to have high triglyceride and low HDL levels. Omega-3 fatty acids can help lower triglycerides and raise HDL, so people with diabetes may benefit from eating foods or taking supplements that contain DHA and EPA. On rare occasions, ALA may not have the same benefit as DHA and EPA because some diabetics lack the ability to efficiently convert ALA.

Another study published in 1994 by the British Nutrition Foundation reported that daily consumption of seal oil (high in omega-3) by Alaskan natives led to a 20% lowering of glucose intolerance and diabetes (Adler, Boyko, Schraer, Murphy, 1994 Nutrition Supplement).

Flax seed and flax seed oil both contain omega 3, an essential fatty acid, and mucilage (a thick gluey substance produced by most plants). Studies have shown that essential fatty acids can suppress hunger without causing changes in blood sugar.

The mucilage in flax seed also contributes to controlling the blood sugar levels by lining the digestive tract, slowing absorption of carbohydrates which can otherwise be processed too quickly, flooding the bloodstream in excess. When they are absorbed slowly through a healthy lined digestive tract they are treated the same as a good carbohydrates, leaving no residue or sugar over-doses. A combination of these two effects can result in prevention or control of diabetes. Suppressing appetite, preventing blood sugar rises and drops and slowing carbohydrate absorption are all contributions made by flax in the diet.

+Eating Disorders

Eating Disorders

Studies suggest that men and women with anorexia nervosa have lower than optimal levels of polyunsaturated fatty acids (including ALA and GLA). To prevent the complications associated with essential fatty acid deficiencies, some experts recommend that treatment programs for anorexia nervosa include PUFA-rich foods such as fish and organ meats (which include omega-6 fatty acids).

+Fatty Liver

Fatty Liver

Fatty liver is most commonly found in patients in the early stages of cirrhosis of the liver with or without excessive alcohol involvement. Fatty liver is also commonly associated with liver pathologies and metabolic disturbances with obesity, diabetes, hyperlipidemia, and exposure to certain toxins.

Fatty liver is defined as lipid infiltration in more than 50% of hepatocytes mainly in the form of big lipid droplets. In patients with fatty liver, recent clinical research has found that the concentration of the long chain omega-3 fatty acid is very low. Also, research has found that an increase in fat droplet size in hepatocytes is associated with a decrease of the percentage of omega-3 fatty acid in the liver triglycerides.

The most common cause of fatty liver today is chronic alcoholism, where the alcohol damages liver cells and causes malfunction of the liver metabolism. This in turn causes lipid, carbohydrates and protein metallic disturbances. Overeating increases lipid carbohydrates and protein intake further compounds the problem. Most commonly this patient will develop obesity, hyperlipidemia, insulin resistance, hypertension and visceral distribution of the adipose tissue.

Recent clinical findings have found patients with end-stage liver disease manifest a wide variety of functional abnormalities that eventually lead to their deaths. Such patients also have low levels of longer chain polyunsaturated fatty acids (PUFA) in plasma. This is due to hepatic damage and impairment of the 20-22 carbon PUFA from their fatty acids 18 (alpha linolenic acid) carbon dietary precursors. This normally takes place principally in the liver.

Long chain omega-3 fatty acids have been proven to decrease the LDL cholesterol (low density lipoprotein), serum triglycerides, platelet aggregability, blood viscosity, hypertension, glycerolipid synthesis, and reduce the fatty droplet deposit to the liver. These fatty acids have also been shown to improve the insulin resistance, liver function, and enhance red cell deformability. In addition, they alter the cellular membrane phospholipids omega-3 fatty acid concentration, which increases the cellular metabolic rate as well as cellular functions. Therefore, directly and indirectly omega-3 long chain polyunsaturated fatty acids improves the general condition of the liver and can effectively treat or even prevent the occurrence of fatty liver. Because fatty liver is a malfunction of the liver as well as a disturbance of metabolism of fat, protein and carbohydrates overeating and overindulgence of alcohol should be eliminated.

+Kidney Disease

Kidney Disease

A newly reported clinical trial has strengthened the argument for recommending daily treatment with omega-3 polyunsaturated fatty acids in patients with immunoglobulin A nephropathy (the most common form of primary glomerulonephritis in the world) who are at high risk for progression of renal disease. Studies are underway that involve a combination of cyclosporine A, a commonly prescribed immunosuppressive agent in solid-organ transplantation, with a high-potency omega-3 polyunsaturated fatty acid to reduce cyclosporine toxicity. Studies reported during the past year show promise that dietary supplementation with omega-3 polyunsaturated fatty acids will substantially decrease vascular access graft thrombosis in patients receiving maintenance hemodialysis and may reduce hypercalciuria in patients who suffer from kidney stones.

+Ligament Injuries

Ligament Injuries

Ligaments are tough bands of fibrous connective tissue (mainly collagen) that link two bones together at a joint. Injuries to ligaments are notoriously slow to heal. Researchers at Purdue University now report the results of an intriguing experiment which shows that eicosapentaenoic acid speeds up the healing of "wounded" ligament cells in vitro. The researchers conclude that dietary supplements with marine oils (omega-3 polyunsaturated fatty acids) could be used to improve the healing of ligament injuries by enhancing the entry of new cells into the wound area by speeding up collagen synthesis.

+Multiple Sclerosis

Multiple Sclerosis

Multiple Sclerosis (MS) is a disease which leaves the patient in an unresponsive body but with mental functions intact. With MS, the insulating membrane that coats the nerve cells unravels, making it difficult for the nerve cells to transmit their signals. Although the molecular cause of multiple sclerosis is unknown, scientists have learned that it is primarily driven by inflammation.

MS is virtually unknown amongst the Eskimos of Greenland. Their high intake of long chain omega-3 fatty acids provides a clue to the prevention and treatment of this condition. Like all inflammatory conditions, multiple sclerosis is characterized by overproduction of ‘bad’ eicosanoids.

Long chain omega-3 fatty acids are anti-inflammatory agents that can cross the blood-brain barrier. Patients with MS are known to have low levels of DHA in the brain. It is also known that long chain omega-3 fatty acids inhibit the production of pro-inflammatory cytokines like gamma interferon, similar effects that are behind the theory of constant injections with beta-interferon. This may explain why populations that consume the most fish have the lowest rates of MS.

+Obesity

Obesity

Increased metabolism

The right kind of fat can help you lose weight. Because omega-3 fatty acids can increase metabolic rates, they are often beneficial for weight loss. The excess weight of some overweight people is largely retained water (edema). Omega-3 fatty acids serve as building materials for series 3 prostaglandin, some of which help the kidneys get rid of excess water held in tissues.

Omega-3 fatty acids increase metabolic rate, oxidation rate and energy production. This effect begins to show up when three or more tablespoons of omega-3 fatty acids per day are used. When metabolic rate goes up, more fat and glucose are burned and less fat deposition takes place. This increased production of energy is the opposite of what happens when we fast or diet on calorie-restricted programs. Fasting and calorie reduction decrease our metabolic rate and lead us to put on weight even on a small intake of food. There is evidence that obesity is the result of gross overeating in only 10% of cases. The other 90% are lacking exercise and choosing foods lacking important essential nutrients.

Because omega-3 fatty acids increase energy, they aid in weight loss by helping people feel like being more active. This induces a positive cycle because activity makes us feel good, builds lean body (muscle) mass, makes us healthier, increases our metabolic rate and resets our fat thermostat to a lover level, helping make weight loss permanent.

Blood sugar control and lower cholesterol

Many people who are overweight suffer from poor blood sugar control, diabetes, and high cholesterol. Studies suggest that overweight people who make omega-3 fatty acids a staple in their low fat diet tend to achieve better control over their blood sugar and cholesterol levels when they follow a weight loss program that includes exercise.

The mucilage in flax aids in controlling the blood sugar levels by lining the digestive tract. This slows absorption of carbohydrates which can otherwise be processed too quickly, flooding the bloodstream in excess. When they are absorbed slowly through a healthy lined digestive tract they are treated the same as a good carbohydrates, leaving no residue or sugar over-doses. Flax can also function as an appetite suppressant.

+Varicose Veins and Raynaud's Disease

Varicose Veins and Raynaud’s Disease

Circulatory problems such as varicose veins and Raynaud's disease benefit from omega-3 supplementation. Omega-3 fatty acids stimulate blood circulation and increase the breakdown of fibrin, a compound involved in clot and scar formation.

Raynaud's phenomenon is characterized by periods of disrupted blood flow in the fingers caused by exposure to cold or stress. The condition is relieved by warming the affected parts. It is estimated that about 4% of the US Population suffers from the primary form of this phenomenon, the so-called Raynaud's disease. Secondary Raynaud's phenomenon occurs in association with connective tissue disease (progressive systemic sclerosis). Researcher at Albany Medical College now report that supplementation with marine oils significantly reduces the symptoms of Raynaud's disease (primary Raynaud's Phenomenon) but has no beneficial effects in Secondary Raynaud's Phenomenon.

+Omega-3 EFAs: Respiratory Conditions and Diseases

+Asthma

Asthma

Anyone who struggles with asthma is all too familiar with the breathlessness, wheezing and coughing brought on by an attack. Since these aversive symptoms appear to be caused largely by leukotrienes, the search is on for remedies that will antagonize leukotriene synthesis.

Preliminary research suggests that omega-3 fatty acid supplements may decrease inflammation and improve lung function in adults with asthma. Omega-6 fatty acids have the opposite effect: they tend to increase inflammation and worsen respiratory function. In a small, well-designed study of 29 children with asthma, those who took fish oil supplements rich in EPA and DHA for 10 months had improvement in their symptoms compared to children who took a placebo pill.

In one study, large doses of marine oil brought about the formation of less aggravating leukotrienes in asthmatics. But Walter C. Pickett, Ph.D., senior research biochemist at Lederle Laboratories in New York, who was involved in this research, notes that it is not yet known whether the change in leukotrienes helps alleviate asthma symptoms. One expert speculates that Eskimos may have a low incidence of asthma because they have hefty amounts of omega-3 fatty acids in their diets continuously from birth. Possibly, marine oils have an impact in the early stages of asthma - before asthmatics are sensitized to substances that bring on attacks. Dr. Pickett agrees it is conceivable that eating fair amounts of fish starting early in life may influence the later development of asthma.

+Cystic Fibrosis

Cystic Fibrosis

Seriously ill Cystic Fibrosis (CF) patients cannot absorb fats and other nutrients properly and therefore often need infusions of essential fatty acids. These infusions are most often based on linoleic acid as many CF patients have been found to have a deficiency in this omega-6 fatty acid. There is now substantial evidence that long-chain omega-3 fatty acids found in fish oils can suppress inflammatory processes such as those involved in CF.

A team of American, Finnish and German researchers completed a small clinical trial aimed at determining if it would be safe and effective to use a fish oil fortified emulsion in the intravenous feeding of CF patients. The trial involved 12 patients; 6 patients were given infusions of a lipid emulsion enriched with fish oils while the remaining 6 (control group) were given infusions of the standard linoleic acid-based emulsion. The fish oil emulsion contained 18.3% eicosapentaenoic acid (EPA), 27.6% docosahexaenoic acid (DHA), 12.7% oleic acid, and 2.5% linoleic acid. The standard emulsion contained 54.5% linoleic acid, 22.4% oleic acid, and 0% EPA and DHA. Both emulsions were administered daily (over a 4-hour period) for 1 month at a dose of 150 mg/kg of body weight.

The researchers found no adverse effects on liver function or coagulation parameters and no toxic or allergic reactions in the patients receiving the fish oil emulsion. There was a tendency for improved lung function in the fish oil group and a tendency towards a worsening in the control group during the trial; however, these effects were not statistically significant. The researchers conclude that intravenous infusions of lipid emulsions containing fish oils are safe for CF patients. They urge additional, longer-term studies to determine if such infusions would be of clinical benefit.

+Omega-3 EFAs: Skin Conditions and Diseases

+Acne

Acne

Many people who begin to use better edible oils are amazed at the difference in their skin. They find that their skin feels creamy, supple, soft, and pleasant to the touch. Hard skin, greasy pores, zits, bumps and acne disappear. These are the most obvious changes that many people notice on using good oils along with balanced nutrition. They also get an enhanced feeling of well-being.

In addition, many clinicians believe that flaxseed (which contains the omega-3 fatty acid ALA) is helpful for treating acne. The fatty acids present in flax seed help to prevent the clogging of pores in the skin and thin the sebum which causes these clogged pores.

+Aging

Aging

No one wants to look older than his or her age. But skin with premature sags and wrinkles ultimately does look older. The skin is actually the largest organ in the body and has a critical role to play: providing a barrier against a hostile environment that includes bacteria, fungi, and perpetual oxidation caused by the sun. Furthermore, aging is an important factor in the appearance of autoimmune disease. The immune system may be suppressed or weakened as a result of factors such as alcohol, caffeine, tobacco, drugs, sugars, poor diet and lack of sleep.

The visual appearance of the skin provides a window into the internal state of the body. Typically, when the skin looks good, the body feels strong and healthy. When the skin has a rosy glow, there is good blood circulation within the skin and probably through the rest of the body. In contrast, a pallor to your skin is often a portent of impending illness, which is indicative of poor blood flow.

One unmistakable sign of aging is the formation of wrinkles. Scientifically speaking, wrinkles are caused by the cross-linking of collagen fibers in the skin, and the cross-linking can be accelerated by inflammation caused by the constant exposure to the sun. The most effective way to reduce wrinkle formation (other that staying completely out of the sun) is to reduce Arachidonic acid (omega-6) levels in the skin, thus decreasing the potential for the production of pro-inflammatory “bad” eicosanoids (PGE2 series).

An even more powerful approach to preventing wrinkles is to increase the levels of "good" eicosanoids (PGE3 series) by increasing the intake of omega-3 fatty acids. Due to their powerful anti-inflammatory actions, these good eicosanoids will do far more to reduce the inflammatory process that leads to wrinkles, than all the fruit acids and vitamin E creams on the market. This is because ‘good’ eicosanoids are both very powerful vasodilators which increase blood flow to make skin healthier. Increased blood, therefore, increases production of the key structural proteins of the skin-collagen and elastin during the aging process. These structural proteins give skin its firmness and elasticity. As the production of collagen and elastin decreases with age, the skin begins to droop and sag. To keep collagen and elastin at increasing levels, it is necessary to increase blood flow to the skin to stimulate the enzymes that produce these structural proteins. With improved blood flow and decreased inflammation, skin will look years younger.

+Atopy Dermatitis

Atopy Dermatitis

An atopic disease is a form of allergy where the hypersensitivity reaction occurs at a location different from the initial contact point between the body and the offending agent (allergen). For example, food taken by mouth may cause an allergic skin reaction - atopic dermatitis. The incidence of atopic diseases such as dermatitis, allergic rhinitis, and asthma is rising in industrialized countries and now affects about 20% of the population.

A team of researchers from the University of Turku and Tufts University in Boston now report that the increase in atopic diseases is closely tied in with an increase in the consumption of omega-6 fatty acids (linoleic acid) which have pushed the ratio of omega-6 to omega-3 (alpha-linolenic, eicosapentaenoic, and docosahexaenoic acids) fatty acids in the diet to an unfavorably high level (10:1 or higher). An increasing dietary intake of linoleic acid has been linked to a rise in atopic diseases in both Germany and Japan. A recent study of Finnish and Swedish school children found that children with a high ratio of eicosapentaenoic acid to linoleic acid had a lower prevalence of atopic diseases while children with allergies tended to have a lower level of docosahexaenoic acid in their blood.

The researchers point out that the metabolic products (Eicosanoids) of omega-6 fatty acids promote inflammation while the metabolites of omega-3 fatty acids dampen inflammation. They also point to several clinical trials, which have shown that supplementation with fish oil or alpha-linolenic acid can reduce the symptoms of atopic dermatitis and asthma. They conclude that an increased intake of omega-3 fatty acids may alleviate atopic diseases caused by an excessive intake of omega-6 fatty acids.

+Eczema

Eczema

Skin disease, especially conditions that cause dry scaly skin like eczema, often result from excessive levels of "bad" eicosanoids (omega-6 PGE 2 series). While eczema is not life threatening, it is a cause of concern because it indicates that a significant inflammatory process is already taking place in the skin.

Research shows eczema stems from the overproduction of "bad" eicosanoids called leukotrienes. Reducing arachidonic acid levels by using high dose marine oil chokes off the production of leukotrienes, while simultaneously increasing the levels of "good" eicosanoids.

Dermatologists usually prescribe corticosteroid creams to reduce inflammation, but these drugs unfortunately knock out "‘good and bad" eicosanoids, which leads to a thinning of the skin. Various studies have indicated that high dose marine oil, without the use of corticosteroid, can contribute to some improvement in eczema.

+Photodermatitis

Photodermatitis

In one study, 13 people with a particular sensitivity to the sun known as photodermatitis showed significantly less sensitivity to UV rays after taking fish oil supplements. Still, research indicates that topical sunscreens are much better at protecting the skin from damaging effects of the sun than omega-3 fatty acids.

+Psoriasis

Psoriasis

Psoriasis is a fairly common skin disease characterized by thick, silvery white scales surrounded by a red, inflamed border. Psoriasis is accompanied by high concentrations of arachidonic acid in the plaques and profound changes in the metabolism of eicosanoids leading to an increase in proinflammatory agents. It is known that eicosapentaenoic acid (EPA) counteracts the formation of these proinflammatory agents and some studies have shown that oral supplementation with fish oils benefits psoriasis patients.

A team of researchers from Austria, the Czech Republic, the Slovak Republic, Germany, and Poland now report that intravenous infusions of a fish oil emulsion is quite effective in ameliorating the symptoms of chronic plaque-type psoriasis. Their double-blind, randomized, placebo-controlled, multicenter trial involved 54 men and 29 women between the ages of 18 and 80 years who had been hospitalized with severe psoriasis. The patients were randomized into two groups. Group 1 (43 patients) received twice daily infusions of a fish oil emulsion (100 ml of a 10% emulsion infused over a period of 90 minutes) while group 2 (40 patients) received twice daily infusions of a placebo emulsion based on linoleic acid.

Physicians assessed the severity of the psoriasis on days 0, 4, 7, 11 and 15 of the two-week trial. Sixteen of the 43 patients (37%) receiving fish oil showed at least a 50% improvement in their condition at the end of the trial as compared to 9 out of 40 patients (23%) in the placebo group.

+Omega-3 EFAs: Vision Related Conditions and Diseases

+Macular Degeneration

Macular Degeneration

Age-related macular degeneration (AMD) is a leading cause of blindness for which treatment options are limited. The macula is responsible for detailed, fine central vision and is located at the center of the retina. Researchers at the Harvard Medical School have just released a major study that points to a close association between the development of AMD and the consumption of certain fats. The major contributors to the increased risk were high intake of linolenic acid and trans fatty acids with a 35% increased risk of AMD. In contrast, a high intake of docsahexaenoic acid (DHA), a main component of marine oils was found to lower the risk of AMD by about 30%.

A questionnaire administered to more than 3,000 people over the age of 49 found that those who consumed more fish in their diet were less likely to have macular degeneration than those who consumed less fish. Similarly, a study comparing 350 people with macular degeneration to 500 without found that those with a healthy dietary balance of omega-3 and omega-6 fatty acids and higher intake of fish in their diets were less likely to have this particular eye disorder. Another larger study confirms that EPA and DHA from fish, four or more times per week, may reduce the risk of developing macular degeneration. Notably, however, this same study suggests that ALA may actually increase the risk of this eye condition.

+Vision Disorder

Vision Disorder

Dr. Barbara Levine, Professor of Nutrition in Medicine at Cornell University, sounds the alarm concerning a totally inadequate intake of DHA (docosahexaenoic acid) by most Americans. DHA is the building block of human brain tissue and is particularly abundant in the grey matter of the brain and the retina. Low levels of DHA have recently been associated with depression, memory loss, dementia, and vision problems. DHA is particularly important for fetuses and infants; the DHA content of the infant's brain triples during the first three months of life.

Optimal levels of DHA are therefore crucial for pregnant and lactating mothers. Unfortunately, the average DHA content of breast milk in the United States is the lowest in the world, most likely because Americans eat comparatively little fish. Making matters worse is the fact that the United States is the only country in the world where most infant formulas are not fortified with DHA. This despite a 1995 recommendation by the World Health Organization that all baby formulas should provide 40 mg of DHA per kilogram of infant body weight.

Dr. Levine believes that postpartum depression, attention deficit hyperactivity disorder (ADHD), and low IQs are all linked to the dismally low DHA intake common in the United States. Dr. Levine also points out that low DHA levels have been linked to low brain serotonin levels which again are connected to an increased tendency to depression, suicide, and violence. DHA is abundant in marine phytoplankton and cold-water fish and nutritionists now recommend that people consume two to three servings of fish every week to maintain DHA levels. If this is not possible, Dr. Levine suggests supplementing with 100 mg/day of DHA.

+Omega-3 EFAs: Women’s Issues

+Dysmenorrhea, Menstrual Pain and Menopause

Issues Related to Menstruation

Dysmenorrhea

Fish oil supplements, particularly if they also include Vitamin B12, can alleviate menstrual discomfort in young women. Menstrual pain is generally attributed to prostaglandins (PG), hence the efficiency of NSAIDS, which inhibits their synthesis. However the PG’s most likely to blame are those derived from omega-6 LC PUFA, rather than those of the omega-3 series, which are less biologically active. Indeed there is evidence that levels of dietary omega-3 LC PUFA are lower in women with dysmenorrhea.

Fish oil plus vitamin B12 should be superior to fish oil alone. It is possible vitamin B12 is involved in the prostaglandin metabolism or has antioxidant effects. They conclude that the supplementations with omega-3 LC PUFA and vitamin B12 may serve as an alternate treatment to NSAID medication against dysmenorrhea in young women because the combination appears to be without adverse effects and is easily administered.

Menstrual Pain

In a study of nearly 200 Danish women, those with the highest dietary intake of omega-3 fatty acids had the mildest symptoms during menstruation. Premenstrual symptoms such as pain, cramps and bloating are often alleviated with omega-3 supplementation. Omega-3 fatty acids are converted into hormone-like substances (type 3 prostaglandins, or PGE3), which help to control contractions of the uterus.

Menopause

During menopause, ovarian function begins to decline, reducing the body’s production of estrogen by about 60% (adrenal glands and fat cells make the remaining amount). During this time of rapid hormonal changes, the body’s eicosanoids balance gets thrown off, giving rise to hot flashes and other discomforts. New evidence suggests that hot flashes may stem from rapidly changing levels of eicosanoids and may be due in part to overproduction of the ‘bad’ eicosanoids PGE 2 series. One reason may be that the plunge in estrogen levels during menopause also leads to a corresponding increase in the production of insulin.

The increase in insulin leads to increased production of Arachidonic acid, the building block of ‘bad’ eicosanoids such as the PGE 2 series. High dose of marine oil (omega-3 fatty acid) will reduce the production of eicosanoids by lowering the level of Arachidonic acid.

Moreover, Japanese and Chinese women who consume large amounts of seafood and soy rarely suffer from hot flashes. Researchers have found that eating 20g of soy protein (which is rich in a chemical called phytoestrogens) per day provides a modest decrease in the variety of menopausal symptoms. However, phytoestrogens are not the cure-all that they were hoped to be because without adequate levels of long chain omega-3 fatty acids, there would not be the full inhibition of excess PGE 2 series production.

+Osteoporosis

Osteoporosis

Studies suggest that omega-3 fatty acids such as EPA help increase levels of calcium in the body, deposit calcium in the bones and improve bone strength.

In addition, studies also suggest that people who are deficient in certain essential fatty acids (particularly EPA and gamma-linolenic acid [GLA], an omega-6 fatty acid) are more likely to suffer from bone loss than those with normal levels of these fatty acids. In a study of women over 65 with osteoporosis, those given EPA and GLA supplements experienced significantly less bone loss over three years than those who were given a placebo. Many of these women also experienced an increase in bone density.

+Pre-eclampsia and Pregnancy

Pre-Eclampsia and Pregnancy

Pre-Eclampsia

During pregnancy, blood lipids, triglycerides and cholesterol may increase several fold. There may also be an increase in blood pressure. The risk of developing pre-eclampsia and subsequent premature birth is increased if these otherwise normal changes are increased above certain levels. Severe forms of pregnancy-induced hypertension have been reported to be beneficially modulated by omega-3 fatty acids (Secher et al, 1991). In light of their very strong hypotriglyceridemic and hypotensive effects, omega-3 fatty acids along with other nutritional factors may be significant for the prevention of pre-eclampsia. The maternal blood pressure responses depend on the ARA/EPA ratio in the vessel wall. It would generally seem prudent to recommend an increased intake of omega-3 fatty acids during pregnancy. EPA will benefit the mother's heart and circulation and DHA will definitely be good for the development of fetal brain and nervous system.

Recent studies have demonstrated that DHA supplementation during pregnancy and lactation is necessary to prevent deficiency of the mother's DHA status during these periods and to meet the high fetal requirement for DHA. It has been shown that premature babies have lower levels of DHA in their tissues as compared to full-term babies. Thus, supplementation of infant formula with DHA/marine oils may be necessary to provide them with as much DHA as is available to their breast-fed counterparts. Feeding infants with formula devoid of omega-3 fatty acids resulted in lack of deposition of DHA in their visual and neural tissues with adverse effects on vision and nervous systems. According to Dr. Connor,

"The signs of omega-3 deficiency in infancy are subtle, for example, omega-3 fatty acid deficiency in infants can translate into

· impaired vision
· abnormalities on the electroretinogram - which measures retinal nerve function
· behavioral changes such as polydypsia (excessive thirst), hyperactivity and perhaps less cognitive ability.

“Some of these changes have been described only in subhuman primates. So it is clearly essential for pregnant and breast feeding women to ensure their dietary intake of omega-3 PUFA is adequate."

Pregnancy

According to Crawford (1995), the first pregnancy-related need for PUFAs (both omega-6 and omega-3) occurs during the three months prior to conception. This critical period for cell commitment and division requires ARA and DHA to facilitate growth and development. It has been suggested that supplementation with fish oil, or increased fish intake, during pregnancy prevents the pregnancy-induced hypertension, prolongs gestation, increases birth weight and reduces the incidence of premature birth (Gerrard et al, 1991, Olsen et al, 1992). Recent data support the view that the intake of DHA during pregnancy should be in the amount of at least 0.1-0.4 g/day (Crawford, 1995).

Research Abstract: Relationship between omega3 long-chain polyunsaturated fatty acid status during early infancy and neurodevelopmental status at 1 year of age Voigt RG, Jensen CL, Fraley JK, Rozelle JC, Brown FR 3rd, Heird WC. J Hum Nutr Diet. 2002 Apr;15(2):111-20

OBJECTIVE: To determine the influence of alpha-linolenic acid (ALA; 18 : 3omega3) intake and, hence, the influence of plasma and/or erythrocyte phospholipid content of docosahexaenoic acid (DHA; 22 : 6omega3) during early infancy on neurodevelopmental outcome of term infants. METHODS: The Bayley Scales of Infant Development (second edition), the Clinical Adaptive Test/Clinical Linguistic and Auditory Milestone Scale (CAT/CLAMS) and the Gross Motor Scale of the Revised Gesell Developmental Inventory were administered at a mean age of 12.26 +/- 0.94 months to 44 normal term infants enrolled in a study evaluating the effects of infant formulas differing only in ALA content (0.4, 1.0, 1.7 and 3.2% of total fatty acids). RESULTS: As reported previously [Jensen et al., Lipids 13 (1996) 107; J. Pediatr. 131 (1997) 200], the group fed the formula with the lowest ALA content had the lowest mean plasma and erythrocyte phospholipid DHA contents at 4 months of age. This group also had the lowest mean score on every neurodevelopmental measure. The difference in mean gross motor developmental quotient of this group versus the group fed the formula with 1.0% ALA but not of the other groups was statistically significant (P < 0.05). Across the groups, motor indices correlated positively with each other and with the plasma phospholipid DHA content at 4 months of age (P=0.02-0.03). The CLAMS developmental quotient correlated with the erythrocyte phospholipid content of 20 : 5omega3 (P < 0.01) but not with DHA. CONCLUSIONS: These statistically significant correlations suggest that the omega3 fatty acid status during early infancy may be important with respect to neurodevelopmental status at 1 year of age and highlight the need for further studies of this possibility.

Fetal stage

DHA is important for optimal nervous system development. During the last trimester of pregnancy, when the fetal demand for neural and vascular growth are greatest, there is an elevated accretion of DHA in the liver and brain of the fetus. A maternal diet high in DHA will greatly enrich the DHA concentration in the blood of the newborn infant. Even levels as low as 0.7g EPA+DHA/day during the period from 25th to 35th week of pregnancy seem to be beneficial (Connor et al, 1995). DHA levels in maternal plasma are lower in multigravidae compared to primigravidae and the smaller the baby, the lower DHA level (Al et al, 1995). Consequently, it is therefore especially important for multigravidae to increase the intake of DHA.

Prevention of allergies in children

Studies have demonstrated that omega-3 fatty acid intake by prospective mothers during pregnancy may protect their babies against the development of allergies. Omega-3 fatty acids have been found to protect against symptoms of hay fever, sinus infections, asthma, food allergies, as well as allergic skin conditions such as hives and eczema.

+The FDA and Omega-3

+The FDA's Qualified Health Claim for Omega-3

FDA Announces Qualified Health Claims for Omega-3 Fatty Acids

The Food and Drug Administration (FDA) today [September 8, 2004] announced the availability of a qualified health claim for reduced risk of coronary heart disease (CHD) on conventional foods that contain eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) omega-3 fatty acids.

Typically, EPA and DHA omega-3 fatty acids are contained in oily fish, such as salmon, lake trout, tuna and herring. These fatty acids are not essential to the diet; however, scientific evidence indicates that these fatty acids may be beneficial in reducing CHD.

"Coronary heart disease is a significant health problem that causes 500,000 deaths annually in the United States," said Dr. Lester M. Crawford, Acting FDA Commissioner. "This new qualified health claim for omega-3 fatty acids should help consumers as they work to improve their health by identifying foods that contain these important compounds."

A qualified health claim on a conventional food must be supported by credible scientific evidence. Based on a systematic evaluation of the available scientific data, as outlined in FDA's "Interim Procedures for Qualified Health Claims in the Labeling of Conventional Human Food and Human Dietary Supplements", FDA is announcing a qualified health claim for EPA and DHA omega-3 fatty acids. While this research is not conclusive, the FDA intends to exercise its enforcement discretion with respect to the following qualified health claim:

"Supportive but not conclusive research shows that consumption of EPA and DHA omega-3 fatty acids may reduce the risk of coronary heart disease. One serving of [name of food] provides [x] grams of EPA and DHA omega-3 fatty acids. [See nutrition information for total fat, saturated fat and cholesterol content.]

In 2000, FDA announced a similar qualified health claim for dietary supplements containing EPA and DHA omega-3 fatty acids and the reduced risk of CHD. FDA recommends that consumers not exceed more than a total of 3 grams per day of EPA and DHA omega-3 fatty acids, with no more than 2 grams per day from a dietary supplement.

The EPA and DHA omega-3 fatty acid qualified health claim is the second qualified health claim that FDA has announced for conventional food. For additional information about FDA qualified health claims visit: http://www.cfsan.fda.gov/~dms/lab-qhc.html.

+Additional Resources and Articles

+Omega-3 Fatty Acids and Antioxidants in Edible Wild Plants
    Artemis P Simopoulos, The Center for Genetics, Nutrition and Health, Washington, DC

Omega-3 Fatty Acids and Antioxidants in Edible Wild Plants
Artemis P Simopoulos, The Center for Genetics, Nutrition and Health, Washington, DC, USA

Abstract

Human beings evolved on a diet that was balanced in the omega-6 and omega-3 polyunsaturated fatty acids (PUFA), and was high in antioxidants. Edible wild plants provide alpha-linolenic acid (ALA) and higher amounts of vitamin E and vitamin C than cultivated plants. In addition to the antioxidant vitamins, edible wild plants are rich in phenols and other compounds that increase their antioxidant capacity. It is therefore important to systematically analyze the total antioxidant capacity of wild plants and promote their commercialization in both developed and developing countries. The diets of Western countries have contained increasingly larger amounts of linoleic acid (LA), which has been promoted for its cholesterol-lowering effect. It is now recognized that dietary LA favors oxidative modification of low density lipoprotein (LDL) cholesterol and increases platelet response to aggregation. In contrast, ALA intake is associated with inhibitory effects on the clotting activity of platelets, on their response to thrombin, and on the regulation of arachidonic acid (AA) metabolism. In clinical studies, ALA contributed to lowering of blood pressure, and a prospective epidemiological study showed that ALA is inversely related to the risk of coronary heart disease in men. Dietary amounts of LA as well as the ratio of LA to ALA appear to be important for the metabolism of ALA to longer-chain omega-3 PUFAs. Relatively large reserves of LA in body fat, as are found in vegans or in the diet of omnivores in Western societies, would tend to slow down the formation of long-chain omega-3 fatty acids from ALA. Therefore, the role of ALA in human nutrition becomes important in terms of long-term dietary intake. One advantage of the consumption of ALA over omega-3 fatty acids from fish is that the problem of insufficient vitamin E intake does not exist with high intake of ALA from plant sources.

Key words: Alpha-linolenic acid, antioxidants, chronic diseases, edible wild plants, evolutionary aspects of diet, omega-3 fatty acids.

Abbreviations: AA: arachidonic acid; AI: Adequate Intake; ALA: alpha-linolenic acid; ARP: antiradical power; DHA: docosahexaenoic acid; DPPH•: 2,2-diphenyl-1-picrylhydrazyl; FRAP: ferric-reducing ability of plasma; LA: linoleic acid; LDL: low density lipoprotein; EPA: eicosapentaenoic acid; ORAC: oxygen radical absorbance assay; PUFA: polyunsaturated fatty acids.

Introduction

In nutritional terms, human physiology evolved in the context of wild plants and animals in the wild. Most likely, human beings made use of both aquatic and terrestrial foods. Over the past 20 years, many studies and clinical investigations have been carried out on the metabolism of polyunsaturated fatty acids (PUFAs) in general and on omega-3 fatty acids in particular. Today we know that omega-3 fatty acids are essential for normal growth and development and may play an important role in the prevention and treatment of coronary artery disease, hypertension, diabetes, arthritis, other inflammatory and autoimmune disorders, and cancer1- 10. Research has been carried out in animal models, tissue cultures, and human beings. The original observational studies have given way to controlled clinical trials. Great progress has taken place in our knowledge of the physiologic and molecular mechanisms of the various fatty acids in health and disease. Specifically, their beneficial effects have been shown in the prevention and management of coronary heart disease11-14, hypertension15-17, type 2 diabetes18,19, renal disease20,21, rheumatoid arthritis22, ulcerative colitis23, Crohn's disease24, and chronic obstructive pulmonary disease25. Epidemiologic studies indicate that fruits and vegetables decrease the risk of chronic diseases, including cancer, cardiovascular and cerebrovascular disease. This protection has been attributed to the various antioxidants contained in them26-29.

Oxidative damage, as a result of normal metabolism or secondary to environmental pollutants, leads to free radical formation which has been considered to play a central role in cancer and atherosclerosis. Therefore, antioxidants, which can neutralize free radicals, may be important in the prevention of these diseases. However, results from intervention trials with single compounds such as vitamins E and C or beta-carotene have not supported any protective effect30-36. In fact, supplementation with beta-carotene resulted in adverse disease outcomes in clinical trials37-40. One reason for the ineffective clinical trials may be the fact that the protective effects of fruits and vegetables most likely result from the action of lesser known antioxidant compounds, or from a mixture of antioxidants present in foods. Thus, a number of dietary antioxidants, such as flavonoids, carotenoids, polyphenols and sulfides, etc., are bioactive and work synergistically as do vitamin C and vitamin E. This hypothesis led to the thinking that the total amount of electron-donating antioxidants in the diet, derived from a combination of various antioxidants occurring naturally in foods, need to be determined. A number of methods have been used to assess the total antioxidant capacity of dietary plants41-43. This paper focuses on omega-3 fatty acids and antioxidants in edible wild plants.

Evolutionary Aspects of Diet

On the basis of estimates from studies in Paleolithic nutrition and modern-day hunter-gatherer populations, it appears that human beings evolved consuming a diet that was much lower in saturated fatty acids than is today's diet44. Furthermore, the diet contained small and roughly equal amounts of omega-6 and omega-3 PUFAs (ratio of 1-2:1) and much lower amounts of trans fatty acids than does today's diet (Fig. 1)45,46 Wild plants contributed higher amounts of vitamin E, vitamin C and other antioxidants than cultivated plants, providing additional protection against cancer and atherosclerosis7.

The current Western diet is very high in omega-6 fatty acids (the ratio of omega-6 to omega-3 fatty acids is 10-20:1) because of the indiscriminate recommendation to substitute omega-6 fatty acids for saturated fats to lower serum cholesterol concentrations48. Table I compares the omega-6: omega-3 intake of various populations49,53. The population of Crete obtained a higher intake of alpha-linolenic acid (ALA) from purslane and other wild plants, walnuts and figs, whereas the Japanese obtained it from canola oil and soybean oil49.

Intake of omega-3 fatty acids is much lower today because of the decrease in fish consumption and the industrial production of animal feeds rich in grains containing omega-6 fatty acids, leading to production of meat rich in omega-6 and poor in omega-3 fatty acids54. The same is true for cultured fish55 and eggs56. Even cultivated vegetables contain fewer omega-3 fatty acids than do plants in the wild57,58. In summary, modern agriculture, with its emphasis on production, has decreased the omega-3 fatty acid content in many foods: green leafy vegetables, animal meats, eggs, and even fish. Although RDAs do not officially exist, the Adequate Intake (AI) of essential fatty acids has been established59 as well as the ratio of 18:2É6 to 18:3É360.

Effects of Dietary ALA Compared with Long-Chain Omega-3 Fatty Acid Derivatives on Physiologic Indexes

Several clinical and epidemiologic studies have been conducted to determine the effects of long-chain omega-3 PUFAs on various physiologic indexes7. Whereas the earlier studies were conducted with large doses of fish or fish-oil concentrates, more recent studies have used lower doses14. ALA, the precursor of omega-3 fatty acids, can be converted to long-chain omega-3 PUFAs and can therefore be substituted for fish oils. The minimum intake of long-chain omega-3 PUFAs needed for beneficial effects depends on the intake of other fatty acids. Dietary amounts of linoleic acid (LA) as well as the ratio of LA to ALA appear to be important for the metabolism of ALA to long-chain omega-3 PUFAs. Indu and Ghafoorunissa61 showed that while keeping the amount of dietary LA constant, 3.7 g ALA appears to have biological effects similar to those of 0.3 g long-chain omega-3 PUFA with conversion of 11 g ALA to 1 g long-chain omega-3 PUFA. Thus, a ratio of 4 (15 g LA: 3.7 g ALA) is appropriate for conversion. This ratio is also consistent with the Lyon Heart Study12. In human studies, Emken et al.62 showed that the conversion of deuterated ALA to longer-chain metabolites was reduced by ~50 % when dietary intake of LA was increased from 4.7% to 9.3% of energy as a result of the known competition between omega-6 and omega-3 fatty acids for desaturation.

TABLE I: Omega-6:omega-3 ratios in various populations
Population	omega-6:omega-3	Reference
Paleolithic	0.79	50
Greece prior to 1960	1.00 - 2.0	51
Current US	16.74	50
Current UK and Northern Europe	15.00	52
Current Japan	4.00	53

Indu and Ghafoorunissa61 further indicated that increasing dietary ALA increases eicosapentaenoic acid (EPA) concentrations in plasma phospholipids after both 3 and 6 wk of intervention. Dihomo-³-linolenic acid (20:3É6) concentrations were reduced but arachidonic acid (AA) concentrations were not altered. The reduction in the ratio of long-chain omega-6 PUFAs to long-chain omega-3 PUFAs was greater after 6 wk than after 3 wk. Indu and Ghafoorunissa were able to show antithrombotic effects by reducing the ratio of omega-6 to omega-3 fatty acids with ALA-rich vegetable oil. After ALA supplementation there was an increase in long-chain omega-3 PUFA in plasma and platelet phospholipids and a decrease in platelet aggregation. ALA supplementation did not alter triacylglycerol concentrations. As shown by others, only omega-3 long-chain PUFAs have triacylglycerol-lowering effects63.

In Australian studies, ventricular fibrillation in rats was reduced with canola oil as much or even more efficiently than with fish oil, an effect attributable to ALA64. Further studies should be able to show whether this result is a direct effect of ALA per se or occurs as a result of its desaturation and elongation to EPA and docosahexaenoic acid (DHA).

The diets of Western countries have contained increasingly larger amounts of LA, which has been promoted for its cholesterol-lowering effect. It is now recognized that dietary LA favors oxidative modification of LDL cholesterol65,66, and increases platelet response to aggregation67. In contrast, ALA intake is associated with inhibitory effects on the clotting activity of platelets, on their response to thrombin68,69, and on the regulation of AA metabolism70. In clinical studies, ALA contributed to lowering of blood pressure71. In a prospective epidemiological study, Ascherio et al.72 showed that ALA is inversely related to the risk of coronary heart disease in men.

ALA is not equivalent in its biological effects to the long-chain omega-3 fatty acids found in marine oils. EPA and DHA are more rapidly incorporated into plasma and membrane lipids and produce more rapid effects than does ALA. Relatively large reserves of LA in body fat, as are found in vegans or in the diet of omnivores in Western societies, would tend to slow down the formation of long-chain omega-3 fatty acids from ALA. Therefore, the role of ALA in human nutrition becomes important in terms of long-term dietary intake. One advantage of the consumption of ALA over omega-3 fatty acids from fish is that the problem of insufficient vitamin E intake does not exist with high intake of ALA from plant sources.

Edible Wild Plants as a Source of Alpha-Linolenic Acid

In view of the fact that a number of studies indicate that 18:3É3 (ALA) is converted to EPA and DHA in human beings, it is important to consider terrestrial sources of omega-3 fatty acids in the food supply. ALA, the precursor to EPA and DHA, was first isolated from hempseed oil in 188773. In plants, leaf lipids usually contain large proportions of 18:3É3, which is an important component of chloroplast membrane polar lipids. Mammals who feed on these plants convert 18:3É3 to EPA and DHA, the long-chain omega-3 fatty acids found in fish.

Wild animals and birds who feed on wild plants are very lean with a carcass fat content of only 3.9%74 and contain about five times more polyunsaturated fat per gram than is found in domestic livestock54,75. Most importantly, 4% of the fat of wild animals contains EPA whereas domestic beef contains very small or undetectable amounts, since cattle are fed grains that are rich in omega-6 fatty acids and poor in omega-3 fatty acids76, whereas a deer that forages on ferns and mosses contains omega-3 fatty acids in its meat.

Lipids of liverworts, ferns, mosses and algae include 16:4É3, 18:3É3, 20:5É3 and 22:6É3. These are of particular interest because, unlike the higher plants in which 18:3É3 and 16:3É3 are the more abundant, they contain long-chain omega-3 fatty acids such as 20:5É3 (liverwort = 9-11 %) depending on their state of development. Mosses growing in or near water contain higher percentages of C20 and C22 PUFAs and are morphologically simpler than those that live in dry habitats77. Thus both the plants, and the animals that feed on them, are good sources of omega-3 fatty acids for human consumption.

In 1984, we initiated a series of studies of the omega-3 fatty acid and antioxidant content of purslane (Portulaca oleracea) and other edible wild plants and compared them to cultivated plants47,57,58,78-83.

Purslane is one of the plants that was part of the diet of hunter-gatherers in the Pacific Northwest section of the U.S. The large native population encountered at contact (ca. 1790-1850) was non-agricultural and obtained their food by foraging, harvesting and sometimes managing, natural, localized species of plants and animals. In a recent study, Norton et al. studied the vegetable food products of the foraging economies of the Pacific Northwest and found them to be valuable sources of calcium, magnesium, iron, zinc and ascorbic acid84. Norton states,

"These members of the Lily, Purslane, Barberry, Currant, Rose, Parsley, Heath, Honeysuckle, Sunflower and Water-Plantain families are among those regularly collected by these foraging groups whose economic strategies were keyed to the use of multiple resources and the storage of large quantities of processed foods. Stored vegetable foods along with dried fish provide ample and nutritious diets during the seasonal periods of resource non-productivity. Analyses show that these native foods are superior to cultigens in necessary fiber, minerals and vitamins making substantial contributions to pre-contact diets."

The results of this study revealed that a wide variety of foods were used to meet nutritional needs and that native preparation and preservation techniques were important factors in retaining nutrients, and in maintaining a balanced diet during seasons of low productivity. The study indicates that vegetable foods were systematically gathered and processed in quantity.

The wide variety of vegetables eaten along the Mediterranean and by foragers contrasts with the relatively narrow variety of crops produced by horticulturists and traditional agriculturists today. Purslane is the eighth most commonly distributed plant in the world. It is eaten both fresh and dry in many parts of the world, including Crete. Table II includes the amount of omega-3 fatty acids in milligrams per gram wet weight of purslane and other commonly eaten leafy vegetables (spinach, buttercrunch lettuce, red leaf lettuce, and mustard greens). As indicated in Table II, purslane contains 8.5 mg of fatty acids per gram of wet weight. In contrast, the other plants are relatively low in lipid content: spinach contains 1.7 mg/g, mustard greens 1.1 mg/g, red leaf lettuce 0.7 mg/g, and buttercrunch lettuce 0.6 mg/g. Purslane, with 4 mg of 18:3É3/g wet weight, is a good nonaquatic source of 18:3É3. Based on the information available from the provisional USDA table85 and our studies57,58, purslane, a wild growing plant, is the richest source of omega-3 fatty acids of any green leafy vegetable yet examined.

TABLE II: Fatty acid content of plants (mg/g of wet weight)
Fatty acid	Purslane	Spinach	Buttercrunch Lettuce	Red Leaf Lettuce	Mustard
14:0	0.16	0.03	0.01	0.03	0.02
16:0	0.81	0.16	0.07	0.10	0.13
18:0	0.20	0.01	0.02	0.01	0.02
18:1ω9	0.43	0.04	0.03	0.01	0.01
18:2ω6	0.89	0.14	0.10	0.12	0.12
18:3ω3	4.05	0.89	0.26	0.31	0.48
20:5ω3	0.01	0.00	0.00	0.00	0.00
22:6ω3	0.00	0.00	0.001	0.002	0.001
Other	1.95	0.43	0.11	0.12	0.32
Total Fatty Acid Content	8.50	1.70	0.601	0.702	1.101

Modified from reference 57.

Edible Wild Plants as a Source of Antioxidants

Consumption of fruits and vegetables has been associated with protection against various diseases, including cardiovascular, cerebro-vascular disease and cancer26-29. It is not known for certain what active dietary constituents contribute to the beneficial effects, but it is often assumed that antioxidant nutrients contribute to this defense. Results from intervention trials on the protective effect of the supplementation with antioxidants such as beta-carotene and vitamin E are not conclusive39. Therefore, the beneficial effect of a high intake of fruits and vegetables on the risk of cardiovascular disease and cancer may rely not on the effect of the well characterized antioxidants, such as vitamin E and C and beta-carotene, but rather on some other antioxidants or non-antioxidant phytochemicals or by an additive action of different compounds present in foods such as alpha-linolenic acid, various phenolic compounds and fiber.

Wild plants are typically known to have higher levels of vitamin C than cultivated ones44. Studies from Paleolithic nutrition indicate that the amount of vitamin C obtained by humans from eating a variety of wild plants was much higher, about 390 mg/day versus the 88 mg average intake obtained today in the US44.

We have determined levels of endogenous antioxidants (alpha-tocopherol, ascorbic acid, beta-carotene and glutathione) in plant leaves sampled simultaneously for lipids as previously reported79. Table III shows the content of alpha-tocopherol, ascorbic acid and beta-carotene in chamber-grown purslane, wild purslane and spinach expressed in mg/100 g fresh weight and in mg/100 g dry weight. The studies were expanded to include 25 commonly eaten wild plants in Crete. In addition to the vitamin E, total phenols and total antioxidant capacity were determined81.

Alpha-Tocopherol and Ascorbic Acid

In a previous survey of the antioxidant content of nine different weed species, it was recorded that levels of alpha-tocopherol ranged from 10 to 83 mg, and levels of ascorbic acid ranged from 2 to 861 mg/100 g dry weight (Table IV)⁸⁶.

TABLE III: Antioxidant content of purslane and spinach leaves
	Alpha-Tocopherol	Ascorbic Acid	Beta-Carotene
Content, mg/100 g fresh weight
Chamber-grown purslane	12.2 ± 0.4	26.6 ± 0.8	1.9 ± 0.08
Wild purslane	8.2 ± 0.3	23.0 ± 0.6	2.2 ± 0.1
Spinach	1.8 ± 0.09	21.7 ± 0.5	3.3 ± 0.5
Content, mg/100 g dry weight
Chamber-grown purslane	230 ± 9	506 ± 17	38.2 ± 2.4
Wild purslane	170 ± 8	36 ± 4	451 ± 14
Spinach	430 ± 15	43.5 ± 3.0	63.5 ± 5.7
Data represent mean value from four analyses each with three replicates per species/type.

Reproduced with permission from reference 58.

TABLE IV: Antioxidant content of different plant species 1
Plant species	Antioxidants, mg/100 g dry weight
	Ascorbic acid	Alpha-tocopherol
Morning glory	2 ± 1	0 ± 3
Lamb's quarter	58 ± 18	12 ± 3
Alfalfa	143 ± 12	10 ± 1
Pigweed	504 ± 24	10 ± 1
Buckwheat	537 ± 27	28 ± 2
Mustard	469 ± 24	50 ± 9
Sicklepod	861 ± 73	60 ± 6
Velvetleaf	92 ± 7	50 ± 4
Jimson weed	114 ± 29	83 ± 16
1Values given for the antioxidants represent the mean ± SE of 6 plants of each species.

Adapted from Table I in reference 86.

Relative to these findings, and other reports, levels of alpha-tocopherol found in purslane, 230 ± 9 mg/100 g dry weight, are up to 10 times higher than has been recorded in other weeds (Tables III and IV)9. Alpha-tocopherol was present in spinach leaves at a level of 30-40 mg/100 g dry weight (Table III). The ascorbic acid content of chamber-grown purslane fell within the range previously reported for other weed species (Table IV)86, but was significantly higher (506 ± 17 mg/100 g dry weight) than the level found in spinach leaves (430 ± 5 mg/100 g dry weight) (Table III).

Beta-Carotene

In photosynthetic tissues of higher plants, beta-carotene and other carotenoids are localized in chloroplasts; while there is little qualitative difference in the pigments present, there is considerable quantitative variation between different species87, 88. The levels of beta-carotene were not significantly different in leaves of chamber-grown (38.2 ± 2.4 mg/100 g dry weight) compared to wild purslane (43.5 ± 3.0 mg/100 g dry weight), but these levels were lower than those present in spinach (63.5 ± 5.7 mg/100 g dry weight) (Table III).

Glutathione

The protective role of glutathione as an antioxidant and detoxifying agent has been demonstrated in various clinical studies. It is a ubiquitous compound that is synthesized rapidly in the liver, kidney, and other tissues, including the gastrointestinal tract. In animal cells, glutathione acts as a substrate for glutathione peroxidase, which reduces lipid peroxides that are formed from polyunsaturated fatty acids (PUFA) in the diet, and as a substrate for glutathione-S transferase, which conjugates electrophilic compounds. Recent studies show that glutathione obtained from the diet is directly absorbed by the gastrointestinal tract and thus dietary glutathione can readily increase the antioxidant status in humans89. Dietary glutathione, in addition to levels supplied by the bile, may be used by the small intestine to decrease the absorption of peroxides. These results indicate that in the intact animal, luminal glutathione is available for use by the intestinal epithelium to metabolize peroxides and other reactive species and to prevent their transport to other tissue.

Dietary glutathione occurs in highest amounts in fresh meats, in moderate amounts in some fruits and vegetables, whereas it is absent or found only in small amounts in grains and dairy products90. Only fresh asparagus at 28.3 mg/100 g and fresh avocado at 27.7 mg/100 g were higher than purslane in glutathione content in a study carried out to determine the glutathione content of 98 food items, identified by the National Cancer Institute, to contribute 90 % or more of calories, dietary fiber, and 18 major nutrients in the US diet90-92.

The potential health effects of dietary intake of glutathione in humans are shown in Table V89,93-101. In a recent study by Flagg et al.102, plasma glutathione concentrations varied widely in humans and were influenced by sex and age (increased with age in men, but decreased with age and were lower in women who used estrogen-containing contraceptives).

TABLE V: Potential health effects of dietary glutathione in humans

Glutathione may protect cells from carcinogenic processes through a number of mechanisms: 1. By functioning as an antioxidant89,93. 2. By binding with mutagenic chemical compounds94,95. 3. By directly or indirectly acting to maintain functional levels of other antioxidants such as vitamins C and E and beta-carotene95-97. 4. Through its involvement in the DNA synthesis and repair98,99. 5. By enhancing the immune response100,101.

Adapted from Jones et al.90.

Glutathione is now known to be widely distributed in plant cells and is the major free thiol in many higher plants103-106. Considerable variations in levels of glutathione have been reported by different studies recording thiol levels in a variety of plant species. This may be partially due to the use of different analytical techniques, and because glutathione levels vary both diurnally107,108 and with developmental and environmental factors109-111. Taking into account these considerations, the levels of glutathione found in purslane, 14.81 ± 0.78 mg/100 g fresh weight, were in the range of those reported for other plant species but significantly higher than the level of 9.65 ± 0.62 mg/100 g fresh weight for spinach (Table VI). Glutathione was present in significantly greater amounts in chamber-grown purslane relative to wild plants, which may have reflected a difference in the developmental stage of the plants analyzed, or in the environmental conditions experienced.

Additional studies were carried out on 25 most commonly eaten wild plants in the Island of Crete81. Table VII contains the scientific names and the uses of the wild plants of Crete. Table VIII shows the alpha-tocopherol and the total phenols content. Finally, Table IX shows the antioxidant activity and antiradical power of the wild plants81.

TABLE VI: Glutathione content of purslane and spinach leaves
	GSH	GSSX	GSH/GSSX
Chamber-grown purslane	14.81 ± 0.78 (0.48)	2.20 ± 0.15 (0.031)	6.73
Wild purslane	11.90 ± 0.63 (0.39)	1.42 ± 0.12 (0.023)	8.38
Spinach	9.65 ± 0.62 (0.31)	2.39 ± 0.20 (0.039)	4.03

Data represent mean values (mg/100 g fresh weight) from four analyses each with three replicates per plant species/type. Figures in parentheses are values expressed as µmol/g fresh weight to allow comparison with data previously reported in the literature. GSH = glutathione; GSSX = glutathione-linked disulfides. Reproduced with permission from reference 58.

TABLE VII: The scientific names and the uses of the Cretan wild plants
No	PLANTS NAMES	USES
1	Papaver rhoeas	Cooked with olive oil, vegetable pie
2	Sonchus Oleraceus	Boiled salad, Cooked with olive oil, vegetable pie, raw salad
3	Pimpinela peregrina	Cooked with oil, vegetable pie
4	Centaurea idaea	Boiled salad
5	Tragopogon Sinuatus	Cooked with olive oil, vegetable pie
6	Crepis Commutata	Boiled salad
7	Helmintotheca echioides	Boiled salad
8	Tordylium apulum	Cooked with oil, vegetable pie
9	Scandix pecten-veneris	Cooked with olive oil, vegetable pie
10	Pontikes	Cooked with olive oil, vegetable pie, raw salad
11	Allium subhirstum	Cooked with olive oil, vegetable pie
12	Rumex ssp.	Cooked with olive oil, vegetable pie
13	Silene Vulgaris	Cooked with olive oil, vegetable pie
14	Crepis vesicaria	Boiled salad
15	Uropermun picroides	Boiled salad
16	Tolpis virgata	Cooked with olive oil, vegetable pie, Boiled salad
17	Hypochoeris radicata	Boiled salad
18	Cichorium pumilum	Boiled salad
19	Oebothera pimpineloides	Cooked with olive oil, vegetable pie
20	Leontodon tuberosus	Cooked with olive oil, vegetable pie
21	Cichorium spinosum	Boiled salad, raw salad
22	Ranunculus ficarioides	Cooked with olive oil, vegetable pie, Boiled salad, raw salad
23	Prasium majus	Cooked with olive oil, vegetable pie
24	Foeniculum vulgare ssp.piperitum	Cooked with olive oil, vegetable pie
25	Stypocaulon scoparium	Raw salad

*Both raw and boiled salads are dressed with olive and lemon or vinegar. Reproduced with permission from reference 81.

TABLE VIII: ±-Tocopherol and Total Phenols content of Cretan edible wild plants
No	Plant Names	±-tocopherol (mg/100g wet wt)	Total phenols (mg/100g wet wt)
1	Papaver rhoeas	0.524	33.5±0.81
2	Sonchus oleraceus	0.294	48.04±0.79
3	Pimpinela peregrina	0.490	47.65±0.33
4	Centaurea idaea	0.108	61.55±1.45
5	Tragopogon Sinuatus	0.206	20.82±0.14
6	Crepis Commutata	0.360	49.08±2.32
7	Helmintotheca echioides	0.029	44.86±1.08
8	Tordylium apulum	2.426	46.87±1.25
9	Scandix pecten-veneris	1.133	46.51±1.13
10	Pontikes	0.360	59.27±1.10
11	Allium subhirstum	1.215	14.54±0.65
12	Rumex ssp.	0.509	102.56±3.13
13	Silene Vulgaris	0.354	40.18±1.20
14	Crepis vesicaria	0.401	49.42±2.87
15	Uropermum picroides	0.482	35.76±0.54
16	Tolpis virgata	0.043	21.46±0.47
17	Hypochoeris radicata	0.193	57.03±0.32
18	Cichorium pumilum	0.420	93.64±0.28
19	Oenothera pimpineloides	0.232	55.05±1.31
20	Leontodon tuberosus	0.099	48.06±0.39
21	Cichorium spinosum	0.398	72.63±0.37
22	Ranunculus ficarioides	0.443	32.99±0.60
23	Prasium majus	1.287	78.72±0.44
24	Foeniculum vulgare ssp.piperitum	1.117	82.521±0.60
25	Stypocaulon scoparium	0.000	6.736±0.52

Reproduced with permission from reference 81.

TABLE IX: Antioxidant Activity and Antiradical Power of Cretan edible wild plants.
N°	Plant Names	Antioxidant Activity(EC50)(mg dry extract/mg DPPH)	ARP (1/EC50)
1	Papaver rhoeas	0,995±0.14	1,005±0.15
2	Sonchus oleraceus	3,664±0.05	0,273±0.004
3	Pimpinela peregrina	2,909±0.29	0,346±0.036
4	Centaurea idaea	1,400±0.011	0,714±0.005
5	Tragopogon Sinuatus	3,679±0.16	0,272±0.012
6	Crepis Commutata	3,169±0.14	0,316±0.014
7	Helmintotheca echioides	2,344±0.17	0,428±0.031
8	Tordylium apulum	2,852±0.13	0,351±0.017
9	Scandix pecten-veneris	2,477±0.11	0,404±0.018
10	Pontikes	7,261±0.25	0,138±0.005
11	Allium subhirstum	2,697±0.08	0,371±0.01
12	Rumex ssp.	2,344±0.17	0,428±0.03
13	Silene Vulgaris	2,852±0.13	0,351±0.02
14	Crepis vesicaria	2,284±0.42	0,438±0.09
15	Uropermum picroides	0,830±0.20	1,205±0.37
16	Tolpis virgata	1,350±0.12	0,741±0.06
17	Hypochoeris radicata	0,761±0.22	1,390±0.45
18	Cichorium pumilum	0,696±0.55	2,039±1.18
19	Oenothera pimpineloides	0,222±0.018	4,520±0.35
20	Leontodon tuberosus	1,194±0.047	0,838±0.03
21	Cichorium spinosum	1,115±0.28	0,944±0.28
22	Ranunculus ficarioides	0,280±0.08	3,812±1.27
23	Prasium majus	0,818±0.27	1,321±0.46
24	Foeniculum vulgare ssp.piperitum	1,041±0.15	0,974±0.14
25	Stypocaulon scoparium	2,367±0.19	0,424±0.035

Reproduced with permission from reference 81.

Phenols

Flavonoids and other phenolic compounds are antioxidants that contribute to the high antioxidant capacity observed in certain fruits and vegetables. There are several thousand different flavonoids present in plants, and many of them have antioxidant activities112. The antioxidant capacities, measured as oxygen radical absorbance assay (ORAC) of some flavonoids were found to be several times stronger on the basis of molar concentration than vitamins E and C112. Such phenolic compounds have already been implicated as playing a role in the protection that fruits and vegetables have against chronic diseases112. However, the extent to which these potentially important antioxidants can be absorbed is not clear, although early evidence indicates that substantial quantities of the flavonoids are absorbed.

Antioxidant Capacity

Various methods have been developed to measure total antioxidant capacity or activity, such as the ORAC43, or the 2,2-diphenyl-1-picrylhydrazyl (DPPH•)113 free radical assay which measures the antiradical power (ARP): the higher the ARP, the more efficient the antioxidant. In general, more than 80% of the total antioxidant capacity in fruits and vegetables comes from ingredients other than vitamin C, indicating the presence of other potentially important antioxidants in these foods43. ORAC varies considerably (20-30 fold) from one kind of fruit or vegetable to another. As expected, the majority of studies have been carried out in cultivated fruits and vegetables. Brussel sprouts are one of the vegetables that show high ORAC activity. Garlic, kale, and spinach are particularly high, as are strawberries and plums.

In a recent paper on the systematic screening of total antioxidants in dietary plants, using the ferric-reducing ability of plasma (FRAP) method43, Halvorsen et al.114 emphasized the need for a systematic analysis in order to facilitate research into the nutritional role of a combined effect of antioxidants in dietary plants.

Conclusions

Current research clearly shows that human beings evolved on a diet that was based on wild plants, particularly green leafy vegetables, meat from animals in the wild, and fish from rivers, lakes and deep cold sea water. This diet provided equal amounts of omega-6 and omega-3 essential fatty acids. Furthermore, the diet contained omega-3 fatty acids from terrestrial sources (predominately ALA) and high amounts of EPA and DHA from both animals and fish. The green leafy vegetables provided antioxidant vitamins, minerals, and various phytochemicals with antioxidant properties.

Studies on wild plants relative to the omega-3 fatty acids and antioxidant content are being carried out in various parts of the world. As expected, they show enormous variation in the content of both omega-3 fatty acids and antioxidants due to variation in climatic conditions and cultivars. In developing new sources of food, the study of the dietary composition of wild plants is essential. Their cultivation should lead to increased production of plants rich in omega-3 fatty acids and antioxidants, both of which reduce the risk of chronic diseases.

References

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Corresponding author: Dr Artemis P Simopoulos. The Center for Genetics, Nutrition and Health 2001 S Street, NW, Suite 530, Washington, DC 20009, USA. Phone: (202) 462-5062. Fax: (202) 462-5241. E-mail: cgnh@bellatlantic.net

Courtesy of the Sociedad de Biología de Chile, © 2007

+Omega-3 Fatty Acids Protect Eyes against Retinopathy, Study Finds
    Department of Health and Human Services, National Institute of Health

Omega-3 Fatty Acids Protect Eyes against Retinopathy
Retinopathies May Be Prevented or Lessened by a Change in Diet
Department of Health and Human Services, National Institute of Health, www.nih.gov

Omega-3 polyunsaturated fatty acids protect against the development and progression of retinopathy, a deterioration of the retina, in mice. This is the major finding of a study that appears in the July 2007 issue of the journal Nature Medicine. The study was a collaborative effort by researchers at Children’s Hospital Boston, the primary pediatric teaching affiliate of Harvard Medical School, Brigham and Women’s Hospital, Massachusetts General Hospital, the University of Goteborg in Sweden, and the National Eye Institute (NEI) and National Institute on Alcohol Abuse and Alcoholism (NIAAA) of the National Institutes of Health (NIH).

Paul A. Sieving, M.D., Ph.D., director of the NEI, said, “This study explores the potential benefit of dietary omega-3 fatty acids in protecting against the development and progression of retinal disease. The study gives us a better understanding of the biological processes that lead to retinopathy and how to intervene to prevent or slow disease.”

The researchers studied the effect of the omega-3 fatty acids EPA and DHA, derived from fish, and the omega-6 fatty acid arachidonic acid on the loss of blood vessels, the re-growth of healthy vessels, and the growth of destructive abnormal vessels in a mouse model of oxygen-induced retinopathy. The retinopathy in the mouse shares many characteristics with retinopathy of prematurity (ROP) in humans. ROP is a disease of the eyes of prematurely born infants in which the retinal blood vessels increase in number and branch excessively, sometimes leading to bleeding or scarring. Infants who progress to a severe form of ROP are in danger of becoming permanently blind. There are also aspects of the disease process that may apply to diabetic retinopathy, a disease in which blood vessels swell and leak fluid or grow abnormally on the surface of the retina, and age-related macular degeneration (AMD), a disease of the macula, the part of the retina responsible for central vision, and a leading cause of vision loss in Americans 60 years of age and older.

The researchers found that increasing omega-3 fatty acids and decreasing omega-6 fatty acids in the diet reduced the area of vessel loss that ultimately causes the growth of the abnormal vessels and blindness. Omega-6 fatty acid contributes to the growth of abnormal blood vessels in the retina.

To further test the apparent beneficial effect of omega-3 fatty acids, the researchers studied mice fed a diet modeled after a traditional Japanese diet (more omega-3 than omega-6 fatty acids) and mice fed a diet modeled after a traditional Western diet (lower amounts of omega-3 fatty acids). In addition, they studied mice genetically altered with a gene which mammals normally lack that converts omega-6 into omega-3 fatty acids. They found that the mice with higher amounts of omega-3 had a nearly 50 percent decrease in retinopathy.

Omega-3 fatty acids create chemical compounds known as bioactive mediators, which protect against the growth of abnormal blood vessels, a condition that characterizes some forms of retinopathy. In part, this occurs because these mediators suppress a type of inflammatory protein called tumor necrosis factor alpha (TNF-alpha). TNF-alpha is found in one type of cell, called microglia, which can be closely associated with retinal blood vessels.

“The retina has one of the highest concentrations of omega-3 fatty acids in the body,” said lead author and NEI fellowship recipient Kip M. Connor, Ph.D., a postdoctoral research fellow at Children’s Hospital Boston. “Given this, it is remarkable that with only a two percent change in dietary omega-3 intake, we observed an approximate 40-50 percent decrease in retinopathy severity.”

“Our findings represent new evidence suggesting the possibility that omega-3 fatty acids act as protective factors in diseases that affect retinal blood vessels,” said John Paul SanGiovanni, Sc.D., NEI staff scientist and the other lead author of the study. “This is a major conceptual advance in the effort to identify modifiable factors that may influence inflammatory processes implicated in the development of common sight-threatening retinal diseases.”

These study results, SanGiovanni emphasized, are important because they provide a reasonable biological explanation for findings from a number of human studies on diet and retinal disease, and they identify low-cost and widely available nutrient-based treatment approaches that may show merit in future research on diseases that damage retinal blood vessels and nerve cells.

"The purpose of our study was to discover and describe the scientific basis for any possible protective role of omega-3 fatty acids against retinopathy,” said Lois E. H. Smith, M.D., Ph.D., senior investigator of the study and associate professor of ophthalmology at Children’s Hospital Boston, an affiliate of Harvard Medical School. “By identifying the fatty acids, lipids and growth factors involved in both the disease and protective processes, we hope to translate this work to influence the outcome in patients. Our study results suggest that increasing omega-3 fatty acid intake in premature infants may significantly decrease the occurrence of ROP. This changing of lipids by dietary means may also translate to AMD and diabetic retinopathy. If clinical trials find that supplementing with omega-3 fatty acids is as effective in protecting humans against retinal disease as demonstrated by the findings of this study, this cost effective intervention could benefit millions of people.”

The National Eye Institute (NEI) is currently conducting the Age-Related Eye Disease Study 2 (AREDS2) that will, in part, assess the effect of omega-3 fatty acids DHA and EPA on the progression of AMD. In addition, an upcoming clinical trial at Children’s Hospital Boston will test the effects of omega-3 supplements in premature infants.

The NEI is part of the National Institutes of Health (NIH) and is the Federal government's lead agency for vision research that leads to sight-saving treatments and plays a key role in reducing visual impairment and blindness. For more information, visit the NEI Website at http://www.nei.nih.gov/.

The National Institutes of Health (NIH) — The Nation's Medical Research Agency — includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.

+Omega-3 Fatty Acids: An Interview with Dr. Frank Sacks
    Professor of Cardiovascular Disease Prevention, Dept of Nutrition, Harvard School of Public Health

Omega-3 Fatty Acids: An Interview with Dr. Frank Sacks
Professor of Cardiovascular Disease Prevention, Department of Nutrition, Harvard School of Public Health

1. What are omega-3 fatty acids, and why should I make sure to include them in my diet?

Omega-3 fatty acids (also known as n-3 fatty acids) are polyunsaturated fatty acids that are essential nutrients for health. We need omega-3 fatty acids for numerous normal body functions, such as controlling blood clotting and building cell membranes in the brain, and since our bodies cannot make omega-3 fats, we must get them through food. Omega-3 fatty acids are also associated with many health benefits, including protection against heart disease and possibly stroke. In addition to these established benefits for cardiovascular disease, omega-3 fatty acids in high doses (e.g. 6-10 capsules per day) are used to treat depression. New studies are identifying potential benefits for a wide range of conditions including cancer, inflammatory bowel disease, and other autoimmune diseases such as lupus and rheumatoid arthritis.

2. What foods are good sources of omega-3 fatty acids? How much do I need to eat of these foods to get enough omega-3s?

There are two major types of omega-3 fatty acids in our diets: One type is alpha-linolenic acid (ALA), which is found in some vegetable oils, such as soybean, rapeseed (canola), and flaxseed, and in walnuts. ALA is also found in some green vegetables, such as Brussels sprouts, kale, spinach, and salad greens. The other type, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), is found in fatty fish. The body partially converts ALA to EPA and DHA.

We do not know whether vegetable or fish omega-3 fatty acids are equally beneficial, although both seem to be beneficial. Unfortunately, most Americans do not get enough of either type. For good health, you should aim to get at least one rich source of omega-3 fatty acids in your diet every day. This could be through a serving of fatty fish (such as salmon), a tablespoon of canola or soybean oil in salad dressing or in cooking, or a handful of walnuts or ground flaxseed mixed into your morning oatmeal.

3. What are omega-6 fatty acids? Should I be concerned about the ratio of omega-6 fatty acids to omega-3 fatty acids in my diet?

Omega-6 fatty acids (also known as n-6 fatty acids) are also polyunsaturated fatty acids that are essential nutrients, meaning that our bodies cannot make them and we must obtain them from food. They are abundant in the Western diet; common sources include safflower, corn, cottonseed, and soybean oils.

Omega-6 fatty acids lower LDL cholesterol (the "bad" cholesterol) and reduce inflammation, and they are protective against heart disease. So both omega-6 and omega-3 fatty acids are healthy. While there is a theory that omega-3 fatty acids are better for our health than omega-6 fatty acids, this is not supported by the latest evidence. Thus the omega-3 to omega-6 ratio is basically the "good divided by the good," so it is of no value in evaluating diet quality or predicting disease.

4. Is it better to get omega-3 fatty acids from food or from supplements?

Certainly foods, since the plants and fish that contain omega-3 fats have other good nutrients, such as protein, vitamins and minerals. People who do not eat fish or other foods rich in omega-3 fatty acids should consider taking an omega-3 supplement of 500 mg per day; fish oil is used in supplements, but there are also vegetarian supplements that have ALA. Studies suggest that people who have already had a heart attack may benefit from higher doses of omega-3 supplements (basically, double the 500 mg), so if you do have heart disease, consult your healthcare provider about whether taking a higher dose of omega-3s makes sense for you.

5. I am a vegetarian, so I do not consume any fish. But I get plenty of ALA in my diet, from canola and soybean oil, ground flax seed, and walnuts. How efficiently does the body convert ALA to DHA and EPA? Should I take an algal DHA supplement?

If you are getting adequate ALA in your diet from oils and nuts, I am not sure you really need to take an algal DHA supplement. As I mentioned above, the body partially converts ALA to EPA and DHA; it is not known if ALA has substantial health benefits as is, or whether it must be converted to EPA and DHA to produce most of the benefits. My current interpretation of the science is that ALA has direct health benefits, through its role in reducing inflammation and protecting the heart against arrhythmias, and it also has indirect health benefits, through its conversion to EPA and DHA.

6. Can omega-3 fatty acids be destroyed by high-heat cooking?

Not if the oil is fresh. In fact, even in frying oil that is used for days, you still can find ALA in it.

+New Findings about Omega-3 Fatty Acids and Depression
    Alan C. Logan, ND, FRSH

New Findings about Omega-3 Fatty Acids and Depression
Alan C. Logan, ND, FRSH

Omega-3 fatty acids are polyunsaturated fatty acids that are considered essential because they cannot be synthesized by the human body. Dietary sources of omega-3 fatty acids include plants (particularly flax, canola, walnuts and hemp) and fish (particularly ocean fish such as sardines, anchovies, salmon and mackerel). Plants contain the parent omega-3, alpha-linolenic acid (ALA), which can be converted into eicosapentanoic acid (EPA) and docosahexanoic acid (DHA).

Dietary fish and fish oil supplements are a direct source of EPA and DHA. The influence of ALA, EPA and DHA in human health has been the subject of intense research over the last three decades. Although best known for cardiovascular benefits, new findings indicate that the influence of omega-3 fatty acids in mental health, particularly EPA, may currently be underestimated. Epidemiological, experimental and new clinical studies have all shown a strong connection between omega-3 fatty acids, or a lack thereof, and major depression.

These exciting new findings are not entirely surprising when one considers that the brain itself is 60% fat and that one-third of all fatty acids are of the polyunsaturated variety. As discussed below, the current research highlights the critical role of these fatty acids in the central nervous system (CNS).

Omega-3 Intake Declines, Depression Rates Climb

There has been a significant drop-off in omega-3 fatty acid intake within Western countries over the last century. The opposite can be said of omega-6 intake. Although essential, omega-6-rich oils are found in abundance in the North American food supply. Currently these omega-6 oils (corn, safflower, sunflower, cottonseed, sesame) are outnumbering omega-3 fatty acids by a ratio of up to 20:1.

This ratio is a long way off the close to 1:1 omega-6 to omega-3 ratio as recommended by the international panel of essential fatty acid experts in the Journal of the American College of Nutrition. The average daily intake of EPA/DHA combined is 130mg in North America, 520mg short of published recommendations and 870mg short of the 1000mg recommended by the American Heart Association in cases of heart disease.

In direct contrast to the depletion of omega-3 fatty acids from the Western food supply, the rates of depression have dramatically increased in Western countries. In addition, depression is now occurring more commonly in younger persons. The average age of onset of depression has continued to dip over the last 100 years. Scientists investigating the change in rates of depression have made it clear that these findings cannot be explained away by changes in attitudes of health professionals or society, diagnostic criteria, reporting bias, institutional or other artifacts. Perhaps the inadequate omega-3 intake, the major deviations in fatty acids ratios and the quarter-century-old message that all fat is unhealthy has had an untold influence on rates of depression.

Fish Consumption and Depression

There have been a number of studies that have examined national and international fish consumption data and compared them to rates of depression. Dr. Joseph Hibbeln of the National Institutes of Health is a pioneer in this area. He, and his group, have shown that higher national consumption of fish for a nation equals lower rates of depression versus countries consuming the least amount of fish. He has also shown that higher fish consumption is correlated with lower risk of postpartum depression and seasonal affective disorder.

Other researchers have shown that even within a nation, fish consumption is associated with lower risk of depression and higher mental health status. Finally, researches are now observing increasing rates of depression in regions of the world that are moving away from traditional omega-3-rich diets to typical Western foods.

Laboratory Tests in Depression

The epidemiological studies clearly suggest that adequate omega-3 fatty acids may be an important protective factor in depression. Correlation, however, does not prove causation. To add to the strength of the epidemiological studies, scientists have examined the levels of omega-3 fatty acids in the blood cells and fat storage cells of those with major depression.

Four studies have shown that those with depression do indeed have lower levels of omega-3 fatty acids in the blood. One of the studies showed that the lower the level of EPA, the more severe the clinical depression. In addition, a recent study showed that the patients with depression have 35% less DHA in fat storage cells versus healthy controls.

Experimental Studies

Over the last decade, neuroscientists have been examining the consequences of omega-3 deficiencies in the central nervous system. Alterations in serotonin and dopamine levels, as well as the functioning of these two important neurotransmitters is evident in an omega-3 deficiency. The changes observed in omega-3 deficiency in animals is strikingly similar to that found in autopsy studies of human depression.

In addition to changing serotonin and dopamine levels and functioning, omega-3 deficiencies are known to compromise the blood-brain barrier, which normally protects the brain from unwanted matter gaining access. Omega-3 deficiency can also decrease normal blood flow to the brain, an interesting finding given the studies which show that patients with depression have compromised blood flow to a number of brain regions. Finally, omega-3 deficiency also causes a 35% reduction in brain phosphatidylserine (PS) levels. This is also of relevance when considering that PS has documented antidepressant activity in humans.

Mechanisms of EPA/DHA Regulation of Mood

DHA is found in high levels in the cells of the central nervous system (neurons); here it acts as a form of scaffolding for structural support. When omega-3 intake is inadequate, the nerve cell becomes stiff as cholesterol and omega-6 fatty acids are substituted for omega-3. When a nerve cell becomes rigid, proper neurotransmission from cell to cell and within cells will be compromised.

While DHA provides structure and helps to ensure normal neurotransmission, EPA may be more important in the signaling within nerve cells. Normalizing communications within nerve cells has been suggested to be an important factor in alleviating depressive symptoms. In addition, EPA can lower the levels of two important immune chemicals, tumour necrosis factor alpha (TNFa) and interleukin 1 beta (IL-1ß), as well as prostaglandin E2.

All three of these chemicals are elevated in depression. In fact, higher levels of TNFa and IL-1ß are associated with severity of depression. Finally, EPA has been hypothesized to increase brain-derived neurotropic factor (BDNF), which is known to be lower in depressed patients. BDNF is neuroprotective, enhances neurotransmission, has antidepressant activity and supports normal brain structure. BDNF may prevent the death of nerve cells in depression.

Clinical Studies

There have been some published case reports indicating that flaxseed oil may be helpful in cases of bipolar depression and the anxiety disorder agoraphobia. The first controlled clinical trial indicating that omega-3 fatty acids may be of benefit in depression was published in 1999. In this case, 9:6 g of EPA/DHA versus placebo led to longer periods of remission and improvement in depressive symptoms in those with bipolar depression.

Some researchers theorize that such high doses of EPA/DHA may not be necessary and that low levels of pure EPA may be of benefit. In a study published in the American Journal of Psychiatry, researchers showed that just 2g of pure EPA could improve the symptoms of treatment-resistant depression. The researchers found that the EPA (versus placebo), when added to an ineffective antidepressant for one month, significantly improved depressive symptoms.

A larger study published in Archives of General Psychiatry replicated these findings, however, this time various doses of EPA were examined. Those on ineffective antidepressants were given 1g, 2g or 4g of pure EPA or a placebo in addition to the medication. Interestingly, the 1g daily dose of EPA led to the most significant improvements over the three-month study; it appeared that less was more. There were significant improvements in depressive symptoms, sleep, anxiety, lassitude, libido and thoughts of suicide.

Researchers from Taiwan Medical University published a recent study in which they found that a 4.4g EPA and 2.2g DHA mix could alleviate depression versus placebo in those with treatment-resistant depression. This was a two-month study involving patients who were on antidepressants that were not working. As with the other omega-3 studies discussed, the fish oil was well tolerated and no adverse events were reported.

There is also evidence that omega-3 oils may be of benefit in treating depressive symptoms outside of major depressive disorder. Canadian researchers showed that Antarctic krill oil (400mg EPA, 240mg DHA) could improve depressive symptoms associated with premenstrual syndrome. Harvard researchers have also shown that just 1g of pure EPA is beneficial in the treatment of borderline personality disorder. This personality disorder, which is particularly difficult to treat, is characterized by both depressive and aggressive symptoms. This was a two-month placebo-controlled study and the results showed that EPA has a mood-regulating effect, improving both depression and aggression versus placebo.

To date, with one exception, all studies conducted on omega-3 fatty acids and mood have had a positive outcome. The singular negative study examined pure DHA in patients with depression. The results in the case showed that DHA alone was no better than placebo in alleviating depressive symptoms.

Conclusion

Although an influence of EPA and DHA on brain physiology and structure is apparent, the precise mechanisms whereby omega-3 fatty acids may alleviate depression remain unknown. The results of the clinical trials reinforce the epidemiological and experimental studies, underscoring the importance of adequate omega-3 intake in those with depression.

The long-term studies of fish oil supplements in the area of cardiovascular health, some spanning three-plus years, have shown that they are safe and well tolerated. Patients with depression or depressive symptoms should discuss omega-3 fatty acids with their health care providers. While scientists continue to unravel the neuropsychological influences of omega-3 fatty acids, it should be recognized that they are not a substitute for appropriate mental health evaluation and care.

Alan C. Logan is a naturopathic physician licensed in Connecticut. Valedictorian of the Canadian College of Naturopathic Medicine, class of 2001, his recent medline-indexed article "Neurobehavioral Aspects of Omega-3 Fatty Acids: Possible Mechanisms and Therapeutic Value in Major Depression" is available to medical professionals by writing to Dr. Logan at clnd@cfs-fm.org.

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