Interest in omega-3 fatty acids began in the 1950s, with several thousand papers in the scientific literature supporting their benefits. Little doubt remains that omega-3 fatty acids are important in human nutrition. As significant structural components of the cell membranes of tissues throughout the body, they are especially rich in the retina, brain, and sperm, in which docosahexaenoic acid (DHA) constitutes 36.4% of total fatty acids. Membrane fluidity is essential for proper functioning of these tissues. In the retina, where omega-3 fatty acids are especially important, deficiency can result in decreased vision and abnormal electroretinogram results. Several studies clearly illustrate the effects of omega-3 deficiency in both animals and humans.
For purposes of discussion, the most prominent forms of Omega-3 fatty acids include alpha-linolenic acid (ALA, 18:3), eicosapentaenoic acid (EPA, 20:5), and docosahexaenoic acid (DHA, 22:6). ALA is present in plant-based sources such as flaxseed oil; EPA and DHA are present in animal and marine sources, such as liver, krill, and fish.
Omega-3 Fatty acids are essential fatty acids, necessary from conception through pregnancy and infancy and throughout life: The ratio of omega-6 to omega-3 fatty acids has increased in industrialized societies because of reduced consumption of foods rich in omega-3 fatty acids and increased consumption of vegetable oils rich in omega-6 fatty acids, i.e., linoleic acid in the form of soy, corn, safflower, and canola oils. Another important feature of omega-3 fatty acids is their role in the prevention and modulation of certain diseases that are common in Western civilization. The following is a partial list of diseases that may be prevented or ameliorated with omega-3 fatty acids, in descending order of importance based on available scientific literature:
- Coronary heart disease and stroke,
- Essential fatty acid deficiency in infancy (retinal and brain development),
- Autoimmune disorders (e.g., lupus and nephropathy),
- Crohn’s disease,
- Cancers of the breast, colon, and prostate,
- Mild hypertension, and
- Rheumatoid arthritis.
Dietary ALA vs. dietary DHA: Within the health community, some debate the ability of individuals to convert dietary sources of ALA into the longer forms of EPA and DHA, which are used by the body for many metabolic functions. This question remains heavily debated despite studies that show the removal of dietary ALA promotes Omega-3 fatty acid deficiency, including DHA, and in spite of many experiments demonstrating dietary inclusion of ALA raises Omega-3 tissue fatty acid content, including DHA. Research shows that ALA is converted to DHA, EPA, and docosapentaenoic acid (DPA, 22:5), depending the body’s needs. Like many other fatty acids, the by-products of metabolizing ALA are reused for synthesizing cholesterol and other fatty acids. In addition, numerous in vitro and animal studies show ALA exerting identical metabolic effects as DHA, although longer treatments or higher concentrations of ALA were needed compared to consuming dietary DHA.
The differences between how the body uses dietary DHA compared to dietary ALA have led to the dogma that ALA is not a useful fatty acid for maintaining DHA levels in human tissues. On the contrary, numerous studies indicate that dietary ALA (found in abundance in flaxseed oil) is a crucial dietary source of Omega-3 fatty acids and including it in one’s diet is critical for maintaining EPA, DPA, and DHA levels in human tissue.
Cardiovascular Benefits of Omega-3 Fatty Acids: The strongest evidence of connecting omega-3 fatty acids and disease prevention is found in the inverse relationship between the amount of omega-3 fatty acids in the diet, blood, and tissues and the occurrence of coronary heart disease and its complications. Effects of omega-3 fatty acids on coronary heart disease have been shown in hundreds of experiments in animals, humans, tissue culture studies, and clinical trials. Omega-3 fatty acids have been shown to be protective of heart disease and, by a variety of mechanisms, prevent deaths from coronary disease, particularly cardiac arrest.
The unique properties of omega-3 fatty acids in coronary heart disease first became apparent while investigating the health of Greenland Eskimos who consumed diets very high in fat from seals, whales, and fish and yet had a low rate of coronary heart disease. Further studies clarified this paradox. The fat the Eskimos consumed contained large quantities of the very-long-chain and highly polyunsaturated fatty acids of EPA and DHA, which are abundant in fish, shellfish, and sea mammals and are scarce or absent in land animals and plants. EPA and DHA are synthesized by phytoplankton, which are the equivalent of oceanic plants that serve as the base of the food chain for marine life.
Dietary omega-3 fatty acids act to prevent heart disease through a variety of actions, including the following:
- Preventing arrhythmias (ventricular tachycardia and fibrillation),
- Acting as prostaglandin and leukotriene precursors,
- Having anti-inflammatory properties,
- Inhibiting synthesis of cytokines and mitogens,
- Stimulating endothelial-derived nitric oxide,
- Acting as an antithrombotic,
- Having hypolipidemic properties with effects on triglycerides and VLDLs, and
- Inhibiting atherosclerosis.
EPA and DHA have strong anti-arrhythmic action on the heart. In experimental animals and tissue culture systems, EPA and DHA prevent the development of ventricular tachycardia and fibrillation. Where omega-3 fatty acid intake was increased, total mortality has been improved in several studies. In one study, men who consumed salmon 1 time/wk had a 70% less likelihood of cardiac arrest. In another study overall mortality was decreased by 29% in men with overt cardiovascular disease who consumed omega-3 fatty acids from fish or fish oil, probably due to reducing cardiac arrests. According to a 1998 Physician’s Health Study in the United States, consumption of 1 fish meal/week was associated with a 52% lower risk of sudden cardiac death compared with consumption of <1 fish meal/month in 20,551 male physicians.
Omega-3 Fatty Acids Essential Components of Cell Membranes in Infancy: Two critical periods are worth noting for adequate consuming omega-3 fatty acids: during fetal development and after birth until the biochemical development in the brain and retina is completed. As already noted, the omega-3 fatty acid DHA is an important constituent of the cell membrane of these neural structures. Omega-3 fatty acid deficiency is manifested in both the blood and in tissue biochemistry. Of note is a strikingly low concentration of DHA, which may fall to as much as one-fifth of the normal amount, which the body attempts to replace with Omega-6 fatty acids. Omega-3–deficient diets fed to pregnant rhesus monkeys that continued after birth induced profound functional changes such as reduced vision, abnormal electroretinograms, impaired visual evoked potential, more stereotypic behavior (e.g., pacing), and disturbed cognitive ability.
Some of these findings have been replicated in infants fed formulas deficient in omega-3 fatty acids. Most studies of premature infants have shown visual impairment and abnormal electroretinograms. A recent study in full-term infants compared standard infant formula with human milk and formulas enriched with DHA, the results of which unequivocally demonstrated the considerable differences in cognitive ability.
All human studies substantiated the omega-3 fatty acid deficiency state in plasma, red blood cells, and occasionally in tissues from autopsied infants. The lower concentrations of DHA in plasma and erythrocytes are mirrored by lower concentrations in the brain and retina. Formula-fed infants have lower concentrations of brain DHA than do infants fed human milk. They also have lower intelligence quotients. During pregnancy, both the mother’s stores and dietary intake of omega-3 fatty acids are of critical importance in insuring that the baby has adequate amounts of omega-3 fatty acids at the time of birth.
All polyunsaturated fatty acids, including DHA, are transferred across the placenta into fetal blood. In addition, EPA and DHA in the mother’s adipose tissue can be mobilized as free fatty acids bound to albumin and be made available to the developing fetus via placenta transport. Several studies in monkeys have indicated that when the mother’s diet is deficient in omega-3 fatty acids, the infant at birth is also deficient with low DHA concentrations observed in their plasma and red blood cells. In humans, consuming fish oil or sardines to pregnant women led to higher DHA concentrations in both the mother’s plasma and red blood cells and in cord blood plasma and red blood cells at the time of birth. Once membrane phospholipids have adequate concentrations of DHA, the brain and retina retain these fatty acids, even though the diet may be deficient afterwards.
Barcelo-Coblijn G, Murphy EJ (2009) Alpha-linolenic acid and its conversion to longer chain n-3 fatty acids: Benefits for human health and a role in maintaining tissue n-3 fatty acid levels. Progress in Lipid Research 48:355-374.
Conner WE (2000) Importance of n-3 fatty acids in health and disease. American Journal of Clinical Nutrition 71(suppl):171S-175S.