Aside from their role as energy sources, fatty acids have many other roles to play in human metabolism. The omega-3 and omega-6 essential fatty acids (also known as n-3 and n-6 fatty acids, respectively) are particularly important. Both of these families of essential fatty acids are also polyunsaturated fatty acids (PUFA’s). (The terms omega-3 and omega-6 refer to the number of carbon units from the acid end of the fatty acid before unsaturation starts.) Common dietary sources of omega-3 fatty acids are marine fish oils and Chia Seeds, which supply a safer and stronger form, plus other essential nutrients. Evening primrose oil is a widely recognised source of gamma-linolenic acid, an omega-6 fatty acid.

The most significant role for essential fatty acids (EFA’s) is as the precursors for prostaglandins. In structure, prostaglandins are twenty-carbon fatty acids that contain a five-carbon ring. Prostaglandins act as hormone activity modulators. That is, they affect the way hormones act upon cells, but do not act as hormones themselves.¹ Prostaglandins control, or are involved in, many physiological processes such as contraction of smooth muscle (particularly uterine muscle), blood supply, nerve transmission, development of the inflammatory response, water retention, electrolyte balances and blood clotting.²

 Outline of the pathways of essential fatty acid metabolism^3,4

As can be seen from the table below, the omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosapentaenoic acid (DHA), and the omega-6 fatty acid, gamma-linolenic acid (GLA), are essential components of the EFA pathways. In fact, the omega-3 and omega-6 pathways are very similar and use the same enzymes. The results of these pathways are various families of prostaglandins.

Vitamin E is, of course, one of the most widely known antioxidants. The physiological function of vitamin E is intimately bound up with oxidation susceptible materials such as lipids.

 Omega-3 fatty acids

A review of the literature on eicosapentaenoic acid (EPA) in particular indicates that the compound appears to have immunostimulant, antithrombotic, ischaemia-protective and cancer-mediating properties.5  Much work has been done on marine oils which contain omega-3 fatty acids, principally EPA and DHA, rather than on the isolated fatty acids.

 Anti-inflammatory

A diet rich in Chia Seeds or fish oil appears to inhibit the generation of pro-inflammatory mediators derived from arachidonic acid and to suppress the responses of target cells and tissues. This, in turn, modulates both the inflammatory and humoral components of the allergic response. The mechanism of these effects appears to be the involvement of omega-3 fatty acids in both the cyclooxygenase and 5-lipoxygenase pathways.⁶

From studies of dietary supplementation with omega-3 fatty acids, it seems that three pathways of synthesis of lipid mediators of inflammation are at least partially inhibited. These are the cyclooxygenase pathway, the 5-lipoxygenase pathway, and the platelet-activating factor pathway. The exact mechanism of the inhibitions has not be elucidated but it seems probable that effects are dependent upon dose and composition of the omega-3 fatty acids, as well as the exact nature of the inflammation state and concurrent medical therapy.⁷

Research on inflammatory responses in rats to monosodium urate, has shown that eicosapentaenoic acid from the diet suppressed the fluid phase (exudate). In contrast, gamma-linolenic acid suppressed the cellular phase of inflammation.⁸

 Cardiovascular

Early studies into dietary omega-3 fatty acids discovered that the Eskimos of Greenland have a very low incidence of ischaemic heart disease, despite a diet rich in animal fats. This low incidence has been attributed to the presence of the omega-3 fatty acids EPA and DHA in the diet.^9,10

In human studies in the elderly, eicosapentaenoic acid intake has been shown to reduce platelet aggregation, thereby reducing the risk of atherosclerosis and stroke. It has been suggested that increased levels of eicosapentaenoic acid increase the levels of platelet vitamin E which in turn decrease platelet aggregation.¹¹

The omega-3 polyunsaturated fatty acids, eicosapentaenoic acid and docosahexaenoic acid, have been reported to successfully lower excessive triglyceride levels, a major indicator for coronary heart disease. Interestingly, cholesterol levels appeared to be unaffected by omega-3 fatty acids in this study.¹²

A population-based case-control study in the United States examined the link between dietary omega-3 polyunsaturated fatty acid intake from seafood and the risk of primary cardiac arrest. A negative correlation was found. An intake of 5.5 g of omega-3 fatty acids per month was associated with a 50% reduction in the risk of primary cardiac arrest.¹³

 Other effects

Marine oil rich in omega-3 fatty acids, principally eicosapentaenoic acid and docosahexaenoic acid, has been reported to have positive effects on rat mammary tumours. Supplementation appeared to reduce both weight and volume of tumours, apparently through effects on arachidonic acid metabolism.¹⁴ Fish oils high in omega-3 fatty acids have been observed to reduce the size and number of chemically-induced preneoplastic lesions in rat pancreas.¹⁵ Omega-3 and omega-6 fatty acids have been shown to kill breast, lung and prostate carcinoma cells in vitro, without having adverse effects on fibroblasts.¹⁶

Studies of breast cancer cells exposed to EPA and DHA in vitro, indicate that these fatty acids inhibit cell growth, while having no impact on growth on normal cells. The research showed that inhibition was not due to cytotoxic effects but rather through the formation of lipid hyperoxide and other oxidation products. This seems to be a result of the differential metabolism of polyunsaturated fatty acids in tumour cells.¹⁷

Omega-3 fatty acids also appear to directly affect T-cell subsets in the immune system. An increase in dietary omega-3 fatty acid content has been seen to correlate to an increase in the T-helper/T-suppresser cell ratio in patients with solid tumours. This immune system boosting occurred principally because of a significant reduction in the number of T-suppresser cells.¹⁸

Essential fatty acid metabolism seems to be linked to the body’s ability to deal with viral infections. Interferon activity requires essential fatty acids to exhibit antiviral effects. Both in-vivo and in-vitro studies indicate that viral infection induces abnormalities in essential fatty acid levels. These abnormalities appear to be responsive to supplementation.¹⁹

 Gamma-Linolenic acid

Evening primrose oil is the most widely known source of gamma-linolenic acid (GLA) and is used extensively in supplementation. Gamma-linolenic acid is the immediate desaturase metabolite of the essential fatty acid linoleic acid (see table). The choice of evening primrose oil has been traditional, but has been borne out by research that indicates that it is the most biologically active of the sources of GLA studied. A number of conditions are known to correspond to impaired synthesis of gamma-linolenic acid, and to respond well to therapeutic doses of GLA. The most notable of these conditions are atopic eczema, premenstrual syndrome along with cyclical mastalgia (breast pain) and diabetes.²⁰

 Premenstrual syndrome (PMS)

Premenstrual syndrome is widely known but poorly defined, with many individual symptoms occurring alone, or in groups.

Difficulties in treating PMS can arise from the impact that life-style has on the condition. Association has been found between PMS and regularity of periods, occupational level and education, with housewives reporting the highest level of symptoms.²¹ The regularity of periods is itself strongly affected by life-style and other factors.

A wide variety of possible explanations for PMS have been suggested, including nutritional deficiency.²² Studies of PMS have had to deal with the strong placebo response of PMS sufferers^20,, which underlines the intimate association of physiological and psychological factors. Investigation of essential fatty acid levels has shown elevated levels of linoleic acid but reduced levels of metabolites²³, indicating a possible alteration of fatty acid metabolism.

The most widely known and accepted use of Evening Primrose oil, and therefore GLA, has been in the management of premenstrual syndrome. Depression and irritability, breast pain and fluid retention associated with PMS have all been seen to respond positively to gamma-linolenic acid supplementation.²⁴

Three possible mechanisms have been mooted for the action of GLA. Firstly, the presence of essential fatty acid may encourage esterification of steroid hormones, thereby increasing their activity. Secondly, the fatty acid environment of the receptor molecules modifies the affinity of the receptor for steroids. Increased levels of polyunsaturated fatty acids may mediate the receptor-ligand response. Thirdly, PMS symptoms may be due to prolactin sensitivity. Prostaglandin E1 is a product of omega-6 fatty acid metabolism and modulates the activity of prolactin.20 Prolactin is a pituitary gland hormone which stimulates milk production.2 Though prolactin levels are not elevated in women experiencing PMS, it is theorised that PMS symptoms may result from an increased sensitivity to the hormone.²⁴

 Atopic eczema

The earlier work of Wright and Burton (1982) showed that oral supplementation with Evening Primrose oil improved the signs and symptoms of atopic eczema in both children and adults in a dose-dependent manner.²⁵ Gamma-linolenic acid applied topically, in conjunction with standard topical steroid treatment for atopic eczema, has been shown to significantly improve the condition.²⁶

It has been suggested that atopy in general is linked to inadequate conversion of the omega-6 fatty acids to prostaglandin E1. Supplementation with Evening Primrose oil increases the level of the prostaglandin being produced, overcoming the deficient conversion.²⁷ Plasma phospholipids of patients with atopic eczema show elevated levels of linoleic acid, the major dietary omega-6 fatty acid, but significantly reduced levels of all subsequent metabolites. Omega-3 fatty acids show similar trends. This indicates that abnormal metabolism, possibly of the delta-6-desaturase, could be responsible for atopic eczema.²⁸ If the functioning of delta-6-desaturase is impaired then that becomes the rate-limiting step for the omega-6 pathway. By introducing gamma-linolenic acid into the system, the rate-limiting step is bypassed and the enzyme deficiency is overcome.²⁹ A meta-analysis of nine trials on gamma-linolenic acid lent weight to the claims for GLA and detected statistically significant correlations between clinical improvement and a rise in levels of dihomo-gamma-linolenic acid and arachidonic acid³⁰, providing further evidence of a specific metabolic alteration.

Since prostaglandin E1 is involved in T-cell maturation in the infant, it has been suggested that the depressed cell-mediated immune response in atopy is a result of inadequate omega-6 fatty acid metabolism during the prostaglandin E1-sensitive T-cell maturation period in infancy²⁷. Horrobin suggests that supplementation of infant feeding formulae, or the mother herself if she is atopic, may prevent the emergence of atopic disorders.²⁰

 Other

Diabetes is associated with a variety of ongoing health problems, including neuropathy which appears to be correlated to delta-6-desaturase metabolism. It is theorised that at least one mechanism of neuropathy is impaired oxygen delivery. Inadequate levels of 6-destructed fatty acids in red cells, it is suggested, reduce the flexibility and mobility of cell membranes, thereby impeding oxygen transmission to nerve cells.²⁰

Gamma-linolenic acid has been examined in relation to rheumatoid arthritis and related inflammatory disorders, and appears to act through its position as a precursor of prostaglandin E1, which suppresses inflammation in a number of animal models.²⁰ Associated conditions, such as systemic sclerosis and Sjogrens’ syndrome, also appear to respond to omega-6 supplementation. Omega-6 fatty acid metabolism has also been implicated in psychophysiological disorders such as schizophrenia, alcoholism and dementia. The exact mechanisms and possible clinical applications have not been determined.²⁰

Omega-6 fatty acid has been linked to a variety of conditions and disorders. The most widely suggested reason is an abnormality in metabolism due to altered functionality of delta-6-desaturase. Due to the assortment of prostaglandins which may result from the omega-6 pathway, the implications of altered metabolism are wide ranging. In disorderition to prostaglandin effects, other metabolites, including oxidised species, have been implicated in disease mediation.

 Vitamin E

Vitamin E was first identified in 1922 as a compound essential for proper reproduction in rats. Vitamin E (alpha-tocopherol) is a lipid-soluble antioxidant and forms a significant part of the body’s antioxidant system. At this point, it appears that effects of vitamin E are due primarily, but not exclusively, to its antioxidant properties.^31,32

Due to its involvement in the protection of lipids and lipoprotein from oxidation ^33,34,35,36 it seems logical that vitamin E plays an important role in essential fatty acid metabolism. This would be even more important if essential fatty acids were used at therapeutic doses.

Principally because of its lipoprotective properties, adequate vitamin E levels have been identified as being important in cardiovascular health. Epidemiological studies show a correlation between low vitamin E status and cardiovascular disease.^35,37,38Atherosclerosis, in particular, appears to be at least partially dependent upon antioxidant status, with an emphasis on vitamin E levels. ^39,40,41,42 Several long-term studies of the effects of vitamin E on cardiovascular disease have been undertaken to search for a definitive causal relation and to determine the most appropriate use of vitamin E in prevention.⁴³

Ageing, and the implication of oxidation in the progression of ageing, has been examined in relation to vitamin E and antioxidants in general. The cellular immune response in aged persons is dependent upon the antioxidant-oxidant balance, with vitamin E playing an important role in maintaining immune function.⁴⁴ Evidence suggests that vitamin E and other antioxidants can protect against macular degeneration and cataracts in the ageing, particular in smokers (smoking is known to reduce antioxidant levels in the body).^45,46

Intimately involved in the question of oxidative damage is the role that oxidation plays in the initiation and propagation of cancers. Numerous studies have shown the protective effects of antioxidants, with various antioxidants having effects in various tissues.^47,48 Beta-carotene and vitamin E appear to have a preventive role in oral cancer ^49,50 and Machlin (1995) suggests that supplemental vitamin E – but not dietary level vitamin E is associated with a reduced risk of certain cancers.⁵¹

Vitamin E may possibly have a role in mediating the effects of oxidative stress from physical exertion during athletic training, but it is a controversial issue and there appears to be little evidence for actual athletic performance improvement due to supplementation.^52,53

References