Nutritional and metabolic effects of dietary fatty acids

Nutritional and metabolic effects of dietary fatty acids

Two types of issue exist in relation to the nutritional and health implications of individual dietary lipids.

1 Whether synthesized endogenously or only obtained from the diet, what are the specific mem-brane, precursor, or metabolic effects of dietary lipids beyond that of providing energy?

2 Whether synthesized endogenously or obtained from the diet, does an excess amount of a dietary lipid have beneficial or deleterious implications for health?

Short- and medium-chain fatty acids

Short-chain fatty acids (1–6 carbons) are mostly derived from carbohydrate fermentation in the large bowel and appear to be mainly used for energy, although they are also substrates in several pathways. Butyrate may have an important role as an energy substrate for enterocytes. Medium-chain fatty acids (8–14 carbons) naturally appear in mammalian milk and are almost exclusively used as energy substrates. They may also be chain elongated to palmitate.

Saturated fatty acids

Palmitate and stearate constitute a major proportion of the acyl groups of membrane phospholipids and all mammals have the capacity to synthesize them. Hence, empirically, they presumably have an impor-tant function in energy metabolism, cell structure, normal development, and growth. The 20- to 24-carbon saturates are also important constituents of myelin. However, in any of these functions, it is unlikely that a dietary source of saturates is necessary. In fact, the brain is unable to acquire saturated fatty acids from the circulation and relies on its own endogenous synthesis for these fatty acids. Furthermore, chronic excess intake and/or synthesis of palmitate and stearate is associated with an increased risk of diabetes and coronary artery disease.

Monounsaturated fatty acids

Little is known about the nutritional or health impli-cations of palmitoleate (16:1n-7), but there is a bur-geoning interest in the main dietary monounsatu-rated fatty acid, oleate, and the health implications of olive oil. In the context of the same total fat intake, the main benefit of higher oleate intake seems to be that this reduces intake of palmitate and stearate and that this helps to lower serum cholesterol.

Partially hydrogenated fatty acids

Partially hydrogenated fatty acids contain a large pro-portion of trans fatty acids that are not naturally occurring but arise directly from food processing. Hence, unlike saturates and cis-unsaturated fatty acids, they are not a necessary component of the diet except in the small amounts found in cow’s milk. Their physical characteristics make them economi-cally suitable for inclusion in a wide variety of baked, fried, and oil-based foods, from which they can easily contribute up to 10% of dietary fat depending on food selection. Epidemiological evidence and some experimental studies show that common dietary trans fatty acids raise LDL cholesterol and lower HDLs in healthy adults, so the main nutritional concern is that they may contribute to an increased risk of cardiovas-cular disease.

Trans fatty acids have also been experimentally shown to compete with and impair the metabolism of other dietary long-chain fatty acids, but the rele-vance of these observations in humans is unclear. Trans fatty acids can be present in baby foods at rela-tively high concentrations but, so far, there is no evi-dence of deleterious effects on growth or development. Some information on the metabolism of trans fatty acids in humans has been gained from tracer studies, but fundamental information, such as the rate at which they are oxidized, is still unknown.

Polyunsaturated fatty acids

Unlike saturates and monounsaturates, a dietary source of n-6 and n-3 polyunsaturates is a necessity for normal growth and development. As with other essential nutrients, this has given rise to assessment of the dietary requirements for polyunsaturates and the implications of inadequate dietary intake of them.

It has been accepted for over 50 years that n-6 polyunsaturates, particularly linoleate, are required in the diet of all mammals, including humans. Official dietary guidelines generally recommend a dietary source of linoleate at 1–2% of energy intake. It has taken much longer to demonstrate that n-3 PUFAs are required by humans. Although this now seems widely accepted among nutrition researchers, some countries, including the USA, still do not yet officially recognize that, as a minimum, α-linolenate is a required nutrient. As with other nutrients, the require-ment for polyunsaturates varies according to the stage of the life cycle, with pregnancy, lactation, and infancy being the most vulnerable. Symptoms of linoleate deficiency are virtually impossible to induce in healthy adult humans, so the concept of “conditional indis-pensability or dispensability” of PUFAs has recently emerged to replace the older but ambiguous term “essential fatty acid.” Linoleate appears to be condi-tionally dispensable in healthy nonpregnant adults, but is not in pregnancy, lactation, or infancy.

Because of the competition between the two fami-lies of PUFAs, deficiency of n-3 PUFA is commonly induced by an excess of dietary linoleate. Hence, dis-cussion of the requirements for linoleate and α-lino-lenate has focused on their ratio in the diet. The ratio of n-6 to n-3 polyunsaturates in human milk (5:1 to 10:1) has been widely viewed as a suitable reference for this ratio in the general diet. In most affluent countries, this ratio remains much higher, at about 20:1, and has been implicated in subclinical deficiency of n-3 polyunsaturates. There is recent evidence to suggest that it is the absolute amounts of long-chain n-3 and n-6 fatty acids that are important in predict-ing health outcomes, and not the dietary ratio of these PUFAs.

Essential fatty acid deficiency

The first experimental model of deficiency of polyun-saturates was total fat deficiency. The elimination of dietary fat had to be extreme because the traces of fat found in starch and dietary proteins were sufficient to prevent reproducible symptoms of fat deficiency. The deficiency symptoms are now well known and involve dry, scaly skin, growth retardation, and repro-ductive failure. Most of these gross symptoms are relieved by linoleate and arachidonate. Although α-linolenate cannot be synthesized de novo, it has little effect on these gross symptoms. However, careful studies using a diet that is extremely deficient in n-3 polyunsaturates and contains an excess of n-6 poly-unsaturates led to deficiency of n-3 polyunsaturates, characterized by delayed and impaired neuronal development and impaired vision. These symptoms have been traced in many species to the inadequate accumulation of docosahexaenoate in the brain and eye. Hence, the main function of n-3 polyunsaturates appears to hinge on synthesis of docosahexaenoate. In contrast, the function of n-6 polyunsaturates involves independent roles of at least linoleate and arachidonate.

Human cases of deficiency of PUFAs, usually involve a clinical disorder, often involving weight loss, trauma such as surgery, or a disease requiring paren-teral nutrition. However, reports of these cases are uncommon and describe dissimilar characteristics, leading one to question whether the same deficiency exists. Recent investigations into the amount of PUFA in the whole body and the rate at which they can be oxidized suggest that traumatic or disease-related processes leading to weight loss affect metabolism of polyunsaturates more severely than simple dietary deficiency in a weight-stable, healthy individual. For example, deficiency of linoleate has been long sus-pected but difficult to demonstrate in cystic fibrosis. Despite poor fat digestion, intake levels of linoleate may not be inadequate but its β-oxidation could well be abnormally high owing to the chronic infectious challenge.

Clinical importance of polyunsaturates

Infant brain and visual development is dependent on adequate accumulation of docosahexaenoate. The 1990s saw intense clinical and experimental assess-ment of the role of docosahexaenoate in early brain development and a widespread concern that many infant formulae do not yet contain docosahexaenoate. Several clinical studies and extensive use of formulae containing docosahexaenoate and arachidonate have shown that they are safe. Many but not all such studies show an improvement in visual and cognitive scores compared with matched formulae containing no docosahexaenoate or arachidonate. The infant brain and body as a whole clearly acquire less docosahexae-noate when only α-linolenate is given. As a whole, these data suggest that docosahexaenoate is a condi-tionally indispensable fatty acid.

Aside from questionable deficiency of polyunsatu-rates in cystic fibrosis , one of the most graphic examples of their deficiency being caused by an inherited disease is Zellweger’s syndrome. This condition causes severe mental retardation and early death. It is a disorder of peroxisomal biogenesis and one outcome is markedly impaired synthesis of doco-sahexaenoate. Dietary supplementation with docosa-hexaenoate appears to partially restore neurological development.

Epidemiological evidence shows that chronic degenerative diseases of affluence are directly associ-ated with the deficiency of n-3 PUFAs. Indeed, coun-tries with relatively high rates of these diseases usually have an adequate to perhaps unnecessarily higher intake of linoleate. High intakes of linoleate have been implicated in death from coronary artery disease and several types of cancer because these diseases are asso-ciated with low intakes of n-3 polyunsaturates. Mental illnesses such as schizophrenia may also be associated with low intake of n-3 polyunsaturates and respond to supplements of n-3 polyunsaturates. A more balanced ratio of intake of n-6 and n-3 polyunsaturates might achieve a reduction in the rate of these degenerative diseases but has not yet been widely investigated.

Diets in Paleolithic times contained no processed food and probably balanced amounts of n-3 to n-6 polyunsaturates and a lower level of saturates. Such diets would be predicted to lead to a lower incidence of degenerative disease. Since the brain has a very high energy requirement, it has also been speculated that human brain evolution beyond that of other pri-mates was dependent on a reliable and rich source of dietary energy and a direct source of long-chain poly-unsaturates, particularly docosahexaenoate.