J. Booyens

Chronic arachidonic acid eicosanoid imbalance: A common feature in coronary artery disease, hypercholesterolemia, cancer and other important diseases. Significance of desaturase enzyme inhibition and of the arachidonic acid desaturase-independent pathway

A chronic imbalance between the essential fatty acid metabolites arachidonic acid, gamma-linolenic acid and eicosapentaenoic acid and of their respective eicosanoid derivatives appears to be implicated in the etiology of many intractable disease. Most notable among these are coronary artery disease, cancer and chronic inflammation. The factors leading to such an imbalance and their relatively simple prophylactic and therapeutic circumvention are discussed briefly.

The Eskimo diet. Prophylactic effects ascribed to the balanced presence of natural cis unsaturated fatty acids and to the absence of unnatural trans and cis isomers of unsaturated fatty acids

In addition to the well recognised roles of eicosapentaenoic acid and possibly docosahexaenoic acid, there are two other major important, but unrecognised, features of the traditional Eskimo staple diet namely that it contains the unsaturated fatty acids (UFA) cis oleic, cis linoleic and cis alpha-linolenic as well as their respective C20 and C22 metabolites in physiologically optimal concentrations and, it is virtually totally devoid of unnatural and potentially hazardous trans and cis isomers of these fatty acids. Large quantities of unnatural trans and cis isomers of UFA are found in the Western diet as partially hydrogenated UFA in many foods. These isomers are formed during the manufacture of margarines and related compounds, as food contaminants during excessive heating of cooking oils for deep-frying and other excessive heat-requiring mass food preparation procedures and it is suggested, as the result of excessive feeding with an unnatural diet of ruminants and non-ruminants for increased meat and/or milk production and of poultry for increased egg and/or meat production. These isomers have been shown to display potentially hazardous metabolic effects which include the competitive inhibition of UFA metabolism at various steps and have been causally implicated in the etiology of ischemic heart disease and cancer. It is suggested that the myth of the safety of trans fatty acids arises from misinterpretation of the observation that increasing dietary cis linoleic acid reduces the toxic effects of trans UFA. It is suggested that the decrease of 20% in the ischemic heart disease mortality in the USA during the past two decades is directly related to a shift in the dietary ratio of unnatural trans and cis UFA isomers: cis linoleic acid in favour of the latter. It is predicted that this ratio will be found to correlate with ischemic heart disease patterns in other countries. Eskimos consume the bulk of their food frozen, raw or dried, seldom boiled, but never deep-fried or after exposure to excessive heat. Moreover the proportionality of cis UFA and their metabolites in their traditional staple diet would render gross tissue UFA utilization relatively independent of desaturase enzyme activity. In the Eskimo tissues these enzymes would function to make the minute, critical UFA metabolic adjustments required to ensure the presence of structural UFA in membranes in functionally optimal quantities and, ensure the synthesis of eicosanoids from dihomogamma-linolenic acid, arachidonic acid and eicosapentaenoic acid in balanced, optimal physiological concentrations for the genetic make-up of Eskimos.(ABSTRACT TRUNCATED AT 400 WORDS)

Margarines and coronary artery disease

In a previous paper we predicted that health effects of dietary fats in humans would require half a century or more to be understood, instead of the decade or so predicted during 1956 by an Editorial in The Lancet. It would seem that our prediction may have been optimistic since it has now been reported that trans unsaturated fatty acids present in high concentrations in margarines promote hypercholesterolemia in humans. Consequently, there has been a call for the reclassification of dietary fats upon the basis of their hypercholesterolemic properties. Using the latter criterion, therefore, many margarine brands would be classified as coronary artery disease risk foods. The primary adverse metabolic action of trans unsaturated fatty acids is the competitive inhibition of delta-6-desaturase, the hepatic enzyme responsible for the initial metabolic desaturation of the essential fatty acids cis linoleic and cis alpha-linolenic acid. In addition to margarines, many other common foods such as deep-fried foods, many convenience foods and bakery products contain relatively high levels of trans fatty acids. Therefore, since it has become virtually impossible to avoid a consistent, daily dietary intake of trans fatty acids, it would appear that a precautionary, preventative supplementation of the diet with supplements containing the direct metabolic products of delta-6-desaturation of the essential fatty acids, would be prudent. Such supplements are readily available.

The presence of trans unsaturated fatty acids in ruminant meat and milk is unnatural

It is proposed that the presence of large quantities of trans unsaturated fatty acid isomers as final metabolic products of the rumen bacteria and their consequent presence in ruminant tissues and milk is completely unnatural. This results from excessive feeding of domestic ruminants and the consequent passage of bacteria containing partially hydrogenated trans fatty acids into the small intestine. Digestion of such bacteria and the subsequent absorption of the released trans fatty acids could account for their unnatural presence in ruminant tissues and secretion in milk. It is also proposed that the feeding of ruminants, poultry and pigs with unsaturated fatty acid-containing concentrates, could also be a source of trans fatty acids which occur in their tissues.

The use of drugs for the inhibition of prostaglandin or leukotriene synthesis from arachidonic acid is theoretically hazardous

It would appear that it has become almost common practice to regard arachidonic acid (AA) as the sole precursor of eicosanoids. The fact that both dihomogamma-linolenic acid (DGLA) and eicosapentaenoic acid (EPA) give rise to distinct families of eicosanoids is commonly almost completely ignored. Elevated tissue levels of AA eicosanoids have been found in and have been implicated in the etiology of a number of diseases. Drugs which selectively block AA mobilization or its eicosanoid metabolism have therefore been developed for therapeutic use in these conditions. The fact that such drugs will also simultaneously block the eicosanoid metabolism from DGLA as well as from EPA is also commonly ignored. It is suggested that the profoundly adverse side-effects displayed by some of these drugs, resulting in some instances in their withdrawal from use, could be the direct result of their concomitant action of interfering with the eicosanoid metabolism of DGLA and EPA. It is further suggested that, before the interactions between the eicosanoids derived from AA and those derived from DGLA and EPA are understood, the use of drugs for the manipulation of AA eicosanoid metabolism in isolation, could be hazardous. This implies that all such drugs currently in use are to be regarded as experimental and provisionally toxic in terms of their effects on the whole system of eicosanoid metabolism. Thus even drugs which have been passed by the FDA and similar Drug Control Councils require total re-evaluation especially in view of the fact that the non-steroidal anti-inflammatory drugs are often prescribed for chronic conditions which require therapy for several years.(ABSTRACT TRUNCATED AT 250 WORDS)

Atherogenesis. An epidemiological model based on the presence of unnatural trans and cis isomers of unsaturated fatty acids in the maternal diet and in mothers milk

The hypothesis that the presence of unnatural trans and cis isomers of unsaturated fatty acids in the maternal diet and in human mothers milk could be responsible for initiating atherosclerosis in utero or in infants is proposed. It is suggested that the key etiological factor involved in the formation of atherosclerotic plaques could be uncontrolled division of smooth muscle cells of the intima resulting from the intracellular excess of linoleic acid and deficiency of its metabolites gamma-linolenic acid and dihomogamma-linolenic acid. This imbalance is brought about by competitive inhibition of the enzyme delta-6-desaturase by unnatural trans and cis unsaturated fatty acids. Delta-6-desaturase is the enzyme responsible for converting linoleic acid to dihomogamma-linolenic acid. The cellular presence of unnatural trans and cis isomers of unsaturated fatty acids would therefore enhance increased levels of linoleic acid and deficiency of its metabolites gamma-linolenic acid and dihomogamma-linolenic acid. It is proposed that prophylaxis against the effects of delta-6-desaturase inhibition could be achieved by the adoption of an Eskimo-like diet containing the essential fatty acid metabolites gamma-linolenic acid and/or dihomogamma-linolenic acid and eicosapentaenoic acid per se in high concentrations.

Cancer: A simple metabolic disease?

Recent studies on the effects of the essential fatty acid metabolic intermediate, gamma-linolenic acid, on the growth of cancer cells in culture and on induced mammary cancer tumours in rats, strongly suggest that the metabolic defect in the cancer cells studied is simply a metabolic block involving the enzyme delta-6-desaturase. The latter enzyme is responsible for the conversion of linoleic acid to gamma-linolenic acid. These observations would suggest that cancer in the cell lines studied could be a relatively simple metabolic disease.