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Yellow Gold - A Fresh Look at an Old Friend

M. Tom Clandinin and Stephanie Cook

Nutrition and Metabolism Research Group,
Department of Agricultural, Food, and Nutritional Science and
Department of Medicine, University of Alberta,
410 Agriculture/Forestry Centre, Edmonton, AB, Canada, T6G 2P5
E-mail: tclandin@gpu.srv.ualberta.ca

Take Home Messages
The general public and health professionals hold a wide range of unfounded beliefs about diet fats. For example, many believe dairy fats are unhealthy.

There is little evidence to suggest that reduction of palmitic acid in the diet of the normal individual will reduce his/her development of atherosclerosis.
There is considerable evidence indicating that plasma cholesterol levels are genetically determined.
The dairy industry should consider how to invest in developing NEW INFORMATION on old products and NEW PRODUCTS for high value added purposes.

Identifying Our Preconceived Notions About Diet Fat

Many of you are convinced that some diet fats are unhealthy?? Much of the general public holds the view that dairy fats contain specific components that are unhealthy and that specific vegetable oils are healthy. For example, many of you believe that corn oil is more healthy that dairy fat?? This view is held in spite of the fact that diet fat is not one oil or fat source, but a mixture of many components that should be in balance. In short, the impact of advertising using only part of the scientific observations has provided the public with a very incomplete and often erroneous impression of the role of fat in the diet. In this article, I would like to provide another perspective.


The importance of plasma cholesterol as a risk factor is clear (Figures 1 and 2). Coronary heart disease (CHD) is rare among populations where plasma cholesterol is below 5.2 mmol/l. Risk appears to increase progressively at levels above this value, and a number of lipid lowering drug trials have shown that CHD rates may be lowered by therapy. Many uncertainties remain.

The Triglyceride Issue
Because serum triglyceride is positively correlated with total cholesterol, obesity, alcohol intake, and diabetes, but negatively correlated with HDL cholesterol, its independent contribution to CHD risk has been difficult to assess. Serum triglyceride emerges as a positive risk factor, but when other risks are taken into account the significance of triglyceride diminishes.

The Framingham group has shown excess CHD risk in men and women with high triglyceride and low HDL irrespective of the total cholesterol level. The French workers, who did not measure HDL, reported excess CHD risk in patients with high triglyceride and normal cholesterol. There is also renewed interest in the possibility that high levels of triglyceride may affect blood coagulation as well as atherogenesis.

For the present, it appears reasonable to conclude that in subjects with high cholesterol, the co-existence of high triglyceride adds little extra risk. In subjects with normal cholesterol, triglyceride > 3 mmol/l may be associated with increased mortality from CHD, particularly if HDL is < 1 mmol/l.

Cholesterol and Cancer

A further area of interest concerns the inverse relationship between serum cholesterol and cancer. If a preclinical cancer effect is not responsible, what alternative explanations may exist? Two other possibilities deserve consideration: First, that some other factor is lowering cholesterol and independently predisposing to cancer; and second that low levels of serum cholesterol per se promote the development of cancer. Both views have their protagonists, but as yet the issue is unresolved.

Japan and Heart Disease

Japan is now the country with the highest longevity in the world. This status was acquired by reducing mortality from stroke and ischaemic heart disease beginning with the period 1965-70. In Japan, fat and cholesterol intake has increased remarkably over the last three decades in accordance with the westernization of lifestyles and in particular, dietary intake of milk and dairy products has increased greatly (Figure 3, 4, and 5).

Many epidemiological follow-up studies of the Japanese have revealed that risk factors for stroke and ischaemic heart disease are no different from those for the US and European countries. In Japan, hypertension was also cited as one of the main risk factors for stroke, while hypertension, hypercholesterolaemia and smoking were risk factors for ischaemic heart disease.

Arachidonic Acid Metabolism
Animals and humans are able to convert 20:4n-6 into a variety of biologically active metabolites which include prostaglandins, thromboxanes, and leukotrienes, collectively known as eicosanoids. The balance of these eicosanoid metabolites is important for regulation of physiological processes such as platelet function, inflammation, thrombosis, and many others. The profile of eicosanoids varies from cell to cell; blood platelets convert arachidonic acid to TXA2, whereas vascular endothelium produces mainly PGI2. TXA2 is a potent vasoconstrictor which induces platelet aggregation and PGI2 is the most potent vasodilator which inhibits platelet aggregation. Balance between these two eicosanoids maintains normal haemostasis and any alteration in the TXA2/PGI2 ratio will affect thrombosis, haemostatic plug formation, and atherogenesis.

Alteration in dietary fat may modify TXA2/PGI2 balance. Eicosapentaenoic acid 20:5n-3 present in fish oil competes with arachidonic acid at the level of cyclo-oxygenase and inhibits TXA2 and PGI2 formation. It appears that 20:5n-3 is converted to TXA3, a weak pro-aggregating agent with PGI3, a potent anti-aggregating agent. Therefore, the overall effect of fish oil consumption is a decrease in platelet aggregation or increased bleeding time. Since arachidonic acid availability is a key factor in eicosanoid formation, increased attention has been given to synthesis and incorporation of 20:4n-6 into phospholipid pools. N-3 fatty acids, particularly 20:5n-3, are incorporated into plasma and tissue phospholipids at the expense of n-6 fatty acids.

From both animal and human studies it is clear that there is considerable metabolic interaction between the effect of dietary C20 and C22 n-3 fatty acids and the metabolism of 18:2n-6. The efficacy of dietary -3 fatty acid intake is determined in part by the interaction and by the overall balance of dietary fatty acids fed. Thus, one can envisage that potential beneficial metabolic effects of dietary n-3 fatty acids will be optimized by dietary background that is low in competing substrates (i.e. low in polyunsaturated to saturated fatty aids) even though the overall level of n-3 fatty acid intake is relatively low.

Genetic Variance in Responsiveness

Cholesterol Intake

In controlled dietary trials with the same subjects, studies have been conducted to determine whether individuals exist with a consistently high or low serum cholesterol response to dietary cholesterol (3). When volunteers successively consumed a low-cholesterol and a high-cholesterol diet with the cholesterol component of the diets provided by egg yolk being the only variable, subgroups of putative hyporesponders and hyperresponding subjects, with mean serum cholesterol increases of 0 and 19%, respectively, were selected from a larger population. These subjects then underwent a second and third experiment. Although the response in each subject was only partly reproducible, selected hyperresponders showed significantly higher serum cholesterol responses in the second and third trial than the hyporesponders (Table 1).

Thus it appears that in humans at least part of the cholesterolaemic response to dietary cholesterol is individually determined. It is also clear that some subjects who appear hyperresponsive in one experiment may appear hyporesponsive in another. This is caused by the diet-independent within-person variability of serum cholesterol. Serum cholesterol fluctuates within subjects on a constant diet with a periodicity of two to three days and an amplitude of up to 1.5 mmol/1. Thus the timing of the actual pre- and post-diet change blood samples can be such that the observed response to diet change appears much larger than the actual mean response.

Diet Fat Intake: Palmitic Acid

For almost 40 years we have realized that dietary fat alters the plasma cholesterol concentration, but the degree to which various fats or their composite fatty acids modulate these effects and the mechanism(s) involved are not well understood. The situation has been recently complicated because the original findings of Keys and Hegsted, with particular regard to the effects of specific fatty acids, have been questioned. Whereas the dietary P/S ratio and intake of total saturated fats were thought to constitute the main impact, attention is now focused increasingly on the contribution from monounsaturated fats. Stearic acid has been shown to be neutral in raising serum cholesterol level and when the Keys equation is modified to treat dietary 16:0 level as neutral, the equation is a better predictor of observed changes in serum cholesterol levels (Figure 6).

Hayes and Khosla hypothesized that 16:0 is neutral (does not raise cholesterol) relative to 18:1 in normocholesterolemic individuals (< 5.2 mmol/L, 200 mg/dL) and/or when dietary cholesterol intake is low (<= 300 mg/d). In such situations 14:0 appears to be the unique cholesterol-raising fatty acid. To test this hypothesis, a study was designed to exchange 5% of energy from 12:0 + 14:0 for 16:0 in normocholesterolemic human subjects consuming diets containing ~200 mg cholesterol/d (Table 2;4). Subjects were members of the Royal Malaysian Army sequestered in a training camp of the army signal school. The results indicate that a dietary combination of 12:0 and 14:0 combination produces a higher serum cholesterol concentration than does 16:0 in healthy normocholesterolemic young men fed a low-cholesterol diet (Table 3).

Effect of Palm Oil, Margarine, Butter on Serum Lipids

In a recent study by Randall Wood (5), 29 healthy, middle-aged men participated in a study containing six dietary fats. The level of test fat consumed by the participants (18 to 20% of total energy) far exceeded the amount most individuals would consume from a single fat source on any dietary regimen. The extreme levels were used to elicit the largest possible change in serum lipids. Despite the high level of test fats consumed, the responses of serum lipids, lipoproteins, and apolipoproteins were unexpectedly small (Table 4).

The butter diet did not elevate total serum cholesterol or LDL cholesterol significantly relative to either baseline in this group of middle-aged men. The degree of elevation of cholesterol in this study was surprisingly low compared with results with institutionalized subjects or patients on liquid formula diets and approximately one-half the rise above pre- study values for a group of hypercholesterolemic men who consumed 34% of their energy as butter for two weeks. In a similar study to the one described here that contained 38 participants, butter produced a small (5%), but significant rise in the total serum cholesterol and LDL- cholesterol relative to baseline and four other dietary fats.

Palm oil, often proclaimed to be absent from many manufactured foods, did not elevate serum cholesterol, even at these high levels. Palm oil-diet lipoprotein and apolipoprotein profiles were equal to or more desirable than the other test fat (5). The sunflower oil diet, high in polyunsaturated fatty acids, reduced total serum cholesterol the most of any diet, along with reduced LDL-cholesterol and apolipoprotein B. Unfortunately, the desirable HDL-cholesterol and apolipoproteins A1 were also reduced.


Collectively these studies suggest clear inconsistency in the suggestion that all saturated fats produce deleterious changes in serum cholesterol levels in normal individuals. It is apparent that palmitic acid may not be hypercholesterolemic as a component of the total diet of normal individuals.


1. Isles, C. G. and Hole, D. J. (1992) Coronary risk factors today: A view from Scotland. In: Cholesterol and Coronary Heart Disease. The Great Debate. The Parthenon Publishing Group, Park Ridge, N.J. USA. pp. 177- 187.
2. Ueshima, H. (1992). Trends in fat and cholesterol intake, serum cholesterol levels, and cardiovascular disease in Japan. In: Cholesterol and Coronary Heart Disease. The Great Debate. The Parthenon Publishing Group, Park Ridge, N.J. USA. pp. 63-78.
3. Katan, M. B. and Beynen, A. C. (1992). Hyporesponders and hyperresponders to changes in diet. In: Cholesterol and Coronary Heart Disease. The Great Debate. The Parthenon Publishing Group, Park Ridge, N.J. USA. pp 177-187.
4. Sundram, K., Hayes, K. C., and Siru, O. H. (1994). Dietary palmitic acid results in lower serum cholesterol than does a lauric-myristic acid combination in normolipemic humans. Am J. Clin Nutr; 59: 841-846.
5. Wood, R., Kubena, K., Tseng, S., Martin, G., and Cook, R. (1993). Effect of Palm Oil on the Serum Lipids and Lipoproteins of normocholesterolemic middle-aged men. J. Nutr. Biochem: 4: 286-297.

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