elongated 20 and 22-carbon forms of both n6 and n3 families) are inversely related to levels of coronary heart disease (CHD). Paradoxically (at least in terms of the American Heart Association dietary recommendations), Hindu vegetarians from India whose diet is composed largely of low-fat grains and pulses (legumes) maintain CHD rates equal to [Begom et al. 1995] or higher [Miller et al. 1988] than those in the USA and countries of Europe, despite their diets' lower total fat content when compared to American and European diets.
Indian populations have consistently exhibited high plasma n6/n3 ratios, low levels of 20:5n3 and 22:6n3, and high levels of 18:2n6 when compared to Western populations [Miller et al. 1988; Reddy et al. 1994; Ghafoorunissa 1984; McKeigue et al. 1985]. All of these EFA profiles are conducive to CHD and occur because of the lack of an appropriate balance of n6/n3, and because of the almost total lack of 20 and 22-carbon fatty acids in commonly consumed plant-based foods.
Regarding the second part of the above comment, it is partially correct to say that omega-3 (n3) fats provide protection against CHD, but it has little to do, directly, with keeping the arteries clear (i.e., atherosclerosis). N3 fats provide protection from CHD in that they lower triglycerides and perhaps VLDL; additionally, they reduce platelet adhesitivity and decrease thrombotic tendencies as well as reducing cardiac arrhythmias [Leaf et al.1988]. However, recent large-scale meta-analyses [Harris 1997] show that n3 fats actually cause a 5-10% rise in LDL cholesterol and a small rise (1-3%) in HDL. Eskimo populations indeed do consume higher levels of both saturated fat and polyunsaturated n3 fats than do Western populations; they also exhibit significantly lower serum LDL and total cholesterol levels than Europeans [Bang and Dyerberg 1980].
Thus, logic (derived from the meta-analytical data) dictates that the n3 fats are not the element responsible for the lower total and LDL serum cholesterol in these populations. Careful analysis of Bang and Dyerberg's data [1980] reveals a much higher protein intake (26% of total calories) compared to the 11% value in Danes. High protein intakes are known to cause drastic inhibition of hepatic VLDL synthesis [Kalopissis et al. 1995] (VLDLs are the source of LDLs), and high-protein diets in humans have been clinically shown to reduce total cholesterol, LDL cholesterol, and triglycerides while simultaneously increasing HDL [Wolfe 1995]. Further, acute consumption of high levels of low-fat (6.5%), lean-beef protein is not associated with a post-prandial rise in insulin but rather an increase in glucagon levels [Westphal et al. 1990].
Consequently, the major reason why Eskimo diets keep serum cholesterol levels low and atherosclerosis at bay is because of their high protein content primarily. There is no doubt that n3 fats also contribute to lowering CHD, but it is not directly mediated by a lowering of LDL cholesterol but rather by other mechanisms previously outlined.
| Effect of fat, protein, and carbohydrate on glucagon levels |
Follow-up question: To clarify the above statement that low-fat (6.5%) beef stimulates higher glucagon levels, isn't it the protein content of beef rather than the fact it is also low in fat that stimulates glucagon? My impression was that fat intake level has little effect on the insulin/glucagon response to food. (Editorial note: Release of insulin not only causes uptake of glucose into cells, but also promotes fat storage. Glucagon is the other side of the equation, causing mobilization of body fat for conversion to energy; that is, it causes fat to be burned.)
As far as I know, there are no good, recent data evaluating the effects of varying protein/fat mixtures upon insulin/glucagon responses in humans. Most of the data involves manipulating carbohydrate, with varying amounts of fat; protein is usually held constant. The Westphal et al. [1990] paper evaluates protein/carbohydrate mixtures on serum glucagon responses. Pure dietary carbohydrate (50g glucose) shows no rise in plasma glucagon, whereas pure protein (actually 93.5% lean beef, 6.5% fat, as mentioned above) causes the greatest rise in glucagon after 1 hour; with roughly equal areas under the curve after 3 hours when comparing pure protein to protein/carbohydrate mixtures (50g glucose/50g protein).
Thus, there appears to be a dose/response effect on glucagon with protein/carbohydrate mixtures, and from the data, it can probably be interpreted that there is a dose/response effect with pure protein. As far as insulin response goes (as opposed to glucagon response), fat/carbohydrate mixtures cause a greater rise than carbohydrate meals alone, presumably because of the stimulatory effect of fat upon glucose-dependent insulinotropic peptide (GIP) [Collier et al. 1988].
Thus, as indicated by the question, there is a dose-dependent effect of dietary protein upon glucagon secretion which is largely independent of either carbohydrate or fat.
| Protein levels and their effect on blood lipids |
Some would dismiss the idea that dietary protein can have any influence upon cardiovascular disease with the argument that there is no difference in CHD incidence in populations consuming high vs. low-protein diets. However, a serious problem with this argument is the lack of much substantial variability in current protein consumption levels worldwide to produce support for this line of reasoning via epidemiological comparisons.
Global surveys of the world's populations indicate a remarkably limited range of protein consumption that varies from about 10 to 15% of total calories [Speth 1989]. Further, except for reports of Inuit and Eskimo diets, I know of no references showing any contemporary populations consuming 15-20% of their calories as protein, much less high-protein diets in the 30-40% range of consumption such as our ancestors or recent hunter-gatherers have sometimes eaten.
Speth [1989] has extensively studied protein intakes in contemporary worldwide populations and notes that most human populations today obtain between 10-15% of their total energy requirements from protein. For Americans the value is 14%, for Swedes it is 12%; for Italian shipyard workers it is 12.5-12.8%; for Japanese it is 14.4%, and for West Germans it is 11.1%. Even among athletes, values rarely exceed 15%. Speth [1989] shows that Italian athletes consumed between 17-18% of their caloric intake as protein; Russian athletes consumed 11-13%; and Australian athletes competing at the 1968 Olympic Games consumed 14.4% of their daily calories as protein. This data clearly demonstrates the relative homogeneity amongst contemporary global populations in their protein consumption levels.
That protein consumption may have anything to do with the atherosclerotic process and hence CHD is an obscure topic which has been rarely examined by the medical and nutritional communities. It is not surprising that few are aware of the literature which supports this concept. However, there are now at least three human clinical trials [Wolfe et al. 1991; Wolfe et al. 1992; Wolfe 1995] demonstrating that isocaloric (calorie-for-calorie) substitution of protein (ranging from 17-27% of total daily calories) for carbohydrate reduces triglycerides, VLDL, LDL, and total cholesterol while increasing HDL cholesterol. Further, acute consumption of high levels of beef protein without carbohydrate evokes an extremely small rise in serum insulin levels and a concomitant substantial rise in glucagon [Westphal et al. 1990]. Both of these acute responses would tend to be associated with a reduced risk for CHD.
Lastly, in animal models, high levels of protein are known to dramatically inhibit hepatic VLDL synthesis [Kalopissis et al. 1995]. VLDLs are the precursor molecules for LDL cholesterol. In their classic study of Inuit, Bang and Dyerberg [1980] have shown that the serum cholesterol levels of the Inuit were 0.48 mmol/liter lower than what would have been predicted by the Keys equation, which estimates plasma lipid levels from dietary saturated fats, polyunsaturated fats, and cholesterol. At the time (1980), it was suggested that the paradoxically low serum cholesterol levels may have resulted from the higher omega-3 (n3) fats found in the Eskimo's seafood-based diet.
However, after almost 30 years of research, meta-analytical studies have shown that n3 fatty acids slightly elevate (by 5-10%) LDL cholesterol concentrations, but do not materially affect total cholesterol [Harris 1997]. Consequently, it may have been the higher dietary protein intake (23-26% of total calories) in the Inuit compared to the Danish controls (11% of total calories as protein) which accounted for these differences. However, since the Keys equation considers dietary monounsaturated fats as neutral (which more recent research indicates is not the case [Gardner et al. 1995]), it is possible that the higher monounsaturated fat content (57.3% of total fat) in the Inuit diet (vs. 34.6% in the Danes) may have also contributed to the plasma cholesterol differences.
| Low-carbohydrate diets by themselves do not eliminate the cholesterol-raising effects of high-saturated-fat diets |
Many people who have been influenced by the recent interest in low-carbohydrate dieting would argue that the cholesterol-lowering effect of the Eskimo diet stemmed from its low carbohydrate content. However, in one of the few (and best-controlled) metabolic ward trials of a carbohydrate-free (<20 gm/day) diet, Phinney and colleagues [Phinney et al. 1983] demonstrated a rather large rise in serum cholesterol (159 to 208 mg/dl) in nine lean, healthy males who participated in this 35-day in-patient trial.
The protein content of the diet was estimated to be 15%, whereas the fat content of the diet represented between 83-85% of total daily calories. Consequently, during the dietary trial, the protein content remained similar to the average daily intake in the U.S. and was not increased. This experiment shows that a carbohydrate-free diet composed of "ground beef, breast of chicken, water-packed tuna fish, powdered egg solids, and cheddar cheese with mayonnaise, heavy cream, sour cream, and cream cheese as primary lipid sources" was definitely hypercholesterolemic.
In a less-well-publicized but highly controlled clinical research center (CRC) study, Gray et al. showed similar results in a 3-week study of 10 healthy males who consumed a diet composed of 73-75% fat, 7-9% carbohydrate, and 16-20% protein. Compared to their standard (normal-carbohydrate) diet, the high-fat diet increased total cholesterol from 156.5 mg/dl to 167.6 mg/dl, and LDL cholesterol increased from 46.6 mg/dl to 55 mg/dl. The total cholesterol/HDL ratio, however, improved on the high-fat diet, going from 3.36 to 3.20.
High-fat, low-carbohydrate diets--as in the Phinney [1983] and Gray studies--characteristically induce other beneficial lipid profiles such as increased HDL levels and decreased triglyceride levels. These blood lipid changes (increased HDL and reduced triglycerides) have also been frequently demonstrated in reduced-carbohydrate diets [Jeppesen et al. 1997; Coulston et al. 1983] in which carbohydrate has been reduced, but not as drastically as in the Phinney and Gray trials.
So in summary, the animal foods of our Stone-Age ancestors were probably non-atherogenic because they contained high levels of protein (>20% of total calories), lower levels of saturated fats, higher levels of monounsaturated fats, higher levels of n3 polyunsaturated fats, little or no trans fats, and higher levels of HUFA (>18-carbon) fats of both the n6 and n3 varieties than modern Western meat-based diets. The higher consumption of animal-based foods would have necessarily reduced the carbohydrate content of the diet, and this would have also benefited certain aspects of the lipid profile as just enumerated.
| Glycemic response of fat combined with carbohydrate |
In a previous comment, I suggested that meals of pre-agricultural peoples tended to produce less of a glycemic response than do modern Western meals. This was based on the observation that hunter-gatherer meals generally were not the elaborate mixtures of fat/carbohydrate/protein that are typical of Western meat/potato meals. Hunter-gatherers quite often would eat only the animal killed for a meal without added plant courses. Thus, protein/fat macronutrient mixtures were the norm. Carbohydrates generally were consumed as they were collected, or separate from animal-based meals. It has been well-established that by mixing fat with carbohydrate, the glycemic response worsens [Collier et al. 1988].
| What is the relevance of genetic differences in individual blood lipid response to high and low-fat diets? |
In view of recent discussions about low-carbohydrate diets and reevaluation of the effects of high-carbohydrate diets, there have been speculations regarding human blood-lipid responses to high and low-carbohydrate diets, and whether or not there is a genetic basis for differential responders. To follow up on this, there is substantial evidence to show that blood-lipid response to variation in dietary fat and cholesterol intake varies widely among individuals [Mistry et al. 1981; Jacobs et al. 1983; Katan et al. 1988], and that this variability is likely attributable to genetic factors with polymorphisms [variant forms of a gene] at several genetic loci, including genes for apolipoproteins and for low-density lipoprotein (LDL) particle size and density [Dreon et al. 1992].
There is an LDL subclass called pattern "B" which is characterized by a preponderance of small, dense LDL particles, elevated triglycerides, low high-density cholesterol (HDL), and increased coronary heart disease (CHD) risk. LDL pattern "B" occurs in approximately 30% of the male population [Austin et al. 1988]. LDL subclass pattern "A" is characterized by larger, more buoyant LDL particles. Low-fat, high-carbohydrate diets induce a reduction in the atherogenic, small, dense LDL in individuals displaying pattern "B", and also cause reductions in LDL cholesterol greater than in subjects displaying pattern "A" [Dreon and Krauss 1997]. These data clearly suggest that low-fat, high-carbohydrate diets may be more effective in lowering LDL cholesterol and small, dense LDL in about 30% of the population, and less effective in 70% of the population.
LDL subclass pattern "B" is influenced by a major gene or genes with a prevalence in the American population estimated to be 25% [Austin et al. 1988]. The specific gene or genes responsible for this trait have not been identified, but there is evidence to show linkage to polymorphic markers near the LDL receptor gene on chromosome 19p [Nishina et al. 1992].
To date, there are no experimental data evaluating the effects of quite low-carbohydrate diets (<30% of total energy) upon blood lipid responses in LDL subclasses "A" or "B". However, Krauss et al. [1995] have clearly shown that all subjects (n = 105), whether subclass "A" or "B", responded to a high-fat diet (46% energy) by substantial increases in LDL cholesterol, and responded to a low-fat diet (23.9% energy) by decreases in LDL cholesterol. The difference was simply in the magnitude of the negative effect experienced, not whether it occurred or not.
This information does not support the contention by some that differential responders to high and low-fat diets bias the interpretation of dietary intervention trials, nor does it lend support to the proposal that high-fat diets can improve blood-lipid profiles. I contend that any improvement in total cholesterol or LDL cholesterol by uncontrolled, self-administered low-carbohydrate diets are an artifact of:
- Reductions in total caloric intake,
- Increases in total protein,
- Unknowing changes in the dietary polyunsaturated/monounsaturated/saturated fat (P:M:S) ratio, and
- Combination of the three.
Further, improvements in triglycerides, VLDL, and HDL can be mainly attributed to reductions in carbohydrate.
Under isocalorically (calorie-for-calorie) controlled conditions in which dietary saturated fat is increased at the expense of any other lipid or macronutrient, there will be a characteristic increase in LDL cholesterol, as shown time and again with meta-analyses [Howell et al. 1997], under metabolic ward conditions [Phinney et al. 1983], and corroborated by in vitro and in vivo data showing that LDL receptors are down-regulated by dietary saturated fat [Brown and Goldstein 1976].
As I hope the foregoing has demonstrated, further studies that have been performed in the years since the low-fat, high-carbohydrate viewpoint first became standard have revealed additional factors affecting blood lipids, and that the previous view has been too simplistic. Serious drawbacks have become apparent in the conventional wisdom about low-fat, high-carbohydrate diets. No longer does this view adequately explain what we have come to know about the effects of macronutrient content with increasing resolution at the biochemical level over the last decade.
We are entering an era of dietary research where the details of underlying biochemical processes that govern lipid responses are being increasingly well-understood. Certain of these details validate the positive health effects that may accrue from the dietary pattern suggested by recently emerging studies of diet in human evolution. Hunter-gatherers who eat high levels of protein, lower levels of carbohydrate, and similar or even higher levels of fat (but with a much different lipid profile) compared to modern Western diets exhibit extremely positive blood lipid profiles and quite low rates of CHD. This presents a serious challenge for researchers, since this result would not be predicted by previous theories about fat in the diet.
While the detrimental role of high levels of saturated fat by itself has been increasingly well-validated, the overall picture of the various other types of fat is turning out to be more complex. Fat is as essential a nutrient as the other macronutrients. More important than the overall level of fat in the diet are the roles and ratios of specific types of fat, such as the positive role of monounsaturated fats and a high n3/n6 polyunsaturated ratio, and the negative effects of trans fatty acids and deficiencies in EFAs.
Where the polyunsaturated fats are concerned, modern diets contain excessive amounts of the n6 fat linoleic acid (that would have been present in lesser amounts in preagricultural diets), which promotes oxidation of cholesterol and consequently formation of atherosclerotic plaque. Also, what saturated fats are consumed by pre-agricultural peoples come from wild animal tissues. Compared to modern domesticated animals, these animal tissues are much higher in the non-atherogenic saturated fat stearic acid and lower in the 14:0 and 16:0 fats that promote high cholesterol.
At the same time, as the roles of various fats in the diet are becoming more well-understood, attention has recently begun to turn to investigation of the biochemical effects on blood lipids of the other macronutrients. By comparison with the voluminous studies performed in recent decades on fatty acids, these have been relatively ignored. However, only by devoting the same detailed attention to the effects of carbohydrate and protein on blood lipid response will we fully understand the role of all the macronutrients on health in relation to each other. As previously mentioned, the hyperinsulinemic effect of excess carbohydrates is looming large as a subject warranting much further study. And what studies have been performed initially on higher protein consumption levels show that they exert very positive effects on blood-lipid profiles.
In this ongoing investigation, the "paleolithic" picture of the foods and macronutrient ratios that would have prevailed during human evolution provides a valuable template: One that can yield key insights for guiding future study into the food consumption patterns to which the human species is genetically best adapted.
--Loren Cordain, Ph.D.
For further Paleodiet research from Dr. Cordain, you can download printable PDFs of his research group's peer-reviewed papers (more than 20 at last count) at his website, plus get information about his 2002 book, The Paleo Diet.
REFERENCES
Artaud-Wild SM et al. (1993) "Differences in coronary mortality can be explained by differences in cholesterol and saturated fat intakes in 40 countries but not in France and Finland. A paradox." Circulation, vol. 88, pp. 2771-2779.
Ascherio A et al. (1997) "Health effects of trans fatty acids." American Journal of Clinical Nutrition, vol. 66, pp. 1006s-1010s.
ASCN/AIN Task Force on Trans Fatty Acids. (1996) "Position paper on trans fatty acids." American Journal of Clinical Nutrition, vol. 63, pp. 663-670.
Austin MA et al. (1988) "Inheritance of low-density lipoprotein subclass patterns: results of complex segregation analysis." American Journal of Human Genetics, vol. 43, pp. 838-846.
Bang HO, Dyerberg J. (1980) "Lipid metabolism and ischemic heart disease in Greenland Eskimos." In: Draper HH (ed.) Advances in Nutrition Research, vol. 3, New York: Plenum Press, pp. 1-22.
Begom R et al. (1995) "Prevalence of coronary artery disease and its risk factors in the urban population of south and north India." Acta Cardiologica, vol. 50, pp. 227-240.
Brown MS, Goldstein JL. (1976) "Receptor-mediated control of cholesterol metabolism." Science, vol. 191, pp. 150-154.
Chen YDI et al. (1992) "Effect of acute variations in dietary fat and carbohydrate intake on retinly ester content of intestinally derived lipoproteins." J Clin Endocrin Metabolism, vol. 74, pp. 28-32.
Collier GR et al. (1988) "The acute effect of fat on insulin secretion." J Clin Endocrin Metabolism, vol. 66, pp. 323-326.
Cordain L, Gotshall RW, Eaton SB. (1997) "Evolutionary aspects of exercise." World Review of Nutrition and Dietetics, vol. 81, pp. 49-60.
Cordain L, Martin C, Florant G, Watkins BA. (1998) "The fatty acid composition of muscle, brain, marrow and adipose tissue in elk: evolutionary implications for human dietary lipid requirements." World Review of Nutrition and Dietetics, vol. 83, p. 225.
Coulston AM et al. (1983) "Plasma glucose, insulin and lipid responses to high-carbohydrate, low-fat diets in normal humans." Metabolism, vol. 32, pp. 52-56.
Crawford MA et al. (1969) "Linoleic acid and linolenic acid elongation products in muscle tissue of syncerus caffer and other ruminant species." Biochem J, vol. 115, pp. 25-27.
Denke MA, Grundy SM. (1991) "Effects of fats high in stearic acid on lipid and lipoprotein concentrations in men." American Journal of Clinical Nutrition, vol. 54, pp. 1036-1040.
Denton D et al. (1995) "The effect of increased salt intake on blood pressure of chimpanzees." Nature Medicine, vol. 1, pp. 1009-1016.
Dietschy JM. (1997) "Theoretical considerations of what regulates low-density lipoprotein and high-density lipoprotein cholesterol." American Journal of Clinical Nutrition, vol. 65, pp. 1581S-1589S.
Dreon DM et al. (1992) "Gene-diet interactions in lipoprotein metabolism." Monographs in Human Genetics, vol. 14, pp. 325-349.
Dreon DM, Krauss RM. (1997) "Diet-gene interactions in human lipoprotein metabolism." J Am Coll Nutr, vol. 16, pp. 313-324.
Eaton S. Boyd; Konner M; Shostak M. (1988) "Stone-agers in the fast lane: chronic degenerative diseases in evolutionary perspective." American Journal of Medicine, vol. 84, pp. 739-749.
Gardner CD et al. (1995) "Monounsaturated versus polyunsaturated dietary fat and serum lipids. A meta analysis." Arterioscler Thromb Vasc Biol, vol. 15, pp. 1917-1927.
Ghafoorunissa. (1984) "Essential fatty-acid nutritional status of apparently normal Indian men." Human Nutrition: Clinical Nutrition, vol. 38C, pp. 269-278.
Gray CG et al. (year unavailable; likely early 1980s) "The effect of a three-week adaptation to a low-carbohydrate/high-fat diet on metabolism and cognitive performance." Naval Research Center Report No. 90-20. Naval Health Research Center, San Diego, California.
Grundy SM. (1986) "Comparison of monosaturated fatty acids and carbohydrates for lowering plasma cholesterol." N Engl J Med, vol. 314, pp. 745-748.
Harris WS. (1997) "n3 fatty acids and serum lipoproteins: human studies." American Journal of Clinical Nutrition, vol. 65(supp), pp. 1645s-1654s.
Hollenbeck CB et al. (1989) "Effects of sucrose on carbohydrate and lipid metabolism in NIDDM patients." Diabetes Care, vol. 12, pp. 62-66.
Howell WH et al. (1997) "Plasma lipid and lipoprotein responses to dietary fat and cholesterol: a meta-analysis." American Journal of Clinical Nutrition, vol. 65, pp. 1747-1764.
Jacobs DR et al. (1983) "Variability in individual serum cholesterol response to change in diet." Arteriosclerosis, vol. 3.
Jeppesen J et al. (1997) "Effects of low-fat, high-carbohydrate diets on risk factors for ischemic heart disease in postmenopausal women." American Journal of Clinical Nutrition, vol. 65, pp. 1027-1033.
Kalopissis AD et al. (1995) "Inhibition of hepatic very-low-density lipoprotein secretion in obese Zucker rats adapted to a high-protein diet." Metabolism, vol. 44, pp. 19-29.
Katan MB et al. (1988) "Congruence of individual responsiveness to dietary cholesterol and to saturated fat in humans." Journal of Lipid Research, vol. 29, pp. 883-892.
Keys A et al. (1965) "Serum cholesterol response to changes in the diet. IV. Particular saturated fatty acids in the diet." Metabolism, vol. 14, pp. 776-787.
Krauss RM, Dreon DM. (1995) "Low-density lipoprotein subclasses and response to a low-fat diet in healthy men." American Journal of Clinical Nutrition, vol. 62, pp. 478s-487s.
Leaf A et al. (1988) "Cardiovascular effects of n3 fatty acids." New England Journal of Medicine, vol. 318, pp. 549-557.
Leonard WR, et al. (1994) "Correlates of low serum lipid levels among Evenki herders of Siberia." American Journal of Human Biology, vol. 6, pp. 329-338.
Louheranta AM et al. (1996) "Linoleic acid intake and susceptibility of very-low-density and low-density lipoproteins to oxidation in men." American Journal of Clinical Nutrition, vol. 63, pp. 698-703.
McKeigue PM et al. (1985) "Diet and risk factors for coronary heart disease in Asians in northwest London." Lancet, 1985;ii, pp. 1086-1090.
Mensink RP et al. (1987) "Effects of monounsaturated fatty acids versus complex carbohydrates on high-density lipoproteins in healthy men and women." Lancet, 1987;1, pp. 122-125.
Mensink RP, Katan MB. (1992) "Effect of dietary fatty acids on serum lipids and lipoproteins. A meta-analysis of 27 trials." Arterioscler Thromb, Aug. 1992, vol. 12, no. 8, pp. 911-919.
Miller GJ. et al. (1988) "Dietary and other characteristics relevant for coronary heart disease in men of Indian, West Indian and European descent in London." Atherosclerosis, vol. 70, pp. 63-72.
Mistry F et al. (1981) "Individual variation in the effects of dietary cholesterol on plasma lipoproteins and cellular homeostasis in man." J Clin Invest, vol. 67, pp. 493-502.
Nelson GJ et al. (1995) "Low-fat diets do not lower plasma cholesterol levels in healthy men compared to high-fat diets with similar fatty acid composition at constant caloric intake." Lipids, vol. 30, pp. 969-976.
Nishina PM et al. (1992) "Linkage of atherogenic lipoprotein phenotype to the low-density lipoprotein receptor locus on the short arm of chromosome 19." Proc Natl Acad Sci, vol. 89, pp. 708-712.
Phinney SD et al. (1983) "The human metabolic response to chronic ketosis without caloric restriction: physical and biochemical adaptation." Metabolism, vol. 32, pp. 757-768.
Reaven GM. (1995) "Pathophysiology of insulin resistance in human disease." Physiol Rev, vol. 75, pp. 473-486.
Reddy S. et al. (1994) "The influence of maternal vegetarian diet on essential fatty acid status of the newborn." European Journal of Clinical Nutrition, vol. 48, pp. 358-368.
Speth JD. (1989) "Early hominid hunting and scavenging: the role of meat as an energy source." Journal of Human Evolution, vol. 18, pp. 329-343.
Stamler J et al. (1986) "Is relationship between serum cholesterol and risk of premature death from coronary heart disease continuous and graded?" JAMA, vol. 256, pp. 2823-2828.
Steinberg D et al. (1989) "Beyond cholesterol: modifications of low-density lipoprotein that increase its atherogenicity." New England Journal of Medicine, vol. 320, pp. 915-924.
Varo P. (1974) "Mineral element balance and coronary heart disease." Internat J Vit Nutr Res, vol. 44, pp. 267-273.
Vega GL et al. (1996) "Hypoalphalipoproteinemia (low high-density lipoprotein) as a risk factor for coronary heart disease." Curr Opin Lipidology, vol. 7, pp. 209-216.
Westphal SA et al. (1990) "Metabolic response to glucose ingested with various amounts of protein." American Journal of Clinical Nutrition, vol. 52, pp. 267-272.
Willett WC et al. (1994) "Trans fatty acids: are the effects only marginal?" American Journal of Public Health, vol. 84, pp. 722-724.
Wolfe BM et al. (1991) "Short-term effects of substituting protein for carbohydrate in the diets of moderately hypercholesterolemic human subjects." Metabolism, vol. 40, pp. 338-343.
Wolfe BM et al. (1992) "High-protein diet complements resin therapy of familial hypercholesterolemia." Clin Invest Med, vol. 15, pp. 349-359.
Wolfe BM. (1995) "Potential role of raising dietary protein intake for reducing risk of atherosclerosis." Can J Cardiol, vol. 11(supp G), pp. 127G-131G.
Yudkin J. (1972) "Sucrose and cardiovascular disease." Proc Nutr Soc, vol. 31, pp. 331-337.
Back to Paleodiet & Paleolithic Nutrition
