fat diets, and are now recommending monounsaturated fat in lieu of carbohydrate
[Grundy 1986; Mensink et al. 1987].
Despite the thousands--
perhaps tens of thousands--
of clinical trials which have been conducted manipulating the macronutrient
(protein, carbohydrate, and fat) content of diet, however, there are perhaps no
more than a half-
dozen which have examined the influence of a high-
protein, low-
carbohydrate diet (with varying fat levels) upon human health and metabolism.
This is somewhat ironic, in that this macronutrient pattern appears to be the
one which nourished humankind (members of the genus Homo) for all of our
time (2.5 million years) on this planet, except for the last 10,000 years since
the advent of grain-
based agriculture.
| The specific dietary context in
which fat and the other macronutrients occur is key, but often
overlooked |
There is little doubt that Paleolithic man consumed (probably preferentially)
the fatty portions of wild game animals. During certain times of the year (late
summer and early fall) the total lipid content of large herbivorous animals was
considerable, and at these times saturated fat consumption could have been high.
At other times, however, it would have been modest (except perhaps for high-
latitude peoples who were the most dependent on animal meat due to a colder
climate less hospitable to plant life), even while the overall yearly
consumption of all forms of fat could have been relatively high. However,
despite the consumption of a largely animal-
based diet that at times can include a high overall level of fats, most modern-
day hunter-
gatherers exhibit low serum cholesterol levels, low blood pressure, and low to
non-
existent mortality rates from coronary heart disease (CHD) [Eaton 1988; Bang and
Dyerberg 1980; Leonard et al. 1994].
At first, this data seems paradoxical in light of the almost universal
recommendations of a low-
fat, high-
carbohydrate diet in the treatment of CHD. However, there are important and
subtle differences between the high-
fat/
animal-
based diets of pre-
agricultural man and the high-
fat diets of modern man which can account for this paradoxical situation:
- Differences in trans fats and oxidation of cholesterol. There is
increasing recognition that for the atherosclerotic process to occur, there
must not only be elevated levels of LDL cholesterol, but that the lipids and
cholesterol carried by LDL must be oxidized [Steinberg et al.
1989]. The macrophages which take up oxidized LDL molecules and eventually
become the foam cells of the atherosclerotic plaque have a scavenger
receptor which is different from native LDL receptors and which does not
down-
regulate. Consequently, continually elevated levels of oxidized LDL in the
plasma tends to promote the atherosclerotic process.
High levels of dietary linoleate increase LDL oxidizability ([Louheranta et
al. 1996]. Because refined vegetable oils were not present in pre-
agricultural diets, the linoleate levels would have been lower than in
Western diets, wherein the vegetable fat consumption has increased 300%
since 1910 and the animal-
fat consumption has decreased slightly [ASCN/AIN Task Force 1996]. Thus the
relatively high levels of vegetable oils consumed in the Western diet, along
with relatively high levels of saturated fats, promote a lipid profile in
which LDL cholesterol is elevated and more prone to oxidation and hence to
the development of CHD.
- Differences in protein intake levels. The protein content of the
paleolithic diet was significantly higher than the average 12-15% of the
Western diet. Recent studies [Wolfe 1995; Wolfe et al. 1991]
show that isocaloric (calorie-
for-
calorie) replacement of carbohydrate with protein lowers total cholesterol,
LDL, VLDL, and triglycerides (TG) while elevating HDL cholesterol--
all of which are favorable responses in terms of blood-
lipid levels. Consequently, a high dietary protein content even in the face
of increasing overall fats, or increasing saturated fat, serves to lower
serum cholesterol levels and reduce the risk for CHD.
- Differences in carbohydrate intake. The carbohydrate content of
pre-
agricultural diets was generally lower than the 45-55% of the Western diet.
Consequently, the post-
prandial (after-
meal) lipemic excursions (changes in blood lipid levels)--
during which LDL molecules are most prone to oxidation--
would have been reduced, since the addition of carbohydrate to a fat-
rich meal exacerbates this swing [Chen et al. 1992]. Pre-
agricultural eating patterns show that fat and protein were generally eaten
together, whereas carbohydrate meals were eaten separately. This eating
pattern would have reduced post-
prandial lipemic excursions. Additionally, the reduced carbohydrate content
of pre-
agricultural diets would have improved the portions of the blood-
lipid profile (TG, VLDL, HDL, Lp(a)) which are worsened by high-
carbohydrate diets [Reaven 1995].
- Differences in fatty-acid intake profiles. Work from our laboratory
[Cordain et al. 1998], as well as that of others, has shown
that the fatty-
acid profiles of storage as well as structural fat are quite different when
contrasting wild to domesticated animals. Of the dietary saturated fats,
12:0, 14:0, and 16:0 are known to elevate plasma cholesterol levels, whereas
18:0 is neutral or perhaps hypocholesterolemic (cholesterol-
lowering). The saturated fat of bone marrow and depot fat in wild animals
contains greater levels of 18:0 and lower levels of 14:0 and 16:0 when
compared to domestic animals.
Additionally, the structural (e.g., polyunsaturated) lipid content in
game meat is also quite different than that in domestic meat. There
generally are higher levels of all n3 ("omega 3")
fats and higher levels of all 20 and 22-carbon fats of both the n3 and n6 ("omega
6") varieties in game meat. The n6/n3 ratio of beef averages
about 15, whereas in wild animals it is about 4-5. Again, higher levels of
n6 lipids in domestic animals, particularly linoleate, tend to increase LDL
oxidizability, whereas the higher levels of n3 fats in game animals are
cardio-
protective.
Consequently, the consumption of saturated fats in pre-
agricultural diets occurred against a background of dietary lipids which was
much different than the background fats in the modern diet. Recent evidence
clearly shows that the composition of fatty acids in a meal can improve
serum lipid values despite widely varying fat levels [Nelson et al.
1995].
- Absence of dairy fats. Pre-agricultural diets by definition would
not have included dairy fats. In modern Western diets, about a third of the
saturated fat is contributed by dairy foods (milk, butter, cheese, ice
cream). In metabolic ward studies, butter fat raised LDL cholesterol levels
significantly higher than beef tallow [Denke and Grundy 1991]. Further, milk
consumption is the best worldwide predictor of CHD mortality of all dietary
elements [Artaud-
Wild et al. 1993]. Bovine milk fat is quite low in the long-
chain cardio-
protective n3 fats, and has a high n6 ratio. Additionally the calcium to
magnesium (Ca/Mg) ratio in milk and dairy products is quite high compared to
the average 1:1 ratio in foods available to pre-
agricultural man. Elevated Ca/Mg ratios have been shown to be positively
related to CHD [Varo 1974]. This data suggests dairy products would be quite
atherogenic, particularly when consumed in a background of other dietary
elements in the Western diet.
- Large disparity in activity levels. Modern man eating a high-
fat diet is generally quite inactive compared to pre-
agricultural man [Cordain, Gotshall, and Eaton 1997]. High levels of
activity serve to improve insulin sensitivity and lower TG and VLDL while
increasing HDL cholesterol.
In all likelihood, the dietary fat levels of pre-
agricultural man could have been quite high (even by modern standards). However,
because of differing types and amounts of carbohydrate, protein, and fatty
acids, as well as differing levels of fiber and antioxidant vitamins and
phytochemicals from a diet rich in plant foods as well as meats, these types of
diets generally would not have elevated cholesterol levels (as confirmed by
values seen in modern hunter-
gatherers [Bang and Dyerberg 1980; Leonard et al. 1994]), nor have
increased LDL oxidizability.
One final comment: Not only does the high sodium content of the Western diet
predispose us to hypertension, osteoporosis, urinary tract stones, menierre's
syndrome, stomach cancer, insomnia, asthma and initiation and promotion of all
types of cancer, it also seems to do the same in our closest relative, the chimp
[Denton et al. 1995].
| Saturated/unsaturated fat
composition of wild animal tissues, and consumption levels in modern vs.
pre-
agricultural peoples |
Our data on the fatty-
acid distribution in tissues of wild animals presented at a recent conference on
the return of n3 fats to the food supply, held at the National Institutes of
Health in Bethesda, Maryland has been recently published in World Review of
Nutrition and Dietetics. [Cordain et al. 1998]. This data
refutes contentions made by some that the overall PUFA in wild-
animal tissues is low. To the contrary, it is relatively high in both brain
(26%) and muscle (36%) as our data shows, and which corroborates earlier work of
Crawford et al. [1969].
The difference in polyunsaturated fatty acids (PUFAs) between the Western
diet and the so-called "paleolithic diet" is that the PUFAs in the
Western diet are predominantly based upon 18-carbon lipids (vegetable oils) with
huge amounts of 18:2n6 (linoleic acid) predominating. The PUFA content of the
paleolithic diet is higher than that of the Western diet (19.2% vs. 12.7% [Bang
and Dyerberg 1980]) with much higher levels of HUFA (>20-carbon lipids) of
both the n6 and n3 families.
Once again, it should be emphasized as well that while pre-
agricultural peoples certainly did consume saturated fat, it cannot compare with
the levels consumed by modern Western populations. Bang and Dyerberg's data
[1980] on Eskimo populations who ate a high-
meat diet is particularly illustrative of this. Of the total dietary fats,
saturated fats comprised 22.8% in Inuit people whereas saturated fats comprised
52.7% of the total dietary fats in a control population of Danes. To point to
saturated fat consumption in pre-
agricultural groups as license to eat freely of such fats ignores the ecological
constraints that would have made modern levels of consumption highly unlikely
for our paleolithic ancestors, and ignores as well the voluminous clinical data
that shows their detrimental effects.
High levels of saturated fat consumption on a year-
round basis only became possible when domesticated animals were bred and fed in
a manner which allowed accumulation of depot fat on a year-
round basis. Wild animals almost always show a seasonal variation in storage
fat, and even the very fattest wild land mammals contain 60-75% less total fat
than the average domesticated animal. Thus, until the advent of the
"Agricultural Revolution" 10,000 years ago, it would have been
extremely difficult, or perhaps impossible, to eat high levels of saturated fat
on a daily basis throughout the year.
| Limitation of the Keys equation in
predicting expected serum cholesterol levels from fat and cholesterol in
the diet |
In our group over the last month or so, we have bandied about the idea of the
ancestral macronutrient compositions (i.e., percent fat, protein, and
carbohydrate) and how they influence health. Clearly, in the normal Western diet
(approximately 45-50% carbohydrate, 35-40% fat, and 10-15% protein), if dietary
saturated fats are reduced, then total and LDL cholesterol are also reduced.
Keys [1965] has published an equation which has been used extensively to predict
changes in serum cholesterol from dietary lipids and cholesterol. Others [Mensink
1992] more recently have confirmed Keys' equation.
However, in perhaps the most well-
controlled, modern dietary study of Greenland Eskimos [Bang and Dyerberg 1980],
it has been shown that ischemic heart disease is very uncommon in these people
(3.5% vs. 45-50% mortality rate in Western countries). The dietary macronutrient
content of these partially Westernized Eskimos was 38% carbohydrate, 39% fat,
and 23% protein, whereas the values for the control group of Danish people were
47% carbohydrate, 42% fat, and 11% protein. Mean total cholesterol levels in the
Eskimos (5.03 mmol/liter) were significantly lower than in the Danes (6.18 mmol/liter)
whereas triglycerides (TG) (0.57 vs. 1.23 mmol/liter) and VLDL (0.43 vs. 1.29
mmol/liter) were much lower in the Eskimos, and HDL levels were significantly
higher (4.00 vs. 3.34 mmol/liter).
Based upon the Keys et al. equation, the actual difference
between the Eskimos' and Danes' total cholesterol levels should have been 0.67
mmol/liter, whereas in actuality it was 1.15 mmol/liter. This data suggests that
the Keys equation may be invalid under circumstances wherein high quantities of
animal products replace traditionally grain-
dominated diets. Possible reasons for this discrepancy include the following
characteristics of the Eskimos' diet:
- Higher protein levels in the face of lowered carbohydrate may induce
different lipoprotein transport mechanisms [Wolfe 1995], and/or
- Differences in polyunsaturated fats between the two diets (high levels of
n3 fats, and high levels of preformed long-
chain fats of both n3 and n6 families).
The bottom line here is that present-
day hunter-
gatherers maintain quite low serum lipid levels despite high consumptions of
animal-
based foods.
Comment: To clarify the above, it appears that the
likely reason the Keys equation fails to correctly predict cholesterol levels in
situations such as the Eskimo study above is that it does not take into account
the effects of carbohydrate on insulin secretion. Hyperinsulinemia now appears
as if it may be one of the largest risk factors for CHD. Both high-
protein and low-
carbohydrate intakes, which were seen in the Eskimo study, promote inhibition of
excess insulin.
Exactly. Ancestral, pre-
agricultural diets were quite high in animal protein, and the carbohydrate that
was consumed was generally of a low glycemic index. These populations also
selectively consumed the fatty portions of the killed animal (brain, bone
marrow, depot fat, perinephral fat, mesenteric fat, tongue, organs, etc.).
However, available evidence from living hunter-
gatherers show that these surrogates of our Stone-
Age ancestors maintain low risk factors for CHD (blood lipid profiles, blood
pressure, insulin sensitivity, body composition, etc.). All of this on a diet
which contains an average 50-65% of its total calories derived from animal
foods, which therefore necessarily entails lower carbohydrate consumption.
Clearly, the Keys equation breaks down when either the macronutrient content
(high protein and low carbohydrate) or the fatty-
acid composition of the diet (or both) varies beyond the range of conditions
from which Keys originally derived his regression. Although there is much
circumstantial evidence to indicate that the Keys equation is erroneous under
these conditions, there is no empirical data that I am aware of which has
specifically investigated or confirmed this concept.
| Clarification of the role of
saturated fats in promoting high cholesterol |
Comment: Some who promote diets based on those of
traditional peoples--
who may at times have eaten higher levels of saturated fat--
suggest that the modern (high) levels of CHD do not have anything to do with
saturated fat from animal sources. Rather, they point to modern processing
techniques as having introduced new food substances into the human diet with
detrimental effects, particularly excess polyunsaturates, hydrogenated oils, and
refined carbohydrates.
There is much evidence to support the second half of this sentiment, but the
evidence does not agree with the first part.
- Hydrogenated oils (trans fatty acids), refined carbohdrates, and
polyunsaturates. There is now substantial evidence that hydrogenated
oils (trans fats) are atherogenic via their hypercholesterolemic effects
[Willett et al. 1994]. And in terms of their cholesterol-
raising properties they may be worse than saturated fats, because they cause
a decrease in HDL cholesterol [Ascherio et al. 1997]. Refined
carbohydrate (sucrose in particular) has been known for more than 30 years [Yudkin
1972] to be implicated in its CHD-
promoting effects, probably through increases in VLDL (the precursor to
LDL), triglycerides, total cholesterol, and perhaps decreases in HDL [Hollenbeck
et al. 1989]. Recently it has been recognized that although
dietary polyunsaturates may lower serum cholesterol levels, they may
actually increase the risk for CHD by increasing the susceptibility of LDL
to oxidation [Louheranta et al. 1996].
So I am in agreement that hydrogenated fats, refined carbohydrates, and
excessive polyunsaturated fats (primarily linoleic acid, 18:2n6) contribute
to the development of CHD via hypercholesterolemic and LDL-
oxidizing mechanisms.
- Saturated animal fats in overall dietary context. However, I cannot
agree with the statement that saturated fats from animals in modern diets
have nothing to do with CHD. It may be possible that the
hypercholesterolemic effects of saturated fats (12:0, 14:0, 16:0) can be
negated or somewhat ameliorated by extremely low levels of dietary
carbohydrates (particularly in insulin-
resistant subjects) or by high levels of dietary protein (>20% of total
calories) via protein's VLDL-
suppressing effects [Kalopissis et al. 1995].
However, it is clear beyond a shadow of a doubt that dietary saturated
fats (12:0, 14:0, and 16:0) elevate serum cholesterol levels within the
context of the "average American diet." A recent meta-
analysis of 224 published studies encompassing 8,143 subjects (many under
metabolic ward conditions) has unequivocally demonstrated the
hypercholesterolemic effect of dietary saturated fats [Howell et al.
1997]. The cellular basis for this observation stems from the regulation of
low-
density lipoproteins (LDLs). When the amount of cholesterol or saturated fat
coming into the body is increased, there is an expansion of the sterol pools
within liver cells, and to a lesser extent, peripheral cells, which causes a
down-
regulation of LDL receptors. As a consequence, LDL in plasma increases [Dietschy
1997].
Some have argued that increases in total plasma cholesterol and LDL may
not necessarily have a direct relationship to mortality from CHD [Stamler et
al. 1986]. Clearly, there are a wide variety of independent risk
factors for CHD including hypertension, homocysteine (increased by
deficiencies primarily in folate, vitamin B-6, and secondarily in B-12),
catecholamines, n6/n3 fatty-
acid ratio, antioxidant status (vitamins E, C, beta-
carotene, phytochemicals, etc.), dietary fiber, cigarette smoking, and
ethanol (alcohol) consumption, which influence a variety of physiological
systems involved with CHD. However, there is powerful evidence (n =
356,222) to indicate that the relationship between serum cholesterol levels
and the risk of premature death from CHD is, nevertheless, continuous and
graded [Stamler et al. 1986].
Therefore, the recommendation by some that it is harmless to consume high
levels of dietary saturated fats within the context of the "average
American diet" appears to not only be erroneous, but probably deadly.
Our hunter-
gatherer ancestors consumed high levels of animal food (probably >55% of
their total daily calories); however, the context under which this was done
was much different than present-
day conditions.
As I have previously mentioned, the carbohydrate content of the diet was
low (~<35% of total calories) and composed of plant foods with high
soluble fiber and low starch content. The protein content of the diet would
have exceeded 20% and may have been as high as 30-40%. The polyunsaturated
fats consumed would have had a low n6/n3 ratio, and there would have been
both ample levels of 20 and 22-carbon fats of both the n6 and n3 variety.
Since marrow contains 70-75% monounsaturated fats and was a favored food, it
is likely that although the fat content of the diet may have been as high as
40%, it was composed of not only a much more favorable n6/n3 polyunsaturated
fat ratio, but higher levels of monounsaturated fats and non-
atherogenic saturated fats such as stearic acid (18:0) as well.
|
|
 |
(Low-Fat/High-Carb Diets vs. Low-Carb/High-Protein Diets: CHD
Risk--continued, Part B)
| The role of essential fatty acids (EFAs)
and the balance of omega-6 to omega-3 fats. |
Question: Regarding saturated fats in context, is it
not the case that:
- A low-fat diet that is deficient in (polyunsaturated) essential fatty
acids (EFAs) will cause heart disease, whereas
A diet high in saturated fat but containing
plenty of polyunsaturated n3 fats (i.e., omega-3s, found in animal foods)
will keep arteries clear, such as in the Eskimo?
The first part of this is essentially correct. Indeed, levels of EFAs (essential
fatty acids--
particularly the chain-
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.
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