Title: Reexamining cholesterol and sodium
Date: 9/1/1994; Publication:
Nutrition Today; Author: Callaway, Wayne
What is the most
healthful diet? Recommendations from organizations such as the American
Heart Association (AHA) and the U.S. Department of Agriculture, and official
reports such as the 1989 U.S. Surgeon General's Report on Nutrition and
Health and the 1990 National Academy of Sciences' Diet and Health Report
make the answer to the question seem clear: Eat a diet that provides no more
than 30% of calories from fat, with no more than one-third of that from
saturated fat; include at least 20 to 35 g of fiber per day, eat at least
five servings of fruits and vegetables, and consume no more than 300
milligrams of cholesterol and 2,400 to 3,000 mg of sodium each day.
Now, a growing chorus
of experts are asking: Are all of these guidelines applicable to everyone?
Few would argue the recommendations that virtually everyone should eat more
fruits, vegetables, and whole grains and that most Americans could benefit
from eating less fat and more fiber. But is there justification for the
recommended across-the-board ceiling on cholesterol of 300 mg and 2,400 to
3,000 mg for sodium? This is a question that the newly formed committee for
the fourth edition of the 1995 Dietary Guidelines for Americans will have to
wrestle with as it works to update its recommendations for the general
public. It won't be an easy task. We, as health and nutrition professionals,
are at a crossroads, attempting to make the not-so-subtle transition from
giving one-size-fits-all dietary recommendations to individualizing them as
much as is realistically possible. A look at the research and history behind
the cholesterol and sodium recommendations provides a glimpse of the issues
policy-making nutrition experts must deal with while developing new
guidelines for healthy eating.
There is little doubt
that elevated plasma cholesterol levels are related to increased risk for
cardiovascular disease (CVD). Disagreement arises, however, over whether
dietary cholesterol by itself is an important determinant of blood
cholesterol levels. Hypercholesterolemic and erogenic effects of large
amounts of dietary cholesterol have been reported in experimental animals,
but experiments on animals tend to test the effects of pharmacological doses
of cholesterol, not amounts comparable to those normally consumed by humans.
Effects on plasma lipids in humans still remain controversial. Least is
known about the independent effects of dietary cholesterol on plasma lipids
in moderately hypercholesterolemic older subjects, the group for whom
dietary modification is most often recommended.(1)
first made by the AHA in the late 1970s to limit total cholesterol intake to
a maximum of 300 mg per day. Rather than being based on a specific study or
studies, the 300-mg number was merely a "best guess" of an appropriate
limit. That number has not been seriously challenged since then. In fact, it
was the maximum recommended limit set in the much more recent 1989 Diet and
However, in a 1984
review of the science behind the AHA's dietary recommendations for
preventing heart disease, Reiser(2) found that "not only are most of the
references obsolete, but many of their conclusions are the antitheses of
those attributed to them." In his insightful paper, Reiser pointed out that
a 1965 study done by Keys,(3) which was cited as part of the basis for the
cholesterol recommendation, actually concluded that "For purposes of
controlling serum [cholesterol] level, dietary cholesterol should not be
ignored, but attention to this factor alone accomplishes little."
In an earlier report
done by Keys,(4) it was concluded that the "findings make it reasonably
clear that the serum cholesterol level of 'normal' men is not significantly
related to differences in the habitual cholesterol intake over a range of
250 to 800 milligrams per day" and, contrary to AHA's recommendation,
"...efforts to control the serum cholesterol by alteration of the intake
within this range are unlikely to succeed."
Although there is much
epidemiological evidence as to the connection between blood cholesterol
levels and heart disease, not all epidemiological studies show a correlation
between dietary cholesterol alone and either serum cholesterol or coronary
heart disease. The correlations, when present, are small and often
statistically weak, and when confounding factors such as fat and saturated
fat intake are accounted for, often are not significant.
affecting public recommendations to lower dietary cholesterol intake
revolves around who is sensitive to dietary cholesterol in the range of
normal intake. Those for whom a difference of 200 mg a day leads to a
significant change in serum cholesterol are at risk for CVD.
responses to dietary intervention designed to lower cholesterol were
reported by McGill as early as 1979.(5) Despite the well-documented, wide
range of responses to dietary cholesterol, he noted that investigators had
been concerned primarily with the average effects of dietary manipulations
and had presented only mean values, making it impossible to detect the
relative proportions of people who responded to dietary cholesterol slightly
or not at all and those who responded with marked elevations. It is this
frequency, he added, of distribution of responses that may be more important
than average responses in determining whether dietary changes should be
recommended for the whole population.
McGill's findings in 1987. Since then, significant heterogeneity has been
observed in terms of dietary fat and cholesterol sensitivity and the
precision of regulatory responses. It has been suggested that most people
are resistant to the cholesterol-raising effects of dietary cholesterol
alone, especially when the diet is low in fat and saturated fat and high in
A recent study found
that, when young men with normal blood cholesterol levels ate one egg per
day as part of a low-fat, low-saturatedfat diet (Step I Diet with 125 mg
from other sources), cholesterol levels increased only 3 mg/dl, a clinically
insignificant amount.(7) It is difficult with the currently available data
to predict the metabolic changes in a nonhyperlipidemic population in
response to modest dietary changes, especially when considering the large
degree of heterogeneity that has been demonstrated in response to more
dramatic dietary interventions used in many studies.(7)
Study variables that
have clouded the true relationship between dietary cholesterol and serum
cholesterol include the form of dietary cholesterol, egg yolk, or
crystalline; the type of diet, natural foods, or formula; the amount of
supplemental cholesterol within or above the range of common intake; the fat
content of the diet; whether the supplemental cholesterol was added to
free-living diets or to those provided by a metabolic kitchen; and the
levels of other components in the diet that might alter the rates of
cholesterol absorption, such as phytosterols.(8)
In a series of human
studies, McNamara(9) found no evidence to support the hypothesis that
reducing dietary cholesterol intake from the current level of about 450
mg/day to the currently recommended maximum of 300 mg/day would reduce
plasma cholesterol levels in the general population. He suggests that
reductions in dietary cholesterol may, however, benefit an unknown
percentage of people who lack precise feedback control of endogenous
cholesterol synthesis. He concluded that the primary determinants of a given
subject's plasma cholesterol level are:
* sensitivity to
dietary saturated fat and
* the degree of
precision of the feedback control responses to dietary
cholesterol--responses which are highly variable from person to person.
It's also been
suggested that individuals are less likely to respond to dietary cholesterol
when a diet low in saturated fatty acids is consumed. Edington(10) found no
significant differences in plasma lipid levels among subjects consuming zero
or nine eggs per week on a diet low in saturated fat. Plasma cholesterol
concentration did not consistently increase when the dietary cholesterol was
increased or decrease with lower intake. There was no evidence of groups of
hyporesponders or hyperresponders, even when dietary cholesterol intake
varied between 90 and 410 mg/day.
levels, rather than having a direct relationship with dietary cholesterol,
are more likely a reflection of the complex interactions of blood lipids
with total dietary fat and saturated, monounsaturated, trans, and
polyunsaturated fatty acids, as well as dietary cholesterol.(11)
Only limited data
exist from studies that examine the effects of changing from a pattern
similar to that of the current dietary intake to one with limited total fat,
saturated fat, and cholesterol intakes. Generally, however, it appears that
moderate amounts of dietary cholesterol within the range that people
ordinarily consume do not affect serum cholesterol, especially among
normocholesterolemic individuals. This begs the question of how effective
the 300-mg daily dietary cholesterol restriction is in controlling blood
It's clear that the
cholesterol message has come across to consumers as a simple one: Dietary
cholesterol = high blood cholesterol. However, if only 25% to 30% of the
general population lacks precise metabolic adaptation for cholesterol, a
valid question is: What benefit is there to the remaining 70% to 75% of the
general population from restricting dietary cholesterol? Further, if the
average rise in the plasma cholesterol of individuals eating supplemental
cholesterol is small, does it carry a sufficient cardiovascular risk to
justify advice for everyone to restrict cholesterol consumption? Also, if a
reduction in total fat and saturated fat obviates the need for a reduction
in cholesterol, are we sending the wrong message to the public?
The need to limit
cholesterol intake may apply more strictly to dietsensitive
hypercholesterolemic individuals than the population in general. Further
studies need to focus on identifying predictors for hyperresponsiveness to
dietary cholesterol so that dietary counseling can be used in the most
efficacious manner, rather than making broad population-based
recommendations that, research suggests, benefit a minority of
In a 1979 report from
the National Institutes of Health Hypertension Task Force it was stated:
"The brevity of this section is indicative of the lack of knowledge
concerning basic mechanisms of hypertension. Research must supply new
knowledge before confident statements concerning prevention can be made."
Rather than consider
these very clearly stated reservations, the government chose to forge ahead
with the Food and Drug Administration's (FDA's) Sodium Initiative, a
nationwide effort to educate the public about the dangers of eating too much
salt. By July 1981, the FDA had dubbed sodium restriction "a national
consensus" and claimed the support of "most of the leading health and
medical experts." The FDA's sodium initiative was successful--too
successful, in fact, increasing consumer concern for dietary sodium far
beyond what science now knows to be the scope and nature of the problem.
While the sodium
hypothesis enjoyed almost unchallenged acceptance in the halls of government
and on the front pages of the nation's newspapers, some scientists grumbled
about the very public campaign against sodium. A group of 13 researchers
wrote in The Lancet in 1984(13): "The usual scientific standards for
weighing evidence and for giving advice which are now well established in
drug development and prescribing seemed to have been forgotten in an
evangelical crusade to present a simplistic view of the evidence which will
prove attractive to the media."
Still, both the 1988
Surgeon General's Report on Nutrition and Health and the National Academy of
Sciences' 1989 report, Diet and Health, retained the recommendation for a
nationwide reduction in dietary sodium (or salt in the case of the Diet and
Health report). The Surgeon General's report did acknowledge, however, that
whether universal sodium restriction would lower population blood pressure
had never been tested.
In 1989, the same year
The Surgeon General's Report was published, the National Institutes of
Health (NIH) had sponsored a meeting of leading hypertension researchers to
discuss "salt and blood pressure."
attendees were unable to reach a consensus as to whether a relationship
between sodium and hypertension did in fact exist and whether a policy of
universal sodium restriction conferred more benefits than additional risks
to healthy Americans.
Two years later, a
FASEB report entitled "Dietary Sodium Chloride and Blood Pressure," which
reviewed available scientific evidence of a sodium/hypertension link,
concluded that "studies within populations have been inconclusive or have
shown low correlations."
One of the studies
considered in the FASEB report was Intersalt,(14) the largest and most
comprehensive study done to date on the connection between sodium intake and
hypertension. The study surveyed 10,079 subjects from 52 centers in 32
countries around the world. Though the interpretation of the results,
including that done by the authors themselves, has come into question, most
who carefully read the study agree that it showed that in Western countries
sodium intake has little to do with hypertension. Rather, the study clearly
shows that within the range of economically advantaged societies' sodium
intakes (roughly 2,300 mg to 4,600 mg/day), there is no association between
population blood pressure and average population sodium excretion.
Even the well-known
study of heart disease and stroke in Framingham, Massachusetts found no
relationship between salt consumption and hypertension.(15)
differences in sodium intake are associated with different blood pressures,
there is no prospective randomized data to support the widely held belief
that restriction of sodium consumption among normotensive persons prevents
the subsequent appearance of hypertension. Salt-sensitive hypertension is
likely to be genetically determined and there is currently no reliable
genetic marker to identify those persons at risk. Based on this inability to
determine the persons at risk, most public health recommendations dictate
that universal sodium restriction is "prudent."
It may not be just the
relationship of sodium to hypertension that is critical, however. It may be,
and probably is, a complex relationship of dietary potassium, calcium, and
magnesium and the interrelationships of the electrolytes which affect blood
pressure--one more reason why the dietary guideline to eat a variety of
foods is an important one. The problem for some people may not be getting
too much of sodium, but not getting enough of other nutrients critical to
the hypertension equation.
In a 1991 article
published in Hypertension,(16) McCarron, who challenges the notion that
dietary salt is a major contributor to the development of hypertension,
stated, "Our future understanding of the effects of dietary NaCl on blood
pressure will be advanced only if we approach the task from the position
that salt's action on blood pressure regulation must be viewed in the
context of the total diet. We must temper the notion that by simply
recommending the lowering of an individual's salt intake, we will be
providing the public with optimal dietary advice as to how to lower
cardiovascular risk through prevention of hypertension."
restriction can, at best, produce modest change in blood pressure for only
some patients, it stands to reason that its widespread application must be
based on the belief that it is harmless.
reviewing the literature and finding moderate sodium restriction to be
helpful only for a minority of patients with mild hypertension, Alderman et
al.(8) also found that moderate sodium restriction actually raised blood
pressure in a certain proportion of patients. A rise in plasma renin,
provoked by salt depletion, may be responsible for this effect through its
vasoconstrictive function. A rise of blood pressure during moderate
restriction of sodium was observed in about 15% of patients. Reporting in
The American Journal of Hypertension, Alderman and Lamport(17) concluded
that "There is no justification for the recommendation that salt intake be
restricted in the general population to avert blood pressure rise. Moderate
salt restriction can not be universally recommended as a treatmetn for
hypertension. It is not a benign panacea, but merely one useful component of
the antihypertensive armamentarium."
More recently, in an
exhaustive review of the literature, Muntzel and Tilman(18) concluded that,
"Although lower NaCl intake may improve blood pressure in some persons, we
have no evidence that this will decrease the occurrence of cardiovascular
disease on a population level. Thus, we should be cautious in issuing
nationwide (or even hypertension-wide) recommendations to reduce dietary
Also untested is the
question of whether diets high in sodium are associated with elevated risks
of heart attacks or shorter lifespans. The sodium/hypertension hypothesis
continues to be the subject of intense debate in the scientific community.
Ausman LM, Carrasco W, Jenner JL, Ordovas JM, Schaefer EJ.
Hypercholesterolemic effect of dietary cholesterol in diets enriched in
polyunsaturated and saturated fat. Arterioscler Thromb 1994; 14:168--75.
Commentary on the Rationale of the Diet-Heart Statement of the American
Heart Association. Am J Clin Nutr 1984; 40:654--8.
(3.)Keys A, Anderson
JT, Grande F. Serum cholesterol response to changes in the diet. II. The
effects of cholesterol in the diet. Metabolism 1965; 14:759--65.
(4.)Keys A, Mickelsen
O, Miller EVO, Chapman, CB. The relation in man between cholesterol levels
in the diet and in blood. Science 1950; 112:79--80.
(5.)McGill, HC. The
relationship of dietary cholesterol to serum cholesterol concentration and
to atherosclerosis in man. Am J Clin Nutr 1979; 32:2664--702.
Karmally W, Siddiqui M, Holleran S, Tall AR, Rumsey SC, Deckelbaum RJ,
Blaner WS, Ramakrishnan RA. Dose-response study of the effects of dietary
cholesterol on fasting and postprandial lipid and lipoprotein metabolism in
healthy young men. Arterioscler Thromb 1994; 14:576--86.
Effects of fat-modified diets on cholesterol and lipoprotein metabolism.
Annu Rev Nutr 1987; 7:173--90.
Madhavan S, Ooi WL, Cohen H, Sealey, JE, Laragh JH. Association of the
renin-sodium profile with the risk of myocardial infarction in patients with
hypertension. N Engl J Med 1991; 324:1098--104.
(9.)McNamara DJ, Kolb
R, Parker TS, Batwin H, Samuel P, Brown CD, Ahrens EH. Heterogeneity of
cholesterol homeostasis in man. J Clin Invest 1987; 79:1729--39.
Geekie M, Carter R, Benfield L, Ball M, Mann J. Serum lipid response to
dietary cholesterol in subjects fed a low-fat, high-fiber diet. Am J Clin
Nutr 1989; 50:58--62.
(11.)Gurr MI. Dietary
lipids and coronary heart disease: old evidence, new perspective. Prog Lipid
Res 1992; 31:195--243.
(12.)Kestin M, Clifton
PM, Rouse IL, Nestel PJ. Effect of dietary cholesterol in normolipidemic
subjects is not modified by nature and amount of dietary fat. Am J Clin Nutr
(13.)Brown JJ, Lever
AF, Robertson JIS, Semple PF, Bing RF, Heagerty AM, Swales JD, Thurston H,
Ledingham JGG, Laragh JH, Hansson L, Nicholls MG, Espiner EA. Salt and
Hypertension. Lancet 1984; 2:1333--4.
Cooperative Research Group. Intersalt: an international study of electrolyte
excretion and blood pressure. Br Med J 1988; 297:319--28.
(15.)Dauber TR, Kannei
WB, Kagan A, et al. Environmental factors in hypertension. In: Stamler J, et
al. (eds.), The epidemiology of hypertension. New York: Grune & Stratton,
(16.)McCarron, DA. A
consensus approach to electrolytes and blood pressure: Could we all be
right? Hypertension 1991; 17(suppl I):I170--2.
Lamport B. Moderate sodium restriction: Do the benefits justify the hazards?
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(18.)Muntzel M, Tilman
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