New NCEP Cholesterol Guidelines
This course is approved by the American Dietetic Association for 4 CPE hours. Good through December 2010
By James J. Kenney, Ph.D., R.D.
Introduction.
The Key Changes
More Aggressive Cholesterol-Lowering Goals (Change
#1
Fasting Blood Lipid Profile Now Used To Screen
For Dyslipidemia (Change #2)
More Aggressive Dietary Guidelines for LDL-C Lowering
(Change #3)
Better Diagnosis of Risk of MI (Change #4)
Recognition of Type 2 DM as a Major MI Risk Factor
(Change #5)
More Focus on Insulin Resistance and Dyslipidemia
(Changes #6,7 & 8)
How Did the ATP III Go Wrong?
Do High-Carbohydrate Diets Necessarily Increase
Fasting TG and RLP?
Fasting TG Levels Often Return To Normal On A High-Carbohydrate
Diet
Do High-Carbohydrate Diet Lower HDL-C Levels and
Increase CHD Risk?
Blood Lipids Changes Due to Genetic and Diet May
Not Be Comparable
A Lower HDL-C Resulting From A High-Carbohydrate
Diet May Not Be Dangerous
Insulin Resistance and C-Reactive Protein Level
Bottom Line: Clinical Trials Show Regression on
Very-Low-Fat Diets
Should SFA Be Replaced With Carbohydrate or Unsaturated
Fat?
But Wouldn't Replacing SFA With UFA Also Prevent
CAD?
Conclusions
On May 15, 2001, the National Cholesterol Education Panel
(NCEP) issued major new clinical practice guidelines on the prevention and treatment
of high cholesterol levels in adults. This was the first major update of the
NCEP guidelines since 1993. An executive summary of the Third Report of the
NCEP Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol
in Adults (a.k.a., Adult Treatment Panel III or ATP III) appeared in the May
16, 2001 issue of the Journal of the American Medical Association. The NCEP
has predicted that the new ATP III guidelines will increase the number of Americans
requiring treatment for elevated cholesterol levels (from 52 million to 65 million)
and nearly triple the number of Americans who will need to take cholesterol
lowering drugs (from 13 million to 36 million Americans). This is in order to
reach the more aggressive blood cholesterol-lowering treatment goals established
by the ATP III.
The key changes established by the ATP III from the previous
NCEP guidelines (set by the ATP II) include the following:
1. More aggressive cholesterol-lowering treatment goals
2. Use of a lipoprotein profile as a first test for diagnosing
dyslipidemia and myocardial infarct (MI) risk
3. New more aggressive dietary guidelines for lowering elevated
low density lipoprotein cholesterol (LDL-C) levels with diet and other lifestyle
changes known as Therapeutic Lifestyle Changes (TLC)
4. Better diagnosis of those at high-risk for a MI)
5. Recognition that people with Type 2 diabetes mellitus
(DM) are at very high risk of MI and require more aggressive treatment of elevated
LDL-C levels
6. Increased focus on elevated triglycerides (TG) levels
and their treatment
7. A new higher cutpoint for establishing a low high density
lipoprotein cholesterol (HDL-C) level as a major risk factor for MIs
8. New guidelines for treating those with the metabolic
syndrome, (a.k.a., "insulin resistance syndrome", "syndrome
X")
From the perspective of this reviewer, the ATP III guidelines
represent:
a) several steps forward in the prevention and treatment
of atherosclerotic related cardiovascular disease
b) a few missteps by ignoring important research
c) a few steps that are probably warranted but not taken
The new ATP III guidelines do not change the total cholesterol
(TC) level categories. They continue to define a TC below 200 mg/dl as "desirable"
even though about 30% of all MIs occur in Americans with a "desirable"
TC.[1]
However, the new ATP III guidelines have established goals
for LDL-C levels that are much more aggressive than the earlier ATP II goals.
These more aggressive LDL-C lowering goals, if achieved, will be much more likely
to prevent or treat successfully atherosclerotic cardiovascular disease than
the ATP II goals. These new cholesterol-lowering goals should help prevent many
more MIs and strokes than the older goals. The new LDL-C categories are shown
in Table 1.
Table 1. ATP III LDL-Cholesterol Categories
LDL-Cholesterol level LDL-Cholesterol Category
<100 mg/dl Optimal
100-129 mg/dl Above Optimal
130-159 mg/dl Borderline High
160-189 mg/dl High
>190 mg/dl Very High
_____________________________________________________
Adapted from JAMA 2001;285:2486-97
In ATP II, an LDL-C level below 130 mg/dl was categorized
as "desirable" but an LDL-C of 100-129 mg/dl is often associated with
progression of atherosclerotic lesions particularly when several other coronary
heart disease (CHD) risk factors are present. So while a LDL-C of <130 mg/dl
was more "desirable" than even higher levels, it was certainly not
"optimal" for either the prevention or treatment of atherosclerotic
disease. A meta-analysis of 14 cholesterol-lowering trials calculated that atherosclerotic
plaque progression ceases around a LDL-C of 100 mg/dl.[2]
No doubt it was this type of data that convinced the ATP III to lower their
LDL-C targets for people at high-risk of CHD.
It should be noted that nearly 10% of CHD patients still
have LDL-C levels below 100 mg/dl although most of these have several other
risk factors for CHD. Therefore, in patients deemed at very high risk for MIs
due to advanced atherosclerosis, an LDL-C clinical target even lower than 100
mg/dl may be warranted in some, if not most, patients.[3]
Several intervention trials are now being conducted to determine if there is
clinical benefit to lowering LDL-C well below 100 mg/dl in patients with clinical
evidence of atherosclerotic disease. Clearly the ATP III's new focus on the
measurement of LDL-C in all adults over age 20 years, along with lower targets
for "safe" LDL-C levels for many patients, is warranted by the bulk
of the scientific research. Whether even lower target levels for LDL-C are clinically
warranted awaits results of ongoing clinical trials. However, the more generous
LDL-C targets for people deemed to be at lower risk of atherosclerotic disease
will certainly allow this disease to progress in many, if not most, people.
If the ATP III now states that an LDL-C of less than 100
mg/dl is "optimal” for people at high risk of CHD why is it not the optimal
goal for those at lower risk of CHD? After all, several hundred thousand Americans
will have MIs and strokes each year even though they are not deemed to be in
the high-risk category by the new NCEP guidelines. Perhaps the ATP III believes
that recommending a diet sufficiently low in animal products and hydrogenated
fat and sufficiently high in minimally processed fruits, vegetables and whole
grains in order to achieve the "optimal" LDL-C level is too drastic
a change in diet to expect most people to comply with. Nevertheless, it seems
that health professionals should be in the business of educating people about
what the scientific evidence suggests is an optimal LDL-C level and what is
the safest and most effective dietary approach to achieving this optimal LDL-C
goal.
The ATP III now recommends that a fasting blood lipid profile
measures serum TC, HDL-C and TG levels in all adults age 20 years and older.
They say this is needed to better screen for dyslipidemia and to assess the
risk of a MI. Earlier NCEP guidelines required a non-fasting TC and HDL-C measurement
only because there was no consensus on the value of measuring TG levels. However,
under the old guidelines, if the TC was 200 mg/dl or higher and/or if HDL-C
was under 35 mg/dl then the measurement of fasting TG levels was recommended
at a follow-up blood test. This became necessary because the older as well as
the new treatment guidelines use the LDL-C level as the primary treatment target.
Most clinical labs do not measure LDL-C directly. Therefore, without measuring
fasting TG level it is not possible to calculate the LDL-C level. LDL-C is usually
calculated as follows:
LDL-C = TC - HDL-C - TG/5 (all values in mg/dl)
In truth, what is called LDL-C actually includes both LDL-C
plus intermediate-density-lipoprotein-cholesterol (IDL-C). There is also cholesterol
in very-low-density-lipoprotein particles (VLDL), chylomicrons and their remnants.
VLDL particles generally have about 1/5 as much cholesterol as they do TG. After
a 10-12 hour fast there is very little chylomicron remnant particles in the
blood. For people who have very high TG levels, this ratio changes and so LDL-C
is generally not estimated if TG levels are over 400 mg/dl.
The ATP III now appears to believe that elevated fasting
TG levels (>150 mg/dl) are an established risk factor for CHD. In fact this
is still a matter of much debate. For example, a comprehensive secondary statistical
analysis of data from the Multiple Risk Factor Intervention Trial (MRFIT), the
Lipid Research Clinics Coronary Primary Prevention Trial (LRCPPT), and the Lipid
Research Clinics Prevalence and Follow-Up Study found, “with few exceptions,
no significant interactions between cholesterol subfractions and triglyceride
levels were found … and triglyceride measurements did not improve discrimination
between those subjects who did and those who did not suffer coronary heart disease
events.”[4] Simply put, in studies of Americans,
there is no consistent relationship between serum TG levels and the risk of
CHD after adjusting the data for confounding variables like HDL-C, BMI, smoking,
etc. For example, the risk of CHD is higher in those who have higher TG levels
but these people often have lower HDL-C levels. Clearly there is nothing close
to a scientific consensus to support the contention that fasting TG levels are
an independent risk factor for CHD. Unfortunately the ATP III’s growing but
unfounded focus on serum fasting TG levels as a CVD risk factor appears to be
playing a role in moving the NCEP dietary recommendations in the wrong direction.
This is particularly true for people who have insulin resistance and elevated
fasting serum TG levels. This will be discussed later.
The ATP III's recommendation to continue using LDL-C as
the primary clinical target for treating dyslipidemia is also becoming more
questionable. This is because very low density lipoprotein cholesterol (VLDL-C)
also appears to be atherogenic or at least is associated with an increased risk
of CHD. A recent analysis of the Lipid Research Clinics Follow-Up Study found
that non-high-density lipoprotein cholesterol (non-HDL-C) was actually a somewhat
better predictor of CVD risk than was LDL-C.[5]
Simply put, non-HDL-C rather than LDL-C should be the primary therapeutic target
for reducing the risk of CVD rather than just the LDL-C.
The ATP III does set a secondary goal of achieving a non-HDL-C
level no more than 30 mg/dl higher than the primary LDL-C goal (see Table 1)
in people who have a fasting TG level of 200 mg/dl or higher. However, most
of the subjects in the LRC Follow-Up Study discussed above had TG levels below
200 mg/dl and in these subjects non-HDL-C was a significantly better predictor
of dying from CVD than was LDL-C. Simply put, research shows that lowering non-HDL-C
reduces the risk of CVD more than lowering LDL-C. No doubt this is because non-HDL-C
includes LDL-C, IDL-C, VLDL-C and chylomiron-C. All of these lipoprotein subfractions
can be associated more atherosclerosis so why should the NCEP continue to focus
primarily on the LDL-C level?
Some members of the ATP III panel have argued that there
is not yet sufficient data to switch from LDL-C to non-HDL-C as the primary
target for treating patients with dyslipidemia. However, the bulk of the data
available suggests that non-HDL-C is a more superior predictor of atherosclerotic
disease than is LDL-C alone. The ATP III’s main argument against switching appears
to be that they have recommended using LDL-C for so long that switching to non-HDL-C
would confuse physicians and the public.[6]
Non-HDL-C is easy to calculate and does not even require a fasting blood lipid
panel. Non-HDL-C = TC - HDL-C. Because non-HDL-C does not require a fasting
blood sample to measure it would be easier on patients and a little less expensive
than using LDL-C to monitor therapeutic success. This does not mean fasting
TG levels should not be measured. If very elevated they can cause pancreatitis
and are often associated with other metabolic problems like renal disease, alcoholism,
hypothyroidism and poorly controlled diabetes. However, when it comes to atherosclerotic
disease, fasting TG levels are of little, if any, diagnostic value. The ATP
III does recommend the use of non-HDL-C as a secondary target of treatment.
So what is an optimal non-HDL-C level? To establish a secondary
treatment target, the NCEP now recommends adding 30 to their LDL-C target. So
if a patient’s LDL-C target was less than 100 mg/dl then his non-HDL-C target
would be less than 130 mg/dl. The ATP III has lowered the "normal"
range for fasting TG levels from less than 200 mg/dl to less than 150 mg/dl.
It is the opinion of this reviewer that an optimal fasting TG level is below
100 mg/dl although a somewhat higher level may still be optimal if the patient
is consuming a very-low-fat (VLF) diet (under 20% of energy from fat). The reason
for this is that elevated fasting TG levels correlate with elevated postprandial
TG levels. Most research suggests that any CVD risk associated with higher fasting
TG levels would be primarily due to the higher postprandial lipemia. Higher
postprandial TG levels are often closely correlated with higher fasting TG levels.
Higher postprandial TG levels are associated with more atherogenic lipoprotein
particles. This will be discussed in detail later. In this reviewer's opinion,
an optimal non-HDL-C level is below 120 mg/dl and perhaps up to 130 mg/dl if
the patient is consuming a VLF, high-carbohydrate diet.
ATP III appears to have abandoned the terminology for the
"Step 1 Diet" and "Step 2 Diet" for lowering LDL-C levels.
What was once the Step 1 diet is now referred to as a "Heart Healthy Diet"
and is recommended for people at a lower risk of atherosclerotic disease. The
Heart Healthy Diet is basically the same as the old "Step 1 Diet"
except the percent of calories from total fat is now 25 to 35% of energy rather
than less than 30% under the older guidelines. The higher intake of fat is achieved
by increasing the amount of monounsaturated fatty acids up to 20% of the total
calories. The intake of saturated fatty acids (SFA) and polyunsaturated fatty
acids (PUFA) and cholesterol on the Heart Healthy Diet are the same as the old
Step 1 diet.
Therapeutic Lifestyle Changes (TLC) are now recommended
for people whose LDL-C remains above the target level. TLC puts more emphasis
on losing excess body fat and increasing daily activity than the earlier ATP
II guidelines. The old "Step 2 Diet" used to lower elevated LDL-C
levels in patients who fail to achieve treatment goals on the Step 1 Diet has
also undergone a few changes. As with the "Heart Healthy Diet", this
new therapeutic diet (called the TLC Diet instead of Step 2 Diet) also adopts
a fat range of 25-35% of energy instead of the old guideline of less than 30%
of energy from fat. The TLC Diet targets for SFA (<7% en) and cholesterol
(<200 mg/d) remain the same as the old Step 2 Diet. However, the TLC Diet
recommends a couple of new twists for lowering elevated LDL-C levels.
One is to eat more soluble fiber rich foods. The goal is
to increase soluble fiber intake to 10 to 25g daily by eating more soluble-fiber
rich foods.
The second new twist is the recommendation to consume 2
grams daily of plant sterol and stanols by consuming food products enriched
in these cholesterol-lowering phytochemicals such as margarine and salad dressings
(e.g., "Benecol" and "Take Control").
Increasing dietary soluble fiber and plant sterols and stanols,
in the diets of patients with elevated LDL-C, makes the TLC Dietary approach
potentially more effective than the old ATP II Step 2 Diet approach. However,
reducing dietary saturated fat and cholesterol to even lower amounts than the
targets for the TLC Diet would certainly make it easier for more people to achieve
their LDL-C goal without cholesterol-lowering medications. There is every reason
to believe that a VLF (<15% en), high-fiber, more vegetarian diet can lower
LDL-C more than the new TLC Diet. This is because such a diet can supply less
than 3.5% of calories from saturated and trans fatty acids and keep daily cholesterol
intake well below 100 mg. No one doubts that greater reductions in SFA, trans
fatty acids (TFA) and cholesterol would lead to greater reductions in LDL-C
levels. A diet higher in carbohydrate and lower in fat would also tend to have
more dietary fiber and this helps lower elevated TC, LDL-C and non-HDL-C levels.
It should also be obvious that achieving a 25g intake of
soluble fiber would be far more difficult on a 35% fat diet than a diet with
only 10-15% of calories from fat. Vegetable oils have no soluble fiber and most
high-fat vegetarian foods (e.g. nuts, seeds, tofu, avocados) have less soluble
fiber for a given energy content than do most fruits, vegetables, beans, peas,
lentils and many grains (especially oats and barely). It should also be noted
that all vegetable oils contain SFA. If one added enough olive oil to increase
the % fat calories from 10% to 35% of energy then the SFA content of the diet
would double (from 3.5% to 7% en.). This extra oil could displace a lot of fiber-rich
foods assuming that energy intake was the same on the diet higher in fat. Of
course, there is growing evidence that higher fat diets tend to promote excessive
energy intake and weight gain over time.[7]
[8]
Even though the NCEP ATP III's new guidelines put more emphasis
on the importance of weight loss for reducing CHD risk factors, they ignore
growing evidence linking higher fat diets with increased energy intake and weight
gain. The ATP III even recommends reducing the calorie density of the diet to
help achieve greater satiety and make weight loss easier. Calorie density appears
more important than % energy from fat in determining ad libitum calorie intake.[9] [10]
However, nearly all foods high in monounsaturated fat (i.e. oils and nuts) also
have a high calorie density whereas all fresh fruits, vegetables, legumes and
many whole grain products (e.g., hot cereals, pasta, corn, brown rice) have
a low to moderate calorie density. Therefore, if one were to switch from a VLF
diet consisting largely of fruits, vegetables, beans and high-water content
whole grain products to a diet with more monounsaturated fat, the calorie density
of the diet would surely increase. This is why this reviewer believes that a
diet lower in fat, saturated fat and cholesterol and higher in fruits, vegetables
and whole grains is preferable to the ATP III’s TLC Diet, at least for patients
who are overweight, for reducing the risk of CHD.
The earlier ATP II guidelines recommended patient were to
be initially screened by simply measuring TC and HDL-C in the non-fasting state.
Only when the HDL-C was less than 35 mg/dl and/or the TC was 200 mg/dl or higher
is more extensive blood lipid measurements recommended. However, many MIs are
known to occur in individuals with a "desirable" TC (of < 200 mg/dl)
and a HDL-C of 35 mg/dl or higher. The new ATP III guidelines call for a complete
fasting (9-12 hours without food) blood lipid profile (TC, LDL-C, HDL-C and
TG) for everyone 20y or older. By recommending a complete blood lipid panel
on all adults and setting more aggressive LDL-C goals the new ATP III guidelines
have taken a step in the right direction. This step should reduce the number
of people at high-risk for a MI who "slipped through the cracks" of
the older ATP II guidelines.
The ATP III continue to make LDL-C levels the primary focus
for preventing and treating CHD. This is probably not the best treatment target.
To compound the problem the NCEP ATP III guidelines use data from the long running
Framingham Heart Study to assess risk of CHD based on TC rather than either
LDL or non-HDL-C levels. Both LDL-C and non-HDL-C are better risk predictors
than TC levels. So why did the ATP III elect to access risk using TC instead?
This was because they had much more long-term data available (from the long-running
Framingham Heart Study) associating risk of MI with TC rather than LDL-C level.
The most aggressive treatment goals for LDL-C levels are
reserved for those patients deemed to be at highest risk of future CHD events.
These patients have a 20% or greater risk of a CHD event within the next 10y
according to the statistics and data generated from the Framingham Heart Study.
The 10y risk of CHD events is calculated based on a risk point system using
only the following CHD risk factors: age, cigarette smoking, gender, systolic
blood pressure level (with or without drug treatment) and the level of TC and
HDL. In determining the treatment goal for LDL-C level the presence of either
clinical atherosclerotic disease and/or diabetes puts the patient in the highest
risk category (regardless of the number of calculated risk points). Family history
of early cardiovascular disease also counts as an additional "risk factor"
along with smoking, age 45+ for men and 55+ for women, low HDL-C (<40 mg/dl),
hypertension and elevated TC. An HDL-C of 60 mg/dl or more is considered to
be a negative risk factor.
Both cost/benefit analysis and risk/benefit analysis was
no doubt used to set the LDL-C treatment goals for initiating TLC and drug therapy.
However, it is likely that many fatal cardiovascular events could be prevented
in patients deemed to be at lower risk if the TLC dietary guidelines were recommended
for all adult Americans (with the exception of the plant sterol/stanol fortified
foods). The TLC diet is not the most effective diet for reducing LDL-C (or non-HDL-C
levels) to the optimal range now recognized by the NCEP.
The failure to recommend the most efficacious diet for lowering
LDL-C levels coupled with the delay of dietary treatment until the patient is
already at fairly high risk of CHD are two of the major short-comings of the
new ATP III guidelines. No doubt, factors such as the added cost of dietary
counseling for millions of Americans, current well-entrenched food habits, preferences
and the potential problems with compliance, with more aggressive dietary guidelines
than those advocated in ATP III, were used in setting the TLC dietary guidelines.
It also appears that the potential for economic harm to the food industry may
have been considerations of the ATP III as well. It also appears that the ATP
III failed to fully understand the "big picture" relationship between
diet, insulin resistance, body weight regulation and the atherosclerotic disease
process. As a result, the TLC dietary guidelines still do not represent the
best approach to prevent and treat CVD.
Twenty-five-year follow-up data from the Seven Countries
Study continues to show dramatic differences in the incidence of CHD mortality
between countries. Migration studies have shown that little, if any of these
major differences in CHD mortality between countries can be explained by genetic
differences. Compared to Japan and Southern (Mediterranean) European countries,
the death rate for CHD was far greater in Northern European countries and the
United States. To be sure much of the difference between countries in terms
of the incidence of CHD could be explained by the higher saturated fat intake
and higher TC and LDL-C levels in Northern Europe and the U.S. compared with
the Mediterranean region and Japan. However, the incidence of fatal CHD was
still at least 2-3 times higher in the U.S and Northern Europe than in Southern
Europe or Japan, even in individuals with similar fasting blood lipid levels.
The increased risk of CHD mortality was also adjusted for differences in age,
smoking status and systolic blood pressure (SBP). These adjustments also did
not remove the much higher risk of CHD death in the U.S and Northern Europe
than in Japan or the Mediterranean region of Europe.[11]
The major differences in the relative risk of fatal CHD
events in people having similar TC levels but very different diets should make
it clear the Framingham Heart Study risk data are far from perfect. Admittedly,
these data when coupled with fasting blood lipid levels do a fairly good job
of predicting the relative risk of developing CHD in people consuming a typical
American diet. However, they appear to grossly over estimate the relative risk
of CHD in people who are consuming either a Mediterranean-style diet or low-fat
Japanese-style diet. As one's diet deviates from a typical American diet to
one with much less saturated fat from red meat and dairy products, it appears
the predictive value of the data from the Framingham Heart Study diminishes.
Reasons for this are not clear but probably include a higher intake of omega
3 fatty acids and phytochemicals in the Mediterranean and Japanese diets that
reduce the propensity of LDL particles to oxidize, reduce inflammatory reactions
and thrombosis.
People with Type 2 DM almost always have some insulin resistance
and frequently dyslipidemia, hypertension and abdominal obesity. As a result
of these and other factors, patients with Type 2 DM have at least 2-3 times
the risk of fatal CVD as people without diabetes but with similar risk factors
for CVD. According to the ATP III, the 10 year risk of a fatal MI in someone
with Type 2 DM is similar to that of someone who as already has evidence of
clinical atherosclerosis (i.e. nonfatal MI, angina, symptomatic carotid artery
disease, peripheral arterial disease, abdominal aortic aneurysm). However, the
risk of death from CHD is actually significantly higher for men with a history
of CHD than those with diabetes but without a history of CHD. The presence of
both diabetes and a history of CHD identifies a particularly high-risk group
for death from CHD.[12]
Both the American Diabetes Association and the NCEP now
recommend lowering LDL-C levels to less than 100 mg/dl in those with Type 2
DM. About two-thirds of patients with Type 2 DM die of CVD compared to a little
less than half the general population. Aggressively lowering LDL-C levels of
patients with Type 2 DM has been shown to reduce their risk of fatal MI. Clearly,
more aggressive control of CVD risk factors in patients with Type 2 DM is scientifically
justifiable. In recognizing diabetes, a major risk factor for developing CVD,
the ATP III has taken a step in the right direction. However, there is reason
to question the use of the TLC Diet as optimal for treating overweight and obese
Type 2 DM patients. This diet recommends 25-35% energy as fat. Diets higher
in fat have several drawbacks in such patients. First, increasing dietary fat
will generally be expected to increase energy density and reduce satiety. Therefore,
a higher fat diet is more likely to promote weight gain and/or make weight loss
more difficult due to increased hunger compared to a higher carbohydrate diet
with a lower ED and higher fiber content. [13]
A second concern is that diets with a higher fat content
tend to increase free fatty acid levels. Increased free fatty acid (FFA) levels
are associated with increased insulin resistance (IR). Greater IR appears to
play a role in the development of Type 2 DM. Replacing dietary carbohydrate
with dietary fat has been shown to increase FFA levels in non-diabetic subjects.[14] Other studies have shown that the fall in FFA levels
in the blood is greatest when the diet is high in fiber and is composed largely
of slowly digested high-carbohydrate foods (low-glycemic index foods). Of course,
the surest way to lower FFA levels in the blood is to increase activity and
lose excess body fat.
While the TLC guidelines do stress the need for regular
exercise in patients with Type 2 DM, these new guidelines also recommend a moderately
high-fat diet (up to 35% en.). Higher fat diets tend to have a higher energy
density and a lower fiber and satiety value than diets higher in minimally processed
plant foods. Because most Type 2 DM patients are overweight and would benefit
from increased fiber intake and weight loss there is reason to question the
wisdom of the ATP III's TLC Diet for such patients. However, if the Type 2 DM
patient is thin and has lost a lot of beta-cell function then such patients
may do better with even more than 35% energy from fat. For more detailed information
about medical nutrition therapy for the treatment and prevention of CVD in people
with Type 2 DM see Diabetes CPE course at www.foodandhealth.com.
Type 2 DM nearly always starts with insulin resistance.
The insulin resistant state is associated with many metabolic changes. Some
of these metabolic disturbances develop long before Type 2 DM or even before
fasting blood sugar levels begin to rise above the normal range. These metabolic
changes can increase the risk of CVD even if they never lead to a diagnosis
of Type 2 DM. This IR metabolic state often includes lower HDL-C levels and
higher fasting and postprandial serum TG levels. It also generally includes
more atherogenic small dense LDL particles, higher insulin levels and an increased
tendency for blood clots to form. While most patients with low HDL-C levels
and elevated TG levels do show evidence of insulin resistance it should be noted
that genetic factors and/or lifestyle factors can result in low HDL-C levels
and/or high fasting TG levels in people with normal insulin sensitivity as well.
The ATP III correctly puts more emphasis on the risk of
CHD due to insulin resistance and the metabolic disturbances associated with
it. This insulin resistant condition is known as the metabolic syndrome (a.k.a.,
syndrome X, insulin resistance syndrome, insulin resistance metabolic syndrome).
However, the ATP III's dietary recommendations for most patients with this metabolic
syndrome suggest to this reviewer some failure to fully understand the role
of diet in causing the metabolic syndrome to develop in genetically susceptible
individuals.
There is compelling scientific evidence that excessive energy
intake, particularly when coupled with an inactive lifestyle, can lead to excessive
body fat stores, IR, impaired glucose tolerance (IGT), Type 2 DM, increased
blood pressure (BP) and dyslipidemia. The adverse changes in blood lipids (dyslipidemia)
that typically accompany IR include elevated fasting and postprandial serum
TG levels, reduced HDL-C and an increasing ratio of small dense LDL particles
(a.k.a., Phenotype B or Pattern B). Small dense LDL particles are believed to
be much more atherogenic than larger LDL particles. In addition, the metabolic
syndrome also promotes thrombosis. All of these metabolic changes have been
associated with an increased risk of a fatal MI or stroke. Clearly there is
a need to diagnose and treat the metabolic syndrome whenever it exists. Waiting
for Type 2 DM to develop or clinical signs of CVD makes no sense.
Unfortunately, there is no simple, cost effective test that
directly measures the presence of insulin resistance or small dense LDL particles.
However, the metabolic syndrome is frequently associated with an increased waist
to hip ratio and other easily measured metabolic changes that can be used to
predict its presence. ATP III establishes risk factors for identifying the likely
presence of the metabolic syndrome using 5 clinical indicators or risk factors.
Table 3 shows how these 5 clinical indicators are used to identify the metabolic
syndrome according to the new NCEP ATP III guidelines. The ATP III guidelines
are a step in the right direction because they do provide a reasonably accurate
way to identify those patients most likely to have insulin resistance and the
associated metabolic syndrome.
Table 3. Clinical Identification of the Metabolic
Syndrome Requires the Presence of 3 or More of These Risk
Factors
Risk Factor Defining Level
Abdominal obesity Waist Circumference
Men >40 inches
Women >35 inches
Triglycerides 150 mg/dl or higher
HDL-C
Men <40 mg/dl
Women <50 mg/dl
Blood pressure 130/85 mmHg or higher
Fasting glucose 110 mg/dl or higher
_____________________________________________________________________
This classification system will certainly miss many younger
and some older people with clinically significant insulin resistance, small
dense LDL particles and a heightened risk of CHD. It will also misclassify some
people who do not have insulin resistance as having the metabolic syndrome.
Nevertheless, given the current problems in directly measuring and diagnosing
insulin resistance, the use of the ATP III's method of assessing the presence
of the metabolic syndrome seems reasonable. What appears to this reviewer to
be less reasonable are the recommended by ATP III's TLC for people who are identified
with the metabolic syndrome. Specifically, the TLC Diet for patients identified
as having the metabolic syndrome appears to be based on an incorrect interpretation
of the scientific evidence.
The NCEP has taken several steps forward with recommendations
aimed at reducing morbidity and mortality form CVD associated with the metabolic
syndrome. However, this reviewer believes the ATP III has also made a few missteps
with the TLC Diet, which makes it less than optimal for promoting weight loss
and preventing CVD in patients with the metabolic syndrome. What follows is
a critical review of scientific evidence that calls into question some of the
recommendations made by ATP III.
The ATP III's dietary guidelines for treating patients whom
have been identified as having the metabolic syndrome, is based primarily on
short-term clinical trials. These studies have consistently shown higher fasting
TG levels and lower HDL-C levels when dietary carbohydrate displaces dietary
fats rich in monounsaturated fatty acids. More recently, the isoenergetic substitution
of carbohydrate with unsaturated fat was also shown to increase small dense
LDL particles. On the surface, these studies do seem to suggest that people
with the metabolic syndrome would be better off with more dietary unsaturated
fat and less dietary carbohydrate. These studies are no doubt the primary reason
the ATP III decided to increase the NCEP's recommendation for dietary fat to
35% of the energy for patients with elevated TG levels, low HDL-C and other
features of the metabolic syndrome. However, there is reason to believe that
such a recommendation may actually end up increasing the very metabolic disturbances
the ATP III believes it will correct. A critical review of the type of research
studies that have misled the NCEP to recommend a higher intake of unsaturated
fat and a lower intake of carbohydrate will reveal where they went wrong.
Much of the research behind the NCEP's recommendation to
increase dietary fat at the expense of carbohydrate comes from studies conducted
at Stanford University. Other researchers at other institutions have duplicated
most of the results from the Stanford group using a similar experimental design.
Unfortunately the experimental design of these studies makes their result of
questionable clinical value. For example, there are serious design flaws in
a study that supposedly demonstrated that a diet higher in carbohydrate and
lower in unsaturated fats alters blood lipids in such a way that the risk atherosclerosis
is increased.[15] This study showed
a lower HDL-C (39 vs. 44 mg/dl) and higher fasting triglycerides (TG) (206 vs.
113 mg/dl) in 8 healthy subjects fed a high-carbohydrate (25% fat) diet compared
to those same subjects fed a high-fat (45% fat) diet for 2 weeks. This type
of finding is similar to earlier studies done by these researchers and others
in patients with Type 2 DM.[16]
In addition to the presumably adverse effects on fasting
blood lipids seen in both of these studies, these researchers also examined
postprandial remnant lipoprotein particles (RLP) and found they too were higher
on the high-carbohydrate diet compared to the diet higher in unsaturated fat.
Numerous studies have shown that elevated postprandial TG levels increase the
risk of CHD.[17] All of the changes in blood lipids (both fasting
and postprandial) seen when dietary carbohydrate replaces unsaturated fat in
short-term clinical trials are presumably associated with an increased risk
of coronary artery disease (CAD). This is because lower HDL-C and higher fasting
TG levels have been consistently correlated with a higher risk of CHD in epidemiological
studies of Americans.
The changes in blood lipids that often result from the isoenergetic
exchange of dietary carbohydrate for monounsaturated fat are also similar to
what is typically seen in people with the metabolic syndrome (i.e., increased
fasting TG and decreased HDL-C). Because the metabolic syndrome is associated
with an increased risk of CAD the authors concluded, "Given the atherogenic
potential of these changes in lipoprotein metabolism, it seems appropriate to
question the wisdom of recommending that all Americans should replace dietary
saturated fat with carbohydrate."[18]
Is such a conclusion justified? There are many reasons to believe such a conclusions
is at best premature and more likely incorrect. Nevertheless it was no doubt
the results of this and similar studies that convinced the ATP III to recommend
a higher fat intake for most people with the metabolic syndrome.
Scientific evidence is accumulating implicating higher postprandial
TG levels with an increased risk of developing CHD.[19]
[20] However, while
postprandial TG levels do correlate fairly closely with fasting TG levels among
people who are consuming similar diets, this is not necessarily the case when
if the diets differ dramatically in the fat to carbohydrate ratio and/or energy
intake.
A crossover design study, that compared the effects of a
VLF diet to a diet higher in fat on blood lipids, may help put the results of
the Stanford study in better perspective. In this study, a VLF (15% fat calories),
high-carbohydrate diet was compared to a higher fat diet (30% of calories).
The VLF diet was fed isocalorically with the more moderate-fat diet (as was
done in all the Stanford studies). However, in this same study, the high-carbohydrate
diet was also fed ad libitum. Both fasting and postprandial lipids were measured.
When the VLF diet was fed isocalorically with a moderate
fat diet, the fasting TG levels were much higher (188 vs. 115 mg/dl) on the
higher carbohydrate diet than on the moderate fat diet.[21]
Just as the Stanford researchers observed in their recent study, the results
of this study also showed that postprandial TG (and presumably RLP) were also
much higher on the higher carbohydrate diet than on the diet higher in unsaturated
fat (see Figure 1 below). HDL-C was also lower (42 vs. 35 mg/dl) on the higher
carbohydrate diet just as it was in the Stanford study. LDL-C was somewhat higher
on the VLF (134 vs. 128 mg/dl) than the moderate fat diet when both diets were
fed isocalorically. However, when the VLF, high-carbohydrate diet was fed ad
libitum, the LDL-C was now lower (119 vs. 128 mg/dl) than on the 30% fat diet.
Remarkably, this was despite a much higher PUFA content (11.2% vs. 2.5% energy)
and P/S (1.6 vs. 0.5) on the 30% fat diet compared to the VLF diet. The P/S
ratio in the Stanford study was also higher on the higher fat diet. And while
the fasting TG levels were still a little higher (130 vs. 115 mg/dl) on the
VLF fed ad libitum compared to the moderate fat diet, the postprandial TG level
was already considerably lower on the VLF diet compared to the 30% fat diet.
Figure 1. Effect of an AHA-Style Diet and a VLF Diet (Fed
either Ad Libitum
or Isocalorically with the AHA-Style Diet)
on Serum TG Levels

Adapted from Lichtenstein. Arterioscler Thromb. 1994;14:1751
As we have seen, an increased fasting and postprandial TG
level may be associated with more potentially atherogenic RLP. As Figure 2 above
clearly shows, even when fasting TG levels are somewhat higher on a higher carbohydrate
diet, they may still be much lower during most of the day on such a diet. Because
most people spend most of the day in the postprandial state, it seems clinically
more relevant to study the impact of dietary changes on postprandial blood lipids
rather than just fasting blood lipid levels. Unfortunately, the ATP III apparently
ignores the fact that when diets are fed ad libitum the postprandial TG level
is often lower on VLF diets than diets high in monounsaturated fat even when
the fasting TG level is somewhat higher on the higher carbohydrate diet.
Data from The Atherosclerosis Risk in Communities (ARIC)
Study found that fasting TG levels were the strongest predictor of postprandial
lipids. The ARIC Study also found that elevated postprandial TG levels were
a better predictor of the amount of atherosclerosis than were fasting TG levels.[22]
More recently, data from the ARIC Study were used to demonstrate that the determinants
of fasting and postprandial blood lipids differ.[23]
Among middle-aged Americans it is clear that fasting TG levels do correlate
fairly well with postprandial TG and this appears to be why fasting TG level
is also a fairly good predictor of atherosclerotic disease. So the ATP III is
correct to be concerned about Americans who do have elevated fasting TG levels
(150 mg/dl or more). However, if two people have the same fasting TG level and
they consume diets that differ dramatically in fat and carbohydrate content
then it should be clear that the rise in postprandial TG levels will be much
greater (and probably more atherogenic) on a high-fat than a very-high-carbohydrate
diet.
Most people spend most of their lifetime in a postprandial
state. Typically 18 or more hours a day is the norm. Therefore it may be inappropriate
to claim that finding higher fasting TG levels as a result of adopting a higher
carbohydrate diet causes an increased risk of CAD. This is because the increase
in postprandial TG levels (and presumably RLP) would be much less with an ad
libitum VLF, high-fiber diet than it would be on an ad libitum diet, which contains
more monounstaturated fat. It should be clear that clinicians cannot assume
the higher risk of CVD often associated with higher fasting and postprandial
TG levels (in people consuming high-fat Western-style diets) would be comparable
to the risk of CVD with a similar fasting TG level in people consuming a VLF
diet. While it seems likely that atherogenic RLP would fall along with postprandial
TG levels on a low-fat diet if fed ad libitum compared to a diet higher in unsaturated
fat over the long-term this remains to be proven. This is an area that deserves
more attention from researchers.
Initially, when dietary carbohydrate replaces UFA and body
weight and dietary energy intake are held constant it is generally true that
most people do experience a rise in fasting TG levels. This is particularly
true if the high-carbohydrate diet is high in refined sugars and low in fiber.
Virtually all the studies which have shown elevated fasting TG levels on a higher
carbohydrate than a diet higher in monounsaturated fat have used primarily refined
carbohydrates and have been very short-term, typically lasting no more than
a few weeks. However, epidemiological studies have shown that neither CHD nor
elevated fasting TG levels are common in human populations consuming diets very
high in carbohydrate but with little refined sugar.[24]
Studies that last much longer than 2-3 weeks typically find
little or no sustained rise in fasting TG levels as a result of increasing the
percent of energy from dietary carbohydrate. When a low-fat, high-carbohydrate
diet consisting largely of whole natural foods is fed to people accustomed to
a typical modern diet it typically takes 4-6 weeks for their fasting TG levels
to stabilize. However, in a few subjects it can take as long as 10 to 18 weeks
for fasting TG levels to stabilize after a switch to a diet much higher in carbohydrate.[25] Figure 2 below shows what
happened to fasting serum TG levels in a group of 54 postmenopausal women who
were placed on a low-fat, high-carbohydrate diet consisting largely of whole
foods.[26]
Figure 2. Effect of increasing dietary carbohydrate
at the expense of fat on fasting plasma triglyceride levels and body weight
in postmenopausal women.

Adapted from Kasim-Karakas SE, et al. Metabolism 1997;46:431
During the first 4 months of this study, dietary carbohydrate
gradually replaced dietary fat in the diet but subjects were required to consume
enough calories to prevent weight loss. During this time, fasting serum TG levels
rose from 151 to 204 mg/dl. In this study, the increase in average fasting TG
levels was much less than that observed in most studies lasting only a few weeks
or less. This was the case, even though the difference in carbohydrate content
of the two diets used in this study (20% increase in calories from carbohydrate)
was similar to that used in most shorter term studies. In the Stanford study,
fasting TG levels increased nearly twice as high on the high-carbohydrate diet
compared with the high monounsaturated fat diet (113 vs. 206 mg/dl) as observed
in this study (151 vs. 204 mg/dl). This was the case even though both high-carbohydrate
diets had the same percent difference in dietary carbohydrate content (20% more
of energy).
There are two likely explanations. First, four months is
long enough for more physiological adjustment to the higher carbohydrate intake
to occur. However, as can be seen from Figure 2, there was a small amount
of weight loss on the VLF diet despite the researchers best efforts to control
body weight. During the second phase of the study, when food intake was ad libitum,
fasting TG levels returned close to baseline within two months. If fasting TG
levels are similar on diets with large differences in carbohydrate and fat content
then postprandial TG levels will always be much lower on the lower fat diet.[27]
Another reason for the greater initial rise in fasting TG
levels observed in the Stanford researchers' study and others like it was that
these researchers used more refined sugar in the high-carbohydrate diet (which
tend to raise TG levels more than natural high-carbohydrate foods). For example,
sucrose and fructose appear to increase fasting and postprandial TG levels more
than starch or glucose, particularly in men. Replacing sucrose and fructose
with starch of glucose has been shown to increase fasting TG levels.[28]
[29] Another study
showed that both fasting and postprandial TG levels were significantly higher
when dietary sucrose displaced starch isocalorically in normal weight women.[30]
Another reason the Stanford study observed elevated fasting
TG levels was that their subjects were on the experimental diets for only 2
weeks. Two weeks is not long enough for the body to biochemically adapt to a
higher carbohydrate intake. Also, the subjects in this study lost a little weight
during the first 4 months of the study despite the researchers best attempts
to get them to maintain their initial body weights. Weight loss tends to lower
TG levels so even the loss of a few pounds can blunt the TG raising effects
of adopting a higher carbohydrate diet. The inability of researchers to control
body weights effectively over long periods of time when they differ dramatically
in fat content may be another reason that nearly all the studies that indicate
large increases in fasting TG levels on higher carbohydrate diets typically
last a few weeks or less.
During the next 8 months of this study the subjects continued
to consume the same high-carbohydrate, low-fat (15% of energy) diet. However,
during this phase the researchers no longer tried to control how much their
subjects ate or what they weighed. During this phase, the subjects' calorie
intake was ad libitum. Their average fasting TG levels gradually returned to
its baseline level. Not surprisingly, in this 8 month period, the subjects lost
another 4.5 pounds consuming a self-selected VLF diet (ad libitum). It is likely
that if people were taught to consume a VLF diet, which consisted largely of
natural plant foods, they would lose excess body fat without any need to count
calories. In addition, in most subjects, the overall blood profile would improve
and their risk of CHD would fall dramatically over time.
Every study published by the Stanford group and others,
which has shown detrimental effects of high-carbohydrate relative to high unsaturated
fat diets on blood lipids, has required their subjects to consume the same energy
level and/or maintain the same body weight on both high-fat and high-carbohydrate
diets. It is because a diet with more fat is generally more calorie dense and
lower in fiber than a higher carbohydrate diet that it would be expected to
lead most people to consume more calories than they would ad libitum on a diet
lower in fat.[31] It appears that the NCEP ATP III
should have been much more concerned about the type of high-carbohydrate foods
consumed than the percent of energy coming from carbohydrate and fat.
It seems likely then that it is only when research subjects
are required (by researchers) to eat past satiety on a very-high-carbohydrate
diet, to prevent weight loss, that potentially adverse metabolic changes result
in most people. Higher fasting TG levels, higher postprandial TG and RLP concern
the ATP III but a comprehensive review of the literature shows the presumably
adverse changes in blood lipids when people first switch to a high carbohydrate
diet are mostly transient unless the high-carbohydrate diet is very high in
sugar and has little fiber.[32]
It should be noted that a high-carbohydrate diet that is high in sugar and refined
white flour and has a high calorie density may not lead to a reduced ad libitum
energy intake. Such a diet may not promote weight loss and may have detrimental
metabolic effects in many people.[33] However, a diet
consisting of less processed and refined high-carbohydrate foods is likely to
increase satiety, aid weight loss, reduce insulin resistance and improve blood
lipids.[34] [35]
The ATP III was also concerned about the often reported
drop in HDL-C levels that frequently accompany the rise in fasting TG levels
in most people who initially switch to a diet much higher in carbohydrate and
much lower in fat. However, just as is the case with higher fasting TG, there
is reason to suspect the ATP III's concern about higher carbohydrate diets promoting
atherosclerosis because of lower levels of HDL-C is unwarranted if one examines
the big picture.
It should be noted that while higher HDL-C levels are typically
associated with a reduced risk of atherosclerotic disease, this is not always
the case. In some patients who have a mutation in the hepatic lipase gene and
also in those who have the apo E3/E4 genotype, HDL-C are often in the normal
range or even elevated and yet these patients are still at higher risk of CHD.[36]
What impact changes in dietary fat and carbohydrate intake have on reverse cholesterol
transport in patients with these genetic abnormalities requires more study.
The drop in HDL-C level and the rise in fasting TG level
are typically observed in short-term studies where the high-carbohydrate and
high-unsaturated fat diets are fed isoenergetically.[37]
[38] However, most
research suggest that both fasting TG and HDL-C levels often return close to
baseline levels if the higher carbohydrate diet is fed ad libitum and for a
long enough time for the body to physiologically adapt to the higher carbohydrate
intake. A big part of that adaption is the loss of excess body fat and improved
insulin sensitivity.
Two studies examined the metabolic effects of a VLF diet
(15% fat) compared to a moderate-fat (30% of energy) diet but in these studies
the VLF diet was fed either isocalorically with the higher fat diet or ad libitum.
In both studies, when the VLF diets were fed at the same calorie level as the
higher fat diets, the VLF diets produced the same potentially adverse metabolic
effects typically associated with the metabolic syndrome (increased fasting
TG and decreased HDL-C). However, these adverse metabolic changes largely disappeared
when the research subjects were allowed to eat the VLF diets ad libitum.[39]
[40]
Data from the National Weight Control Registry, which has
examined people who have successfully lost weight and kept it off long-term,
clearly shows that most do so with a low-fat diet and regular exercise. Indeed,
over 90% of those who successfully lost weight and kept it off consumed a diet
with less than 30% fat calories.[41] This is consistent with the conclusions
of a recent review of popular diets. They conclude, "Diets that are high
in carbohydrate and low to moderate in fat tend to be lower in energy. The lowest
energy intakes were observed for those on a vegetarian diet. The diet quality
as measured by the HEI (Healthy Eating Index) was highest for the high carbohydrate
groups and lowest for the low carbohydrate groups. The BMIs were significantly
lower for men and women on the high carbohydrate diet: the highest BMIs were
noted for those on a low carbohydrate diet."[42]
In the real world, a more vegetarian diet that is lower
in fat and has more fiber will usually lead to reduction in ad libitum energy
intake. Over time this lower energy intake leads to a lower BMI.[43]
Weight loss nearly always lowers both fasting and postprandial TG levels and
raises HDL-C. However, the studies the ATP III uses to justify recommending
a diet with more unsaturated fat all controlled energy intake and body weight
of their subjects. Therefore, the experimental design of these studies prevented
perhaps the major metabolic advantage of higher carbohydrate diets from occurring.
In addition, all of the studies associating adverse metabolic changes with a
lower fat diet were also of very short duration, typically lasting no more than
a few weeks. This may not be long enough for people accustomed to a high-fat
diet to metabolically adjust to a VLF, high carbohydrate intake. Therefore,
the recommendation of the ATP III for people with the metabolic syndrome to
consume a higher fat diet (35% en) appears to be based on short-term studies
with a design flaw that leaves their results with little relevance for most
patient living in the real world.
Another problem with the new ATP III guidelines is the assumption
that differences in blood lipids that arise from short-term changes in diet
mean the same thing as differences observed between people in Framingham, Massachusetts.
In Framingham most people consume a similar diet so differences in fasting TG
levels or HDL-C levels are probably largely due to differences in genetic factors
and differences in body weight, activity level, smoking, etc. In addition, the
differences in blood lipids that result from dietary changes are often transient
whereas the differences in blood lipids between people in Framingham tend to
remain fairly stable over time. A 20-year old man with a low HDL-C level is
quite likely to end up as a 30 or 50 year old man with low HDL-C level. Research
shows that differences in blood lipids between people in a cultural fairly homogeneous
population tend to track each other over time. However, changes in blood lipids
that result from a change in diet are sometimes transient.
Data from Framingham and other epidemiological studies have
shown an increased risk of CAD was correlated with a lower HDL-C level and often
with a higher fasting TG level. Few people doubt that higher fasting TG and
lower HDL-C are usually associated with an increased risk of CAD in people eating
a typical high-fat Western diet. Nor does there appear to be much doubt that
higher levels of postprandial RLP are associated with a more rapid progression
of atherosclerosis in people eating high-fat, Western-style diets. However,
there are no studies to show that higher levels of fasting TG and postprandial
RLP and lower HDL-C resulting from switching to a diet higher in carbohydrate
and lower in fat actually promotes atherosclerosis. The ATP III apparently believes
that changes observed in blood lipids during short-term clinical trials are
detrimental. However, there is no solid clinical research that demonstrates
that such lipid changes really do promote atherosclerosis and increase the risk
of CAD in people who adhere to high-carbohydrate diets for a prolonged period
of time.
Another problem with the idea that high-carbohydrate diets
promote changes in blood lipids that increase the risk of CAD is that it seems
to conflict with most epidemiological cross-cultural observations. Population
studies of people consuming high-carbohydrate diets have shown that CAD is far
less common in those populations than it is in America and other countries where
diets high in animal products and fat are the norm.[44]
However, in these populations not only is the consumption of carbohydrate higher
but the intake of SFA and cholesterol are much lower and fiber intake is often
much higher than they are in Americans. There may also be differences in activity
and other lifestyle factors that could account for at least some of the differences
in CAD risk between Americans and the high-carbohydrate diet consuming populations.
The ATP III apparently believe that the drop in HDL-C seen
in short-term studies when dietary carbohydrate displaces fat isocalorically
means there is an increased the risk of CAD in the long-run. There are several
reasons to believe this is not the case. First, there is growing evidence that
the drop in HDL-C that results from restricting dietary fat intake does not
lead to a permanently lower HDL-C. This is because replacing high-fat foods
with high-carbohydrate foods usually reduces ad libitum energy intake. A lower
energy intake leads to weight loss and a lower body weight. A lower body weight
usually leads to an increase in HDL-C. For example, a study by Thuesen in Europe
found that when a group of hypercholesterolemic men were placed on an ad libitum
VLF, near vegetarian diet for 3 months their energy intake decreased and they
lost about 16.5 lbs. On this VLF, high-carbohydrate diet, their LDL-C levels
dropped from 236 to 139 mg/dl (-41%) and their fasting TG dropped from 170 to
145 mg/dl (or -15%) but their average HDL-C was essentially unchanged (36 to
37 mg/dL or +3%).[45]
This same study followed these men for another 9 months. Those who continued
to consume a VLF diet for another 9 months saw their HDL-C levels continue to
increase.
It should be noted that fasting plasma TG levels also fell
on average in the Thuesen study which is the opposite of what the Stanford group
has repeatedly observed in short-term studies where both the high-fat and high-carbohydrate
diets were fed isocalorically over a very short time frame. The results of the
Thuesen study clearly demonstrate that when a VLF, high fiber, near vegetarian
diet is fed ad libitum to patients at high risk of CAD (many of whom would be
identified as having the metabolic syndrome by the ATP III criteria), the changes
in their blood lipids are usually favorable over the long-term. Indeed, other
studies have shown that in many patients a VLF, near vegetarian diet leads to
regression of atherosclerotic plaque.[46]
By contrast, this same showed that those subjects in the control group who were
instructed to follow what the NCEP now calls a "Heart Healthy Diet"
experienced progression of their atherosclerotic lesions even though most were
also taking "statin" drugs to help lower their blood lipids.
Another reason to question concerns about a drop in HDL-C
when dietary carbohydrate replaces monounsaturated fat is that research has
shown that the fractional clearance rate of cholesterol is much faster on VLF
diets than it is on diets higher in fat.[47] This means that
it is likely that the amount of cholesterol transported back to the liver from
the arteries is not impaired on a high-carbohydrate diet even if the HDL-C level
does drop. In animals studies, reverse cholesterol transport was not impaired
despite a much lower HDL-C on a high-carbohydrate diet compared to a high-fat
diet.[48]
In addition to assisting reverse cholesterol transport,
HDL particles may help protect against atherosclerotic disease in other ways.
For example, HDL particles contain proteins that can potentially reduce the
oxidative modification of LDL particles. This is important because these oxidized
LDL particles are believed to play the primary role in the initiation and growth
of atherosclerotic plaques. Oxidized LDL particles attached macrophages to the
artery wall. These macrophages release chemicals that trigger local inflammation
within the artery wall. The examination of HDL particles taken from CAD patients
with normal HDL-C levels has shown that their HDL particles do block the oxidation
of LDL particles. Indeed, these HDL particles were actually shown to promote
LDL oxidation and create a proinflammatory state.[49] This same research group fed mice
a high-fat atherogenic diet and found that they developed pro-inflammatory HDL
particles. By contrast when these same mice were fed a low fat, high-fiber chow
diet their HDL particles prevented the formation of pro-inflammatory, oxidized
LDL particles.[50]
So while HDL-C levels do often fall initially when most
people first adopt a VLF diet, it is not clear that this lower HDL-C level necessarily
increases the risk of CAD. Furthermore, in most patients, the adoption of a
high-fiber, VLF, more vegetarian diet will result in weight loss. Over the long-run
weight loss will eventually result in HDL-C levels returning to close baseline
levels in most patients and even higher levels in many patients who lose and
keep off a lot of body fat. Epidemiological evidence does suggest that HDL-C
may be somewhat lower in human populations who consume very high carbohydrate
diets. However, these same human populations have also been shown to have a
very low incidence of CAD. So while the ATP III recommendation for an HDL-C
below 40 as a risk factor seems appropriate for people consuming a typical high-fat
atherogenic American diet it is questionable whether this same target is warranted
for individuals who adopt a VLF more vegetarian diet that is high in fiber.
C-reactive protein (CRP) is a nonspecific marker of chronic
low level inflammation in the body. Growing research suggests inflammatory processes
are involved in atherosclerotic plaque formation, progression, rupture and in
thrombosis.[51] Inflammatory cytokines
trigger the release of an enzyme (sphingomylinase) from both macrophages and
arterial endothelial cells into the intracellular space. This enzyme has been
shown to cause the aggregation and fusion of LDL particles inside the artery
wall, leading to the formation of a growing pool of cholesterol-rich lipid.
Increasing evidence suggests this may be the primary mechanism leading to the
formation of the necrotic lipid core of atherosclerotic plaques.[52] The release of sphinogomylinase
has been shown to increase in mice models of systemic inflammation.[53] This suggests that it is because
CRP is a good marker of low-level systemic inflammation that it is a good predictor
of atherosclerotic plaque growth. Plaques with growing necrotic lipid cores
are more likely to rupture and trigger a MI or thrombotic stroke.
Not surprisingly, there is growing evidence that higher
levels of CRP are associated with an increased risk of morbidity and mortality
from CHD.[54] [55]
CRP levels have been shown to correlate positively with insulin resistance,
the metabolic syndrome, obesity and increased abdominal fat stores.[56]
While the new CRP guidelines put more emphasis on losing excess body fat, the
TLC Diet recommended by the ATP III specifically increases the fat content of
the diet to 35% of calories for those with the metabolic syndrome. The TLC Diet
recommended for patients with the metabolic syndrome is inconsistent with research
showing the most effective diet for successful long-term weight control is one
very low in fat. People who have been successful at losing a lot of weight and
keeping it off most often consume a diet quite low in fat and do a lot more
exercise than the TLC recommends.[57] [58]
[59]
A recent study of 83 obese women showed that the loss of
7.9 kg over 12 weeks on a VLF (15% en) diet resulted in a mean 26% drop in CRP
levels. The drop in CRP level was proportional the amount of weight lost.[60]
While the ATP III’s primary focus is on lowering LDL-C levels there is growing
evidence that excessive abdominal fat can increase the risk of CVD in many ways.
Greater amounts of abdominal fat promote inflammation and coagulation but inhibit
fibrinolysis.[61] A VLF, low energy density diet,
that is high in fiber, is probably best for reducing ad libitum energy intake.
Therefore, it seems likely that such a VLF is also preferable to a diet with
a higher fat content for treating overweight or obese patients with the metabolic
syndrome. Unfortunately, the ATP III guidelines specifically recommend a diet
higher in fat (35% en) for patients identified with the metabolic syndrome.
The ATP III focus primarily on blood lipid changes observed
in short-term clinical trials has led to dietary recommendations that may prove
counterproductive for achieving the reduction of other CVD risk factors such
as excess body fat stores and elevated levels of CRP.
If high-carbohydrate diets are more atherogenic than diets
higher in fat, what are we to make of several studies that have reported that
VLF, near-vegetarian diets cause regression of atherosclerosis in most patients
who already have advanced coronary artery disease?[62]
[63] [64]
[65] By contrast,
there are no comparable studies showing a regression of atherosclerotic plaques
with a diet higher in fat.
If diets higher in carbohydrate do result in a more atherogenic
lipoprotein profile (as the ATP III apparently believes), how can we reconcile
such a belief with the results of a 12-year study that found that a VLF, near
vegetarian diet greatly reduced deaths from CAD? This study also showed that
a VLF also markedly reduced overall mortality in older subjects (all of whom
had had a previous heart attack) compared to the control group who maintained
a typical high-fat American diet?[66] Obviously a more vegetarian, high-carbohydrate
diet is much less atherogenic than a typical American diet, which is much higher
in saturated fat, hydrogenated fat and cholesterol. It seems clear that a VLF,
near vegetarian diet composed largely of natural, minimally processed plant
foods is both safe and efficacious for the prevention and treatment of atherosclerosis
and its sequelae.
In healthy people, the benefits of lowering serum cholesterol
by reducing dietary fat and increasing dietary carbohydrate have been well documented
in terms of preventing CAD.[67] There really can
be no rationale debate about whether replacing dietary saturated fatty acids
(SFA) with carbohydrate will help to prevent CAD in the average American. Perhaps
there are some people in America that would do better healthwise on a diet higher
in unsaturated fat and lower in carbohydrate. However, this has not been demonstrated
clinically with hard end points like MI, stroke and total mortality. Even if
there are some patients who would do better on a high -unsaturated fat diet
compared to a high-carbohydrate diet there is no cost effective diagnostic test(s)
to determine who these patients are.
It is hard to understand the reluctance of the NCEP to recommend
replacing foods high in SFA and cholesterol with foods high in carbohydrate
and fiber. There is overwhelming scientific data to support such a recommendation
as a safe and effective public health policy for all Americans who need to reduce
their risk for CAD. Extreme reductions in dietary fat and cholesterol coupled
with a marked increase in dietary carbohydrate and fiber has been proven to
reverse atherosclerosis in clinical trials. Switching to a VLF, more vegetarian
diet from a typical American diet has also been shown to reduce the overall
risk of dying for patients with pre-existing advanced CAD. Those who would advocate
replacing SFA with unsaturated fatty acids (UFA) should be aware that there
is no such proof that diets higher in UFA reverses CAD. Therefore, it seem a
leap of faith, rather than science to believe replacing SFA with UFA prevents
CAD more effectively than consuming more fruits, vegetables, beans and whole
grains instead of the monounsaturated oils.
No one knows for sure at this point, although changes in
blood lipids certainly do suggest that this would be the case. Replacing SFA
with UFA does lower serum total cholesterol (TC) and LDL-C levels about as much
as replacing SFA with carbohydrate. Replacing saturated fat with monounsaturated
fat does not lower HDL-C levels and may lower fasting TG levels. However, there
is concern that diets higher in monounsaturated fat may increase the tendency
of blood to clot due to higher levels of clotting factor VII.[68]
[69] The authors
of a Danish study conclude, “A low-fat, high-fiber diet may not only reduce
the atherogenic but also the thrombogenic tendency of an individual compared
with a diet corresponding to the average Danish diet”.[70]
If a diet higher in carbohydrate and fiber and lower in total fat reduces the
risk of thrombosis, it may be particularly beneficial for patients with advanced
atherosclerotic lesions because most MIs are caused in part by thrombosis and
impaired fibrinolysis.
Perhaps the ATP III believe that even if a diet higher in
monounsaturated fat doesn’t reduce thrombosis it may still improve blood lipids
and this should help reverse atherosclerotic lesions. However, no one has shown
that a diet high in MUFA would actually cause regression of atherosclerotic
lesions. Indeed, in one monkey study, a diet high in MUFA did improve TC and
other blood lipid levels compared to a diet high in SFA. The change in blood
lipids in the monkeys was in the same direction as seen in humans fed similar
diets. However, despite what appeared to be "improved blood lipids",
atherosclerosis progressed to a similar degree in the monkeys fed the high-MUFA
diet as those fed the high-SFA diet.[71] So at least in
animal models, "improving blood lipids" does not necessarily slow
the progression of atherosclerosis. The results of this study call into question
the wisdom of assuming that changes in blood lipids in response to dietary changes
mean the same thing as differences in blood lipids observed between individuals
who are all consuming a similar diet. In this latter case, the differences in
blood lipids would be largely due to genetic factors.
The results of most clinical trials have shown that ad libitum
energy intake falls and body fat stores diminish when people are switched from
a typical modern diet to a diet with a lower fat content. This is consistent
with observational data from human populations that generally show that cultural
groups that consume diets higher in fat generally have greater average BMIs
than cultural groups consuming diets low in fat and high in fiber. Studies of
human cultures typically find a low prevalence of obesity and also a low prevalence
of CHD and Type 2 DM where a VLF intake is the norm.[72]
More recently, carefully controlled studies have consistently shown that the
primary mechanism by which reducing dietary fat leads to weight loss is the
resulting decrease in ED of the lower fat diet.[73]
Because of the extremely high energy density of refined
oils and most high-fat foods (e.g. nuts, nut butters, seeds) it is far more
difficult to plan a diet with a low energy density if these foods are not more
limited. A diet with 35% fat compared to a diet with only 10% fat would tend
to be more energy dense and this would make weight loss without hunger more
difficult. The metabolic syndrome is caused largely by excessive ad libitum
energy intake over time coupled with a sedentary lifestyle. From this reviewer’s
perspective it makes much more sense to recommend a diet very low in fat for
people with this syndrome. As has been shown in this review, the presumably
adverse metabolic effects the ATP III seems so concerned about with diets higher
in carbohydrate and lower in fat are likely to prove transient in the real world.
The presumably adverse impact of high-carbohydrate diets
on blood lipids is limited primarily to short-term clinical trials in which
the research subjects' calorie intake is artificially manipulated (i.e., controlled
by researchers). The high-carbohydrate study diet is composed largely of sugar
and other refined carbohydrates with little or no fiber. This is the Stanford
model the ATP III bases their recommendation on for higher fat intake for those
with the metabolic syndrome. However, by requiring research subjects to consume
the same energy intake and maintain the same body weight on both high-fat and
low-fat diets, these studies have shown metabolic changes that are reason for
concern particularly for those with the metabolic syndrome. It is clear that
people with the metabolic syndrome really need to lose excess body fat and participate
in regular exercise. These reduce insulin resistance and the adverse metabolic
changes that can increase CVD risk factors and promote the development of Type
2 DM. People with the metabolic syndrome do not require more dietary fat because
increased dietary fat tends to promote weight gain over time.
At least some members of the ATP III are well aware of these
arguments. The flawed experimental design of studies comparing high-fat and
high-carbohydrate diets was explained in a letter to the editor, the Stanford
Group, University of Texas Southwestern Medical Center group, and the University
of California, Berkeley group.[74] [75]
[76] Nevertheless,
the ATP III still choose to promote a diet higher in fat for people with the
metabolic syndrome.
Research in the future should compare a high-carbohydrate
diet consisting largely of natural foods that are high in fiber like fruits,
vegetables, whole grains, and beans with a similar diet to which olive oil had
been added. Both diets would need to be fed ad libitum (rather than imposing
artificial controls on their research subjects' energy intake). If such a study
were done, it would likely find that a VLF, high-fiber diet does not produce
the adverse changes in blood lipids the ATP III is so concerned about. In part,
the favorable effects of the VLF diet compared to one higher in fat would be
due to a reduction in energy intake and weight loss. Indeed, any changes in
blood lipids that such a diet caused must be viewed as favorable simply because
a VLF, near vegetarian diet has been proven to reverse atherosclerosis. This
is something diets higher in fat have not been shown to do. Why does the ATP
III want physicians and dietitians to abandon the only dietary approach ever
proven to atherosclerotic disease in human subjects? For the ATP III to recommend
a TLC Diet with higher dietary fat content for people with the metabolic syndrome
does not make sense because increased dietary fat tends to promote weight gain.
Such dietary advice is based on short-term studies with a questionable experimental
design that makes their findings largely irrelevant to the real world.
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