The main goal of the 2015 U.S. Dietary Guidelines Advisory Committee (DGAC) report appears to move away from recommending any specific optimal diet or to focus primarily on specific nutrients but rather to help guide Americans in choosing an overall healthy dietary pattern.

Overall Good Recommendations

It is hard to argue with the DGAC’s statement that a “healthy dietary pattern is higher in vegetables, fruits, whole grains, low- or nonfat dairy, seafood, legumes, and nuts; moderate in alcohol; lower in red and processed meats; and low in sugar-sweetened foods and drinks and refined grains.”1

One might quibble with the suggestion that “low-fat” dairy products ought to be included because many “low-fat” dairy products are still quite high in saturated fat and cholesterol. However, to its credit, the DGAC report continues to recommend limits on the intake of saturated fat, trans fat, and salt (sodium).

Tragic Flaw

The most obvious tragic flaw in an otherwise mostly science-based report was the Advisory Committee’s questionable decision to no longer include any limit on dietary cholesterol intake.

Surprisingly Little Said About Dietary Cholesterol

Despite all the media hype about the DGAC’s most controversial decision, the report itself had surprisingly little to say about dietary cholesterol or why the committee members decided to dump the long-standing dietary guideline for Americans to limit their intake of cholesterol to no more than 300mg/day. This is all the DGAC’s report had to say about that specific decision:

“Cholesterol. Previously, the Dietary Guidelines for Americans recommended that cholesterol intake be limited to no more than 300 mg/day. The 2015 DGAC will not bring forward this recommendation because available evidence shows no appreciable relationship between consumption of dietary cholesterol and serum cholesterol, consistent with the conclusions of the AHA/ACC report. [2, 35] Cholesterol is not a nutrient of concern for overconsumption.”

So there on page 90 are the 4 lines explaining their rational for dumping a cholesterol guideline. Perhaps the two references sited provide convincing new scientific evidence that dietary cholesterol does not actually raise total cholesterol and LDL cholesterol, or perhaps that higher levels of serum cholesterol are no longer believed to promote atherosclerosis and cardiovascular disease (CVD)?

Let’s take a closer look at those two references and see whether or not they really provide credible scientific support for dumping the long-standing U.S. Dietary Guideline to limit dietary cholesterol:

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Reference #2: Eckel RH, Jakicic JM, Ard JD, de Jesus JM, Houston Miller N, Hubbard VS, et al. 2013 AHA/ACC guideline on lifestyle management to reduce cardiovascular risk: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014;129(25 Suppl 2):S76-99. PMID: 24222015.

Eckel RH, et al, do conclude from the data they reviewed from observational studies that: “…there is insufficient evidence to conclude that lowering dietary cholesterol reduces the risk of CVD.”

Inadequacies Of Observational Studies

Of course, nutrition researchers have long known that data from observational studies often miss what is almost certainly a causal association between cardiovascular disease and dietary components such as cholesterol, salt, and saturated fat. One well-known problem is that observational data can easily miss a real causal association due to a very inaccurate assessment of people’s dietary cholesterol intake.

The Eckel review and the new DGAC’s report ignored far more reliable data from controlled clinical trials. These trials have demonstrated that for most people, increasing dietary cholesterol does in fact increase total serum cholesterol, LDL cholesterol (LDL-C), and apo B levels.

And even if current intake were assessed accurately, what people eat today may be different from what they were eating years ago. Indeed, in a homogenous population, the variation in dietary cholesterol intake varies more from day to day than does average variation between individuals, making it easy to mischaracterize an individual’s average cholesterol intake based on short-term dietary assessments.

Another confounder is that coronary artery disease (CAD) develops slowly over several decades, and it is not uncommon for people to reduce their intake of cholesterol-rich foods after they are told they are at elevated risk for CAD. This may also tend to cause data based on observational evidence to be subject to serious confounding known as reverse causation.

So, observational data is simply too unreliable for definitive conclusions about whether or not a dietary variable does or does not increase serum cholesterol levels “appreciably” or influences the risk of CVD.

Controlled Clinical Trials

Importantly, the Eckel review and the new DGAC’s report ignored far more reliable data from controlled clinical trials. These trials have demonstrated that for most people, increasing dietary cholesterol does in fact increase total serum cholesterol, LDL cholesterol (LDL-C), and apo B levels.

(Apo B, also called apolipoprotein B-100 or apolipoprotein B, is a protein that is involved in the metabolism of lipids and is the main protein constituent of lipoproteins such as very low-density lipoprotein, or VLDL, and low-density lipoprotein, or LDL, the “bad cholesterol.”)

Well-Established Impact Of Increased Dietary Cholesterol

Couple the well-established impact of increased dietary cholesterol causing higher levels of serum apoB-containing lipoprotein cholesterol levels with the strong and consistent evidence linking a higher serum cholesterol with more atherosclerosis and more deaths from coronary artery disease (CAD), and it leaves one wondering: Why did the DGAC make the decision to tell Americans there is no credible scientific basis for putting any limit on cholesterol intake?

We are also left wondering: Why did the Advisory Committee elect to review data from less reliable observational studies rather than better quality data from controlled clinical trials?

Perhaps the DGAC’s second reference was more convincing?

Reference #35. Shin JY, Xun P, Nakamura Y, He K. Egg consumption in relation to risk of cardiovascular disease and diabetes: a systematic review and meta-analysis. Am J Clin Nutr. 2013;98(1):146-59. PMID: 23676423.

Here Is What the Shin JY, et al, Review Reported:

RESULTS: A total of 22 independent cohorts from 16 studies were identified, including participants ranging in number from 1,600 to 90,735 and in follow-up time from 5.8 to 20.0 y. Comparison of the highest category (≥1 egg/d) of egg consumption with the lowest (<1 egg/wk or never) resulted in a pooled HR (95% CI) of 0.96 (0.88, 1.05) for overall CVD, 0.97 (0.86, 1.09) for ischemic heart disease, 0.93 (0.81, 1.07) for stroke, 0.98 (0.77, 1.24) for ischemic heart disease mortality, 0.92 (0.56, 1.50) for stroke mortality, and 1.42 (1.09, 1.86) for type 2 diabetes. Of the studies conducted in diabetic patients, the pooled HR (95% CI) was 1.69 (1.09, 2.62) for overall CVD.

CONCLUSIONS: This meta-analysis suggests that egg consumption is not associated with the risk of CVD and cardiac mortality in the general population. However, egg consumption may be associated with an increased incidence of type 2 diabetes among the general population and CVD co-morbidity among diabetic patients.

Dr. Shin did report that eating more eggs (and presumably cholesterol) was significantly associated with a 42% greater risk of developing type 2 diabetes.

So Dr. Shin’s review article was also based mainly on observational data with very imprecise determination of dietary cholesterol intake. It is likely the latter that made it difficult to find a direct correlation between egg consumption (and presumably cholesterol consumption) and CAD.

Type 2 Diabetes

Nevertheless, Dr. Shin did report that eating more eggs (and presumably cholesterol) was significantly associated with a 42% greater risk of developing type 2 diabetes. And in those who developed type 2 diabetes, Dr. Shin reported they had a 69% greater risk of developing serious CAD in subjects who reported consuming more than one egg a day compared to those who reported consuming less than one egg per week.

Again, the data were primarily from observational studies with all the problems such data have due to the imprecise measures of cholesterol intake over time and numerous confounding variables. One likely confounder is that subjects with a genetic predisposition to have a higher serum cholesterol level would have been more likely told to reduce their egg and cholesterol intake and/or were put on cholesterol-lowering drugs compared to those without such a genetic predisposition. Could this standard medical practice have largely eliminated a real causal association between eating more eggs (or cholesterol) and a greater risk of CVD?

Establishing Causal Relationship

Bottom Line: Observational data alone do not establish a causal relationship. For that, one needs well designed, randomized controlled clinical trials. It is very difficult to determine one’s egg or cholesterol intake over a long period of time. But in a randomized controlled clinical trial, it is pretty easy to determine one’s serum cholesterol level at any given point in time and to determine with some accuracy how many eggs and how much cholesterol someone is currently consuming on a weekly or monthly basis.

Since we know that higher serum cholesterol and especially nonHDL-C levels are associated with more CAD over the long term, and we know that increased dietary cholesterol elevates mostly nonHDL-C levels in the blood, is it not fair to ask why the DGAC chose to ignore such better quality data? Why ignore more reliable and precise data and instead draw conclusions from reviews from observational studies in which the precision of dietary cholesterol assessment is questionable and in which there are known and suspected confounding variables that could easily explain why a real causal association may not have been observed?

Do Clinical Trials Show That Egg Cholesterol Increases Serum Cholesterol?

Yes. Reliable data from well-designed controlled clinical trials have consistently shown that increasing dietary cholesterol leads to higher serum cholesterol. Couple that evidence with the proven causal association between higher total serum cholesterol (TC), nonHDL cholesterol, and LDL cholesterol levels with more CAD over time, and one has to wonder why the DGAC’s report chose to ignore such compelling evidence.

Let’s take a brief look at some of the most credible evidence from well-designed randomized controlled clinical trials that specifically examined the impact of increasing dietary cholesterol (from eggs) on total serum cholesterol levels and/or other serum lipoprotein fractions such as LDL cholesterol levels.

Serum Cholesterol Increased By 25%

Perhaps the most tightly controlled clinical trial ever conducted on the impact of dietary cholesterol on serum cholesterol levels was done by Dr. Fred Mattson and associates in 1972.2 This study demonstrated that increasing dietary cholesterol from 0 to 317mg for every 1,000 calories eaten in a formula diet that was fed to incarcerated men (harder to cheat when in jail) increased the average total serum cholesterol by about 25% over 6 weeks.

In this trial, total serum cholesterol increased for the first 3 weeks in all 3 groups to which dietary cholesterol was added but remained largely unchanged in the group consuming the cholesterol-free formula. There also appears to be no adaption to the higher dietary cholesterol diet over the next 3 weeks as the average serum cholesterol levels for the 3 groups with 106, 212, and 317mg of added cholesterol per 1,000 calories of formula remained at the elevated levels for the next 3 weeks. The results of Dr. Mattson’s study are shown in Figure 1. graph. Click on graph to enlarge.

One Extra-Large Egg

Another study3 that examined the impact of increasing dietary cholesterol on blood lipids also showed that more eggs and dietary cholesterol elevated the levels of atherogenic apoB-containing lipoproteins in the blood. In this study, Dr. Frank Sacks examined the effect of adding one extra-large egg to the diet of a group of 17 lacto-vegetarian college students. (Lacto-vegetarians are vegetarians who also eat dairy products.)

The basal diets of these students were quite low in dietary cholesterol because they were avoiding both eggs and meats and consuming only moderate amounts of dairy products. Dr. Sacks at Harvard Medical School reported that when his subjects added one extra-large egg a day to their baseline diet for 3 weeks, the result was an average increase in their LDL cholesterol of 12% and an average increase of their apoB level of 9%. Both these increases were statistically significant.

The DGAC seems to think these increases would not have an appreciable impact on people’s risk of CVD over a lifetime, but that seems to be unwarranted speculation.

Egg Industry Funding

Of course, the studies of Drs. Mattson and Sacks were not funded by the Egg Nutrition Center (ENC) or the American Egg Board (AEB), but those of other researchers were, those whose trials somehow missed the well-established hypercholesterolemic impact of increasing dietary cholesterol in human subjects.

Minimizing the Effect Of Dietary Cholesterol On Serum Cholesterol

Indeed, it appears that some researchers have become adept at designing studies that minimize the well-established hypercholesterolemic impact of increasing dietary cholesterol on serum total cholesterol, nonHDL cholesterol, LDL cholesterol, and apoB levels. Sometimes they accomplish this by selecting subjects known to be less responsive to dietary cholesterol changes than average, such as obese, insulin resistant subjects.

They also use free-living subjects whose dietary compliance is not carefully monitored. Poor compliance with dietary instruction in free-living subjects makes it much harder to show real causal associations seen in well-controlled clinical trials.

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Or they put people on calorie-restricted diets that are known to blunt the hypercholesterolemic impact of both dietary saturated fat and cholesterol during the weight-loss phase.

Or they vary dietary cholesterol from a high level to a somewhat higher level even though it is known that the impact of dietary cholesterol on serum cholesterol declines with increasing dietary cholesterol intake. This is especially true if all or most of that increased dietary cholesterol occurs at a single meal.

It is a sad commentary that with nutrition research it seems increasingly common that those who sponsor the research get what they paid for.

By contrast, if we focus on the results of studies that were not funded by the egg industry, from carefully-controlled clinical trials with good compliance, these studies generally demonstrate that increasing dietary cholesterol while holding other dietary factors and body weight constant results in significantly increased levels of cholesterol-rich, atherogenic apoB-containing lipoproteins in the blood/serum.

Bottom Line: Data from controlled clinical trials by researchers with no economic incentive to show eggs don’t raise serum cholesterol levels have fairly consistently shown that increasing dietary cholesterol from low levels up to several hundred milligrams per day significantly increases total cholesterol, LDL cholesterol, nonHDL cholesterol, and/or apoB levels.

More Plaque-Ridden Arteries

Another study4 that documented the potential dangers of consuming more dietary cholesterol from egg yolks was published in 2012 by scientists at the Stroke Prevention & Atherosclerosis Research Centre in Ontario, Canada. The researchers evaluated the diets of more than 1,200 people (average age 61) who already had CAD. The researchers asked them about their daily diets and about any other CVD risk factors they might have, such as smoking, elevated blood pressure, or diabetes. Then, using carotid ultrasound imaging, the researchers determined the amount of atherosclerosis in their carotid arteries and found a significant correlation between consuming more whole eggs and having more atherosclerotic plaque-ridden arteries.

The scientists’s data also showed that increased dietary cholesterol intake over a lifetime was even more likely to be associated with more atherosclerotic plaque build-up than being obese or even having higher serum cholesterol levels.

The egg industry must have been concerned about consumer reaction to this new study because immediately after its online publication, doctors affiliated with the industry shot out press statements criticizing the study, pointing out, for example, that the subjects with the higher egg intakes also tended to be heavy smokers. However, these press statements failed to mention that the Canadian scientists had in fact looked for a statistically significant correlation between egg yolk consumption and smoking history, and they had found none.

Public health ought not be converted into a political battle and biased by economic special interests.

Egg Whites Vs Whole Eggs Study

Another carefully controlled clinical trial5 conducted by researchers at the University of Sao Paulo in Brazil fed either 3 egg whites daily to one group of healthy young men or 3 whole eggs daily to another group of young, healthy men for 15 days. Except for the variation in egg consumption, both groups of men were consuming the same foods.

Their meals were prepared daily by the university and were consistent with the healthier dietary practices being advocated by the 2015 DAGC report. The diet was low in saturated fat but high in a variety of whole foods like fruits, green vegetables, beans, chicken, and fish.

Dr. Thais Cesar and colleagues reported that among the men in the group eating 3 egg whites daily, total intake of dietary cholesterol averaged only 174 milligrams per day. By contrast, among the men eating 3 whole eggs daily, their daily dietary cholesterol intake averaged a whopping 804 milligrams. This large daily increase in dietary cholesterol significantly increased blood cholesterol levels. On average, LDL cholesterol levels were nearly 40% higher in subjects consuming 3 whole eggs compared to those consuming only 3 egg whites.

Dr. Cesar concluded: “A high-cholesterol diet clearly enhances LDL cholesterol levels.” At the end of the study, the egg white eaters had average LDL levels of only 86 mg/dl, while the average LDL levels for the group consuming the whole eggs was 120 mg/dl. Is this the type of change in LDL cholesterol levels the DGAC experts decided was not “appreciable”?

What Happens In the Hours Right After We Eat

As if this marked increase in total cholesterol and LDL cholesterol levels were not alarming enough, Dr. Cesar and colleagues also reported more troubling news about the impact that all that extra dietary cholesterol was having on the postprandial blood lipids of their subjects. (“Postprandial” is the period right after eating meals, or what is often described as the nonfasting state.)

In addition to raising fasting LDL cholesterol levels, the subjects consuming the 3-whole-eggs-a-day diet had so much extra cholesterol in their chylomicrons for several hours right after eating (the postprandial state) that their liver’s ability to efficiently remove these artery-clogging chylomicron remnants from their bloodstream was significantly hindered.

Chylomicrons are believed to be another class of atherogenic, apoB-containing lipoprotein particles. (In a recent Pritikin Perspective article titled “Good, Bad, and Badder Cholesterol,” chylomicrons were described as the “badder cholesterol.”)

In a nutshell, chylomicrons are largely responsible for transporting the fat, cholesterol, and other fat-soluble dietary components from the gut to the liver and other cells throughout the body. Once chylomicrons have “unloaded” most of their fat (or triglyceride) content, they become cholesterol-rich chylomicron remnants, which are cleared from the blood by the liver.

Cholesterol-Stuffed Chylomicrons

However, if these chylomicron remnants are stuffed with more dietary cholesterol, they tend to “hang around” in the bloodstream even longer. These chylomicron remnants, like other apoB-containing lipoproteins in the blood, can enter the artery walls and deliver dietary cholesterol to the artery walls just as LDL and remnant VLDL particles do. Therefore, it is almost certain that cholesterol-enriched chylomicron remnants damage the artery wall and promote the growth of atherosclerotic plaques over time.

It should be noted that these adverse changes to postprandial blood lipids will occur even in people whose fasting blood cholesterol levels are little affected by the increase in dietary cholesterol. This suggests that even in those whose fasting blood lipids seem unaffected by increased dietary cholesterol, they may still end up with more atherosclerosis and an increased risk of CAD in response to consuming more dietary cholesterol.

Dr. Cesar’s study found that eating 3 egg yolks daily “increased the residence time of chylomicron remnants, which may have undesirable effects related to the development of coronary artery disease.”

Postprandial Lipemia

There is growing evidence that atherosclerosis is caused in part by postprandial lipemia [a rise in triglyceride-rich lipoproteins after eating], and this has bolstered concerns about the potentially atherogenic potential of chylomicron-rich remnants.

In 2013, Dr. Anette Varbo examined the association between developing CAD and variations in blood lipids in 60,608 people in Copenhagen.6 Of those, 10,668 had developed CAD. Dr. Varbo and colleagues looked for genetic markers that impact various blood lipid levels by genotyping these 60,608 Danes. She found that people who had a genetic predisposition to clear cholesterol-rich remnant lipoproteins more slowly after meals were significantly more likely to develop more inflammation and suffer from CAD (also called ischemic heart disease – IHD).

Dr. Varbo’s Conclusions— “Elevated nonfasting remnant cholesterol is causally associated with low-grade inflammation and with IHD, whereas elevated LDL cholesterol is associated causally with IHD without inflammation.”

Dr. Varbo and colleagues subsequently published an article7 reviewing the evidence implicating various lipoprotein particles with risk factors for CAD. They reported: “Genetic studies of variants associated with elevated remnant cholesterol levels show that an increment of 1 mmol/L (39 mg/dL) in levels of nonfasting remnant cholesterol associates with a 2.8-fold increased risk of IHD, independently of high-density lipoprotein cholesterol levels. Results from genetic studies also show that elevated levels of remnant cholesterol are causally associated with both low-grade inﬂammation and IHD. However, elevated levels of LDL cholesterol are associated with IHD, but not with low-grade inﬂammation. Such results indicate that elevated LDL cholesterol levels cause atherosclerosis without a major inﬂammatory component, whereas an inﬂammatory component of atherosclerosis is driven by elevated remnant cholesterol levels.”

In the nonfasting, postprandial state, the remnant lipoprotein particles transporting cholesterol in the blood include both the remnants of VLDL particles produced in the liver and the remnants of chylomicron particles produced by the intestinal mucosa. Diets higher in fat and cholesterol increase the amount of cholesterol in chylomicron particles and so ultimately increase the cholesterol content of chylomicron remnants. Chylomicrons and their remnants, along with VLDL remnants, deliver cholesterol to the artery wall, and, unlike LDL cholesterol particles, do not need to be oxidized to get picked up by macrophages. Cholesterol-filled macrophages or “foam cells” are largely believed to play a central role in promoting atherosclerotic disease and increasing the release of inflammatory cytokines within the artery wall, which increases the risk of plaque rupture and a heart attack.

The Big Question…

So if the scientific evidence clearly demonstrates that dietary cholesterol from eggs (or anything else) will increase both fasting and postprandial serum cholesterol levels, and if higher serum cholesterol levels in apoB-containing lipoproteins are still a well-accepted major risk factor for developing atherosclerosis and increasing the risk of heart disease, then what is it that could be motivating the DGAC Report to recommend dropping any limit on dietary cholesterol from the proposed 2015 US Dietary Guidelines?

Could political and/or economic considerations be motivating forces for this Advisory Committee’s recommendation to drop cholesterol from the 2015 U.S. Dietary Guidelines?

46% Greater Risk Of CAD Events

Also ignored by the DGAC were studies like the one by Drs. Richard Shekelle and Jeremiah Stamler.8 These researchers followed a cohort of 1,824 middle-aged men for 25 years. They observed that their intake of dietary cholesterol was significantly associated with an increased risk of death from CAD, from other cardiovascular diseases (CVD) combined, from all CVD combined, and from all causes combined. They found that relative hazard of death from all CVD combined associated with a higher cholesterol intake was 46% comparing the lowest and top quintiles of dietary cholesterol consumption (an average difference of 184 mg cholesterol per 1,000-calorie intake). The 46% greater CAD event risk for those in the top quintile was after adjustment for age, intake of other dietary lipids, and other coronary risk factors (even including serum cholesterol level).

The scientists also found that when they stratified into 3 groups according to initial serum cholesterol level (those with less than 220 mg/dl, those between 220-259 mg/dl, and those 260 mg/dl or above), the corresponding relative hazard ratios for those with the top versus bottom quintile of dietary cholesterol intake were 1·58, 1·50, and 1·41, respectively.

So the results of the Shekelle and Stamler study showed that increased dietary cholesterol intake was significantly associated with a greater risk of CAD events, and this increased risk was partially independent of the increase in serum fasting cholesterol levels.

“…dietary cholesterol is atherogenic”

Drs. Shekelle and Stamler concluded: “These results are further evidence for the concepts that dietary cholesterol is atherogenic in man, and that the effect is partly independent of serum cholesterol.”

The results of this study indicate that increased dietary cholesterol appears to be promoting atherosclerosis and increasing the risk of having a heart attack that is partially independent of the effects of that increased dietary cholesterol on fasting serum lipoprotein levels. If dietary cholesterol does indeed promote atherosclerosis in ways that are independent of fasting total cholesterol and LDL cholesterol levels, it seems likely that increased dietary cholesterol may be doing so at least in part by enriching chylomicron particles with more cholesterol.

Statins

Couple Drs. Shekelle and Stamler’s data with the research of Dr. Varbo and colleagues pointing to the likely atherogenicity of postprandial lipemia, and we may have an explanation as to why statin drugs may slow the progression of atherosclerosis but seem less able to reverse CAD compared to diets very low in fat and cholesterol and high in fiber, even when statins lower fasting LDL cholesterol levels to what appear to be physiologically optimal levels of less than 70 to 75mg/dl.9,10

Since statins do not impact the absorption of dietary cholesterol and fat, they will have little impact on the production of cholesterol-enriched chylomicrons and their remnants. This may be why so many people taking statins still end up with their CAD progressing, and why the #1 cause of death in people taking statins is a heart attack.

Two Ways Dietary Cholesterol Promotes Atherosclerosis

There appear to be two different ways in which dietary cholesterol can promote atherosclerosis. One well-documented way is to increase serum cholesterol levels and mostly apoB-containing lipoproteins (nonHDL cholesterol in fasting blood) known to deliver cholesterol to the artery wall.

However, there is growing evidence that dietary cholesterol leads to more cholesterol being absorbed from the gut. This increased dietary cholesterol then enriches the cholesterol content of chylomicron particles produced by the intestinal mucosa cells and dumped into the lymphatic system. As we have seen from the data from Drs. Varbo, Shekelle, and Cesar above, there is reason to believe this increases chylomicron cholesterol and alters postprandial blood lipids in ways that promote atherosclerosis that are partially independent of fasting blood lipid levels.

Reducing Cholesterol Absorption

The cholesterol-lowering drug Zetia (ezetimbe) is known to work by reducing the absorption of cholesterol from the gut. Plant sterols and tocotrienols also appear to act in a similar way. Reducing cholesterol absorption reduces both postprandial chylomicron cholesterol content and also ends up reducing other apoB-100-containing lipoproteins in fasting blood. Collectively, these fasting apoB-containing lipoproteins are nonHDL cholesterol.

In effect, one can reduce cholesterol absorption either with drugs like Zetia and resins like cholestyramine or by increasing the dietary intake of plant sterols and tocotrienols and dietary fiber. Alternatively, one can reduce cholesterol absorption from the gut simply by consuming fewer cholesterol-containing foods, with egg yolks being the single largest source of dietary cholesterol for most Americans.

Zetia works to lower plasma levels of total serum cholesterol and LDL cholesterol by inhibiting the activity of the Niemann-Pick C1-like 1 (NPC1L1) protein in the intestinal mucosa cells. This protein enhances the absorption of cholesterol and the excretion of plant sterols. Because this inhibition of NPC1L1 reduces the absorption of dietary cholesterol, it reduces the cholesterol content of chylomicrons and their cholesterol-rich remnants.

Mutations and Dietary Cholesterol

Human mutations are known to occur that also inactivate a gene encoding for NPC1L1 and so can mimic the action of an inhibitory drug like Zetia (or plant sterols). People who have these genetic mutations can be studied to estimate what would happen if the absorption of dietary cholesterol were reduced or enhanced over a lifetime.

In 2014, Dr. Nathan Stitzel and colleagues sequenced the exons of NPC1L1 in 7,364 patients with coronary heart disease and in 14,728 controls without such disease who were of European, African, or South Asian ancestry.11 (Exons are a segment of a DNA or RNA molecule.) The scientists identified carriers of inactivating mutations (nonsense, splice-site, or frameshift mutations). In addition, they genotyped a specific inactivating mutation (p.Arg406X) in 22,590 patients with CAD and in 68,412 control subjects without evident CAD. They then tested the association between the presence of an inactivating mutation and both plasma lipid levels and the risk of coronary heart disease. They then sequenced their genes and identified 15 distinct NPC1L1 inactivating mutations. They observed 1 of every 650 persons was a heterozygous carrier for 1 of these 15 genetic mutations.

Lower LDL Cholesterol

Not surprisingly, the heterozygous carriers of these NPC1L1 inactivating mutations had a mean LDL cholesterol level that was 12 mg/dl lower on average than that in people who absorbed dietary cholesterol normally because they made normal amounts of NCP1L1 (p<0.05).

The subjects with this genetic mutation were found to have a relative reduction of 53% in the risk of developing CAD. In short, naturally occurring mutations that disrupt NPC1L1 function were found to be associated with reduced plasma LDL cholesterol levels and a reduced risk of coronary heart disease.

What does this data on a genetic mutation that impairs the absorption of cholesterol from the gut tell us about the likely impact of absorbing more cholesterol?

More Cholesterol Eaten, More Cholesterol Absorbed

For one thing, it suggests that the vast majority of Americans who lack this rare genetic mutation will be absorbing more cholesterol from their gut when they consume more dietary cholesterol.

The DGAC was not concerned about this increase in the amount of dietary cholesterol absorbed, claiming that it does not have an “appreciable” effect on LDL cholesterol levels. However, a more troubling question for the DGAC argument is, how did a mere 12mg/dl decrease in LDL cholesterol over a lifetime translate into a 53% decreased risk of developing CAD in those who have this NCP1L1 mutation?

For the average middle-aged American, that 12mg/dl drop in LDL cholesterol would be only about a 6% reduction in LDL cholesterol. Yet long-term clinical trials of lowering LDL cholesterol with high-dose statin drugs show that reductions in LDL cholesterol of close to 40 to 60% on average translate into reduced risk of CAD deaths of perhaps 30 to 40%.

Cholesterol Absorption and Postprandial Blood Lipids

What could be the plausible mechanism by which a naturally occurring mutation in NCP1L1 reduces dietary cholesterol absorption from the gut? Could it be that reducing cholesterol absorption from the gut reduces postprandial changes in blood lipids and perhaps other CVD risk factors that are promoting atherosclerosis and CAD in ways that are largely independent of fasting LDL cholesterol levels?

Because statin drugs work in the liver to block cholesterol synthesis, they have no appreciable impact on NCP1L1 or cholesterol absorption from the gut. If postprandial lipemia plays a major role in the progression of atherosclerosis, then this may explain why statins often slow the progression of atherosclerosis but rarely reverse it. Indeed, one reason why statins may be less effective for reducing the risk of having a heart attack may be because too many patients actually start consuming more cholesterol-rich foods after their doctors tell them their fasting LDL cholesterol looks “great.”

Atheroslosclerosis – Largely a Postprandial Phenomenon?

Clearly, there is a need for more research on the impact of dietary cholesterol on both fasting and postprandial blood lipids. However, from this reviewer’s perspective, it appears Dr. Zilversmit back in 1979 was onto something when he postulated that atherosclerosis may well be largely a postprandial phenomenon.12

Will the 2015 U.S. Dietary Guidelines On Cholesterol Be a Win For Propaganda and a Loss For Science?

The dropping of any limit of dietary cholesterol intake for Americans in the 2015 U.S. Dietary Guidelines (if adopted) would be a major victory for the American Egg Board in the long-standing battle between the American Egg Board (AEB) and nutrition researchers. It will be a loss for those who favor science over dogma and profits.

Here is a link that shows some of the AEB’s long-running PR efforts to distort and misrepresent the scientific data that clearly show eating more eggs increases serum cholesterol levels.

The new DGAC guidelines continue to recommend limits on saturated fat and trans fat but no longer for dietary cholesterol. So what is the rational for limiting saturated fatty acids (SFA) and trans fatty acids (TFA)?

The main reason to limit these “bad” fats is the research proving that increased dietary intake of SFA and TFA increase the levels of total cholesterol, LDL cholesterol, nonHDL cholesterol, and apoB in the blood coupled with data proving that higher levels of these blood lipids promotes more atherosclerosis and leads to more coronary artery disease (CAD).

So the new guidelines absolutely are not saying that Americans no longer need be concerned about elevated levels of atherogenic apoB-containing lipoproteins in the blood, right? The new USDG say to limit SFA and TFA largely because they raise nonHDL cholesterol levels. Higher nonHDL cholesterol levels are known to promote atherosclerosis and lead to more heart attacks. Can’t argue with that logic, right?

In short, the USDG agree that the best scientific evidence continues to show that higher total cholesterol, LDL cholesterol, nonHDL cholesterol, and apoB levels promote more atherosclerosis and lead to more heart attacks in the long term. But the DGAC says there is no longer any need to limit dietary cholesterol even though the best quality scientific evidence continues to demonstrate that increasing dietary cholesterol also raises those same atherogenic apoB-containing lipoproteins, as do SFA and TFA. Does that make sense?

The Effects Of Increasing LDL Cholesterol By 10%

A recent study showed that people who have a genetic variant that increases their LDL cholesterol level about 10% over their entire lives compared to those without that genetic variant have a 50% increased risk of having a heart attack over their lifetime compared to those whose serum cholesterol levels are only 10% lower, thanks to their genes. Once again, solid scientific evidence shows that higher total cholesterol, LDL cholesterol, nonHDL cholesterol, and apoB levels (whether due to genes and/or diet) promote atherosclerosis and lead to more heart attacks. Even lowering them with statins and other drugs for a few years significantly reduces the risk of dying from a heart attack, despite the fact that these drugs themselves are not completely innocuous.

So while higher nonHDL cholesterol levels are still “bad,” the new DGAC report tells us that more dietary cholesterol is no longer something Americans should try to limit. Does this mean that the scientific evidence now demonstrates that all the prior U.S. Dietary Guidelines to limit dietary cholesterol intake must have been wrong about dietary cholesterol increasing total cholesterol, LDL cholesterol, nonHDL cholesterol, and apoB levels? No.

Does it at least mean that a high intake of dietary cholesterol won’t increase your risk of CAD provided your serum cholesterol levels don’t increase much or remain low, the result of taking statins or other drugs? Perhaps not if dietary cholesterol does in fact alter postprandial lipoprotein levels in ways that allow atherosclerotic plaques to progress and/or become more inflamed. A growing body of research, ignored by the DGAC, strongly suggests that this is the case. Science is finding that dietary cholesterol appears to promote atherosclerosis in ways that are at least partially independent of fasting blood lipoprotein levels. Should this evidence have been ignored by the DGAC experts? No.

How the Proposed 2015 U.S. Dietary Guidelines Might Lead To More Atherosclerosis

Perhaps the DGAC dropped a cholesterol limit to better focus on the overall dietary choices than on single substances. After all, most foods high in cholesterol are also high in saturated fat, so limiting saturated fat alone would encourage Americans to cut back on fatty meats, cheese, and butter. Why not just simplify the message, the committee members may have decided, and tell Americans to cut back on saturated fat? Getting people to limit cholesterol intake would happen automatically if they can get Americans to reduce saturated fat, so they may have felt that also telling them to limit dietary cholesterol would have been largely redundant.

But many of us remember when, in 1977, USDG experts decided it was too complicated to tell Americans to just avoid saturated fat, so they told them to reduce all fat. The result was that the commercial food industry started making foods lower in total fat but not necessarily with any improvement in the ratio of omega-6 polyunsaturated fats to saturated fats. And when the food industry cut the fat content of many food products, they often increased the sugar, salt, and refined grains. In retrospect, those 1977 goals should have focused more on saturated fats and dietary cholesterol and less on the percentage of fat calories. Can we now predict what might go wrong with removing any focus on dietary cholesterol in the 2015 US Dietary Guidelines?

What Might Go Wrong With Removing Any Focus On Dietary Cholesterol?

Is it possible that by taking away any limit on dietary cholesterol and focusing instead on saturated fat, the American egg industry will start promoting the consumption of eggs by pointing out that they are lower in saturated fat than, say, salmon? A 7-ounce raw piece of salmon contains 6g of saturated fat but only 109mg of cholesterol. By comparison, 3 whole eggs, raw, contain 4.8g of saturated fat but 561mg of cholesterol.

So according to the proposed 2015 USDG, the 3 eggs become the “better” choice than salmon because they have less saturated fat even though the 3 eggs have more than 5 times the cholesterol content as the salmon, and far fewer omega-3 fatty acids.

Also, a pound of raw shrimp contains 731mg of cholesterol but less than 1/2g of saturated fat. If dietary cholesterol is of no concern, then there is really no reason not to consume a lot shrimp. However, that extra cholesterol from a pound of shrimp would be expected to increase fasting serum cholesterol levels by 10 to 15%, and would likely alter postpransdial blood lipids in ways that also promote atherosclerosis.

And that 10 to 15% increase in LDL cholesterol would likely be even greater if the pound of shrimp at the “all you can eat” buffet are consumed in place of beans or tofu.

Eat More Squid, Shrimp, and Eggs? And Less Tofu, Beans, and Salmon?

Indeed, one cup of tofu has 4 times more saturated fat than does one pound of raw shrimp or squid. Eating a lot of eggs and shrimp instead of salmon and tofu would not lower the levels of atherogenic lipoproteins in the blood and reduce the risk of CAD but would actually increase the risk. However, if one looks only at saturated fat content and ignores dietary cholesterol, what message do the new DGAC experts think might be a plausible result?

If Americans stop focusing on dietary cholesterol, they may well end up eating more squid, shrimp, and eggs but less tofu, beans, and salmon. That would be a logical interpretation of the new 2015 US Dietary Guidelines if one accepts the DGAC’s seemingly-naïve idea that dropping any limit on dietary cholesterol won’t have any “appreciably” bad effects on the health of Americans.

We shall see?

As we’ve witnessed in the past, researchers often underestimate the ability of the commercial food industry to exploit advice that on the surface seems simpler for the public but creates an opening to promote foods that are of questionable value for promoting better health. I’d hate to see history repeat itself based on what from my perspective is a naïve position on the likely consequences of their decision to drop any limit on dietary cholesterol. What do you think?

Bottom Line On the Proposed 2015 U.S. Dietary Guidelines:

While there is much to like about the DGAC’s report, their decision to drop any limit on dietary cholesterol does not appear to be based on the most credible scientific evidence. Why did the DGAC apparently choose to ignore all the data from well-designed controlled clinical trials that have clearly shown that greater consumption of dietary cholesterol significantly increases total serum cholesterol, LDL cholesterol, nonHDL cholesterol, and apoB?

In the last several years, evidence also continues to mount that suggests that dietary cholesterol also increases postprandial chylomicron cholesterol levels, and there is growing credible evidence that more chylomicron cholesterol promotes atherosclerosis and CAD independently of elevations of fasting apoB-containing lipoprotein cholesterol levels.

Since there is a well-established causal association between increased levels of these atherogenic apoB-containing lipoproteins in the blood and an increased risk of CAD, does it not appear that the DGAC’s conclusions about dietary cholesterol are not based on the most credible scientific evidence?

From this reviewer’s perspective, the DGAC’s decision to drop any limits on dietary cholesterol intake will result in Americans consuming more dietary cholesterol. That increased dietary cholesterol will promote atherosclerosis and will tend to increase the risk of CAD, leaving this reviewer to suggest that in the long term the committee members who pushed for this change may well be the ones ending up having egg on their faces.

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