Dietary Guidelines, Cholesterol & You!

[JeffN]

Dietary Guidelines, Cholesterol & You!
Jeff Novick, MS, RDN

As we have all heard, it seems the upcoming Dietary Guidelines will withdraw their recommendation to limit dietary cholesterol, which first appeared as a recommendation as part of the American Heart Association guidelines in 1961.

http://www.washingtonpost.com/blogs/won ... l/?hpid=z1

Have we been wrong all these years?

As with my recent discussions on saturated fat, part of this discussion is whether cholesterol is harmful in-and-of-itself as a component of the diet or is cholesterol just a marker for an unhealthy dietary pattern high in animal products, which would also be high in animal protein, high in saturated fat, low in fiber, etc. Is cholesterol a harmful component that should be reduced or is it a marker of an unhealthy dietary pattern that should be switched to a healthy plant-based dietary pattern. Is it a harmful component, a marker or both.

This seems to be the issues.

To clear this up, let's look at two studies in particular that address whether dietary cholesterol matters, one very old and one very new.

The first one, Effect of dietary cholesterol on serum cholesterol in man, was done in 1972 and published in The American Journal of Clinical Nutrition. (The American Journal of Clinical Nutrition JUN 25: 1972, pp. 589-594.) You can find a full text copy of the study online here for free...

http://m.ajcn.nutrition.org/content/25/ ... pdf#page=1

This was a very well done study that used controlled formula diets in a very controlled setting over 11 weeks. You can read the details of the study in the "Materials and methods" section. Basically, the subjects, who were inmates of the Philadelphia prison system were fed their usual prison diet for 7 days, then over the next 7 days, had their diets gradually switched over to an experimental formula diet that contained no cholesterol. Then, for 21 days, they were all kept exclusively on the cholesterol free formula diet. At this point, the 7 inmates with the highest blood cholesterol levels and the 7 with the lowest blood cholesterol levels were removed from the study. The remaining 56 subjects were divided into 4 groups. Over the next 6 weeks, each group was fed the exact same diet with the only difference being the amount of cholesterol in it. One groups formula had no cholesterol, the second had 106 mg, the third 212 mg and the fourth 317 mg, each per 1000 calories. The results showed that for each 100 mg/1000 calories increase in dietary cholesterol, serum cholesterol increased 12 mg per 100 ml with the serum cholesterol of group 4 increasing 25%.

The conclusion stated, "relatively greater importance should be given to dietary cholesterol as a determinant of serum cholesterol in the United States population."

That was in 1972 and their results were in line with the work of Keys and Hegsted, who I have discussed before.

The second one, Inactivating Mutations in NPC1L1 and Protection from Coronary Heart Disease, was just recently published in November of 2014 in the New England Journal of Medicine. (N Engl J Med 2014; 371:2072-2082November 27, 2014DOI: 10.1056/NEJMoa1405386). You can see a copy of the abstract of study online here…

http://www.nejm.org/doi/pdf/10.1056/NEJMoa1405386

and you can read about it here

http://news.wustl.edu/news/Pages/27658.aspx

Basically, there are people who as a result of a genetic variant have LDL levels that average 12 mg/dl lower than the general population, which is about a 10% percent reduction from average LDL levels. It turns out that they also have about half the risk of coronary heart disease as does the general population.

So, let’s put all of this together.

As we saw in the first study, dietary cholesterol, even as a component of the diet, raised serum cholesterol about 25%. Interestingly, this is about the same percentage we see cholesterol and LDL lowered in studies on this way of eating.

These two studies show an average drop of 23% in total cholesterol and LDL “bad” cholesterol in just 21 days.

Short-Term Reductions in Serum Lipids through Diet and Exercise
New England Journal of Medicine, 323: 1142, 1990;
http://www.nejm.org/doi/full/10.1056/NE ... 0183231613

Plasma Lipid Lowering in Short-term Life-style Change
Arch Intern Med. 1991;151(7):1275-1276. doi:10.1001/archinte.1991.00400070053004.
http://archinte.jamanetwork.com/article ... eid=615244

(NOTE: The 23% if an average and we have seen drops of 50% or more in those who come to the programs with the highest cholesterols and LDLs).

So, yes, cholesterol, like saturated fat, is both a harmful component of the diet and a marker for an unhealthy animal-based dietary pattern. Recommendations to reduce &/or eliminate cholesterol should remain and the best way to do that is to switch from a unhealthy animal-based dietary pattern based to a healthy lower fat, lower calorie-dense dietary dietary pattern based predominately on minimally processed plant foods.

In Health
Jeff


Special thanks to my friend and colleague Jay Kenny, PhD, RD, who reminded me of the 1972 Mattson study.

[JeffN]

Q: The first study you mention is over 40 years old. Isn't there anything more up-to-date you could have used?

A: If you follow my work, and have spent some time reading the Hot Topics and FAQ in this forum, then you know of the body of evidence supporting my perspective. I used the above as it is a very unique study in many way and to show just how far back we have known this information. There are few studies that are as tightly controlled as this one was.

Remember, time doesn't invalidate good science, nor does it make it. Higher quality research does. There are many classic studies that are still valid today that were down decades ago.

On the other hand, there are many studies being done today that are very poorly done but unfortunately get attention in the news as being valid because they are new.

In Health
Jeff

[JeffN]

This issue continues to circulate and in a discussion this morning, my colleague Jay Kenney, PhD, RD reminded me of another study confirming that dietary cholesterol remains relevant.

In his own words...

"Then there is Dr. Cesar's study. Another carefully controlled clinical trial conducted by researchers at the University of Sao Paulo in Brazil. They fed either three egg whites daily to one group of healthy young men or three whole eggs daily to another group of young, healthy men for 15 days. Except for the variation in egg yolk consumption both groups of men were consuming the same foods. Their meals, were prepared daily by the university, and were consistent 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. Cesar and colleagues reported that among the men in the group eating three egg whites daily, total intake of dietary cholesterol averaged only 174 milligrams per day. By contrast, among the men eating three whole eggs daily their daily dietary cholesterol intake averaged a whopping 804 milligrams/day. This large daily increase in dietary cholesterol significantly increased blood cholesterol levels. On average LDL-C were nearly 40% higher (120 vs 86mg/dl) in subjects consuming 3 whole eggs daily compared to those consuming only 3 egg whites daily. Dr. Cesar concluded that “A high-cholesterol diet clearly enhances LDL-C levels." Here's the reference:

Cesar TB, Oliveira, Mesquita CH, Maranhao RC. High cholesterol intake modifies chylomicron metabolism in normolipidemic young men. J Nutr 2006:136;971-6 or http://jn.nutrition.org/content/136/4/971.full.pdf+html

The much higher cholesterol levels in those consuming whole eggs vs egg whites certainly appears to point to the saturated fat and cholesterol content as the main reason eggs raise serum cholesterol levels as the yolks have all the fat and cholesterol while the whites have the majority of the protein. So it is hard for me to explain these results if it were animal protein rather than cholesterol being the main reason eggs raise serum cholesterol levels."

If you look at Table 1, there is no significant difference between the two diets in regard to total fat, saturated fat, carbohydrates, protein, fiber or total energy. The only significant difference is in the intake of dietary cholesterol, which went from 174 mg to 804 mg.

Dietary cholesterol still matters.

In Health
Jeff

[JeffN]

Associations of Dietary Cholesterol or Egg Consumption With Incident Cardiovascular Disease and Mortality
JAMA. 2019;321(11):1081-1095. doi:10.1001/jama.2019.1572

https://jamanetwork.com/journals/jama/f ... le/2728487

Key Points
Question Is consuming dietary cholesterol or eggs associated with incident cardiovascular disease (CVD) and all-cause mortality?

Findings Among 29 615 adults pooled from 6 prospective cohort studies in the United States with a median follow-up of 17.5 years, each additional 300 mg of dietary cholesterol consumed per day was significantly associated with higher risk of incident CVD (adjusted hazard ratio [HR], 1.17; adjusted absolute risk difference [ARD], 3.24%) and all-cause mortality (adjusted HR, 1.18; adjusted ARD, 4.43%), and each additional half an egg consumed per day was significantly associated with higher risk of incident CVD (adjusted HR, 1.06; adjusted ARD, 1.11%) and all-cause mortality (adjusted HR, 1.08; adjusted ARD, 1.93%).

Meaning Among US adults, higher consumption of dietary cholesterol or eggs was significantly associated with higher risk of incident CVD and all-cause mortality in a dose-response manner.

Abstract
Importance Cholesterol is a common nutrient in the human diet and eggs are a major source of dietary cholesterol. Whether dietary cholesterol or egg consumption is associated with cardiovascular disease (CVD) and mortality remains controversial.

Objective To determine the associations of dietary cholesterol or egg consumption with incident CVD and all-cause mortality.

Design, Setting, and Participants Individual participant data were pooled from 6 prospective US cohorts using data collected between March 25, 1985, and August 31, 2016. Self-reported diet data were harmonized using a standardized protocol.

Exposures Dietary cholesterol (mg/day) or egg consumption (number/day).

Main Outcomes and Measures Hazard ratio (HR) and absolute risk difference (ARD) over the entire follow-up for incident CVD (composite of fatal and nonfatal coronary heart disease, stroke, heart failure, and other CVD deaths) and all-cause mortality, adjusting for demographic, socioeconomic, and behavioral factors.

Results This analysis included 29 615 participants (mean [SD] age, 51.6 [13.5] years at baseline) of whom 13 299 (44.9%) were men and 9204 (31.1%) were black. During a median follow-up of 17.5 years (interquartile range, 13.0-21.7; maximum, 31.3), there were 5400 incident CVD events and 6132 all-cause deaths. The associations of dietary cholesterol or egg consumption with incident CVD and all-cause mortality were monotonic (all P values for nonlinear terms, .19-.83). Each additional 300 mg of dietary cholesterol consumed per day was significantly associated with higher risk of incident CVD (adjusted HR, 1.17 [95% CI, 1.09-1.26]; adjusted ARD, 3.24% [95% CI, 1.39%-5.08%]) and all-cause mortality (adjusted HR, 1.18 [95% CI, 1.10-1.26]; adjusted ARD, 4.43% [95% CI, 2.51%-6.36%]). Each additional half an egg consumed per day was significantly associated with higher risk of incident CVD (adjusted HR, 1.06 [95% CI, 1.03-1.10]; adjusted ARD, 1.11% [95% CI, 0.32%-1.89%]) and all-cause mortality (adjusted HR, 1.08 [95% CI, 1.04-1.11]; adjusted ARD, 1.93% [95% CI, 1.10%-2.76%]). The associations between egg consumption and incident CVD (adjusted HR, 0.99 [95% CI, 0.93-1.05]; adjusted ARD, −0.47% [95% CI, −1.83% to 0.88%]) and all-cause mortality (adjusted HR, 1.03 [95% CI, 0.97-1.09]; adjusted ARD, 0.71% [95% CI, −0.85% to 2.28%]) were no longer significant after adjusting for dietary cholesterol consumption.

Conclusions and Relevance Among US adults, higher consumption of dietary cholesterol or eggs was significantly associated with higher risk of incident CVD and all-cause mortality in a dose-response manner. These results should be considered in the development of dietary guidelines and updates.

[JeffN]

Meta-regression analysis of the effects of dietary cholesterol intake on LDL and HDL cholesterol.
Vincent MJ, et al. Am J Clin Nutr. 2019.

https://www.ncbi.nlm.nih.gov/pubmed/30596814/

Abstract
Background: Elevated low-density lipoprotein (LDL) cholesterol is a major risk factor for cardiovascular disease. Dietary guidance recommends reducing saturated fatty acid, trans fatty acid, and cholesterol intakes to reduce circulating LDL cholesterol. Cholesterol intake may also affect high-density lipoprotein (HDL)-cholesterol concentrations, but its impact has not been fully quantified.

Objectives: The aims of this study were to investigate the dose-response relation between changes in dietary cholesterol intake and changes in lipoprotein-cholesterol markers for cardiovascular disease risk and to provide a reference for clinicians on how changes in dietary cholesterol intake affect circulating cholesterol concentrations, after accounting for intakes of fatty acids.

Methods: We used a Bayesian approach to meta-regression analysis, which uses Markov chain Monte Carlo techniques, to assess the relation between the change in dietary cholesterol (adjusted for dietary fatty acids) and changes in LDL and HDL cholesterol based on the use of data from randomized dietary intervention trials.

Results: Fifty-five studies (2652 subjects) were included in the analysis. The nonlinear Michaelis-Menten (MM) and Hill models best described the data across the full spectrum of dietary cholesterol changes studied (0-1500 mg/d). Mean predicted changes in LDL cholesterol for an increase of 100 mg dietary cholesterol/d were 1.90, 4.46, and 4.58 mg/dL for the linear, nonlinear MM, and Hill models, respectively.

Conclusions: The change in dietary cholesterol was positively associated with the change in LDL-cholesterol concentration. The linear and MM models indicate that the change in dietary cholesterol is modestly inversely related to the change in circulating HDL-cholesterol concentrations in men but is positively related in women. The clinical implications of HDL-cholesterol changes associated with dietary cholesterol remain uncertain.