Eggs and Heart Disease

[Eggs and Heart Disease mp3]

What’s the deal with eggs?

It seems that some foods like eggs and margarine are on a perpetual pendulum with the media and, by extension, public opinion. Some days the egg is vilified as a harbinger of heart disease, while other days everything is coming up roses for the little guy. Case in point: Here is a recent article from a local Charleston news station stating

A new study suggests just three egg yolks per week can accelerate heart disease almost as much as smoking.

This article is based off a recent study from Canada published in the journal Atherosclerosis.1 Contrast this with the Harvard School of Public Health’s official position on eggs:

Recent research has shown that moderate egg consumption—up to one a day—does not increase heart disease risk in healthy individuals and can be part of a healthy diet.

So which is it? Three eggs a week is as bad as smoking or one egg per day is perfectly healthy? It cannot be both. So what should we believe?

As of now the link between serum cholesterol2 and heart disease is about as near to a capital-F Fact as you get in nutrition science.  So when you hear that eggs are really high in cholesterol compared with most other foods commonly consumed in the United States, one logical conclusion you could draw from this (if you eat a fair amount of eggs) is the following: If I stop eating eggs I will reduce my risk of heart disease. However, the waters of truth become muddier when you try to examine the actual science behind this bit of conventional wisdom.

Lucky for us my colleague Carrie Dennett did most of the leg work and found the best research available on the subject. What follows is adapted from her research.

Epidemiological Studies

  • An analysis of data from the Framingham Heart Study in 1982 was one of the first epidemiological studies to suggest that there was no significant association between egg consumption and coronary heart disease (CHD), myocardial infarction, or all-cause mortality.3
  • The “Harvard Egg Study” looked at the association between egg consumption and the risk of CHD in two prospective cohorts, the Health Professionals Follow-up Study and the Nurses’ Health Study. After adjustment for age, smoking and other CHD risk factors, there was no significant association between recent or long-term consumption of up to 1 egg per day and risk of CHD or stroke. However, subjects with existing hypercholesterolemia, cardiovascular disease, diabetes, or cancer were excluded from analysis.4
  • Djousse and Gaziano examined the association between egg consumption and CVD and total mortality among 21,327 participants from the Physicians’ Health Study I. The authors concluded that consumption of up to 6 eggs per week does not influence the risk of myocardial infarction, stroke, or total mortality in healthy U.S. male physicians.5 Individuals who ate beyond six eggs per week, however, did see an increase in CVD risk.
  • Data from the First National Health and Nutrition Examination Survey (NHANES-1) and the NHANES-1 Epidemiological Follow-up Study (NHEFS) was examined and a multivariate analysis found no significant difference in the relative risk of incident stroke, ischemic stroke, coronary artery disease (CAD) and mortality between low (1 egg/week or less), moderate (1-6 eggs/week), and high egg consumers (greater than 6 eggs/week).6 One important exception were high-egg-consuming diabetics who had twice the normal risk of CAD.
  • The Japan Public Health Center-based prospective study on cancer and CVD, which involved 90,735 men and women (ages 40-69), found no association between almost daily egg consumption and CHD incidence.7
  • Researchers in Spain looked at egg consumption among 14,185 subjects from the prospective cohort participating in the SUN (Seguimiento Universidad de Navarra) Project and found no association between the highest level of egg consumption (greater than 4 eggs/week) and the lowest (less than 1 egg/week).8

All of the above studies suggest that eggs are relatively benign and have little effect on one’s risk of cardiovascular disease. However, there would have to be at least a few that show some detrimental associations of eggs. After all, the well-ingrained idea that eggs are risky business has to be more than just a hunch, right? And indeed there are a handful of such studies.

  • Australian Aborigines were followed from 1988-89 to 2002 and it was found that consumption of 2+ eggs per week was associated with a 2.6-fold increased risk of CHD.9
  • A prospective study of 10,802 men and women in the United Kingdom found a 2.7-fold increased risk of death among subjects who consumed 6 or more eggs per week.10

However, Carrie notes in the podcast that the authors of the first paper did not collect information on fruit and vegetable intake and thus were unable to determine if there was an inverse association between high fat consumption and low intake of fruits and vegetables. Furthermore, the authors of the second paper used a food frequency questionnaire (FFQ) that was validated only for fiber intake. This means it has been shown that the FFQ they used measures fiber intake fairly accurately, but it has not been proven that it can do the same for other nutrients.

Controlled Trials

It was noted in the podcast that hyperlipidemic individuals are usually excluded from major studies like these. An exception that we discussed was a randomized, placebo-controlled crossover trial of 40 hyperlipidemic adults by Njike et al.11 Study subjects were randomly assigned to daily consumption of two hardboiled eggs or egg substitute for six weeks, separated by a 4-week washout. They found that egg consumption did not have a detrimental effect on endothelial function or plasma lipids. What was interesting, though, was that the egg substitute group showed a significant improvement in endothelial function, total cholesterol, and LDL cholesterol. Similar results were seen in an identically structured study by Katz et al that used treatment with daily consumption of either two eggs or oats for 6 weeks by 50 healthy men and women (mean age 56 years).12

Carrie also mentioned a study involving hyper- and hyporesponders13 of dietary cholesterol. A randomized crossover trial in Mexico examined the effect of dietary cholesterol from eggs.14 The subjects (30 boys and 30 girls aged 8-12 years) were randomly assigned to eat either two whole eggs or egg substitute for 30 days, with a three-week washout period. Each child was then classified as a hyperresponder or hyporesponder based on their degree of plasma cholesterol response. The hyperresponders had an increase in LDL and HDL cholesterol during the period of whole egg consumption, with the LDL:HDL ratio remaining the same. Hyporesponders had no significant alterations to LDL or HDL.

Of course now we get into even more complicated waters when we include discussions of not just total cholesterol but also LDL:HDL ratios. The previous study even mentions differentiating the small, dense LDL particles from larger, more buoyant LDL particles. There is actually a big difference between the two types, with the former more strongly linked to the heart diseases that we all want to try and avoid. But that is perhaps a topic for another day.

Choline

Carrie also brought up the fact that eggs were a major dietary source of choline. However, we were both having some trouble trying to remember what good non-animal sources of choline were available to vegetarians and vegans. Luckily Wikipedia never disappoints.15 Vegans should have no trouble incorporating some of those foods into their diet. Although, on a gram-for-gram basis eggs seem to be a good way to go, otherwise you’ll have to eat an entire pound of spinach to get a similar amount of choline that one egg’ll give ya.

Bottom Line

Eating a few eggs a week is not likely to increase your risk of heart disease, especially if you’re already healthy. On the other hand, if you have diabetes or some other metabolic disorder such as hyperlipidemia or hypercholesterolemia you should be mindful of how many eggs you are eating in a given week. You may need to limit your egg consumption to only 1 or 2 per week. In any case, discuss it with your primary physician.

  1. which is not a fringe journal
  2. the cholesterol circulating in your blood vessels
  3. Dawber TR, Nickerson RJ, Brand FN, et al. Eggs, serum cholesterol, and coronary heart disease. The American Journal of Clinical Nutrition 1982;36(4):617-25.
  4. Hu FB, Stampfer MJ, Rimm EB, et al. A Prospective Study of Egg Consumption and Risk of Cardiovascular Disease in Men and Women. JAMA: The Journal of the American Medical Association 1999;281(15):1387-94.
  5. Djoussé L, Gaziano JM. Egg consumption in relation to cardiovascular disease and mortality: the Physicians’ Health Study. The American Journal of Clinical Nutrition 2008;87(4):964-9.
  6. Qureshi A, Suri M, Ahmed S, et al. Regular egg consumption does not increase the risk of stroke and cardiovascular diseases. Med Sci Monitor 2007;13(1):CR1-8.
  7. Nakamura Y, Iso H, Kita Y, et al. Egg consumption, serum total cholesterol concentrations and coronary heart disease incidence: Japan Public Health Center-based prospective study. British Journal of Nutrition 2006;96(05):921-8.
  8. Zazpe I, Beunza JJ, Bes-Rastrollo M, et al. Egg consumption and risk of cardiovascular disease in the SUN Project. European Journal of Clinical Nutrition 2011;65(6):676-82.
  9. Burke V, Zhao Y, Lee AH, et al. Health-related behaviours as predictors of mortality and morbidity in Australian Aborigines. Preventive Medicine 2007;44(2):135-42.
  10. Mann JI, Appleby PN, Key TJ, et al. Dietary determinants of ischaemic heart disease in health conscious individuals. Heart 1997;78(5):450-5.
  11. Njike V, Faridi Z, Dutta S, et al. Daily egg consumption in hyperlipidemic adults: Effects on endothelial function and cardiovascular risk. Nutrition Journal 2010;9(28).
  12. Katz DL, Evans MA, Nawaz H, et al. Egg consumption and endothelial function: a randomized controlled crossover trial. International Journal of Cardiology 2005;99(1):65-70.
  13. Hyperresonders in this context means those individuals who have an increase in serum cholesterol in proportion to increased dietary cholesterol. Hyporesonders are those individuals that do not see such an increase in serum cholesterol.
  14. Ballesteros MN, Cabrera RM, del Socorro Saucedo M, et al. Dietary cholesterol does not increase biomarkers for chronic disease in a pediatric population from northern Mexico. The American Journal of Clinical Nutrition 2004;80(4):855-61.
  15. That’s not true. I’ve been disappointed by Wikipedia a few times.
Advertisements

Lipids, Inflammation, and Atherosclerosis

[Lipids, Inflammation, and Atherosclerosis mp3]

Today’s guest is the venerable Dr. Michael Rosenfeld, cardiovascular disease researcher and college professor extraordinaire. Most of his studies focus on atherosclerosis and the myriad factors that influence it.

Aside from being a pain-in-the-ass to pronounce, what exactly is atherosclerosis?

Before discussing the etiology of the disease it is important to have an understanding of how lipids are transported by the body. This is actually a more complex issue than one might suppose. Think about it: the human body is essentially an aquatic environment, and we all know that lipids are insoluble in water and will aggregate with other lipids in polar environments. So how would you be able to reliably and consistently transport dietary fat from your intestines to your liver and other organs and tissues as needed? You also need to consider that while some blood vessels are large in diameter others are quite small. Organisms like us have evolved a system to transport fats using what are called lipoproteins. They are basically tiny balls of triglycerides and cholesterol with a surface coat of various proteins and phospholipids that allow them to move about and interact in the polar environment of human plasma. There are essentially four kinds of lipoproteins: chylomicrons, very-low density lipoproteins (VLDL), low-density lipoproteins (LDL), and high-density lipoproteins (HDL). I won’t go into great detail about all of them right now, but each contains varying amounts of triglycerides and cholesterol and have slightly different proteins on their surfaces.

What do lipoproteins have to do with atherosclerosis? I’ll tell you. LDL particles are like the hot dog vendors at baseball games. They swim around the blood saying “Hiyoooo! Who needs cholesterol?? Get your cholesterol here! Use it for all kinds of things: bile salts, vitamin D, lipids rafts, testosterone… you name it! I got some fresh hot cholesterol just for you.” If a cell needs some cholesterol then it manufactures an LDL receptor, sticks it onto the cell membrane, and grabs any available circulating LDL. The LDL particle gets endocytosed and the cell can then use the delicious, gooey cholesterol for whatever it needs.

So what’s the problem? The problem is that LDL has a tendency to migrate through the endothelial cell layer of blood vessel walls and become trapped in the intima where it becomes oxidized or modified in some way. The oxidized/modified LDL particles trigger an immune response which ultimately leads to macrophages – informally known as scavengers or sometimes even garbage collectors – coming in and engulfing the oxidized/modified LDL. Now one of two things can happen here: 1) The cholesterol from macrophages can be handed off to HDL particles. The HDL can then take up this cholesterol and transport the it back to the liver to be recycled. The HDL could also give it to other lipoproteins in the blood. This process is known as reverse cholesterol transport. Or 2) The macrophage can hang out in the intima and continue to gobble-up incoming modified/oxidized LDL particles. This will lead to the formation of foam cells.1, 2


To make a long story short one or two or five foam cells within the vessel wall is no big deal, but over time, if the conditions are right, foam cells can accumulate within the vessel walls leading to a host of things you don’t want to happen with your arteries such as: narrowing of the blood vessel, chronic inflammation, recruitment of more macrophages, rupturing foam cells leading to all the oxidized LDL spilling out all over the place, migrating smooth muscle cells into the intima to wall-off the lesion, formation of a necrotic core filled with dead cells and cholesterol, and eventually rupture of the vessel wall (called a thrombosis) when all the contents spill out and can slow or stop the flow of blood. Platelets are then mobilized to repair the damage, but this probably only exacerbates the problem. If the thrombosis occurs in a coronary artery this can be deadly.


Inside an artery with advanced atherosclerosis

So what does this have to do with nutrition? There are several risk factors for atherosclerosis that can be manipulated via the diet. The following are risk factors that are considered to be “definitely modifiable” in the scientific and medical literature:

  • Cholesterol
  • HDL
  • Triglycerides
  • Blood Pressure
  • Cigarettes
  • Diabetes
  • Obesity
  • Sedentary Lifestyle
  • Alcohol

The following risk factors are classified as “potentially modifiable”

  • Lipoprotein(a)
  • Oxidized Lipids
  • Glucose Intolerance
  • Homocysteine

And there are some factors you just can’t do anything about

  • Age
  • Sex
  • Genetics

Now one might think that levels of cholesterol in the blood are directly related to the amount of cholesterol ingested in the diet. It appears to make logical sense, right? As it turns out dietary cholesterol doesn’t have a huge effect on circulating cholesterol. Most of us only absorb roughly 50% of dietary cholesterol. Even if you do ingest quite a bit of cholesterol from your diet your cells can compensate somewhat by down-regulating things like endogenous cholesterol synthesis. There is even a remarkable case study about a farmer that ate approximately 25 eggs a day (which adds up to an enormous amount of dietary cholesterol) and still had more or less normal serum cholesterol levels. The author claims that farmer was able to maintain cholesterol homeostasis by producing a ton of bile acids (made from cholesterol) and probably excreting most of it in the stool. Bear in mind, however, that this guy was probably an outlier as many case-studies are.

 

Okay, if dietary cholesterol doesn’t have a huge influence on serum cholesterol, then just what the hell does? Surprisingly saturated fat intake has a much larger effect on LDL than actual cholesterol intake. What do I mean by this? Well many studies have shown that if you subsist on a diet where your main source of fat is of the saturated kind, then it is likely that your LDL levels are high, but if you switched to fats consisting of mainly mono- and polyunsaturated fatty acids then your LDL levels are likely to drop significantly. Good news, right? Sure, olive oil all around! Oh, and with the caveat that your HDL levels could also decrease. Bummer. The good news is that LDL levels will decrease much more than the HDL. And just to further complicate matters the short and medium-chain saturated fatty acids commonly found in plant-based fats like coconut oil and palm oil don’t have the effect that other saturated fatty acids do when it comes to increasing serum cholesterol. This is because short-chain fatty acids (SCFA) and medium-chain fatty acids (MCFA) are processed differently by the body; they are not packaged into lipoproteins like other fats are but instead hitch a ride on serum albumin to get to their destinations. Think of the long-chain fatty acids (LCFA) as having to get on an enormous and crowded bus to get anywhere, whereas the SCFAs and the MCFAs are small and fit and can get on a bike to go where they need. That’s kinda where the metaphor stops, though.3

What else can you do to reduce your risk of atherosclerosis? They are all in the list.

  • If you’re obese you should lose weight, not just because of the reduced risk of atherosclerosis but also the substantial decreased risk in a legion of diseases, cancers, and what-have-you.
  • If you’re still smoking then I assume you are well aware of the above risks but choose to ignore them.
  • Get your blood pressure under control if you’re hypertensive.
  • Exercise regularly or at least semi-regularly.
  • Try not to get old. If you figure out how to do this let me know.
  • If you have Type 2 diabetes and you can’t shake it then at least learn to manage your glucose levels.
  • If you have hyperhomocysteinemia then you may have a B vitamin deficiency. Potentially an easy fix.
  • There are some gene therapies being studied right now if you have a genetic disorder that causes hypercholesterolemia.
  • There is also a large and growing body of evidence on phytochemicals and their antioxidant and protective effects.
  • There is also a substantial amount of evidence regarding omega-3 fatty acids and their role in modulating inflammation. Take this into account please.
  • If all else fails or you just want to keep eating steak and ice cream then talk to your doctor about statins.

This is all boilerplate stuff, of course. If you are reading this blog then I assume you are at least marginally interested in nutrition and already heed most of these recommendations. I didn’t get too much into inflammation in this post, but Dr. Rosenfeld and I talk about it more in the podcast. Inflammation truly deserves one or more posts on its own.

  1. Word on the street is that when the blokes that were first researching atherosclerosis were dissecting and examining diseased blood vessels they came upon a type of cell that looked like beer foam, and that’s how the foam cells got their name.
  2. It’s actually more complicated than that as you can probably imagine. It seems that if a macrophage ingests unmodified LDL then it can maintain normal cholesterol homeostasis, and get rid of the excess via reverse cholesterol transport. If the macrophage ingests a lot of oxidized LDL then it will become a foam cell.
  3. Wait… lemme try to extend it… So these buses sometimes get stuck on the highway and then the macrophage troll that hides underground comes and gobbles up the bus. If there are a bunch of buses then the troll will gobble those up as well and if he eats enough LDL buses then he morphs into the foam troll. Then foam troll can use his new powers of chemotaxis to silently call other trolls like a dog whistle and if enough buses and trolls show up then you have a traffic jam and everybody dies. Got it?

Astrup A, et al. (2011) The role of reducing intakes of saturated fat in the prevention of cardiovascular disease: where does the evidence stand in 2010? Am J Clin Nutr. 93:684-688.

Breslow JN. (2006) n-3 Fatty acids and cardiovascular disease. Am J Clin Nutr. 83:1477S-1482S.

Fernandez ML and West KL. (2005) Mechanisms by which Dietary Fatty Acids Modulate Plasma Lipids. J Nutr. 135:2075–2078.

Genest J. (2003) Lipoprotein disorders and cardiovascular risk. J Inherit Metab Dis. 26:267-287.

Glass CK and Witztum JL. (2001) Atherosclerosis: The Road Ahead. Cell. 104:503–516.

Grundy, SM. (1990) Cholesterol and Atherosclerosis: Diagnosis and Treatment. New York, NY: Gower Medical Publishing.

Grundy SM. (1991) Multifactorial Etiology of Hypercholesterolemia Implications for Prevention of Coronary Heart Disease. Arterioscler Thromb Vasc Biol. 11:1619-1635.

Kern F. (1991) Normal Plasma Cholesterol in an 88-Year Old Man Who Eats 25 Eggs a Day: Mechanisms of Adaptation. NEJM. 324:896-899.

Loscalzo J (Ed.) (2005) Molecular Mechanisms of Atherosclerosis. Abingdon, Oxon: Taylor & Francis.

Nicolosi RJ, et al. (2001) Dietary Effects on Cardiovascular Disease Risk Factors: Beyond Saturated Fatty Acids and Cholesterol. J Am Coll Nutr. 20:421S-427S.

Ross R. (1999) Atherosclerosis – An Inflammatory Disease. NEJM. 340:115-126.

Siri-Tarino SW, et al. (2010) Saturated fat, carbohydrate, and cardiovascular disease. Am J Clin Nutr. 91:502-509.