Just before going on my break, I wrote about a recent study showing that meat-eaters have bacteria in their digestive tracts that turn carnitine (found in high amounts in red meat) into TMAO which causes atherosclerosis (see Carnitine, Red Meat, TMAO & CVD). That very day, a meta-analysis was released indicating that carnitine supplements can reduce mortality in people who have had heart attacks (1).

Does that meant that red meat actually prevents heart disease via it’s carnitine content?

When someone has a heart attack, their carnitine levels become depleted. The meta-analysis showed that supplementing with large doses of carnitine (an optimal dosage of 6-9 g/day, many times more than one could get from eating red meat) can reduce mortality, particularly in the first 5 days after the heart attack.

Ventricular arrhythmias and angina were also reduced, but heart failure and second heart attacks were not. The paper did not show how long these studies lasted – this information might have been included in their on-line charts, but I could not access them. Many of the studies were not double-blinded and there were some other methodological problems, so it’s not even clear whether carnitine does provide a benefit for all of these parameters, though I would not be surprised if the reduction in 5-day post-heart attack mortality holds true.

In any case, this meta-analysis has basically nothing to do with the study on carnitine and TMAO.

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Reference

1. Dinicolantonio JJ, Lavie CJ, Fares H, Menezes AR, O’Keefe JH. L-Carnitine in the Secondary Prevention of Cardiovascular Disease: Systematic Review and Meta-analysis. Mayo Clin Proc. 2013 Apr 15. doi:pii: S0025-6196(13)00127-4. 10.1016/j.mayocp.2013.02.007. [Epub ahead of print] | link

This is red meat week!

If you haven’t heard about it by now, a new paper was released this week looking at the link between carnitine, gut bacteria, a molecule called TMAO, and atherosclerosis. The multi-part study was performed by researchers at the Cleveland Clinic, among other places, and was reported in the New York Times, Culprit in Heart Disease Goes Beyond Meat’s Fat, and today’s episode of Science Friday, Red Meat’s Heart Risk Goes Beyond the Fat (1).

The Science Friday episode is 13 minutes long and is a good overview of the research, though I will go over it here briefly.

Carnitine is an amino acid (but not a protein amino acid) that is used by the body to transport fatty acids into the cell’s mitochondria to be burned as energy. For this reason, there have been many trials of carnitine supplementation with hopes that it could increase fat loss and related conditions. The trails have been mixed (1). In food, carnitine is found in the highest amounts in beef (56-162 mg per 4 oz serving according to the NIH), while other foods have much lower amounts (a chicken breast has only 3-5 mg per 4 oz).

While humans can produce carnitine, and most people can produce all they need, only bacteria can break it down (1). Some bacteria convert carnitine into a molecule called trimethylamine (TMA) and when this happens, the liver converts TMA to trimethylamine-N-oxide (TMAO).

In 2011, in the VeganHealth.org article, Choline, I reported on a study by this same group of researchers that indicated that the metabolism of choline, by gut bacteria and then the liver, results in TMAO. The researchers found that high blood levels of TMAO were associated with cardiovascular disease.

This time, they studied carnitine rather than choline, and they came to a similar conclusions. They also found that vegetarians do not have the bacteria in their guts needed to produce TMAO out of carnitine; not that this really matters given that we eat little to no carnitine.

Based on their studies using mice , the researchers believe that TMAO prevents the metabolism of cholesterol by the liver and diverts it to the blood vessels where it becomes plaque.

In my series Of Meat and Mortality, I did not mention that the Harvard study found that saturated fat and cholesterol in red meat only moderately accounted for the increase in cardiovascular disease associated with red meat. This theory about TMAO causing heart disease might explain the finding by Harvard and also help explain why poultry has not had an association with mortality from cardiovascular disease while red meat has.

This is not the final word on carnitine and heart disease and it will be interesting to see what future research shows.

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Reference

1. Koeth RA, Wang Z, Levison BS, Buffa JA, Org E, Sheehy BT, Britt EB, Fu X, Wu Y, Li L, Smith JD, Didonato JA, Chen J, Li H, Wu GD, Lewis JD, Warrier M, Brown JM, Krauss RM, Tang WH, Bushman FD, Lusis AJ, Hazen SL. Intestinal microbiota metabolism of l-carnitine, a nutrient in red meat, promotes atherosclerosis. Nat Med. 2013 Apr 7. doi: 10.1038/nm.3145. [Epub ahead of print] | link

Released last week:

Heart disease rates of all vegetarians compared to all non-vegetarians were calculated for EPIC-Oxford from 1993 until 2009 (1). These participants were all thought to be free of heart disease at the beginning of the study. The results showed that vegetarians had a statistically significant, ~30% reduced risk of heart disease (.68, .58-.81). That is a fairly impressive finding for a nutrition study.

All results were adjusted for age, smoking, alcohol, physical activity, education, socioeconomic status, oral contraceptives, and hormone replacement therapy. The findings held after adjusting for body mass index (BMI) and removing the first two years of follow-up. (See the table in EPIC-Oxford: Heart Disease (2013) of VeganHealth.org for the relative risks.)

The researchers believed the difference in heart disease rates to be due mainly to the lower non-HDL cholesterol and systolic blood pressure of the vegetarians. The non-vegetarians had an average total cholesterol level of 222 mg/dl vs. 203 mg/dl for the vegetarians, while HDL was 52 vs. 50 mg/dl respectively. Systolic blood pressure was 134 for non-vegetarians and 131 mm Hg for vegetarians.

Given that vegetarians had cholesterol levels an average of 203 mg/dl – a full 33% higher than the 150 mg/dl, upper-end-of-healthy that many of the very low-fat doctors recommend – it might come as a surprise to learn that, in the authors’ words, “On the basis of the absolute rates of hospitalization or death from IHD [ischemic heart disease], the cumulative probability of IHD between ages 50 and 70 y was 6.8% for nonvegetarians compared with 4.6% for vegetarians.”

In other words, with cholesterol levels that high in both groups, you might think they would have a very high rate of heart disease, but, from what I can tell (see reference #2), their rates are relatively comparable to the general population of the United States (2).

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Reference

1. Crowe FL, Appleby PN, Travis RC, Key TJ. Risk of hospitalization or death from ischemic heart disease among British vegetarians and nonvegetarians: results from the EPIC-Oxford cohort study. Am J Clin Nutr. 2013 Jan 30. [Epub ahead of print] | link

2. Prevalence of Coronary Heart Disease — United States, 2006–2010
Morbidity and Mortality Weekly Report (MMWR) for October 14, 2011. Accessed February 3, 2013. | link (PDF)

I have a question in my inbox from someone asking if there “is anything to the ‘no oil’ diets,” such that Dr. Caldwell Esselstyn promotes. My answer is – certainly there is something to it. Dr. Esselstyn (1) and Dr. Dean Ornish (2) have used a very low-fat, plant-based diet (10% of the calories as fat) as part of a cholesterol-lowering program that has decreased the amount of plaque in patients’ arteries and led to much better outcomes than typical treatment for heart disease. Dr. Neal Barnard and the Physician’s Committee for Responsible Medicine have used a very low-fat, vegan diet to treat type-2 diabetes with impressive outcomes (link).

But is it the only healthy diet that all vegans should eat? Let’s look at some other evidence.

A 2000 cross-sectional report (3) on cholesterol levels in men from EPIC-Oxford found the following:

So the vegan men were eating a diet of 30% of their calories as fat while still maintaining cholesterol levels of 158 mg/dl. Some people would consider this level of cholesterol too high, and while trials of people with heart disease who lower their cholesterol levels to below 150 mg/dl have shown a great benefit in doing so, it is not clear (to me, anyway) that people without a history of high cholesterol and heart disease need to go as low as 150 mg/dl. Low calories (or body weight) and saturated fat may be the most important aspect of lowering cholesterol levels.

A cross-sectional study on cholesterol levels is not the highest form of evidence compared to the clinical trials I mentioned earlier. What about trials of higher fat diets?

The Eco-Atkins diet, a high-protein, higher fat version of a vegan diet found better changes in blood lipids and higher levels of satiety when compared to a lower fat, near-vegan diet (4). But this trial only lasted 4 weeks, not nearly long enough to measure heart disease outcomes. Cholesterol levels of the people on Eco-Atkins went from 257 to 205 mg/dl – nowhere near as low as the very low-fat diets generally achieve, but, again, it was only four weeks long.

Most of the very low-fat diets do not allow for many nuts. While nuts have consistently been associated with positive health outcomes (lower body weight, better cholesterol levels, etc.), one vegan doctor, who uses low-fat diets to treat heart disease, told me that many of his patients binge on nuts when they are part of their diets and so he suggests they avoid them. I’ve heard from others that if they eat nuts they gain weight. It doesn’t completely surprise me that someone on a very low-fat diet might binge on nuts – they might be craving the fat or protein. But if you are someone who can eat nuts in moderation, then having some is most likely beneficial for preventing heart disease and long-term weight maintenance.

Though it may be rare, or even extremely rare, some people who follow a very low-fat diet find that they lose their libido and regain it upon eating more fat.

Earlier this month, Jeff Nelson of Vegsource.com wrote an article, How the ethical argument fails veganism. In it, he disagrees with my co-founder of Vegan Outreach, Matt Ball, and my co-author of Vegan For Life, Ginny Messina, as to whether the health argument is the way to go when spreading veganism. He also disparages “AR dietitians” in general, of which I can’t help but notice that I am one.

Aside from the fact that Matt nor I care about veganism as anything more than a tool for protecting animals and the environment, the central thesis of Nelson’s article is that people who become vegan for health reasons are more likely to stick with the diet than people who go vegan for ethical reasons. He says that people who go vegan for ethical reasons are usually not as educated about health and nutrition due to being persuaded by organizations that do not give them adequate information; so they eat processed foods and end up concluding that a vegan diet is not healthier. The people who go vegan for health reasons, on the other hand, understand the importance of avoiding processed foods and oils, and their health improves.

While many people do well on a whole-foods only, very low-fat vegan diet, my experience has been that such diets can sometimes result in failure to thrive, while many people do thrive on a vegan diet that includes more fat and processed foods.

The vegans I know are mostly animal advocates, and, therefore, are dedicated to being vegan. Very few of them had been diagnosed with heart disease or type-2 diabetes before becoming vegan, so they are not necessarily in the same boat as people who become vegan to treat their disease. The vast majority of the vegan, animal advocates I have know have stayed vegan, and most eat processed foods. From soy foods to french fries to desserts made with white flour and sugar, the vegans I know eat ‘em. Of course, most of them also eat more fruit, vegetables, whole grains, legumes and nuts than the average American.

My cholesterol tends to be around 150 mg/dl. If I were eating a very low-fat diet, it might be even lower, possibly decreasing my risk for heart disease. But I crave protein and feel better when eating a good amount, possibly due to my fairly intensive weight lifting. I do much better eating soyfoods and other processed foods such as pasta, than when eating only whole plant foods.

There are health issues that might prevent people from eating only whole foods, such as digestive problems, and those have to be dealt with on a case by case basis.

I generally tell people who have metabolic syndrome that they should tend towards a whole-foods diet, greatly limiting added oils but including nuts, while those who are not as much at risk can afford to eat more processed foods, especially those high in protein and/or pastas (which generally do not raise blood sugar as high as other processed grains). Monitoring your weight, cholesterol, and blood sugar levels is a good idea to see if the diet you are eating is working for you.

At some point there might be clinical trials examining cardiac outcomes in people on vegan diets that are not so low in fat or in vegans who have not been diagnosed with heart disease. We do have some data on heart disease in vegans from the 1999 meta-analysis, but it isn’t much.

References

1. Esselstyn CB Jr. Updating a 12-year experience with arrest and reversal therapy for coronary heart disease (an overdue requiem for palliative cardiology). Am J Cardiol. 1999 Aug 1;84(3):339-41, A8. | link

2. Ornish D, Scherwitz LW, Billings JH, Brown SE, Gould KL, Merritt TA, Sparler S, Armstrong WT, Ports TA, Kirkeeide RL, Hogeboom C, Brand RJ. Intensive lifestyle changes for reversal of coronary heart disease. JAMA. 1998 Dec 16;280(23):2001-7. Erratum in: JAMA 1999 Apr 21;281(15):1380. | link

3. Allen NE, Appleby PN, Davey GK, Key TJ. Hormones and diet: low insulin-like growth factor-I but normal bioavailable androgens in vegan men. Br J Cancer. 2000 Jul;83(1):95-7. | Link

4. Jenkins DJ, Wong JM, Kendall CW, Esfahani A, Ng VW, Leong TC, Faulkner DA, Vidgen E, Greaves KA, Paul G, Singer W. The effect of a plant-based low-carbohydrate (“Eco-Atkins”) diet on body weight and blood lipid concentrations in hyperlipidemic subjects. Arch Intern Med. 2009 Jun 8;169(11):1046-54. Erratum in: Arch Intern Med. 2009 Sep 14;169(16):1490. | link

I just updated Mild B12 Deficiency – Cardiovascular Disease & Homocysteine with the following from a study that just came out:

A 2012 randomized, placebo-controlled, crossover clinical trial tested B12 supplementation’s effects on flow-mediated dilation (FMD) of the brachial artery and intima-media thickness (IMT) of the carotid artery, both of which are markers of cardiovascular disease (1). The study was done in Hong Kong and there were 50 vegetarians, two of whom were vegan. Twelve subjects (24%) had serum vitamin B-12 between 203-406 pg/ml and 35 subjects (70%) < 203 pg/ml. After 12-week periods of 500 µg of B12 per day, average homocysteine levels went from 16.7 to 11.3 µmol/l. Brachial artery FMD significantly increased and carotid IMT significantly decreased, both of which improves cardiovascular function, after vitamin B12 but not after placebo treatment. These positive effects appeared to be better correlated with the correction of vitamin B12 deficiency than with the lowering of homocysteine. The authors noted that the effects “on carotid intima-media thickness was quite subtle and of uncertain biological significance.”

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I was surprised that with 500 µg B12 per day, homocysteine levels did not decrease even further, especially since these participants were shown to have good folate status. The study contained no control group of non-vegetarians, so it’s not clear if the same results would be found for non-vegetarians, though rarely do non-vegetarians have an average homocysteine level as high as 16.7 µmol/l.

In any case, this appears to be the first direct evidence on cardiovascular function to show that mild vitamin B12 deficiency could have a negative effect.

None of the participants experienced side effects, including skin reactions, while on the B12 supplementation regimen.

Reference

1. Kwok T, Chook P, Qiao M, Tam L, Poon YK, Ahuja AT, Woo J, Celermajer DS, Woo KS. Vitamin B-12 supplementation improves arterial function in vegetarians with subnormal vitamin B-12 status. J Nutr Health Aging. 2012;16(6):569-73. | link

Here’s something I’ve been mentioning in my talks lately. A 2000 study measured the percentage of calories as fat in the diet as well as cholesterol levels in a subset of EPIC-Oxford vegan and non-vegan men. Here is what they found:

Vegans ate 30% of their calories as fat compared to 34% for meat-eaters. Not a huge difference and many people would be horrified at such a high fat intake on behalf of the vegans. Yet, their cholesterol levels were well below what is commonly considered the danger zone.

What accounts for this? The vegans’ much lower intake of saturated fat probably explains a lot. But the vegans’ 20% fewer calories also probably accounts for much of their lower cholesterol levels. Addendum 1/27/12: Additionally, higher fiber intake and zero or near-zero cholesterol intake all likely contribute to the vegans’ lower cholesterol levels. Clarification 1/30/12: People who exercise a lot can eat more calories without cholesterol levels increasing as long as they are not eating so much that they gain body fat (thanks, Ginny).

Some people might point out that ideal cholesterol levels are actually less than 150 mg/dl, so 158 mg/dl is too high. While many clinical trials in people with heart disease (and normally on cholesterol-lowering medication) show a benefit to getting levels below 150 mg/dl, I have not seen evidence that this is ideal, or even desirable in people without diagnosed heart disease or normally high cholesterol. Instead, the observational studies I’ve seen measuring cholesterol levels and mortality have not shown a benefit from cholesterol levels less than 160 mg/dl.

I would not completely rule out the idea that studies have not shown reduced mortality in people with cholesterol levels less than 160 mg/dl because they have not included enough people with cholesterol levels that low and who do not have such low levels due to undiagnosed disease. But “not completely ruling out something” is a far cry from saying there is good evidence that it is true.

The reason I think this is particularly important is anecdotal evidence that people on long-term, low-fat diets can find them hard to stick with. I know there are some exceptions – people who find them easy to stick with, but I sense that there are more who find it difficult. When people crave meat, they tend to think they are craving the protein. But meat is also about 50% fat on average and it would not surprise me if such people are often craving fat as much or more than protein. Eating a diet closer to 30% fat might prevent such cravings.

Yes, lots of qualifiers above that I’m not 100% certain of everything I’m saying. But I think there is enough evidence that I should share it with readers rather than just keeping it to myself until “further studies” are done.

Reference

Allen NE, Appleby PN, Davey GK, Key TJ. Hormones and diet: low insulin-like growth factor-I but normal bioavailable androgens in vegan men. Br J Cancer. 2000 Jul;83(1):95-7. Link

In 2009, preliminary cross-sectional data on blood pressure rates among various diet groups were reported from Adventist Health Study 2. Just today, a more thorough report was posted at PubMed. The 2012 report only included whites and the results did not appear to be adjusted. But, in any case, vegans had a 63% reduced risk of having high blood pressure, as compared to regular meat-eaters, which was highly statistically significant. Lacto-ovo vegetarians had a 43% reduced rate, which was also statistically significant. More details can be seen in Table 12 of Disease Markers of Vegetarians at VeganHealth.org.

Body mass index was able to account for most of the differences in blood pressure between the diet groups, though other factors probably play a small role, such as higher potassium and lower sodium intakes, and lower insulin levels and blood viscosity.

Reference

Pettersen BJ, Anousheh R, Fan J, Jaceldo-Siegl K, Fraser GE. Vegetarian diets and blood pressure among white subjects: results from the Adventist Health Study-2 (AHS-2). Public Health Nutr. 2012 Jan 10:1-8. [Epub ahead of print] Link

Hear ye, hear ye – another cross-sectional study on vegans has been released!

This time, it’s from Brazil (1). The main focus of the study was to determine how fast various lipids (triglycerides and cholesterol) were removed from the blood.

21 vegans were compared to 29 omnivores. The vegans had lower intakes of calories, saturated fat, and total fat. Vegans had similar triglyceride removal to omnivores, but they had faster cholesterol removal. Vegans also showed a lower rate of transferring cholesterol to HDL particles which is, apparently, a good thing.

The authors conclude that these findings, along with the vegans’ lower LDL cholesterol levels, puts vegans at a lower risk for atherogensis (fatty build up in the arteries).

Reference

1. Vinagre JC, Vinagre CG, Pozzi FS, Slywitch E, Maranhão RC. Metabolism of triglyceride-rich lipoproteins and transfer of lipids to high-density lipoproteins (HDL) in vegan and omnivore subjects. Nutr Metab Cardiovasc Dis. 2011 Sep 19. Link

In my post of yesterday about the semi-vegetarians in Chad, I said that there is a steady flow of cross-sectional studies on semi-vegetarians from developed countries and their cardiovascular disease markers. Today I’m reporting on another one that can roughly go in that category, although the subjects were actual vegetarians (171 males) from a temple in China (1). They were mostly vegan, though some occasionally eat eggs and milk. They were compared to 129 omnivores.

Intima-media thickness is a measure of the thickness of the artery wall that has been shown to predict cardiovascular disease. To make a long story short, the vegetarians had thinner carotid intima-media indicating less atherosclerosis.

Other results were all over the board. For example, even though vegetarians had lower BMI, they had higher waist to hip ratios. Surprisingly, the vegetarians had much lower homocysteine levels, but the homocysteine levels for both groups were “off the charts” at 76 and 125 µmol/l respectively. I’ve never heard of homocysteine levels so high (normal is between 6 and 12 µmol/l) and it makes me think their measuring methods were not calibrated to other studies’ methods.

One final tidbit: Total cholesterol for vegetarians and omnivores was 164 and 193 mg/dl.

The take home message: Make sure you have a reliable source of vitamin B12. (Just kidding!)

1. Yang SY, Zhang HJ, Sun SY, Wang LY, Yan B, Liu CQ, Zhang W, Li XJ. Relationship of carotid intima-media thickness and duration of vegetarian diet in Chinese male vegetarians. Nutr Metab (Lond). 2011 Sep 19;8(1):63. Link

Ginny Messina: Tips to help Bill Clinton get the most out of his vegan diet