A reader (thanks, Syd!) pointed out an article in The Huffington Post that was critical of the Cleveland Clinic study suggesting carnitine causes cardiovascular disease (see Carnitine, Red Meat, TMAO & CVD).

While the Huffington Post article was one of many criticizing the Cleveland Clinic study, it was the only one I saw that made any good points. The article is Does Carnitine Really Cause Heart Disease? by Alan Gaby, MD, who is the past president of the American Holistic Medical Association. Towards the very end of the article, Dr. Gaby says, “It is noteworthy that the observed association between heart disease and carnitine levels disappeared completely when the researchers corrected for differences in kidney function.”

This is true – when the researchers corrected for a number of conditions, including kidney function and TMAO levels, the association of carnitine with major adverse cardiac events (MACE) disappeared. The researchers used that model to say that it proved that TMAO was the problem, not carnitine, and it didn’t occur to me in my first analysis that perhaps TMAO levels were high simply because the kidneys couldn’t clear the TMAO. After reading Dr. Gaby’s article I downloaded the online supplementary material and found that kidney function did progressively get worse as carnitine levels increased among the subjects, and this trend was statistically significant. So it seems plausible that perhaps the higher TMAO levels were simply a result of poor kidney function. But this is such an obvious possibility that I couldn’t believe the researchers didn’t consider it and perhaps run an unreported model to test for it. I then wrote the corresponding author of the study, Dr. Stanley Hazen, who is out of the office until the end of the month.

But there’s more. On Thursday, I awoke to news that the Cleveland Clinic group of researchers had published yet another study on TMAO! This time, it was on eggs and lecithin (1). In 2011, they had reported that choline can increase TMAO levels and TMAO was associated with the existence of cardiovascular disease in a cross-sectional study (more info). This time, they were testing phosphatidylcholine (lecithin) from eggs to see if it increased TMAO levels. It did.

Then they performed a prospective study much like the one in the carnitine study (maybe even an arm of the same one?) to see if TMAO was associated with more MACE. Once again, people with higher TMAO levels also had poorer kidney function. But even after adjusting for kidney function, TMAO was still significantly associated with MACE (1.43, 1.05–1.94).

That fully adjusted model included age, sex, smoking status, systolic blood pressure, LDL, HDL, diabetes, C-reactive protein, myeloperoxidase, glomerular filtration rate (kidney function), total white-cell count, body-mass index, medications (aspirin, statins, ACE inhibitor, ARB, or beta-blocker), and the extent of disease as seen on angiography. That’s a lot of adjustments some of which might even be too much, dampening the true effect of TMAO.

As things stand, it appears that kidney function is not the cause of high TMAO and that TMAO might, after all, be a significant cause of MACE. Stay tuned – this story is not over.

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Reference

1. Tang WHW, Wang Z, Levison BS, Koeth RA, Britt EB, Fu X, Wu Y, Hazen SL. Intestinal Microbial Metabolism of Phosphatidylcholine and Cardiovascular Risk. N Engl J Med 2013(April 25, 2013);368:1575-1584. | link

I have finally finished my article on choline! It is posted at VeganHealth.org.

After all was said and done, it was much ado about not much. Still, it is important that the issue of choline in vegan diets has now been researched.

Here is the summary from the article:

Choline is found in a wide range of plant foods in small amounts. Eating a well-balanced vegan diet with plenty of whole foods should ensure you are getting enough choline. Soymilk, tofu, quinoa, and broccoli are particularly rich sources.

The Dietary Reference Intake (DRI) for choline is 550 mg/day for men and 425 mg/day for women. It is based on only one study comparing those amounts to 50 mg/day, with no intermediary amounts examined. Eating less than 50 mg/day can result in liver damage, but it is very unlikely that a vegan would have such a low intake.

Some people have genetic mutations that increase the need for choline; it is not clear how much choline such people need but the DRI is probably adequate for almost everyone. If you suspect any sort of liver dysfunction, it might be worth talking to your physician about boosting your choline intake or supplementing with it in moderate amounts.

The data on choline and chronic disease (cardiovascular disease, dementia, and cancer) is somewhat mixed. Ideal amounts appear to be about 300 mg per day. Most vegans probably get about that much from the foods they eat.

Vegan women who are considering getting pregnant should make sure they are meeting the DRI for choline to reduce the risk of neural tube defects, and might need a modest supplement.

End summary.

As part of writing this article, I recorded everything I ate from one day and then calculated the amount of choline. When I recorded the food I ate, I didn’t know how much choline was in any of it as I had never done more than casually browse the USDA’s list of the choline content of foods. I actually expected it to be quite low, so it came as a nice surprise to find I met the recommendations I had already formulated before conducting the diet analysis. You can see my diet record in Table 2 of the article.

My choline intake came to 343 mg. However, there was no amount listed for hummus (or garbanzo beans) in the USDA database. Based on other legumes, I would assume at least 20 mg for 1/2 cup of hummus which would boost my intake to 363 mg. I was pretty surprised that after I plugged everything into the database, the only foods without values were hummus, canola oil, and grapeseed oil.

I list eating .5 cup of tofu. That was actually my estimate for the amount of tofu in Tofurky (4 slices for lunch and a 1/2 sausage for dinner). Tofurky is made from pressed tofu.

Not too long before I started writing this article, I purchased a bottle of choline supplements and started taking 300 mg twice a day (600 mg total). As I got further along in the choline research, I decided it might not be such a good idea to take so much. And since doing my diet analysis, I haven’t seen much need to to take any at all. It had been an experiment to see if taking choline would make me feel any different and I didn’t notice any change after a few weeks.

In conclusion, most vegans are probably getting enough choline in their diets.

I’d like to give special thanks to Jean Bettanny for doing another fantastic job in proofing the choline article!