A few months ago, an article appeared in Nature Medicine http://www.ncbi.nlm.nih.gov/pubmed/23563705 claiming that carnitine, found in red meat and energy drinks, may contribute to heart disease via its conversion by our intestinal flora to the metabolite trimethylamine oxide (TMAO), which causes arthrosclerosis in mice and therefore, it is assumed, in humans. As is often the case, the popular press had a heyday and sensationalist headlines appeared everywhere to the effect that red meat is a killer. However, there were several flaws in the study and many things that were not taken into account by the authors, which I will try to clear up and make sense of here.
To conduct this study, the authors gave volunteers a steak plus a capsule of carnitine to eat for breakfast and their TMAO levels were then measured – they remained flat though slightly elevated – that is to say, no sudden surge occurred. They were then given broad-spectrum antibiotics for a week to suppress gut flora and the challenge was repeated, this time with minimal detectable TMAO. After 3 weeks to allow the gut flora to re-populate, the test was conducted again and showed an surge in TMAO levels. The study also “showed” that meat eaters have meat-induced changes to their intestinal flora which also results in raised TMAO levels, which vegans do not experience.
In order to support their hypothesis that meat eaters only have intestinal flora which encourages conversion of carnitine to TMAO, mice were fed drinking water composed of 1.3% carnitine and the authors found that the resulting alteration in intestinal flora led to a 10-fold increase in TMAO levels after ingesting carnitine. Convincing, right? Well, not when we consider that if the mice were drinking their usual water intake – about 5ml per day – the amount of carnitine they were ingesting works out, in human terms, as the equivalent of a thousand steaks per day. If this isn’t enough, the species of gut bacteria that showed up in mice after this challenge and which were responsible for the rise in TMAO levels have never been found in humans, leading the authors to conclude that “microbes identified from the distal gut of the mouse represent genera that are typically not detected in humans”. Surely then we cannot draw any conclusions about similar mechanisms in humans as far as the relationship between carnitine and TMAO goes?
The sole vegan control used in the study and whose post-carnitine TMAO levels were used to show that non-meat eaters do not experience this surge, was male. However, it is important to understand that androgens (male hormones) suppress the enzyme responsible for converting trimethylamine – the precursor of TMAO – to TMAO, resulting in lower levels of it; thus comparing a male vegan control with female omnivores to show that non-meat eaters produce less TMAO as a result of meat-induced gut floral changes is hardly a true or fair representation.
One of the most obvious things to point out is that the study did not rely solely on food – volunteers were all given an extra supplement to increase levels of carnitine. The steak alone provided 180 mg of carnitine and the supplement 250 mg. This cannot be taken as a true representation of the general population and their risk, since nowhere in the paper is any indication given of TMAO levels after eating steak alone – which is what most people would do – more on this later. From the small sample sizes used, it is impossible to say whether the TMAO produced was a result of it having been converted from ingested carnitine or whether it was already present in the body – not convincing enough to state that “red meat leads to heart disease”.
It is also interesting that there was no surge in TMAO until after 3 weeks of antibiotic treatment, when the flora had had a chance to regenerate. The difference in TMAO levels after this time could well be attributed to dysbiosis, (where unhealthy gut bacteria outweighs healthy) which is a common occurrence after antibiotics treatment. Could it be that a healthy balance of intestinal flora is needed for the healthy metabolism of carnitine? It certainly wouldn’t be a strange notion, as proper digestion cannot occur without healthy intestinal flora.
In previous studies 1, 2, it was found that seafood and fish, which contain trimethylamine, generated far higher levels of TMAO than beef and also that TMAO levels from eating red meat were no higher than from eating white meats. So why is red meat held to be responsible as opposed to seafood and fish? And if carnitine is being held responsible for atherosclerosis via its conversion to TMAO then surely it would hold true that fish and seafood, which generate far higher levels, are the real killers? However, time and time again we see that cultures whose diets are rich in fish appear to be almost free of heart disease and many studies correlate fish consumption with a reduced risk of heart disease.
The other possibility that the authors did not consider is that vitamin B2, or riboflavin, is needed for the conversion of trimethylamine to TMAO and vegans are often deficient in this vitamin. This may account for the lower levels of TMAO in the vegan control and should certainly have been important enough for consideration.
And finally, as is often the case when comparing omnivores with vegans, little consideration is given to the other differences in eating habits – such as increased fruit and vegetable intake in vegans. We metabolise proteins very differently in the presence of the components of fruits and vegetables and this often accounts for differences in health outcomes.
As with most studies conducted in this way and focusing on an isolated nutrient and its effects on the body, cause and effect are almost impossible to correlate. Linking one particular nutrient or food component to a specific biological effect is simply ignoring the biological effects of all of the other components in that food, which is at best misleading but realistically is simply bad science. All foods are synergistic and thus work as a whole and this is often why studies on a single vitamin, mineral or nutrient using synthetic supplementation do not work and yield misleading results. Carnitine in a steak, alongside all its other components and a good amount of vegetables will metabolise very differently from pure synthetic carnitine in the form of a supplement, such as was used in the study.
Let us not forget that red meat has some very important nutrients for health, first and foremost amino acids which are used to build protein – necessary not only for building muscle and balancing blood sugar but also for detoxification. Red meat of course also contains iron, of which it is estimated that up to 70% of female teenagers are deficient. However, vitamin C is needed for the absorption of iron and so we come again to the importance of eating vegetables with each meal. And carnitine itself is an important amino acid, helping the body use fat for energy. Interestingly, carnitine has actually been shown in studies to improve heart function 3 and reduce cholesterol 4 – something not mentioned in the study.
I believe that the best lessons to take home from this study are to eat most things in moderation – red meat intake should probably not exceed a couple of times a week, to make sure meat is of high quality, grass fed if possible and above all, ensure a good serving of vegetables with every meal.
- 1 http://www.ncbi.nlm.nih.gov/pubmed/10456680
- 2 http://www.ncbi.nlm.nih.gov/pubmed/6842395
- 3 http://www.sciencedirect.com/science/article/pii/S0002870300043003