'Red meat chemical' link to heart disease

“A nutrient abundant in red meat… could raise the risk of heart disease,” the Mail Online website warns.

Its story is based on a study of the nutrient L-carnitine, which is found in red meat, dairy products and some dietary supplements.

A diet high in red meat has been thought to increase heart disease risk, although a very recent study has cast doubt on this, suggesting that only processed meat increases heart disease risk. The study looked at one of the supposed factors in any possible heart disease-related risk from red or processed meat.

In a series of experiments, researchers found evidence that naturally occurring gut bacteria broke down L-carnitine into a product called trimethylamine-N-oxide (TMAO). TMAO is known to contribute towards the hardening of the arteries (atherosclerosis) – a major risk factor for heart disease.

Overall, this study provides some evidence of an association between L-carnitine and heart disease, not a direct cause and effect.

Even if L-carnitine does have this effect, sticking to current UK recommendations (no more than 70g of red or processed meat daily) would mean you were consuming only minimal levels of L-carnitine and therefore not at the level of risk seen by this research, which looked at much higher levels of L-carnitine consumption.

Where did the story come from?

The study was carried out by researchers from Cleveland Clinic in Ohio, US and was funded by various grants from the US National Institutes of Health. The study was published in the peer-reviewed journal, Nature Medicine.

The headline somewhat exaggerated the findings and implications of the research, but overall this story was covered appropriately in the media and coverage reported correctly that part of the study was carried out in mice.

The Mail Online deserves praise for providing a comprehensive and detailed, yet easy to understand, summary of what was a complex series of related experiments.

What kind of research was this?

This was a series of experimental studies looking at the effect of a nutrient called L-carnitine (found in red meat and dairy products) on heart disease risk.

The researchers wanted to assess (as previous research had suggested) whether naturally occurring bacteria converted L-carnitine into a waste product called TMAO (trimethylamine-N-oxide).

TMAO is thought to speed up the build-up of plaque in the arteries (known as atherosclerosis), which is a risk factor for heart disease.

Although the researchers carried out part of their investigations in humans, some testing was performed in mice. It is often difficult to interpret the results of animal research, and caution should be exercised when trying to generalise the findings to humans.

What did the research involve?

In this study. the researchers carried out a series of investigative tests on both humans and mice.

For the human tests, researchers gave the nutrient L-carnitine (found in red meat and dairy products) in the form of a supplement to 77 healthy volunteers, including 26 who were vegans or vegetarians. Some of the meat-eating volunteers were given an extra eight-ounce sirloin steak (equivalent to 180mg of L-carnitine).

The participants were then given antibiotics for one week to supress bacteria in the gut from converting L-carnitine into TMAO. They were then given L-carnitine again. Their blood and urine were tested at the start of the experiment and up to three weeks after ingestion of L-carnitine. Some people also had their faeces tested.

As part of their investigations, the researchers separately checked the levels of L-carnitine in the blood of 2,595 people who were having heart check-ups. They did this to see if there was an association between L-carnitine levels and known cardiovascular disease, or risk of a cardiovascular event (such as a heart attack).

Finally, the researchers looked at the build-up of plaque in the mice’s arteries by comparing a group of mice fed L-cartinine for 10 weeks with normally fed mice. Some of these mice were pre-treated with antibiotics.

What were the basic results?

The main results from this study include:

• Meat-eating volunteers produced more TMAO than vegans or vegetarians following ingestion of L-carnitine
• There was a significant association between L-carnitine concentrations and risk of cardiovascular event among people undergoing heart check-ups, but only in those that had high TMAO concentrations. The researchers noted that this result suggests that TMAO rather than L-carnitine is the main driver of this association.
• Faecal analysis showed significant associations of L-carnitine with levels of TMAO in the blood.
• Feeding L-carnitine to mice doubled the risk of the animal developing plaque build-up in the arterial walls, but only when they had their usual gut bacteria. When the animals were treated with gut-clearing antibiotics, L-carnitine in the diet did not lead to arterial wall build-up.

How did the researchers interpret the results?

One of the lead researchers, Dr Stanley Hazen from the Cleveland Clinic in Ohio, is reported as saying “discovery of a link between L-carnitine ingestion, gut microbiota metabolism and cardiovascular disease risk has broad health-related implications. Carnitine metabolism suggests a new way to help explain why a diet rich in red meat promotes atherosclerosis”.

He goes on to say that “a diet high in carnitine actually shifts our gut microbe composition to those that like carnitine, making meat eaters even more susceptible to forming TMAO and its artery-clogging effects. Meanwhile, vegans and vegetarians have a significantly reduced capacity to synthesize TMAO from carnitine, which may explain the cardiovascular health benefits of these diets”.

The study concludes that there is ‘public health relevance, as L-carnitine is a common over-the-counter dietary supplement’. In an accompanying press release, Dr Hazen recommends that people not use L-carnitine supplements unless advised to for medical reasons.

Conclusion

Overall, this study provides some evidence of a link between L-carnitine found in red meat and increased levels of a compound that is linked to risk of cardiovascular disease.

It is important to note that this research does not provide evidence of a causal link, only an association. Further research, perhaps a cohort study, comparing health outcomes between people who eat high levels of L-carnitine and those who eat low levels, would be required to better establish cause and effect.

This study importantly reconfirms the warning that dietary supplements are not necessarily healthy, effective or safe for everyone. The level of proof required for claiming safety of dietary supplements is not the same as that required for marketing drugs.
For more information read Supplements: who needs them? A Behind the Headlines special report.

Finally, this research does not alter the recommendation that adults should limit their intake of red or processed meat to 70g per day. Eating this amount would mean that your intake of L-carnitine will be minimal and should not affect your health.

Analysis by NHS Choices. Follow Behind the Headlines on Twitter.