Red meat and heart disease risk: Researchers identify mechanisms involving gut bacteria

11 Dec 2018 --- New mechanisms that demonstrate how the regular consumption of red meat is linked to increased chances of heart-related diseases and how gut bacteria affect the process have been published. Concurrent studies carried out at the Cleveland Clinic Center for Microbiome and Human Health have discovered note the difference between red meat and other protein source consumption on the development of heart disease.

The findings ultimately support how taking note of lifestyle factors, such meat consumption, can lower heart disease risk, as well as highlighting the potential for producing drugs that inhibit the production of the harmful gut bacteria.

Previous research has shown that a gut bacteria byproduct formed during digestion may be the cause of cardiovascular diseases like heart attacks and strokes. This particular gut byproduct is called TMAO (trimethylamine N-oxide). When bacteria in the gut digest choline, lecithin and carnitine, which are nutrients found in animal products, they produce TMAO.

The researchers led by Dr. Hazen, Director at the Cleveland Clinic Center, set out to build upon pre-existing research with a dietary intervention study published in the European Heart Journal.

The new study found that diets rich in red meat increased circulating TMAO levels when compared to diets rich in white meat or non-meat protein sources. Chronic meat consumption raises TMAO levels and hinders the kidneys’ ability to expel it, which increases TMAO levels even more.

The study randomly provided 113 participants with complete meal plans including either red meat, white meat or vegetable protein sources as 25 percent of their daily caloric intake. All participants had a wash-out diet in between meal plans. This is a stage before a clinical trial is commenced. It can be passive “when a placebo or no treatment is given” or active “when treatment is used.”

The participants who followed the red meat diet showed high levels of TMAO in their blood and urine. This group had on average three times the TMAO levels compared to those who followed white meat and non-meat diets. Some red meat diet participants had ten times the levels of TMAO than the white meat and non-meat diet participants.

After the red meat diet participants cut it out, their TMAO levels decreased over the span of one month. Additionally, the results of the study revealed that chronic dietary choices affect kidney function by impacting their ability to expel compounds. For instance, while the red meat diet decreased the excretion of TMAO, it increased the excretion of carnitine and other carnitine-derived metabolites. 

“This is the first study of our knowledge to show that the kidneys can change how effectively they expel different compounds depending on the diet that one eats, excluding salts and water,” says Dr. Hazen.

“We know lifestyle factors are critical for cardiovascular health. These findings build upon our previous research on TMAO's link with heart disease. They provide further evidence for how dietary interventions may be an effective treatment strategy to reduce TMAO levels and lower subsequent risk of heart disease,” he adds.

Further study shows potential for treatment
A further study from the same team published in the Journal of Clinical Investigation, showed a potential new way of preventing cardiovascular disease by further exploring a gut microbial pathway that converts carnitine into TMAO.

Carnitine is a nutrient found in red meat and some energy drinks and supplements, that is converted into TMAO via a two-step process endorsed by specific gut bacteria. The first step is similar in both meat eaters and vegans and vegetarians. However, the second step, involving TMAO formation, is significantly enhanced in meat eaters. 

The researchers discovered that a daily carnitine supplement can promote TMAO levels even in people who follow non-meat diets. Previously, Dr. Hazen and his team published yet another study, in which the team had designed a potential new class of drugs that could prevent heart disease and clotting risk by interrupting the microbial pathway that converts choline into TMAO.

The team compared the effect of oral carnitine supplements on meat eaters versus vegetarians. At baseline, vegetarians demonstrated a limited ability to produce TMAO from carnitine, while meat eaters rapidly produced TMAO. After one month of supplementation, both groups showed an increased capacity to produce TMAO.

“It is remarkable that vegans and vegetarians can barely make TMAO from dietary carnitine. The striking new finding about the pathway induced by ingesting carnitine, even if only provided as a supplement in a capsule form, provides important insights about new interventions to inhibit TMAO, which may help reduce risks for cardiovascular disease,” says Dr. Hazen.

“By uncovering this new pathway, we can potentially develop new treatments to interrupt this process before both the development and progression of cardiovascular disease,” says Dr. Hazen.

In favor of a vegan diet, a comparative study by the American Heart Association (AHA) has shown that a vegan diet is more effective in reducing the risk of coronary heart disease than the AHA recommended diet. 

Meat-based protein sources have previously been identified as factors associated with an elevated risk for heart failure in middle-aged men by a study published in Circulation: Heart Failure. Researchers also suggest that the type of protein source may be significant, with processed meat being a less healthy protein source than fish, nuts or plant sources.

A further team of researchers says it has linked sensitivity to an allergen in red meat to the buildup of plaque in the arteries of the heart. While high saturated fat levels in red meat have long been known to contribute to heart disease for people in general, the finding suggests that a subgroup of the population may be at heightened risk for a different reason – a food allergen. The study, which is supported by the National Heart, Lung, and Blood Institute, part of the National Institutes of Health and appears in Arteriosclerosis, Thrombosis, and Vascular Biology.

Lastly, research published in research published in The Lancet Public Health found that following a low-carb diet could shorten life expectancy by four years, with animal-based proteins and fats being the most harmful.