Studies suggests bacteria in your gut may play a role in your risk of heart disease through a surprising mechanism: the breakdown of a widely consumed compound in protein known as L-carnitine - the truth according to Dr. J. Mercola

By Dr. Mercola

Nearly 100 trillion bacteria, fungi, viruses and other microorganisms compose your body’s microflora, and it’s becoming increasingly clear that these tiny organisms play a major role in your health.

Gut microbes are particularly prominent in the news lately, and one of the most talked-about studies suggests bacteria in your gut may play a role in your risk of heart disease through a surprising mechanism: the breakdown of a widely consumed compound in protein known as L-carnitine.

As a result, the media has mounted a virtual campaign warning that red meat eaters may be at higher risk of heart disease. But does the research really back up that claim? Some nutritional experts disagree, pointing out the many weaknesses in the study, and why giving up meat to prevent heart disease may be premature, if not downright wrong.

This 6 person study may be one of the worst and most publicized since last year's media attack stating eggs were as bad for you as smoking.

Microflora Composition--A New Explanation for the Link Between Red Meat and Heart Disease?

It’s widely stated that eating red meat causes heart disease, an association that is often blamed (incorrectly) on its impact on cholesterol levels. Yet, research has repeatedly shown that the dietary cholesterol-heart disease connection is incorrect.

So while the featured study may offer intriguing clues to the importance of gut bacteria, and how gut bacteria is influenced by your diet, it’s doubtful that this latest hypothesis linking heart disease to red meat consumption via another pathway is entirely correct.

For example, a 2010 study from Harvard found no evidence that eating red meats leads to heart disease.¹

That said, the featured study published in Nature Medicine² claims to shed some light on why some people who eat red meat develop heart disease while others do not – and the reason may come down to differences in gut bacteria.

The study,³ by researchers from the Cleveland Clinic, found that human gut bacteria can metabolize L-carnitine, a substance found in red meat, energy drinks and dietary supplements, and in so doing produce a byproduct called trimethylamine-N-oxide (TMAO). TMAO is thought to encourage fatty plaque deposits to form within arteries (atherosclerosis), and therefore, the more TMAO you have in your blood the greater your risk of heart disease might be.

Interestingly, people with diets high in L-carnitine, i.e. meat eaters, had a gut microbe composition that was more prone to forming TMAO, while vegetarians and vegans did not. Even after consuming large amounts of L-carnitine in a steak or supplement, the vegetarians and vegans in the study did not produce significant amounts of TMAO.

This, the authors believe, means that eating red meat alters your gut flora in a way that predisposes your body toward TMAO production, and subsequently, heart disease. This was confirmed by giving the omnivores a course of antibiotics, after which they did not produce TMAO. Stanley Hazen, MD, PhD, the study’s lead author, said in a statement:⁴

“The bacteria living in our digestive tracts are dictated by our long-term dietary patterns… 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.”

Is Red Meat Being Inaccurately Singled Out as a Heart Disease Promoter?

The latest study is not the first to link gut bacteria to heart disease. In 2011, the same researchers, Hazen and colleagues, used data from nearly 2,000 people and showed that when the bacteria in your gut break down lecithin, a type of fat found in meat, eggs, dairy and other animal foods along with baked goods and dietary supplements, and its metabolite choline, it also leads to the creation of TMAO and, subsequently, increases your risk of heart disease.⁵

In response to this and the current study, many have wondered whether red meat and other animal foods, along with supplements containing L-carnitine, lecithin or choline should be avoided. Chris Masterjohn PhD, who is currently researching fat-soluble supplements at the University of Illinois, rebutted the 2011 findings stating:⁶

“...previous studies have shown that supplements with salts of free choline do in fact generate TMAO, but uncontaminated phosphatidylcholine, the main form of choline found in food, does not. Moreover, choline-rich foods like liver and eggs did not produce more TMAO than a control breakfast, but seafood, which is generally contaminated with some trimethylamine or TMAO, did.”

Masterjohn also disagrees with the group’s latest findings, in which the researchers claim that carnitine in red meat contributes to heart disease via the same pathway, i.e. the creation of TMAO. According to Masterjohn, incomplete reporting of data in the paper combined with “wild runaway inferences” by the press has generated a grossly misleading picture of red meat’s impact on heart disease, while simultaneously ignoring the food group that actually generates the most TMAO.

He points out that red meat is only one of many foods that increases TMAO when eaten, and cites data from a 1999 study that evaluated TMAO excretion following consumption of 46 different foods, which shows that red meat generated no more TMAO than fruits and vegetables. In fact, some veggies, such as peas, cauliflower and carrots generated more TMAO than beef did! Still, none of the foods generated TMAO at levels that were statistically different from the control. (Similarly, there was no statistically significant difference between different kinds of meats, compared to the control.)

Previous Research Shows Seafood Produces More TMAO than Any Other Food, Including Beef

The 1999 study did show however, one food group that stood out as a major source of TMAO, and that was seafood. Virtually all fish and invertebrates, with few exceptions (including trout and cockles) produced statistically significant more TMAO than the “light breakfast” control alone. And, according to Masterjohn’s own statistical test, all invertebrates except clams and cockles, and all fish except tuna, trout, plaice, and roe produced significantly more TMAO than beef. He writes:

“The single 'representative female omnivore' from the [2013] Nature Medicine⁷ paper excreted similar amounts of TMAO in her urine as the six subjects from the 1999 study after consuming red meat, suggesting that, had they measured the response to seafood, the authors of the Nature Medicine paper would also have found much greater excretion of TMAO after consumption of seafood than after consumption of red meat

The difference between seafoods and red meat in the 1999 paper is like the difference between night and day. To take the most extreme example, halibut generated over 107 times as much TMAO as red meat. It seems obvious from this study that if any foods should be singled out for the production of TMAO, it should be seafoods. Yet the Nature Medicinepaper makes no mention of fish and the New York Times⁸ article only mentions fish to point out that it has less carnitine than red meat (and thus, by inference, will generate less TMAO, though that is clearly not the case, presumably because seafood tends to be contaminated with trimethylamine or TMAO itself...)

If we are to single out red meat as a source of TMAO, we should be able to identify other foods with which it should be replaced that generate less TMAO. Yet this 1999 study, which had a small sample size but tested an expansive number of foods, found that there basically are no other foods that generate meaningfully less TMAO than red meat.”

Axing Beef to Prevent Heart Disease Looks Like Another Red Herring...

Chris Kresser L.Ac has also weighed in on this issue,⁹ comparing the hypothesis that red meat causes heart disease via TMAO to the patently false notion that dietary cholesterol and saturated fat cause heart disease by raising serum cholesterol. Kresser lists three reasons for not taking the featured study at face value:

1. Inconsistent epidemiological evidence
2. “Healthy user” bias, and
3. Inconclusive and insufficient evidence on the role of TMAO in heart disease

“...even if Paleo meat eaters have higher TMAO levels than vegans and vegetarians, we still don’t have evidence proving a causal relationship between TMAO and cardiovascular disease,” he writes. “Once again, the supposed link between cholesterol and saturated fat and heart disease should serve as a reminder not to jump to hasty conclusions that unnecessarily deprive people of nutrient-dense, healthy foods. It is virtually impossible to control for all of the possible confounding factors.”

Should You Avoid L-Carnitine and Choline-Rich Foods and Supplements?

Masterjohn offers an in-depth critique of the featured study’s data in his recent Weston A Price article,¹⁰ so for more information I recommend reading it in its entirety. For example, he points out that the study does not include any data for eating steak alone (the steak was consumed with a carnitine supplement); the data also does not indicate if TMAO differences are due to a single outlier or a fundamental gender difference, or if the antibiotic treatment is a confounding factor as none of the vegans were given antibiotics. According to Masterjohn:

“There is no data in this paper showing that TMAO increases in response to steak alone in anyone.”

At this time, more investigation is still needed to support the assumption that red meat and other animal foods, along with supplements containing L-carnitine, lecithin or choline should be avoided. What’s more, these substances occur naturally in a wide range of foods, making it nearly impossible, and likely inadvisable, to avoid them entirely.

In terms of L-carnitine, an omnivorous diet provides 20 to 200 mg/day, compared to a strict vegetarian diet, which would add about 1 mg/day.¹¹ But even non-dairy infant formulas are sometimes fortified with L-carnitine, and the substance is also found in seafood, chicken breast, avocado and cheese (although in far lower amounts than are found in red meats, especially beef). It’s also important to realize that both L-carnitine and choline are essential nutrients your body needs. Choline, for instance, is linked to beneficial epigenetic changes in fetuses that likely last into adulthood, while L-carnitine has been shown to improve insulin sensitivity in type 2 diabetes.

Masterjohn also points out that while there were significant differences in the intestinal bacterial strains between omnivores and vegans, which might account for why TMAO levels were 45 percent higher in the meat eaters, intestinal flora may not be the sole answer. He writes:

“While it is possible that intestinal flora accounts for the difference, it is disappointing that the authors did not consider other possibilities, such as differences in the activity of the enzyme that converts trimethylamine to TMAO. For example, vitamin B2 is the main cofactor for the enzyme, and vegans are three times as likely to be deficient in vitamin B2 as vegetarians and omnivores.

...While antibiotics wipe out TMAO levels in humans and mice, showing that intestinal bacteria are necessary for its formation, the authors provide no clear evidence that the specific differences in intestinal bacteria between vegetarians and vegans on the one hand and meat-eaters on the other cause the observed difference in TMAO levels. It is unclear whether the 45 percent higher TMAO levels in meat-eaters represents something that we should regard as 'unhealthy.' As I pointed out above, for all we know it could be due to riboflavin (vitamin B2) deficiency among the vegans.”

The Link Between Whole Grains and Gut Bacteria that Drive TMAO Production

Jeff Leach with the Human Food Project has also weighed in on the featured study. His article is well worth reading in its entirety as well. He expounds on many of the same issues as Masterjohn and Kresser, but also focuses much of his discussion on the role of gut bacteria in the conversion of carnitine to TMAO. He writes, in part:¹²

“If we assume for the moment that TMAO can accelerate atherosclerosis, then the observation that enriched levels of Prevotella are associated with higher levels in of TMAO become more interesting – especially as enrichment of this group of bacteria seems to occur in vegans and vegetarians as well as omnivores. So what causes enrichment of Prevotella?

In a paper published in 2010, Italian researchers found that rural African kids in Burkina Faso had super high levels of Prevotella, while a similar aged group of kids in suburban Italy had none.The striking dietary difference between the kids in Burkina Faso and the Italian kids was whole grain consumption... whole grains made up >50% of the daily calories in this [African] village... In contrast, the Italian kids got ~25% of their daily calories from highly processed bread, biscuits, pasta, and rice... All in all, a much more diverse diet, though apparently devoid of whole grains but high in processed foods. As mentioned, the Italian kids had no traceable amounts of Prevotella in their stool samples...

In the Burkina Faso paper, the researchers attributed the high levels of Prevotella to grain-based carbohydrates... it doesn’t appear that dietary fiber in general is driving enrichment of Prevotella... So, it appears somehow specific to the starch in grains or the dietary fiber in grains.”

The Bottom Line...

According to Masterjohn, to interpret the featured study “as an indictment of red meat makes no sense.”

“Even if physiological levels of TMAO contribute to heart disease in humans (which is a big 'if' at this point) and even if red meat were to raise TMAO substantially more than most other foods (which appears to be false), it wouldn’t in any way whatsoever follow that eating red meat causes heart disease. The biological effects of a food cannot possibly be reduced to one of the biological effects of one of the food’s components. Believing such a thing would require believing not only that the particular component has no other relevant biological effects, but that there are no relevant biological effects of any of the other tens of thousands of components of that food

...If the carnitine in red meat were promoting atherosclerosis through its conversion to TMAO, however, then red meat should be no more dangerous than potatoes and carrots and the real killer should be seafood. How likely is this to be true?”

Indeed... Countless studies have shown the health benefits associated with a seafood-rich diet, including its value for preventionof heart disease. Personally, I believe the best option is not to avoid these potentially beneficial substances in your diet but to optimize your gut bacteria so it favors health-promoting, rather than disease-causing, processes.

Testing Your Breath May Reveal Gut Bacteria Linked to Obesity

Another area where gut bacteria are making headlines is related to your weight. One study last month revealed that as much as 20 percent of the substantial weight loss achieved from gastric bypass, a popular weight loss surgery, is actually due to shifts in the balance of bacteria in your digestive tract.¹³

Separate research has also revealed that a breath test of the gases given off by your gut bacteria may help predict your likelihood of becoming obese. The study found that people with high levels of hydrogen and methane in their breath are more likely to have a higher body-mass index (BMI) and proportion of body fat.¹⁴ This, the researchers believe, may be because the related gut bacteria influence your body’s ability to extract calories from food, leading to weight gain.

Previous research has also shown that lean people tend to have higher amounts of various healthy bacteria compared to obese people. For example, one 2011 study found that daily intake of a specific form of lactic acid bacteria could help prevent obesity and reduce low-level inflammation.¹⁵ Taken together, the research adds to the growing knowledge that nurturing the growth of beneficial bacteria in your gut is likely to have significant benefits to your health and may be essential for:

• Protection against over-growth of other microorganisms that could cause disease
• Digestion of food and absorption of nutrients and certain carbohydrates
• Producing vitamins, absorbing minerals and eliminating toxins
• Preventing allergies
• Maintaining natural defenses

Numerous studies have also shown that your gut flora plays a role in:

• Mood, psychological health, and behavior
• Celiac disease
• Diabetes
• Weight gain and obesity
• Metabolic syndrome

Your Gut Flora is Constantly Under Attack

Your gut bacteria are vulnerable to your diet and lifestyle. If you eat a lot of sugar, refined grains, GMOs and processed foods, for instance, your gut bacteria are going to be compromised because processed foods in general will destroy healthy microflora and feed bad bacteria and yeast. Your gut bacteria are also very sensitive to:

• Antibiotics
• Chlorinated water
• Antibacterial soap
• Agricultural chemicals
• Pollution

Because of this, you need to avoid processed, refined foods in your diet (this is essential for heart disease prevention, too) and regularly reseed your gut with good bacteria by taking a high-quality probiotic supplement or eating non-pasteurized, traditionally fermented foods such as:

• Fermented vegetables
• Lassi (an Indian yoghurt drink, traditionally enjoyed before dinner)
• Fermented milk, such as kefir
• Natto (fermented soy)

One of the reasons why fermented foods are so beneficial is because they contain lactic acid bacteria as well as a wide variety of other beneficial bacteria. Also, if fermented with a probiotics starter culture, the amount of healthy bacteria in a serving of fermented vegetables can far exceed the amount you’ll find in commercial probiotics supplements, making it a very cost effective alternative. Ideally, you want to eat a variety of fermented foods to maximize the variety of bacteria you’re consuming.

Nurturing Your Gut Flora is One of the Foundations of Optimal Health

Mounting research indicates the bacterial colonies residing in your gut may play key roles in the development of cancer, asthma, allergies, obesity, diabetes, autoimmune diseases and even brain-, behavioral- and emotional problems like ADHD, autism and depression. The heart disease connection is also now emerging, as discussed, although I’d hesitate to draw any conclusions from it as of yet.

Overall, I believe it would be unwise to try to eliminate foods just because they’re known to raise TMAO, as they’re all healthy and appear to include everything from meats to vegetables and seafood It’s far more likely that maintaining a healthy gut flora is paramount to prevent heart disease, and if you’re going to eliminate a food to protect your beneficial gut bacteria, it would beprocessed foods, not fresh whole foods of any kind.

Another confounding factor not addressed is the fact that meat from confined animal feeding operations (CAFO’s) are a source of hidden antibiotics, which wreak havoc on your gut bacteria. So that too may have played a role. This is reason alone to make sure you only buy organically raised grass-fed meats, as they’re not allowed to use antibiotics as growth promoters.

Previous research has shown that around age 60, there is a significant drop in the number of bacteria in your gut. According to Dr. Sandra McFarlane from the microbiology and gut biology group at the University of Dundee, people over 60 typically have about 1,000-fold less "friendly" bacteria in their guts compared to younger adults, and increased levels of disease-causing microbes.¹⁶ What this means is that it’s incredibly important to actively nurture your gut flora health, especially as you get older.

Eating fermented foods should be your primary strategy, but if you don't enjoy the taste of fermented foods, taking a probiotic supplement is definitely advised. However, before you give up on fermented foods, it is best to start with small amounts like half a teaspoon and use them as a condiment integrated with your food, similar to a salad dressing. If you still don't want to eat them then it is important to note that while I do not generally advocate taking a lot of supplements, a high-quality probiotic is an exception. I recommend looking for a probiotic supplement that fulfills the following criteria, to ensure quality and efficacy:

• The bacteria strains in the product must be able to survive your stomach acid and bile, so that they reach your intestines alive in adequate numbers
• The bacteria strains must have health-promoting features
• The probiotic activity must be guaranteed throughout the entire production process, storage period and shelf life of the product

Through my years of clinical practice, I've found that no single probiotic supplement works for everyone. However, more people seem to respond favorably to Lactobacillus sporogenes than any other probiotic, so when in doubt, that's a great place to start.