Reviewed by Stanley Hazen, MD, PhD, Department Chair of Cellular and Molecular Medicine and Section Head of Preventive Cardiology and Rehabilitation at the Cleveland Clinic
An artery-damaging compound linked with higher risk for atherosclerosis and heart attacks —trimethylamine N-oxide (TMAO)—also increases risk for heart failure, kidney failure and strokes, according to a string of recent research from the Cleveland Clinic.
In a lab study published in January in the journal Circulation Heart Failure, TMAO and choline (found in egg yolks and some other foods) led to worsening heart failure problems like heart enlargement, worse cardiac function and fluid retention.
The researchers studied lab animals, but the study sheds more light on earlier findings in people. In a 2015 study in the same journal, high TMAO was associated with more severe heart failure. And in a 2014 study that tracked 720 people with heart failure for five years, high TMAO doubled the risk for death. Having type 2 diabetes doubles the risk for this condition, in which the heart can’t pump enough blood to meet the body’s needs. Of interest: In both studies, TMAO levels were significantly higher in people with diabetes than in those without blood-sugar problems.
TMAO also raises risk for two other health conditions that are of particular concern for people with diabetes:
TMAO threatens heart and brain health by encouraging the deposit of more cholesterol in artery walls. It also interferes with the process that whisks LDL cholesterol out of the body for elimination in the stool.
TMAO winds up in the bloodstream after gut bacteria convert choline and l-carnitine – found in red meat, egg yolks, high-fat dairy products and some other foods – into TMA (trimethylamine). The liver then converts TMA into TMAO. In two human studies, Stanley Hazen, MD, PhD, Department Chair of Cellular and Molecular Medicine and Section Head of Preventive Cardiology and Rehabilitation at the Cleveland Clinic and his team found that TMAO levels increased after people ate two hard-boiled eggs2 or an 8-ounce sirloin steak.3 Meat-eaters saw levels rise more than vegetarians did; their gut bacteria included more of the bugs that convert choline and l-carnitine into TMA.
In late December, the Cleveland Clinic researchers announced they’d found a potential antidote. A chemical called DMB stops gut bacteria from producing TMA.4 In a lab study, DMB kept TMAO levels in the blood lower and also led to a shrinking of artery plaque and lower levels of TMA-producing gut bacteria. The study was published in the December 17, 2015 issue of the journal Cell.5
DMB is also found in some cold-pressed extra virgin olive oil (EVOO) as well as some types of grapeseed oil, balsamic vinegar and red wine. Dr. Hazen says it’s too soon to recommend a human diet that thwarts TMAO, but does note that one study showed a Mediterranean diet was associated with lower TMAO levels, and the degree of adherence to the diet tracked with TMAO levels. Another eating strategy is to follow a diet that’s low in meat and eggs and higher in extra virgin olive oil – that’s a recipe for the Mediterranean diet, which has already been shown to confer significant heart-health benefits. “I strongly encourage the Mediterranean diet because it has the best outcome data reported,” Dr. Hazen says. In one recent study, he notes, people who consumed a Mediterranean diet, which includes specifically avoiding red meat and ingesting EVOO, a 30% reduction in cardiovascular events over almost 5 years was observed. 6
Meanwhile, other researchers agree that more research is needed. Other foods may also increase TMAO, says Andrew Mente, PhD, a Professor in the Department of Clinical Epidemiology & Biostatistics at Canada’s McMaster University. In a recent study in the Canadian Journal of Cardiology, Mente and others found that higher TMAO levels but not higher blood levels of l-carnitine were associated with higher risk for heart disease in 1,286 Canadians.7
“The findings on TMAO do not necessarily mean that the association is mediated by red meat or eggs,” Mente says. “Eggs might even be protective, as some prospective studies have shown. Furthermore, fish intake is also associated with higher TMAO, yet fish is considered to be beneficial against cardiovascular disease. The truth is that we do not yet understand the foods that drive the effect of TMAO on CVD. It is possible that other dietary sources may also increase TMAO including processed foods and carbohydrates.”
1. Organ CL, Otsuka H, Bhushan S et al. Choline Diet and Its Gut Microbe-Derived Metabolite, Trimethylamine N-Oxide, Exacerbate Pressure Overload-Induced Heart Failure. Circ Heart Fail. 2016 Jan;9(1):e002314. http://www.ncbi.nlm.nih.gov/pubmed/26699388. Accessed February 1, 2016.
2. Tang WH , Wang Z , Shrestha K et al. Intestinal microbiota-dependent phosphatidylcholine metabolites, diastolic dysfunction, and adverse clinical outcomes in chronic systolic heart failure. J Card Fail. 2015 Feb;21(2):91-6.http://www.ncbi.nlm.nih.gov/pubmed/25459686
3. Nichols GA, Gullion CM, Koro CE, Ephross SA, Brown JB. The incidence of congestive heart failure in type 2 diabetes: an update. Diabetes Care. 2004 Aug;27(8):1879-84. http://care.diabetesjournals.org/content/27/8/1879.long. Accessed February 1, 2016.
4. Tang WH, Wang Z, Kennedy DJ et al. Gut Microbiota-Dependent Trimethylamine N-Oxide (TMAO) Pathway Contributes to Both Development of Renal Insufficiency and Mortality Risk in Chronic Kidney Disease. Circulation Research, 2014; 116 (3): 44. http://circres.ahajournals.org/content/116
1 Tang WH, Wang Z, Levison BS et al. Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk. N Engl J Med. 2013 Apr 25;368(17):1575-84. http://www.nejm.org/doi/full/10.1056/NEJMoa1109400. Accessed Feberaury 1, 2016.
2 Tang WH, Wang Z, Levison BS et al. Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk. N Engl J Med. 2013 Apr 25;368(17):1575-84. http://www.nejm.org/doi/full/10.1056/NEJMoa1109400. Accessed February 1, 2016.
3 Koeth RA, Wang Z, Levison BA et al. Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis. Nat Med. 2013 May; 19(5): 576–585. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3650111/. Accessed February 1, 2016.
4 Wang Z, Roberts AB, Buffa JA et al: Non-lethal inhibition of gut microbial trimethylamine production for the treatment of Atherosclerosis. Cell Volume 163, Issue 7, p1585–1595. http://www.cell.com/cell/abstract/S0092-8674%2815%2901574-3?. Accessed February 1, 2016.
5 Wang Z, Roberts AB, Buffa JA et al: Non-lethal inhibition of gut microbial trimethylamine production for the treatment of Atherosclerosis. Cell Volume 163, Issue 7, p1585–1595. http://www.cell.com/cell/abstract/S0092-8674%2815%2901574-3?. Accessed February 1, 2016.
6 Estruch R, Ros E, Salas-Salvadó J, Covas MI, et al; PREDIMED Study Investigators. Primary prevention of cardiovascular disease with a Mediterranean diet. N Engl J Med. 2013;368:1279-1290. http://www.nejm.org/doi/full/10.1056/NEJMoa1200303. Accessed February 1, 2016.