Researchers at the Cleveland Clinic found that people with high blood levels of a chemical called phenylacetylglutamine (PAG) are at high risk for heart failure that affects more than 6.2 million North Americans (Circulation: Heart Failure, Dec 16, 2022;e009972). PAG is formed primarily in the colon where bacteria there make it from the amino acid phenylalanine that is found in meat and other rich sources of protein. The higher the blood level of PAG, the more severe the heart failure risk. Earlier studies show that PAG is also associated with increased risk of heart attacks, strokes, arterial clotting, plaque formation and premature death (Cell, Mar 5, 2020;180(5):862-877.e22).

How PAG Can Damage Your Heart and Blood Vessels
The same researchers have reported that elevated levels of PAG predicted future risk for heart attacks, strokes and death (Circ Res, Jul 31, 2020;127(4):553-570). Rat studies have shown that PAG weakens heart muscle contractions and causes clots to form, but giving the rats beta blocker drugs helped to prevent these serious side effects. Human patients with high PAG levels were also at significant risk for heart failure. PAG stimulates adrenergic receptors on platelets to markedly increase risk for forming clots that cause heart attacks and strokes (Nature Reviews Cardiology, Mar 24, 2020;17:265). Beta blocker drugs block adrenergic receptors and the release of the stress hormones adrenaline and noradrenaline, so beta blockers are used to help treat high blood pressure, angina heart pain, heart failure and some heart rhythm disorders (J Cardiovasc Dev Dis, Sept 2021;8(9):101).

TMAO Also Increases Risk for Heart Attacks and Strokes
Increased heart attack risk is also directly related to blood levels of TMAO and its precursors (Arteriosclerosis, Thrombosis and Vascular Biology, Aug 1, 2022;42(9):e273–e288). A study that followed nearly 4,000 adults over age 65 for 12.5 years found that eating unprocessed red meat, total meat and animal-sourced foods in general are all associated with higher risk of heart disease. Unprocessed red meat specifically showed a 15 percent increased risk associated with each 1.1 serving of meat per day. Eating large amounts of poultry, eggs or fish did not show the same association. This study also showed that blood glucose, insulin and inflammation are associated with eating meat and increased risk for heart attacks. Colon bacteria make a chemical called TMA that comes from eating meat and some energy drinks and supplements that are rich sources of choline, lecithin and carnitine. TMA is absorbed from the colon into the bloodstream, travels to the liver and is converted there to TMAO that directly causes plaques to form in arteries, where they can break off and cause heart attacks.

My Recommendations
In the future, blood tests for PAG and TMAO are likely to be used to predict your risk for suffering a heart attack or stroke. For now, you can reduce your risk by limiting or avoiding meat from mammals (beef, pork and so forth) and processed meats, and following a plant-based diet that includes lots of vegetables, whole grains, beans, nuts and other seeds. This way of eating is perhaps the most important part of the Anti-Inflammatory Lifestyle that I recommend for everyone. When you follow an anti-inflammatory diet and eliminate other known sources of inflammation that you can control with your lifestyle, you reduce your risk for heart attacks, strokes, diabetes, and the many other debilitating diseases and conditions that are linked to inflammation.