New research from the University of Colorado Boulder has offered some of the clearest evidence to date showing how the gut microbiome produces a metabolite that, over time, contributes to age-related declines in cardiovascular health.
High blood levels of trimethylamine-N-Oxide (TMAO), a metabolic byproduct of digestion, have been strongly linked to negative cardiovascular health. When one eats red meat, eggs or other animal proteins, certain types of gut bacteria feed on chemicals in those foods and produce TMA, or trimethylamine, which is then turned into TMAO in the liver.
A number of studies have linked TMAO to heart disease, however, until now it hasn’t been clear exactly how this metabolite causes cardiovascular damage. A robust new study, published in the journal Hypertension, is offering one of the first thorough mechanistic investigations illustrating how TMAO damages the cardiovascular system.
“Our work shows for the first time that not only is this compound directly impairing artery function, it may also help explain the damage to the cardiovascular system that naturally occurs with age,” says Vienna Brunt, first author on the new study.
The researchers first examined a large cohort of healthy adults and found that TMAO blood levels increased in relation to age, regardless of heart or vascular health. In older adults the researchers saw a direct correlation between higher TMAO levels and worsening artery function.
In subsequent mouse studies the researchers found feeding young animals TMAO rapidly degraded vascular health. After several months of being fed TMAO the young animals’ vascular function effectively resembled that seen in very old mice.
The speeding up of age-related vascular decline through TMAO supplementation seen in the animal studies may explain a similar mechanism observed in humans. The researchers hypothesize increasing TMAO levels could play a role in the age-related decline of cardiovascular health in humans.
“Aging is the single greatest risk factor for cardiovascular disease, primarily as a result of oxidative stress to our arteries,” says Doug Seals, senior author on the study. “But what causes oxidative stress to develop in our arteries as we age? That has been the big unknown. This study identifies what could be a very important driver.”
The good news is that TMAO levels may be controllable either through dietary modifications or drugs that disrupt the production of the metabolites in the first place. Backing up prior research findings, the study affirmed dimethyl butanol, a compound found in olive oils and red wine, blocked the gut bacteria production of TMA.
The next steps for the research will be to begin homing in on compounds that block TMAO production in the hopes of developing an effective clinical therapy to prevent age-related vascular decline. In the short-term, the researchers suggest dietary interventions are the best way for people to maintain heart health in older age. And while plant-based meals won’t eliminate TMAO production altogether, dropping some red meat from a diet will certainly reduce one’s general levels of this damaging metabolite.
The new study was published in the journal Hypertension.
Source: University of Colorado Boulder