PAH carnitine deficiency can be treated with supplements: Study
Supplementing increased TMAO, which may increase atherogenesis risk
Oral carnitine supplements were well tolerated and blood levels of the molecule increased in people with pulmonary arterial hypertension (PAH), a pilot study shows.
Carnitine transports fatty acids — the building blocks of fatty molecules — into the cells’ powerhouses, the mitochondria, where they are broken down to produce energy. Some studies indicate PAH patients may have a carnitine deficiency, which can be linked to heart issues.
“Our study demonstrated the feasibility of carnitine supplementation in PAH and that relative carnitine deficiency may be rapidly overcome through this intervention,” the researchers wrote. Supplementation didn’t change measures of heart function, heart damage, and exercise capacity, however.
“Carnitine consumption and effect of oral supplementation in human pulmonary arterial hypertension: A pilot study,” was published as a research letter in Pulmonary Circulation.
PAH is a type of pulmonary hypertension caused by the narrowing of the pulmonary arteries, the blood vessels that supply the lungs. This leads to high blood pressure and may cause right heart failure, the most common cause of death among PAH patients. Metabolic abnormalities, including a deficiency in carnitine may occur with PAH.
Benefits of carnitine supplement
Based on research in mice and humans that showed benefits of carnitine supplementation in heart health, researchers at Vanderbilt University Medical Center conducted a pilot Phase 1 study (NCT04908397) to see if carnitine in the diet and supplements may increase its blood levels in PAH patients, and whether it can increase the breakdown of fat.
Nine adults with PAH had all their food and nutritional supplementation intake recorded on the first study visit, and underwent a six-minute walk test (6MWT) to measure exercise capacity. Twelve weeks later, the food diary was repeated and the patients had an echocardiography to assess heart health, and another 6MWT.
This was followed by carnitine supplementation (50 mg/kg per day) for two weeks. Blood samples were collected at the first study visit, 24 hours after carnitine supplements were started and again two weeks later. The 6MWT was performed a final time at the last visit.
Most participants had idiopathic, or unknown cause, PAH and were women with a mean age of 47.3. The time since their diagnosis was 7.9 years and all the participants had no to slight functional limitations (World Health Organization functional class 1 or 2), with relatively preserved right heart function.
Before taking carnitine, all the participants reported daily consumption of meat and/or seafood, which are sources of carnitine. Four participants used one or more non-carnitine supplements and one used a probiotic, which are live microorganisms ingested to alter the gastrointestinal flora to benefit health. Blood levels of carnitine remained constant during this period.
Carnitine levels increased among seven patients who completed the two-week supplementation (65.1 vs. 44 micromolar). In eight patients with available data, carnitine levels increased a day after starting supplementation (58.1 vs. 40.9 micromolar).
Supplementing with carnitine significantly increased levels of trimethylamine‐N‐oxide (TMAO), a molecule generated from carnitine that may increase the risk for plaque formation within blood vessels, called atherogenesis. This increase was most notable in three patients, while the others had minimal or no change.
Changes in TMAO may be associated with carnitine breakdown by specific gut microorganisms and may be treated, said the researchers, who noted consistent with this is the fact that the patient who took probiotics had a marked TMAO increase. The study’s sample size was too small to draw firm conclusions, however.
There were no significant changes in right heart function, in the levels of a biomarker of heart damage called NT‐proBNP, or in patients’ exercise capacity. Carnitine supplementation was well tolerated. One patient reported mild digestive symptoms.
“Further study is warranted to determine if carnitine supplementation may improve [right heart] function in PAH while monitoring for adverse events mediated through TMAO,” the researchers wrote.
About the Author
