Lonza takes issue with warning about L-carnitine metabolite

By Hank Schultz

- Last updated on GMT

©Getty Images - Kittiya
©Getty Images - Kittiya

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Swiss L-carnitine supplier Lonza has said focus on a lone metabolite that has a poorly understood relation to cardiovascular disease presents an incomplete picture of the benefits of the ingredient. The warning about the metabolite figured into a recently published review of L-carnitine studies.

The recent review of studies done with L-carnitine concluded that longer term supplementation is probably required for best results.  But the authors said long term use of the ingredient could also raise levels of TMAO (trimethylamine N-oxide), a compound possibly implicated in cardiovascular disease.

The review was published in the Journal of the International Society of Sports Nutrition. ​ The review as put together by researchers from Poland and Italy.

L-carnitine is an amino acid produced in the body that helps turn fat into energy. It has been studied as a ‘fat burner,’ to increase performance, speed recovery and to help fight sarcopenia. The researchers took each of these end points in turn to see what evidence backs L-carnitine for these uses.

In the commercial market, Lonza with its Carnipure ingredient has a dominant position​, but is getting increasing competition from Chinese suppliers.

Review finds range of effects supported by data

The study design called for a search on the PubMed and Web of Science databases.  In all, 1,295 studies were identified.  The researchers were looking for studies of at least 12 weeks duration that were done on healthy subjects with no other supplement ingredients included and no use of drugs. After removing duplicates and applying the eligibility criteria, only 11 clinical trials done in humans cleared the eligibility bar. 

The researchers found some evidence to support the use of carnitine increased muscle carnitine content and alters muscle fuel metabolism during exercise in humans as well as restricting fat accumulation.  The review noted that one study found good results for L-carnitine  supplementation for obese subjects, though these effects seemed restricted to the truly obese and were muted in subjects with lower BMIs.

The evidence for L-carnitine supplementation in weight training is mostly conflicting, the authors said.  Studies have in general not found a strength boost with L-carnitine supplementation, with the exception of lower body strength. 

Some of the strongest evidence for the use of the ingredient comes from its effects in sarcopenia. L-carnitine has been shown to increase fat free mass and reduce total body fat mass in centenarians​. 

L-carnitine supplementation has also been shown to reduce muscle soreness post exercise, the authors said. 

Going to the dark side

The ‘dark side’ of the L-carnitine picture has to do with increased levels of, TMAO in the blood following supplementation with the ingredient, the authors said. TMAO is a metabolite that arises from the digestion of red meat which is also the richest source of L-carnitine.  TMAO has been associated with an increased risk for a number of diseases.

According a Harvard Medical School publication from 2019​, “Three recent analyses have linked high blood levels of TMAO with a higher risk for both cardiovascular disease and early death from any cause. In one of those studies, researchers found that people with higher levels of TMAO in their blood may have more than twice the risk of heart attack, stroke, or other serious cardiovascular problems, compared with people who have lower levels. Other studies have found links between high TMAO levels and heart failure and chronic kidney disease.”

The authors concluded that the best results from L-carnitine supplementation seem to come from longer term use of at least three months, because of the ingredient’s low bioavailability.  But longer term use also raises TMAO levels, they said, which they characterized as a Gordian knot future research will need to untangle.

“It is also clear that prolonged LC (L-carnitine) supplementation elevates fasting plasma TMAO, a compound supposed to be pro-atherogenic. Therefore, additional studies focusing on long-term supplementation and its longitudinal effect on the TMAO metabolism and cardiovascular system are needed,”​ they concluded.

Supplier disputes warning on TMAO

Lonza, a major supplier of L-carnitine in the form of its Carnipure ingredient, disputed the dire nature of the researchers’ warnings about TMAO, noting that its ingredient has been used in supplements for years without ill effects. The jury is out on the import TMAO levels, said Aouatef Bellamine, PhD, Lonza’s senior science manager. The firm’s view is laid out in a review paper authored by Bellamine and experts from a Spanish institution and German nutrition consulting firm. 

The paper, titled Trimethylamine N-Oxide in Relation to Cardiometabolic Health—Cause or Effect?, ​was published in May of this year in the journal Nutrients. ​While elevated TMAO levels are observed in some disease conditions, whether this is a causative situation or is part of a feedback loop is unclear, the authors argue.  TMAO is the oxidation product of trimethylamine, a molecule formed by bacteria in the colon from L-carnitine and other sources. Thus, TMAO is part of a complicated biochemical pathway and focusing on levels of the molecule in isolation as a red flag for cardiovascular disease may present an incomplete picture, they said.  

Increases in TMAO levels during CVD/T2D progression (beyond the observed wide natural interindividual variability in TMAO levels) could be the result of disease-related dysbiosis. Another factor in such variability is related to the methodology itself. Indeed, most studies reported plasma TMAO only without considering TMA or urinary secretion. Perhaps it would be more relevant toconsider the plasma TMA/TMAO ratio as a marker,”​ the authors wrote.

“In conclusion, increased TMAO levels may be a compensatory mechanism in response to disease. Further research and intervention studies with relatively low levels of TMAO may be needed to confirm this theory,”​ they added.

Source: Journal of the International Society of Sports Nutrition
17, Article number: 49 (2020)
The bright and the dark sides of L-carnitine supplementation: a systematic review
Authors: Sawicka AK, Renzi G, Olek RA

DOI: 10.3390/nu12051330
Trimethylamine N-Oxide in Relation to Cardiometabolic Health—Cause or Effect?
Authors: Papandreou C, Moré M, Bellamine A

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