Betaine May Explain Why Exercise Benefits Health

Exercise is known to benefit health, yet scientists are still working to understand the reasons at the deepest molecular level. A new small-scale, long-term study may provide an important explanation: it identifies the metabolite betaine as a major contributor to exercise’s benefits.

Betaine is a small molecule present in foods including sugar beet and spinach. Although it has previously been associated with better health, it had not until now been tied to exercise.

A research team headed by scientists at Xuanwu Hospital, Capital Medical University, in China found that sustained exercise raises betaine levels in the body through the kidneys.

In addition, betaine can reproduce certain positive effects of exercise, most notably a slowing of biological ageing, or geroprotection. This molecule could potentially help people remain healthier for longer.

"This study gives us a fresh way to turn how our body works into something we can target with chemicals," says biophysicist Liu Guang-Hui, from the Chinese Academy of Sciences.

"It opens the door to geroprotective treatments that can tweak how multiple organs work together."

How exercise increases betaine

The researchers examined exercise’s effects in 13 healthy male volunteers. They used multi-omics, an approach that tracks changes at the body’s most fundamental levels, spanning genes, proteins, the immune system and small molecules such as betaine.

Following one 5-kilometre run, the team observed an intense but brief stress reaction. A month of consistent running, by contrast, produced more lasting improvements in several respects: less cellular ageing and damage, alongside a healthier gut microbiome and immune system.

The kidneys of these volunteers also emerged as a key finding, as they were generating substantially more betaine. Experiments in mice then showed that betaine inhibits an enzyme known as TBK1, which has already been associated with inflammation and ageing in the body.

Put another way, elevated betaine is not merely the result of regular, sustained exercise. These chemical increases actively underpin some of exercise’s advantages, particularly its anti-ageing effects.

"Our study delineated the molecular blueprint through which exercise reshapes human physiology, providing mechanistic insights into its health benefits," the researchers write in their published paper.

"The identified exercise-induced factors, including betaine, offer potential for developing 'exercise in a pill' to promote healthy aging."

Betaine and the prospect of geroprotective treatments

It is important to note that the researchers are not proposing that people will soon take pills in place of going to the gym. Many benefits of exercise were outside the scope of this research, including stronger muscles and improved mental health.

Nevertheless, betaine and the other biological changes identified in the study could guide the development of medicines designed to lower the risk of age-related disease and maintain the body in better condition. Such treatments might be relevant both for older people and for those unable to exercise for different reasons.

Considerably more research is required, involving far larger groups of people and much longer exercise periods. Even so, the finding that betaine plays a vital part offers a promising avenue for further investigation.

"This redefines 'exercise as medicine'," Guang-Hui says.

The research was published in Cell.