Highlights
- Betaine might be the exercise in a bottle we need to slow down aging
- Betaine, also known as TrimethylGlycine (TMG) is a natural metabolite produced by the kidneys
- Scientists tested 13 men who undertook regular exercise for 25 days (running 5 km alternate days then everyday) with ‘multi-omic’ analysis
- After regular exercise their kidneys produced 70% more betaine
- Betaine binds to an blocked an enzyme called TBK1 which in turn reduced the a key pathway that leads to chronic inflammation, a leading cause of age-related diseases (‘inflammaging’)
What is betaine and what does it do?
Betaine or TrimethylGlycine (TMG) is a natural metabolite produced in the kidneys by the action of an enzyme called Choline Dehydrogenase (CHDH). One of its key functions is to donate its three methyl groups, which act as critical tags for a wide variety of cellular functions such as gene regulation, protein and lipid function and stability, energy metabolism to name a few. Betaine is available in supplement form and is taken by many to provide additional methyl groups for sustaining normal cellular functions. Natural food sources of Betaine include wheat bran and wheat germ, spinach and beets.
Evidence that Betaine might be exercise in a bottle
Researchers wanted to test the effect of long-term exercise on the human body after long-term exercise. So they tested to 13 somewhat sedentary men and had them run 5 kilometers, first every other day, and everyday soon thereafter for 25 days. They found that long-term exercise reduced markers of inflammation while short-term exercise increased inflammation.
Since chronic inflammation is a major cause of many of the age-related damages and diseases, the researchers then wanted to dig deeper into what changes occur in the body that led to reduced inflammation. After extensive analysis of their blood biomarkers, inflammatory factors, plasma proteins, metabolites, and gene expression, they found that that increase in Betaine production from the kidney’s, in response to long-term exercise can block inflammation.
In vitro and in vivo mouse studies confirmed Betaine’s ability to decrease inflammation and lower senescence biomarkers:
- Betaine blocks production of pro-inflammatory proteins IL-6 and TNF-α
- Reduces adhesion of immune cells that can cause inflammation
- Reduces aging biomarkers in mice: SA-β-Gal and p21
When aging mice were given 1% Betaine daily for 8-weeks, there were many signs of reversals of age-associated frailties:
- concentrations in the kidneys of aged mice increased to levels comparable to those induced by LE
- mice had significantly improved motor coordination, muscle strength and spatial memory ability, and significantly reduced depression-like behaviors
- Reduced markers of aging: SA-β-Gal and p21
- Reduced lipid deposition, and reduced fibrosis in the kidney, liver, lung, and skin. Also restoration of skeletal muscle and outer-skin (epidermis) architecture
- Inhibit the immune kinase TBK1 signaling pathway and reduce the proinflammatory cytokines TNF-α and IL-1β
- It also activated the AMPK/SIRT1/PGC-1α signaling pathway which is a sign of improved cellular energy metabolism and improved metabolic fitness
While this is a mouse study and it still needs to be confirmed in human studies, these findings suggest Betaine can mimic the effects of long-term exercise and act to reverse age-associated changes in the body.
Dobrijević, D., et. al., Betaine as a Functional Ingredient: Metabolism, Health-Promoting Attributes, Food Sources, Applications and Analysis Methods. Molecules. 2023 Jun 17;28(12):4824.https://doi.org/10.3390/molecules28124824
Liu, Y., et.al., Betaine: a promising novel anti-aging substance as an exercise mimetic. Front Pharmacol. 2025 Aug 28;16:1672934. https://doi.org/10.3389/fphar.2025.1672934
Geng, L., et.al., Systematic profiling reveals betaine as an exercise mimetic for geroprotection. Cell. 2025 Sep 18;188(19):5403-5425.e33. https://doi.org/10.1016/j.cell.2025.06.001