Betaine: A supplement that mimics exercise benefits

Supplements
#1

Unlocking exercise’s anti-aging key: Betaine as first oral mimetic | EurekAlert!

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#2

For those interested in what form to take, I asked ChatGPT 5.

So which form is most likely to give the greatest exercise-mimetic + anti-inflammatory benefits?

Putting it together:

  1. Betaine anhydrous (trimethylglycine TMG)

  • Directly studied in:

  • Mechanistic rationale for being an exercise mimetic (TBK1 inhibition, homocysteine / methylation modulation, mitochondrial and metabolic adaptations) is built around this exact molecule.Frontiers+1

  • Doses used in studies commonly range from 2–6 g/day for 2–14 weeks.

  1. Betaine HCl

  • Evidence base focuses on hypochlorhydria and digestion, not systemic adaptations.PMC+1

  • At matched betaine doses, systemic effects should in theory be similar (since HCl dissociates), but in practice:

    • Doses are lower and taken with meals.

    • Trials have simply not measured the endpoints you care about (exercise-mimetic markers, systemic inflammation).

  1. Betaine nitrate
  • No RCTs isolating this form for performance or inflammation outcomes; expert review explicitly calls its current use “unjustified” based on the evidence.jn.nutrition.org
  • Any performance edge likely comes from the nitrate, which you could obtain just as well (and more cheaply / predictably) from established nitrate sources like beetroot juice.
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#3

This paper implies that betaine is a key factor in lifespan extension of several interventions on C. Elegans. Senolytics Enhance the Longevity of Caenorhabditis elegans by Altering Betaine Metabolism

Dosing doesn’t matter much, it’s effective at a broad range of doses.

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#4

I make a pre-workout mix that includes Betaine HCI.

#5

IMO: You should change from the HCL form to the Betaine anhydrous (trimethylglycine, “TMG”) unless you are using it fo digestive purposes.

1. The main forms of betaine

  1. Betaine anhydrous (trimethylglycine, “TMG”)

  • Neutral zwitterion; the form naturally present in food and tissues.

  • Almost all work on methylation, homocysteine, NAFLD, and inflammation uses this form (often just called “betaine”).MDPI+1

  1. Betaine hydrochloride (betaine HCl)

  • Betaine + HCl salt; designed as a gastric acid support for hypochlorhydria.

  • Human data primarily show it can transiently re-acidify the stomach; outcome measures are gastric pH and digestion, not systemic anti-inflammatory or performance endpoints.PMC+2PubMed+2

2. Evidence for exercise-mimetic / performance effects

2.1 Conceptual “exercise mimetic” evidence

  • A 2025 opinion piece in Frontiers in Pharmacology argues that betaine is a promising exercise mimetic, based on multi-omics work showing that long-term exercise in humans upregulates renal betaine metabolism and that betaine directly inhibits TBK1, reducing pro-inflammatory cytokines and cellular senescence markers in animal models.Frontiers
  • This work, and the underlying mechanistic literature, all refer to betaine itself (trimethylglycine), not betaine HCl or nitrate as special entities.

2.2 Human performance trials (by form)

Almost all sports-nutrition RCTs use betaine anhydrous:

  • Resistance training & performance in athletes

    • Multiple trials in strength-trained men and women, typically 2–2.5 g/day betaine anhydrous for 6–9 weeks, sometimes up to 5 g/day, show modest improvements in certain strength or power outcomes, though results are mixed.MDPI+1

Bottom line: Betaine anhydrous (trimethylglycine, “TMG”) is the form to use unless you are using it for hypochlorhydria and digestion.

#6

Sorry, I misspoke, I use trimethylglycine, “TMG”

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