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Betaine Anhydrous (TMG): Benefits, Dosage, Side Effects & Science

Betaine anhydrous, also known as trimethylglycine (TMG), is a naturally occurring compound that donates methyl groups and helps cells manage fluid balance. It’s used clinically to manage very high homocysteine in rare genetic disorders and is popular in sports nutrition for potential strength and body‑composition benefits.

What Is Betaine Anhydrous (TMG)?

Betaine anhydrous, or Trimethylglycine (TMG), is a compound found naturally in beets, spinach, and shellfish. Structurally, it is the amino acid glycine with three methyl groups attached.

In the body, it serves two critical roles:

  1. Methyl Donor: It donates methyl groups to facilitate cellular processes (methylation).
  2. Osmolyte: It helps cells maintain hydration and structural integrity under stress.

Important Distinction: Supplement labels must read "Betaine Anhydrous" or "TMG." Do not confuse this with Betaine HCl, which is a stomach acid supplement used for digestion. They are not interchangeable.

How Betaine Works (Mechanism of Action)

TMG’s primary mechanism is lowering homocysteine, a potentially harmful amino acid, by donating a methyl group to convert it back into methionine. This supports the body's production of SAMe (S-adenosylmethionine), a universal methyl donor involved in neurotransmitter and DNA synthesis.

For athletes, TMG acts as an osmolyte, drawing water into muscle cells (similar to creatine). Research suggests this cellular hydration protects enzymes and proteins during high-intensity stress, potentially delaying fatigue and signaling muscle growth.

Key Benefits & Effects

1. Strength, Power & Muscular Endurance

While not a stimulant, TMG has shown consistent ergogenic effects in resistance-trained athletes. A systematic review in the Journal of Strength and Conditioning Research concluded that 2.5 g daily improves muscle endurance (volume) and power output.

  • The Sweet Spot: Benefits are most pronounced in squat/bench press volume and cycling sprint power.
  • Timeline: Unlike caffeine, it requires chronic loading. Effects typically appear after 1–2 weeks of supplementation.

2. Body Composition (Lean Mass)

Several trials have observed that betaine supplementation, combined with periodized weight training, may reduce fat mass and increase lean muscle mass. One landmark study found that subjects taking 2.5 g/day for 6 weeks improved body composition significantly more than placebo, potentially due to enhanced lipolysis (fat breakdown) and protein synthesis support.

3. Homocysteine & Heart Health

High levels of homocysteine are a risk factor for cardiovascular issues. TMG is clinically proven to lower fasting homocysteine levels by approximately 10–20% in healthy adults, serving as a "backup" methylation pathway when folate or B12 levels are suboptimal.

Effective Dosage (Latest Research)

Minimum Effective Dose

  • 1,000 mg (1 g) per day: This is sufficient to support general methylation and manage mild homocysteine elevations.

Optimal Dose for Performance

  • 2,500 mg (2.5 g) per day: This is the standard clinical dose for sports performance.
    • Protocol: Most successful studies split this into two doses of 1.25 g (e.g., morning and afternoon/pre-workout) to improve absorption and reduce gastrointestinal distress.

Upper Safe Dose

  • In healthy populations, doses up to 6 g/day appear safe.
  • Higher doses (up to 20 g) are used strictly under medical supervision for homocystinuria (a genetic disorder) but are not recommended for general supplementation due to side effects.

Best Timing for Maximum Results

  • Chronic Intake: Timing is secondary to consistency. TMG must build up in the system.
  • With Meals: Taking TMG with food helps minimize potential stomach upset.
  • Pre-Workout: Some athletes prefer taking half their daily dose 30–60 minutes pre-workout to maximize the "osmolyte" hydration effect during the session.

Synergistic Ingredients

  • Creatine: TMG helps the body synthesize creatine naturally. Stacking them ensures that the body's methylation resources aren't depleted by creating creatine, potentially offering a complementary power benefit.
  • B-Complex (Folate, B6, B12): Since these vitamins also manage homocysteine, combining them with TMG provides comprehensive methylation support.
  • Choline: TMG is a metabolite of choline. Ensuring adequate choline intake supports the same pathways.

Evidence Grade & Clinical Research Summary

Grade: B (Performance). While not as overwhelmingly proven as creatine (Grade A), Betaine Anhydrous has a solid, growing body of evidence supporting its use for muscle endurance and power in trained individuals at the 2.5 g dose.Grade: A (Homocysteine). The ability of TMG to lower homocysteine is a well-established biological fact.Grade: C (Fat Loss). While promising, body composition changes are often small and strictly dependent on rigorous exercise. It is not a "fat burner" in sedentary individuals.

Plain-English take: If you are an intermediate or advanced lifter looking to squeeze out a few extra reps or slightly improve power output, 2.5 g of TMG is a cheap, safe, and effective add-on. If you don't train hard, you likely won't notice physical changes.

Safety, Side Effects & Contraindications

  • Gastrointestinal Issues: Mild diarrhea, nausea, or indigestion can occur, especially if 2.5 g is taken all at once on an empty stomach. Fix: Split the dose and take with food.
  • Body Odor: In rare cases, TMG can cause a "fishy" body odor. This is due to the byproduct trimethylamine. It is harmless but socially inconvenient.
  • Cholesterol: Some long-term data suggests TMG may slightly increase total and LDL cholesterol. While the increase is usually small, individuals with existing lipid issues should monitor their blood work.
  • Kidney Disease: As an osmolyte that affects fluid balance, TMG should be used with caution by those with renal disease.

Frequently Asked Questions

How much TMG should I take per day?

For athletic performance and body composition, the research-backed dose is 2.5 grams (2,500 mg) per day. For general health/methylation, 1 gram is usually sufficient.

Is TMG the same as Betaine HCl?

No. TMG (Betaine Anhydrous) is for performance and methylation. Betaine HCl is an acid supplement for digestion. Do not mix them up.

How long does it take to see results?

For physical performance, allow 2 to 6 weeks of daily supplementation to saturate levels and allow training adaptations to occur.

Can I take TMG with Creatine?

Yes. They stack very well together. TMG may actually help the body synthesize and utilize creatine more efficiently by sparing methyl groups.