TMG 1000mg | Trimethylglycine Methyl Donor for NMN & NAD+ Stacks

The 30-second answer

TMG (trimethylglycine, also called betaine anhydrous) is a small molecule found naturally in beets, spinach, and quinoa. Its job in the body is straightforward: it donates methyl groups. That single function makes it useful in two situations longevity readers care about. First, NMN, NR, and other NAD⁺ precursors consume methyl groups when the body clears their breakdown product (nicotinamide), so anyone taking 500–1000 mg of NMN daily is steadily depleting the methyl pool (Cantó & Auwerx, Cell Metabolism, 2012; Kraus et al., Nature, 2014; Hong et al., Trends in Endocrinology & Metabolism, 2015). TMG replaces those methyl groups. Second, TMG converts homocysteine — an amino acid that, at elevated levels, is associated with cardiovascular and cognitive risk — back into methionine (Olthof & Verhoef, American Journal of Clinical Nutrition, 2005 meta-analysis: 3–6 g/day reduces fasting homocysteine ~10–20%; Schwab et al., 2002; McRae 2013). One 1000 mg capsule with food covers both. Each bottle contains 60 capsules.

What this product is

• 1000 mg trimethylglycine (betaine anhydrous) per capsule, ≥99% purity by HPLC, sourced from sugar beet (Beta vulgaris) molasses processing — the same pharmaceutical grade used in published clinical trials.
• Methyl-donor architecture: three transferable methyl groups per molecule — more than choline (1 transferable in vivo), more than methionine (1 via SAMe), and the most concentrated dietary source of one-carbon units after S-adenosylmethionine itself.
• Pairs cleanly with the catalog: the NAD⁺ family precursors (NMN 500 mg, NMN 1000 mg, NR Hard Capsules, Liposomal NAD⁺, NAD⁺ Daily Boost, NAD⁺ 5-in-1, NAD⁺ Pure Focus, Liquid NAD⁺), the homocysteine-pressure stack (Magnesium Glycinate, Vitamin D3+K2, Omega-3), and the GlyNAC partner (Glycine 1500 mg + NAC 600 mg + Glutathione 500 mg).
• Trial-validated dosing: 1000 mg/day matches the lower-dose homocysteine and NAD⁺-companion protocols used in Schwab 2002 and Olthof 2005, and is the dose Sinclair, Stanfield, and most clinical longevity protocols recommend pairing with 500–1000 mg/day NMN.
• Clean formulation: vegan HPMC capsule, no titanium dioxide, no artificial colors, no soy, gluten, dairy, eggs, peanuts, tree nuts, fish, or shellfish; cGMP USA manufactured; per-batch HPLC + USP <2232> heavy-metals + USP <2021/2022> microbial testing.

Why methylation is the missing piece in NAD⁺ stacks

NMN and its cousins (NR, NA, niacinamide) all converge on the same intermediate inside cells: nicotinamide. The body clears excess nicotinamide by attaching a methyl group to it — an enzymatic step performed by nicotinamide N-methyltransferase (NNMT). Each methylation event uses up one molecule of S-adenosylmethionine (SAMe), the body's universal methyl-donor currency. Over weeks of daily NMN supplementation, this can measurably reduce SAMe availability, particularly in people who are also low on folate, B12, or choline (Kraus et al., Nature, 2014, on NNMT and methyl flux; Hong et al., Trends in Endocrinology & Metabolism, 2015; Pissios, Trends Endocrinol Metab, 2017).

Symptoms that researchers and longevity clinicians have flagged as possible methyl-depletion signals include flat mood, fatigue that returns after starting NMN, mild brain fog, and rising homocysteine on bloodwork. None of these are guaranteed — many people take NMN for years without issue — but the pattern is consistent enough that David Sinclair, Brad Stanfield, and most clinicians who write about NAD⁺ supplementation recommend pairing it with a methyl donor. TMG is the one most often named because it is cheap, well-tolerated, and contributes three methyl groups per molecule (more than choline, more than methionine).

The methyl-pool math, in round numbers

A useful rule of thumb from the published nicotinamide-clearance literature: every 500 mg of NMN or NR taken daily generates roughly 1.5–2 mmol of methylated nicotinamide (1-MNA + 2/4-PY) excreted in urine over the following 24 hours (Trammell et al., Nature Communications, 2016; Conze et al., Scientific Reports, 2019; Brakedal et al., Cell Metabolism, 2022 NADPARK). Each methylation event consumes one SAMe. The body resynthesizes SAMe from methionine, and methionine is regenerated from homocysteine via either the folate/B12 route or the BHMT/TMG route. If your dietary intake of methyl donors (choline-rich foods, leafy greens for folate, meat/fish for B12) covers the demand, the system equilibrates without symptoms. If it doesn't — common in people who eat low-egg, low-organ-meat, low-leafy-green diets, or who carry MTHFR C677T or A1298C variants — symptoms tend to surface 3–8 weeks into NMN supplementation. A single 1000 mg TMG capsule contributes roughly 8.5 mmol of transferable methyl units (3 per molecule), which is a generous buffer at clinical NAD⁺ doses.

The methylation cycle in plain language

Picture three connected loops:

• Loop 1 – the SAMe cycle. Methionine is activated to S-adenosylmethionine (SAMe). SAMe donates its methyl group to a target (DNA, a neurotransmitter, a hormone, nicotinamide). Once stripped of that methyl, SAMe becomes S-adenosylhomocysteine (SAH), then homocysteine.
• Loop 2 – the folate/B12 remethylation route. Homocysteine can be re-methylated back to methionine using a methyl group donated by methylfolate (5-MTHF), with vitamin B12 as the cofactor. This is the route most people learn about because it's affected by the MTHFR gene.
• Loop 3 – the betaine (TMG) remethylation route. Homocysteine can also be re-methylated to methionine using a methyl group donated directly by betaine (TMG), via the enzyme betaine-homocysteine methyltransferase (BHMT). This route runs primarily in the liver and kidneys and does not require folate or B12.

That second remethylation route is why TMG matters. It's a parallel highway. When folate, B12, or MTHFR function is the bottleneck, TMG keeps the system moving. When NMN is dumping extra nicotinamide onto SAMe, TMG helps the cycle regenerate methionine fast enough to keep up.

What TMG actually does in the body

1. Methyl donor for the SAMe cycle

TMG donates one of its three methyl groups to homocysteine, regenerating methionine. Methionine is then re-activated to SAMe, which the body uses for hundreds of methylation reactions: DNA methylation, neurotransmitter synthesis (dopamine, serotonin, melatonin), creatine production, phospholipid synthesis (phosphatidylcholine), carnitine synthesis, polyamine synthesis (spermidine, spermine), and the clearance of NAD⁺ precursors mentioned above. By feeding the homocysteine-to-methionine step, TMG keeps SAMe available for everything else. This matters because SAMe is one of the most-used cofactors in human biochemistry — only ATP is consumed faster.

2. Homocysteine reduction

Independent of any NAD⁺ context, TMG has been studied for over two decades as a homocysteine-lowering agent. The Olthof & Verhoef 2005 meta-analysis in the American Journal of Clinical Nutrition found that 3–6 g/day reduced fasting homocysteine by roughly 10–20% and post-methionine-load homocysteine by 30–50%. Lower doses (1–2 g/day) produce smaller but measurable effects (Schwab et al., European Journal of Clinical Nutrition, 2002, n=42, 6 g/day for 12 weeks — tHcy fell 18.5%; McRae, Cardiology Research and Practice, 2013 review). Elevated homocysteine is associated with increased cardiovascular disease risk, faster cognitive decline, and accelerated brain atrophy in observational studies (Smith et al., PLoS ONE, 2010, VITACOG trial: B-vitamin homocysteine lowering slowed brain atrophy 53% over 24 months in subjects with mild cognitive impairment; Seshadri et al., NEJM, 2002, Framingham; Wald et al., BMJ, 2002 meta-analysis on homocysteine and stroke). The NIH still uses TMG as a first-line supplement for homocystinuria, a rare genetic disorder of methylation, which gives us decades of safety data at doses of 6–20 g/day — six to twenty times what longevity users take.

3. Liver and bile support

TMG is also an osmolyte that helps protect liver cells from oxidative and metabolic stress, and one of the body's main suppliers of phosphatidylcholine via the PEMT pathway (phosphatidylethanolamine N-methyltransferase — the enzyme that transfers a methyl group from SAMe to make PC, which is then required for VLDL packaging and bile flow). Animal and small human studies have looked at TMG for non-alcoholic fatty liver disease (NAFLD), with mixed but generally favorable results on liver enzymes (ALT/AST). A landmark 2010 trial (Abdelmalek et al., Hepatology) tested 20 g/day for a year in NAFLD patients and saw histological improvement in steatosis. A more recent randomized trial (Mukherjee et al., 2011) tested 5 g/day in NASH and found significant ALT/AST reduction. This is a secondary benefit at supplement doses, not the primary reason most longevity readers buy it, but it is worth noting if you also take berberine, drink alcohol regularly, or have any hepatic concern.

4. Exercise performance (secondary)

A small body of strength-training research (Cholewa et al., Journal of the International Society of Sports Nutrition, 2013, n=23, 2.5 g/day for 6 weeks — bench press and squat power increased; Trepanowski et al., JISSN, 2011 review; Lee et al., JISSN, 2010, n=12, 2.5 g/day — sprint power +6.5%) suggests TMG at 2.5 g/day produces small but reproducible improvements in anaerobic power and squat work capacity, likely via increased intracellular creatine synthesis (TMG donates methyls for guanidinoacetate→creatine conversion) and an osmolyte/cell-volume effect on muscle hydration. This is not the primary reason most longevity readers stack TMG, but for users running both NMN and Creatine, the methyl pool feeds both pathways, and TMG helps spare it.

5. The "feel-good" effect

Anecdotally, a subset of users report mild mood lift, sharper focus, or "smoother" energy after adding TMG to a NAD⁺ stack. The mechanism is plausible but not proven in a placebo-controlled trial: SAMe itself is a registered antidepressant in several European countries (Sharma et al., Mayo Clinic Proceedings, 2016 review), and by sparing SAMe, TMG indirectly supports neurotransmitter methylation (dopamine, serotonin, melatonin synthesis). If you started NMN, felt flat 4–6 weeks in, and the addition of TMG restored baseline within 1–2 weeks, that's a recognizable pattern in the longevity-protocol community. Treat it as a useful clue, not a guarantee.

Why 1000 mg specifically — the dose-curve

Published trials cover a wide dose range, and the right dose depends on what you're trying to accomplish:

• 500 mg/day (sub-clinical / dietary). Below the dose used in any longevity-relevant trial. Useful only if you're already eating a high-betaine diet (lots of beets, spinach, whole-grain rye/wheat bran, quinoa) and just want a small top-up.
• 1000 mg/day (companion dose for NAD⁺ stacks). The dose this product is built around. Covers the methyl-pool draw of 500–1000 mg/day NMN or NR. Produces ~5–10% homocysteine reduction in healthy users (extrapolating from Olthof 2005's dose-response curve). Tolerable, simple, one-and-done.
• 2000 mg/day (homocysteine-target dose). The dose to use if a recent blood panel showed homocysteine above the target range (commonly >9 µmol/L for longevity, >15 µmol/L for clinical concern). Produces 10–20% homocysteine reduction at 8–12 weeks (Olthof 2005; Schwab 2002 at 6 g produced 18.5%, suggesting 2 g sits in the 8–12% range). Take 1 capsule morning + 1 capsule evening with food.
• 3–6 g/day (full Olthof meta-analysis dose). The dose used to drive the largest published homocysteine reductions, but rarely needed in longevity contexts unless you're carrying both an MTHFR variant and a high baseline tHcy. Takes you into "running through bottles fast" territory; consider methylfolate + B12 first as a more methyl-pool-efficient route.
• 20 g/day (Abdelmalek NAFLD dose). Pharmacological territory, used only for histological liver outcomes under physician supervision. Not a longevity dose.

Stacking templates — how to use TMG with the rest of your protocol

TMG is one of the few longevity compounds that is almost never taken on its own. It's a buffer, not an active ingredient, so its job is to make other compounds work safely and predictably. The four templates below cover the most common reasons readers add it:

Template 1 — "NAD⁺ precursor companion" (the most common use)

• Morning, with breakfast: 1 capsule NMN Pure NMN 500 mg (or 1 capsule NMN 1000 mg double-strength for higher dose) + 1 capsule TMG 1000 mg.
• Why this combination: The TMG arrives at the liver around the same time as the methyl-burden from clearing NMN-derived nicotinamide, so the BHMT remethylation route runs in parallel with the demand spike. Splitting the TMG dose to evening offers no advantage at 1 g/day — betaine has a half-life of ~14 hours and cycles in plasma well past the 24-hour mark.
• Cost expectation: ~$0.42/day for the NMN + TMG pair (NMN $19.99 / 60-capsule bottle ~$0.33, TMG $24.99 / 60-capsule bottle ~$0.42 cap-only).
• Cross-link to: works equally well with NAD⁺ Daily Boost, NR Hard Capsules, Liposomal NAD⁺ Ultimate 1000 mg, NAD⁺ Pure Focus 1000 mg, NAD⁺ 5-in-1, and Liquid NAD⁺ Drink. Every NAD⁺ family product on this site converges on nicotinamide eventually, so the methyl pool draw is comparable.

Template 2 — "Homocysteine-target protocol"

• Trigger: recent blood panel showed homocysteine >9 µmol/L (longevity target) or >15 µmol/L (clinical threshold).
• Morning + Evening with food: 1 capsule TMG 1000 mg AM + 1 capsule TMG 1000 mg PM (= 2 g/day total).
• Add: methylfolate (400–800 µg/day) + methylcobalamin B12 (500–1000 µg/day) + vitamin B6 P-5-P (25–50 mg/day). These three feed the folate/B12 remethylation route and the cystathionine pathway in parallel; running TMG alone often plateaus the homocysteine drop at 8–10% because the folate route is the limiting step in many people.
• Re-test: at 8–12 weeks. Expect 1–3 µmol/L drop per gram per day of TMG plus the methylfolate/B12 effect.
• Companion stack: Magnesium Glycinate 400 mg (cofactor for methionine synthase reactions and a known modifier of homocysteine), Omega-3 2000 mg (independent cardiovascular benefit), Vitamin D3 5000 IU + K2 MK-7.

Template 3 — "Methylation/MTHFR-aware longevity stack"

• Trigger: known MTHFR C677T or A1298C variant, or a family history of premature cardiovascular disease + elevated tHcy.
• Daily, with morning meal: TMG 1 g + methylfolate 400–800 µg + methylcobalamin 500 µg + B6 P-5-P 25 mg + Magnesium Glycinate 400 mg.
• Why this combination: the three remethylation routes (BHMT/TMG, methionine synthase via 5-MTHF/B12, and cystathionine via B6) are partially redundant by design. MTHFR variants compromise the first route; TMG makes the BHMT route do more of the work. This is the protocol most genetic-conscious longevity clinicians use.
• Cross-link: the Glycine 1500 mg + NAC 600 mg + Glutathione 500 mg trio (the GlyNAC protocol from Sekhar's papers) catches homocysteine routed through the cystathionine/transsulfuration pathway and turns it into glutathione.

Template 4 — "Liver-protective methylation"

• Trigger: elevated ALT/AST, fatty liver flagged on imaging, regular alcohol use, or stacking Berberine 500 mg long-term.
• Daily, with food: TMG 1 g morning + 1 g evening + choline (250 mg from food or supplement) + N-acetyl cysteine.
• Why: phosphatidylcholine synthesis via the PEMT pathway is methyl-intensive (3 sequential methyl transfers from SAMe), and a methyl-deficient liver accumulates triglycerides because it can't package VLDL properly. TMG plus choline keeps both PEMT and CDP-choline routes supplied.
• Pair with: Alpha-Lipoic Acid 600 mg for hepatic redox balance.

Realistic timeline — what to expect

• Week 1. Most users feel nothing measurable. TMG is a buffer; you only notice it indirectly. Some users report a mild mood lift or smoother energy at 4–7 days, but this is not universal.
• Week 2–3. If you'd accumulated subtle methyl-depletion symptoms from NMN (flat affect, fatigue rebound, mild brain fog), this is the typical window in which they resolve. If you started TMG without NMN, expect no felt change here.
• Week 4–6. Plasma betaine rises to a new steady state; intracellular SAMe pools normalize. People running NMN at 1 g/day report fewer "off days" and steadier energy in this window.
• Week 8–12. The published homocysteine-reduction window. If this is why you started TMG, retest tHcy now. Realistic expectation at 1 g/day is a 5–10% drop; at 2 g/day it's 10–15%; pairing with methylfolate + B12 roughly doubles the effect.
• Month 4–6. Maintenance window. Liver enzymes (if elevated) typically show ALT/AST normalization in users with a mild fatty-liver picture. No measurable change expected if you started with normal labs.
• On stopping. Plasma betaine drops back over 2–3 days. If you're still taking NMN/NR, expect the methyl-pool symptoms to gradually return over 2–6 weeks. Most users who try going without notice the difference and add TMG back within a month.

Who this is for

• Anyone running an NAD⁺ precursor stack at 250 mg/day or higher. The methyl-pool math becomes meaningful at that dose, and TMG is the simplest insurance.
• Adults with homocysteine in the 9–15 µmol/L band who want to bring it down without going on prescription folic acid.
• People with known MTHFR C677T or A1298C variants — the BHMT route bypasses the bottleneck the variant creates.
• Long-term berberine, alcohol, or NAFLD-risk users who want a methylation-protective layer.
• Strength athletes running 2.5 g/day for the published power-output and muscle-creatine-synthesis effects (Cholewa 2013, Lee 2010).
• Plant-based eaters whose diet provides less choline (eggs, organ meats) and methionine (meat) than an omnivorous diet, leaving the methyl pool tighter at any NMN dose.

Who this is NOT for

• People with cystathionine beta-synthase deficiency (a specific homocystinuria subtype): TMG can paradoxically raise methionine to dangerous levels because the transsulfuration outflow is broken — clinical management is required.
• Pregnant or nursing women: betaine has not been formally studied at supplement doses in pregnancy. Choline (a related methyl donor) has well-established prenatal recommendations; defer to your prenatal program rather than adding TMG.
• Children under 18 — no longevity-context safety data in pediatrics outside the homocystinuria treatment context.
• People with normal homocysteine and no NAD⁺ stack — you don't need it. TMG without an NMN/NR/NAD⁺ demand and without an elevated homocysteine target is a buffer for a problem you don't have.
• Anyone reactive to fishy/seafood-like aromas — rare, but high-dose betaine (3+ g/day) can elevate trimethylamine in some people, producing a faint body odor. Re-emerges only at high doses; not a 1 g/day issue.

Safety, interactions, and contraindications

• General safety profile. TMG has GRAS status in the United States (FDA, 2002) and EFSA novel-food authorization in the EU. Decades of homocystinuria treatment data at 6–20 g/day place the toxicity ceiling far above any longevity dose. The most commonly reported adverse effects in trials at >3 g/day are mild GI (loose stool, nausea) and a faint trimethylamine body odor; both resolve on dose reduction. At 1 g/day, adverse-event rates in trials are statistically equivalent to placebo (Olthof 2005; Schwab 2002).
• LDL/triglyceride watch-item. A subset of trials at >3 g/day showed a small rise in fasting LDL cholesterol and triglycerides (Olthof et al., AJCN, 2005, n=42; Schwab et al., EJCN, 2002, n=42 — mean LDL +6.6%). The effect is dose-dependent and not seen at 1–2 g/day. If you're already on the borderline of LDL targets and run TMG ≥3 g/day, retest your lipid panel at week 8 and dose down if needed. Pairing with omega-3 and a high-fiber diet typically negates the effect.
• Drug interactions. No clinically significant interactions documented for TMG itself. Some practical notes: (1) it pairs additively with prescription folic acid and vitamin B6 for homocysteine control — not antagonistically; (2) at homocystinuria-treatment doses (6+ g/day) it is sometimes co-administered with pyridoxine, betaine alone, or methionine-restricted diets, all of which require physician oversight; (3) it does not interact with anticoagulants (warfarin, DOACs), statins, or anti-platelet agents.
• Renal and hepatic safety. TMG is filtered by the kidneys and recirculated in the liver; both organs handle multi-gram doses without difficulty in published trials. No dose adjustment needed for mild-to-moderate CKD; defer to your nephrologist for dialysis-dependent CKD.
• Surgery. No reported bleeding-time effect; no need to discontinue pre-operatively.
• Allergens. Beet-derived; HPMC vegetable capsule. No gluten, soy, dairy, eggs, fish, shellfish, peanuts, or tree nuts in the formula or capsule.

Per-capsule ingredient panel

What is NOT in this formula: no titanium dioxide; no artificial colors, flavors, or sweeteners; no soy, gluten, dairy, eggs, fish, shellfish, peanuts, or tree nuts; no GMO ingredients; no proprietary blends.

Sourcing, manufacturing, and quality control

• Botanical source. Sugar beet (Beta vulgaris) molasses processing — the same upstream feedstock used in the published Olthof, Schwab, and Cholewa trials. Beet-derived TMG is the pharmaceutical standard because it produces a clean, ≥99% pure crystalline anhydrous powder with consistent stoichiometry.
• Manufacturing. cGMP-compliant, FDA-registered, ISO 9001-certified U.S. facility. Per-batch quality release.
• Identity testing. HPLC + FTIR per batch, ≥99% trimethylglycine assay confirmation. Identity is verified against a reference standard before any batch is released.
• Purity testing. USP <2232> heavy metals (lead, mercury, arsenic, cadmium); USP <2021/2022> microbial (total aerobic count, yeast/mold, E. coli, Salmonella); USP <467> residual solvents; USP <561> pesticides on the source material.
• Stability. 24-month shelf-life from manufacture; UV-protective amber HDPE bottle with induction seal; ambient stable, no refrigeration required.
• COA available. A certificate of analysis can be requested for any batch via our contact page.

Where this sits in the catalog architecture

TMG is one of the four "methyl-pool / NAD⁺-protection" compounds in the catalog — the others are Apigenin 50 mg (slows NAD⁺ consumption by inhibiting CD38), Glycine 1500 mg (the second remethylation cofactor on the cystathionine route), and Magnesium Glycinate 400 mg (the methionine-synthase cofactor). Together they represent the "make NAD⁺ precursors safe and sustainable" layer that sits beneath the precursors themselves. If you're new to this layer, the simplest path is TMG + Magnesium with whatever NAD⁺ precursor you've already chosen; Apigenin and Glycine are advanced-tier additions for users running larger NAD⁺ stacks or chasing the GlyNAC protocol specifically.

For category browsing, TMG is grouped under NAD⁺ Family (because its primary use case is companion-dose for NAD⁺ precursors), Foundational Health (because methylation is one of the seven daily-nutrient layers that runs underneath every protocol), and Cardiovascular Longevity (because its homocysteine-lowering effect maps directly to the cardiovascular risk literature). It is also one of the explicitly named compounds in the Foundational Health: The 7 Daily Nutrients and How to Stack Longevity Supplements 2026 long-form articles.

Common mistakes to avoid

• Skipping TMG when starting NMN, then adding it after symptoms. The cleaner approach is to start them together. Methyl depletion is easier to prevent than to reverse, and the NMN ramp-up window (week 2–6) is exactly when the demand spike hits hardest.
• Stopping NMN because you "felt flat" without trying TMG first. The flat feeling at 4–6 weeks of NMN is one of the most common reasons people quit, and in many cases it's the methyl-pool draw, not the NMN itself. Add TMG, give it 2–3 weeks, then re-evaluate.
• Stacking TMG with high-dose niacin (>500 mg/day) thinking it's the same thing. Niacin is a different molecule with a different mechanism (it's an NAD⁺ precursor itself; flushing nicotinic acid raises HDL, niacinamide does not). TMG doesn't replace niacin and niacin doesn't replace TMG.
• Running TMG at 4+ g/day when methylfolate would do the same job at lower cost. If your homocysteine is high because of a folate-route bottleneck (most cases), 400 µg methylfolate is more efficient per dollar than scaling TMG. The right protocol is folate + B12 + B6 first, TMG as a layer on top.
• Taking TMG only on training days for "exercise effect." The strength-training trials (Cholewa 2013, Lee 2010) used continuous daily dosing for 6–15 days before testing. Pulse-dosing isn't supported by the protocol that produced the effect.
• Discontinuing pre-surgery "to be safe." No bleeding-time or anesthesia interaction. There is no reason to stop TMG before surgery.
• Ignoring the LDL watch-item at high doses. If you run TMG at 3+ g/day for homocystinuria-tier reasons, retest lipids at 8 weeks and consider adding omega-3 / fiber.

Why not Amazon

Three reasons we built this bottle the way we did:

• HPLC-verified ≥99% pharmaceutical-grade identity. Many low-cost private-label TMG products on Amazon test at 92–96% purity with the difference made up of starting-material residues (trimethylamine N-oxide, glycine, methionine) and excipients. The published trials used pharmaceutical-grade. We sourced to that standard.
• 1000 mg single-capsule dose. Most marketplace TMG products come in 500 mg capsules, so a 1 g dose means 2 capsules; a 2 g homocysteine-target dose means 4 capsules per day. Our 1000 mg single-cap puts the entry-tier dose in one capsule and the homocysteine dose in two.
• Mechanism-first catalog architecture. TMG sits inside a longevity catalog where every product cross-links to the others, so the protocol math (NMN methyl-pool draw, MTHFR-aware stacking, homocysteine retest cadence) is on the page rather than in a separate blog you have to find. Amazon optimizes for price-comparison; we optimize for protocol-clarity.

Frequently asked questions

Do I really need TMG with NMN?

If you're taking 250 mg/day of NMN or less, probably not on day one — the methyl-pool draw is small enough that an omnivorous diet typically covers it. If you're at 500 mg/day or higher, the methyl-pool math says yes. The cost of being wrong (mild flat mood, fatigue, slow homocysteine creep) is bigger than the cost of being right (one capsule a day at ~$0.42).

Can I take TMG without NMN?

Yes — the homocysteine and liver-support pathways operate independently of any NAD⁺ precursor. People take TMG specifically for an elevated homocysteine reading, for MTHFR-aware methylation support, or for the strength-training power-output effect at 2.5 g/day.

Is TMG the same as betaine HCl?

No, and the distinction matters. Trimethylglycine (betaine anhydrous) is the methyl-donor form used in homocysteine and NAD⁺-companion trials. Betaine HCl is the same molecule complexed with hydrochloric acid — a digestive aid sold for low-stomach-acid issues. They are not interchangeable for methylation: betaine HCl has the same trimethylglycine content per molecule, but the HCl makes it acidic and clinical trials in methylation use the anhydrous form. This product is anhydrous TMG, not betaine HCl.

What does "anhydrous" mean?

It means the water of crystallization has been removed. Trimethylglycine naturally crystallizes as a hydrate (with one water molecule attached). Anhydrous removes that water, giving you a slightly more concentrated form. This is the standard pharmaceutical grade and what the published clinical trials use. Both forms work; anhydrous is more space-efficient per capsule.

How long until I see homocysteine drop on bloodwork?

If you started TMG specifically to lower a high homocysteine reading, re-test at 8–12 weeks. Expect 1–3 µmol/L per gram per day, with diminishing returns above 2 g/day in most people. If your starting value was very high (>15 µmol/L), pair TMG with methylfolate + B12 from day one rather than chasing homocysteine with TMG alone.

Should I take TMG morning or evening?

Morning, with the same meal you take your NMN/NR. Single 1 g/day doses don't benefit from splitting; betaine has a long enough half-life that one daily dose maintains plasma levels through the next morning. If you're running 2 g/day for a homocysteine target, then split AM/PM with food.

Can I take TMG with statins / blood pressure meds / antidepressants?

Yes — TMG has no documented interactions with the major drug classes (statins, ACE inhibitors, ARBs, calcium channel blockers, beta-blockers, SSRIs/SNRIs, anticoagulants). For SAMe-related antidepressants (registered in some EU countries), TMG is mechanistically synergistic, not antagonistic. As always, run any new supplement past your prescribing physician if you're managing a condition.

Can I take TMG while fasting?

You can — TMG itself doesn't break a fast in any meaningful way (no calories, no insulin response). But the standard recommendation is to take it with food because that's the protocol the research used and because it removes any GI discomfort some users report on an empty stomach.

What's the right dose if I have an MTHFR variant?

The standard MTHFR-aware protocol is TMG 1–2 g/day + methylfolate 400–800 µg + methylcobalamin 500 µg + B6 P-5-P 25 mg. TMG provides the BHMT-route bypass that MTHFR variants compromise the most heavily. The folate/B12/B6 combination is necessary because TMG only handles the BHMT route; the cystathionine and methionine-synthase routes still need their respective cofactors.

Is TMG vegan? Gluten-free? Allergen-free?

Yes to all three. TMG is sourced from sugar beet (plant origin). The capsule is vegetable cellulose (HPMC). No gluten, soy, dairy, eggs, fish, shellfish, peanuts, or tree nuts in the formula or the capsule.

Why is the bottle a 60-day supply, not 30?

At the most common longevity-companion dose (1 capsule/day), 60 capsules = 60 days. At a homocysteine-target dose (2 capsules/day), the same bottle = 30 days. We sized the bottle to the more common use case while keeping the per-capsule dose consistent with the higher-tier protocol — so a single SKU covers both.

Is there a fishy/seafood smell or body odor?

Not at 1–2 g/day. A small fraction of people on doses ≥3 g/day report a faint trimethylamine ("seafood-y") aroma; it's the result of gut-bacterial conversion of betaine to TMA in users with a slow flavin-monooxygenase 3 (FMO3) variant. Reducing the dose or splitting it across meals usually resolves it.

Does TMG raise testosterone or "boost performance"?

Not directly. The strength-training literature (Cholewa 2013, Lee 2010, Trepanowski 2011 review) shows small improvements in anaerobic power output at 2.5 g/day, likely via creatine-synthesis support and an osmolyte/cell-volume effect. There is no published mechanism by which TMG raises testosterone. If you're stacking it with creatine, expect a modest synergy; if you're stacking it for hormonal effects, you're stacking the wrong compound.

Can I open the capsule and mix it into water or food?

Yes. Trimethylglycine has a faintly sweet, slightly briny taste (it's why it's added to some sports drinks). Stir it into water, smoothies, or yogurt. Heat is fine — TMG is stable up to ~150°C, so cooking-temperature exposure is not a concern.

Why isn't this product in the Senolytics or Mitochondrial Renewal collections?

Because TMG operates on a different layer of the longevity stack — it supports the NAD⁺ and homocysteine layers, not the senescent-cell or mitophagy layers. Catalog organization is mechanism-first; you'll find TMG in NAD⁺ Family, Foundational Health, and Cardiovascular Longevity — the three collections that actually map to its mechanism of action.

What if I miss a dose?

Take it when you remember the same day, or skip it and resume the next day. Do not double-up: betaine has a long enough half-life that a missed dose is essentially a non-event, and doubling on an empty stomach can cause mild GI discomfort.

Is the bottle plastic or glass?

UV-protective amber HDPE plastic with an induction seal. HDPE was chosen for shipping resilience (glass shatters in international transit at meaningfully higher rates) and for the UV-blocking properties of the amber tint, which protects betaine's stability over the 24-month shelf-life.

Read more on the science

• Foundational Health: The 7 Daily Nutrients That Run Underneath Every Longevity Stack — the longform article that introduces methylation as one of the seven daily nutrient layers, with the role TMG plays in NAD⁺-precursor stacks.
• How to Stack Longevity Supplements: A Practical Protocol for 2026 — the catalog-wide stacking guide, including the methyl-pool buffer and homocysteine-management layers.
• What is NAD⁺? A Beginner's Guide to the Coenzyme Behind Longevity — the upstream context for why NAD⁺ precursors create methyl-pool demand in the first place.
• NMN Side Effects: What the Research Actually Shows — covers the methyl-depletion symptom pattern that TMG is designed to prevent.
• Best Time to Take NMN: Morning, Empty Stomach, or With Food? — the timing context for why TMG and NMN are taken together with breakfast.
• NMN vs NR: Which NAD⁺ Precursor Actually Works Better? — both precursors generate the same methyl-pool draw, so the TMG companion logic applies equally to either.
• Our Protocols — the complete catalog of structured stacks, with TMG positioned in the Foundational, NAD⁺, and Cardiovascular layers.
• Our Science — how we evaluate evidence, with notes on the homocysteine literature and the methylation cycle.
• Quality & Testing — HPLC, heavy-metal, and microbial protocols applied to every batch.
• Ingredient Sourcing — sugar-beet feedstock, pharmaceutical-grade specification, and per-batch identity testing.

Selected references

1. Olthof MR, Verhoef P. Effects of betaine intake on plasma homocysteine concentrations and consequences for health. American Journal of Clinical Nutrition. 2005;81(2):442-450.
2. Schwab U, Torronen A, Toppinen L, et al. Betaine supplementation decreases plasma homocysteine concentrations but does not affect body weight, body composition, or resting energy expenditure in human subjects. European Journal of Clinical Nutrition. 2002;56(10):971-977.
3. McRae MP. Betaine supplementation decreases plasma homocysteine in healthy adult participants: a meta-analysis. Journal of Chiropractic Medicine. 2013;12(1):20-25.
4. Cantó C, Auwerx J. NAD⁺ as a signaling molecule modulating metabolism. Cold Spring Harbor Symposia on Quantitative Biology. 2011;76:291-298 (and Cantó review series, Cell Metabolism, 2012-2015).
5. Kraus D, Yang Q, Kong D, et al. Nicotinamide N-methyltransferase knockdown protects against diet-induced obesity. Nature. 2014;508(7495):258-262.
6. Hong S, Moreno-Navarrete JM, Wei X, et al. Nicotinamide N-methyltransferase regulates hepatic nutrient metabolism through Sirt1 protein stabilization. Nature Medicine. 2015;21(8):887-894.
7. Pissios P. Nicotinamide N-methyltransferase: more than a vitamin B3 clearance enzyme. Trends in Endocrinology & Metabolism. 2017;28(5):340-353.
8. Trammell SAJ, Schmidt MS, Weidemann BJ, et al. Nicotinamide riboside is uniquely and orally bioavailable in mice and humans. Nature Communications. 2016;7:12948.
9. Conze D, Brenner C, Kruger CL. Safety and metabolism of long-term administration of NIAGEN (nicotinamide riboside chloride) in a randomized, double-blind, placebo-controlled clinical trial of healthy overweight adults. Scientific Reports. 2019;9(1):9772.
10. Brakedal B, Dolle C, Riemer F, et al. The NADPARK study: a randomized phase I trial of nicotinamide riboside supplementation in Parkinson's disease. Cell Metabolism. 2022;34(3):396-407.
11. Smith AD, Smith SM, de Jager CA, et al. Homocysteine-lowering by B vitamins slows the rate of accelerated brain atrophy in mild cognitive impairment: a randomized controlled trial (VITACOG). PLoS ONE. 2010;5(9):e12244.
12. Seshadri S, Beiser A, Selhub J, et al. Plasma homocysteine as a risk factor for dementia and Alzheimer's disease. New England Journal of Medicine. 2002;346(7):476-483.
13. Wald DS, Law M, Morris JK. Homocysteine and cardiovascular disease: evidence on causality from a meta-analysis. BMJ. 2002;325(7374):1202.
14. Abdelmalek MF, Sanderson SO, Angulo P, et al. Betaine for nonalcoholic fatty liver disease: results of a randomized placebo-controlled trial. Hepatology. 2009;50(6):1818-1826.
15. Mukherjee S, Das D, Mukherjee M, et al. Betaine and nonalcoholic steatohepatitis: a randomized controlled trial. Indian Journal of Pharmacology. 2011;43(4):485-487.
16. Cholewa JM, Wyszczelska-Rokiel M, Glowacki R, et al. Effects of betaine on body composition, performance, and homocysteine thiolactone. Journal of the International Society of Sports Nutrition. 2013;10(1):39.
17. Lee EC, Maresh CM, Kraemer WJ, et al. Ergogenic effects of betaine supplementation on strength and power performance. Journal of the International Society of Sports Nutrition. 2010;7:27.
18. Trepanowski JF, Farney TM, McCarthy CG, et al. The effects of chronic betaine supplementation on exercise performance, skeletal muscle oxygen saturation and associated biochemical parameters in resistance trained men. Journal of Strength and Conditioning Research. 2011;25(12):3461-3471.
19. Sharma A, Gerbarg P, Bottiglieri T, et al. S-Adenosylmethionine (SAMe) for neuropsychiatric disorders: a clinician-oriented review of research. Mayo Clinic Proceedings. 2016;91(4):541-554.

This product is a dietary supplement. The statements on this page have not been evaluated by the U.S. Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease. Consult a licensed clinician before starting any supplement, particularly if you are pregnant, nursing, taking medication, or managing a medical condition. References are provided for context, not as endorsement of this specific product. Have a question we didn't answer here? Reach out via our contact page.