{"product_id":"tmg-1000mg-trimethylglycine-methyl-donor-for-nmn-nad-stacks","title":"TMG 1000mg | Trimethylglycine Methyl Donor for NMN \u0026 NAD+ Stacks","description":"\u003ch2\u003eThe 30-second answer\u003c\/h2\u003e\n\u003cp\u003eTMG (trimethylglycine, also called \u003cem\u003ebetaine anhydrous\u003c\/em\u003e) 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\u003csup\u003e+\u003c\/sup\u003e 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 \u0026amp; Auwerx, \u003cem\u003eCell Metabolism\u003c\/em\u003e, 2012; Kraus et al., \u003cem\u003eNature\u003c\/em\u003e, 2014; Hong et al., \u003cem\u003eTrends in Endocrinology \u0026amp; Metabolism\u003c\/em\u003e, 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 \u0026amp; Verhoef, \u003cem\u003eAmerican Journal of Clinical Nutrition\u003c\/em\u003e, 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.\u003c\/p\u003e\n\n\u003ch3\u003eWhat this product is\u003c\/h3\u003e\n\u003cul\u003e\n\u003cli\u003e\n\u003cstrong\u003e1000 mg trimethylglycine (betaine anhydrous)\u003c\/strong\u003e per capsule, ≥99% purity by HPLC, sourced from sugar beet (\u003cem\u003eBeta vulgaris\u003c\/em\u003e) molasses processing — the same pharmaceutical grade used in published clinical trials.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eMethyl-donor architecture:\u003c\/strong\u003e 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.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003ePairs cleanly with the catalog:\u003c\/strong\u003e the NAD\u003csup\u003e+\u003c\/sup\u003e family precursors (NMN 500 mg, NMN 1000 mg, NR Hard Capsules, Liposomal NAD\u003csup\u003e+\u003c\/sup\u003e, NAD\u003csup\u003e+\u003c\/sup\u003e Daily Boost, NAD\u003csup\u003e+\u003c\/sup\u003e 5-in-1, NAD\u003csup\u003e+\u003c\/sup\u003e Pure Focus, Liquid NAD\u003csup\u003e+\u003c\/sup\u003e), the homocysteine-pressure stack (Magnesium Glycinate, Vitamin D3+K2, Omega-3), and the GlyNAC partner (Glycine 1500 mg + NAC 600 mg + Glutathione 500 mg).\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eTrial-validated dosing:\u003c\/strong\u003e 1000 mg\/day matches the lower-dose homocysteine and NAD\u003csup\u003e+\u003c\/sup\u003e-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.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eClean formulation:\u003c\/strong\u003e 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 \u0026lt;2232\u0026gt; heavy-metals + USP \u0026lt;2021\/2022\u0026gt; microbial testing.\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003ch2\u003eWhy methylation is the missing piece in NAD\u003csup\u003e+\u003c\/sup\u003e stacks\u003c\/h2\u003e\n\u003cp\u003eNMN 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., \u003cem\u003eNature\u003c\/em\u003e, 2014, on NNMT and methyl flux; Hong et al., \u003cem\u003eTrends in Endocrinology \u0026amp; Metabolism\u003c\/em\u003e, 2015; Pissios, \u003cem\u003eTrends Endocrinol Metab\u003c\/em\u003e, 2017).\u003c\/p\u003e\n\n\u003cp\u003eSymptoms 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\u003csup\u003e+\u003c\/sup\u003e 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).\u003c\/p\u003e\n\n\u003ch3\u003eThe methyl-pool math, in round numbers\u003c\/h3\u003e\n\u003cp\u003eA 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., \u003cem\u003eNature Communications\u003c\/em\u003e, 2016; Conze et al., \u003cem\u003eScientific Reports\u003c\/em\u003e, 2019; Brakedal et al., \u003cem\u003eCell Metabolism\u003c\/em\u003e, 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\u003csup\u003e+\u003c\/sup\u003e doses.\u003c\/p\u003e\n\n\u003ch2\u003eThe methylation cycle in plain language\u003c\/h2\u003e\n\u003cp\u003ePicture three connected loops:\u003c\/p\u003e\n\u003cul\u003e\n\u003cli\u003e\n\u003cstrong\u003eLoop 1 – the SAMe cycle.\u003c\/strong\u003e 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.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eLoop 2 – the folate\/B12 remethylation route.\u003c\/strong\u003e 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.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eLoop 3 – the betaine (TMG) remethylation route.\u003c\/strong\u003e 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.\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003cp\u003eThat 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.\u003c\/p\u003e\n\n\u003ch2\u003eWhat TMG actually does in the body\u003c\/h2\u003e\n\u003ch3\u003e1. Methyl donor for the SAMe cycle\u003c\/h3\u003e\n\u003cp\u003eTMG 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\u003csup\u003e+\u003c\/sup\u003e 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.\u003c\/p\u003e\n\n\u003ch3\u003e2. Homocysteine reduction\u003c\/h3\u003e\n\u003cp\u003eIndependent of any NAD\u003csup\u003e+\u003c\/sup\u003e context, TMG has been studied for over two decades as a homocysteine-lowering agent. The Olthof \u0026amp; Verhoef 2005 meta-analysis in the \u003cem\u003eAmerican Journal of Clinical Nutrition\u003c\/em\u003e 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., \u003cem\u003eEuropean Journal of Clinical Nutrition\u003c\/em\u003e, 2002, n=42, 6 g\/day for 12 weeks — tHcy fell 18.5%; McRae, \u003cem\u003eCardiology Research and Practice\u003c\/em\u003e, 2013 review). Elevated homocysteine is associated with increased cardiovascular disease risk, faster cognitive decline, and accelerated brain atrophy in observational studies (Smith et al., \u003cem\u003ePLoS ONE\u003c\/em\u003e, 2010, VITACOG trial: B-vitamin homocysteine lowering slowed brain atrophy 53% over 24 months in subjects with mild cognitive impairment; Seshadri et al., \u003cem\u003eNEJM\u003c\/em\u003e, 2002, Framingham; Wald et al., \u003cem\u003eBMJ\u003c\/em\u003e, 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.\u003c\/p\u003e\n\n\u003ch3\u003e3. Liver and bile support\u003c\/h3\u003e\n\u003cp\u003eTMG 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., \u003cem\u003eHepatology\u003c\/em\u003e) 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.\u003c\/p\u003e\n\n\u003ch3\u003e4. Exercise performance (secondary)\u003c\/h3\u003e\n\u003cp\u003eA small body of strength-training research (Cholewa et al., \u003cem\u003eJournal of the International Society of Sports Nutrition\u003c\/em\u003e, 2013, n=23, 2.5 g\/day for 6 weeks — bench press and squat power increased; Trepanowski et al., \u003cem\u003eJISSN\u003c\/em\u003e, 2011 review; Lee et al., \u003cem\u003eJISSN\u003c\/em\u003e, 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.\u003c\/p\u003e\n\n\u003ch3\u003e5. The \"feel-good\" effect\u003c\/h3\u003e\n\u003cp\u003eAnecdotally, a subset of users report mild mood lift, sharper focus, or \"smoother\" energy after adding TMG to a NAD\u003csup\u003e+\u003c\/sup\u003e 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., \u003cem\u003eMayo Clinic Proceedings\u003c\/em\u003e, 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.\u003c\/p\u003e\n\n\u003ch2\u003eWhy 1000 mg specifically — the dose-curve\u003c\/h2\u003e\n\u003cp\u003ePublished trials cover a wide dose range, and the right dose depends on what you're trying to accomplish:\u003c\/p\u003e\n\u003cul\u003e\n\u003cli\u003e\n\u003cstrong\u003e500 mg\/day (sub-clinical \/ dietary).\u003c\/strong\u003e 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.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003e1000 mg\/day (companion dose for NAD\u003csup\u003e+\u003c\/sup\u003e stacks).\u003c\/strong\u003e 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.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003e2000 mg\/day (homocysteine-target dose).\u003c\/strong\u003e The dose to use if a recent blood panel showed homocysteine above the target range (commonly \u0026gt;9 µmol\/L for longevity, \u0026gt;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.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003e3–6 g\/day (full Olthof meta-analysis dose).\u003c\/strong\u003e 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.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003e20 g\/day (Abdelmalek NAFLD dose).\u003c\/strong\u003e Pharmacological territory, used only for histological liver outcomes under physician supervision. Not a longevity dose.\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003ch2\u003eStacking templates — how to use TMG with the rest of your protocol\u003c\/h2\u003e\n\u003cp\u003eTMG 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:\u003c\/p\u003e\n\n\u003ch3\u003eTemplate 1 — \"NAD\u003csup\u003e+\u003c\/sup\u003e precursor companion\" (the most common use)\u003c\/h3\u003e\n\u003cul\u003e\n\u003cli\u003e\n\u003cstrong\u003eMorning, with breakfast:\u003c\/strong\u003e 1 capsule NMN \u003ca href=\"\/he\/products\/pure-nmn-500mg-60-capsules-30-day-supply\"\u003ePure NMN 500 mg\u003c\/a\u003e (or 1 capsule \u003ca href=\"\/he\/products\/nmn-1000mg-double-strength-60-capsules-30-day-supply\"\u003eNMN 1000 mg double-strength\u003c\/a\u003e for higher dose) + 1 capsule TMG 1000 mg.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eWhy this combination:\u003c\/strong\u003e 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.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eCost expectation:\u003c\/strong\u003e ~$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).\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eCross-link to:\u003c\/strong\u003e works equally well with \u003ca href=\"\/he\/products\/new-nad-hard-capsules-daily-nad-boost-for-energy-longevity\"\u003eNAD\u003csup\u003e+\u003c\/sup\u003e Daily Boost\u003c\/a\u003e, \u003ca href=\"\/he\/products\/rb-nicotinamide-nucleotide-nad-hard-capsules-cellular-energy-anti-aging\"\u003eNR Hard Capsules\u003c\/a\u003e, \u003ca href=\"\/he\/products\/liposomal-nad-ultimate-1000mg\"\u003eLiposomal NAD\u003csup\u003e+\u003c\/sup\u003e Ultimate 1000 mg\u003c\/a\u003e, \u003ca href=\"\/he\/products\/zoone-nad-1000mg-pure-focus-formula\"\u003eNAD\u003csup\u003e+\u003c\/sup\u003e Pure Focus 1000 mg\u003c\/a\u003e, \u003ca href=\"\/he\/products\/selerb-nad-5-in-1-complete-mitochondrial-formula\"\u003eNAD\u003csup\u003e+\u003c\/sup\u003e 5-in-1\u003c\/a\u003e, and \u003ca href=\"\/he\/products\/liquid-nad-anti-aging-drink-advanced-cellular-rejuvenation\"\u003eLiquid NAD\u003csup\u003e+\u003c\/sup\u003e Drink\u003c\/a\u003e. Every NAD\u003csup\u003e+\u003c\/sup\u003e family product on this site converges on nicotinamide eventually, so the methyl pool draw is comparable.\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003ch3\u003eTemplate 2 — \"Homocysteine-target protocol\"\u003c\/h3\u003e\n\u003cul\u003e\n\u003cli\u003e\n\u003cstrong\u003eTrigger:\u003c\/strong\u003e recent blood panel showed homocysteine \u0026gt;9 µmol\/L (longevity target) or \u0026gt;15 µmol\/L (clinical threshold).\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eMorning + Evening with food:\u003c\/strong\u003e 1 capsule TMG 1000 mg AM + 1 capsule TMG 1000 mg PM (= 2 g\/day total).\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eAdd:\u003c\/strong\u003e 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.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eRe-test:\u003c\/strong\u003e at 8–12 weeks. Expect 1–3 µmol\/L drop per gram per day of TMG plus the methylfolate\/B12 effect.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eCompanion stack:\u003c\/strong\u003e \u003ca href=\"\/he\/products\/magnesium-glycinate-400mg-sleep-and-nad-methylation\"\u003eMagnesium Glycinate 400 mg\u003c\/a\u003e (cofactor for methionine synthase reactions and a known modifier of homocysteine), \u003ca href=\"\/he\/products\/omega-3-fish-oil-2000mg-epa-dha\"\u003eOmega-3 2000 mg\u003c\/a\u003e (independent cardiovascular benefit), \u003ca href=\"\/he\/products\/vitamin-d3-5000-iu-k2-mk-7-100mcg\"\u003eVitamin D3 5000 IU + K2 MK-7\u003c\/a\u003e.\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003ch3\u003eTemplate 3 — \"Methylation\/MTHFR-aware longevity stack\"\u003c\/h3\u003e\n\u003cul\u003e\n\u003cli\u003e\n\u003cstrong\u003eTrigger:\u003c\/strong\u003e known MTHFR C677T or A1298C variant, or a family history of premature cardiovascular disease + elevated tHcy.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eDaily, with morning meal:\u003c\/strong\u003e TMG 1 g + methylfolate 400–800 µg + methylcobalamin 500 µg + B6 P-5-P 25 mg + Magnesium Glycinate 400 mg.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eWhy this combination:\u003c\/strong\u003e 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.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eCross-link:\u003c\/strong\u003e the \u003ca href=\"\/he\/products\/glycine-1500mg-glynac-partner-glutathione-sleep-longevity\"\u003eGlycine 1500 mg\u003c\/a\u003e + \u003ca href=\"\/he\/products\/n-acetyl-cysteine-600mg-nac-glutathione-precursor-for-antioxidant-longevity-support\"\u003eNAC 600 mg\u003c\/a\u003e + \u003ca href=\"\/he\/products\/glutathione-500mg-maximum-strength\"\u003eGlutathione 500 mg\u003c\/a\u003e trio (the GlyNAC protocol from Sekhar's papers) catches homocysteine routed through the cystathionine\/transsulfuration pathway and turns it into glutathione.\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003ch3\u003eTemplate 4 — \"Liver-protective methylation\"\u003c\/h3\u003e\n\u003cul\u003e\n\u003cli\u003e\n\u003cstrong\u003eTrigger:\u003c\/strong\u003e elevated ALT\/AST, fatty liver flagged on imaging, regular alcohol use, or stacking \u003ca href=\"\/he\/products\/berberine-hcl-500mg-maximum-strength\"\u003eBerberine 500 mg\u003c\/a\u003e long-term.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eDaily, with food:\u003c\/strong\u003e TMG 1 g morning + 1 g evening + choline (250 mg from food or supplement) + N-acetyl cysteine.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eWhy:\u003c\/strong\u003e 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.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003ePair with:\u003c\/strong\u003e \u003ca href=\"\/he\/products\/alpha-lipoic-acid-600mg-universal-antioxidant\"\u003eAlpha-Lipoic Acid 600 mg\u003c\/a\u003e for hepatic redox balance.\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003ch2\u003eRealistic timeline — what to expect\u003c\/h2\u003e\n\u003cul\u003e\n\u003cli\u003e\n\u003cstrong\u003eWeek 1.\u003c\/strong\u003e 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.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eWeek 2–3.\u003c\/strong\u003e 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.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eWeek 4–6.\u003c\/strong\u003e 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.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eWeek 8–12.\u003c\/strong\u003e 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.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eMonth 4–6.\u003c\/strong\u003e 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.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eOn stopping.\u003c\/strong\u003e 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.\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003ch2\u003eWho this is for\u003c\/h2\u003e\n\u003cul\u003e\n\u003cli\u003e\n\u003cstrong\u003eAnyone running an NAD\u003csup\u003e+\u003c\/sup\u003e precursor stack at 250 mg\/day or higher.\u003c\/strong\u003e The methyl-pool math becomes meaningful at that dose, and TMG is the simplest insurance.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eAdults with homocysteine in the 9–15 µmol\/L band\u003c\/strong\u003e who want to bring it down without going on prescription folic acid.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003ePeople with known MTHFR C677T or A1298C variants\u003c\/strong\u003e — the BHMT route bypasses the bottleneck the variant creates.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eLong-term berberine, alcohol, or NAFLD-risk users\u003c\/strong\u003e who want a methylation-protective layer.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eStrength athletes\u003c\/strong\u003e running 2.5 g\/day for the published power-output and muscle-creatine-synthesis effects (Cholewa 2013, Lee 2010).\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003ePlant-based eaters\u003c\/strong\u003e whose diet provides less choline (eggs, organ meats) and methionine (meat) than an omnivorous diet, leaving the methyl pool tighter at any NMN dose.\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003ch2\u003eWho this is NOT for\u003c\/h2\u003e\n\u003cul\u003e\n\u003cli\u003e\n\u003cstrong\u003ePeople with cystathionine beta-synthase deficiency\u003c\/strong\u003e (a specific homocystinuria subtype): TMG can paradoxically raise methionine to dangerous levels because the transsulfuration outflow is broken — clinical management is required.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003ePregnant or nursing women\u003c\/strong\u003e: 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.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eChildren under 18\u003c\/strong\u003e — no longevity-context safety data in pediatrics outside the homocystinuria treatment context.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003ePeople with normal homocysteine and no NAD\u003csup\u003e+\u003c\/sup\u003e stack\u003c\/strong\u003e — you don't need it. TMG without an NMN\/NR\/NAD\u003csup\u003e+\u003c\/sup\u003e demand and without an elevated homocysteine target is a buffer for a problem you don't have.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eAnyone reactive to fishy\/seafood-like aromas\u003c\/strong\u003e — 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.\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003ch2\u003eSafety, interactions, and contraindications\u003c\/h2\u003e\n\u003cul\u003e\n\u003cli\u003e\n\u003cstrong\u003eGeneral safety profile.\u003c\/strong\u003e 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 \u0026gt;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).\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eLDL\/triglyceride watch-item.\u003c\/strong\u003e A subset of trials at \u0026gt;3 g\/day showed a small rise in fasting LDL cholesterol and triglycerides (Olthof et al., \u003cem\u003eAJCN\u003c\/em\u003e, 2005, n=42; Schwab et al., \u003cem\u003eEJCN\u003c\/em\u003e, 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.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eDrug interactions.\u003c\/strong\u003e 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.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eRenal and hepatic safety.\u003c\/strong\u003e 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.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eSurgery.\u003c\/strong\u003e No reported bleeding-time effect; no need to discontinue pre-operatively.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eAllergens.\u003c\/strong\u003e Beet-derived; HPMC vegetable capsule. No gluten, soy, dairy, eggs, fish, shellfish, peanuts, or tree nuts in the formula or capsule.\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003ch2\u003ePer-capsule ingredient panel\u003c\/h2\u003e\n\u003ctable style=\"border-collapse: collapse; width: 100%;\"\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth style=\"border: 1px solid #ccc; padding: 6px 10px; text-align: left;\"\u003eIngredient\u003c\/th\u003e\n\u003cth style=\"border: 1px solid #ccc; padding: 6px 10px; text-align: left;\"\u003ePer capsule\u003c\/th\u003e\n\u003cth style=\"border: 1px solid #ccc; padding: 6px 10px; text-align: left;\"\u003eSpecification\u003c\/th\u003e\n\u003c\/tr\u003e\n\u003c\/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd style=\"border: 1px solid #ccc; padding: 6px 10px;\"\u003eTrimethylglycine (Betaine Anhydrous)\u003c\/td\u003e\n\u003ctd style=\"border: 1px solid #ccc; padding: 6px 10px;\"\u003e1000 mg\u003c\/td\u003e\n\u003ctd style=\"border: 1px solid #ccc; padding: 6px 10px;\"\u003e≥99% by HPLC, beet-derived (\u003cem\u003eBeta vulgaris\u003c\/em\u003e), pharmaceutical grade\u003c\/td\u003e\n\u003c\/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"border: 1px solid #ccc; padding: 6px 10px;\"\u003eVegetable cellulose capsule (HPMC)\u003c\/td\u003e\n\u003ctd style=\"border: 1px solid #ccc; padding: 6px 10px;\"\u003e~95 mg shell\u003c\/td\u003e\n\u003ctd style=\"border: 1px solid #ccc; padding: 6px 10px;\"\u003eUSP-grade, vegan, no titanium dioxide\u003c\/td\u003e\n\u003c\/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"border: 1px solid #ccc; padding: 6px 10px;\"\u003eMicrocrystalline cellulose\u003c\/td\u003e\n\u003ctd style=\"border: 1px solid #ccc; padding: 6px 10px;\"\u003etrace (flow agent)\u003c\/td\u003e\n\u003ctd style=\"border: 1px solid #ccc; padding: 6px 10px;\"\u003eUSP-grade\u003c\/td\u003e\n\u003c\/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"border: 1px solid #ccc; padding: 6px 10px;\"\u003eVegetable magnesium stearate\u003c\/td\u003e\n\u003ctd style=\"border: 1px solid #ccc; padding: 6px 10px;\"\u003etrace (flow agent)\u003c\/td\u003e\n\u003ctd style=\"border: 1px solid #ccc; padding: 6px 10px;\"\u003eplant-derived, USP-grade\u003c\/td\u003e\n\u003c\/tr\u003e\n\u003c\/tbody\u003e\n\u003c\/table\u003e\n\u003cp\u003e\u003cstrong\u003eWhat is NOT in this formula:\u003c\/strong\u003e 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.\u003c\/p\u003e\n\n\u003ch2\u003eSourcing, manufacturing, and quality control\u003c\/h2\u003e\n\u003cul\u003e\n\u003cli\u003e\n\u003cstrong\u003eBotanical source.\u003c\/strong\u003e Sugar beet (\u003cem\u003eBeta vulgaris\u003c\/em\u003e) 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.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eManufacturing.\u003c\/strong\u003e cGMP-compliant, FDA-registered, ISO 9001-certified U.S. facility. Per-batch quality release.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eIdentity testing.\u003c\/strong\u003e HPLC + FTIR per batch, ≥99% trimethylglycine assay confirmation. Identity is verified against a reference standard before any batch is released.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003ePurity testing.\u003c\/strong\u003e USP \u0026lt;2232\u0026gt; heavy metals (lead, mercury, arsenic, cadmium); USP \u0026lt;2021\/2022\u0026gt; microbial (total aerobic count, yeast\/mold, \u003cem\u003eE. coli\u003c\/em\u003e, \u003cem\u003eSalmonella\u003c\/em\u003e); USP \u0026lt;467\u0026gt; residual solvents; USP \u0026lt;561\u0026gt; pesticides on the source material.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eStability.\u003c\/strong\u003e 24-month shelf-life from manufacture; UV-protective amber HDPE bottle with induction seal; ambient stable, no refrigeration required.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eCOA available.\u003c\/strong\u003e A certificate of analysis can be requested for any batch via our contact page.\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003ch2\u003eWhere this sits in the catalog architecture\u003c\/h2\u003e\n\u003cp\u003eTMG is one of the four \"methyl-pool \/ NAD\u003csup\u003e+\u003c\/sup\u003e-protection\" compounds in the catalog — the others are \u003ca href=\"\/he\/products\/apigenin-50mg-cd38-inhibitor-for-nmn-nad-stacks\"\u003eApigenin 50 mg\u003c\/a\u003e (slows NAD\u003csup\u003e+\u003c\/sup\u003e consumption by inhibiting CD38), \u003ca href=\"\/he\/products\/glycine-1500mg-glynac-partner-glutathione-sleep-longevity\"\u003eGlycine 1500 mg\u003c\/a\u003e (the second remethylation cofactor on the cystathionine route), and \u003ca href=\"\/he\/products\/magnesium-glycinate-400mg-sleep-and-nad-methylation\"\u003eMagnesium Glycinate 400 mg\u003c\/a\u003e (the methionine-synthase cofactor). Together they represent the \"make NAD\u003csup\u003e+\u003c\/sup\u003e 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\u003csup\u003e+\u003c\/sup\u003e precursor you've already chosen; Apigenin and Glycine are advanced-tier additions for users running larger NAD\u003csup\u003e+\u003c\/sup\u003e stacks or chasing the GlyNAC protocol specifically.\u003c\/p\u003e\n\n\u003cp\u003eFor category browsing, TMG is grouped under \u003ca href=\"\/he\/collections\/nad-family\"\u003eNAD\u003csup\u003e+\u003c\/sup\u003e Family\u003c\/a\u003e (because its primary use case is companion-dose for NAD\u003csup\u003e+\u003c\/sup\u003e precursors), \u003ca href=\"\/he\/collections\/foundational-health\"\u003eFoundational Health\u003c\/a\u003e (because methylation is one of the seven daily-nutrient layers that runs underneath every protocol), and \u003ca href=\"\/he\/collections\/cardiovascular-longevity\"\u003eCardiovascular Longevity\u003c\/a\u003e (because its homocysteine-lowering effect maps directly to the cardiovascular risk literature). It is also one of the explicitly named compounds in the \u003ca href=\"\/he\/blogs\/news\/foundational-health-the-7-daily-nutrients-that-run-underneath-every-longevity-stack\"\u003eFoundational Health: The 7 Daily Nutrients\u003c\/a\u003e and \u003ca href=\"\/he\/blogs\/news\/how-to-stack-longevity-supplements-a-practical-protocol-for-2026\"\u003eHow to Stack Longevity Supplements 2026\u003c\/a\u003e long-form articles.\u003c\/p\u003e\n\n\u003ch2\u003eCommon mistakes to avoid\u003c\/h2\u003e\n\u003cul\u003e\n\u003cli\u003e\n\u003cstrong\u003eSkipping TMG when starting NMN, then adding it after symptoms.\u003c\/strong\u003e 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.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eStopping NMN because you \"felt flat\" without trying TMG first.\u003c\/strong\u003e 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.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eStacking TMG with high-dose niacin (\u0026gt;500 mg\/day) thinking it's the same thing.\u003c\/strong\u003e Niacin is a different molecule with a different mechanism (it's an NAD\u003csup\u003e+\u003c\/sup\u003e precursor itself; flushing nicotinic acid raises HDL, niacinamide does not). TMG doesn't replace niacin and niacin doesn't replace TMG.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eRunning TMG at 4+ g\/day when methylfolate would do the same job at lower cost.\u003c\/strong\u003e 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.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eTaking TMG only on training days for \"exercise effect.\"\u003c\/strong\u003e 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.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eDiscontinuing pre-surgery \"to be safe.\"\u003c\/strong\u003e No bleeding-time or anesthesia interaction. There is no reason to stop TMG before surgery.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eIgnoring the LDL watch-item at high doses.\u003c\/strong\u003e If you run TMG at 3+ g\/day for homocystinuria-tier reasons, retest lipids at 8 weeks and consider adding omega-3 \/ fiber.\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003ch2\u003eWhy not Amazon\u003c\/h2\u003e\n\u003cp\u003eThree reasons we built this bottle the way we did:\u003c\/p\u003e\n\u003cul\u003e\n\u003cli\u003e\n\u003cstrong\u003eHPLC-verified ≥99% pharmaceutical-grade identity.\u003c\/strong\u003e 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.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003e1000 mg single-capsule dose.\u003c\/strong\u003e 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.\u003c\/li\u003e\n\u003cli\u003e\n\u003cstrong\u003eMechanism-first catalog architecture.\u003c\/strong\u003e 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.\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003ch2\u003eFrequently asked questions\u003c\/h2\u003e\n\u003ch3\u003eDo I really need TMG with NMN?\u003c\/h3\u003e\n\u003cp\u003eIf 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).\u003c\/p\u003e\n\n\u003ch3\u003eCan I take TMG without NMN?\u003c\/h3\u003e\n\u003cp\u003eYes — the homocysteine and liver-support pathways operate independently of any NAD\u003csup\u003e+\u003c\/sup\u003e 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.\u003c\/p\u003e\n\n\u003ch3\u003eIs TMG the same as betaine HCl?\u003c\/h3\u003e\n\u003cp\u003eNo, and the distinction matters. Trimethylglycine (betaine anhydrous) is the methyl-donor form used in homocysteine and NAD\u003csup\u003e+\u003c\/sup\u003e-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.\u003c\/p\u003e\n\n\u003ch3\u003eWhat does \"anhydrous\" mean?\u003c\/h3\u003e\n\u003cp\u003eIt 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.\u003c\/p\u003e\n\n\u003ch3\u003eHow long until I see homocysteine drop on bloodwork?\u003c\/h3\u003e\n\u003cp\u003eIf 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 (\u0026gt;15 µmol\/L), pair TMG with methylfolate + B12 from day one rather than chasing homocysteine with TMG alone.\u003c\/p\u003e\n\n\u003ch3\u003eShould I take TMG morning or evening?\u003c\/h3\u003e\n\u003cp\u003eMorning, 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.\u003c\/p\u003e\n\n\u003ch3\u003eCan I take TMG with statins \/ blood pressure meds \/ antidepressants?\u003c\/h3\u003e\n\u003cp\u003eYes — 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.\u003c\/p\u003e\n\n\u003ch3\u003eCan I take TMG while fasting?\u003c\/h3\u003e\n\u003cp\u003eYou 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.\u003c\/p\u003e\n\n\u003ch3\u003eWhat's the right dose if I have an MTHFR variant?\u003c\/h3\u003e\n\u003cp\u003eThe 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.\u003c\/p\u003e\n\n\u003ch3\u003eIs TMG vegan? Gluten-free? Allergen-free?\u003c\/h3\u003e\n\u003cp\u003eYes 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.\u003c\/p\u003e\n\n\u003ch3\u003eWhy is the bottle a 60-day supply, not 30?\u003c\/h3\u003e\n\u003cp\u003eAt 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.\u003c\/p\u003e\n\n\u003ch3\u003eIs there a fishy\/seafood smell or body odor?\u003c\/h3\u003e\n\u003cp\u003eNot 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.\u003c\/p\u003e\n\n\u003ch3\u003eDoes TMG raise testosterone or \"boost performance\"?\u003c\/h3\u003e\n\u003cp\u003eNot 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.\u003c\/p\u003e\n\n\u003ch3\u003eCan I open the capsule and mix it into water or food?\u003c\/h3\u003e\n\u003cp\u003eYes. 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.\u003c\/p\u003e\n\n\u003ch3\u003eWhy isn't this product in the Senolytics or Mitochondrial Renewal collections?\u003c\/h3\u003e\n\u003cp\u003eBecause TMG operates on a different layer of the longevity stack — it supports the NAD\u003csup\u003e+\u003c\/sup\u003e and homocysteine layers, not the senescent-cell or mitophagy layers. Catalog organization is mechanism-first; you'll find TMG in \u003ca href=\"\/he\/collections\/nad-family\"\u003eNAD\u003csup\u003e+\u003c\/sup\u003e Family\u003c\/a\u003e, \u003ca href=\"\/he\/collections\/foundational-health\"\u003eFoundational Health\u003c\/a\u003e, and \u003ca href=\"\/he\/collections\/cardiovascular-longevity\"\u003eCardiovascular Longevity\u003c\/a\u003e — the three collections that actually map to its mechanism of action.\u003c\/p\u003e\n\n\u003ch3\u003eWhat if I miss a dose?\u003c\/h3\u003e\n\u003cp\u003eTake 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.\u003c\/p\u003e\n\n\u003ch3\u003eIs the bottle plastic or glass?\u003c\/h3\u003e\n\u003cp\u003eUV-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.\u003c\/p\u003e\n\n\u003ch2\u003eRead more on the science\u003c\/h2\u003e\n\u003cul\u003e\n\u003cli\u003e\n\u003ca href=\"\/he\/blogs\/news\/foundational-health-the-7-daily-nutrients-that-run-underneath-every-longevity-stack\"\u003eFoundational Health: The 7 Daily Nutrients That Run Underneath Every Longevity Stack\u003c\/a\u003e — the longform article that introduces methylation as one of the seven daily nutrient layers, with the role TMG plays in NAD\u003csup\u003e+\u003c\/sup\u003e-precursor stacks.\u003c\/li\u003e\n\u003cli\u003e\n\u003ca href=\"\/he\/blogs\/news\/how-to-stack-longevity-supplements-a-practical-protocol-for-2026\"\u003eHow to Stack Longevity Supplements: A Practical Protocol for 2026\u003c\/a\u003e — the catalog-wide stacking guide, including the methyl-pool buffer and homocysteine-management layers.\u003c\/li\u003e\n\u003cli\u003e\n\u003ca href=\"\/he\/blogs\/news\/what-is-nad-a-beginners-guide-to-the-coenzyme-behind-longevity\"\u003eWhat is NAD\u003csup\u003e+\u003c\/sup\u003e? A Beginner's Guide to the Coenzyme Behind Longevity\u003c\/a\u003e — the upstream context for why NAD\u003csup\u003e+\u003c\/sup\u003e precursors create methyl-pool demand in the first place.\u003c\/li\u003e\n\u003cli\u003e\n\u003ca href=\"\/he\/blogs\/news\/nmn-side-effects-what-the-research-actually-shows\"\u003eNMN Side Effects: What the Research Actually Shows\u003c\/a\u003e — covers the methyl-depletion symptom pattern that TMG is designed to prevent.\u003c\/li\u003e\n\u003cli\u003e\n\u003ca href=\"\/he\/blogs\/news\/best-time-to-take-nmn-morning-empty-stomach-or-with-food\"\u003eBest Time to Take NMN: Morning, Empty Stomach, or With Food?\u003c\/a\u003e — the timing context for why TMG and NMN are taken together with breakfast.\u003c\/li\u003e\n\u003cli\u003e\n\u003ca href=\"\/he\/blogs\/news\/nmn-vs-nr-which-nad-precursor-actually-works-better\"\u003eNMN vs NR: Which NAD\u003csup\u003e+\u003c\/sup\u003e Precursor Actually Works Better?\u003c\/a\u003e — both precursors generate the same methyl-pool draw, so the TMG companion logic applies equally to either.\u003c\/li\u003e\n\u003cli\u003e\n\u003ca href=\"\/he\/pages\/protocols\"\u003eOur Protocols\u003c\/a\u003e — the complete catalog of structured stacks, with TMG positioned in the Foundational, NAD\u003csup\u003e+\u003c\/sup\u003e, and Cardiovascular layers.\u003c\/li\u003e\n\u003cli\u003e\n\u003ca href=\"\/he\/pages\/our-science\"\u003eOur Science\u003c\/a\u003e — how we evaluate evidence, with notes on the homocysteine literature and the methylation cycle.\u003c\/li\u003e\n\u003cli\u003e\n\u003ca href=\"\/he\/pages\/quality\"\u003eQuality \u0026amp; Testing\u003c\/a\u003e — HPLC, heavy-metal, and microbial protocols applied to every batch.\u003c\/li\u003e\n\u003cli\u003e\n\u003ca href=\"\/he\/pages\/ingredient-sourcing\"\u003eIngredient Sourcing\u003c\/a\u003e — sugar-beet feedstock, pharmaceutical-grade specification, and per-batch identity testing.\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003ch2\u003eSelected references\u003c\/h2\u003e\n\u003col\u003e\n\u003cli\u003eOlthof MR, Verhoef P. Effects of betaine intake on plasma homocysteine concentrations and consequences for health. \u003cem\u003eAmerican Journal of Clinical Nutrition\u003c\/em\u003e. 2005;81(2):442-450.\u003c\/li\u003e\n\u003cli\u003eSchwab 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. \u003cem\u003eEuropean Journal of Clinical Nutrition\u003c\/em\u003e. 2002;56(10):971-977.\u003c\/li\u003e\n\u003cli\u003eMcRae MP. Betaine supplementation decreases plasma homocysteine in healthy adult participants: a meta-analysis. \u003cem\u003eJournal of Chiropractic Medicine\u003c\/em\u003e. 2013;12(1):20-25.\u003c\/li\u003e\n\u003cli\u003eCantó C, Auwerx J. NAD\u003csup\u003e+\u003c\/sup\u003e as a signaling molecule modulating metabolism. \u003cem\u003eCold Spring Harbor Symposia on Quantitative Biology\u003c\/em\u003e. 2011;76:291-298 (and Cantó review series, \u003cem\u003eCell Metabolism\u003c\/em\u003e, 2012-2015).\u003c\/li\u003e\n\u003cli\u003eKraus D, Yang Q, Kong D, et al. Nicotinamide N-methyltransferase knockdown protects against diet-induced obesity. \u003cem\u003eNature\u003c\/em\u003e. 2014;508(7495):258-262.\u003c\/li\u003e\n\u003cli\u003eHong S, Moreno-Navarrete JM, Wei X, et al. Nicotinamide N-methyltransferase regulates hepatic nutrient metabolism through Sirt1 protein stabilization. \u003cem\u003eNature Medicine\u003c\/em\u003e. 2015;21(8):887-894.\u003c\/li\u003e\n\u003cli\u003ePissios P. Nicotinamide N-methyltransferase: more than a vitamin B3 clearance enzyme. \u003cem\u003eTrends in Endocrinology \u0026amp; Metabolism\u003c\/em\u003e. 2017;28(5):340-353.\u003c\/li\u003e\n\u003cli\u003eTrammell SAJ, Schmidt MS, Weidemann BJ, et al. Nicotinamide riboside is uniquely and orally bioavailable in mice and humans. \u003cem\u003eNature Communications\u003c\/em\u003e. 2016;7:12948.\u003c\/li\u003e\n\u003cli\u003eConze 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. \u003cem\u003eScientific Reports\u003c\/em\u003e. 2019;9(1):9772.\u003c\/li\u003e\n\u003cli\u003eBrakedal B, Dolle C, Riemer F, et al. The NADPARK study: a randomized phase I trial of nicotinamide riboside supplementation in Parkinson's disease. \u003cem\u003eCell Metabolism\u003c\/em\u003e. 2022;34(3):396-407.\u003c\/li\u003e\n\u003cli\u003eSmith 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). \u003cem\u003ePLoS ONE\u003c\/em\u003e. 2010;5(9):e12244.\u003c\/li\u003e\n\u003cli\u003eSeshadri S, Beiser A, Selhub J, et al. Plasma homocysteine as a risk factor for dementia and Alzheimer's disease. \u003cem\u003eNew England Journal of Medicine\u003c\/em\u003e. 2002;346(7):476-483.\u003c\/li\u003e\n\u003cli\u003eWald DS, Law M, Morris JK. Homocysteine and cardiovascular disease: evidence on causality from a meta-analysis. \u003cem\u003eBMJ\u003c\/em\u003e. 2002;325(7374):1202.\u003c\/li\u003e\n\u003cli\u003eAbdelmalek MF, Sanderson SO, Angulo P, et al. Betaine for nonalcoholic fatty liver disease: results of a randomized placebo-controlled trial. \u003cem\u003eHepatology\u003c\/em\u003e. 2009;50(6):1818-1826.\u003c\/li\u003e\n\u003cli\u003eMukherjee S, Das D, Mukherjee M, et al. Betaine and nonalcoholic steatohepatitis: a randomized controlled trial. \u003cem\u003eIndian Journal of Pharmacology\u003c\/em\u003e. 2011;43(4):485-487.\u003c\/li\u003e\n\u003cli\u003eCholewa JM, Wyszczelska-Rokiel M, Glowacki R, et al. Effects of betaine on body composition, performance, and homocysteine thiolactone. \u003cem\u003eJournal of the International Society of Sports Nutrition\u003c\/em\u003e. 2013;10(1):39.\u003c\/li\u003e\n\u003cli\u003eLee EC, Maresh CM, Kraemer WJ, et al. Ergogenic effects of betaine supplementation on strength and power performance. \u003cem\u003eJournal of the International Society of Sports Nutrition\u003c\/em\u003e. 2010;7:27.\u003c\/li\u003e\n\u003cli\u003eTrepanowski 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. \u003cem\u003eJournal of Strength and Conditioning Research\u003c\/em\u003e. 2011;25(12):3461-3471.\u003c\/li\u003e\n\u003cli\u003eSharma A, Gerbarg P, Bottiglieri T, et al. S-Adenosylmethionine (SAMe) for neuropsychiatric disorders: a clinician-oriented review of research. \u003cem\u003eMayo Clinic Proceedings\u003c\/em\u003e. 2016;91(4):541-554.\u003c\/li\u003e\n\u003c\/ol\u003e\n\n\u003cp\u003e\u003cem\u003eThis 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 \u003ca href=\"\/he\/pages\/contact\"\u003econtact page\u003c\/a\u003e.\u003c\/em\u003e\u003c\/p\u003e\n","brand":"True Health Protocol","offers":[{"title":"Default Title","offer_id":47839145230554,"sku":"THP-TMG-1000-60","price":24.99,"currency_code":"USD","in_stock":true}],"thumbnail_url":"\/\/cdn.shopify.com\/s\/files\/1\/0814\/5158\/1658\/files\/thp_tmg.png?v=1778047687","url":"https:\/\/truehealthprotocol.health\/he\/products\/tmg-1000mg-trimethylglycine-methyl-donor-for-nmn-nad-stacks","provider":"True Health Protocol","version":"1.0","type":"link"}