Betaine (TMG): Benefits, Homocysteine, Foods & Betaine HCl

Dr. Josh Axe Vitamin Advisor · 4–5 questions

Which supplements belong in your top 5?

What's your biggest goal right now?

Immunity & getting sickEnergy & fatigueGut & digestionSleep & stressHormones & thyroidJoints & inflammationBlood sugar & weightBrain, focus & moodHeart healthSkin

Betaine is a small nutrient with a steady job in your liver. Its chemical name, trimethylglycine, describes it: the amino acid glycine carrying three methyl groups, small chemical tags your body passes from molecule to molecule. Betaine hands one of those tags to homocysteine, which turns it back into methionine, and that handoff is how betaine helps keep homocysteine in check.12

You get betaine from food, and your body makes more from choline.16 When homocysteine runs high, my protocol looks for the root causes first, then pairs TMG with a methylated B complex and retests.10

Betaine also comes in a second supplement form, betaine HCl, which delivers hydrochloric acid to your stomach. I use it in my gut-repair protocols, with guidance.911

Did you know?

• Betaine has a second job besides donating methyl groups. As an osmolyte, it helps cells hold their water and protects proteins and enzymes from stresses like dehydration, high salt and extreme temperature.1

• A cup of cooked spinach carries about 160 mg of betaine, against 31 mg in a cup of raw spinach, because a cup holds far more leaves once they've wilted.1213

• Very little betaine is wasted: in a study of eight men who each tried a betaine-rich diet and a supplement, only about 1.5% of the supplement's betaine left the body unchanged in urine.14

Advertisement

What is betaine?

Betaine, trimethylglycine, TMG and betaine anhydrous are four names for one compound.115 Most of its methyl-donor work happens in your liver and kidneys.12

Betaine is also an approved prescription medicine. As betaine anhydrous powder, it's used to lower very high homocysteine in homocystinuria, a rare inherited disorder, usually at 6 grams a day split into two doses.16

Is betaine the same as betaine HCl?

Betaine HCl, short for betaine hydrochloride, is betaine bound to hydrochloric acid. In your stomach it releases that acid, and the acid is what people take it for.8 TMG supplies betaine itself, as a methyl donor.3

What is betaine good for?

How does betaine work in your body?

Betaine passes its methyl groups along a short chain inside your liver, and trials in people have measured the start and end of that chain in the blood.

Betaine benefits, ranked by evidence

Ordered by how much human research backs each one, betaine's benefits start with lower homocysteine, followed by strength and power and liver enzymes in fatty liver disease, with mixed results for body fat and early evidence for betaine HCl and stomach acid.

Does betaine lower homocysteine?

Homocysteine is an amino acid your body makes from methionine and then has to recycle, using either betaine or folate and vitamin B12.127 When recycling falls behind, it builds up in your blood, and higher levels track with heart and brain risk. In a pooled analysis of 30 studies covering 5,073 heart-disease events and 1,113 strokes, a 25% lower homocysteine, about 3 µmol/L, was linked with an 11% lower risk of heart disease and a 19% lower risk of stroke.31 In 1,092 older adults from the Framingham Study followed for a median of eight years, a level above 14 µmol/L nearly doubled the risk of Alzheimer's disease.32 Lowering homocysteine has been tested against outcomes too: a review of 15 trials with 71,422 people found that B vitamins that lower homocysteine cut stroke rates from 5.1% to 4.3% compared with placebo, across the 10 trials and 44,224 people with stroke results, while heart attack rates didn't differ.21

Betaine lowers homocysteine reliably. A 2013 analysis pooled five placebo-controlled trials in healthy adults taking 4 to 6 grams a day for 6 to 24 weeks, and homocysteine fell 1.23 µmol/L more than on placebo, about 11.8% of where people started.3 A 2022 analysis of randomized trials found a 1.30 µmol/L drop, and its subgroup analysis found that doses under 4 grams a day lowered homocysteine as well.19

Smaller doses work too. In a placebo-controlled trial, four groups of 19 healthy men and women, 76 in all, took 1.5, 3 or 6 grams of betaine or a placebo every day for six weeks. Fasting homocysteine ended 12%, 15% and 20% lower than placebo. The effect started right away: on the first day, the rise in homocysteine after a methionine test drink was already 23% smaller at 3 grams and 35% smaller at 6 grams.4

The pattern held in other designs. In 34 healthy adults who took 1, 3 and 6 grams a day for a week each, with no placebo group, homocysteine fell 10% at 3 grams and 14% at 6 grams, while the 1.1% change at 1 gram was too small to be significant; adding 1 mg of folic acid to the 6-gram dose lowered it a further 5%, and blood betaine climbed with each dose, from 31 to 255 µmol/L.2 In 43 physically active young men who each tried betaine and placebo for 21 days, 2.5 or 5 grams a day lowered homocysteine from 17.1 to 15.6 µmol/L with no change in cholesterol, triglycerides or liver enzymes.33 And in 36 adults with mildly high homocysteine, betaine and folic acid, which recycle homocysteine through separate reactions, each lowered the fasting level compared with placebo over six weeks, by 1.8 µmol/L on 6 grams of betaine a day and 2.7 µmol/L on 800 micrograms of folic acid, and only betaine blunted the spike that follows a methionine test dose.27

Betaine with B vitamins

My protocol pairs TMG with a methylated B complex, and I recommend methylfolate rather than folic acid.1034 Two trials tested a similar pairing made with folic acid. In 100 adults in southern China with high homocysteine (92 analyzed), a daily tablet of 1 gram of betaine with 400 micrograms of folic acid, 8 mg of vitamin B6 and 6.4 micrograms of vitamin B12 lowered homocysteine by 3.87 µmol/L more than placebo over 12 weeks, a 10.1% greater drop. Neither the people nor the researchers knew who got what, and a supplement company made the tablets.35 In 298 women in rural Gambia, a daily drink with 4 grams of betaine, 800 micrograms of folic acid, B12 and vitamin B2 lowered homocysteine by 23.6% compared with no supplement over 12 weeks, and by 8.8% more than a 15-nutrient tablet; the women knew which one they got, and staff watched every dose.36

What's a healthy homocysteine level? {#testing}

Conventional labs flag homocysteine above 15 µmol/L as high.3710 My optimal target is under 7 µmol/L, the functional range in my 25 Root Cause Bloodwork Markers guide and my 2026 High Blood Pressure Protocol.1038 On my show, I've described it this way: "if you get advanced cellular blood work, you can check for a marker called homocysteine, and this will tell you how well methylation is going in your body."34

My father-in-law died unexpectedly of a heart attack, and as I shared on my show, he had been "getting normal blood work and labs done, and everything showed normal."39 It's one of the reasons I push for the right blood markers.

When homocysteine runs above target, my guide looks for the root cause first:10

• MTHFR variants. The common C677T and A1298C variants of the MTHFR gene slow one step of methylation. As I've put it, you have "a little bit more of a bottleneck than other people."1034

• Low folate, B12 or B6. Your body needs all three to keep homocysteine from building up; see the signs of folate deficiency.10

• Low choline and betaine intake. The foods in the next section and pasture-raised egg yolks cover both.10

• An underactive thyroid. Low thyroid output slows methylation; see the common thyroid problems.10

• Heavy coffee and alcohol intake. My guide lists heavy intake of either one as a root cause of high homocysteine.10

The actions in my guide follow from there: a methylated B complex daily, TMG at 500 to 1,000 mg a day, pasture-raised egg yolks for choline, and a retest at three months, since homocysteine "responds quickly."10 Test, don't guess.

Which foods are high in betaine?

Values from USDA FoodData Central (SR Legacy) and the USDA Database for the Choline Content of Common Foods, Release Two. Per-serving amounts are calculated from the per-100-gram values at each record's serving weight.265121340

Food betaine does the same work as a supplement. In eight healthy men who each tried both for two weeks, a betaine-rich diet supplying about 800 mg a day raised blood betaine and blunted the rise in homocysteine after a methionine test dose as well as a supplement of 0.5 grams twice a day, and the food version tended to do a little more, a difference that wasn't significant.14 A cup of raw beets, a cup of cooked spinach and a quarter cup of dry quinoa add up to about 603 mg.

In Heal Your Cells, Dr. Will Cole and I describe beets as "rich in betaine to thin bile and support methylation."41 Roast them, grate them raw into a salad or blend them into beetroot juice. For choline, the nutrient your body turns into betaine, add pasture-raised egg yolks; see the health benefits of eggs.106

What is betaine HCl, and who is it for?

Stomach acid does several jobs at once. As my SIBO and reflux protocols lay out, it kills most of the bacteria you swallow, it frees vitamin B12 from food, and your absorption of non-heme iron, the form in plant foods, depends on it.942 When it runs low, from age, stress or acid-blocking medication, more bacteria survive the trip into the small intestine.9 A 2020 review notes that older adults also take longer to re-acidify the stomach after a meal.43 In autoimmune gastritis, where the stomach's acid-making cells are destroyed, researchers have proposed mealtime acid supplementation as a way to ease digestive symptoms.44

How you eat matters too, because your body makes more of its own acid when you're calm. As I explained on my show, "If you get out of your fight or flight response and lower cortisol, typically your body can produce more enzymes, hydrochloric acid, and bile. So when you are sitting down eating, take your time, relax, don't be working, don't be watching things, just relax and chew, and then take a short 15-minute walk afterwards."45

From there, the protocols add support at meals. In the Replace step of my leaky gut protocol, I use digestive enzymes with HCl at every meal that includes protein.11 For small intestinal bacterial overgrowth, betaine HCl is on my list "with guidance," and as I wrote on my SIBO page, "I use it to address the underlying cause, not as an antimicrobial."946 Many products pair betaine HCl with pepsin, the stomach's protein-digesting enzyme, which fits that same enzymes-with-acid approach at protein meals. Who should skip betaine HCl is covered in the safety section below.

The human research measures what betaine HCl does to stomach acid. In a pilot study, six healthy adults with normal stomach acid took an acid-blocking drug for four days. On the fifth day, once their stomach pH had risen above 4, 1,500 mg of betaine HCl dropped stomach pH from 5.2 to 0.6 within 30 minutes. It took about 6 minutes to fall below pH 3, it stayed there for about 73 minutes, and everyone tolerated it well.8

A meal raises stomach pH for a while, and mealtime is when the protocols above use betaine HCl. In 9 healthy adults who each tried several doses, knowing which they got, a meal raised stomach pH, and it took about 49.7 minutes to come back down on its own; after food, the 1,500 and 3,000 mg doses weren't enough, and 4,500 mg of betaine HCl brought it back in about 17.3 minutes.18

How much betaine should you take a day?

Stay under 4 grams a day unless a practitioner is guiding a higher dose; the cholesterol finding behind that limit is in the safety section.19 Split larger amounts into two doses, the way the prescription label and the liver trials did; at 4 grams a day, the liver trial gave 2 grams twice a day, with or without food.167

For betaine HCl, my leaky gut protocol lists digestive enzymes with HCl or betaine at 1 to 2 capsules with each meal, and for SIBO it's "with guidance."119

Betaine side effects and who should be careful

• Betaine HCl with ulcers, NSAIDs or acid-reducing medicine. As I wrote on my SIBO page, "Avoid it if you have ulcers or take NSAIDs without medical guidance."46 Because of the interaction described above, ask the doctor who prescribed an acid blocker before combining them, and don't stop a prescribed medicine on your own.847 My leaky gut protocol notes possible mild reflux for 2 to 3 days.11

• Cholesterol at higher TMG doses. In three placebo-controlled studies of healthy adults, 6 grams a day for six weeks raised LDL cholesterol by about 14 mg/dL (0.36 mmol/L), visible by week two, while HDL didn't change.15 Pooled analyses found total cholesterol up about 13 to 14 mg/dL, and in a subgroup analysis, doses under 4 grams didn't raise lipids.4819 In the liver trials, LDL held steady at 2 to 8 grams a day.7 If your LDL or ApoB runs high, recheck your cholesterol when you retest homocysteine.

• Stomach upset. In the liver trials, about 35% of people reported mild digestive symptoms, most often an upset stomach (about 11%) or bloating (10%); the symptoms faded as they kept taking it, and none of the 70 participants cut back or stopped because of a side effect.7 Nausea and stomach upset are the most common side effects on the prescription label.16 Take it with food and split larger amounts.

• Homocystinuria. If you have this inherited disorder, betaine is a prescription medicine your specialist manages. The label warns that brain swelling has been reported in people whose methionine levels ran very high, so methionine is monitored; don't change the dose on your own.16

• Pregnancy and nursing. The prescription label's limited pregnancy reports haven't identified a risk, but there's no data on breastfeeding, so get your betaine from food during those times.16

The bottom line

Betaine: frequently asked questions

References

1. Craig SA. Betaine in human nutrition. Am J Clin Nutr. 2004;80(3):539-49. doi:10.1093/ajcn/80.3.539. PMID:15321791
2. Alfthan G, Tapani K, Nissinen K, et al. The effect of low doses of betaine on plasma homocysteine in healthy volunteers. Br J Nutr. 2004;92(4):665-9. doi:10.1079/bjn20041253. PMID:15522136
3. McRae MP. Betaine supplementation decreases plasma homocysteine in healthy adult participants: a meta-analysis. J Chiropr Med. 2013;12(1):20-5. doi:10.1016/j.jcm.2012.11.001. PMID:23997720
4. Olthof MR, van Vliet T, Boelsma E, et al. Low dose betaine supplementation leads to immediate and long term lowering of plasma homocysteine in healthy men and women. J Nutr. 2003;133(12):4135-8. doi:10.1093/jn/133.12.4135. PMID:14652361
5. U.S. Department of Agriculture, Agricultural Research Service. Beets, raw (SR Legacy, FDC ID 169145). FoodData Central. Accessed October 3, 2026.
6. Abdelmalek MF, Angulo P, Jorgensen RA, et al. Betaine, a promising new agent for patients with nonalcoholic steatohepatitis: results of a pilot study. Am J Gastroenterol. 2001;96(9):2711-7. doi:10.1111/j.1572-0241.2001.04129.x. PMID:11569700
7. Lim AS, Cruz SN, Uddin AA, et al. Pilot trials of oral betaine in participants with metabolic dysfunction-associated steatotic liver disease and elevated alanine aminotransferase. Hepatology. 2026;83(6):1515-1528. doi:10.1097/HEP.0000000000001477. PMID:40758380
8. Yago MR, Frymoyer AR, Smelick GS, et al. Gastric reacidification with betaine HCl in healthy volunteers with rabeprazole-induced hypochlorhydria. Mol Pharm. 2013;10(11):4032-7. doi:10.1021/mp4003738. PMID:23980906
9. Axe J. SIBO Protocol: The 60-Day Healing Protocol. DrAxe.com; 2026. p. 20, "Top 8 SIBO remedies" (honorable mentions: betaine HCl with guidance) and p. 12, "Why SIBO comes back" (the acid barrier).
10. Axe J, Cole W. 25 Root Cause Bloodwork Markers. DrAxe.com; 2025. Homocysteine page (optimal under 7 µmol/L; conventional under 15; actions to take).
11. Axe J. Healing Leaky Gut: The 30-Day Healing Protocol. DrAxe.com; 2025. The 6R Protocol, Replace (days 8–14).
12. U.S. Department of Agriculture, Agricultural Research Service. Spinach, cooked, boiled, drained, without salt (SR Legacy, FDC ID 168463). FoodData Central. Accessed October 3, 2026.
13. U.S. Department of Agriculture, Agricultural Research Service. Spinach, raw (SR Legacy, FDC ID 168462). FoodData Central. Accessed October 3, 2026.
14. Atkinson W, Slow S, Elmslie J, et al. Dietary and supplementary betaine: effects on betaine and homocysteine concentrations in males. Nutr Metab Cardiovasc Dis. 2009;19(11):767-73. doi:10.1016/j.numecd.2009.01.004. PMID:19346114
15. Olthof MR, van Vliet T, Verhoef P, et al. Effect of homocysteine-lowering nutrients on blood lipids: results from four randomised, placebo-controlled studies in healthy humans. PLoS Med. 2005;2(5):e135. doi:10.1371/journal.pmed.0020135. PMID:15916468
16. Eton Pharmaceuticals. Betaine anhydrous powder, for solution [prescribing information]. DailyMed, U.S. National Library of Medicine. Revised February 2023. Accessed October 3, 2026.
17. Zawieja E, Machek S, Zanchi NE, et al. Effects of chronic betaine supplementation on exercise performance: Systematic review and meta-analysis. J Sports Sci. 2024;42(22):2131-2144. doi:10.1080/02640414.2024.2423578. PMID:39514262
18. Surofchy DD, Frassetto LA, Benet LZ. Food, Acid Supplementation and Drug Absorption - a Complicated Gastric Mix: a Randomized Control Trial. Pharm Res. 2019;36(11):155. doi:10.1007/s11095-019-2693-5. PMID:31485804
19. Ashtary-Larky D, Bagheri R, Ghanavati M, et al. Effects of betaine supplementation on cardiovascular markers: A systematic review and Meta-analysis. Crit Rev Food Sci Nutr. 2022;62(23):6516-6533. doi:10.1080/10408398.2021.1902938. PMID:33764214
20. 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):1818-26. doi:10.1002/hep.23239. PMID:19824078
21. Martí-Carvajal AJ, Solà I, Lathyris D, et al. Homocysteine-lowering interventions for preventing cardiovascular events. Cochrane Database Syst Rev. 2017;8(8):CD006612. doi:10.1002/14651858.CD006612.pub5. PMID:28816346
22. Zawieja E, Durkalec-Michalski K, Sadowski M, et al. Betaine supplementation improves CrossFit performance and increases testosterone levels, but has no influence on Wingate power: randomized crossover trial. J Int Soc Sports Nutr. 2023;20(1):2231411. doi:10.1080/15502783.2023.2231411. PMID:37409757
23. Nieman DC, Sakaguchi CA, Williams JC, et al. Betaine Supplementation Improves 60 km Cycling Time Trial Performance and One-Carbon Metabolism in Cyclists During Recovery. Nutrients. 2025;17(17):2765. doi:10.3390/nu17172765. PMID:40944155
24. Gao X, Zhang H, Guo XF, et al. Effect of Betaine on Reducing Body Fat-A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Nutrients. 2019;11(10):2480. doi:10.3390/nu11102480. PMID:31623137
25. Ashtary-Larky D, Bagheri R, Tinsley GM, et al. Betaine supplementation fails to improve body composition: a systematic review and meta-analysis. Br J Nutr. 2022;128(5):975-988. doi:10.1017/S0007114521004062. PMID:34743773
26. U.S. Department of Agriculture, Agricultural Research Service. Quinoa, uncooked (SR Legacy, FDC ID 168874). FoodData Central. Accessed October 3, 2026.
27. Steenge GR, Verhoef P, Katan MB. Betaine supplementation lowers plasma homocysteine in healthy men and women. J Nutr. 2003;133(5):1291-5. doi:10.1093/jn/133.5.1291. PMID:12730412
28. Schwab U, Törrönen 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. Am J Clin Nutr. 2002;76(5):961-7. doi:10.1093/ajcn/76.5.961. PMID:12399266
29. Cholewa JM, Wyszczelska-Rokiel M, Glowacki R, et al. Effects of betaine on body composition, performance, and homocysteine thiolactone. J Int Soc Sports Nutr. 2013;10(1):39. doi:10.1186/1550-2783-10-39. PMID:23967897
30. Cholewa JM, Hudson A, Cicholski T, et al. The effects of chronic betaine supplementation on body composition and performance in collegiate females: a double-blind, randomized, placebo controlled trial. J Int Soc Sports Nutr. 2018;15(1):37. doi:10.1186/s12970-018-0243-x. PMID:30064450
31. Homocysteine Studies Collaboration. Homocysteine and risk of ischemic heart disease and stroke: a meta-analysis. JAMA. 2002;288(16):2015-22. doi:10.1001/jama.288.16.2015. PMID:12387654
32. Seshadri S, Beiser A, Selhub J, et al. Plasma homocysteine as a risk factor for dementia and Alzheimer's disease. N Engl J Med. 2002;346(7):476-83. doi:10.1056/NEJMoa011613. PMID:11844848
33. Zawieja E, Durkalec-Michalski K, Muzsik-Kazimierska A, et al. The Effect of 3-Week Betaine Supplementation on Blood Biomarkers of Cardiometabolic Health in Young Physically Active Males. Metabolites. 2022;12(8):731. doi:10.3390/metabo12080731. PMID:36005603
34. Axe J. The Hidden Reason Your Body Can't Heal Itself! The Dr. Josh Axe Show. 2026.
35. Lu XT, Wang YN, Mo QW, et al. Effects of low-dose B vitamins plus betaine supplementation on lowering homocysteine concentrations among Chinese adults with hyperhomocysteinemia: a randomized, double-blind, controlled preliminary clinical trial. Eur J Nutr. 2023;62(4):1599-1610. doi:10.1007/s00394-023-03087-y. PMID:36717385
36. James PT, Jawla O, Mohammed NI, et al. A novel nutritional supplement to reduce plasma homocysteine in nonpregnant women: A randomised controlled trial in The Gambia. PLoS Med. 2019;16(8):e1002870. doi:10.1371/journal.pmed.1002870. PMID:31408467
37. Malinow MR, Bostom AG, Krauss RM. Homocyst(e)ine, diet, and cardiovascular diseases: a statement for healthcare professionals from the Nutrition Committee, American Heart Association. Circulation. 1999;99(1):178-82. doi:10.1161/01.cir.99.1.178. PMID:9884399
38. Axe J. The High Blood Pressure Protocol. DrAxe.com; 2026. Companion labs table (homocysteine: conventional 0–15 µmol/L, optimal under 7).
39. Axe J. The Truth About LDL & Heart Disease. The Dr. Josh Axe Show. 2026.
40. Patterson KY, Bhagwat SA, Williams JR, Howe JC, Holden JM. USDA Database for the Choline Content of Common Foods, Release Two. U.S. Department of Agriculture, Agricultural Research Service, Nutrient Data Laboratory; January 2008.
41. Axe J, Cole W. Heal Your Cells. Avery; 2026. ISBN 9798217181353. "Foods for a Younger Detox System" (beets) and Precision Healing Protocols (methylation profile).
42. Axe J. Acid Reflux & GERD Protocol: The 30-Day Healing Protocol. DrAxe.com; 2026. p. 13, "What reflux depletes."
43. Guilliams TG, Drake LE. Meal-Time Supplementation with Betaine HCl for Functional Hypochlorhydria: What is the Evidence? Integr Med (Encinitas). 2020;19(1):32-36. PMCID: PMC7238915. PMID:32549862
44. Taylor L, McCaddon A, Wolffenbuttel BHR. Creating a Framework for Treating Autoimmune Gastritis-The Case for Replacing Lost Acid. Nutrients. 2024;16(5):662. doi:10.3390/nu16050662. PMID:38474790
45. Axe J. Complete Guide to Healing Leaky Gut Naturally. The Dr. Josh Axe Show. 2026.
46. Axe J. SIBO: Symptoms, Causes, Diet, Tests & Treatment. DrAxe.com. 2026. Remedy 10, "Betaine HCl & digestive enzymes."
47. Yago MR, Frymoyer A, Benet LZ, et al. The use of betaine HCl to enhance dasatinib absorption in healthy volunteers with rabeprazole-induced hypochlorhydria. AAPS J. 2014;16(6):1358-65. doi:10.1208/s12248-014-9673-9. PMID:25274610
48. Zawieja EE, Zawieja B, Chmurzynska A. Betaine Supplementation Moderately Increases Total Cholesterol Levels: A Systematic Review and Meta-Analysis. J Diet Suppl. 2021;18(1):105-117. doi:10.1080/19390211.2019.1699223. PMID:31809615

This article is for educational purposes. See our medical disclaimer.