Betaine Anhydrous

• Homocysteine Reduction
• Liver Protection
• Methylation Support
• Cardiovascular Health

• Exercise Performance
• Digestive Health
• Cellular Hydration
• Detoxification Support
• Protein Synthesis

Betaine anhydrous (trimethylglycine, TMG) exerts its biological effects through two primary mechanisms: as a methyl donor in biochemical pathways and as an osmolyte that protects cells from environmental stress. As a methyl donor, betaine participates in the methionine cycle, where it donates a methyl group to homocysteine, converting it to methionine through the enzyme betaine-homocysteine methyltransferase (BHMT). This reaction is crucial for maintaining healthy homocysteine levels, as elevated homocysteine is associated with cardiovascular disease, cognitive decline, and other health issues. The methionine produced is then converted to S-adenosylmethionine (SAMe), the body’s universal methyl donor, which is essential for numerous methylation reactions including DNA methylation, neurotransmitter synthesis, phospholipid production, and detoxification processes.

Through this methylation support, betaine influences gene expression, cellular repair, and overall metabolic function. As an osmolyte, betaine helps maintain cellular water balance and protects proteins, enzymes, and cellular components from environmental stressors such as heat, dehydration, and high salinity. This osmoprotective function is particularly important in the liver and kidneys, where betaine helps maintain cellular hydration and function under stress conditions. In liver health, betaine reduces fat accumulation in the liver through multiple mechanisms: it enhances mitochondrial function and fatty acid oxidation, increases hepatic insulin sensitivity, and promotes the export of triglycerides from the liver.

These effects make betaine beneficial for non-alcoholic fatty liver disease (NAFLD) and alcoholic liver disease. For cardiovascular health, beyond homocysteine reduction, betaine may improve endothelial function, reduce inflammation, and modulate lipid metabolism, though these mechanisms are still being elucidated. In exercise physiology, betaine appears to enhance performance through several pathways: as an osmolyte, it increases cellular hydration and resilience to exercise-induced stress; it may enhance creatine synthesis, supporting ATP production; it potentially increases nitric oxide production, improving blood flow to muscles; and it may promote protein synthesis and reduce protein breakdown, supporting muscle growth and recovery. For digestive health, betaine supports stomach acid production (particularly when supplemented as betaine HCl, a different form than betaine anhydrous), which aids protein digestion and nutrient absorption.

It also supports the integrity of the intestinal lining and may help modulate the gut microbiome. At the cellular level, betaine influences energy metabolism by enhancing mitochondrial function and efficiency, potentially through improved electron transport chain activity and reduced oxidative stress. It also supports methylation-dependent detoxification pathways in the liver, helping to eliminate toxins and waste products.

1.5-6 grams per day, typically divided into 2-3 doses

Betaine is highly water-soluble and readily absorbed in the gastrointestinal tract, primarily in the duodenum and jejunum. Oral bioavailability is estimated to be approximately 80-90%. Peak plasma concentrations typically occur within 1-2 hours after ingestion.

Taking with meals containing protein may enhance utilization due to betaine’s role in protein metabolism, Dividing daily doses (e.g., 2-3 times per day) maintains more consistent blood levels, Micronized forms may offer improved dissolution rate and absorption, Liposomal delivery systems potentially enhance cellular uptake, Combining with cofactors involved in methylation pathways (B vitamins, especially B6, B12, and folate) may enhance metabolic effects, Adequate hydration supports betaine’s osmolyte functions

Betaine can be taken with or without food, though taking with meals may improve tolerance and reduce potential gastrointestinal discomfort. For exercise performance, taking a dose approximately 60-90 minutes before training may be beneficial. For homocysteine reduction and methylation support, dividing the daily dose into 2-3 servings provides more consistent support for these biochemical pathways. For liver support, consistent daily use is more important than specific timing.

If using higher doses (>3g daily), dividing into multiple doses throughout the day may reduce the risk of digestive discomfort. Avoid taking large doses immediately before bedtime as some individuals report increased energy that may interfere with sleep.

• Gastrointestinal discomfort
• Nausea
• Diarrhea
• Stomach upset
• Fishy body odor (rare, typically at high doses)
• Headache (uncommon)
• Dry mouth (uncommon)

• Pregnancy and breastfeeding (insufficient safety data, though used medically for homocystinuria during pregnancy under supervision)
• Severe renal disease (use with caution due to limited research)
• Known hypersensitivity to betaine
• Bipolar disorder (theoretical concern due to effects on methylation and neurotransmitters)
• Active peptic ulcer disease (may increase stomach acid production in some forms)

• Medications metabolized by methylation pathways (theoretical interaction)
• Antifolate drugs (methotrexate, trimethoprim) – potential interaction with one-carbon metabolism
• Medications for Parkinson’s disease (levodopa) – theoretical concern about methylation affecting neurotransmitter balance
• NSAIDs – potential additive effects on stomach irritation
• Alcohol – may affect betaine’s liver-protective effects
• Chemotherapy drugs (consult oncologist before use)

No established upper limit from regulatory bodies. Clinical studies have used up to 20 grams daily for homocystinuria without serious adverse effects, though such high doses are rarely needed for general health purposes. For general supplementation, most practitioners recommend not exceeding 6 grams daily without medical supervision. Betaine is generally considered to have a wide safety margin as it is a naturally occurring metabolite in the body.

In the United States, betaine anhydrous has a dual regulatory status. As a dietary supplement, it is regulated under the Dietary Supplement Health and Education Act (DSHEA) of 1994, and the FDA does not approve it for the treatment, prevention, or cure of any disease. However, betaine anhydrous is also approved as a prescription drug (Cystadane) for the treatment of homocystinuria, a rare genetic disorder. This creates a unique situation where the same compound is both a prescription drug and an available dietary supplement.

The FDA has not established a specific recommended daily allowance (RDA) for betaine.

Eu: In the European Union, betaine is regulated as both a food supplement and as a medicine (Cystadane) for homocystinuria. The European Food Safety Authority (EFSA) has evaluated health claims for betaine but has not approved claims related to homocysteine reduction or liver function due to insufficient evidence meeting their standards. Novel food authorization was granted for betaine as a food supplement in 2014.

Canada: Health Canada regulates betaine as a Natural Health Product (NHP) when used as a supplement and as a prescription drug (Cystadane) for homocystinuria. Several betaine products have received Natural Product Numbers (NPNs) with approved claims related to liver function and homocysteine metabolism.

Australia: The Therapeutic Goods Administration (TGA) regulates betaine as a listed complementary medicine when used as a supplement and as a prescription medicine for homocystinuria. Various betaine preparations are included in the Australian Register of Therapeutic Goods (ARTG).

Japan: Betaine is recognized as a food ingredient in Japan. Some betaine products may be marketed under the Foods with Function Claims system, though specific approved claims vary.

China: Betaine is regulated primarily as a food additive and ingredient in dietary supplements in China. It is also recognized as a treatment for homocystinuria when prescribed by physicians.

low to medium

$0.20-$1.00 per day for typical doses (1.5-6g)

Betaine anhydrous offers excellent value compared to many other supplements targeting similar health benefits. Powder forms provide the best cost efficiency, with a month’s supply often costing $6-15 for effective doses. Capsules and tablets are more convenient but typically cost 2-3 times more per gram than powder. For homocysteine management, betaine is more cost-effective than SAMe (another methyl donor), which can cost $1-4 per day, though some may find SAMe more effective for certain conditions like depression.

When compared to prescription treatments for elevated homocysteine, betaine supplements are significantly more affordable, though medical-grade betaine (Cystadane) used for homocystinuria is considerably more expensive. For liver health, betaine represents good value compared to many specialized liver supplements, with comparable or better evidence for effectiveness in conditions like NAFLD. In sports nutrition, betaine is moderately priced compared to other performance-enhancing supplements, with a month’s supply typically costing $10-30 depending on dosage and brand. The cost-effectiveness increases when purchasing in bulk (250g-1kg containers of powder).

For general methylation support, betaine is one of the more affordable options, especially compared to specialized methylation support formulas. Overall, betaine represents a good value proposition, particularly for homocysteine management, liver support, and as part of a comprehensive approach to exercise performance enhancement.

Pure betaine anhydrous powder: 2-3 years when properly stored; Tablets and capsules: typically 2-3 years; Liquid formulations: 1-2 years if preserved properly

Store in a cool, dry place away from direct sunlight. Airtight containers are essential as betaine anhydrous is hygroscopic and readily absorbs moisture from the air. Refrigeration is not necessary but may extend shelf life in very hot or humid climates. Once opened, powder forms should be used within 6-12 months for maximum potency. Desiccant packets included in containers should be kept in place to maintain dryness.

Moisture (betaine anhydrous is highly hygroscopic and can absorb water from the environment, potentially forming betaine monohydrate), Heat (accelerates degradation reactions, especially in the presence of moisture), Light exposure (particularly UV light), Oxygen (oxidation can affect stability over time), pH extremes (highly acidic or alkaline environments can accelerate degradation), Microbial contamination (particularly in liquid formulations or when moisture is introduced to powder), Interactions with other ingredients in multi-component supplements

Synthesis Methods

Natural Sources

Quality Considerations

Betaine has a relatively recent history as a dietary supplement compared to many traditional botanical remedies, with its use primarily driven by scientific discoveries rather than traditional healing practices. Betaine was first isolated from sugar beets (Beta vulgaris) in the 19th century, which gave rise to its name. In 1869, the German chemist Wilhelm Scheibler first isolated betaine from sugar beet juice, identifying it as a nitrogenous compound. However, its biological significance remained largely unknown for decades.

In the early 20th century, researchers began to understand betaine’s role in biological methylation processes. By the 1950s, scientific studies had established betaine’s function as a methyl donor and its relationship to homocysteine metabolism. The first medical application of betaine emerged in the 1980s when it was found to be effective in treating homocystinuria, a rare genetic disorder characterized by elevated homocysteine levels. In 1985, betaine was approved as an orphan drug (marketed as Cystadane) for the treatment of homocystinuria, marking its first official therapeutic use.

During the 1990s, as research on homocysteine as a risk factor for cardiovascular disease intensified, interest in betaine as a homocysteine-lowering agent grew. This period saw the beginning of betaine’s transition from a medical treatment for a rare genetic disorder to a more widely used dietary supplement. In the early 2000s, research began to explore betaine’s potential benefits for liver health, particularly in conditions like non-alcoholic fatty liver disease (NAFLD) and alcoholic liver disease. This expanded the interest in betaine beyond homocysteine management.

Around the same time, the athletic performance community began to take notice of betaine, with early studies suggesting potential benefits for muscle strength, power, and endurance. By the 2010s, betaine had become a common ingredient in sports nutrition supplements, particularly pre-workout formulations. In recent years, research has continued to explore betaine’s diverse effects, including its role in protein synthesis, cellular hydration, and methylation support for overall health. While betaine does not have the long historical use of many botanical supplements, its presence in traditional diets rich in beets, spinach, and whole grains means humans have been consuming it throughout history, albeit without specific knowledge of its benefits.

Today, betaine is recognized as both a medical treatment for specific conditions and a dietary supplement with a range of potential health benefits, supported by a growing body of scientific research.

Borsook ME, Borsook H. (2011) Treatment of Hyperhomocysteinemia in Renal Disease and End-stage Renal Disease. Current Opinion in Nephrology and Hypertension, Cholewa JM, Guimarães-Ferreira L, Zanchi NE. (2014) Effects of betaine on performance and body composition: a review of recent findings and potential mechanisms. Amino Acids

Studies on betaine supplementation for metabolic syndrome, Research on betaine’s effects on exercise recovery and muscle protein synthesis, Trials examining betaine’s potential in liver diseases beyond NAFLD, Studies on betaine’s effects on cognitive function and brain health