Betaine: Benefits and Side Effects
Betaine supplementation can provide health benefits including reducing homocysteine levels and anti-inflammatory effects, but may moderately increase total cholesterol levels, which should be considered when evaluating cardiovascular risk. 1
Beneficial Effects of Betaine
Betaine functions as an important osmoprotectant, protecting cells, proteins, and enzymes from environmental stress (e.g., low water, high salinity, extreme temperature) 2
As a methyl donor, betaine participates in the methionine cycle primarily in the human liver and kidneys, supporting proper methylation processes 2
Betaine supplementation significantly decreases plasma homocysteine concentrations, which may reduce risk for cardiovascular diseases 3
Betaine has demonstrated anti-inflammatory properties through several mechanisms:
- Ameliorates sulfur amino acid metabolism against oxidative stress
- Inhibits nuclear factor-κB activity and NLRP3 inflammasome activation
- Regulates energy metabolism
- Mitigates endoplasmic reticulum stress and apoptosis 4
These anti-inflammatory effects may provide benefits in several conditions including obesity, diabetes, cancer, and Alzheimer's disease 4
Some evidence suggests betaine supplementation could potentially promote adiposity reductions and/or lean mass gains, though mechanisms are not fully understood 5
Potential Side Effects and Risks
Betaine supplementation at doses of at least 4g/day for a minimum of six weeks may moderately increase plasma total cholesterol levels by approximately 0.34 mmol/L 1
Serum total and LDL-cholesterol concentrations may be higher with betaine supplementation compared to placebo 3
A concern with enteral administration of betaine is its potential conversion into methylamine-N-oxide (MAO) by gut microflora and subsequent metabolism by the liver into trimethylamine-N-oxide (TMAO), which may have negative long-term impact on cardiovascular health 6
Acute ingestion of high doses of betaine may cause a fishy body odor 6
Dosing Considerations
Betaine has been investigated with doses ranging from 500 to 9,000 mg/day for ergogenic and clinical effects 5
In studies examining homocysteine-lowering effects, doses of 6g/day have been used effectively 3
The upper limit (UL) for adults has been defined at 3.5 g/day 6
For patients with homocystinuria (CBS deficiency), betaine is used as an adjunct to treatment as a methyl donor that remethylates homocysteine to methionine 6
Special Populations
In patients with cystic fibrosis, choline depletion (which is metabolically related to betaine) is common despite enzyme treatment and may result in liver, fatty acid, and muscle abnormalities 6
For individuals with homocystinuria due to CBS deficiency who are non-responsive to vitamin treatment, betaine may be used as an adjunct to treatment along with a methionine-restricted, cystine-supplemented diet 6
Betaine may be particularly beneficial in conditions where methylation processes are impaired, such as in cases with MTHFR 677TT genotype 6
Monitoring Recommendations
When using betaine supplementation, monitor lipid profiles due to potential increases in total and LDL cholesterol 1, 3
In patients with cardiovascular risk factors, carefully weigh the benefits of homocysteine reduction against potential increases in cholesterol 1
For patients with renal dysfunction, consider monitoring TMAO levels, as betaine metabolism may contribute to this uremic toxin 6
Choline and betaine status might be quantified indirectly through their role in one-carbon metabolism 6