Avoid in individuals with a known allergy or hypersensitivity to betaine anhydrous or cocamidopropylbetaine, a form of betaine.

In the majority of clinical trials among healthy volunteers and renal disease patients, no adverse effects have been reported. In other studies, reported adverse effects are primarily gastrointestinal, such as diarrhea, stomach upset, gastrointestinal irritation, and nausea. However, these transitory events were not severe enough to require discontinuation of betaine use during clinical trials.

Betaine may also cause mental changes or body odor. Use cautiously in patients with psychiatric conditions.

Use cautiously in patients with renal disease or who are obese, as betaine may increase total cholesterol, LDL, HDL, and triglyceride levels when it is taken with folic acid and vitamin B6.

Betaine is not recommended in pregnant or breastfeeding women due to a lack of available scientific evidence.

Currently, there has been no recommended daily allowance (RDA) set by the United States Food and Nutrition Board for betaine. Manufacturers recommend that betaine powder be dissolved in water, juice, milk, or formula prior to administration and be administered in two doses of 3 grams each. For cardiovascular disease (hyperhomocysteinemics), 2-15 grams daily for up to 17 years has been used. For hyperhomocysteinemia, 1-6 grams daily of betaine for up to six weeks has been used. For nonalcoholic steatohepatitis, Cystadane® up to 20g daily for up to one year has been used.

In children, 250 milligrams per kilogram daily in children 6-14 years-old with cystathionine beta-synthase deficiency for three to six months has been used.

Although not well studied in humans, betaine supplementation may lower homocysteine concentrations that are elevated by alcohol use.

Patients with renal disease may experience increases in total cholesterol, LDL, HDL, and triglycerides when betaine is taken with folic acid and vitamin B6. Betaine may increase total cholesterol and LDL cholesterol in obese patients. Caution is advised in patients with high cholesterol or those taking cholesterol-lowering medications.

Patients with renal disease may experience increases in total cholesterol, LDL, HDL, and triglycerides when betaine is taken with folic acid and vitamin B6. Betaine may increase total cholesterol and LDL cholesterol in obese patients. Caution is advised in patients with high cholesterol or those taking cholesterol-lowering herbs or supplements, such as red yeast rice.