Synopsis

Source of validity: Scientific
Rating (out of 5): 3

5-Methyltetrahydrofolate glucosamine (5-MTHF GlcN) is a bioactive, stable form of folate (vitamin B9) used in dietary supplements. Its use in cardiovascular disease (CVD) is based on scientific understanding of folate’s role in homocysteine metabolism. Elevated homocysteine levels are an established risk factor for CVD, and folate is required to convert homocysteine to methionine, thus lowering plasma homocysteine concentrations.

Several studies have shown that supplementation with folate, including 5-MTHF (which is more bioavailable than folic acid and does not require enzymatic activation), effectively reduces homocysteine levels. Some meta-analyses suggest that homocysteine lowering with folate may modestly reduce the risk of stroke, but evidence for reduction in coronary heart disease events is less clear. Large randomized controlled trials (RCTs), such as the HOPE-2 trial, found that folic acid (and B vitamins) lowered homocysteine but did not significantly reduce major cardiovascular events. However, some population-based studies, especially in regions without folic acid fortification, indicate a potential benefit in stroke reduction.

5-MTHF glucosamine specifically is used in individuals with MTHFR polymorphisms, who have impaired conversion of folic acid to active folate, thus potentially providing a more effective option for homocysteine lowering. However, direct high-quality RCTs using 5-MTHF glucosamine for primary or secondary prevention of CVD are lacking.

In summary, while there is scientific rationale and some supporting evidence for using active folate forms like 5-MTHF to lower homocysteine, the translation to clear cardiovascular benefit—especially with 5-MTHF glucosamine specifically—remains only moderately supported (evidence rating: 3/5).

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