Written by Rhiannon Davis. Reviewed by Jenny Wordsworth.

When it comes to fertility, the role of essential nutrients is often underestimated. Folate, along with vitamins B6 and B12, plays a crucial role in reproductive health, particularly for individuals with MTHFR (methylenetetrahydrofolate reductase) mutations, who are more prone to elevated homocysteine levels. High homocysteine is not only linked to cardiovascular disease but has also been associated with recurrent pregnancy loss. So, can the right combination of B vitamins improve pregnancy outcomes? 

Homocysteine and Pregnancy Loss

Homocysteine is an amino acid found in the blood that, when elevated, has been linked to an increased risk of miscarriage, preeclampsia, and other pregnancy complications. Women with MTHFR mutations are particularly vulnerable, as their bodies have a reduced ability to process folate effectively, resulting in potentially higher homocysteine levels.

A small but significant study investigated whether supplementing with methylfolate (5 mg/day), vitamin B6 (50 mg/day), and vitamin B12 (1 mg/week) could reduce homocysteine levels and improve pregnancy outcomes. The results were striking: average homocysteine levels in the participants were significantly lowered after supplementation, from a pretty high level (19.4) to a much lower and likely healthier level (6.9), and this change was statistically meaningful.

More importantly, 7 out of 16 women who had experienced three or more miscarriages went on to conceive and deliver healthy babies within a year of starting supplementation.

The Bigger Picture: Do Lower Homocysteine Levels Always Lead to Better Outcomes?

The ability of B vitamins to lower homocysteine levels is well-documented. Studies have shown that B6, B12, and folate can significantly reduce homocysteine concentrations, which is beneficial not only for reproductive health but also for cardiovascular and cognitive function. However, research outside the fertility field has found mixed results regarding whether lowering homocysteine translates into meaningful health benefits. For example, studies on stroke patients and the elderly found that while B vitamin supplementation successfully reduced homocysteine levels, it did not always result in improved vascular or cognitive function.

So why is fertility different? The answer may lie in the severity of homocysteine elevation and the unique physiological demands of pregnancy. Unlike stroke patients or older adults, women trying to conceive with MTHFR mutations often start with significantly high homocysteine levels, which may have a more direct and measurable impact on their fertility. Additionally, pregnancy is a highly dynamic state that requires optimal methylation and nutrient availability, making B vitamin support particularly valuable.

What This Means for Women Trying to Conceive

If you have experienced recurrent pregnancy loss or have been diagnosed with an MTHFR mutation, it may be worth discussing homocysteine testing with your healthcare provider. If your levels are elevated (above 15-20 μmol/L), targeted supplementation with methylfolate, B6, and B12 could help. 

However, not all folate supplements are created equal. Many preconception supplements contain synthetic folic acid, which is not as efficiently converted in individuals with MTHFR mutations. Instead, choosing a supplement with methylfolate, the active form of folate, ensures better absorption and utilisation by the body.

The Key Takeawaya

While the research is still evolving, the evidence to date supports the role of folate, B6, and B12 in reducing homocysteine levels and improving pregnancy outcomes, particularly for women with MTHFR mutations. Given the low cost and high safety profile of these vitamins, supplementation may be a simple yet effective way to support fertility and a healthy pregnancy. If you suspect homocysteine might be a factor in your fertility journey, a conversation with a healthcare provider could be the next step toward a personalised plan that supports your reproductive health.