Together Health's Folate supplement is a safe and effective option for people with MTHFR gene mutations looking to support their diet.

Vitamin B9 is a very complicated nutrient; many different conversions are required in the body before it is useful. The nutrient also has many different forms, and conversions differ depending on the form. However, very simply, when the body receives a form that requires conversion (most forms), it needs to convert it to an active form to utilise it; this active form is 5-methyltetrahydrofolate (5-MTHF), a methylated form.

People with MTHFR gene mutations have a reduced capacity to convert non-active forms of folate (natural vitamin B9) or folic acid (synthetic vitamin B9) into the active form the body requires.

Folic acid needs an additional conversation step to folate, which occurs in the liver. Still, both folic acid and the various forms of folate (other than 5-MTHF) eventually need a conversation step that involves the enzyme methylenetetrahydrofolate reductase—which the MTHFR gene provides instructions for the body to make.

These mutations, therefore, can cause the body's capacity to generate 5-MTHF to decrease anywhere from 17 to 75%¹. Therefore, people affected by these mutations must consume 20-300% more than someone without. However, filling this gap with folic acid can be dangerous because of the high risk of unmetabolised folic acid.

Unmetabolised folic acid refers to folic acid that remains in the bloodstream without being converted into its active form. This occurs for anyone when the intake of synthetic folic acid (from supplements or fortified foods) exceeds the body's ability to convert it to 5-MTHF. Therefore, people with a reduced ability to convert folic acid to 5-MTHF are at a greater risk of unmetabolised folic acid syndrome; factors such as age, intestinal pH, alcohol, folic acid dose and duration of supplement all affect someone's risk of elevated unmetabolised folic acid levels. However, people with MTHFR gene mutations are at particular risk. Unmetabolised folic acid is a concern because of its long-term health effects; it has been linked to serious health implications that are still not fully understood.

These concerns do not exist for any forms of folate; it's perfectly safe to consume higher amounts than the recommended daily amounts. In fact, no upper limit (the amount that, if regularly exceeded, may cause health concerns) exists for folate—high intakes have never been reported to cause adverse effects.

Our product, then, is perfectly safe to take for people with MTHFR gene mutations. But does it contain enough?

Folate in food can contain both the active form of folate, which does not require any conversion and forms that do need conversion. As our product contains folate extracted from spinach, it also contains a mixture of forms. Spinach is one of the richest sources of folate, and analysis² of spinach has shown it to contain, on average, 52% active, methylated folate, which requires no conversion. This figure is also collaborated by the analysis tests of our folate extract.

Our product contains 400μg, and the daily recommended amount (RDA) is 200μg. Based on the spinach analysis, the product, on average, provides the full 200μg RDA in a form requiring no conversion and around another 200μg that will get anywhere between 17% and 75% conversion, depending on the individual (our product is highly absorbed). However, spinach's 52% active folate is an average and can't be guaranteed. But we also need to consider our dietary intake. The mean dietary intakes³ ranges from 285 μg/ds to 479 μg/ds. The sources of this vary greatly and, therefore, the amount that needs converting. But as we have established, people with the gene mutations will still convert some of the non-active vitamin B9 they consume into 5-MTHF, just less than those without a mutation.

As there is a lot of variation between individual dietary intakes and the degree to which mutations affect conversion, it's therefore not possible to be certain what folate intake and eventual active folate levels an individual will have. Still, the figures allow for a large margin of error for anyone with an MTHFR gene mutation to obtain the folate they require when supplementing with our Folate supplement.

¹Servy, E. J., Jacquesson-Fournols, L., Cohen, M., & Menez, Y. J. R. (2018). MTHFR isoform carriers. 5-MTHF (5-methyl tetrahydrofolate) vs folic acid: a key to pregnancy outcome: a case series. Journal of Assisted Reproduction and Genetics, 35(8), 1431–1435. https://doi.org/10.1007/s10815-018-1225-2

²Shohag, M. J. I., Wei, Y., Yu, N., Zhang, J., Wang, K., Patring, J., He, Z., & Yang, X. (2011). Natural Variation of Folate Content and Composition in Spinach (Spinacia oleracea) Germplasm. Journal of Agricultural and Food Chemistry, 59(24), 12520–12526. https://dx.doi.org/10.1021/jf203442h

³Park, J. Y., Nicolas, G., Freisling, H., Biessy, C., Scalbert, A., Romieu, I., Chajès, V., Chuang, S.-C., Ericson, U., & Wallström, P. (2012). Comparison of standardised dietary folate intake across ten countries participating in the European Prospective Investigation into Cancer and Nutrition. British Journal of Nutrition, 108(3), 552–569. https://doi.org/10.1017/S0007114511005733