Folate is one of the essential B vitamins and has been the subject of nutritional research for decades. The nutrient was initially known under the collective term "folic acid," but modern science now clearly distinguishes between synthetic folic acid and the biologically active forms of folate. One of these active forms is 5-methyltetrahydrofolate (5-MTHF) , which is increasingly used in high-quality dietary supplements.
From folic acid to active folate – a brief historical overview
Folate was first isolated from spinach leaves in the 1940s. To meet the increasing demand in medicine and food fortification, synthetic folic acid was later developed because it is stable, inexpensive, and has a long shelf life. For decades, it was considered the standard form in supplements and fortified foods.
However, advances in biochemistry made it clear that folic acid is not a biologically active form . It must first be converted in the human body through several enzymatic steps before it can be used in metabolic processes. Its biological utilization is therefore indirect and delayed compared to already active folate. It was precisely at this point that 5-MTHF became the focus of research.
What is 5-MTHF?
5-MTHF is the natural, bioactive main form of folate in the human bloodstream . It is normally produced from dietary folates or from synthetic folic acid through enzymatic conversion, particularly via the enzyme methylenetetrahydrofolate reductase (MTHFR).
The crucial difference: 5-MTHF can be used directly in folate-dependent metabolic pathways without having to be activated beforehand.
Scientific background: Why shape matters
Over the past two decades, numerous studies have shown that genetic variations – particularly in the MTHFR gene – can influence the conversion of folic acid to active folate. Depending on the variant, this conversion can be less efficient.
A widely cited review article by Bailey & Gregory (1999) describes in detail the different forms of folate, their bioavailability, and their role in one-carbon metabolism. The authors show that 5-MTHF is the dominant circulating form of folate and plays a central role in methylation processes.
Another important study by Prinz-Langenohl et al. (2009) compared the bioavailability of 5-MTHF with synthetic folic acid. The results indicate that 5-MTHF contributes at least as effectively, and in some cases even more efficiently, to increasing folate status – without detectable unmetabolized folic acid in the blood.
Technological development of modern 5-MTHF forms
The use of 5-MTHF in dietary supplements was long a challenge, as the molecule is more sensitive than folic acid. Only through modern stabilization technologies, such as calcium or glucosamine salts (e.g., calcium L-methylfolate), has a stable, everyday-use supplement form become possible.
This development marks an important step towards differentiated micronutrient supply, which takes into account not only the quantity but also the biochemical form of a nutrient.
Conclusion
The development of 5-MTHF exemplifies the shift in modern nutritional science: away from purely synthetic standard solutions and towards biologically differentiated, biocompatible forms of nutrients . While classical folic acid has historically played an important role, current research shows that active folate forms such as 5-MTHF represent a sensible, contemporary advancement – especially where metabolic individuality needs to be taken into account.
Studies (selection):
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Bailey, L.B., & Gregory, J.F. (1999). Folate metabolism and requirements . Journal of Nutrition.
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Prinz-Langenohl, R. et al. (2009). Bioavailability of 5-methyltetrahydrofolate versus folic acid . American Journal of Clinical Nutrition.
Notice
Dietary supplements are intended to complement the diet . They are not a substitute for a balanced and varied diet and a healthy lifestyle, and are not intended to diagnose, treat, cure, or prevent any disease.
