Folates

Folate Common Names

Folate | Vitamin B9 | Folic Acid | Folinic Acid | Calcium Folinate | L-5'-Methyltetrahydrofolate | 5'-Methyltetrahydrofolate | L-Methylfolate | Methyl THF | Pteroyl-L-Glutamate

Top Benefits of Folates

  • Supports genetic stability*
  • Supports production and maintenance of new cells*
  • Supports cardiovascular function*

What Are Folates?

Folates encompass all the different forms of vitamin B9 (the ninth of the B-vitamins discovered). These include folic acid (used in food fortification and most supplements), folinic acid (also called calcium folinate) and L-5'-methyltetrahydrofolate. Folates got their name from the Latin word for leaf (folium), because leafy green vegetables (e.g., lettuce, spinach) are one of the better food sources. Beans, lentils, nuts, and seeds are also good sources. Folates are critical for the production and maintenance of new cells, playing a key role in DNA expression and repair. Folates are a central player in a process called methylation or methyl donation. This process has widespread interactions with metabolic function. As an example, methylation is one of the main ways the expression of genes is changed to match our genes to diet, lifestyle and environment. 

Neurohacker’s Folate Sourcing

The main form of folate used in dietary supplements and food fortification is folic acid. Calcium folinate and L-5'-methyltetrahydrofolate are used less commonly: these two forms are often described as "active" forms because they require less metabolic work to be used in the body than folic acid. Gene polymorphisms affecting folate metabolism are fairly common. The folic acid form is most affected by gene polymorphisms (i.e., it's more difficult for some people to activate this form). Because of this, some experts believe it's better to avoid supplementing the folic acid form, and instead use the calcium folinate and L-5'-methyltetrahydrofolate forms. In our folate stack, we use both of these active forms and do not include folic acid. We believe it's important to include both calcium folinate and L-5'-methyltetrahydrofolate, because they enter the folate cycle at different points, which is consistent with one of our principles of offering full pathway support. Folate sourcing is focused on ensuring they are non-GMO, gluten-free and vegan.

Folate Dosing Principles and Rationale

Folates follow a threshold dosing pattern (see Neurohacker Dosing Principles) where most of the functional benefits occur at amounts close to the advised intake (400 µg DFE* for non-pregnant adults). In general, the folic acid form used in food fortification and many supplements has high bioavailability (absorption is excellent). But it’s fully converted to metabolically active folates in the digestive tract and liver only when given at low-to-moderate doses (< 260 µg DFE*). Some folic acid might not be activated at higher doses (it goes into the blood as unmetabolized folic acid).(1, 2) It’s thought that unmetabolized folic acid in the blood, but not biologically active folates, might not be ideal for health.(3–5) Since the folic acid form is used to fortify many foods, an average person will be getting some exposure to folic acid in the diet. To ensure that our products do not contribute to unmetabolized folic acid in the blood, we opted to not use the folic acid form. Instead, the folate stack uses the biologically active forms (calcium folinate and L-5'-methyltetrahydrofolate) to increase DFE amount given. These active forms of folate also have the advantage of being better used by persons that have some gene variants affecting folate metabolism. Put another way, the goal is to increase folates, but not folic acid, that reach the blood and tissues. Calcium folinate and L-5'-methyltetrahydrofolate accomplish this goal without the risk of increasing unmetabolized folic acid.

*DFE stands for dietary folate equivalents.

Folate Key Mechanisms

Cellular function

  • Folate coenzymes mediate the transfer of one-carbon units (one-carbon metabolism) (6, 7)
  • Folate coenzymes act as cofactors for several enzymes involved in key metabolic pathways, specifically in nucleic acid (DNA and RNA) and amino acid metabolism (6, 7)
  • Methyltetrahydrofolate is used by the cytosolic enzyme methionine synthase to generate methionine and tetrahydrofolate from homocysteine (6, 7)
  • Methionine is required for the synthesis of S-adenosylmethionine (SAMe), a methyl group donor used in many biological methylation reactions (6, 7)
  • Methionine synthase is essential for the methylation of nucleic acids (DNA and RNA) and proteins (6, 7)
  • Adequate folate status is needed to maintain NAD+ levels (8–10)


Cardiovascular and cerebrovascular function

  • Downregulates homocysteine levels (protects cardiovascular function); synergistic with vitamin B6 and vitamin B12 (11–13)


Nutrient Synergies

  • Vitamin B12 - The main safety concern associated with high doses of folic acid supplementation is that it might mask a vitamin B12 deficiency. Because of this, vitamin B12 is often given in combination with folic acid, especially if higher amounts of folic acid or other folates are used.
  • Methyl Donors - Key methyl donor nutrients include trimethylglycine (betaine), folates, vitamin B6, vitamin B12, and S-adenosylmethionine: One or more of these nutrients are often given together.

References

1. P. Kelly, J. McPartlin, M. Goggins, D. G. Weir, J. M. Scott, Am. J. Clin. Nutr. 65, 1790–1795 (1997).

2. M. R. Sweeney, J. McPartlin, J. Scott, BMC Public Health. 7, 41 (2007).

3. M. S. Morris, P. F. Jacques, I. H. Rosenberg, J. Selhub, Am. J. Clin. Nutr. 91, 1733–1744 (2010).

4. K. E. Christensen et al., Am. J. Clin. Nutr. 101, 646–658 (2015).

5. A. M. Troen et al., J. Nutr. 136, 189–194 (2006).

6. J. M. Berg, J. L. Tymoczko, G. J. Gatto, L. Stryer, Eds., Biochemistry (W.H. Freeman and Company, 8th ed., 2015).

7. O. Stanger, Curr. Drug Metab. 3, 211–223 (2002).

8. I. G. Beraia, Vopr. Pitan., 36–38 (1984).

9. S. J. James, L. Yin, M. E. Swendseid, J. Nutr. 119, 661–664 (1989).

10. S. M. Henning, M. E. Swendseid, W. F. Coulson, Male Rats Fed Methyl- and Folate-Deficient Diets with or without Niacin Develop Hepatic Carcinomas Associated with Decreased Tissue NAD Concentrations and Altered Poly(ADP-ribose) Polymerase Activity. The Journal of Nutrition. 127 (1997), pp. 30–36.

11. J. Selhub, Annu. Rev. Nutr. 19, 217–246 (1999).

12. E. Lonn et al., N. Engl. J. Med. 354, 1567–1577 (2006).

13. D. Serapinas et al., Reprod. Toxicol. 72, 159–163 (2017).


*These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.