Folate (as Calcium Folinate)

COMMON NAME

Folate | Vitamin B9 | Calcium folinate | Folinic Acid

TOP BENEFITS OF FOLATE

Supports genetic stability*

Supports production and maintenance of new cells*

Supports cardiovascular function* 

WHAT IS FOLATE?

Folates can be thought of as a family of related but slightly different vitamer forms all of which have vitamin B9 activity (the ninth of the B-vitamins discovered). They include folic acid, calcium folinate (also called folinic acid) 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. Folate is critical for the production and maintenance of new cells, playing a key role in DNA expression and repair. Folate is 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. Calcium folinate is considered to be an active form of folic acid [1,2], because it does not require the action of an enzyme (dihydrofolate reductase) needed to activate folic acid [3], is rapidly converted into 5-methyltetrahydrofolate (the major transport and storage form of folate in the body) [4–9]. 

NEUROHACKER’S FOLATE SOURCING

The main form of folate typically used in dietary supplements is folic acid. In general, the folic acid 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) [10,11]. It’s been hypothesized that unmetabolized folic acid in the blood, but not biologically active folates, might not be ideal for health [12–14]. Because of this, we opted to use the more metabolically active form of calcium folinate, which requires less metabolic work to be used in the body than folic acid and which is rapidly converted into 5-methyltetrahydrofolate [4–6].* 

Folate as calcium folinate is a non-GMO, gluten-free, and vegan ingredient.

FOLATE DOSING PRINCIPLES AND RATIONALE

Research suggest that 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). Since there’s some contribution of folates from the diet (partly through food fortification with folic acid), our recommended dosing is selected to ensure that the combination of what we provide, and what’s found even in a diet that’s low in folates, will provide at least the advised intake, but not an excessive amount of folates.*

‡DFE stands for dietary folate equivalents.

FOLATE KEY MECHANISMS

Supports Cellular Function*

Folate coenzymes mediate the transfer of one-carbon units (one-carbon metabolism) [15,16]

Folate coenzymes act as cofactors for several enzymes involved in key metabolic pathways, specifically in nucleic acid (DNA and RNA) and amino acid metabolism [15,16]

Adequate folate status is needed to maintain NAD+ levels [17–19]


Supports Healthy Brain Function*

Supports healthy cognitive function [20–25]

Supports neurotransmitter synthesis (e.g., dopamine, norepinephrine, serotonin) [26,27]

Supports healthy blood-brain barrier function [28]

Supports neuroprotective and neuronal repair functions [29–34]

Supports a healthy mood and positive outlook [35–39]


Supports Healthy Cardiovascular and Cerebrovascular Function*

Influences homocysteine levels (supports protection of cardiovascular function); complementary to vitamin B6 and vitamin B12 [40–42]


Complementary Ingredients*

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.


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


REFERENCES 

[1]Y.D. Gristan, L. Moosavi, in: StatPearls, StatPearls Publishing, Treasure Island (FL), 2021.

[2]Y. Menezo, K. Elder, A. Clement, P. Clement, Biomolecules 12 (2022).

[3]F. Scaglione, G. Panzavolta, Xenobiotica 44 (2014) 480–488.

[4]V.M. Whitehead, R. Pratt, A. Viallet, B.A. Cooper, Br. J. Haematol. 22 (1972) 63–72.

[5]R.F. Pratt, B.A. Cooper, J. Clin. Invest. 50 (1971) 455–462.

[6]H. Taguchi, J. Nutr. Sci. Vitaminol. 27 (1981) 283–290.

[7]N. Gordon, Dev. Med. Child Neurol. 51 (2009) 180–182.

[8]K. Hyland, J. Shoffner, S.J. Heales, J. Inherit. Metab. Dis. 33 (2010) 563–570.

[9]I.D. Goldman, in: M.P. Adam, H.H. Ardinger, R.A. Pagon, S.E. Wallace, L.J.H. Bean, K.W. Gripp, G.M. Mirzaa, A. Amemiya (Eds.), GeneReviews®, University of Washington, Seattle, Seattle (WA), 2008.

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

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

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

[13]K.E. Christensen, L.G. Mikael, K.-Y. Leung, N. Lévesque, L. Deng, Q. Wu, O.V. Malysheva, A. Best, M.A. Caudill, N.D.E. Greene, R. Rozen, Am. J. Clin. Nutr. 101 (2015) 646–658.

[14]A.M. Troen, B. Mitchell, B. Sorensen, M.H. Wener, A. Johnston, B. Wood, J. Selhub, A. McTiernan, Y. Yasui, E. Oral, J.D. Potter, C.M. Ulrich, J. Nutr. 136 (2006) 189–194.

[15]J.M. Berg, J.L. Tymoczko, G.J. Gatto, L. Stryer, eds., Biochemistry, 8th ed, W.H. Freeman and Company, 2015.

[16]O. Stanger, Curr. Drug Metab. 3 (2002) 211–223.

[17]I.G. Beraia, Vopr. Pitan. (1984) 36–38.

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

[19]S.M. Henning, M.E. Swendseid, W.F. Coulson, The Journal of Nutrition 127 (1997) 30–36.

[20]F. Ma, X. Zhou, Q. Li, J. Zhao, A. Song, P. An, Y. Du, W. Xu, G. Huang, Curr. Alzheimer Res. 16 (2019) 622–632.

[21]H. Chen, S. Liu, L. Ji, T. Wu, Y. Ji, Y. Zhou, M. Zheng, M. Zhang, W. Xu, G. Huang, Mediators Inflamm. 2016 (2016) 5912146.

[22]F. Ma, Q. Li, X. Zhou, J. Zhao, A. Song, W. Li, H. Liu, W. Xu, G. Huang, Eur. J. Nutr. 58 (2019) 345–356.

[23]F. Ma, T. Wu, J. Zhao, F. Han, A. Marseglia, H. Liu, G. Huang, J. Gerontol. A Biol. Sci. Med. Sci. 71 (2016) 1376–1383.

[24]J. Durga, M.P.J. van Boxtel, E.G. Schouten, F.J. Kok, J. Jolles, M.B. Katan, P. Verhoef, Lancet 369 (2007) 208–216.

[25]J.G. Walker, P.J. Batterham, A.J. Mackinnon, A.F. Jorm, I. Hickie, M. Fenech, M. Kljakovic, D. Crisp, H. Christensen, Am. J. Clin. Nutr. 95 (2012) 194–203.

[26]S.M. Stahl, J. Clin. Psychiatry 69 (2008) 1352–1353.

[27]A.L. Miller, Altern. Med. Rev. 13 (2008) 216–226.

[28]P.J. Stover, J. Durga, M.S. Field, Curr. Opin. Biotechnol. 44 (2017) 146–152.

[29]Y. Lin, A. Desbois, S. Jiang, S.T. Hou, Neuroreport 15 (2004) 2241–2244.

[30]H.-L. Yu, L. Li, X.-H. Zhang, L. Xiang, J. Zhang, J.-F. Feng, R. Xiao, Br. J. Nutr. 102 (2009) 655–662.

[31]F.S. Quan, X.F. Yu, Y. Gao, W.Z. Ren, Genet. Mol. Res. 14 (2015) 12466–12471.

[32]I.I. Kruman, T.S. Kumaravel, A. Lohani, W.A. Pedersen, R.G. Cutler, Y. Kruman, N. Haughey, J. Lee, M. Evans, M.P. Mattson, J. Neurosci. 22 (2002) 1752–1762.

[33]G. Kronenberg, C. Harms, R.W. Sobol, F. Cardozo-Pelaez, H. Linhart, B. Winter, M. Balkaya, K. Gertz, S.B. Gay, D. Cox, S. Eckart, M. Ahmadi, G. Juckel, G. Kempermann, R. Hellweg, R. Sohr, H. Hörtnagl, S.H. Wilson, R. Jaenisch, M. Endres, J. Neurosci. 28 (2008) 7219–7230.

[34]B.J. Iskandar, A. Nelson, D. Resnick, J.H.P. Skene, P. Gao, C. Johnson, T.D. Cook, N. Hariharan, Ann. Neurol. 56 (2004) 221–227.

[35]W. Zheng, W. Li, H. Qi, L. Xiao, K. Sim, G.S. Ungvari, X.-B. Lu, X. Huang, Y.-P. Ning, Y.-T. Xiang, J. Affect. Disord. 267 (2020) 123–130.

[36]D. Mischoulon, M.F. Raab, J. Clin. Psychiatry 68 Suppl 10 (2007) 28–33.

[37]M.J. Taylor, S. Carney, J. Geddes, G. Goodwin, Cochrane Database Syst. Rev. (2003) CD003390.

[38]J.E. Alpert, M. Fava, Nutr. Rev. 55 (1997) 145–149.

[39]S.N. Young, A.M. Ghadirian, Prog. Neuropsychopharmacol. Biol. Psychiatry 13 (1989) 841–863.

[40]J. Selhub, Annu. Rev. Nutr. 19 (1999) 217–246.

[41]E. Lonn, S. Yusuf, M.J. Arnold, P. Sheridan, J. Pogue, M. Micks, M.J. McQueen, J. Probstfield, G. Fodor, C. Held, J. Genest Jr, Heart Outcomes Prevention Evaluation (HOPE) 2 Investigators, N. Engl. J. Med. 354 (2006) 1567–1577.

[42]D. Serapinas, E. Boreikaite, A. Bartkeviciute, R. Bandzeviciene, M. Silkunas, D. Bartkeviciene, Reprod. Toxicol. 72 (2017) 159–163.