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Other studies suggest that folate insufficiency due to MTHFR deficiency is bypassed by 5-MTHF supplementation. 27-29 Hence, active 5-MTHF, such as Quatrefolic, appears to be a preferred option for folate supplementation in individuals with MTHFR polymorphism.
Some people can have symptoms and also seem to have normal levels of these vitamins. And some people may have low levels despite having no symptoms. Identifying the cause
When to see a GP
Folate deficiency causes a reversible arrest in the S-phase of the cell cycle. ( A) Representative histogram of the cell cycle of LCL using alcohol fixation and propidium iodide DNA staining. LCLs were cultured for 10 days in standard RPMI medium (red curve) and in medium without FA (blue curve). ( B) Graph represents the average proportion of cells in the G0/G1, S, and G2 phase of cells cultured in standard RPMI medium and in folate-deficient medium ( n = 10). ( C, D) Concentration-dependent reversal of the proportion of cells in the S-phase. LCLs were cultured in folate-deficient medium for one week and then cultured for 72 h in the presence of different concentrations (6.25 nM, 12.5 nM, 25 nM and 50 nM) of FA ( C) or 5-Me-THF ( D). In each experiment, 1 × 10 6 cells of each LCL were analysed. Values are means ± SD. Statistical differences were determined by ANOVA with Tukey’s multiple comparison test. n.s. (not significant) p> 0.05, * p≤ 0.05, ** p≤ 0.01, *** p≤ 0.001, **** p< 0.0001 compared to control ( n = 10).
But the relationship between folate and cancer is a complicated one, especially for people at high risk of colon cancer. [29] Colorectal adenomas, or polyps, are pre-cancerous growths in the large intestine. A multiyear trial looked at whether high-dose folic acid supplements could prevent new polyps in people who had a history of polyps. [30] The study found that taking a daily pill with 1,000 micrograms of folic acid offered no protection against new polyps, and, more worrisome, increased the risk of developing multiple or more serious polyps. Some studies have explored the effects of 5-MTHF supplementation for individuals with MTHFR polymorphisms—wild-type CC or homozygous TT. Prinz-Langenohl et al 27 demonstrated that 5-MTHF supplementation isn’t affected by MTHFR gene polymorphism. In another chronic, bioavailability study, Litynski et al have shown a significant prolonged effect in reducing Hcy levels at six months after ceasing treatment with 5-MTHF in homozygous individuals (TT), at 12.1 ± 2.5 as compared to 16.9 ± 6.8 for folic acid ( P< .01). 28 Armitage JM, Bowman L, Clarke RJ, Wallendszus K, Bulbulia R, Rahimi K, Haynes R, Parish S, Sleight P, Peto R, Collins R. Effects of homocysteine-lowering with folic acid plus vitamin B12 vs placebo on mortality and major morbidity in myocardial infarction survivors: a randomized trial. JAMA. 2010 Jun;303(24):2486-94. Human lymphoblastoid cell line cells (LCLs) were a kind gift from the National Laboratory for the Genetics of the Israeli Population (NLGIP), a human diversity biobank at Tel Aviv University, Tel Aviv, Israel ( n = 35). LCLs are generated from fresh lymphocytes isolated from blood samples donated by consenting healthy adults and transformed by the Epstein-Barr virus (EBV); therefore, they can be grown in culture. Besides that, their nuclear DNA remains intact after immortalization; consequently, LCLs are a preferred method of storing an individual’s genetic material in biobanking [ 31]. These cell lines display the full spectrum of enzymes of the folate-homocysteine metabolism pathway and their reactions, and are a great model for studying metabolites of the folate-homocysteine cycle. LCLs were cultured in a RPMI 1640 medium (R5886, Sigma-Aldrich, Darmstadt, Germany) supplemented with 10% foetal bovine serum (Thermo Fisher Scientific, Gibco, Waltham, MA, USA), 4 mM l-glutamine, 100 U/mL penicillin, and 100 µg/mL streptomycin (all from Sigma-Aldrich, Darmstadt, Germany). For the experiments, LCLs were cultured in a RPMI 1640 without folic acid (L0503, Biowest, Nuaillé, France) supplemented with the same concentrations of foetal bovine serum, l-glutamine, penicillin, and streptomycin as classical RPMI 1640. When folate-free media was supplemented with serum, detectable levels of FA, (approximately 0.6 nM) were determined. On the other hand, standard RPMI medium (R5886, Sigma-Aldrich, Darmstadt, Germany) contains approximately 2266 nM (1 mg/L) of FA, an almost 4000-fold higher concentration compared to folate-free medium. Pitkin RM. Folate and neural tube defects. The American journal of clinical nutrition. 2007 Jan 1;85(1):285S-8S.We appreciate that NOW conducts comprehensive in-house testing on the safety, purity, and quality of their supplements, and that this supplement fits a variety of dietary needs. It is vegan, free of common food allergens, kosher, halal, and non-GMO. However, it is not a good fit for those who can’t metabolize folic acid. Most people get enough folate from food, so it is rare to have a folate deficiency. However, taking a folate supplement is beneficial, and even recommended, for some populations. When 6.25 nM, 12.5 nM, 25 nM, and 50 nM 5-Me-THF were added into folate-deficient medium, the proportion of cells in the S-phase decreased to 16.1% ( p = 0.038), 14.5% ( p = 0.0032), 12.9% ( p = 0.0002), and 12.0% ( p< 0.0001), respectively ( Figure 2D). When the equimolar concentrations of FA were added, the proportions of cells in the S-phase were 18.9% (n.s.; p = 0.38), 17.0% ( p = 0.024), 16.1% ( p = 0.0042), and 13.7% ( p< 0.0001), respectively ( Figure 2C). Taking too much folate from supplements or fortified foods can hide a vitamin B12 deficiency. Being deficient in vitamin B12 can lead to permanent brain and nerve damage. Taking too much folic acid may also increase the risk of some cancers, although more research is needed.
Jain R, Manning S, Cutler AJ. Good, better, best: clinical scenarios for the use of L-methylfolate in patients with MDD. CNS Spectrums. 2020;25(6):750-764. doi:10.1017/S1092852919001469 a specialist in nutrition (a dietitian) – if your GP suspects you have a vitamin B12 or folate deficiency caused by a poor diet Not all third-party testing is created equal. It is not uncommon for supplement companies to pay labs for certificates after conducting minimal to no testing. Another larger case series included 33 couples with fertility problems that had lasted for at least four years, such as recurrent fetal loss, premature ovarian insufficiency, or abnormal sperm parameters. Two-thirds of them had failed ART attempts. 52 For all the couples, at least one of the partners was a carrier of one of the two main MTHFR isoforms (C677T or A1298C), and the women had been previously treated unsuccessfully with high doses of FA (5 mg/day). The third party certifications we can trust are: ConsumerLab.com, NSF, and USP. However, these certifications are difficult to obtain and/or expensive for manufacturers, so many companies choose not to get their products tested by one of these three organizations.Rimm EB, Willett WC, Hu FB, Sampson L, Colditz GA, Manson JE, Hennekens C, Stampfer MJ. Folate and vitamin B6 from diet and supplements in relation to risk of coronary heart disease among women. JAMA. 1998 Feb 4;279(5):359-64.
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