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Perhaps one of our most critical processes that underpins our health and well-being is one called methylation. This process which underlies so many body functions is the addition of a ‘methyl group’ to other molecules. Yet this seemingly simple chemical process, occurring billions of times every second, is important for our mood, brain function, supporting energy levels, detoxifying harmful substances, helping our immune system, supporting growth and repair, and lots more. It's a process that is called upon a lot when we are under stress, so can potentially become depleted. And perhaps, you could argue, it’s something we all need to make sure we’re supporting. Are you one of those people?
Methylation is dependent on supply of folate from foods. The body creates an important substance called methylfolate or 5-MTHF (the active form of folate or ‘folic acid’). Together with vitamin B12, especially the more active ‘methylcobalamin’ form, this then results in a substance called SAMe (S-adenosyl methionine) which can then give up its 'methyl group’ thus promoting methylation in a whole host of processes, including:
In fact, poor methylation has been linked to many health complaints, including: Alzheimer’s disease,[i] polycystic ovary syndrome (PCOS),[ii] birth defects,[iii] multiple sclerosis (MS),[iv] depression[v], autism[vi], migraines [vii] or heart disease[viii].
What can affect methylation and makes us less able to perform this vital function?
As well as methylfolate and methylcobalamin, other nutrients such as zinc, magnesium, choline, B6 and B2 are also needed for proper methylation, thus deficiencies in any of these can reduce our ability to 'methylate' and perform all of those vital functions effectively, which can have a knock-on effect on different body systems. For example, if you are vegetarian, your intake of B12, B6, zinc and choline may be low, while carnivores may not have enough folate or magnesium, especially if they’re not eating enough green leafy vegetables. In addition, if you are suffering with digestive complains such as IBS or use acid blocking medication for your heartburn, your absorption of those nutrients may be significantly reduced.
We also need to consider drains on methylation – certain lifestyle and environmental factors that can put stress on methylation and divert its attention from other important tasks. Stress, both psychological and physiological (e.g. frequent infections, blood sugar imbalances, excessive exercise) can be a big drain, because it relies on production of various hormones and neurotransmitters, which are driven by methylation. High sugar diet and high exposure to environmental toxins (non-organic cosmetics, heavy metals, plastics, tobacco smoking etc), would also be high on the list of so called ‘methyl depletors’.
Our genetic make-up may mean that some of us are predisposed to methylate less well. Amongst many genes that we know of, the MTHFR gene (methylenetetrahydrofolate reductase) has been very well studied and linked to all of those conditions we discussed. This gene produces an enzyme responsible for methylfolate synthesis. Certain, relatively common ‘mutations’ in this gene can reduce our ability to produce methylfolate by up to 70%[ix], which can have a deleterious effects on methylation.
We can now test for this and other genetic variants through several labs offering nutritional testing. A registered Nutritional Therapist, who’s had genetic training would be able to order and help you interpret such tests, providing dietary and lifestyle recommendations to suit your individual requirements. Genetic testing however, is not essential for everyone and does not provide all the answers. You can safely and effectively support your methylation without even knowing whether you have this gene mutation or not, but if you have a serious or multiple chronic conditions, this extra bit of information can sometimes be helpful to further personalise your lifestyle plan and help you achieve better results more quickly.
So how do you know if you have a potential problem with methylation?
If you have one or a combination of the following symptoms/conditions:
Methylfolate and folic acid - what's the difference?
As we’ve already established, folate in a form of methylfolate is crucial for methylation. Dietary sources provide different forms of this vitamin, which often need to be converted to methylfolate. In supplements however, the most widely used form is folic acid. Supplementation with folic acid has been useful for many purposes. For example, in pregnant women it has had an incredibly positive effect on the rates of neural tube defects (NTDs), by reducing their incidence by up to 70%.[x]
Despite its benefits, some of us may not be able to process folic acid effectively. That’s why supplementing with a more bioavailable form, such as methylfolate is beneficial for everyone, but especially for those people affected by methylation problems. By supplementing with 5-MTHF, you are skipping a few enzymatic processes, meaning that it can be quickly absorbed into the bloodstream to do its job. A specific form, called Quatrefolic® has been shown to be the most effective and absorbable form of folate available on the market and far surpasses folates found in food, folic acid or even other forms of methylfolate available (e.g.metafolin).[xi]
A good and strong multivitamin containing methylfolate and methylcobalamin can provide a great baseline for overall methylation support, while individual nutrients in a liquid form may be particularly useful if you require a specific dose, struggle with digestive issues or find it difficult to swallow capsules.
Dietary and lifestyle strategies to optimise methylation
Environmental and lifestyle support:
[i] McCaddon A. Vitamin B12 in neurology and ageing; clinical and genetic aspects. Biochimie. 2013; 95(5):1066-1076.
[ii] Wang XX et al. Genome-wide DNA methylation and gene expression patterns provide insight into polycystic ovary syndrome development. Oncotarget. 2014;5(16):6603-6610.
[iii] Donnan J et al. A systematic review of the risk factors associated with the onset and natural progression of spina bifida. Neurotoxicology. 2016. [Epub ahead of print].
[iv] Neven KY et al. Repetitive element hypermethylation in multiple sclerosis patients. BMC Genet. 2016;17(1):84
[v] Gandolfo G et al. Association of the COMT synonymous polymorphism Leu136Leu and missense variant Vak158Met with mood disorders. J Affect Disord. 2015; 177:108-113.
[vi] Shaik Mohammad N et al. Clinical utility of folate pathway genetic polymorphisms in the diagnosis of autism spectrum disorders. Psychiatr Genet. 2016;26(6):281-286.
[vii] Liu A et al. Analysis of the MTHFR C677T variant with migraine phenotypes. . BMC Research Notes 2010;3:213.
[viii] Wernimont SM et al. Polymorphisms in serine hydroxymethyltransferase 1 and methylenetetrahydrofolate reductase interact to increase cardiovascular disease risk in humans. J Nutr.2011;141(2):255-60.
[ix] Frosst P et al. A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nat Genet. 1995;10:111-13.
[x] NHS, available at: http://www.nhs.uk/conditions/spina-bifida/pages/causes.aspx. Accessed 02.03.2017
[xi] Miraglia N et al. Enhanced oral bioavailability of a novel folate salt: comparison with folic acid and a calcium folate salt in a pharmacokinetic study in rats. Minerva Ginecol. 2016;68(2): 99-105.
[xii] Rossi M, Amaretti A, Raimondi S. Folate Production by Probiotic Bacteria. Nutrients. 2011;3(1):118-134.
[xiii] Gibson GR, Beatty ER, Wang X & Cummings JH. Selective stimulation of bifidobacteria in the human colon by oligofructose and inulin. Gastroenterol. 1995 108:975-982.
[xiv] Bouhnik Y et al. Effects of fructo-oligosaccharides ingestion on fecal bifidobacteria and selected metabolic indexes of colon carcinogenesis in healthy humans. Nutr Cancer. 1996;26(1):21-9.
[xv] Thakur VS et al. Plant Phytochemicals as Epigenetic Modulators: Role in Cancer Chemoprevention. The AAPS Journal. 2014;16(1):151-163.
[xvi] Food Standards Agency. Survey of total and inorganic arsenic in rice drinks. Last updated: May 2009. Available at: https://www.food.gov.uk/science/research/surveilla...
[xvii] Monrad M et al. Low-level arsenic in drinking water and risk of incident myocardial infarction: a cohort study. Environ Res. 2017; 154: 318-324
[xviii] Rima D, et al. Oxidative Stress Induced Damage to Paternal Genome and Impact of Meditation and Yoga - Can it Reduce Incidence of Childhood Cancer? Asian Pac J Cancer Prev. 2016;9;17(9):4517-4525.
[xix] Harkess KN et al. Preliminary indications of the effect of a brief yoga intervention on markers of inflammation and DNA methylation in chronically stressed women. Translational Psychiatry. 2016;6(11):e965.
[xx] Ren H. et al. Epigenetic Changes in Response to Tai Chi Practice: A Pilot Investigation of DNA Methylation Marks. Evidence-Based Complementary and Alternative Medicine, 2012:Article ID 841810: 9 pages.