Epinutrients and epigenetics are an exciting area of scientific research that shows how environmental influences, such as diet and nutrition, can affect the expression of our genes (or gene activity). As nutrition is one of the most important signals to our genes, for the purpose of this week’s blog we will take a look at ‘epinutrients’ and how these powerful nutritional compounds can impact our genes and benefit our health.
Genes are the building blocks of life and contain important information for making proteins which dictate the function of our cells. When the information stored in our DNA is converted into instructions for making proteins, it is called ‘gene expression’, which is a tightly controlled process that allows a cell to respond to its changing environment. Gene expression acts as both an on/off switch to control when proteins are made and also acts as a volume control that increases or decreases the number of proteins made.1
The genetic information stored in our DNA represents our genotype (which is our unique sequence of DNA), whereas the phenotype is the interpretation of that information, and results from the interaction between our genotype and our environment. Modifying the expression of genes through environmental factors can therefore impact on our development, ageing, and health in general.
Methylation is the transfer of one carbon methyl group from one molecule to another that either activates or deactivates that molecule and is fundamental to a range of metabolic processes such as:
- Histamine clearance
- Cell division
- DNA and RNA synthesis
- Hormone biotransformation
- Neurotransmitter synthesis, and so on
It is an ever-changing process that acts in response to nutritional and environmental influences and occurs around a billion times per second. Methylation is largely dependent on the presence of specific nutrients that act as cofactors to keep the ‘methylation cycle’ moving optimally. It is also the process by which our epigenetics regulate gene expression.
Epigenetic mechanisms switch genes on and off via several processes, a key one of which is called DNA methylation. DNA methylation (a subsection of methylation) is a process by which methyl groups are added to the DNA molecule. The process of DNA methylation tells the body which genes should be turned on or off and therefore activates or inhibits the production of proteins.
When working well, DNA methylation can have a positive effect on many aspects of health. Impaired methylation however can lead to the production of proteins that might not be needed or the suppression of proteins that are. This can potentially increase the risk of many conditions.2 For example, if not methylating properly you may not be able to switch off cancer genes, or activate tumour suppressing ones. Importantly, the risks can be modified by ensuring the availability of sufficient methyl donor nutrients through the diet and their cofactors (epinutrients).
Epinutrient, simply means a nutrient that can have an epigenetic effect and these powerful compounds can directly affect the epigenome due to their functional roles in driving DNA methylation.3 They can be thought of as molecules that regulate gene expression by providing the building blocks for and directing methylation processes.4 Below we will take a look at some of the main ones.
Methyl donor nutrients are used to create methyl groups (a single carbon atom and three hydrogen atoms — CH3). The primary methyl donor for methylation is S-adenosylmethionine (SAMe), which requires folate, choline, betaine, and some of the B vitamins. Having the correct amount of methyl donors is vital for balanced DNA methylation.
Folate, a water-soluble B vitamin is perhaps the most well-known nutrient in relation to methylation and is a key component of the one carbon group used to methylate DNA. It is also involved in DNA synthesis and maintenance. Active folate donates a methyl group to homocysteine to convert it to methionine, thus supporting healthy homocysteine levels. Methionine can then be used to form S-adenosylmethionine. Moderate elevations in plasma homocysteine concentration have been reported to be associated with DNA hypomethylation.5
In those with the MTHFR gene variants (thought to affect over 40% of the population), folate and folic acid metabolism is impaired so that it is not efficiently reduced to its active form. A major consequence of folate deficiency is a build-up of homocysteine, which corresponds to a greater risk of developing cardiovascular disease, neurodegenerative disease, diabetes, and most inflammatory diseases (as homocysteine is a highly inflammatory free radical).
Sources – folate is mainly present in green leafy vegetables, such as kale, spinach, and collard greens, while its synthetic form (folic acid) is often used in the fortification of foods and in some dietary supplements. Folic acid, however, may block active folate site receptors. Furthermore, a build-up of unmetabolized folic acid is potentially toxic and may pose health risks. Methylated B vitamins are often the preferred choice for many as methylfolate (the active form of folate) is more easily absorbed and can bypass the MTHFR enzyme. A good quality multivitamin containing the active form can provide a good place to start for overall support.
The water-soluble vitamins B2, B6, and B12 have an important catalytic role in folate and one-carbon metabolism.7 Vitamin B12 is the coenzyme of methionine synthase, which catalyses the reaction of homocysteine to methionine. B12 deficiency varies widely in the population from 2.5% to 26% and even higher levels of deficiency are found in different sub-populations such as children, young adults, pregnant women and the elderly.6 People at increased risk also include those with genetic mutations (MTR, MTRR), low stomach acid or other digestive conditions leading to malabsorption. Our body should convert B12 obtained from food to the activated form, although many of us do not adequately process this conversion.
Sources – food sources containing vitamin B12 are mainly animal products, so vegetarian or vegan diets may be lacking in this important nutrient. Meat, poultry, fish and eggs are sources of B12 although obtaining optimal levels may be challenging through diet alone. Including a good quality supplement with the active form, methylcobalamin, may also be of benefit.
Choline is an indirect methyl group donor for one-carbon metabolism and subsequently DNA methylation.7 The fact that diet can modify DNA methylation was appreciated decades ago when it was observed that a diet very low in choline and methionine resulted in the decreased methylation of cytosines in the DNA of liver, which was linked to the development of liver cancer.7,8
Sources – the richest dietary sources of choline can be found in eggs, meat, liver, fish, beets, mushrooms and dairy products.
Betaine is a direct methyl donor as it donates a methyl group to homocysteine, resulting in its conversion to methionine. Betaine is a source of up to 60% of the methyl groups required for the methylation of homocysteine.9 Cumulative evidence suggests a significant contribution of choline and betaine to methyl metabolism and DNA methylation and accordingly to gene regulation in carcinogenesis.10
Food sources – spinach, beets, wholegrains, seafood and wheatbran
Methionine is a sulphur-containing amino acid that is abundant in animal food sources such as meat, poultry, fish and eggs and plant-based sources such as nuts, beans and lentils. It is important as it is a precursor for s-adenosylmethionine, the universal methyl donor for DNA methylation.
There are many more nutrients that have epigenetic activity and can help to drive methylation processes. These can be referred to as methylation adaptogens4 or epigenetic modifiers, as they are capable of influencing the enzymes that help to carry out methylation. These include flavonoids such as quercetin, curcumin, rosmarinic acid and EGCG. Flavonoids are one of the largest groups of phytonutrients and can exert numerous health benefits. For example, EGCG found in green tea, may help to prevent hypermethylation and support the re-expression of good genes through passive demethylation.4 Quercetin may help to optimize genetic expression and slow down ageing.4
Furthermore, emerging research suggests that specific bioactive food components, including tea polyphenols, genistein from soybean, or isothiocyanates from plant foods, might inhibit the development of disease by reducing DNA hypermethylation status in critical genes associated with disease.11,12
In addition vitamins A, D and C are important methylation adaptogens and active de-methylating nutrients.4
Just as we can take steps to ensure our diet is naturally high in methylation supporting nutrients, we can also ensure that we minimise or exclude those factors that can negatively impact on methylation and gene expression. These include:
- exposure to toxins, such as pesticides
- chronic stress
- excessive alcohol intake
- lack of exercise
- excessive sugar
- poor diet
- trans fats, and so on.
Signs that you may need methylation support
- fatigue – methylation affects energy metabolism
- high homocysteine – implicated in many diseases and often due to a shortage of active folate
- problems detoxifying – detoxification processes may also be impaired, which can result in toxic burden and sensitivities
- hormonal imbalances
- mood disorders – methylation is needed for the production of several key mood-modulating neurotransmitters
- allergies – methylation is involved in the detoxification of excess histamine
- imbalanced Th1/Th2
- chronic disease – DNA/RNA expression alters potentially resulting in disease
We have in our hands the ability to positively influence our health through nutrition and we can do so by paying attention to the wide range of epinutrients found in wholefoods and their powerful effects on modifying the expression of our genes. Our genes are therefore only the starting point in our journey to health.
Our status of nutrients such as folate and B12 are likely to correlate with DNA methylation and if suboptimal can offer a potential way forward in reaching health goals, particularly in relation to conditions where impaired DNA methylation is associated. The optimisation of the methylation cycle can therefore become a potential route to better health.
Increasing our intakes of a range wholefoods can ensure we are obtaining many of the health promoting compounds, and where needed, the addition of supplements containing the active forms of nutrients may be supportive.
It is worth noting however that some people may not initially tolerate methyl donor supplementation well and to be mindful of this. Too much methylation can be as problematic as too little. Well formulated multi-nutrient formulae with supportive levels of methylated nutrients appropriate for age and sex of a person are usually safe for all but if you are oversensitive, which can be a sign of over-methylation, we advise you seek the help and advice of a nutritional therapist trained in nutrigenetic counselling.
- Environmental influences, such as nutrition, can affect the expression of our genes
- Genes contain important information for making proteins which dictate the function of cells
- Gene expression acts as both an on/off switch to control when proteins are made
- Methylation is fundamental to a range of metabolic processes
- Methylation is largely dependent on the presence of specific nutrients that keep the ‘methylation cycle’ moving optimally
- Epigenetic mechanisms switch genes on and off via several processes, a key one is DNA methylation
- Impaired methylation can lead to the production of proteins that might not be needed or the suppression of proteins that are
- Epinutrient, simply means a nutrient that can have an epigenetic effect and they have functional roles in driving DNA methylation
- Primary methyl donor is S-adenosylmethionine which requires folate, choline, betaine, and some of the B vitamins
- Having the correct amount of methyl donors is vital for balanced DNA methylation
- Many more nutrients help to drive methylation processes – methylation adaptogens
- These include flavonoids such as quercetin, curcumin, rosmarinic acid and EGCG
- Vitamins A, D and C are important methylation adaptogens
- Fatigue, problems detoxifying, hormonal imbalances, chronic disease may be signs that methylation support is needed
If you have questions regarding the topics that have been raised, or any other health matters, please do contact our team of Nutritional Therapists.
- What is gene expression? – YourGenome (2022). (Accessed: 6 October 2022).
- Kadayifci, F.Z., Zheng, S. and Pan, Y.X. (2018) ‘Molecular Mechanisms Underlying the Link between Diet and DNA Methylation’, International journal of molecular sciences, 19(12).
- Mazzio, E.A. and Soliman, K.F.A. (2014) ‘Epigenetics and nutritional environmental signals’, Integrative and comparative biology, 54(1), pp. 21–30.
- Epinutrients – The Secret Ingredient That Makes Food Your Medicine (2021). (Accessed: 23 September 2022).
- Yi, P. et al. (2000) ‘Increase in plasma homocysteine associated with parallel increases in plasma S-adenosylhomocysteine and lymphocyte DNA hypomethylation’, The Journal of biological chemistry, 275(38), pp. 29318–29323.
- Ogunkolade, B.W. et al. (2021) ‘An integrative epi-transcriptomic approach identifies the human cartilage chitinase 3-like protein 2 ( CHI3L2) as a potential mediator of B12 deficiency in adipocytes’, Epigenetics [Preprint].
- Anderson, O.S., Sant, K.E. and Dolinoy, D.C. (2012) ‘Nutrition and epigenetics: an interplay of dietary methyl donors, one-carbon metabolism and DNA methylation’, The Journal of nutritional biochemistry, 23(8), pp. 853–859.
- Wilson, M.J., Shivapurkar, N. and Poirier, L.A. (1984) ‘Hypomethylation of hepatic nuclear DNA in rats fed with a carcinogenic methyl-deficient diet.’, Biochemical Journal, 218(3), p. 987.
- Pellanda, H. (2013) ‘Betaine homocysteine methyltransferase (BHMT)-dependent remethylation pathway in Human healthy and tumoral liver’, Clinical Chemistry and Laboratory Medicine, 51(3), pp. 617–621.
- Mahmoud, A.M. and Ali, M.M. (2019) ‘Methyl Donor Micronutrients that Modify DNA Methylation and Cancer Outcome’, Nutrients, 11(3).
- Fang, M., Chen, D. and Yang, C.S. (2007) ‘Dietary Polyphenols May Affect DNA Methylation’, The Journal of Nutrition, 137(1), pp. 223S-228S.
- Choi, S.W. and Friso, S. (2010) ‘Epigenetics: A New Bridge between Nutrition and Health’, Advances in nutrition (Bethesda, Md.), 1(1), pp. 8–16.
Last updated on 25th October 2022 by cytoffice