What is Methylation?
Methylation is a metabolic process that occurs in every cell and organ in our body. Life would not exist without it. Methylation occurs when one molecule passes a methyl group (a carbon atom with three hydrogens attached to it) to another molecule. This takes place around a billion times per second in our body. Methylation is critical for detoxification, immune function, DNA production, energy, cognitive function and controlling inflammation. Poor methylation leads to many chronic conditions.
Methylation in Trisomy 21
Research indicates that methylation patterns in Trisomy 21 (T21) newborns are different from typical newborns proving the extra chromosome changes the activity of methylation in people with T21 1. In addition, adults with T21 have different methylation patterns to newborns with T21 due to a ‘lifetime of environmental exposure’. Methylation is a dynamic process that changes all the time and is influenced by our environment and genetics, even in T21 1.
In T21, the gene DNMT3L (DNA methyltransferase 3L) sits on chromosome 21 and influences enzymes DNMT3a and 3b which are DNA methylators, and may be the cause of hypermethylation in T21 9.
In addition, the CBS gene, located on chromosome 21 is overexpressed in T21 creating low levels of homocysteine, methionine, SAH and SAMe. Low production of SAMe, our primary methyl donor results in hypomethylation (low methylation output). SAMe is required to convert serotonin to melatonin, which helps us go to sleep, to make glutathione for detoxification, to make proteins such as myelin the sheath around our nerves essential for nerve function, the creation of CoQ10, creatine and carnitine, essential for mitochondria, heart, muscles, and cellular energy production, and the conversion of norepinephrine to epinephrine our neurotransmitters involved in focus and speech, along with dopamine 2.
Supplementing the diet with SAMe end-products such as creatine*, choline (phospatidylcholine) and carnitine has been shown in research to increase DNA methylation 10. This is known as ‘methyl conserving’, as these compounds use up to 80% of your SAMe to be made. When we supplement with these nutrients directly, methylation doesn’t have to work so hard.
Methylation is driven by nutrients
Fortunately, methylation is a nutrient driven cycle, so we can improve its function through nutritional supplementation. A landmark study by Professor Jill James (2001) proved that the addition of folate and vitamin B12 to the diet resulted in increased methionine and SAMe production in people with T21 3. This showed that despite the extra chromosome causing poor methylation, we could improve it. This study was a turning point in nutrigenomic treatment of people with T21 because methylation plays such a critical role in health and development.
Until recently it was thought that the health and development of a person with T21 couldn’t be changed. Research into methylation proves that nutritional optimisation can enhance methylation activity.
The Agouti mouse experiment
A really good example of how diet affects methylation is illustrated by Randy Jirtle and his experiment with Agouti mice in 2003 4. Jirtle’s experiment proved that something as subtle as diet can change our gene expression. Mice fed a diet rich in methylation nutrients were small, slim, dark and disease free. Mice deprived of methylation nutrients grew overweight, with yellow coats and developed obesity and diabetes (see Image 1). A subsequent experiment (2006) revealed that Genistein, a phytoestrogen, modified gene expression and reduced disease risk despite not donating any nutrients to the methylation cycle. A further study showed that Genistein in addition to methyl nutrients such as folate and B12 reduced the damaging effects of Bisphenol A (BPA) on gene expression.
This is important, because it proves that methylation is affected by other factors apart from nutrition. In fact current research shows that our environment has a significant impact on methylation; stress, adequate sleep, exercise, toxins, the microbiome. If these things are out of balance, our SAMe is going to be used up rapidly, depriving us of methyl donors we need for cognition, speech, digestion, muscle growth, immunity and more. 5
Methylation ‘adaptogens’
Polyphenols such as Resveratrol, Curcumin and EGCg support methylation and the production of SAMe by reducing stress, inflammation and toxins 6, 7, 8 and are associated with balancing hypo and hypermethylation, like adaptogenic herbs which balance our adrenal glands 5. They are considered to be methylation ‘adaptogens’. Isn’t nature incredible!
A Methyl donor rich diet
If we provide our bodies with the best micronutrients and lifestyle behaviours, we can optimise methylation 5. A diet rich in methyl donors includes foods such as beets, greens, liver and is a low glycaemic, anti inflammatory diet (see Infographic). The second diagram (Image 2) below shows which nutrients are required for each section of the methylation cycle to function efficiently. The best way to understand what nutrients your child needs is to do functional medicine testing. I have found testing an invaluable tool for revealing what specific nutrients a child is deficient in. In many cases children are deficient in nutrients primarily because of stress, inflammation, dysbiosis, poor sleep draining nutrients more quickly than can be made. When we treat the root cause of stress and replace these nutrients its amazing how quickly they begin to respond and thrive.
It is thought that in future epigenetic analysis such as tests which look at methylation, will become routine practice 5. Methylation status is currently assessed using Organic Acid and Amino Acid testing. Because children with T21 are born with an atypical pattern of methylation monitoring this cycle allows us to optimise it with diet and supplements as discussed.
1) Organic Acid tests examine the following things which affect methylation; folate, B12 and all B vitamins, CoEnzyme Q10, Glutathione, Amino Acids, ATP production, Neurotransmitters – Dopamine, Serotonin, Adrenalin/ Noradrenalin, Candida and dysbiosis.
2) Amino acid tests analyse amino acids related to methylation cycle function; Homocysteine, Taurine, Serine, Cysteine, Tyrosine, Methionine, Tryptophan, Ornithine and Argine (Urea cycle).
If you would like to organise a test order and review you can email me at:
c-pod@outlook.com
www.theconciouspod.com
* creatine supplementation is not recommended for people with Trisomy 21 as it causes kidney stress.
Image 1:
Image 2: click image to enlarge (Fitzgerald K, 2016)
Infographic: Methylation foods for trisomy 21 (click on link below)
References
1. Henneman P, Bouman A, Mul A, Knegt L, van der Kevie-Kersemaekers AM, et al. (2018) Widespread domain-like perturbations of DNA methylation in whole blood of Down syndrome neonates. PLOS ONE 13(3): e0194938
2. Yasko, A , ‘Pathways to Recovery’, (2009) Neurological Research Institute, Bethel Maine.
3. Pogribna M, Melnyk S, Pogribny I, Chango A, Yi P, James SJ. Homocysteine metabolism in children with Down syndrome: in vitro modulation. Am J Hum Genet. 2001 Jul;69(1):88-95. Epub 2001 Jun 5
4. Waterland R.A., Jirtle R.L, Transposable Elements: Targets for Early Nutritional Effects on Epigenetic Gene Regulation, Molecular and Cellular Biology Aug 2003, 23 (15) 5293-5300;
5. Fitzgerald, K, Hidges R, “Methylation Diet and Lifetsyle’, 2016, Ebook
6. Lou XD, Wang HD, Xia SJ, Skog S, Sun J. Effects of resveratrol on the expression and DNA methylation of cytokine genes in diabetic rat aortas. Arch Immunol Ther Exp (Warsz). 2014 Aug;62(4):329-40
7. Reuter S, Gupta SC, Park B, Goel A, Aggarwal BB. Epigenetic changes induced by curcumin and other natural compounds. Genes Nutr. 2011;6(2):93–108.
8. Yiannakopoulou EC.Targeting DNA methylation with green tea catechins. Pharmacology. 2015;95(3-4):111-6.
9.Lu, J., Mccarter, M., Lian, G., Esposito, G., Capoccia, E., Delli-Bovi, L.C., Hecht, J., Sheen, V., 2016. Global hypermethylation in fetal cortex of Down syndrome due to DNMT3L overexpression. Hum. Mol. Genet. 25, 1714–1727
10. Otero NK, Thomas JD, Saski CA, Xia X, Kelly SJ. Choline supplementation and DNA methylation in the hippocampus and prefrontal cortex of rats exposed to alcohol during development. Alcohol Clin Exp Res. 2012;36(10):1701–1709.
