pcells with epigenetics to DNA.JPG

Are stem cells epigenetic? By Sydney Strupp

Now, note the diagram above. See the blue ball on the top? That represents an iPS cell, an undifferentiated cell that can be determined to become anything. Stem cells are like this cell-many different cell types can come from it. iPS cells are typically seen in a developing zygote. They have a very “clean” DNA, meaning not a lot of epigenetic markers on it until it becomes determined to be a certain kind of cell by cellular determinants in the cytoplasm. So, the iPS cell now spurred by the determinants, travels down the slope into one of the four pockets, becoming that cell. To become that cell type, proteins add methyl groups to certain regions of the DNA and suddenly, by the grace of epigenetics, the unspecialized cell becomes specialized.

The important thing to understand from my rambling nonsense is that all cells start and end with the same DNA, it’s just altered via epigenetic markers. Your kidney cells have the same DNA as your heart. Thankfully, the methyl additions to your DNA are permanent enough to stop a kidney cell from developing in your heart. That’s because heart cells are so specialized uniquely, using an entirely different region of DNA (mostly) that unless the cell had the correct determinants in it’s cytoplasm, the proteins would never add methyl groups for the cell to become that type of cell. They would be at the very bottom of the trough, in one of the deepest pits.

Now, finally getting back to your question. Are stem cells epigenetic? Well, they’re more like the lack of epigenetics. They have very naked DNA that is waiting to be methylated into many different types of cells. They are waiting for the right determinants to “roll them down the hill” into the cell of choice.

Increasing Methylation , one of anti-aging factors

The Methylation Cycle, preventing fatigue and aging

Rich van Konynenburg’s idea is that ineffective methylation is a major cause of fatigue. There are many possible reasons but those that he’s identified for which methylation is essential are:

  • To produce vital molecules such as Co Q-10 and carnitine.
  • To switch on DNA and switch off DNA. This is achieved by activating and deactivating genes by methylation. This is essential for gene expression and protein synthesis. Proteins of course make up the hormones, neurotransmitters, enzymes, immune factors and are fundamental to good health. When viruses attack our bodies, they take over our own DNA in order to replicate themselves. If we can’t switch DNA/RNA replication off then we will become more susceptible to viral infection.
  • To produce myelin for the brain and nervous system.
  • To determine the rate of synthesis of glutathione which is essential for detoxification.
  • To determine the rate of synthesis of glutathione which is an essential anti-oxidant as glutathione-peroxidase. Furthermore oxidative stress blocks glutathione synthesis – yet another vicious cycle!
  • To control sulphur metabolism of the body, not just glutathione but also cysteine, taurine and sulphate. This is an important process for detoxification.
  • As part of folic acid metabolism. This also switches on synthesis of new DNA and RNA.
  • For normal immune function. The methylation cycle is essential for cell mediated immune function and blockages here will mean that infections will not be adequately dealt with. I know this clinically because many patients tell me that once they get on to their B12 injections (an essential co-factor for methylation) this seems to protect them from getting infections.

The overall effect here is that if the methylation cycle doesn’t work, the immune system malfunctions, the detoxification system malfunctions, our ability to heal and repair is reduced and the anti-oxidant system malfunctions.

The Bio-chemistry

(You can ignore this bit if you like because it’s not essential to know but it’s interesting.)

There are four cornerstones to the methylation cycle and on each cornerstone sit four molecules namely homocysteine, methionine, S-adenosylmethionine (SAMe) and S-adenosylhomocysteine. Each of these molecules leads into the next one by means of enzymes. The important co-factors that allow this to happen are the B vitamins such as folic acid, vitamin B12 and vitamin B6. In converting from S-adenosyl methionine into S-adenosyl homocysteine, a methyl group is given up and this can be used to stick on to other molecules – hence the name, the methylation cycle.

However, there is a particular bio-chemical glitch here. In order for the methylation cycle to work these B vitamins have to be in their activated form, namely methylcobalamin, folinic acid and pyridoxyl-5-phosphate. In order to get cobalamin into methylcobalamin, the methylation cycle has to be working. So if this cycle has crashed completely, the body can’t make methylcobalamin in order to get it up and running again. Since this cycle is so fundamental to other biochemical cycles including trans-sulphuration and folate metabolism, it can’t change the vitamin B6, folic acid and cobalamin into the active forms necessary for the methylation cycles to work.

This means that in order to get this cycle up and running initially we have to prime the pump with the activated vitamins, but hopefully once the methylation cycle is up and running, it can function on the vitamins in normal states.

Dr Myhill wrote:

The important cycles which I know to be major players include blood sugar wobbles, allergy problems, sleep cycles, mitochondrial function, anti-oxidant status, the NO/OONO cycle, thyroid and adrenal hormones cycles and de-toxification

We don’t have a simple test to see how well the methylation cycle works. What we can do is measure levels of homocysteine and SAMe

The Methylation Cycle – which supplements to take to support

This is the package of supplements to support the methylation cycle. It needs to be taken in addition to everything else, i.e. the standard nutritional package (multivits, multiminerals, EFAs, vits C + D) and the mitochondrial rescue package (D-ribose, acetyl-L-carnitine, CoQ10, etc.)! But the methylation package will change with time because as the methylation cycle starts to work again, it will start to stand on its own feet. Everyone”s package will be a bit different depending on how poorly their cycle is working. One day we will have the biochemical tests to tailor make each package for each person, but until then I suggest the following regime for those sufferers who have been taking vitamin B12 in oral form (as either hydroxocobalamin or cyanocobalamin):

For two months a daily dose of

  •  Methylcobalamin 1 mg sublingually
  •  Methyltetrahydrofolate 800mcg (ActiFolate)
  •  Pyridoxal-5-phosphate 100mgs (50mgs twice daily)
  •  Glutathione 250mgs daily
  •  Phosphatidyl Serine 200mgs (100mgs twice daily) – BioCare

If you are better – fine! If you are worse – it may be the reaction to the methylation package because it may cause an acute detox reaction (see below). Slow down the regime – take smaller amounts of the supplements and build up slowly. If you are unchanged – swap the sublingual B12 for injected B12 ie:

Daily subcutaneous injections methylcobalamin 0.5mgs (this is a bit more expensive than cyanocobalamin). Some CFSs will not respond clincially until 5mgs daily is injected. B12 is very safe with no known toxicity- as a colleague commented – the only way you could kill yourself with B12 would be to drown in the stuff! I would prefer people to start with this regime but I know many do not fancy the idea of injections – actually I am a wimp too, but they are easy and almost painless.

  •  Methyltetrahydrofolate 800mcg (ActiFolate)
  •  Pyridoxal-5- phosphate 100mgs (50mgs twice daily)
  •  Glutathione 250mgs daily
  •  Phosphatidyl Serine 200mgs (100mgs twice daily) – BioCare

If you are better – fine! If you are worse – it may be the reaction. If you are unchanged, add in:

  •  Tri-methylglycine or TMG (not to be confused with betaine hydrochloride, so always ensure that you are taking pure-grade TMG)
  •  Lecithin (phosphatidyl choline) and Phosphatidyl Ethanolamine.
  •  S-adenosyl methionine (SAMe) directly as a supplement 400mgs daily