From the Desk of Carolyn Dean MD ND

Well it turns out it hasn’t gone anywhere, it’s just waiting for its best friends, magnesium and methylated B Vitamins to help it out. If you are deficient in magnesium and B vitamins, your methylation pathways don’t work probably or go missing. Instead of looking for missing cofactor nutrients, genetics got involved and confused the whole issue. The Genome Project allowed the public to find out their genetic sequences and the MTHFR genes showed up as mutations in a good number of people. But I’m getting way ahead of myself. Let me start at the beginning.

Carolyn Dean MD ND


Methylenetetrahydrofolate reductase (MTHFR) is an enzyme that breaks down the amino acid homocysteine. If the MTHFR gene that codes for this enzyme mutates, it may contribute to a variety of health conditions. People have two MTHFR genes, inheriting one from each of their parents. Mutations can affect one (heterozygous) or both (homozygous) of these genes.

There are two common types, or variants, of MTHFR mutations: C677T and A1298C. These gene mutations are relatively common. Around 47% of people of Hispanic descent and 36% of Europeans are carriers for the C677T variant.

Homocysteine Rising

When protein breaks down, it produces homocysteine, which means that you’ll have elevated levels on a high protein diet, which means everyone is susceptible because we all need protein. Homocysteine has the ability to oxidize cholesterol, which is not a good thing, because oxidized cholesterol ends up trying to plug up artery walls that are damaged by lack of collagen because of Vitamin C deficiency.

NOTE: Medicine says that it’s oxidized cholesterol that damages blood vessels but, in fact, it’s trying to patch up the damage caused by weakened collagen. Excess calcium in the blood stream will then precipitate onto these cholesterol patches and cause arteriosclerotic plaques.

Back to homocysteine: Most people say that it’s the B vitamins that are responsible for breaking down homocysteine and keeping it in check. However, the major enzymes involved in metabolizing homocysteine are magnesium-dependent.

NOTE: In the development of heart disease, magnesium has a role to play every step of the way by reducing homocysteine levels, naturally thinning the blood, preventing free radicals, balancing blood sugar, reducing high blood pressure, eliminating inflammation, and dissolving calcification.

Homocysteine and the B Vitamins

It’s not just B vitamins but it’s methylated B vitamins (B2, B6, folate, B12) that prevent the buildup of homocysteine by adding an important methyl group to the biochemical processing of protein.

Elevated homocysteine is a clear indication of impaired methylation. However currently it’s being equated with genetic polymorphism or mutation. So, people get their 23 and Me genetic DNA testing and are told that they have a few hundred gene abnormalities one of which may be MTHFR. But that doesn’t mean they will express it because if you have enough magnesium and methylated B vitamins, you won’t!

That’s the bit of information that’s lost in the black hole that’s created by genetic testing. I say that, because if you are told you have a few hundred genetic abnormalities, what are you going to think? You probably think that you can’t influence your genes and therefore you’re stuck with knowing you have all these potential problems. You treat your genetic test as a diagnosis not just a possibility. What you aren’t told is that genes are turned on and off by nutrient cofactors which gives more evidence that you should take nutrient building blocks to stay healthy and happy.

If don’t have saturation levels of magnesium and B vitamins you can develop high levels of homocysteine which are being found in an alarming list of conditions:

  • Autism
  • Seizure disorder
  • Neurological condition
  • Alzheimer’s disease
  • Lyme disease
  • Chronic infections
  • Low T cells or reduced NK cells
  • Diabetes
  • Allergies
  • Fertility issues
  • Miscarriage
  • Cardiovascular disease
  • Chronic fatigue
  • Anxiety or any psychiatric illness
  • Eye disorders
  • Coronary artery diseases
  • Atherosclerosis
  • Myocardial infarction
  • Ischemic stroke
  • Thrombotic events
  • Cancer development and progression
  • Osteoporosis
  • Neurodegenerative disorders
  • Pregnancy complications
  • Delayed healing processes
  • Poor COVID-19 outcomes, etc.

Suzy Cohen who wrote Drug Muggers comments on the MTHFR gene mutations She says “Poor magnesium levels can lead to methylation problems, and that increases depression, whether or not you have the A1298 or C677T snp (polymorphism).”

Another thing you will hear about methylation is that it declines as we age, but so does our need for nutrients and our intake of nutrients.

What is Methylation?

Methylation is a biochemical process that involves the transfer of a methyl group to various molecules in the body. And as noted above, magnesium is a mineral that plays a key role in the methylation cycle. Magnesium is involved in up to 1,000 essential metabolic reactions and 80% of known metabolic function in the body. Magnesium is also a cofactor in the betaine pathway, which converts homocysteine back to methionine. Some people need extra magnesium to support their methylation, and methylation may increase the demand for magnesium in the cells.

An optimum level of homocysteine is between 10-12 µmol/L. When homocysteine is elevated in the cells, it causes magnesium deficiency because magnesium is constantly being used up to break it down. An amazing 20-40% of the general population have high levels of homocysteine in the blood but it isn’t even a standard blood test, likely because there is no drug treatment to lower homocysteine. This is especially important because people with high levels have almost four times the risk of suffering a heart attack compared to people with normal levels. Some say that high homocysteine is an even stronger marker than high cholesterol for heart disease and blood clotting disorders.

I say the more relevant marker may be low magnesium since the major enzymes involved in homocysteine metabolism are magnesium-dependent. Some doctors blame too much protein in the diet for hyperhomocysteinemia. However, when magnesium, vitamin B6, vitamin B12, and folate are deficient, the body is not able to properly digest dietary protein. Magnesium and the B vitamins were readily available in the typical diet a hundred years ago; now that they are absent, homocysteine becomes elevated resulting in heart disease.

When these metabolic nutrients are reintroduced through diet and supplements, the high homocysteine levels are reversed and the symptoms of heart disease diminish.

Ongoing research confirms that B6, B12, and folate together with magnesium are necessary to prevent blood vessel damage induced by high levels of homocysteine in the blood. However, magnesium is often left out of the prescription for hyperhomocysteine in favor of the B vitamins because of this epidemic of genetic testing that shows a high incidence of abnormalities in MTHFR methylation enzymes.

Researchers have found that high homocysteine is a marker for “all cause mortality”, which underscores that a deficiency in essential nutrients has far-reaching effects on the body beyond heart disease.

Too Much Information?

I’ll add this bit even though it’s probably overkill. Besides homocysteine undergoing remethylation to methionine using the methylated Bs and magnesium, the body also metabolizes homocysteine through the transsulfuration pathway to cystathionine. This process requires vitamin B6, which is another reason to take your B vitamins.

NOTE: A high protein, Paleo, Keto or Carnivore diet could be setting you up for more problems if you don’t have enough magnesium and methylated B Vitamins to help metabolize homocysteine.

What Can We Do?

It’s simple. I recommend a low dose methylated Bs: B2, B6, methylfolate, B12, plus L-Methionine and a picometer magnesium for everyone.

Carolyn Dean MD ND
The Doctor of the Future