by William Clearfield, D.O. for Longevinex

I watched a very popular 1967 movie last week, ‘The Graduate.’ In it, 21-year-old Benjamin, played by Dustin Hoffman, is advised at his college graduation party about a future commodity he should consider for his career.

“I have one word for you,” says Mr. McGuire, one of Benjamin’s parents’ wealthy friends. “Plastics. The future is plastic.”

And I, dear reader, have one word for you:


Go ahead, try pronouncing it: “Meth-el-ay-shun.” It’s one of those complex scientific terms my mother loved to hear me say.

“Oh, my son, the doctor! He uses such fancy, schmancy words. I don’t understand half of them, but listen to him talk! Did I get my money’s worth or what?”

“Yes, Mom,” I said.

Every mother’s dream. With less than an estimated 0.2% of the United States adult population even aware of this term, why should you, dear reader, be interested?

Let me explain why.

Methylation is a biochemical process where a molecule called a methyl group, composed of one carbon atom bound to three hydrogen atoms (-CH3), is added to another molecule.

But remember, Mom was so proud to hear that, or any explanation. “My son, the doctor!”

Adequate methylation is essential for countering the aging process. It is crucial for maintaining DNA integrity and repair mechanisms. As one matures (Mom would never say ‘ages’; ‘age’ and ‘old’ are four-letter words in her book), DNA damage accumulates, leading to cellular dysfunction and disease.

Adequate methylation contributes to DNA repair and maintenance, influencing how genes are turned on or off and slowing down age-related changes. It reduces the risk of age-related diseases such as cardiovascular disease, neurodegenerative deterioration, and cancers.

Your liver, the body’s primary detoxification organ, uses a methylation pathway, specifically B6, B12, folate, and SAMe, to attach various molecules to toxins, making them water-soluble for excretion.

During methylation, liver cells add a methyl group to a toxin, making it less harmful and easier to eliminate. The nutrients required for this process include vitamins B6, B12, folate, and SAMe.

Methylation is also necessary for producing glutathione, our most potent protector against free radical and toxin damage.

Methylation regulates gene expression. With aging, changes in the methylation patterns of genes occur, leading to altered gene function. Proper methylation helps maintain regular gene activity, essential for healthy aging. It prevents tumor cell growth by silencing oncogenes and stimulating tumor suppressor genes, which is crucial as cancer is more common in older age.

Cellular senescence, a cell’s cessation of division, is a crucial indicator of aging. Methylation plays a pivotal role in cellular senescence by protecting telomeres, the protective caps at the ends of chromosomes. Telomeres serve as “buffers” against the wear and tear associated with aging.

Methylation plays a role in converting homocysteine into methionine, mitigating age-related health risks. High levels of homocysteine, due to poor methylation, are associated with cardiovascular diseases, cognitive decline, and bone health issues.

Critical for preserving brain function, methylation is involved in synthesizing neurotransmitters like serotonin and dopamine and in neurotransmitter metabolism. Poorly methylated patients are more susceptible to neurological disorders such as Alzheimer’s, Parkinson’s, and Huntington’s Disease, autism spectrum disorders, cognitive decline, mood disorders, depression, and anxiety. Adequate methylation is critical for age-defying brain function and overall health.

Balanced methylation is a fundamental building block of the immune system. Sufficient methylation prevents autoimmune conditions.

Proper methylation regulates the expression of genes involved in and reduces chronic inflammatory responses.

Lifestyle changes you can undertake to improve methylation include:

  1. Balanced Diet: Eat a diet rich in natural, whole foods, especially those high in folate and B vitamins, like leafy greens, legumes, nuts, and whole grains.
  2. Reduced Alcohol Consumption: Excessive alcohol interferes with the absorption of B vitamins, which are necessary for proper methylation.
  3. Stress Reduction: Incorporate stress-management techniques like mindfulness, yoga, or meditation. Choose methods that suit your personality so they are enjoyable.
  4. Regular Exercise: Physical activity supports healthy methylation.
  5. Sleep: Good sleep hygiene is essential for maintaining adequate methylation processes and optimal health.
  6. Environmental Toxins: Avoid exposure to pollutants, heavy metals, and chemicals to improve methylation.
  7. Smoking: The adverse health effects of smoking interfere with methylation. Quitting is advised.
  8. Weight: Maintain a healthy weight, as obesity hinders methylation.

Foods with B12

Nutraceutical interventions to improve methylation include:

  1. Vitamin B12, Folate (B9), and Vitamin B6: These vitamins work together to produce S-adenosylmethionine (SAMe), involved in immune function and mood. Deficiencies in these vitamins can lead to various health issues. Recommended doses include B12 500 mcg minimum per day, Folate 400 mcg/day, and B6 (pyridoxal 5′-phosphate) 1-2 mg/day.
  2. Betaine (Trimethylglycine): Provides methyl groups for homocysteine, creatine, and carnitine, balances fluids, and has positive effects on fatty infiltration of the liver. Recommended dose: 1.5-3 mg/day.
  3. Choline: Supports cognitive function, fetal neural development, and detoxification. Recommended dose: Adult female 425 mg/day; Adult male 550 mg/day.
  4. Magnesium: Acts as a cofactor in the methylation pathway, aids in DNA synthesis and repair, supports SAMe production, and is essential for neurotransmitter formation. Recommended dose: 300-400 mg/day.
  5. Zinc: A methyl donor that stabilizes DNA and RNA. Deficiency leads to cell death. Recommended dose: Females 8 mg/day, Males 11 mg/day.
  6. Milk Thistle: A liver detox agent that acts as an antioxidant and anti-inflammatory agent. Recommended dose: 140-210 mg 2-3x/day.
  7. Green Tea Extract: Reduces the effect of DNA methyltransferase 1 (DNMT1), a suppressor of tumor genes. It is neuroprotective and cardioprotective, and an antioxidant. Recommended dose: 1-2 grams of tea per cup, 2-3 times daily.
  8. SAMe: Provides a leading methyl donor for various bodily functions. Recommended dose for mood support: 400-1600 mg in 2-4 doses; for joint support: 600-1200 mg/day; for liver dysfunction: 600-1200 mg/day.
  9. Methylation Adaptogens: These include Curcumin, Anthocyanins, Quercetin, Rosmarinic Acid, Lycopene, and Sulforaphane. They have various health benefits, including anti-inflammatory and antioxidant effects, and are found in a variety of foods and herbal extracts.

One Last Wrinkle in the Pie: The MTHFR Methylation Genetic Defect

The MTHFR Methylation Genetic Defect

With our newfound understanding of the pivotal role of the methylation pathway in maintaining well-being, we must mention the MTHFR (methylenetetrahydrofolate reductase) genetic defect.

The MTHFR gene encodes an enzyme essential for converting a form of folic acid (Vitamin B9) into another, which is necessary for converting homocysteine into methionine. There are at least 40 MTHFR genetic defect variations with symptoms ranging from ocular issues to cognitive deficits.

The most common MTHFR variants are linked to increased homocysteine levels in the blood, indicating an increased risk of various health issues.

Associated medical syndromes with MTHFR defects include ADHD, autism, autoimmune diseases, cardiovascular disease, chronic fatigue, colon cancer, digestive issues, hormonal issues, migraines, and schizophrenia.

Diagnosis of MTHFR defects involves measuring homocysteine levels in the blood and testing for MTHFR variants. Tests for folic acid, B6, and B12 levels may also indicate an MTHFR defect.


  1. Dietary Changes: Increase intake of natural folate-rich foods.
  2. Supplementation: Use Methylfolate instead of folic acid, add B vitamins, especially vitamin B12, and Omega 3 Fatty Acids.
  3. Lifestyle Modifications: Reducing alcohol intake, avoiding smoking, and minimizing exposure to toxins improve methylation efficiency.
  4. Regular Exercise: Improves overall health and aids the body’s methylation processes.
  5. Homocysteine Levels: Maintain “Normal Levels” < 11 umol/L, “Optimal Levels” < 10 umol/L.
  6. Medication Review: Review medications and supplements that may interfere with folate metabolism.
  7. Genetic Counseling: Beneficial for those considering starting a family, as MTHFR mutations can impact pregnancy and fetal development.


Ensuring optimal methylation levels plays a key role in slowing or reversing the impact of age-related illnesses. It contributes significantly towards promoting healthy aging by sustaining DNA integrity, regulating gene expression, affecting cellular senescence and telomere length, regulating homocysteine levels, bolstering neurological health, and mitigating chronic inflammation.

Knowledge is indeed power. We at Longevinex are committed to providing you with valuable information to preserve and enhance your health and well-being!

Thanks for the great head start, Mom!


Dr. Bill Clearfield


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