Integrative Medicine at Crossroads

Single Carbon Metabolism

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Single Carbon Metabolism:

Carbon atoms form the substrate of living things. Many important metabolic processes involve the chemistry of molecules that contain a single carbon atom. Methylation and Carboxylation are two such processes that are very important to background functions that create and sustain good health. When optimal function is disrupted many chronic health problems can evolve. This is a discussion of Methylation and Carboxylation.


Homocysteine is a metabolic byproduct of normal cellular metabolism. It is produced in the process of one carbon molecule, (methyl-group), metabolism. This chemical reaction occurs in all of the cells of our body. One carbon molecule metabolism is an essential reaction in the process of repair of genetic material.

Homocysteine is a toxin to the cells that line our arterial tree, (endothelial cells). Accumulation of Homocysteine is associated with many degenerative diseases such as Coronary Artery Disease, Arteriosclerosis, Stroke and Alzheimer’s disease. Homocysteine activates inflammatory processes in the endothelial cells that lead to oxidation of molecules in the cells. This leads to the generalized inflammatory process that causes “hardening of the arteries”.

Homocysteine elevation is a marker for inadequate repair of our genetic material. Our genes are always experiencing injury. This occurs from oxidative stress that may result from radiation, toxins in the environment or normal metabolic processes that are occurring in an imbalanced manner. One expert has calculated that the genetic material of the average cell receives 100,000 oxidative hits per day. Fortunately, we have an elaborate repair mechanism that is constantly working to correct injury to our genetic material. Scientists use many techniques to look for genetic injury. One technique that is common in the research world is to look at the size of the nuclei of our white blood cells, (lymphocytes). When the nuclei are smaller than average it is a sign of excessive injury to the genetic material with inadequate repair. This phenomenon is called micronucleation, (small nuclei).  Micronucleation can be induced in the laboratory by a variety of stressors such as radiation, chemical poisons, and excessive temperature. Scientists have observed excessive levels of micronucleation in healthy young people when the Homocysteine levels are greater than 7.5. In these individuals, supplementation with the nutrients that lower Homocysteine corrected the excessive micronucleation. The inference is that an inadequacy of essential nutrients inhibits the process of gene repair and increase the chance of permanent injury to a genetic material. This is one of the processes by which normal cells are turned into cancer cells. 

Homocysteine levels commonly rise with age. Eating red meat will elevate homocysteine because red meat is high in an amino acid called methionine. Individuals with elevations in homocysteine should limit red meat intake. A reduction in renal function will also result in an elevation of homocysteine. This is a common occurrence with the aging process. Prescription medications and OTC medications such as aspirin, acetaminophen and ibuprofen can cause renal dysfunction. The use of these products should be minimized in older individuals. Inadequate fluid intake will also reduce renal function. I recommend that people drink 6-8, 8 ounce glasses of water per day. Minimize drinks that cause dehydration such as caffeinated beverages.

Supplements that lower homocysteine include folic acid, Vitamin B2, Vitamin B6, Vitamin B12, Betaine and SAMe. The dose of folic acid will vary depending on the background condition of the individual. Generally a dose of 800 micrograms per day is adequate. If this proves inadequate we increase the dose of Folic acid to 5-10 mgs per day. This can only be obtained by prescription from a medical doctor.  Some individuals cannot convert Folic acid to Folinic acid, which is the active form of folate. We can then use Folinic acid in a dose of 800-1,600 mcgms per  day.  In addition I recommend 25 mgs of B6 and 1000 micrograms of B12 daily to optimize homocysteine metabolism.

We monitor Homocysteine levels as part of our Cardiovascular and Cancer Risk Assessment process. Supplement regimens are individualized for each patient.

In general I will include supplementation with Methyl Folate and Methyl B12.

Recommended OTC products may include:

  • Methyl Assist; 1-3 capsules daily
  • SAMe 200 mgs, twice daily
  • Betaine 1 capsule twice daily


Unbalanced Carboxylation may lead to bone loss or osteoporosis. In addition it may lead to the deposition of calcium in non-bony tissue such as the area around our joints and the arteries of our body. This is a contributing factor to arteriosclerosis and the consequences of arteriosclerosis including hypertension, heart disease, stroke and dementia.

Carboxylation can be supported with Vitamin K supplementation. Vitamin K is often deficient in our diets and is under produced by the bacteria in our gut. Supplementation with Vit K has been shown to help thicken bone and reduce calcification in the arteries.