Reduce Homocysteine : CerefolinNAC

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Reduce Homocysteine

Reduce Oxidative Stress

Normalize Acetylcholine

Homocysteine is an amino acid produced as the body digests dietary protein called methionine.

Homocysteine circulates through the blood stream or is converted back into methionine.

Homocysteine is converted back to methionine by a metabolic pathway called remethylation. L-methylfolate and methylcobalamin (vitamin B₁₂) are needed for this conversion. L-methylfolate offers superior homocysteine reduction.

Homocysteine is converted into cysteine by a metabolic pathway called transulfuration. Vitamin B₆ is needed for this conversion.

Elevated levels of homocysteine result from abnormalities in the function of enzymes involved in homocysteine metabolism or from deficiencies of the vitamin cofactors: folate, cobalamin (B₁₂), and pyridoxine HCl (B₆). Elevated homocysteine is referred to as hyperhomocysteinemia.

What are Normal Homocysteine Levels?

Guidelines of the American Heart Association state that plasma homocysteine levels should be below 10 micromoles (µmol) per liter.

How Do You Reduce Homocysteine Levels?

Folate and cobalamin (vitamin B₁₂) work to reduce homocysteine levels by converting it back to methionine.
Pyridoxine (vitamin B₆) facilitates the breakdown of homocysteine to cysteine and other waste products.

The B vitamins are water-soluble and are not significantly stored by the body. Excess quantities are excreted by the kidneys and do not affect the Cytochrome P450 metabolism of drugs in the liver. B-Vitamins must be replenished regularly through diet to maintain essential tissue levels. These vitamins are rapidly depleted in conditions interfering with their intake or absorption.

What Causes Homocysteine Levels to Rise?

Diseases/Conditions
Folate, B12 and B6 deficiencies Dementia & Alzheimer's disease Depression Chronic Fatigue Syndrome Chronic Kidney Disease Down's syndrome GI disorders	Chronic alcoholism Hypothyroidism Diabetes Myocardial infarction Thrombosis, Stroke Cancer
Enzyme Deficiencies
Cystathionine beta-synthase Methionine synthase Methyltetrahydrofolate reductase (MTHFR) C->T polymorphism
Demographics
Increasing age Tobacco use Post menopause
Drugs that decrease absorption of folate
Metformin Levodopa (Parkinson's disease) Cholestyramine -lower high levels of cholesterol in the blood Sulfasalazine- ulcerative colitis and rheumatoid arthritis. Colestipol- lower high levels of cholesterol in the blood Colchicine- gout and gouty arthritis Methotrexate- cancer, psoriasis, and rheumatoid arthritis. NSAIDS Examples include: ibuprofen, naproxen Pyrimethamine- malaria Phenytoin and carbamazepine (seizures)

The Role of Homocysteine Metabolism in De Novo Synthesis of Acetylcholine

This graph illustrates technical information presented in: Ueland PM, Refsum H, Schneede J. Determinants of plasma homocysteine. In: Robinson, K, ed. Homocysteine and VascularDisease. Dordrecht, The Netherlands: Kluwer Academic Publishers; 2000:59-84.

The homocysteine cycle (1-carbon metabolism)

Homocysteine is formed from methionine.
Methionine transfers a methyl group to form S-adenosylmethionine (SAM)
The transfer of methyl groups from methionine to SAM then forms S-adenosyl homocysteine (SAH). S-adenosyl homocysteine is readily hydrolysed to homocysteine.
Methionine may be "regenerated" from homocysteine by using the enzyme methionine synthase, and L-methylfolate as the methyl group donor. This reaction is dependent on vitamin B12.

Homocysteine Metabolism in the Brain is Limited to Remethylation

Homocysteine may also be "degraded" by transulfuration into cysteine. The transulfuration reaction is controlled by the cystathionine-ßenzyme, which is dependent on vitamin B6.

Transulfuration requires the enzyme cysthionine ß-synthase (CBS) and B₆. Minimal amounts of CBS are found in brain tissue making the transulfuration pathway inefficient. Therefore, B₆ has limited effectiveness in homocysteine metabolism in the brain.

The brain is dependent upon the work of methionine synthase and a sufficient supply of vitamin B₁₂ and L-methylfolate for methyl donation.

This illustration represents information presented in: Miller A. The Methionine-Homocysteine cycle and its effects on cognitive diseases. Alternative Medical Review. 2003;8(1):7-19.