Biomarkers

What is S-adenosylhomocysteine (SAH)? High and low values | Lab results explained

S-adenosylhomocysteine (SAH) is the end-product of methylation reactions in the body. SAM ultimately donates a methyl group for methylation (DNA, detoxification, etc.) resulting in SAH formation. SAH is also the metabolic precursor of all the homocysteine (Hcy) produced in the body. In literature, SAH is sometimes referred to as AdoHcy.

SAH is hydrolyzed to homocysteine; however, this reaction is readily reversible, and the dynamics strongly favor SAH synthesis. Therefore, any elevation in homocysteine will lead to an increase in SAH. [L] In spite of the reversible nature of this reaction, efficient cellular removal of homocysteine allows sustained SAH metabolism and homocysteine production. [L]

SAH accumulation is implicated in many chronic clinical conditions. [L], [L], [L] SAH is a potent feedback inhibitor in methyltransferase reactions. SAH’s pathogenicity lies in its binding affinity for, and inhibition of, methyltransferase enzymes within many tissue components, including

DNA, RNA, phospholipids, and others. One example of SAH accumulation is in vascular cell phenotypic changes and atherosclerotic disease development.52 Therefore, plasma SAH levels have been shown to be a more sensitive marker for clinical cardiovascular disease, renal disease, and Alzheimer’s disease than plasma homocysteine. [L] ,[L], [L], [L], [L]

Methylation reactions are ultimately dependent on SAH removal. [L], [L]

Genetic SNPs, or nutritional deficiencies that hinder Hcy or adenosine metabolism, can induce SAH accumulation and subsequent hypomethylation defects, which are implicated in a variety of diseases, as previously outlined. [L], [L

Nutritional therapies that encourage Hcy metabolism (i.e. folate, B12, betaine, choline) may passively lower SAH levels. [L], [L], [L]

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References:

– Yi P, Melnyk S, Pogribna M, Pogribny IP, Hine RJ, James SJ. Increase in plasma homocysteine associated with parallel increases in plasma S-adenosylhomocysteine and lymphocyte DNA hypomethylation. J Biol Chemistry. 2000;275(38):29318- 29323. [L]

– James SJ, Melnyk S, Pogribna M, Pogribny IP, Caudill MA. Elevation in S-Adenosylhomocysteine and DNA Hypomethylation: Potential Epigenetic Mechanism for Homocysteine-Related Pathology. J Nutr. 2002;132(8):2361S-2366S. [L]

– Kerins DM, Koury MJ, Capdevila A, Rana S, Wagner C. Plasma S-adenosylhomocysteine is a more sensitive indicator of cardiovascular disease than plasma homocysteine–. Am J Clin Nutr. 2001;74(6):723-729. [L]

– Wagner C, Koury MJ. S-Adenosylhomocysteine—a better indicator of vascular disease than homocysteine?–. Am J Clin Nutr. 2007;86(6):1581-1585. [L]

–  Chang PY, Lu SC, Chen CH. S-adenosylhomocysteine: a better marker of the development of Alzheimer’s disease than homocysteine? J Alzheimers Dis. 2010;21. [L]

– Xiao Y, Zhang Y, Wang M, et al. Plasma S-adenosylhomocysteine is associated with the risk of cardiovascular events in patients undergoing coronary angiography: a cohort study. Am J Clin Nutr. 2013;98(5):1162-1169. [L]

– Capdevila A, Burk RF, Freedman J, Frantzen F, Alfheim I, Wagner C. A simple rapid immunoassay for S-adenosylhomocysteine in plasma. J Nutr Biochem. 2007;18(12):827-831. [L]

– Chang PY, Lu SC, Chen CH. S-adenosylhomocysteine: a better marker of the development of Alzheimer’s disease than homocysteine? J Alzheimers Dis. 2010;21(1):65-66. [L]

– Garibotto G, Valli A, Anderstam B, et al. The kidney is the major site of S-adenosylhomocysteine disposal in humans. Kidney Int. 2009;76(3):293-296. [L]

– Wilson AS, Power BE, Molloy PL. DNA hypomethylation and human diseases. Biochim Biophys Acta (BBA). 2007;1775(1):138-162 [L]

– Guerra-Shinohara EM, Morita OE, Pagliusi RA, Blaia-d’Avila VL, Allen RH, Stabler SP. Elevated serum S-adenosylhomocysteine in cobalamin-deficient megaloblastic anemia. Metabolism. 2007;56(3):339-347. [L]

– Green TJ, Skeaff CM, McMahon JA, et al. Homocysteine-lowering vitamins do not lower plasma S-adenosylhomocysteine in older people with elevated homocysteine concentrations. Br J Nutr. 2010;103(11):1629- 1634. [L]

– Stabler SP, Allen RH, Dolce ET, Johnson MA. Elevated serum S-adenosylhomocysteine in cobalamin-deficient elderly and response to treatment–. Am J Clin Nutr. 2006;84(6):1422-1429. [L]

WHAT DOES IT MEAN IF YOUR S-ADENOSYLHOMOCYSTEINE (SAH) RESULT IS TOO LOW?

– Unknownclinical significance

– Lack of SAM/ methyl donors

WHAT DOES IT MEAN IF YOUR S-ADENOSYLHOMOCYSTEINE (SAH) RESULT IS TOO HIGH?

– ACHY deficiency or need for Vitamin B3 cofactor

– Elevated Hcy

– High SAH: marker for CVD risk and poor methylation recycling

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A chronic elevation in homocysteine levels results in a parallel increase in intracellular or plasma SAH, which is a more sensitive biomarker of cardiovascular disease than homocysteine and suggests that SAH is a critical pathological factor in homocysteine-associated disorders. Previous reports indicate that supplementation with folate and B vitamins efficiently lowers homocysteine levels but not plasma SAH levels, which possibly explains the failure of homocysteine-lowering vitamins to reduce vascular events in several recent clinical intervention studies. [L]

Disclaimer:

Test results may vary depending on your age, gender, health history, the method used for the test, and other things. Your test results may not mean you have a problem. Ask your healthcare provider what your test results mean for you. 

The information on healthmatters.io is NOT intended to replace a one-on-one relationship with a qualified health care professional and is not intended as medical advice.

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