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Hyperhomocysteinemia affecting cardiovascular and other major organ events

Khan, Safinaz MDa; Rashid, Rubaya MDb; Ataullah, A.H.M. MDc; Rahman, Md Moshiur MSd,

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IJS: Short Reports: July/September 2022 - Volume 7 - Issue 3 - p e40
doi: 10.1097/SR9.0000000000000040
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An essential nutrient, vitamin B12 acts as coenzymes for the conversion of homocysteine (HCY), a sulfur-containing amino acid to a methionine. High HCY is an indication of vitamin B12 or folic acid deficiency, commonly involving the cardiovascular system and resulting in damage to major organs. The normal level of HCY is <15 µmol/L. When the level crosses 50 µmol/L, known as hyperhomocysteinemia (HHCY).

Whenever excess HCY accumulates in the blood, causes disruption of the arterial lining by the process of inflammation and reactive oxygen species. Evidence of blood coagulation and vascular calcification have been found also1. Damaging of arteries can give rise to complications such as atherosclerosis, coronary artery disease, stroke, fibrillation2. Homocysteine is regarded as an independent risk factor for developing cardiovascular disease.

Patient with end-stage renal disease or acute kidney injury has compromised renal excretory function. As a result, HCY piles up in the blood and gives rise to cardiovascular complications—a global cause of mortality in renal failure patients3. Traditional risk factors such as diabetes, smoking, obesity are not sufficient to explain the high death rate due to cardiac problems in renal failure patients. Thus, a nontraditional biomarker, HCY is being used nowadays. Obese women with high HCY are at a high risk of developing chronic renal failure, where reducing weight has proved a positive impact4.

Abnormal HCY and DNA methylation are interrelated. High HCY results in demethylation of DNA, which is responsible for psoriasis—a multifactorial chronic inflammatory disorder of the skin. Mortality from myocardial infarction, stroke is commonly found in psoriatic patients. HCY is known to have atherogenic properties5. Along with oxidative stress, inflammatory cells and cytokines play an important role to develop plaques and resulting in cardiovascular complications6,7. A choice of treatment might be artificial narrowband ultraviolet ray B for these patients to reduce cardiovascular events8.

Coronary artery disease has been reported as the primary cause of death in type 2 diabetes mellitus (DM), which finally developed into acute myocardial infarction and can also lead to macrovascular and microvascular complications. Elevated HCY interrupts the blood-retinal barrier and is associated with age-related macular degeneration9,10.

The relation between thyroid antibodies and HCY in hypothyroid and hyperthyroid is been clear. HCY is impaired in defective thyroid function. Thyroid peroxidase antibody influences HCY to cause cardiac events in graves’ disease11. HHCY in subclinical hypothyroidism and autoimmune thyroiditis increase the tendency of atherosclerosis and coronary artery disease by stimulating chemokines and lowering circulating anti-oxidants12.

Homocystinuria, a rare genetic disorder presents with valvular disease and atherosclerosis. Decreasing HCY can potentially reduce cardiovascular risk13.

HCY is toxic to our neurons and leads to Alzheimer disease, Parkinson disease, stroke. HCY promotes reactive oxygen species and blood clotting. In traumatic brain injury blood-brain barrier integration is disrupted and inflammatory cells get infiltrated, gradually plaque formation is the outcome14. Levodopa is the treatment of choice for Parkinson disease. In these patients, dietary supplementation with vitamins and folic acid can markedly reduce the level of HCY15. High HCY also promotes brain atrophy.

In modern days, the significant role of HCY has widely been practiced as a biomarker not only for prognostic purposes but also for diagnosis and treatment. The positive response is found in treating patients with coronary artery atherosclerosis16.

Complete metabolism of HCY requires folic acid, vitamin B6, and vitamin B12. Folic acid degrades HCY and prevents deleterious effects on arterial walls. This also improves endothelial function. Therefore, complimentary folic acid with or without vitamin B12 can improve vascular activity and counter mortality and morbidity from cardiovascular complications17.

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Author contribution

All authors contributed equally to the manuscript.

Conflicts of interest disclosure

The authors declare that they have no financial conflict of interest with regard to the content of this report.

Research registration unique identifying number (UIN)



Md Moshiur Rahman.


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Copyright © 2022 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of IJS Publishing Group Ltd.