This publication written by Dong-Mei Zhang et al 1 describes the investigation of serum homocysteine and its role in cognitive impairment.

The authors investigate hyperhomocysteinemia (increased levels of serum homocysteine) and its association with an increased risk of cognitive impairment. According to Sudha Seshadri et al 2, an increased plasma homocysteine level is a strong independent risk factor for the development of dementia and Alzheimer’s disease, where they say that the risk of developing Alzheimer disease doubles with a plasma homocysteine level greater than 14 μmol/L, as well as being at major risk of suffering from coronary artery disease. Homocysteine levels increase with age, with common adult levels in Western populations being 10 to 12 μmol/L.

The graph below is taken from Axis-Shield 5 who carry out in-vitro diagnostic testing. The graph shows that the higher the homocysteine level, the greater the risk of developing coronary artery disease/Alzheimer’s disease.

Kamlesh 1

Homocysteine is a homologue of the amino acid cysteine, with an extra methylene bridge. It is biosynthesised in the body through metabolism of methionine (S-demethylation). Metabolism of homocysteine is aided by vitamin B12, folic acid and vitamin B6. As well as other factors, deficiencies in these vitamins may increase serum homocysteine levels. Hyperhomocysteinemia can contribute to a greater risk of developing diseases such as cardiovascular diseases/retinal vascular disease as well as neuropsychiatric diseases. B vitamins have therefore been considered as a possible option to reduce the risk of Alzheimer’s and dementia.

The authors wanted to address the discrepancy in the existing literature on the therapeutic effect of vitamin B and folates in patients with significant cognitive deficits, secondary to Alzheimer’s disease or dementia. They carried out a meta-analysis of randomized controlled trials in elderly patients with poor cognitive ability secondary to Alzheimers or dementia, who received homocysteine lowering B vitamins supplements and had serum homocysteine levels reported.

Existing evidence on vitamin B supplement induced reduction of cognitive decline by lowering homocysteine levels is conflicting. The authors mention other studies where daily folic acid supplements were taken by people with folate deficency (Durga et al 3, 800μg/d for 3 years and Fioravanta et al 4 15mg/d for 60 days), showing an improved cognitive performance. These results were not included in the meta-analysis because the serum homocysteine levels were not reported.

The overall results suggested that folate in combination with vitamin B12 and/or B6 supplements failed to offer any significant advantage in slowing down or preventing the progression of cognitive decline, although Vitamin B supplements were shown to significantly reduce homocysteine levels.

Blog written by Kamlesh Bala

1 Dong-Mei Zhang et al, Journal of Geriatric Psychiatry and Neurology 2017, Vol 30 (1) 50-59

2 Seshadri S, Beiser A, Selhub J et al, N Engl J Med 2002; 346:476-483

3. Durga J et al, Lancet. 2007; 369 (9557): 208-216

4. Fioravanti M et al, Arch Gerontol Geriatr. 1998; 26 (1): 1-13

5. http://www.homocysteine.co.uk/measuring-homocysteine/

Keywords: Hyperhomocysteinemia, homocysteine, cognitive decline


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