Elevated homocysteine associated with all-cause mortality risk: study

By Olivia Brown

- Last updated on GMT

© vovashevchuk / Getty Images
© vovashevchuk / Getty Images

Related tags Homocysteine Stroke B vitamins Inflammation Folic acid

A new study has revealed a significant positive association between plasma homocysteine (Hcy) levels and the risk of all-cause mortality in adults with stroke, particularly in those of older age.

It was observed that by every 1 μmol/L increase in Hcy plasma concentration resulted in an increase in mortality rate of 5.3% in the studied population.

Furthermore, an inverse association was established between the participant mortality rates and vitamin B12 and folate levels, suggesting that intakes may lower the risk associated with elevated Hcy levels.

The Chinese researchers conclude: “These findings suggest that plasma Hcy levels might be a useful indicator for assessing risk of all-cause mortality in clinical practice.”

Stroke prevalence

Stroke is a leading cause of death across the globe, with reports​ suggesting a 23.8% increase in the occurrence of stroke deaths in recent years. Thus, there has been a significant focus on improving stroke outcomes in sufferers, with limited currently available effective treatments.

Homocysteine is an amino acid. Vitamins B12, B6 and folate break down homocysteine to create other chemicals your body needs.

Elevated levels of plasma homocysteine is a known risk factor​ for stroke due to resultant damage to vascular structures through oxidative stress and inflammation, as well as atherosclerosis promotion. Such elevated levels can be caused by deficiencies in vitamin B12 or folate.

Whilst previous studies​ have suggested a potential association between hyperhomocysteinemia (HHcy) and stroke occurrence, whether Hcy levels can predict mortality rates in stroke patients remains unclear.

Given the potential of the prevention of elevated homocysteine concentrations through vitamin B supplementation, the researchers sought to further examine the association between Hcy, vitamin B12, and folate and all-cause mortality in adults with stroke.


The researchers utilised the National Health and Nutrition Examination Survey (NHANES) data from 1999-2006, and linked this with the most recent 2019 National Death Index (NDI). The data included 431 participants with stroke, aged over 20 years old with an average age of 64.8.

During the 10-year follow up period, it was reported that 316 deaths occurred. It was observed that Hcy was positively associated with all-cause mortality in adults with stroke, with a strong association found in older patients.

Furthermore, it was noted that stroke patients with plasma Hcy levels in the fourth quartile had a 1.631-fold higher risk of all-cause mortality compared to those in the first quartile. Every 1 μmol/L increase in Hcy concentration increased mortality in these patients by 5.3%.

Folate and vitamin B12 levels were inversely associated with all-cause mortality in adults with stroke.


The researchers conclude that, based on their findings, there was an association between all-cause mortality in adults with stroke and levels of Hcy. In addition, folate and B12 were found to be inversely associated with mortality in these adults.

Explaining the effect of the B-vitamins, the researchers say: “Folate and vitamin B12 are the major nutritional determinants of homocysteinemia. Folate and vitamin B12 effectively reduce the Hcy concentration by participating in its metabolic pathways.”

They add that the effect may have been more prominent in older adults due to the possible age-related dietary deficit of B-vitamins and physiological reduction in renal function, both contributing to prevalence of HHcy.

Yet, they stress that causality cannot be concluded on due to the chosen study design. Therefore, they urge for further RCTs with high levels of control to further investigate the effect.



Source: Frontiers in Nutrition


“Associations between homocysteine, vitamin B12, and folate and the risk of all-cause mortality in American adults with stroke”

Panpan Zhang, Xia Xie, and Yurong Zhang

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