AsianScientist (Jul. 17, 2026) – Chronic fatigue has become a hallmark of modern life. Far from being just a personal inconvenience, it is a growing public health issue that reduces quality of life, lowers workplace productivity, increases absenteeism, and drives up healthcare costs.
Persistent fatigue can also impair concentration, thinking, and decision-making, increasing the risk of mistakes and accidents at work while reducing motivation to engage in healthy behaviours. Although a lack of rest is often blamed, researchers say inadequate nutrition may be an important but overlooked factor.
To investigate this possibility, Japanese researchers investigated whether homocysteine (Hcy), a biomarker that rises when folate (B9) and vitamin B12 are deficient, is associated with fatigue. The findings were published in the journal Nutrients.
For the study, the researchers measured blood levels of Hcy, folate, and vitamin B12 in 600 healthy Japanese adults.
Participants also completed the Chalder Fatigue Scale, a questionnaire that measures physical and mental tiredness, and the Visual Analogue Scale, which assesses subjective experiences such as fatigue and motivation. The scientists found that people with higher Hcy levels generally had lower levels of folate and vitamin B12, regardless of sex. When the data were analysed separately by sex, elevated Hcy was associated with greater physical fatigue in men and lower motivation in women.
The study also found that folate and vitamin B12 themselves were not directly associated with fatigue or motivation, suggesting that Hcy may reflect broader metabolic changes rather than vitamin status alone.
Homocysteine is a naturally occurring amino acid produced during metabolism and is normally broken down with the help of vitamins B6, B12, and folate.
Previous studies have suggested that elevated Hcy may interfere with the production of brain chemicals such as dopamine and serotonin, which regulate energy, mood, and motivation. However, the current study did not directly examine these biological mechanisms.
The researchers also observed differences between men and women. Women generally have lower Hcy levels than men, partly because oestrogen helps regulate homocysteine metabolism. Hormonal differences and variations in brain function may therefore contribute to the sex-specific findings, although this remains speculative.
Despite previous research linking elevated Hcy to oxidative stress, the team did not find evidence of such a relationship using the markers included in the study.
The researchers, however, cautioned that this does not rule out a connection, as different studies measure oxidative stress in different ways. They said maintaining adequate levels of B vitamins remains important because they help regulate homocysteine and are already known to support cardiovascular and brain health.
However, the findings did not show that lowering Hcy through diet or supplements would reduce fatigue or improve motivation.
“This suggested relationship between vitamin B12, folate, and fatigue in healthy individuals may represent the first report of its kind,” said Hiroaki Kanouchi, Professor, Graduate School of Human Life and Ecology, Osaka Metropolitan University. “Blood homocysteine levels have traditionally raised concerns in relation to cardiovascular disease, dementia, and fractures. However, our findings suggest that attention should also be paid to fatigue and motivation in the future. To prevent an increase in homocysteine levels, it is important to avoid deficiencies in vitamin B12 and folate. Maintaining a well-balanced diet on a daily basis is essential,” he added.
The authors also noted several limitations to the study.
As the study was cross-sectional, it cannot establish cause and effect. Fatigue and motivation were measured using self-reported questionnaires, and the researchers did not assess inflammation, stress hormones, or other biological markers that could help explain the findings.
The researchers added that larger, long-term studies and clinical trials are needed to determine whether reducing homocysteine levels can improve fatigue.
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Source: Osaka Metropolitan University; Image: magnific/armmypicca
This article can be found at Associations of Plasma Homocysteine Reflecting Vitamin B12 and Folate Status with Fatigue-Related Outcomes in Healthy Adults
Disclaimer: This article does not necessarily reflect the views of AsianScientist or its staff.
