Vitamin B12 and folate deficiencies linked to chronic fatigue, reveals research

Chronic fatigue has become increasingly common in modern life as people juggle heavier workloads and less downtime. While exhaustion is often blamed on stress or lack of sleep, researchers say poor nutrition may also play an important role.

A research team led by Professor Hiroaki Kanouchi from Osaka Metropolitan University's Graduate School of Human Life and Ecology investigated whether deficiencies in certain vitamins could be connected to fatigue and motivation levels. The scientists focused on folate (B9) and vitamin B12, two nutrients that help regulate homocysteine (Hcy), a substance in the blood that tends to rise when these vitamins are lacking.

Blood Marker Linked to Fatigue and Motivation

The study included around 600 healthy Japanese adults. Researchers measured blood levels of homocysteine, folate, and vitamin B12, then evaluated participants' fatigue and motivation using the Chalder Fatigue Scale questionnaire and a Visual Analog Scale.

The team found that participants with higher homocysteine levels generally had lower levels of folate and vitamin B12, regardless of sex.

Researchers then looked more closely at how homocysteine levels related to fatigue in men and women separately. Their analysis also accounted for factors that could influence fatigue, including age, sleep duration, workload, and eating habits.

The results showed that men with higher homocysteine levels were more likely to report greater physical fatigue. In women, elevated homocysteine levels were linked to lower motivation.

Vitamin Deficiencies May Affect Energy Levels

"This suggested relationship between vitamin B12, folate, and fatigue in healthy individuals may represent the first report of its kind," said Professor Kanouchi.

"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."

Reference: Kanouchi, H.; Yamamoto, A.; Kuwabara, A.; Takenaka, S.; Nishikubo, E.; Nomura, Y.; Naruto, T.; Watanabe, K.; Mizuno, K.; Watanabe, Y. Associations of Plasma Homocysteine Reflecting Vitamin B12 and Folate Status with Fatigue-Related Outcomes in Healthy Adults. Nutrients 2026, 18, 941. https://doi.org/10.3390/nu18060941