
Scientists have uncovered a potential nutritional link to chronic fatigue. Healthy adults with signs of vitamin B12 and folate deficiencies were more likely to experience fatigue or lower motivation.
Chronic fatigue has become a common part of modern life. Many people struggle with long work hours, packed schedules, and persistent exhaustion that never seems to go away. While fatigue is often blamed on stress or a lack of rest, researchers say nutrition may also play an important role.
A 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 linked to fatigue and motivation levels in otherwise healthy adults.
Vitamin Deficiencies and a Key Blood Marker
The researchers focused on folate (B9) and vitamin B12, two nutrients that are essential for normal body function. When levels of these vitamins are too low, concentrations of homocysteine (Hcy), a blood biomarker, tend to rise.
To explore a possible connection, the team measured blood levels of homocysteine, folate, and vitamin B12 in nearly 600 healthy Japanese adults. Participants also completed assessments of fatigue and motivation using the Chalder Fatigue Scale questionnaire and a Visual Analog Scale.
The initial analysis found that people with higher homocysteine levels generally had lower levels of vitamin B12 and folate, regardless of sex.

Different Effects in Men and Women
The researchers then examined men and women separately to better understand how homocysteine levels related to fatigue and motivation.
Their analysis took into account several factors that could influence fatigue, including age, sleep duration, workload, and dietary habits.
The results showed that men with higher homocysteine levels were more likely to report greater physical fatigue. Among women, higher homocysteine levels were associated with lower motivation.
Nutrition’s Possible Role in Chronic Fatigue
“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.”
The findings suggest that nutrition could be an overlooked factor contributing to feelings of fatigue and reduced motivation, even among healthy people. While homocysteine has long been studied for its connection to conditions such as heart disease, dementia, and bone fractures, this research points to another possible consequence of elevated levels: feeling more tired and less motivated.
The study was published in the journal Nutrients.
Reference: “Associations of Plasma Homocysteine Reflecting Vitamin B12 and Folate Status with Fatigue-Related Outcomes in Healthy Adults” by Hiroaki Kanouchi, Ayaka Yamamoto, Akiko Kuwabara, Shigeo Takenaka, Eiji Nishikubo, Yukihiro Nomura, Takehiro Naruto, Kyosuke Watanabe, Kei Mizuno and Yasuyoshi Watanabe, 16 March 2026, Nutrients.
DOI: 10.3390/nu18060941
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6 Comments
As someone with chronic fatigue, I have been taking b12 and folate for years and have had no improvements. I suspect the lower levels of those vitamins are symptoms, not causes, of chronic fatigue. Whatever causes the fatigue is what also causes the low b12 and folate. Not the other way around.
Cause and effect—smart to not take for granted which is which. I wish you the best in finding answers.
Fyi. Taking B12 supplements is not simple.
For some it doesn’t matter how many they eat, they need tablets that dissolves in the mouth (look up intrinsic factor). Some needs injections and some needs special types of b12 vitamin.
Higher levels in a blood test doesn’t even mean you are doing well. Because it doesn’t say anything about how good your body is at using the vitamin.
If in deficiency you probably also need other types of vitamins to help you get used of the b12.
And once you have started a treatment, doctors have a really hard time using blood samples for anything without rushing to the wrong conclusions.
Taking them is not the same as actually absorbing them. B12, in my judgment, is the most difficult nutrient for the body to absorb. That’s because it’s a multistep process — getting it out of food, transporting it to its absorption site, absorbing it, etc. Problems with absorbing B12 are well recognized.
I would suggest that your statement — while correct that you are taking them — doesn’t mean that you are absorbing them. I would suggest getting your B12 and folate checked via blood tests.
No mention of the MTHFR gene many people have which means they can only take specially methylated b vitamins,including folic acid , prescribed by a doctor or they will have problems..
I was hoping to see in the study that serum B12 could be normal while still being indicative of B12 deficiency.