The link between chronic fatigue and deficiency of two B vitamins

Chronic fatigue is quite common, and it is not simply a matter of too little sleep and too much work. Japanese researchers have found that low levels of vitamin B12 and folate (vitamin B9) may contribute to increasing fatigue and lack of motivation in otherwise healthy individuals. The Japanese study was published in the journal Nutrients.

Chronic fatigue has become more widespread in our modern world, particularly because of increasing demands, rapid societal changes, and constant exposure to device screens, making it difficult for many people to keep up or simply relax. However, while excessive workloads and lack of sleep are often blamed for chronic fatigue and low motivation, poor dietary habits, blood sugar imbalances, and deficiencies of specific nutrients may also play a crucial role.
To investigate this, a team of Japanese researchers from Osaka Metropolitan University focused on vitamin B12 and folate (vitamin B9). First, these B vitamins are important for blood formation and energy metabolism. Second, they are required for the conversion of the amino acid homocysteine into another important amino acid, cysteine, following the breakdown of proteins.
Homocysteine is a byproduct of metabolism, but when blood levels become too high, homocysteine acts as a toxin that can contribute to chronic inflammation, oxidative stress, and circulatory disorders. There is also an increased risk of oxidative stress in the brain, where free radicals can damage nerve cells.

The connection between vitamin B12, folate, energy, and homocysteine

The new study included approximately 600 healthy Japanese adults. Through blood tests, the researchers measured the participants’ levels of vitamin B12, folate, and homocysteine. They then assessed the participants’ degree of chronic fatigue and motivation using validated scales and questionnaires (the Chalder Fatigue Scale and the Visual Analog Scale).
The researchers found that participants with the highest blood levels of homocysteine generally had lower levels of vitamin B12 and folate.
The researchers then took a closer look at how homocysteine levels were associated with fatigue in men and women. The analysis also included other factors that may affect fatigue, including age, sleep habits, work demands, and dietary patterns.
The study revealed that men with higher blood levels of homocysteine generally reported greater physical fatigue. In women, elevated homocysteine levels were more strongly associated with a lack of motivation.

A new perspective on vitamin B12, folate, and energy levels

Vitamin B12 and folate are already known to help regulate the body’s homocysteine levels. Elevated homocysteine is also known to be associated with cardiovascular disease, dementia, and bone fractures.
According to the Japanese researchers, their study is the first to demonstrate a link between elevated homocysteine levels, chronic fatigue, and lack of motivation.
As a result, greater attention should be paid in the future to how homocysteine affects energy levels and how adequate intakes of vitamin B12 and folate from diet or supplements help regulate homocysteine levels.

Sources of vitamin B12 and folate and reasons for widespread deficiencies

The various B vitamins are found primarily in whole and green foods such as whole grains, vegetables, legumes, nuts, seeds, and brown rice. They are also present in liver, meat, fish, and eggs.
Vitamin B12 is found exclusively in animal-derived foods, and it is the only B vitamin that can be stored in the body. This means that it may take many months, or even more than a year, before a vitamin B12 deficiency becomes apparent in people who follow a plant-based diet.
In addition, stress, aging, stimulants, and several types of medication can impair the body's absorption or utilization of various B vitamins.

References:

Hiroaki Kanouchi et al. Associations of Plasma Homocysteine Reflecting Vitamin B12 and folate Status with Fatigue-Related Outcomes in Healthy Adults. Nutrients 2026

Osaka Metropolitan University. Vitamin B12 and folate deficiencies linked to chronic fatigue. ScienceDaily 2026.