Chronic Fatigue Syndrome: The Roles of Gut Health and Vitamins B12 & Folic Acid
Chronic fatigue syndrome, or myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), is a debilitating condition characterized by severe exhaustion that is not relieved by rest and is often worsened by physical or mental activity. For decades, its causes have remained unclear, but recent research points to important biological factors involving both gut health and nutrition.
A study by researchers at Cornell University, published in Microbiome, found that ME/CFS patients exhibit significant differences in their gut microbiome and immune system. By analysing stool and blood samples from 48 individuals with ME/CFS and 39 healthy controls, researchers were able to identify patients with 83 percent accuracy. The findings suggest the potential for a non-invasive diagnostic tool for a condition that has traditionally been difficult to diagnose.
The study revealed that people with ME/CFS had reduced diversity of gut bacteria and fewer species known for their anti-inflammatory effects. Researchers also identified inflammatory markers in the blood, suggesting increased intestinal permeability, or "leaky gut." This may allow bacteria or bacterial products to enter the bloodstream and trigger immune responses that contribute to fatigue and other symptoms.
Researchers say these findings provide evidence that ME/CFS is associated with measurable biological abnormalities rather than being purely psychological. Although it remains unclear whether gut changes cause the disease or result from it, the research raises the possibility of future treatments involving dietary changes, prebiotics, or probiotics.
Nutrition may also influence fatigue levels. A study from Osaka Metropolitan University examined the relationship between vitamin B12, folate (vitamin B9), and fatigue in approximately 600 healthy Japanese adults. The researchers focused on homocysteine, a blood compound that increases when levels of these vitamins are low.
Participants with higher homocysteine levels generally had lower vitamin B12 and folate levels. Elevated homocysteine was linked to greater physical fatigue in men and lower motivation in women, even after accounting for factors such as age, sleep, workload, and eating habits. These findings suggest that vitamin deficiencies may contribute to fatigue even in otherwise healthy individuals.
Professor Hiroaki Kanouchi noted that homocysteine is traditionally associated with cardiovascular disease and dementia, but the study indicates it may also be relevant to fatigue and motivation. Maintaining adequate vitamin B12 and folate levels through a balanced diet may therefore support energy and overall well-being.
Together, these studies highlight the biological foundations of fatigue. In ME/CFS, alterations in the gut microbiome and immune system may play an important role, while nutritional deficiencies can contribute to fatigue in the broader population. Although fatigue has many possible causes, growing evidence suggests that underlying physiological processes—including gut health and nutrient status—deserve greater attention in both research and clinical care.
Source:
Reduced diversity and altered composition of the gut microbiome in individuals with myalgic encephalomyelitis/chronic fatigue syndrome. Microbiome, 2016; 4 (1) DOI: 10.1186/s40168-016-0171-4
Associations of Plasma Homocysteine Reflecting Vitamin B12 and Folate Status with Fatigue-Related Outcomes in Healthy Adults. Nutrients, 2026; 18 (6): 941 DOI: 10.3390/nu18060941