Two B vitamin deficiencies are now suggested as common causes of persistent fatigue, according to new research that challenges how doctors currently test for them. The study, involving more than 600 people in Japan, found that low levels of vitamin B12 and folate – also known as B9 – showed only weak correlations with tiredness when measured by standard blood tests, but a different marker known as homocysteine proved far more telling.
Fatigue is one of the most frequent reasons patients see their GP in the UK – so common that doctors use the shorthand TATT, “tired all the time”, in medical notes. The causes are notoriously broad: pregnancy, depression, carbon monoxide poisoning, chronic fatigue syndrome (also called myalgic encephalomyelitis) and countless other conditions can all leave people feeling drained. Yet the possibility of a B vitamin shortfall rarely springs to mind. “These are nutrients the public are less familiar with,” said Dr Dan Baumgardt, an academic GP at the University of Bristol who was not involved in the study.
The new study
Researchers at Osaka Metropolitan University, led by Professor Hiroaki Kanouchi, gave questionnaires to more than 600 participants to assess physical fatigue, mental fatigue and motivation. They also measured blood levels of vitamin B12, folate and homocysteine. The results, published in the journal Nutrients, showed that higher homocysteine levels – indicating a possible B12 or folate deficiency – were linked with worse fatigue in men and weaker mental motivation in women. However, the direct blood tests for the two vitamins themselves showed only small correlations. “We recommend measuring homocysteine concentrations,” Professor Kanouchi said. The study does not prove that the deficiencies were causing the fatigue, but it does support the need for a trial of supplementation for persistent tiredness, he added.
Why B vitamins matter
B12 and folate are essential for a large group of metabolic processes, including making DNA – which means they are vital for tissue growth and repair – and producing the brain signalling chemicals that regulate mood and motivation. Without enough of these nutrients, the body struggles to maintain energy and cognitive function. When people begin to run low on B12, Professor Martin Warren, a micronutrient researcher at the Quadram Institute, explained, symptoms can develop very slowly. “Gradually, your energy levels drop, you become slightly more tired, you get a little bit of brain fog, all of these things creep up and you might think it’s the ageing process.”
The diagnostic challenge
Despite the growing recognition of B vitamin deficiencies, diagnosing them remains fraught with difficulty. The NHS guidelines body, Nice, includes blood tests for B12 and folate on its list of possible investigations for fatigue, but they are classified as “additional investigations” – not part of the first round of tests, points out Dr James Gill, a GP and lecturer at Warwick Medical School. Moreover, standard blood tests for B12 and folate can be unreliable. Levels in the blood may not reflect what is actually available in the body’s tissues. A different blood test, for homocysteine – a substance involved in the same metabolic pathways as B12 and folate – can give a truer picture. People deficient in these vitamins usually have elevated homocysteine. Yet GPs often cannot order homocysteine tests themselves; such tests typically have to be requested by hospital doctors, which means they happen far less frequently.
Dr Gill said that even when blood tests come back normal or borderline, if a GP suspects a deficiency they can still recommend treatment. “If a patient is very close to the border, let’s just give you some more,” he said. Both vitamins can be taken as tablets, and B12 can also be given by injection for a quick boost.
The complexities of diagnosing these deficiencies extend beyond test access. Some symptoms of B12 deficiency – such as mouth ulcers, pins and needles in the feet, memory problems or “brain fog” – can easily be mistaken for other conditions or simply put down to getting older. Left untreated, deficiency can cause more serious neurological problems, including numbness, muscle weakness, disturbed vision, confusion, depression and anxiety. In severe or prolonged cases, neurological damage can become irreversible. Other signs include a sore red tongue, breathlessness, feeling faint, headaches, pale skin, palpitations, tinnitus, loss of appetite, weight loss, diarrhoea and problems with balance and coordination.
Who is at risk
Certain groups are particularly vulnerable. Vegans are at high risk because B12 is found naturally only in animal products. Vegetarians also need to be careful. Fortified foods such as Marmite and some breakfast cereals can help – a single teaspoon of Marmite provides a substantial portion of the daily recommended intake for both B12 and folate. For those on plant-based diets, regular supplementation is strongly advised: daily doses of 25–100 micrograms or a weekly dose of 2,000 micrograms are commonly recommended. People with Crohn’s disease, which reduces nutrient absorption, are also at increased risk, as are those taking the diabetes drug metformin or long-term acid-reducing medicines known as proton pump inhibitors. These drugs can interfere with the body’s ability to absorb B12 because stomach acid is needed to free the vitamin from proteins in food.
Dietary solutions
For those who suspect their B vitamin levels might be too low, diet offers a straightforward way to improve them. Good sources of B12 include all forms of meat, fish, eggs, dairy products, and fortified foods such as some breakfast cereals and Marmite. Folate is abundant in beans, other pulses and green leafy vegetables. “Some people soldier on but anybody who is feeling persistent tiredness should go and see their GP,” said Dr Baumgardt. “If it’s a medical problem we might determine the cause.”