By Martin Warren
Quadram Institute
June 20, 2026

Vitamin B12 is needed in only trace amounts, yet its absence can have far-reaching effects.

Two micrograms is an almost unimaginably small amount. It weighs less than a tiny fragment of a grain of table salt. Yet adults need only around this amount of vitamin B12 each day, depending on the guideline used, to support red blood cells, nerves, and DNA production.

In 2026, it will be 100 years since George Minot and William Murphy reported that a liver-rich diet could treat pernicious anemia, then a frequently fatal disease. Their work transformed medicine and eventually led scientists to identify vitamin B12 as the substance in liver that treated the disease.

But the route to that breakthrough began with an unexpected clue from animal experiments. The American physician and pathologist George Whipple had shown that liver helped dogs recover from anemia caused by blood loss. Blood-loss anemia happens when the body loses red blood cells through bleeding. Pernicious anemia is different: the problem is not bleeding but poor absorption of vitamin B12. Even so, Whipple’s experiments pointed researchers towards the liver as a source of a powerful blood-forming factor.

Patients with pernicious anemia who had been close to death often improved dramatically within weeks of eating liver-rich diets. The success of liver treatment eventually led scientists to isolate the deep red compound now known as vitamin B12, or cobalamin.
Why Vitamin B12 Deficiency Remains Common

Despite decades of research, vitamin B12 deficiency remains common, particularly among older adults, vegans, vegetarians, and people with conditions that affect absorption. Some people do not consume enough B12 because it is naturally found mainly in foods from animals, including meat, fish, eggs, and dairy products. Others struggle to absorb it properly.

This becomes more common with age. Some older people produce less stomach acid, which is needed to release B12 from food. Others develop autoimmune gastritis, in which the immune system damages stomach cells involved in producing acid and intrinsic factor, the protein needed for vitamin B12 absorption. Weight-loss surgery and some medicines used for diabetes or acid reflux can also reduce absorption.

The symptoms of deficiency can develop slowly and are often mistaken for normal aging. People may feel exhausted, weak, or short of breath. Some develop numbness or tingling in their hands and feet, poor balance, memory problems, or what many describe as “brain fog.” These symptoms are not specific to B12 deficiency, so persistent tiredness, tingling, or balance problems should be checked rather than assumed to be a simple vitamin problem.

People at higher risk, including vegans, vegetarians, older adults, and those taking medicines that affect stomach acid or diabetes treatment, may need testing or supplementation advice from a health professional.
How Low B12 Causes Fatigue and Anemia

Doctors have traditionally linked tiredness in B12 deficiency to anemia. Without enough vitamin B12, the bone marrow cannot produce healthy red blood cells. Instead, it releases unusually large and immature cells that carry oxygen less effectively around the body.

But anemia may not be the only reason people with low B12 feel exhausted.

In humans, vitamin B12 is directly needed by only two enzymes, the proteins that help chemical reactions happen in the body. One helps the body make DNA, which cells need when they divide. The other helps mitochondria process certain fats and protein building blocks. Mitochondria are the tiny structures inside cells that help turn food into usable energy.
Vitamin B12, Mitochondria, and Energy Production

This mitochondrial role has attracted growing interest from researchers studying aging, muscle function, and vitamin B12 status. A 2026 study explored what happens when cells do not have enough B12. Researchers found that low B12 could interfere with the DNA inside mitochondria and reduce energy production in laboratory models of skeletal muscle (muscle cells studied outside the human body).

A related study in aged female mice found that B12 supplementation improved several signs of mitochondrial health in muscle, including the number and structure of mitochondria. Together, this work points to one possible reason why some people with low B12 report fatigue before obvious anemia is detected.

These findings do not mean vitamin B12 supplements can reverse aging or act as an energy booster for people whose B12 levels are already normal.

Scientists have suspected a link between B12 and mitochondrial function for many years because one of the two B12-dependent enzymes works inside mitochondria. Earlier research has also suggested that low B12 status may be linked with poorer muscle function in older adults, although much of this work is observational and cannot prove cause and effect.
Are Vitamin B12 Injections Worth It?

So if you’re feeling persistently tired, is it worth paying for vitamin B12 injections at a wellness clinic or medispa? For most people, no. B12 injections are an established treatment for diagnosed deficiency, particularly when absorption is impaired, and the NHS uses hydroxocobalamin injections for vitamin B12 deficiency anemia.

But there is little evidence that B12 shots boost energy, weight loss, or performance in people whose B12 levels are already normal. The more useful first step is to find out what is causing the tiredness.

The story of vitamin B12 is unusual because the body needs so little of it, yet the consequences of deficiency can be profound. Long before scientists understood its chemistry, doctors recognized that something in the liver could restore strength, appetite, and vitality to desperately ill patients.

A century later, researchers are still finding that this tiny cobalt-containing molecule does more than prevent anemia. It may also help explain how cells maintain energy and function as the body ages.

Martin Warren receives funding from the Biotechnology and Biological Sciences Research Council (BBSRC) as well as the Advanced Research and Invention Agency (ARIA).

Adapted from an article originally published in The Conversation. The Conversation

https://theconversation.com/