The four stages of vitamin B12 deficiency

Given up animal foods? How to ensure you don’t get to stage four. The damage could be irreversible.

Maria Cross MSc
Sep 16 · 8 min read
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If you recently switched to a 100% plant-based diet, you can relax for quite some time. The adult liver can store enough vitamin B12 to last 1–5 years. But after that, and without “careful planning”, your health could suffer serious and irreversible damage.

You often hear and read that a plant-based diet can be a healthy one, with enough careful planning. Unfortunately, further details of what that entails are not always forthcoming. So, in the interests of ensuring a carefully planned plant-based diet, I outline below the four stages of vitamin B12 deficiency — and how to make sure you don’t get to stage four.

Vitamin B12, also known as cobalamin because it contains the trace element cobalt, is not found in plant foods. It is made by bacteria in the guts of animals and migrates from gut to muscle. A water-soluble vitamin, B12 is crucial to the brain and nervous system, red blood cell formation and DNA.

The central nervous system is especially vulnerable to vitamin B12 deficiency.

Writing in the British Medical Journal in 2013, researchers describe the case of a 25-year-old man with low blood (or more accurately, serum) B12 and myelopathy.

Myelopathy, a general term for degeneration of the spinal cord, is the most common neurological syndrome of vitamin B12 deficiency and is a sign of early stage four deficiency. If detected in time, the condition is fully reversible.

The man in question sought medical help for a tingling sensation in both hands that had spread up his arms. Described as a “strict vegetarian”, he was treated immediately with B12 injections, which led to a rapid resolution of his symptoms. As the researchers conclude:

“Early diagnosis and treatment are crucial in order to prevent the irreversible damage to the nervous system.” (Verma et al)

You will only become aware of any symptoms at stage 4.


This is when “serum depletion” becomes evident. It is possible to detect low levels of the B12 carrier protein TCII. TCII levels drop within just a few days of absence of the vitamin.

As stage one progresses to stage 2, low vitamin B12 can be detected at a cellular level. Like stage 1, there are no discernible symptoms.

At this stage, there is another detectable change in the blood. Levels of an amino acid called homocysteine begin to rise above normal, creating a condition sometimes called ‘hyperhomocysteinuria’. It’s a see-saw act: as B12 levels rise, homocysteine levels fall, and vice versa.

Raised homocysteine (Hcy) in the blood is an indication of B12 deficiency.

Normal homocysteine metabolism is regulated by a trio of B vitamins: B12, folate (B9) and vitamin B6, working together as cofactors. To lower blood levels of Hcy, you just need a regular and adequate intake of these three vitamins.

Deficiency of B6 is uncommon, as this vitamin is widely distributed in a broad range of foods. Folate deficiency is more common, and can be reversed by eating lots of leafy green vegetables, such as spinach and kale, though the richest dietary source is offal, especially beef liver. Beans are also a good source.

Vitamin B12 is the tricky one, the one most likely to be missing from diet.

Because vitamin B12 is found exclusively in animal source foods, the most vulnerable groups are vegetarians and vegans.

I should add at this point that B12 deficiency can be brought about by other causes other than avoidance of animal source foods and I cover this in a separate article on the subject. But dietary avoidance is the main cause of deficiency.

B12 deficiency was once thought to be rare in vegetarians but is now known to be common among people on all the different vegetarian variations. Researchers have observed stage 3 deficiency in over 60% of vegetarians.

This is the clinical deficiency stage — signs and symptoms start to appear. Some of these are more serious than others, and some are more obvious than others.

Early, mild symptoms of stage 4 vitamin B12 deficiency include:

  • Fatigue
  • Depression
  • Anxiety
  • Loss of appetite
  • Pallor
  • Hair loss
  • Numbness or tingling in the hands and feet
  • Poor memory.

Memory problems and slow mental processes are the most commonly reported cognitive problems associated with deficiency of this vitamin.

Both the blood and the central nervous system are most likely to be affected at this stage. Megaloblastic anaemia is not uncommon. This is a condition in which abnormal red blood cells are produced by bone marrow.

Megaloblastic anemia resulting from cobalamin deficiency may also be associated with neurological symptoms. The initial neurological symptom may be tingling or numbness in the hands or feet. Additional symptoms develop over time including balance or gait problems, vision loss due to degeneration (atrophy) of the nerve that transmits impulses from the retina to the brain (optic nerve), and mental confusion or memory loss.”

One possible neurological outcome is myelopathy, as experienced by the young man documented in the British Medical Journal. There may also be neuropathy (nerve damage) and dementia. Peripheral neuropathy (damage to nerves in the body’s extremities) is seen in 25% of patients with vitamin B12 deficiency.

A major concern is a form of myelopathy that affects the spinal cord called ‘subacute combined degeneration’ (SCD). Myelin sheaths and axons are destroyed in the white matter of the spinal cord. The myelin is the protective layer wrapped around the nerve. Fortunately, SCD:

Another indication of stage 4 deficiency is depression.

One study compared vitamin B12 levels in 100 vegetarians with 100 omnivores. Vitamin B12 was significantly lower in the vegetarian group, and the frequency of depression was 31% compared with 12% in the omnivores. Psychosis was found in 11% of the vegetarians compared with 3% of the omnivores. The researchers concluded that:

“Vegetarians have vitamin B12 deficiency and are more prone to developing neuropsychiatric and neurological problems.” (Kapoor et al).

In older people, cognitive function may decline, and dementia arise. The elderly — whether vegetarian or omnivore — are vulnerable to B12 deficiency, a factor that can be easily overlooked when symptoms of dementia arise. It is estimated that 10%–15% of people over the age of 60 have vitamin B12 deficiency.

A number of such cases have been reported in the press. In 2011, the New York Times reported the case of an 85-year-old woman who was diagnosed with Alzheimer’s after becoming increasingly confused and forgetful. Fortunately, she was tested for vitamin B12, and found to be deficient. After receiving weekly B12 injections, she recovered her mental health sufficiently to continue living independently and alone.

Last year (2018), the Journal of Alzheimer’s Disease published a Consensus Statement on the link between B12 deficiency and dementia. The researchers concluded that screening for raised homocysteine should be carried out in memory clinics, and people found to have high levels should be offered supplementary B vitamins. Apparently, this is something that already happens in Sweden.

If left untreated, stage four will progress to irreversible damage to the central nervous system.

Despite the potentially devastating consequences of untreated vitamin B12 deficiency, it is possible to continue on a plant-based diet if you know what you are doing. This means being informed of alternative sources of B12, and making sure you have enough of those sources.

If you are at all concerned about your B12 status, I recommend that your first step should involve testing.

There are two tests that are quite useful — blood (serum) vitamin B12 and homocysteine levels.

A blood vitamin B12 test may provide an early warning sign that you have low levels of this vitamin, and have arrived at stage 1 and/or 2, and are possibly heading towards stage three.

If you have high homocysteine (stage 3) you probably want to know about it. Fortunately, it’s a relatively straightforward test that you can do it at home.

If you’re in the UK, don’t expect your doctor to arrange a test for you. (Though you can always ask.) Your alternative option is to arrange a private test. For details of how to go about this, see York Laboratories or Genova Diagnostics. Below is a sample report from York Laboratories.

If you are outside the UK, see your healthcare provider, or have a look at the Genova Diagnostics website.

The recommended daily amount of B12 is 2.4mcg in the US and 1.5mcg in the UK. These are estimates based on what is thought sufficient to prevent megaloblastic anaemia.

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Nobody absorbs all the vitamin B12 they consume. Even omnivores can only expect to digest and absorb around 50% of this vitamin from meat and fish.

Although vegetarians generally eat dairy foods and eggs, the quantity of B12 is quite low in these foods, and the absorption rate is not great either. That would explain why they are frequently deficient in this vitamin, but not to the same extent as vegans.

There are various forms of B12, natural and synthetic. The type most commonly used in supplements is cyanocobalamin, a synthetic form not found in nature. It is cheap, so popular with manufacturers. The body has to convert it into methylcobalamin, a natural form.

So, if you are already taking a B12 supplement, check the label to see what form it’s in. Oral vitamin B12 supplements overall have a low absorption rate — 0.5% — 4%. That is why supplements of this vitamin generally tend to be made in very high doses. An oral dose of 1000mcg, which is quite typical, delivers around 5–40mcg of B12. Researchers suggest an oral dose of 50–100mcg daily, or 2,000mcg weekly, for healthy vegetarian adults, taking into account the rate of absorption.

“Vegetarians should thus take preventive measures to ensure adequate intake of this vitamin, including regular consumption of supplements containing B12.” (Pawlak et al).

Sometimes processed food manufacturers add vitamin B12 (along with other nutrients) to their products, so that they can make a big deal of this on the packaging. Personally, I think this is very misleading, as you might (reasonably) assume that fortification eliminates the need to take additional supplements. The truth is, fortification is usually made with low amounts of the synthetic form of B12.

“In some countries, certain foods are fortified, such as breakfast cereals, with Cbl. However, the quantities used are quite variable and the consumption of such foods cannot guarantee sufficiency in the absence of other sources.” (Rizzo et al)

I contacted a few companies, who confirmed that they fortify with the artificial form cyanocobalamin, including the manufacturer of an oat ‘milk’ who helpfully added in their email to me that:

“… we assume that people who are lacking in this vitamin take supplements, hence we believe that cyanocobalamin is effective for the majority of our consumers.”


In short, I would define “careful planning” as informed supplementing, preferably with natural vitamin B12 and at a level sufficient to ensure adequate absorption. Fortified foods are fine if you like that sort of thing, but don’t see them as a guarantee of adequate B12 provision, or a guarantee against the irreversible damage of stage four deficiency.

Feed Your Brain

Exploring the link between diet and mental health

Maria Cross MSc

Written by

Nutritionist and nutrition science writer, specialising in diet and mental health. Subscribe to AllYouCanEat.org.uk for free brain food guide. @MariaXCross

Feed Your Brain

Exploring the link between diet and mental health

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