What is a Vitamin B12 Deficiency?
Vitamin B12 is an essential vitamin that plays a key role in many of the body’s metabolic processes. All cells require a constant supply of small amounts of B12 in order to function optimally. For this reason it is extremely important for humans and most animals to maintain a good supply.
Vitamin B12 is necessary for DNA synthesis, cell division, hematopoiesis (blood formation), synthesis of hormones and neurotransmitters, protection of nerve fibres in the spinal cord and the brain (myelin sheath) and the breakdown of homocysteines. Fehlt das Vitamin, kann die Gesundheit des Körpers langfristig nicht aufrecht erhalten werden und eine Reihe sich immer weiter verschlimmernder Symptome tritt auf.
Development of a Vitamin B12 Deficiency
A vitamin B12 deficiency typically exists as a result of either malabsorption or an increased vitamin B12 requirement. Impairments of the stomach or intestinal tract and an increased strain on the body as a result of stress or environmental pollution can create a situation whereby the body can no longer achieve a sufficient supply of vitamin B12 through the diet alone. This is often the case, when the diet doesn’t contain overly much vitamin B12 in the first place – such as in cases of vegetarian or vegan diets.
The causes of a B12 deficiency are above all a consequence of the poor nutrition that we are subject to on a global scale and the generally stressful lifestyles we lead in the modern world, which commonly lead to impairments in the digestive organs.
Prevention and Treatment of a Vitamin B12 Deficiency
As a result of the complicated absorption mechanism of vitamin B12, it is quite difficult in many cases to cover the body’s vitamin B12 need through food alone; which is why vitamin B12 supplements provide the answer for both treatment and prevention of a vitamin B12 deficiency. Today, many products are available with the naturally occurring vitamin B12 forms – methylcobalamin, adenosylcobalamin and hydroxocobalamin – exactly as they are found in our body and in foods. A practical prevention dose for oral intake would be around 250 µg per day, but in existing deficiencies or in cases of increased requirement, this figure would be roughly 500 µg as a recommendation.
Whether a vitamin B12 deficiency is present or not can be determined most easily via use of a vitamin B12 urine test. This measures the MMA acid in urine, which increases when there is a lack of vitamin B12 present. This is considerably more reliable than the blood tests available, which are much less useful due to their inability to differentiate between active and inactive B12.
Vitamin B12 Deficiency: Symptoms
Vitamin B12 fulfills 5 different duties within the body. It regulates and influences:
- The synthesis of DNA ( -> cell division, blood formation)
- Energy metabolism (->production of energy in the mitochondria)
- Lipid metabolism (development of cell membranes, development of myelin sheath, protection of nerves in central nervous system and brain)
- The synthesis of hormones and neurotransmitters
- Detoxification (homocysteine, cyanide, nitrous oxide and many more)
Due to the diverse role of the vitamin, a B12 deficiency can exhibit a whole range of physical and mental symptoms that are sometimes severe. Fatigue and depression are known indications of a deficiency, as well as anemia and nerve damage.
- Impaired production of neurotransmitters and hormones can result in mental and cognitive disorders
- Disrupted hematopoiesis (blood formation) can lead to anemia and a severely impaired metabolism
- An increase in homocysteine levels can cause heart and vascular disease, damage to the retina and vascular dementia (MID/VCI)
- Nerve damage can evoke unexplained pain, paralysis and loss of coordination
- Demyelination of the spinal cord can lead to symptoms similar to those suffered in multiple sclerosis
- Impaired utilization of vitamin B9 (folic acid) can lead to severe deficiency symptoms in pregnant women and may cause developmental abnormalities of the fetus
Mild physical symptoms
Severe physical symptoms
Overview of the typical symptoms of a vitamin B12 deficiency. Some symptoms may also have other causes.
How Does a Vitamin B12 Deficiency Progress?
Despite ultimately leading to serious health problems, it can take a long time for a vitamin B12 deficiency to be discovered. It can take up to 20 years from the start of a deficiency until serious physical or psychological symptoms develop. During this time the body is already suffering from a lack of B12, but this often goes undiagnosed.
This is usually because the early symptoms, such as tiredness, depression and mild inflammations are rarely identified as symptoms of a vitamin B12 deficiency, even by doctors. Unfortunately in most cases tests are only carried out when the patient has developed more serious symptoms in the later stages of a deficiency, meaning the individual has already suffered a lack for many years that has gone undetected.
Generally a vitamin B12 deficiency progresses in following stages:1
1. Vitamin B12 count in the bloodstream drops
Due to a supply shortage or absorption problems the concentration of vitamin B12 in the blood sinks.
2. Depleted store/cell depletion
The vitamin B12 stores in the liver and somatic cells become depleted causing levels in the bloodstream to decrease continuously. This is when initial symptoms might be first experienced (mental issues, depression, lethargy, tiredness, weakened immunity, mouth inflammation (stomatitis) etc.).
3. Impaired metabolic activity
Low vitamin B12 levels can significantly affect a number of bodily functions. DNA synthesis is dramatically slowed down and homocysteine levels in the bloodstream increase significantly. General health deteriorates notably and physical symptoms become apparent.
4. Clinical manifestation
Emergence of the more severe deficiency symptoms. These can have very serious implications which are sometimes irreversible, or even fatal, as is the case with pernicious anemia.
How quickly these stages develop depends on the cause of the deficiency. If caused by absorption issues the fourth stage may in some cases occur within a few years, whereas vegans for example, with otherwise good health and nutrition can live up to 20 years with mild symptoms, before more the serious ones manifest.
The ‘Vicious Cycle’ of a Vitamin B12 Deficiency
The subtle progression of a B12 deficiency has resulted in the common misconception that we survive healthily with low levels of it. Recent studies indicate, however, that vitamin B12 deficiency is extremely common but rarely identified. In particular the psychological symptoms such as depression, which precede the more severe physical symptoms are rarely properly diagnosed as being the result of a B12 deficiency.
Due to the nature of the metabolic cycle, when a B12 deficiency develops it tends to become a vicious cycle. Some of the symptoms that occur as a result of a B12 shortage can negatively impact our absorption capabilities, which then in turn reinforces these symptoms. It is extremely important that this vicious cycle is broken. This is possible by initially administering a very high dose of vitamin B12 to replenish the body’s store quickly.
What Causes a Vitamin B12 Deficiency?
The main causes of a vitamin B12 deficiency can be categorised in three ways:
1. Nutrition and lack of B12
The daily requirement of vitamin B12 from food is estimated at 3 micrograms (significantly dependant on age, gender and situation). Over time, insufficient intake of B12 from our diet can lead to a deficiency. This could be due to an unbalanced or purely vegan or vegetarian diet.4
Vitamin B12 can actually be made in the human digestive tract from intestinal bacteria. Unfortunately for the most part this is produced at a point where the essential vitamin can no longer be absorbed and so goes unused and is excreted with the faeces.
B12 is not found in all diet types. The vitamin is produced exclusively by microorganisms and is found in varying concentrations in all animal foodstuffs, but is almost impossible to find in plant foods. Because of this vegans and vegetarians should pay particularly close attention to their vitamin B12 intake.
Risk groups for a B12 deficiency through an insufficient diet:
2. Increased consumption of vitamin B12 (stress)
In stressful situations our need for vitamin B12 heavily increases. Stress here refers to all types of high physical and mental strain, such as heavy manual labour, loud noise, competitive sport, psychologically stressful situations, fear, anxiety, sadness, heartache, spiritual changes and crises or overworked immune system due to infection.
This increased demand is determined by two factors. Firstly, in stressful situations absorption of vitamin B12 is made more difficult, because blood supply to the intestinal organs is poor and the ratio of gastric acid to enzymes is affected. Secondly, vitamin B12 is required for the production of other hormones such as norepinephrine (noradrenaline) and serotonin. Due to the high release of norepinephrine in many stressful situations vitamin B reserves are used up quickly. A deficiency will develop if there is an insufficient reserve.
During pregnancy and breastfeeding, the body’s B12 requirement increases significantly too – here, it is of particularly critical importance to ensure a sufficient supply, because a deficiency can impact upon the development of the child and have long term significance.5
Additionally, the presence of toxins can lead to a significant vitamin B12 requirement. This is particularly the case for smokers, as vitamin B12 is used to neutralize the cyanide content in smoke.6 This can also be a serious issue in cases of general anesthetic – as vitamin B12 is required to bind to the nitrogen for detoxification, which significantly depletes the body’s B12 storage and can result in a severe deficiency.7
Risk groups for a deficiency through increased requirement:
- Those in pregnancy and breastfeeding stages
- People with high stress levels
- Anyone who has recently undergone local or general anesthetic
- Those often exposed to air pollution or heavy metals
3. Malabsorption of vitamin B12
When suffering from digestive disorder it will not be able to properly absorb vitamin B12, even when it has a sufficient supply. This could be caused by gastrointestinal infection, gastritis or stress due to interaction with heavy metals and medication.
Vitamin B12 can only be absorbed via the oral mucosa and the final section of the small intestine (the ileum). A special glycoprotein called intrinsic factor (IF) is required for this process, which is secreted by the stomach’s parietal cells. Without intrinsic factor only very small amounts of vitamin B12 will be absorbed through passive diffusion. In these cases an very high dose of B12 would be necessary to ensure enough was obtained.
The health of the gastrointestinal tract is therefore highly important for vitamin B12 in enabling absorption and a number of illness affecting this area can seriously impact this. These illnesses are particularly widespread in developed countries due to poor eating habits and in accordance with this B12 deficiencies are also common. Even small problems affecting the mucous membrane appear to reduce the absorption rate of vitamin B12 significantly, which can very easily result in a supply shortage.
Current findings show that the majority of illnesses caused by a deficiency are the result of impaired absorption, for example, gastritis or agitated gastrointestinal mucosa. It is not currently known how the relationship between intake and absorption affects one another, because the data on this topic show no consistencies.
Here are some of the many possible causes of absorption problems:
How Common is a Vitamin B12 Deficiency?
Just how commonplace vitamin B12 deficiencies are has not been fully investigated. This is partially due to the fact that there is not yet a precise method of measuring the body’s B12 levels and also because opinions regarding what defines a B12 deficiency greatly differ. Many researchers today believe that the current suggested threshold is far too low and that a more accurate minimum requirement of vitamin B12 would realistically be much higher.
Currently B12 serum levels (blood concentration) lower than 200pg/mol are considered deficient. However, many scientists now consider levels under 350pg/mol to be deficient. Recent studies even claim that a realistic value would be set at about 500-600 pg/mol. This view is explored in the findings of Mitsuyama and Kogoh,8 Tiggelen9 and David Brownstein.10
The current deficiency definition indicates that around 2-7% of the younger generation and 14-40% of the older generation suffer from a lack of B12.12-14
Particularly at risk are the elderly and above all vegetarians and vegans: differing studies came to the same conclusion, which was that around 20-70% of vegetarians and 60-90% of vegans are currently suffering from an acute vitamin B12 deficiency.14-17
However, in light of recent discussions regarding the accuracy of these figures it is possible that deficiencies are far wider reaching. A study from Tufts University which evaluated the results from the Framingham Heart Study involving 3000 test subjects ascertained that levels of B12 lower than 350pg/mol were deficient and that 39% of those who were tested fell into this category.18 This is a significantly higher value than the official projection of 2-7%.
Studies from 2013 and 2014 found that over 80% of the test subjects had a vitamin B12 value below 300 ng/ml – which points to a latent undersupply for further sections of the general public.18,19
Who is at Risk of a Vitamin B12 Deficiency?
Studies such as the one mentioned above show that a deficiency can occur in all age groups among meat eaters, vegans and vegetarians alike. However, certain groups of people hold a higher risk:
- Vegans and vegetarians
- People aged 50+
- Those with stomach and intestinal disorders
- Heavy smokers and coffee drinkers
- People taking certain medication (see table above)
- Alcoholics and drug addicts
Vitamin B12 Deficiency: Test and Diagnosis
At present, no means of diagnosing a vitamin B12 deficiency can give an absolute answer, but the following methods are used to determine information about the levels of vitamin B12 in our bodies:
Until recent years vitamin B12 deficiency was determined by measuring its concentration in the blood. However, this method has proven to be somewhat inaccurate, because blood tests also factor in forms of B12 that have little to no use in the body (vitamin B12 analogs).
Test score indications in the United States:
|strong deficiency||< 150 pg/ml|
|deficiency||< 200 pg/ml|
|slight lack||200-300 pg/ml|
|hypervitaminosis||> 1000 pg/ml|
More recently other test methods have been developed:
Holotranscobalamin HoloTC test
This method measures levels of the biologically usable vitamin B12 in the blood, but gives no indication of the B12 levels in cells and body stores.
|deficiency||< 35 pmol/l|
|deficiency possible||35 – 50 pmol/l|
|deficiency unlikely||>50 pmol/l|
This test measures the homocysteine levels in the blood, which are typically raised in the presence of a B12 deficiency. The results are usually analysed in conjunction with a blood test, because there are other known factors that can cause high homocysteine levels.
|deficiency likely||> 12 µmol/l|
|deficiency unlikely||5 – 12 µmol/l|
Methylmalonic acid (MMA) test
In cases of a cellular deficiency the body produces increased amounts of methylmalonic acid (MMA). This can be measured in the blood and urine and provides reliable information concerning present deficiencies. Today it is the easiest means of testing and is recommended by many researchers as the best method.
> 3.6 mmol MMA/mol creatinine
2 mg MMA/g creatinine
< 3.6 mmol MMA/mol creatinine
2 mg MMA/g creatinine
Researchers at the University of Florida have developed a breath test, which determines the levels of vitamin B12 against the CO2 content of the air we breathe. The test is currently still being trialed.19
Vitamin B12 Deficiency: Treatment
Whether caused by malabsorption, insufficient supply through the diet or even stress-induced, the key to treating a vitamin B12 deficiency lies in vitamin B12 supplements. Depending on the severity of the deficiency, the following treatments can be recommended.
|Type of Deficiency||Treatment|
(slightly low values, no symptoms)
|250 µg /day (oral)|
Hydroxo- and/or Methylcobalamin
(Low values, some light symptoms)
|500 µg /day (oral)|
Hydroxo- and/or Methylcobalamin
(very low values, clear symptoms)
4 weeks 1000µg Hydroxocobalamin (injections)
500 – 1000 µg/day (oral)
Hydroxo- and/or Methylcobalamin
Vitamin B12 supplements contain different forms of vitamin B12 as their active ingredient, which each have specific advantages and disadvantages. In general, it is recommended to avoid the synthetic cyanocobalamin and instead use one of the natural forms – methylcobalamin, adenosylcobalamin and hydroxocobalamin. Further information on the differences between the active ingredients can be found in the article types of vitamin B12.
An initial treatment with injections of infusion is recommended for seriously low values or severe symptoms, in order to defeat the deficiency quickly and to fill up the body’s b12 store. Absorption through this method is considerably higher than with oral supplements, so the B12 reaches its destination quicker.
In all other cases, oral supplements are absolutely sufficient. Today they are even recommended for cases of severe anemia, because they can almost match the effectiveness of injections when taken in high doses.
When choosing supplements, there are several points to focus on: 1. The active ingredient, 2. The dosage, 3. The type (pill, capsule, spray, etc), 4. The additives.
Advice on choosing the right supplement for you can be found here: vitamin B12 supplements.
We will soon be bringing you a product review and comparison of all current B12 supplements on the market. This will be added to the website once updated.
Vitamin B12 Deficiency – What’s the Right Dosage?
The table above gives a rough guide on dosage levels or vitamin B12 treatments. Here is a further explanation of this:
Cases of insufficient intake – for example as a result of a vegan diet, require an initial intake of large doses (~ 500 µg), in order to refill the body’s B12 store. After that, doses can be transferred to one designed to cover the RDA, since these vitamin dosages are typically overdosed anyway to account for the imperfect absorption mechanisms in the body. The recommended average dose for covering the body’s vitamin B12 requirement would be around 250 µg for a standard requirement and around 500 µg for an increased requirement.
In cases of malabsorption, it is equally important to discover the cause of the malabsorption as it is to take vitamin B12 supplements. Until this has been determined, B12 should be taken in considerably high doses. With oral supplements, such as vitamin B12 pills or capsules, this would be around 500 µg/day.
Cases of increased requirement and for the elderly require a dosage of around 500 µg a day as a recommendation. More information about dosages of vitamin B12 supplements can be found in our article vitamin B12 dosage.
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