Silent vitamin B12 deficiency is very common

Version 3.00[1]

First published in 2007. Last updated on December 17, 2014


By Jaan Suurküla, M.D.




Vitamin B12 is of vital importance for the normal functioning of the brain and the peripheral nervous system. A mild deficiency may cause tiredness, fatiguability, sleep disturbances, memory disturbances, concentration disturbances, irritability. A deficiency, even at a fairly early stage, may damage the brain and the peripheral nerves.


B12 deficiency, when pronounced, may cause irreversible neurological and brain-damage and has been found in a considerable majority of Alzheimer dementia cases. Also chronic depression, mano-depressive illness and other psychiatric disorders are associated with B12 Deficiency. Myocardial infarction and stroke are other well documented consequences.  Vitamin B12 plays a more multifaceted role in the physiology than formerly known.


Recent research has shown that vitamin B12 deficiency is common. One study reported that 39% of the US population had low or near low values[2]. Deficiency is found in a considerable majority of vegetarians.


The deficiency risk cases increases with age. A combination of age above 50 and vegetarianism engenders a very high risk of B12 deficiency. But B12 deficiency has even been found in teenagers who are vegetarians.


Measuring the vitamin in blood with the standard test (serum Cobalamin) is not reliable. Some can have a pronounced deficiency in the brain with normal B12 in blood (this has been discovered through cerebral liquor analysis).


Also, the laboratory reference values have been wrong, and still are in most countries, allowing much too low B12 values. Consequently many people with deficiency are wrongly classified as normal. Therefore the extent of B12 deficiency has long been underestimated.





Vitamin B12 is very important for the normal functioning of the nervous system


This includes such basic functions as enabling fatty acid synthesis of nerve cell (neuronal) membranes and the synthesis of important neurotransmitters (signal substances) like serotonin and dopamine. Also it is needed for the synthesis of myelin, which is vital for impulse transmission in the nervous system.


Early deficiency symptoms may be vague


Early and even fairly pronounced deficiency does not always cause distinct or specific symptoms. Common early symptoms are tiredness or an increased mental fatigability. Decreased concentration and decreased memory.  Irritability and depression.


Sleep disturbances may occur, because B12 is important for the regulation of the sleep wake cycle by the pineal gland (through melatonin)[3]. Treatment with B12 normalizes the melatonin level, and thereby the sleep disturbance. The quality of sleep has been found to be significantly improved[i]. Cyanocobalamin was not found to have any effect on sleep.


I have had cases with pronounced deficiency but still no subjective symptoms – perhaps some sleep disturbance. One patient had extreme B12 deficiency but still only a minor memory disturbance and some general weakness. It is my experience that many doctors miss the diagnosis.


More pronounced symptoms

Seasonal Affective Disorder (SAD), with severe seasonal depressions has a known connection with disturbed pineal (melatonin) functioning including disturbed sleep-wake rytm[ii].


B12 deficiency may be present in severe psychiatric disorders including paranoid and shizo-affective psychoses [iii], violent behavior, severe chronic therapy-resistant depressions  (just a drastic example: Rajamani A 2008 [4] [iv]), mano-depressive illness[5] including acute mania[v] and chronic asthenia (fatigue) and they consistently improve remarkably or get fully symptom-free with high dose B12 therapy[6].



IMPORTANT NOTE to vegan mothers: The need for B12 is increased during pregnancy and the child may become deficient if you take standard multivitamin supplements, see the case report about the baby who had pronounced B12 deficiency at the verge of brain damage because the mother had not taken enough B12. It is quoted in this footnote: [7] (its scientific reference is here: Guez et al 2012 [vi]).


Severe deficiency


This may harm the brain. For example about 50 percent of Alzheimer’s dementia cases were found to have low B12 in a recent Swedish study (this percentage is based on an old and much too low B12 minimum concentration limit in blood, so deficiency may be much more common in Alzheimer’s – perhaps the major or only cause).


A major cause for the brain damage in Alzheimer is believed to be the neurotoxic amino acid homocystein which increases considerably with B12 deficiency. Homocystein exists normally in the body, but it can only be tolerated in low amounts. Vitamin B12 is required for decomposing it, so a deficiency leads to a harmful build-up of this brain toxin. The brain dysfunction caused by too little vitamin B12 adds to the toxic effects of homocystein in producing the symptoms of Alzheimer’s disease.


IMPORTANT: In Alzheimer also a deficient uptake of B12 into the brain plays an important role according to scientific studies. To compensate for this, administration of high doses over long time is needed. Unfortunately, therapy has often been insufficient as it has stopped when the blood level is “normalized” (according to the old normal values). In reality a high blood level has to be achieved for optimal results and treatment should go by the presence of clinical signs and not by the blood levels, because healing takes time and experience indicates that high dose treatment is required.


Epileptic symptoms have been reported [vii] [viii].  


Inflammation of the visual nerve (Optical neuritis) with decreased vision or even blindness may occur.


Also the peripheral nervous system is affected. The first symptoms are tingling, needle-prick or burning sensations in the toes and later in the fingertips. Later numbness in the hands and feet, like “walking on clouds” and balance disturbances. The muscles get weak and shaky. The bladder and bowel control gets increasingly impaired.  Impotence may occur. The sense of smell may decrease. There are many varieties and atypical patterns may appear [ix].


Many other disturbances, not yet known to be connected to B12 may be there. But you can have pronounced brain deficiency without any of these peripheral symptoms.


Vitamin B12-deficiency may also cause a special kind of anaemia (so called megaloblastic anaemia whose signs clearly differ from iron deficiency). This anaemia was formerly thought to be a good indicator of B12-deficiency so the laboratory values were established with anaemia as the only criterion which caused important under-diagnosis of the deficiency.


In anaemia perniciosa (see below) there may also be Gastro-intestinal symptoms, including soreness of the tongue that may be smooth, at least on the sides, flatulence, heartburn, diarrhoea or constipation.



IMPORTANT: Scientific research has clearly established that there may be pronounced brain affection without any anaemia. It seems that a critical factor in such conditions is deficient uptake of B12 into the brain, which requires higher blood levels for enough B12 to reach the brain. So you may have sufficient B12 for preventing the anaemia but too little for the protecting the brain.


IMPORTANT: Severe deficiency with neurological symptoms may occur even in teenagers if they have been on a vegetarian, B12-free diet. This example deserves to be quoted:


A 14-year-old white girl suffered from severe neurologic disturbances caused by vitamin B12 deficiency, due to failure to provide vitamin B12 supplementation to a strictly vegetarian diet. The disturbances resolved completely following treatment with vitamin B12. [Ashkenazi S, et al (1987)[x] ]

So if you are a vegetarian parent, be very careful to have B12 tested regularly unless you supplement.


IMPORTANT: Treatment with B12 can, unless they have reached a severe degree, fully reverse the disturbances caused by deficiency, provided it is done with high doses and for a sufficiently long time.



Other symptoms and disorders associated with B12-deficiency


Here are some examples of disorders that have responded positively to B12- treatment according to clinical observations (not experimentally confirmed):


·         Aphtous stomatitis (whitish painful spots in the mouth) cured,

·         erythema nodosum (a nodular skin disorder) cured,

·         Hyperpigmentation of the skin, fully recovered[xi]

·         bursitis cured,

·         Localized hypopigmentation (greying) of hair. Reversed [xii].

·         sulphite sensitivity including asthma caused by it cured,

·         chronic contact dermatitis cured, 

·         chronic urticaria,

·         Bell’s palsy (facialis nerve paresis),

·         breast cancer improved or cured, herpes zoster,

·         vitiligo,

·         Blepharospasm

·         Hepatitis improved.

·         Macula degeneration of the eyes has been halted.


Other functions of Vitamin B12


·         Vitamin B12 has been found to be necessary for the production of DNA all over the body (in cooperation with Folic acid).

·         Vitamin B12 is involved in cellular repair.


·         Vitamin B12 (as adenosylcobalamin) is involved in the biochemical processes of extracting energy from proteins and fats.






Serum Cobalamin


This test measures vitamin B12 in blood serum. It is not considered to be a very good indicator. But this may partly be because the commonly reference value is wrong, allowing much too low B12 levels as “normal”. 


The present lower limit is about 200 picograms/litre (pg/l) = 145  picomol/litre (pm/l)  (there is a minor variation between different labs). In Sweden, the measure picomol is used, while, for example in Germany, picograms are mostly used.


IMPORTANT: Japanese research has found good reasons to raise the lower allowed limit considerably. There, 550 pg/l = 400 pm/l is now established as the border value for deficiency.


Some clinical researchers believe, on the basis of clinical experience, that 600-700 pg/l or more is optimal.



Addition Dec 2014


A new test -Holotranscobalamin (HoloTC)


HoloTC has been found to be a considerably better indicator of B12 deficiency than serum Cobalamin. It is still in the evaluation phase (although developed in the 80-ies, but only recently being commercialized) and all results indicate that it is better than other markers for early B12 deficiency. Transcobalamin is a protein that enables B12 to enter the cells. HoloTC is Cobalamin bound to transcobalamin and is also called “active vitamin B-12”. It correlated very strongly (.9) with Cobalamin inside the erythrocytes, while the correlation of serum Cobalamin was .8 and that of Homocysteine .78 in one study (for a thorough evaluation, see Valente E et al 2011 [xiii] ). For reference values, see footnote [8]. Hopefully this promising test will become generally available soon.


As HoloTC is not yet generally established, it is not enough to test vitamin B12 to exclude deficiency, you need also to test Homocystein at least. There are several reports in the literature about misleading indications from using the old reference values of serum Cobalamin. One case study reported that the patient had a fully “normal” serum Cobalamin value (489 pg/l), but the clinical signs were suspicious and testing with Homocystein and MethylMalonicAcid (presented further below) showed considerable derangements (Mar, N et al (2012) [xiv]. 


A group has recently reported, on the basis of a study on 1359 serum samples, that a combination of HoloTC and MethylMalonicAcid seems to be the most reliable indicator of deficiency [xv]. For their conclusion, see footnote[9].




This is an amino acid that exists normally in the body and requires B12 for its decomposition. So an abnormally increased level of Homocystein is an indirect and fairly good indicator of B12 deficiency that seems to be more sensitive than vitamin B12 in blood. Moreover, Homocystein is an aggressive free radical and neurotoxin, so there are good reasons to check it.


IMPORTANT: Research indicates that the commonly accepted level of Homocystein is much too high. It has been about 14-15 micromol/l but research has found that at that level the risk for cardiovascular disease is considerably increased  (see diagram below). Ideally it should not be higher than 6,3 micromol/l (0,85 mg/ml):


This prospective study showed that a homocysteine level above 6.3 µmol/L was associated with a 35% increase in the risk of myocardial infarction. Each 5-µmol/l increment in homocysteine above 6.3 µmol/L, increased the risk of coronary infarction by 60% in men and 80 % in women. Ref.:Am Heart Assoc. J Nov 15 2825-2830, 1995, Homocysteine


Homocystein may sometimes be the only parameter that is increased in the cerebrospinal liquor in B12 deficiency in the brain.


Because there may be greatly reduced uptake of B12 into the brain, there may be deficiency in the brain only.


Consequently, all the blood tests can be normal and yet an important, brain damaging deficiency can be there. Homocystein in cerebrospinal liquor is not a standard test yet.

So the generally available test methods are not fully reliable. 


But it is important to test anyway, because

  • If one of the tests is positive you will have a strong reason to correct the deficiency.
  • Homocystein causes other serious trouble, so it is good to check it anyway.
  • If you treat with high dose B12 without testing it will influence the tests for several years. So you will not know for sure if you had a B12 deficiency.


Folic acid


This vitamin also required for Homocystein decomposition, so it is good to check it also, although it is not an indicator of B12 deficiency.


The normal range is 7 - 34 nmol/l, or 3 – 15 ng/l,


Vegetarians often have higher levels, which is not harmful, as the “normal value” only reflects the situation in the population and not what is physiologically beneficial or necessary.


If Folic acid is normal but Homocystein increased, it indicates that B12 deficiency alone is the cause of increased Homocystein. If both B12 and Folic acid are low, then both have to be taken to normalize Homocystein, which is a toxic substance (see below).


MethylMalonicAcid (MMA)


It is considered a useful indicator of deficiency and is a substance that, like Homocystein, increases with deficency.

B12-deficiency is indicated by a value over 0.4 µmol/L (4.7 µg/dL). (Increases also in the case of some genetic disorders, in renal insufficiency, pregnancy and old age). Because of some sources of error it needs to be combined with some other test.



Addition Dec 2014

MethylMalonicAcid has been widely researched in recent years. Its usefulness has been confirmed. A possibly better alternative is to measure it in the urine where the concentration is 40 times higher than in the blood. A Chinese study found that this was a sensitive early predictor of B12-related neuropathy in Diabetics.

(Sun A et al 2014 [xvi] )

The combination of MMA with HoloTC is considered to be the best indicator of B12 deficiency [xvii].


Ex juvantibus test


Even if your B12 test values are normal, I recommend you to consider taking vitamin B12 for safety, if you suspect you have a deficiency, as B12 is non-toxic (except for Cyanocobalamin). Take B12 especially if you are a vegetarian or are above 50. If you feel definitely better after a few weeks, sleep better, more energy, less foggy etc, you probably had a deficiency (this diagnosis method is used by physicians when there is no good test available or is too expensive - it is called “ex juvantibus diagnosis”).




1. The most common cause is deficient intake. This is why a considerable proportion of vegetarians have deficiency. The number may still be underestimated as the testing methods are not sensitive enough and the incidence of deficiency has therefore been underestimated, perhaps to a great extent.


2. Stomach disturbances may cause deficiency, because B12 is taken up in the stomach:


  • An increasingly common cause is the use of the very popular stomach acid reducing agents, so called “proton pump inhibitors” like for example Nexium, Losec, Omeprazol, Pariet and Rifun and “Histamin receptor antagonists” like Cimitidin, Zantac and Tagamet. One study found that Omeprazol decerased B12 uptake by 80% .There is no obvious reason to believe that Omeprazol is worse than the others in this respect –probably all proton pump inhibitors and Histamin receptor antagonists cause a similar drastic decrease.  
  • Another quite common cause is Helicobacter infection, which is the major cause of gastritis. This means that all gastritis patients should check their B12. One study found Helicobacter infection in 56% of patients with B12 deficiency.
  • Stomach operations where part of it has been removed (Billroth I or II). If you have had such an operation it is important to supplement with B12.
  • Obesity operations where the stomach is operated so as to decrease uptake. Also in this case it is important to supplement with B12.
  • “Perniciosa” – a condition that causes an atrophy of the stomach mucosa, preventing the uptake. Chronic Helicobacter infection is a major cause.  The gastric symptoms are not very dramatic, other than heartburn, gases and bad digestion. Medically it is actually called “Anaemia Perniciosa”, because the B12 deficiency causes anaemia and this has formerly been the major concern and focus of treatment. However this has been a dangerously narrow view, because all other B12 deficiency symptoms may be associated with it and they may be important even when not obvious. It is my experience from my time as a specialist in internal medicine that this issue has been seriously underestimated.



3. A number of drugs disturb the uptake or destroy the vitamin. This includes among others,

·         Oral contraceptives,

·         Antidiabetic drugs containing the substance Metformin, which in my opinion should not be used considering that B12 deficiency is especially harmful, causing grave complications in diabetics (see “Causes” below). There are other good alternatives.

·         The antibiotics

o   Metronidazol (Flagyl, Filmet)

o   Chloramphenicol (Banned in several countries and allowed in most others only as a last resort)

o   Neomycin

·         Smoking also decreases B12.

·         Four cups of Coffee reduced B12 by 15% in one study.


4. Intestinal disorders may also disturb the digestion or uptake of the vitamin. Disturbances of the gastrointestinal flora, for example after antibiotics (already one tablet of antibiotics can sometimes upset the flora importantly), Crohn’s disease, Gluten intolerance-caused intestinal disorder, pancreatic insufficiency.


5. Certain parasites may consume B12 – Giardlia lamblia and tapeworm especially.


6. Diabetes Mellitus I and II have a strong association with B12 deficiency according to recent research. It worsens their complications considerably so great attention to B12 is required in this disorder. For a good review, see Kirbige D, Mwebaze R (2013) [xviii]. For their conclusion see this footnote: [10]


7. Age. Above about 50 the ability to take up B12 decreases to an increasing extent according to some studies. But with very good health, this may not need to be the case. One reason for reduced uptake in older people may be the increasing incidence of Helicobacter infection with increasing age. 




Homocystein damage: Homocystein is a toxic amino acid that damages the cells in various tissues.


This includes damage to the arteries. Recent research has established that homocystein is a major cause of arteriosclerotic diseases including stroke and myocardial infarction. For example, one study found that regular intake of the major nutrients required to lower homocysteine, namely vitamin B12, folic acid and vitamin B6 caused a more than 60% decrease in vascular disease. When one of them is deficient, the homocystein increases to harmful levels.


Especially if you have cardiovascular diseases in your family there are strong reasons to check B12, folic acid and Homocystein in serum.


There is also evidence indicating that homocystein also causes other age-related degenerative diseases and cancer.


The knowledge of the complications of Homocystein toxicity and B12 deficiency is yet incomplete as this problem has long been underdiagnosed and greatly underestimated. Still as of today (2014) most physicians are unaware of the seriousness of this issue or underdiagnose it because they rely only on vitamin Cobalamin in serum for diagnosis, even in cases where there are symptoms associated with deficiency.


Food sources of vitamin B12


Mung bean and chick bean sprouts contain B12. However, it has not been established whether this is a form that can be absorbed by humans.


Vegetables in general are very low in B12. A paper by Mozafar (1994) reported that if they are grown on cow dung, which is rich in B12, they contain some B12. However the contents are so low that they provide far from sufficient amounts.  Also the B12 contents were very variable. This research has not been validated. It does not provide a scientific basis for the belief among some vegans that vegetables grown in manure-fertilized soil provides sufficient amounts of B12 – an opinion that Mozafar did not share although his paper is being quoted by vegans as evidence for such vegetables being a sufficient source of B12. A comment on this issue is found in


B12 is damaged relatively slowly at boiling, so not much B12 is probably lost in low- or medium level pasteurization of milk (low level = 63 degr C, medium=72 degr C). 

Milk products like Yoghurt, cottage cheese made from yoghurt, cream and butter may have been exposed to high level pasteurization (85-95 degr C for 15 min) which is commonly required for these products in many countries. This might reduce the B12 content. One study reported about 10% reduction of B-vitamins after pasteurization (Haddad GS 1983 [xix]) while no specific study on B12 was found as of dec 2014.


Ultrahigh pasteurization means heating to 135 degrees Celsius (= 275 Fahrenheit) in -15 seconds and may perhaps damage B12 but I found no research about it.
In any case, the amount in milk and milk-products is far from enough to cure a deficiency. But it may perhaps be enough to prevent deficiency if you use milk-products regularly.
It was formerly believed that Algae including Spirulina and Chlorella contained B12 but this was due to insufficient measurement methods. More recently it has been found that they contain a form of Cobalamin that cannot be used by humans. 


The richest sources are non-vegetarian:


Organ foods including liver, kidney, heart, brain. Egg yolk. Clams, Oysters, crabs, sardines, salmon.


IMPORTANT  None of the food sources are sufficient to effectively and rapidly cure a deficiency. In such a case there is no option but to take Vitamin B12.




When a deficiency has been diagnosed or is suspected the only safe way is to take a Vitamin B12 preparation.


  1. Take Methylcobalamin. It is easily found in the Internet.
  2. Dosage: Methylcobalamin sublingual tablets, 5 mg (5000 microgram) a day until all symptoms are gone. Don’t stop as long as you note an improvement and even the continue for at least 4 weeks, because there may remain subtle damage that you cannot sense.


Let the tablet dissolve under the tongue. Avoid swallowing and keep it for a good while in the mouth not eating afterward so that all is taken up through the mouth mucosa. This is because some have decreased or low uptake ability through the stomach.


Methylcobalamin is available through the internet, but customs in some countries may stop it unless you have a physicians prescription for it.


  1. After all symptoms are gone, take 1000 mcg per day if you have had deficiency symptoms from the nervous system, because this may indicate that your uptake into the nervous system is not so good (but it is not necessarily so – the symptoms may just have been due to a very low intake). Otherwise you can take 3-500 mcg depending on what size is available. Not until recently it was realized that higher doses and higher blood levels are required to prevent brain damage but there is yet no consensus about dosage. Also there is not clinically available method for finding out the absorption into the brain in the individual case. Blood levels  are useless, as they may be normal and still there may be a considerable deficiency in the  nervous system. As B12 is completely non-toxic, there is no risk in taking more than the body needs. 300 –500 mcg is probably a good safety margin but stay updated.


  1. If you have a family history of Alzheimer, continue taking at least 1000 mcg, because it is known that the uptake into the brain is decreased in Alzheimer cases. This may be a genetic factor leading to a slow build-up of brain damage due to B12 deficiency, so don’t wait for taking a high dose until the first Alzheimer symptoms appear.


  1. If you have an amalgam disorder or have or have had much amalgam in your teeth, you may need to take 10.000 mcg Methylcobalamin per day for ˝-1 year or more, because it seems that mercury may make brain uptake much more difficult (there seems to exist differences in this regard, perhaps caused by genetic factors). If you have mercury-related problems, it is good, if possible, to take the treatment under the supervision of an expert on amalgam problems (unfortunately very few doctors are).


  1. Cyanocobalamin, should not be used. It has been the predominant variety in the pharmacies. It is a synthetic variety that is not effective in restoring all damage from  B12 deficiency, especially in the nervous system, which is of paramount importance.


Highly poisonous Cyanide is created when Cyanocobalamin is metabolized. At normal doses, the amount is considered insignificant. But it may become significant when high doses are injected, which is common in the case of neurological symptoms. There are cases reports about people who got serious complications after Cyanocobalamin injections. One case developed blindness after only 3 injections according to Nutt NR (2014)[xx]. The use of Cyanocobalamin is especially hazardous for people with kidney dysfunction or with a genetic abnormality reducing the ability to eliminate cyanide.


From a medical standpoint there exists no justification for the use of Cyanocobalamin as Cobalamin natural compounds are available (Methylcobalamin, Adenosylcobalamin). The only reason for the existence of Cyanocobalamin on the market has been purely commercial – it has been more profitable because it is easier to produce than the natural and healthy varieties and the physicians have not taken this issue seriously enough.


You can contribute to a change by refusing to accept prescriptions with Cyanocobalamin and ask the physician if he knows that there are healthy alternatives (many don’t know).


  1. Injections are not necessary. They can cause allergy to vitamin B12. They are commonly offered, when there is a pronounced deficiency or neurological symptoms. It has been scientifically confirmed that B12 is as well absorbed through the mouth (sublingually). Usually injections are given once a week or a month, which brings about a very un-physiological situation with large swings in the concentration (before injection a low level and after injection a huge dose in the blood – it is a biochemical shock treatment that I believe should be avoided). Better take a sublingual tablet (sublinguette) every day to maintain a fairly even level.
  2. If Homocystein is increased, it is desirable to consider taking vitamin B6 also. It is required for metabolizing homocystein. In modern industrialized food processing it is very often destroyed. Especially microwave ovens harm B6 easily. So if you don't prepare your food yourself, but depend largely on processed and microwaved foods you are likely to have B6 deficiency also. B6 is sensitive to heat, so B6 rich vegetables like Broccoli, should only be cooked a short time - 5-10 min, enough only to soften. And the liquid must be included as much of the vitamin gets dissolved into the water.
  3. If Folic acid is low, take that as well. This is because B12 alone is not enough to effectively reduce the homocystein if either of the other one are lacking. Vegetarian food is rich in folic acid, provided you eat the broth.


                                                              i.      B6: Take 10 mg/day

                                                            ii.      Folic acid: Take 0,8-1 mg/day (a higher dose is not useful).


Recent News


A new B12 source has been found – the missing link for vegans?


Sept 16 2014: A bacterial species, Thaumarcheota, found in the oceans and freshwaters has been found to produce B12. They are among the most abundant organisms on the planet.

Source: New bacterial source of vitamin B12 identified

By Nathan Gray+, 16-Sep-2014.



Comment: This is interesting, because is “among the most abundant species on the planet”. Therefore it may be speculated if they provide a solution to the mystery that vegetarians in some areas in the world, for example in the Himalaya, with no intake of known B12 sources don’t seem to have a deficiency. For example, strictly vegan Indians from the Himalayan region had no deficiency, but developed it in England in spite of having precisely the same diet there. This indicates that, while in Himalayas their B12 did not come from the food items.


It is interesting that B12 is found in high amounts in cow manure. Could it be so that the cow harbors large amounts of Thaumarcheota? If so, it does not seem far-fetched to suggest that it could exist in humans too, producing B12 in the intestines.


For more about this, see my blog posting “A new B12 source is discovered – the missing link for vegans?





Concluding advice


B12 deficiency is common in the USA especially in people over 50 and in a large majority of vegetarians. Also it is common among Diabetics and aggravates their complications importantly.


Therefore if you belong to said categories, do check your B12 and homocystein. Deficiency can appear after a few years on vegetarian diet. If you have taken antibiotics any time in your life without actively correcting the gastrointestinal flora, or have been taking contraceptives or ant-acidic drugs for gastritis, and have a Helicobacter infection, you have especially strong reasons to check B12.


IMPORTANT: In these cases, take B12 “ex juvantibus”, that is, as a treatment-response test, even if you have normal test values but have some tiredness, or depression tendencies, or sleep disturbances or irritability or other symptoms mentioned above. Take Methylcobalamin 5 mg (5000mcg) and check if the symptoms decrease or disappear (you don’t need to have all symptoms – they appear to a different extent in different persons). If there is a distinct improvement probably had a B12 deficiency.


After eliminating the symptoms, if you are a vegetarian, either take a 5 mg tablet of Methylcobalamin every week. It has been believed that this is usually enough as it is stored in the liver (however, recent research indicates that liver storage has been overestimated, but this issue is not yet settled).


The content of B12 foods like milk products are not reliable enough. If you still want to rely on food only, do check your B12 at least once a year.


It is really important to test B12 and Homocystein before taking high dose B12. Otherwise you might have a severe deficiency that you don’t take seriously enough and don’t treat accordingly, which may be harmful, because of the damaging effect of homocystein and B12 deficiency combined.


It is my experience that B12 deficiency has been greatly underdiagnosed so far. It appears to be a much more common cause of health problems, especially in vegetarians and elderly, than doctors have realized, partly because they are applying outdated normal valuses, but mostly because of lack of knowledge about the disorder. It may cause serious damage to the nervous system including Alzheimer.


So be vigilant about it.




Copyright © 2007 Jaan Suurküla. You are allowed to quote parts or the whole of this text provided you include a reference to the source including the URL of this article like this:

Jaan Suurküla ”Silent vitamin B12 deficiency is very common.” version 3.00





[1] Version info: The number before the comma is changed when a major update has been made (eg 2,0). The first number after the comma designates minor additions or updates of content (eg 1,1), The second number indicates reformulations for improved clarity (eg 1,01). The third number indicates changes in editing only (eg 1,001).

[2] Judy McBride,   “B12 Deficiency May Be More Widespread Than Thought”. USDA research service newsletter, Aug 2, 2000, This result was based on measuring 3000 persons in the Framingham study, that picked a representative sample of the US population. The crterium for deficency was a value below 258 pmol/liter, which is far below the recently established minimum value of 400 pmol/l. So a much greater part than 39% of the US population probably has B12 deficiency.

[3] The concentration of melatonin in SAD patients was on average 2.4 times as high as in the control group according to one study.  See Karadottir R, Axelsson J. "Melatonin secretion in SAD patients and healthy patients matched with respect to age and sex." Int J Circumpolar Health. 60, 4:548-51, 2001.

[4] This is just a example of several reports: Rajamani A (2008): Excerpt: “ unusual presentation of long standing psychotic symptoms without anaemia in a 31 year old male, who presented to a tertiary care psychiatric facility. His physical examination revealed hyper pigmentation of extremities and posterior column involvement. Laboratory investigations confirmed normal haemoglobin and low serum B12 levels. He recovered dramatically with short term anti psychotic medication and intramuscular cobalamin supplementation. He remained asymptomatic and functionally independent at two years follow up.

[5]     Prof. Christopher Reading, in Australia, has shown that manic-depressive illness runs in the same families as pernicious anemia. He also found an association between latent pernicious anemia (B12 deficiency), on the one hand, and periodic psychosis, schizo-affective psychosis and manic depressive psychosis, on the other (Reading CM.  Latent pernicious anemia: A preliminary report.  Medical Journal of Australia 1975, 1: 91-4.).

[6] J. Dommisse. “Subtle Vitamin-B12 Deficiency and Psychiatry: A Largely Unnoticed but Devastating Relationship?” Medical Hypotheses  (1991) 34, 131-140.  He reports experiences of intractable chronic psychiatric disorders that have been cured or significantly improved with B12. This includes cases who had “normal” B12 values according to the old standards.


[7] “An exclusively breastfed 5-month-old Italian male infant, who was born after a normal full-term pregnancy to a vegan mother who was apparently daily treated with a multivitamin oral preparation during the second and third trimester, was hospitalised because of poor weight gain, feeding difficulties, severe pallor, muscle hypotonia and somnolence.”..” The child was diagnosed as having vitamin B12 and iron deficiency due to nutritional inadequacy and was immediately treated with packed red blood cells, intramuscular vitamin B12 injections, and iron supplementation. A few days after the start of therapy, his hemoglobin levels and other hematological parameters rapidly improved, and a clinical improvement was observed within few weeks.” (Guez S et al 2012).

[8] Reference values for HoloTC (Valente E, et al 2011):

·         HoloTC<20 pmol/L. Probably deficient.

·         HoloTC 20-30 pmol/L* Additional testing (RBC, folat).

·         HoloTC >30 pmol/L Probably not deficient

[9] Testing for vitamin B12 deficiency should start with holotranscobalamin measurement. Holotranscobalamin between 23 and 75 pM should be followed by MMA testing that can filter substantial number of deficient cases in the grey range in individuals with normal renal function. (Hermann R, Obeid R, 2013)

[10] Biochemical and clinical vitamin B12 deficiency has been demonstrated to be highly prevalent among patients with type 1 and type 2 diabetes mellitus. It presents with diverse clinical manifestations ranging from impaired memory, dementia, delirium, peripheral neuropathy, sub acute combined degeneration of the spinal cord, megaloblastic anemia and pancytopenia.



[i] Mayer G et al „Effects of vitamin B12 on performance and circadian rhythm in normal subjects.“ Neuropsychopharmacology. 1996 Nov;15(5):456-64.

[ii] Ikeda M, Asai M, Moriya T, Sagara M, Inoue S, Shibata S. ”Methylcobalamin amplifies melatonin-induced circadian phase shifts by facilitation of melatonin synthesis in the rat pineal gland.” Brain Res. 1998 Jun 8;795(1-2):98-104.

[iii] Berry N, Sagar R, Tripathi BM. Catatonia and other psychiatric symptoms with vitamin B12 deficiency.; Acta Psychiatr Scand. 2003 Aug; 108(2):156-9.


[iv] Rajamani, A Praveen R (2008); Chronic psychosis associated with vitamin B12 deficiency Association of Physicians of India. Journal 56: 115-6, 2008


[v] Kumar S ; Acute Reversible Mania as a Presenting Feature Of Vitamin B12 Deficiency; 7: 309-311; 2004

[vi] Guez S et al. (2012) “Severe vitamin B12 deficiency in an exclusively breastfed 5-month-old Italian infant born to a mother receiving multivitamin supplementation during pregnancy”; BMC Pediatrics, 12:85. 2012. 

[vii] Vitamin B12 deficiency in a child presenting with epileptic spasms. Case report. Journal of Pediatric Neurology 12, Number 1; 2014


[viii] Kumar S. Recurrent seizures: An unusual manifestation of vitamin B12 deficiency. Neurol India 2004;52:122-3

[ix] Ahn T-B et al; Unusual neurological presentations of vitamin B12 deficiency European Journal of Neurology Volume 11: 339–341, 2004

[x]Ashkenazi S, et al (1987) Vitamin B12 deficiency due to a strictly vegetarian diet in adolescence. Clin Pediatr (Phila).; 26:662-3. 1987 Abstract in NCBI.

[xi] Katsunori Mori, Iwao Ando, Atsushi Kukita.Generalized Hyperpigmentation of the Skin due to Vitamin B12 Deficiency . Journal of Dermatology; 28:282–285, 2001

[xii] Bhat RY, Varma C; Reversible hypopigmentation of hair secondary to vitamin b12 deficiency; Our Dermatol Online; 4:101-102; 2013. Case study, on 3 yr old boy.


[xiii] Valente E et al (2011) “Diagnostic accuracy of holotranscobalamin, methylmalonic acid, serum cobalamin, and other indicators of tissue vitamin B₁₂ status in the elderly.” Clin Chem. 2011 Jun;57(6):856-63. Quote: “Today, we can conclude that holoTC seems more suitable than total vitamin B-12 for diagnosis of vitamin B-12 deficiency. 

[xiv] Mar, N et al; Pitfalls in the Diagnosis of Vitamin B12 Deficiency; Open Journal of Hematology, 2012,3-2


[xv] Herrmann W, Obeid R; Utility and limitations of biochemical markers of vitamin B12 deficiency European Journal of Clinical Investigation: 43:231–237, 2013

[xvi] Sun A et al (2014); Urinary Methylmalonic Acid as an Indicator of Early Vitamin B12 Deficiency and Its Role in Polyneuropathy in Type 2 Diabetes; Journal of Diabetes Research

Volume 2014 (2014)

[xvii] Herrmann W, Obeid R; Utility and limitations of biochemical markers of vitamin B12 deficiency European Journal of Clinical Investigation: 43:231–237, 2013

[xviii] Kirbige D & Mwebaze R; Vitamin B12 deficiency among patients with diabetes mellitus: is routine screening and supplementation justified? Journal of Diabetes & Metabolic Disorders, 12:17, 2013

[xix] Haddad GS and Loewenstein M. Effect of several heat treatments and frozen storage on thiamine, riboflavin, and ascorbic acid content of milk. J Dairy Sci, 1983. 66(8): p. 1601-6.

[xx] Nutt NR. „Re: Vitamin B12 deficiency“ BMJ 2014;349:g5226