Silent vitamin B12 deficiency is very common

Version 1.111[1]

Last updated on 15 September 2009

By Jaan Suurküla, M.D.

Summary

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 pronounced deficiency may damage the brain and has been found in a majority Alzheimer dementia cases. Also chronic depression, mano-depressive illness and other severe psychiatric disorders are associated with B12 Deficiency.

Recent research has shown that vitamin B12 deficiency is very common. One study in the US reported that 39% of the population had low or near low values[2]. Deficiency is much more common among vegetarians and the risk increases the longer you have been vegetarian. The percentage increases with age. A combination of age above 50 and vegetarianism engenders a very high risk of B12 deficiency. But B12 deficency may occur even in teenagers who are vegetarians.

Measuring the vitamin in blood 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).

But 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. This includes the result mentioned above.

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Deficiency symptoms may be vague

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

Early and even fairly pronounced deficiency does not always cause distinct or specific symptoms. Common early symptoms are tiredness or an increased mental fatiguability. 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. Seasonal Affective Disorder (SAD), with severe seasonal depressions has a know connection with disturbed pineal (melatonin) functioning including disturbed sleep-wake rytm[4].

Severe psychiatric disorders including paranoid and shizoaffective psychoses, violent behavior, severe chronic therapyresitant depressions, mano-depressive illness[5] and chronic asthenia (fatigue) are associated with abnormally low B12 levels and improve remarkably or heal with high dose B12 therapy[6].

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 general weakness. It is my experience that many doctors miss the diagnosis.

Severe deficiency 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 buildup 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.

Other research indicates that in Alzheimer also a deficient uptake of B12 into the brain plays an important role. 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 very high blood level has to be achieved for optimal results.

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. 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 anemia (so called megaloblastic anemia whose signs clearly differ from iron deficiency). This anemia was formerly thought to be a good indicator of B12-deficiency so the laboratory values were established with anemia as the only criterion. But extensive research has clearly established that there may be a pronounced brain affection without any anemia. It seems that a critical factor in such conditiona is deficient uptake of B12 into the brain, which requires higher blood levels in order for enough B12 to reach the brain.

Especially in perniciosa (see below) there may also be symptoms from the Gastro-intestinal channel, including soreness of the tongue that may be smooth, at least on the sides, flatulence, heartburn, diarrhea or constipation.

Treatment with B12 can reverse the disturbances caused by deficiency.

The list of symptoms and disorders caused by B12-deficiency is steadily growing. Here are some examples of disorders that have responded postively to B12- treatment:

Aphtous stomatitis (whitish painful spots in the mouth) cured, erythema nodosum (a nodular skin disorder) cured, bursitis cured, sulfite sensitivity including asthma caused by it cured, chronic contact dermatitis cured, chronic urticaria, Bells palsy (facialis nerve paresis), breast cancer improved or cured, herpes zooster, vitiligo, hepatitis improved. Macula degeneration of the eyes has been halted.

Testing

Vitamin B12 in blood serum is not considered to be a reliable indicator. But this may be simply because that the commonly used lower normal limit is wrong, allowing much too low B12 levels.

The present lower limit is about 200 picograms/litre (pg/l) = 145 picomol/liter (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.

Recent research has found compelling evidence demonstrating that the lower normal limit should be raised considerably. In some countries, including Japan, where it has been best researched, 550 pg/l = 400 pm/l is now established as the minimum level. Some clinical researchers maintain, on the basis of clinical experience that an even higher level 600-700 pg/l or more is optimal.

It is not enough to test vitamin B12 to exclude deficiency, you need also to test homocystein at least.

Homocystein is an amino acid that requires B12 for its decomposition. So an 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.

Research indicates that also the normal acceptable lower limit for homocystein may be wrong. It was about 14-15 micromol/l. But a recent study indicates that it should not be higher than 6,3 micromol/l (0,85 mg/ml).

Not seldom only Homocystein in the cerebrospinal liquor is increased in vitamin B12 deficiency in the brain. Consequently, all the blood tests can be normal and yet an important 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 is also required for Homocystein decomposition, so it is good to check it also. The normal range of folic acid is 7 - 34 nmol/l, or 3 – 15 ng/l, but vegetarians often have higher, and that is not harmful, as the “normal value” only reflects the situation in the population and not what is desirable.

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

A third test is MethylMalonicAcid (MMA). It is believed to be a sensitive indicator of deficiency, but there is too little knowledge yet about the normal range. Presently it is believed it should not be higher than about 0,3 micromol/l, but it may be a too high value, as there has been general tendency for underestimation of the deficiency.

Even if the test values are normal and you are a vegetarian, I recommend you to consider taking vitamin B12 for safety, if you suspect you have a deficiency, as B12 is totally untoxic. If you feel clearly better, you had deficiency (this diagnosis method is used by physicians when the tests are negative, but a deficiency is suspected - it is called “exjuvantibus diagnosis”).

Causes

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 such ause 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%.
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 (Bilroth). 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 atrophia 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 “Anemia Perniciosa”, because the B12 deficency causes anemia but all other deficiency symptoms may be associated with it.

3. A number of drugs disturb the uptake or destroy the vitamine. This includes among others, Oral contraceptives, certain Antidiabetic drugs (containing the substance Metformin), the antibiotics Flagyl, Chloramphenicol and Neomycine. 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.

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.

Complications

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 a greater than 60% decrease in vascular disease among users of the major nutrients required to lower homocysteine, namely vitamin B12, folic acid and vitamin B6. 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 underestimated.

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, although, if they are grown on cow dung, which is rich in B12, there may be some B12 in vegetables.

B12 is damaged relatively slowly at boiling, so no 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 somewhat, but I have found no research about it. Ultrahigh pasteurization means heating to 135 degrees Celcius (= 275 Fahreneheit) in one second and may therefore damage B12 but I found no research about it.

In any case, the amount in milk and milkproducts is far from enough to cure a deficiency. But it may enough to prevent deficiency if you use milkproducts regularly.

It was formerly believed that Algae including Spirulina and Chlorella contained B12. But this is a form that cannot be used by humans.

The best sources are non-vegetarian:

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

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

Treatment

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

Take Methylcobalamin. It is easily found in the Internet.
Dosage: Methylcobalamin sublingual tablets, 5 mg (5000 microgram) a day until all symptoms are gone. Don’t stop as long as you note any improvement. 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.

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.

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 genetical factor leading to a slow buildup of brain damage due to B12 deficiency, so don’t wait for taking a high dose until the first Alzheimer symptoms appear.

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 ½-1 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 genetical 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).

Cyanocobalamin, which is the predominant variety in the pharmacies, is less effective. It is an unttatural variety that has a weak effect on the brain. But if methylcobalamin is not available, it is better take cyanocobalamin than nothing. If there is a suspicion of severe brain disorder, you should not accept cyanocobalamin other than provisionally until you can get Methylcobalamin. Highly poisonous Cyanide is created when Cyancobalamin is metabolized. At normal doses, the amount is considered insignificant. But it may become hazardous when high doses are used (which is common in the case of neurological symptoms) especially for people with kidney dysfunction or with a genetic abnormality reducing the ability to eliminate cyanide.
Injections are not necessary. They are commonly offered, when there is a pronounced deficiency or neurological symptoms. Injections can cause allergy to vitamin B12. It has been scientifically confirmed that B12 is as well absorbed through the mouth (sublingually).
If Homocystein is increased, it is desirable to consider taking vitamin B6 also It is required to metabolize homocystein, but it is commonly not lacking in vegetarians. But in modern industrialized food processing it is very often destroyed. Especially microwave owens 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 senstive 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. 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. Dosage:

i. B6: Take 10 mg/day

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

Conclusion

Do check your B12 and homocystein especially if you have been a vegetarian for a few years. If you have taken antibiotics any time in your life without actively correcting the gastrointestinal flora, or have been taking contraceptives or antacidic drugs for gastritis with Helicobacter, you have especially strong reasons to check B12.

Even if you have normal test values but have some tiredness, or depression tendencies, or sleep disturbances or irritability or other symptoms mentioned above, do take Methylcobalamaine 5 mg (5000mcg) anyway until the symptoms decrease or disappear (you don’t need to have all symptoms – they appear to a different extent in different persons). And thereafter, if you are a vegetarian, either take milk products regluarly and/or take a 5 mg tablet of Methylcobalamine 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).

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 treat effectively enough, 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. So be vigilant about it.

[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, http://www.ars.usda.gov/is/pr/2000/000802.htm?pf=1. 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] See e.g. 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.

[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.