An In-depth Look at Vitamin B12
Though the body only requires a very small amount of vitamin B12, it is absolutely critical to our health. B12 works in many body processes including the synthesis of DNA, red blood cells and the insulation sheath (the myelin sheath) that surrounds nerve cells and speeds the conduction of the signals along nerve cells.
In order to absorb the small amounts of B12 found in food, the stomach secretes intrinsic factor (IF), a special digestive secretion that increases the absorption of the vitamin in the small intestine. However, oral administration of B12 from supplements is able to be absorbed in sufficient quantities, even in the treatment of pernicious anemia.
Vitamin B12 is found in significant quantities only in animal foods. The richest sources are liver and kidney, followed by eggs, fish, cheese and meat. Strict vegetarians (vegans) are often told that fermented foods, such as tempeh, are excellent sources of vitamin B12. However, in addition to tremendous variation of B12 content in fermented foods, there is some evidence that the form of B12 in these foods is not exactly the form that meets are body requirements and is therefore useless. Hence, at this time vegetarians should supplement their diets with vitamin B12.
Deficiency Signs & Symptoms
Unlike other water-soluble nutrients, vitamin B12 is stored in the liver, kidney and other body tissues. As a result, signs and symptoms of B12 deficiency may not show until five to six years of poor dietary intake or inadequate absorption. The classic deficiency symptom is pernicious anemia; however, it appears that a deficiency will actually affect the brain and nervous system first.
A B12 deficiency will result in impaired nerve function that can cause numbness, pins and needles sensations, or a burning feeling in the feet, as well as impaired mental function, which in the elderly can mimic Alzheimer’s disease. Deficiency is thought to be quite common in the elderly and is a major cause of depression in this age group (discussed later).
In addition to anemia and nervous system symptoms, a B12 deficiency will also result in a smooth, beefy red tongue; and diarrhea due to the fact that rapidly reproducing cells such as those which line the mouth and the entire gastrointestinal (GI) tract will not be able to replicate without B12 (folic acid supplementation will mask this deficiency symptom).
Determination of vitamin B12 deficiency is best achieved by measuring the level in the blood (serum cobalamin).
Decline of B12 Levels With Aging
Several investigators have found the level of vitamin B12 declines with age and that B12 deficiency is found in three to 42 percent of persons aged 65 and over. It is very important to diagnose cobalamin deficiency early in the elderly because it is easily treatable and, if left untreated, can lead to impaired neurological and cognitive function.
In one study among 100 consecutive geriatric outpatients who were seen in office-based settings for various acute and chronic medical illnesses, but not for B12 deficiency-related diseases like pernicious anemia, it was shown that measuring the level of B12 in the blood (serum cobalamin) provides tremendous cost-to-benefit ratio.1 An undiagnosed B12 deficiency may be a factor in many elderly people being placed in nursing homes needlessly.
The most common form of B12 is cyanocobalamin; however, in the body B12 is active in only two forms—methylcobalamin and adenosylcobalamin. Methylcobalamin is the only active form of B12 that is available commercially in tablet form in the U.S. While methylcobalamin is active immediately upon absorption, cyanocobalamin must be converted to either methylcobalamin or adenosylcobalamin by the body removing the cyanide molecule (the amount of cyanide produced in this process is extremely small) and adding either a methyl or adenosyl group.
Cyanocobalamin is not active in many experimental models while either methylcobalamin or adenosylcobalamin demonstrate exceptional activity. For example, in a model examining the ability of B12 to extend life in mice with cancer, methylcobalamin and adenosylcobalamin led to significant increases in survival time, while cyanocobalamin had no effect. Methylcobalamin has also produced better results in clinical trials than cyanocobalamin and should therefore be considered the best available form.
Oral vs. Injectable
Although it is popular to inject vitamin B12, injection is not necessary as the oral administration of an appropriate dosage can result in effective elevations of B12 in the blood. This fact has gone relatively ignored among most physicians. In the U.S, oral vitamin B12 therapy is rarely used despite the fact that it has been shown to be fully (100 percent) effective in the long-term treatment of pernicious anemia.
It has now been established that the mean absorption rate of oral cyanocobalamin by patients with pernicious anemia is 1.2 percent across a wide range of dosages. Since the daily turnover rate is about 2 mcg, an oral dosage of 100 to 250 mcg daily results in a mean absorption of 1.2 to 3 mcg, respectively—a dosage that is sufficient for many, but not all patients. Higher dosages are necessary for most patients to benefit from oral therapy. For oral vitamin B12 in the treatment of pernicious anemia, the recommended dosage is 2,000 mcg daily for at least one month followed by a daily intake of 1,000 mg of vitamin B12 (preferably methylcobalamin).
Vitamin B12 supplementation is appropriate in many conditions, including impaired mental function in the elderly, depression, sleep-wake cycle disturbances, diabetic neuropathy, low sperm counts, multiple sclerosis and tinnitus (ringing in the ears). A brief review of vitamin B12 in these disorders is provided below.
• Impaired Mental Function & Depression in the Elderly (senility) is often a result of reversible nutritional factors such as low vitamin B12 levels. For example, one study analyzed the plasma homocysteine, serum cobalamin and blood folate in 296 consecutive patients referred to a geriatric psychiatric ward in Sweden for diagnosis of mental disease.2 Patients who were found to be deficient in B12 or folic acid, or who had elevated levels of homocysteine, were given B12 and/or folic acid. When individuals with low cobalamin levels were supplemented with B12, significant clinical improvements were noted.
In other studies, supplementation with vitamin B12 has shown tremendous benefit in reversing impaired mental function as a result of low levels of B12. In one larger study, a complete recovery was observed in 61 percent of cases of mental impairment due to low levels of B12.3 The reason why 39 percent did not respond is probably a result of longterm low levels of B12. Several studies have shown the best clinical responders are those who have been showing signs of impaired mental function for less than six months.
Serum vitamin B12 levels are significantly low, and B12 deficiency significantly common in Alzheimer’s disease patients. Supplementation of B12 and/or folic acid may result in complete reversal in some patients, but generally there is little improvement in patients who have had Alzheimer’s symptoms for greater than six months. It has been hypothesized that prolonged low levels of vitamin B12 may lead to irreversible changes that will not respond to supplementation.
Vitamin B12 deficiency can also cause depression, especially in the elderly. Correcting an underlying deficiency results in a dramatic improvement in mood.
• Sleep-Wake Disorder is characterized by excessive daytime sleepiness, restless nights and frequent nighttime awakenings. Taking 3 mg of methylcobalamin sublingually first thing in the morning can lead to improved sleep quality, increased daytime alertness and concentration, and improved mood in people with sleep-wake disorder both in elderly and young subjects.4,5 Much of the benefit appears to be a result of methylcobalamin influencing melatonin secretion—taking it in the morning shuts down daytime melatonin allowing for an increased nighttime secretion. Low levels of melatonin in the elderly may be a result of low vitamin B12 status.
• Diabetic Neuropathy has been met with some success when treated with vitamin B12 supplementation. It is not clear if this is due to the correcting of a deficiency state or the normalization of the deranged B12 metabolism seen in diabetics. Clinically, diabetic neuropathy is very similar to that of classical B12 deficiency. Although the best results have been obtained with injectable methylcobalamin, higher dosages (e.g., 2 to 3 mg per day) of methylcobalamin given orally may produce as good of results.
• Sperm Counts & Sperm Motility are reduced in cases of B12 deficiency, due to B12 being critically involved in cellular replication. Even in the absence of a B12 deficiency, supplementation appears to be worthwhile in men with sperm counts less than 20 million per ml or a motility rate of less than 50 percent. In one study, 27 percent of men with sperm counts less than 20 million given 1,000 mcg per day of B12 were able to achieve a total count in excess of 100 million.6 In another study, 57 percent of men with low sperm counts given 6,000 mcg per day demonstrated improvements.7
• Multiple Sclerosis (MS) is another cause of demyelination within the central nervous system (CNS). Acquired vitamin B12 deficiency, as well as inborn errors of metabolism involving this vitamin, are well-known causes of demyelination of nerve fibers in the CNS. There are several reports in the medical literature that B12 levels in the serum, red blood cell and CNS are low in MS. The coexistence of a B12 deficiency in MS may aggravate the disease or promote another cause of progressive demyelination.
• Tinnitus is a condition where vitamin B12 supplementation is appropriate. B12 is involved in stabilizing nerve activity as it is an essential cofactor for methylation of myelin basic protein and Cell membrane phospholipids. B12 deficiency results in neurological dysfunction including demyelination and nerve cell death. Because of the vitamin’s essential role in neurological function, one study sought to determine the incidence of B12 deficiency in three groups of subjects: those with chronic tinnitus and noise-induced hearing loss, those with noise-induced hearing loss only and those with normal hearing.8 Patients with tinnitus and noise-induced hearing loss demonstrated B12 deficiency in 47 percent of cases. This hearing loss was significantly more than the group with noise-induced hearing loss only (27 percent) and the group with normal hearing (19 percent).
These results suggest a relationship between vitamin B12 deficiency and auditory dysfunction. Further support is offered by the fact that B12 supplementation results in some improvement in tinnitus and associated complaints. Determination of B12 status appears to be warranted in patients with chronic tinnitus and noise-induced hearing loss.
Safety Issues & Interactions
No clear toxicity has ever been reported.
Since B12 works to reactivate folic acid, a deficiency will result in a folic acid deficiency if folic acid levels are only marginal. A high intake of folic acid may mask a B12 deficiency because it will prevent the changes in the red blood cells, but will not counteract the deficiency in the brain.
1 Yao Y, et al.: Decline of serum cobalamin levels with increasing age among geriatric outpatients. Arch Fam Med. 1994;3:918-22.
2 Nilsson K, et al.: Plasma homocysteine in relationship to serum cobalamin and blood folate in a psychogeriatric population. Eur J Clin Invest. 1994;24:600-6.
3 Healton EB, et al.: Neurologic aspects of cobalamin deficiency. Medicine 1991;70:229-45.
4 Ohta T, et al.: Treatment of persistent sleep-wake schedule disorders in adolescents with methylcobalamin (vitamin BI2). Sleep. 1991;14:414-418.
5 Takahashi K: A multicenter study on sleep-wake rhythm disorders in Japan: a preliminary results. Jpn J Psychiatry Neurol. 1992;46(1):231-2.
6 Sandler B and Faragher B: Treatment of oligospermia with vitamin B12. Infertility. 1984;7:133-8.
7 Kumamoto Y, et al.: Clinical efficacy of mecobalamin in treatment of oligospermia. Results of a double-blind comparative clinical study. Acta Urol Japan. 1988;34:1109-32.
8 Shemish A, et al.: Vitamin B12 deficiency in patients with chronic-tinnitus and noise-induced hearing loss. Am J Otolarygol. 1994;14:94-9.
Michael T. Murray, ND, is widely regarded as one of the world’s leading authorities on natural medicine. He is a graduate, former faculty member and serves on the Board of Regents of Bastyr University in Seattle, WA. The author of more than 30 books on health nutrition, Murray is also director of product development and education for Natural Factors Nutritional Products. For more information, visit www.doctormurray.com.