Vitamin B12 (Cobalamine)

There appears to be some confusion among practitioners of natural medicine about whether oral, sublingual or intramuscular administration is preferable for patients requiring vitamin B12 therapy.

Blood levels of B12 indicate that sublingual B12 becomes available as early as 15 minutes after administration and are still elevated at 24 hours, suggesting that a once-daily dose of 2000-4000mcg would be an effective preventive measure. Allergy[/glossary] and Immunology, 1987]

A year’s supply of 1,000mcg vitamin B12 tablets costs under $20, which is less than the cost of going to the doctor’s office for injections. On the other hand, patients who are likely to be noncompliant with oral therapy should be seen regularly by a doctor and treated with intramuscular injections.

When vitamin B12 is being used for its pharmacological effects, as in the treatment of fatigue, Bell’s palsy, diabetic neuropathy, subdeltoid bursitis, or asthma, intramuscular injections appear to be preferable to oral administration. Although there is little published research in this area, clinical observations suggest that orally administered vitamin B12 is not particularly effective against these conditions. It appears that very high serum concentrations are usually needed for vitamin B12 to exert its pharmacological effects, and that these serum concentrations can be achieved only with IM administration.

Although cyanocobalamin and hydroxycobalamin are the most commonly encountered supplemental forms of vitamin B12, adenosyl- and methylcobalamin are the primary forms of vitamin B12 in the human body, and are the metabolically active forms required for B12-dependent enzyme function. Evidence indicates these coenzyme forms of vitamin B12, in addition to having a theoretical advantage over other forms of B12, actually do have metabolic and therapeutic applications not shared by the other forms of vitamin B12.

It is important to remember that circulating levels of vitamin B12 are not always a reflection of tissue levels, and that even if an adequate supply of cobalamin appears in the circulation, a functional deficiency of the coenzyme forms might coexist in tissues and other body fluids. Although cyanocobalamine will usually increase circulating levels of cobalamin, its ability to increase tissue levels of the active forms of vitamin B12 can be limited in a range of sub-clinical and clinical conditions. Even in a best case scenario, the activation of cyano- to either adenosyl- or methylcobalamine does not occur instantly, possibly occurring over 1-2 months, and requires the interaction of GSH, reducing agents, possibly alpha-tocopherol, and in the case of Methylcobalamine, SAMe and the active form of folic acid.

The use of either hydroxycobalamine and/or methylcobalamine offers a significant biochemical and therapeutic advantage over other existing forms of vitamin B12 (most commonly cyanocobalamine), and should be considered as a first-line choice for correcting vitamin B12 deficiency and treating conditions shown to benefit from cobalamin administration.

Here is a story shared by Dr. David Gregg regarding the use of B12 and DMSO to enhance absorption without the use of injections.

I discovered another approach which I experimented with personally and which eventually led me to discover what I interpreted to be a very common Vitamin B12 deficiency, independent of the age group. This surprised and puzzled me very much.

Back in 1994 when I was focusing on learning as much as I could about vitamin B12, an experiment came to mind which I decided to try on myself. I saw a bottle of DMSO (dimethylsulfoxide) on the shelf of my health food store and remembered that DMSO is not only absorbed directly through the skin, but it also would carry with it any impurities dissolved in it. This can be a serious problem if the impurities are toxic.

However, I also realized that if I dissolved vitamin B12 in it, it might carry it directly to my blood stream through my skin. I tried it and the results were dramatic for me, far greater than any impact I had ever felt from oral or sublingual tablets. I put some of my vitamin B12 tablets obtained at a health food store into a two liquid ounce bottle with an eyedropper and filled it with DMSO. It took a couple of days for the tablets to fall apart. Once they did, I put an eyedropper load on one arm and rubbed it in. In approximately one hour I started to feel very good, which was a sense of general strength and well being. This lasted all day.

When I tried it again the next day, I got no such feeling. I also didn’t experience any bad effects either. Since I knew that approximately one month’s requirement of B12 is stored in your liver, I reasoned that my system was simply fully supplied with Vitamin B12 and that I wouldn’t need to use it again for a month or so. When I tried it again a month or so later, I got a significant boost from it again. Since then I have continued to use it on a once every month or so basis.

With time I decided to also add folic acid and a multiviamin-multimineral tablet to give the solution a broader base of nutritional support. I use a two ounce bottle with an eyedropper, add 10mg of vitamin B12 (ten 1000 mcg tablets), 9.6 mg of folic acid (twelve 800 mcg tablets) and a single multivitamin-multimineral tablet and fill it with 99.9% DMSO (leaving a bubble at the top so it can be mixed when shaken). All ingredients were obtained from my local health food store.

The tablets are mostly binder and take a few days to fall apart. They don’t fully dissolve, but that doesn’t seem to matter in terms of potency. I now use this regularly on approximately a once every month or two basis. It serves as a reasonable mood elevator for me, and I believe it contributes significantly to my general health. My interpretation is I seem to become deficient in vitamin B12 even though I take oral supplements regularly.

Over time I have told a number of other people about this and many have chosen to try it. (I strongly recommended that they consult their physician first.) Of those who have chosen to make up solutions and try it, approximately 50% have told me that they noticed a very significant energy boost, and this was not limited to elderly people. It seemed to be independent of age, from age 25 and up.

Some also found a benefit if they used it as frequently as once every two weeks and others were like me, finding the best time span between use to be in the once-a-month or so range. If I interpret this to indicate B12 deficiencies, the 50% number is much higher than I would have expected, and the impact on young people was particularly unexpected. Is this an indication that there is something happening in our environment that is causing a broad base of Vitamin B12 deficiencies? When I read the news article about automobile exhaust and the production of enough nitrous oxide to affect the greenhouse effect, a light turned on. This may the cause. If so, it is a very important issue.

It is my hope that this article will stimulate a thorough investigation into this issue to systematically evaluate if it is true, and result in an organized effort towards a solution.


Vitamin B12 (Cobalamine) can help with the following


Current Smoker

See the link between Increased Lung Cancer Risk and this vitamin.


Senile Dementia

Please see the link between Increased Risk of Alzheimer’s and Vitamin B12.


Myasthenia Gravis

To enhance acetylcholine levels take vitamin B12 1000mcg sublingually each day.


Multiple Sclerosis / Risk

Please also see the article about the approach that Fred Klenner, MD used with MS.


Anemia, Megaloblastic

Megaloblastic anemia is usually caused by a B12 deficiency, and only secondarily by a folic acid deficiency.




IBS (Irritable Bowel Syndrome)

Vitamins B12, A, D, E and K along with calcium and a lactose-free diet are often recommended by clinicians treating IBS.



Histadelia (Histamine High)

Histadelic (undermethylated) persons, get much worse if they take folates & B-12 which can increase methyl trapping. [Willam Walsh, Ph.D., past senior scientist, Pfeiffer Treatment Center]

The Immune System  

Chronic Fatigue / Fibromyalgia Syndrome

Although little controlled scientific research exists on the effectiveness of vitamin B-12 for the treatment of Chronic Fatigue Syndrome, many doctors and patients are trying this therapy. Two well-known CFS researchers and clinicians, Dr. Paul Cheney and Dr. Charles Lapp, believe that it can be helpful for some patients in managing the symptoms of CFS or fatigue.

Based on three studies in the New England Journal of Medicine which showed that vitamin B-12 injections were beneficial for people with “CFS-like neurological symptoms and normal blood counts,” Dr. Lapp and Dr. Cheney decided to try various doses in their own patients with the hope that this might become an effective treatment option.

They began treating patients with injections of cyanocobalamin, a form of vitamin B-12 that is easily accessible in the U.S. Their informal survey of patients showed that 50-80% of their patients improved to some extent. These patients reported increased energy and sense of well-being within 12-24 hours after administration, and the effects lasted an average of 2-3 days. However, results were highly variable; effective doses ranged from 1000mcg injected daily to 5000mcg injected three times a week; many patients required up to six weeks of treatment to receive consistent results. Dr. Lapp and Dr. Cheney now recommend injections of 3000mcg of cyanocobalamin every 2-3 days.



Helicobacter Pylori Infection

H. Pylori infection may result in Vitamin B12 deficiency.



Vitamin B12 injections at 1mg daily for two weeks has eliminated pain in the majority of cases of shoulder and hip bursitis.

Lab Values  



Low B12 levels have been found to be related to self-reported overall distress level and specifically to depression, anxiety, confusion, and possibly nervousness as well as to clinically rated depressed and anxious mood.


Sulfite Sensitivity

Supplementation with B12 may reduce sulfite sensitivity. In one study the oxidative action of vitamin B12 was able to block a sulfite-induced bronchospasm in 4 out of 5 asthmatic children. In another study, the following conditions responded to B12 use: Intractable asthma – 18 out of 20 patients improved; Chronic urticaria – 9/10 improved; Chronic contact dermatitis – 6/6 improved; Atopic dermatitis – 1/10 greatly improved and 5/10 moderately improved with 1000mcg IM once weekly for 4 weeks. [J Allergy 2: 183- 5, 1951]

Blood levels of B12 indicate that sublingual B12 becomes available as early as 15 minutes after administration and is still elevated at 24 hours, suggesting that a once-daily dose of 2000-4000mcg would be an effective prophylactic measure. [Bhat N.K. – Presentation at the 43rd Annual Meeting, American Academy of Allergy and Immunology, 1987]






In people with sleep wake disorders, taking methylcobalamin (3 mg daily) has often led to improved sleep quality, increased day time alertness and concentration, and improved mood. Much of the benefit appears to be a result of methylcobalamin influencing melatonin secretion.

Twenty subjects (mean age 36 years) were randomly assigned to treatment for 14 days with 3 mg cyanocobalamin or methylcobalamin after 9 days. The results indicated a significant advantage for methylcobalamin. Methylcobalamin supplementation led to a significantly improved sleep quality, shorter sleep cycles, increased feelings of alertness, better concentration, and a feeling of waking up refreshed in the morning. Some of the interesting findings included the fact that methylcobalamin was significantly more effective even though blood levels of cobalamin increased more significantly in the cyanocobalamin than the methylcobalamin group.

However, methylcobalamin might be considered to have a low therapeutic potency and better suited as a booster for other treatment methods of the disorders. [ Psychiatry Clin Neurosci. 1999 Apr;53(2):211-3]



Nervous System  

Bell's Palsy

Methylcobalamin, a form of vitamin B12, was compared with steroids in a trial involving 60 patients with Bell’s palsy. The shortest time required for complete recovery of facial nerve function occurred in the group receiving Methylcobalamin alone. A therapeutic dose would be a minimum of 1500mcg and a maximum of 6000mcg per day, by injection. It was administered by intramuscular injection 3 times weekly for 8 weeks (or until recovery). The results of this study have not been validated, and administration of methylcobalamin has not become a common treatment.

Cyanocobalamin is reported to have worked in a couple chronic cases at high doses also. [J Indian Med Assoc 33: pp.129- 31, 1959]


Nervous Breakdown Tendency

Chronic mild to moderate B12 deficiency may be associated with nervousness. A study was carried out on 1081 healthy young men aged 17-29 which measured current mental state through the ‘Adjective Check List’ test. There was a very high correlation between those found to be chronically deficient in vitamin B12 (based on repeated measures of plasma cobalamin levels) and those who were found to be significantly more anxious.


Organ Health  


Vitamin B12 (with or without folic acid) has been reported in studies from the 1950s to help some people with hepatitis.[1] [2] Vitamin B12 injections are likely to be more beneficial than oral administration, though 1,000mcg taken orally each day can also be supplemented.

[1] Campbell RE, Pruitt FW. Vitamin B12 in the treatment of viral hepatitis. Am J Med Sci 1952;224: pp.252–62
[2] Campbell RE, Pruitt FW. The effect of vitamin B12 and folic acid in the treatment of viral hepatitis. Am J Med Sci 1955;229: pp.8–15



In one clinical trial, weekly 1,000mcg intramuscular injections produced definite improvement in asthmatic children. Of 20 patients, 18 showed less shortness of breath on exertion, as well as improved appetite, sleep, and general condition. When given sublingually prior to a sulfite challenge, vitamin B12 appears to be especially effective in cases of asthma caused by sulfite sensitivity.


Increased Risk of Lung Cancer

See the link between Increased Lung Cancer Risk and folic acid.


Increased Risk of Alzheimer's / Dementia

Low levels of vitamin B12 have been linked to an increased risk Alzheimer’s disease. [Neurology, May 2000] It remains unclear as to whether B12 supplementation will reduce the risk.

All ages of Alzheimer’s patients have been found to have lower serum B12 levels, compared to normals and patients with other forms of dementia in several other studies.

Supplementation of B12 and/or folic acid may result in complete reversal in some patients, but there is generally little improvement in patients who have had Alzheimer’s symptoms for longer than six months. Some scientists hypothesize that prolonged low levels of vitamin B12 may lead to irreversible changes.

Researchers have known for some time that there is a genetic marker, called e4 allele, which indicates a high risk

for dementia. About 15% of the population has this marker. It’s also well-known that people who have dementia or

Alzheimer’s, as well as many older people in general, often have low levels of vitamin B12. Evidence points to a clear link between e4 allele and vitamin B12. People who had the high-risk genotype plus low levels of vitamin B12 had a significantly poorer memory than any other combination that was tested. Simply raising the levels of vitamin B12 showed a marked

improvement, even though the genetic condition still exists. [American Psychological Association, 5 April 2004]

See also the link with Alzheimer’s risk and the use of B complex.



The results of the following study suggest that topical application of vitamin B12 is a safe and effective eczema treatment.

Vitamin B12 inhibits production of inflammatory cytokines and can trap nitric oxide, making it less harmful. A study investigated the effect of a topical application of a vitamin B12 containing cream on eczema severity in 41 people aged 18 to 70 years. The participants were randomly assigned to apply a vitamin B12 cream (containing 0.07% cyanocobalamin, a form of vitamin B12) to affected areas on one side of the body, and a placebo cream to affected areas on the other side of the body two times per day for eight weeks. The severity and extent of eczema was rated at the beginning of the study and at two, four, six, and eight week intervals thereafter. The participants and doctors also assessed each treatment’s effectiveness and how well it was tolerated.

For all participants, the extent and severity of eczema were significantly less on the side of the body treated with the vitamin B12 cream than on the side treated with the placebo cream. Both the doctors and the study participants rated the vitamin B12 cream as superior to the placebo cream in effectiveness and tolerability. Only a few mild adverse reactions (local skin irritation) were associated with use of the vitamin cream. [British Journal of Dermatology 2004;150: pp.977-83]

It does not appear that vitamin B12 cream is readily available at this time. One large United States compounding pharmacy was contacted and they were not producing it as of June 2005. However, they were willing to make a 0.07% cream on a prescription basis (not for resale). If interested, you could have your doctor contact McGuff Compounding Pharmacy and request this item. Apothecure also offers a 200mcg/ml gel on a prescription basis.



Vitamin B12 injections, at least 1000mcg weekly, has been reported to reduce the frequency and severity of urticaria in chronic cases. [J Am Geriatr Soc 1964;12: pp.79-85]


May do some good
Likely to help
Highly recommended
Reasonably likely to cause problems
Avoid absolutely



Situated or administered under the tongue, for example sublingual glands or sublingual tablets.


Vitamin B-12. Essential for normal growth and functioning of all body cells, especially those of bone marrow (red blood cell formation), gastrointestinal tract and nervous system, it prevents pernicious anemia and plays a crucial part in the reproduction of every cell of the body i.e. synthesis of genetic material (DNA).


(mcg): 1/1,000 of a milligram in weight.


Involving the use of drugs.

Diabetes Mellitus

A disease with increased blood glucose levels due to lack or ineffectiveness of insulin. Diabetes is found in two forms; insulin-dependent diabetes (juvenile-onset) and non-insulin-dependent (adult-onset). Symptoms include increased thirst; increased urination; weight loss in spite of increased appetite; fatigue; nausea; vomiting; frequent infections including bladder, vaginal, and skin; blurred vision; impotence in men; bad breath; cessation of menses; diminished skin fullness. Other symptoms include bleeding gums; ear noise/buzzing; diarrhea; depression; confusion.


A group of symptoms caused by abnormalities in motor or sensory nerves. Symptoms include tingling or numbness in hands or feet followed by gradual, progressive muscular weakness.


The bursa is a fluid-filled pad that allows your muscles to easily slide over other muscles and bones. Bursitis occurs when this pad becomes inflamed. It usually occurs when you overuse or injure a specific joint, but it can also be caused by a bacterial infection. Symptoms include pain and inflammation around joints such as the elbow, hip, shoulder, big toe, ankle or knee.


A lung disorder marked by attacks of breathing difficulty, wheezing, coughing, and thick mucus coming from the lungs. The episodes may be triggered by breathing foreign substances (allergens) or pollutants, infection, vigorous exercise, or emotional stress.


The cell-free fluid of the bloodstream. It appears in a test tube after the blood clots and is often used in expressions relating to the levels of certain compounds in the blood stream.


Specific protein catalysts produced by the cells that are crucial in chemical reactions and in building up or synthesizing most compounds in the body. Each enzyme performs a specific function without itself being consumed. For example, the digestive enzyme amylase acts on carbohydrates in foods to break them down.


A heat stable molecule that must be associated with another enzyme for the enzyme to perform its function in the body. It is necessary in the utilization of vitamins and minerals.


The chemical processes of living cells in which energy is produced in order to replace and repair tissues and maintain a healthy body. Responsible for the production of energy, biosynthesis of important substances, and degradation of various compounds.

Folic Acid

A B-complex vitamin that functions along with vitamin B-12 and vitamin C in the utilization of proteins. It has an essential role in the formation of heme (the iron containing protein in hemoglobin necessary for the formation of red blood cells) and DNA. Folic acid is essential during pregnancy to prevent neural tubular defects in the developing fetus.


(mg): 1/1,000 of a gram by weight.

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