What do we know about vitamin B12 deficiency?

Victoria, British Columbia by night. (Dr. Noorali Bharwani)
Victoria, British Columbia by night. (Dr. Noorali Bharwani)

Even after more than 100 years, vitamin B12 (cobalamin) is still the subject of intense research.

Vitamin B12 plays an important role in red blood cell formation, cell metabolism, nerve function and the production of DNA. As we know, the function of DNA is to store all of the genetic information that a person needs to develop, function, and reproduce.

Vitamin B12 is also necessary for normal bone marrow and central nervous system function. The vitamin is absorbed in the distal ileum (where the small bowel joins the large bowel). Its absorption in the distal ileum requires intrinsic factor.

Where can you find intrinsic factor?

Intrinsic factor is a natural substance normally found in the stomach. Lack of intrinsic factor leads to vitamin B12 deficiency and pernicious anemia, and can cause brain and nervous system problems. There may be cognitive decline. There may be peripheral neuropathy. Quite often the presentation can be very suttle and potentially serious.

Vitamin B-12 deficiency is associated with dementia and low cognitive function, but it’s not clear whether vitamin B-12 supplements might help prevent or treat dementia.

The discovery of vitamin B12

“The discovery of vitamin B12, the elucidation of its role in metabolism, and the effects and treatment of its deficiency occurred in distinct phases over more than 100 years, and it was the subject of two separate Nobel Prizes,” says an article in Ann Nutr Metab 2012 (The discovery of vitamin B12 – authors Scott and Molloy).

The next advance was made with the discovery that a gastric component, which was named intrinsic factor, was missing in pernicious anemia. Many years later, intrinsic factor was found to be a glycoprotein that formed a complex with vitamin B12, promoting its absorption through ileal receptors.

The article says vitamin B12 is still the subject of intense research and, in particular, its role in preventing some irreversible neurological lesions remains unclear.

The incidence of vitamin B12 deficiency increases with age. The condition affects five to 20 per cent of adults older than 60 years.

The main source of vitamin B12 is animal-based foods such as meat, fish, eggs, and dairy products. In addition, some vegetable-based foods have been fortified with vitamin B12.

Individuals who do not consume these foods are more susceptible to vitamin B12 deficiency.

Other common causes include autoimmune gastritis (which causes pernicious anemia), malabsorptive states (e.g., pos-gastrointestinal surgery), and certain medications like metformin, proton pump inhibitors and histamine-2 receptor antagonists.

Managing B12 deficiency

The recommended daily amount of vitamin B12 for adults is 2.4 micrograms. Most people get enough of it from a balanced diet.

But it is important to recognize that certain segment of the population is vulnerable to be B12 deficient. If left untreated, vitamin B12 deficiency can lead to anemia, fatigue, muscle weakness, intestinal problems, nerve damage and mood disturbances.

All people over 65 years of age who are malnourished, all people in institutions or psychiatric hospitals, and all people with hematological or neuropsychiatric symptom should have their serum B12 levels measured.

Older adults, vegetarians, vegans and people who have conditions that affect their ability to absorb vitamin B12 from foods might benefit from the use of oral supplements.

Vitamin B12 supplements also are recommended for women who are pregnant or breastfeeding. Vitamin B12 is transferred through the placenta to the fetus during pregnancy and through breast milk after birth. Infants who drink breast milk from a mother who consumes adequate amounts of vitamin B12 or infants who drink infant formula, will receive enough vitamin B12.

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Short Supply of Injectable Vitamin B12 Causes Distress Among Patients

"When I'm in turmoil, when I can't think, when I'm exhausted and afraid and feeling very, very alone, I go for walks." -Jim Butcher, Storm Front An unidentified walker in Kin Coulee Park, Medicine Hat, AB. (Dr. Noorali Bharwani)
"When I'm in turmoil, when I can't think, when I'm exhausted and afraid and feeling very, very alone, I go for walks." -Jim Butcher, Storm Front
An unidentified walker in Kin Coulee Park, Medicine Hat, AB. (Dr. Noorali Bharwani)

It has been nine months or more, injectable vitamin B12 (Cyanocobalamin) has been in short supply.

The obvious question is: why? According to media report, the drug maker Sandoz Canada had to close a manufacturing plant in Quebec in February 2012, to upgrade it to meet U.S. Food and Drug Administration standards. A second company found it too much to cope with the shortage and increased demand.

Here is the good news. Last week I asked Larry Legare, AHS Provincial Pharmacy Director, South Zone, about the availability of B12 injections. He said, “I have just received notification that Vitamin B12 1000 mcg/ml 1ml amp may be available as early as next month. This is earlier than we anticipated.” He added that there will be very limited stock available initially and stock may become unavailable again until sufficient supplies can be released to meet the current demand.

Legare says for many people with vitamin B12 deficiency, treatment with high-dose oral administration of vitamin B12 (1000–2000 mcg per day) is as effective as injectable (intramuscular or deep subcutaneous) administration. There are many reasons why some patients prefer or need to have monthly injections rather than take pills on a daily bases. I have covered this topic in the past in great detail. For more information visit my website.

It is estimated as many as five per cent of Canadian adults have a vitamin B12 deficiency. It is also reported that 30 per cent of the adults older than 50 may have vitamin B12 deficiency. It is estimated up to 40 per cent of the general population may be deficient in this vitamin. Sometimes figures are irrelevant, it is the people we worry about.

The most common cause is pernicious anemia. It is also common among vegans and people with celiac or Crohn’s diseases. Without vitamin B12, the body has trouble building the red blood cells that carry oxygen and allowing the brain and nervous system to function properly. The result is a feeling of chronic fatigue.

Legare says either oral or injection formulations are effective for treating B12 deficiency. The daily requirement is 2-3mcg. Dosing with intramuscular or deep subcutaneous injections of 100mcg daily for five to 10 days, then 100-200mcg monthly until levels are normalized followed by 100mcg monthly for maintenance.

High oral doses in the range of 1000 to 2000mcg daily are just as effective. It can be used sublingually (2000mcg). The benefit to sublingual vitamin B12 vs. oral is not well defined.

I am sure you have discussed your needs with your doctor. I hope help will be here soon. I wish you all the best. Stay positive (sometimes it is difficult to do that) and keep smiling (that can be difficult too). But don’t give up.

Start reading the preview of my book A Doctor's Journey for free on Amazon. Available on Kindle for $2.99!

More on Vitamin B12: Diagnosis and Treatment

My last column was on vitamin B12, also known as Cobalamin. Some of my colleagues said that I took a very simplistic approach to diagnosis and treatment of vitamin B12 deficiency. There is more to it than what my column implied.

In this column I will elaborate on the following two points: diagnosis and oral vs. injection treatment of B12 deficiency.

Is blood test a good way of confirming the diagnosis of B12 deficiency?

I discussed this point with Dr. Michael O’Connor, Medical Director of the Medicine Hat Regional Hospital Laboratories. He said there is a difference between the very common asymptomatic B12 deficiency and the much less common symptomatic and clinically apparent B12 deficiency. He says interpretation of low B12 result is hugely dependent on the clinical situation of that individual patient.

If the patient has symptoms of B12 deficiency (anaemia, neurological and psychiatric problems) and the blood results shows B12 to be low then the diagnosis of B12 deficiency is easy to make. If an individual has no symptoms then there is probably no role for screening for B12 deficiency, says Dr. O’Connor.

The process is difficult because there is lack of a diagnostic gold standard among the many available tests, there are too many patients with sub-clinical deficiency and there is decreased availability of reliable tests to identify the causes of a patient’s cobalamin deficiency, says an article in Hematology.

How to treat B12 deficiency: by oral pills or monthly injections?

I received the following information from the Medicine Hat Regional Hospital Pharmacy.

Either oral or injection formulations are effective for treating B12 deficiency.

The main mechanism of B12 absorption is via its binding of intrinsic factor in the stomach and its subsequent absorption in the intestine. Approximately 60 per cent of cobalamin is absorbed by this system. A secondary mechanism of its absorption does not require intrinsic factor and involves passive diffusion across the intestinal wall. When given orally only one per cent of a dose will be absorbed by this mechanism.

The daily requirement of cobalamin is 2-3mcg. Dosing with intramuscular or deep subcutaneous injections to treat deficiency involves 100mcg daily for five to 10 days, then 100-200mcg monthly until levels are normalized followed by 100mcg monthly for maintenance.

High oral doses in the range of 1000 to 2000mcg daily are just as effective for treating deficiency due to the secondary mechanism of absorption. Cobalamin can also be administered sublingually both safe and effectively (2000mcg). The benefit to sublingual cobalamin vs. oral is not well defined.

There are disadvantages to give patients regular injections of B12. They are: pain at the injection site, injection site reactions, inconvenience and higher cost due to the need for a health professional to administer the injection.

Despite these disadvantages injection treatment is still preferred for those patients who are unable to take medications orally, those who experience severe diarrhea or vomiting, those with compliance issues to a daily dosage regimen, as well as those with neurological symptoms.

Oral and sublingual cobalamin have no evidence of toxicity when used at high doses, are cost effective, less burdensome to the patient and are equally as efficacious when used at the appropriate doses as compared to injection dosage forms. The only disadvantage to choosing an oral or sublingual regimen is the potential for adherence issues. Hence oral cobalamin is an excellent option for treatment and prevention of mild to moderate cobalamin deficiency.

Start reading the preview of my book A Doctor's Journey for free on Amazon. Available on Kindle for $2.99!

Vitamin B12 Deficiency

Dear Dr. B: Can you please tell me about vitamin B12 deficiency?

Answer: This is a very important subject. I have written about this in the past. And it is worth repeating as 30 per cent of the adults older than 50 may have vitamin B12 deficiency. It is estimated up to 40 per cent of the general population may be deficient in this vitamin.

Vitamin B12, also known as cobalamin, was first isolated in 1948 and was immediately shown to be effective in the treatment of pernicious anaemia. Pernicious anaemia is a fairly common condition in which the stomach does not have enough acid and does not make intrinsic factor normally. Intrinsic factor is essential for the absorption of B12 in the stomach.

Absorption of B12 is also impaired in individuals who have had intestinal illness or intestinal surgery, which makes it hard for the intestines to absorb vitamin B12. Absorption of vitamin B12 from foods is complex. A defect in any step can lead to deficiency.

B12 is obtained primarily from animal proteins (red meat, poultry, fish, eggs, and dairy). But the vegetarians can get enough of it from legumes. The cause of B12 deficiency is not usually poor diet but problems with absorption as explained earlier.

Our body needs vitamin B12 to make blood cells. Persons with the deficiency may have no symptoms or may have symptoms related to blood disorder or disorders of the nervous system including psychiatric problems. Fatigue may be one of the first indications of B12 deficiency.

The liver stores most of the body’s B12 followed by the kidneys, heart, spleen, and brain. The stored B12 can last up to two years in conditions where our body is deprived of B12.

The diagnoses of B12 deficiency is made by checking the blood levels in patients who have symptoms or who are prone to B12 deficiency. Screening for B12 deficiency (by way of a blood test) is recommended in the following groups of people:

-all elderly patients who are malnourished
-all patients in institutions and psychiatric hospitals
-all patients who have blood disorders, neurological or psychiatric problems.

Treatment is by B12 injections on regular basis for the rest of person’s life.

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The golf season has started. It’s time to have little fun here before we get miserable on the golf course. Here is a joke from Golf Digest:

A man is stranded for years on a desert island. One day he looks up to see a gorgeous blond in scuba gear wading out of the water.

“Want a cigarette?” she asks, opening a waterproof pocket on her right arm, pulling out a pack and lighting one for him.

“How about a sip of whiskey?” she asks next, opening a pocket on her left arm and removing a flask.

As the man puffs on the cigarette and sips the whiskey, she slowly begins to unzip the front of her wet suit.

“Want to play around?” she asks.

And he says, “Oh, Lord, don’t tell me you’ve got a set of golf clubs in there, too.”

Start reading the preview of my book A Doctor's Journey for free on Amazon. Available on Kindle for $2.99!