by Royce Bailey M.D., M.P.H., F.A.A.C.

The vitamin, B₁₂ (Cyanocobalamin), was discovered in 1948. It is a water soluble vitamin, so you need a regular supply and also because it is water soluble it is unlikely for you to over dose on it. Vitamin B₁₂ helps maintain healthy nerve cells, normal electrical function of the body’s synapses and robust red blood cells (improving oxygen and CO2 carrying capacity). It is also needed to help make DNA and RNA, the genetic material in all our cells. Vitamin B₁₂ contains the metal cobalt, thus the name cobalamin.

Where Is B₁₂ Found?

It is found in nuts, seeds, potato skins, nutritional (brewer’s) yeast, B₁₂ fortified foods (breads, breakfast cereals) and animal products. B₁₂ can be found in fermented soybean products such as tempeh, natto, and miso; in single cell micro-organisms such as algae, Spirulina and Chlorella; and in seaweed products. It is very rare to see B₁₂ deficiency in 3rd world countries, despite their restricted diets.

Symptoms Of B₁₂ Deficiency

Signs, symptoms, and health problems associated with vitamin B₁₂ deficiency can be a common cause of pernicious anemia, sprue, disorders of blood (macrocytic anemia-red cells are too large and the bone marrow can not make enough red cells), nerve damage, fatigue, lightheadedness, change in appetite, nausea, bleeding gums, soreness of the mouth or tongue, constipation or diarrhea, mis-diagnosed as fibromyalgia and has been implicated in a spectrum of neuropsychiatric disorders (mood swings, depression, irritability, psychosis, dementia, nervousness, confusion, headaches, memory loss). Deficiency also can lead to neurological changes such as numbness and tingling in the hands and feet, tremors and difficulty in maintaining balance. Signs of vitamin B₁₂ deficiency in infancy include: failure to thrive, movement disorders, delayed development, and megaloblastic anemia . One or more of these symptoms does not mean you have B₁₂ deficiency, but you should work with your health care provider to be sure.

So What Can Cause B₁₂ Deficiencies?

Hematologic, neurologic and psychiatric abnormalities, gastric or bowel (ileum surgery, like I’ve had with my Crohn’s disease), folic acid or iron deficiency, prolonged use of stomach acid blockers (proton pump inhibitors, H2 blockers), chronic gastric problems (like I’ve had), being greater than age 50 (like I am). Some medications may decrease absorption of vitamin B₁₂ (Metformin) and chronic use of those medications may result in a need for additional vitamin B₁₂. Other causes can include: smoking, pregnancy, birth control pills, having a high or low thyroid level, antibiotic use and rarely, being vegan.

Homocysteine

The role of B₁₂ deficiency in hyperhomocysteinemia and the promotion of atherosclerosis is only now being explored. Homocysteine is an amino acid normally found in blood, but elevated levels have been linked with coronary heart disease and stroke. Elevated homocysteine levels may impair endothelial vasomotor function, which determines how easily blood flows through blood vessels. High levels of homocysteine also may damage coronary arteries and make it easier for blood clotting cells called platelets to clump together and form a clot, which may lead to a heart attack Adding folic acid (green leafy veggies) to your diet may help lower homocysteine levels but adding B₁₂ also appears to be essential. Why we need both folic acid and B₁₂ is seen in B₁₂ deficiency anemia. Folic acid can correct the anemia that is caused by vitamin B₁₂ deficiency. Unfortunately, folic acid will not correct the nerve damage also caused by vitamin B₁₂ deficiency. Permanent nerve damage can occur if vitamin B₁₂ deficiency is not treated.

How Do I Know If I Am B₁₂ Deficient?

The diagnosis of vitamin B₁₂ deficiency is typically based on blood measurement of your serum vitamin B₁₂ level; however, about 50 percent of patients with subclinical disease have normal B₁₂ levels. A B₁₂ level in the normal range does not ensure that your B₁₂ levels are healthy. A more sensitive method of screening for vitamin B₁₂ deficiency is measurement of serum methylmalonic acid and homocysteine levels, which are increased early in vitamin B₁₂ deficiency.

Pernicious Anemia

Anemia can result from a variety of medical problems, including deficiencies of vitamin B₁₂, vitamin B₆ folate and iron, but the most famous B₁₂ deficiency is pernicious anemia. It is the name given more than a century ago to describe the then fatal vitamin B₁₂ deficiency anemia that results from severe gastric atrophy, a condition that prevents gastric cells from secreting Intrinsic Factor (IF). IF is a substance normally present in the stomach. Vitamin B₁₂ must bind with IF before it can be absorbed and used by your body. An absence of IF prevents normal absorption of vitamin B₁₂ and results in pernicious anemia. Up to 30 percent of adults aged 50 years and older may have atrophic gastritis, and an increased growth of intestinal bacteria, and are unable to normally absorb vitamin B₁₂ from their food. Occasionally, the liver doesn’t convert cyanocobalamin into adequate amounts of methylcobalamin. The interruption of one or any combination of these steps places a person at risk of developing B₁₂ deficiency. Our liver stores B₁₂ for between four to twenty years, so it may take years for any symptoms to show up.

What They Didn’t Know To Tell Me In Medical School-1970s

When I was in medical training in the late 1970s we used the Schilling test for detection of pernicious anemia (B₁₂ deficiency-lack of functioning IF), but now we use serologic (blood) testing for parietal cell and intrinsic factor antibodies. Low vitamin B₁₂ concentrations in your cells could be the result of a low vitamin B₁₂ intake or due to a disturbance in the absorption, transport or cellular uptake of this vitamin. Vitamin B₁₂ is bound to the protein in food. Hydrochloric acid in the stomach releases vitamin B₁₂ from proteins in foods during digestion and then it is bound to haptocorrin (HC)*. HC is transferred to the duodenum (the first part of the small bowel after the stomach), where IF, arriving from the stomach and binds to vitamin B₁₂. The IF-vitamin B₁₂ complex is absorbed via the IF-B₁₂ receptor, and vitamin B₁₂ is subsequently bound to transcobalamin II (TC II) and released into the circulation. TC II facilitates the transport of vitamin B₁₂ in blood to various tissues. Only 20% of the vitamin B₁₂ in plasma is bound to TC II, the remaining 80% is bound to HC (TC 1+TC III).

Why Don’t All Vegan’s Get B₁₂ Deficiency?

Did God make a mistake? “Oops, I forget to make a supply of B₁₂ for mankind after sin?” Vegans have normal B₁₂ levels, but can’t produce B₁₂, but every human, chicken, cow or any other animal can’t produce it either. So how do vegetarian humans and animals get there B₁₂? Bacteria in the small bowel manufacture B₁₂ in very small doses. That’s why taking antibiotics may cause B₁₂ deficiency, if your other mechanisms of absorption aren’t working properly. Mammals need less B₁₂ on a low plant based protein diet, but need more on a high animal based protein diet. More B₁₂ is needed on a low fat diet as well.

There Is A Second Way To Absorb B₁₂

Approximately 1 percent of any oral or bacteria produced B₁₂ is absorbed by TC I-III’s second mechanism. This pathway is important in relation to preventing B₁₂ deficiencies, because it bypasses the IF pathway. Once absorbed, vitamin B₁₂ binds to TC II and is transported throughout the body.

Alzheimer’s And B₁₂

Researchers have long been interested in the potential connection between vitamin B₁₂ deficiency and dementia. B₁₂ is one of the battery of tests routinely done on new psychiatric patients in the hospital. A recent review examined correlations between cognitive skills, homocysteine levels, and blood levels of folic acid, vitamin B₁₂ and vitamin B₆. The authors found that vitamin B₁₂ deficiency may decrease levels of substances needed for the metabolism of neurotransmitters. Neurotransmitters are chemicals that transmit nerve signals. Reduced levels of neurotransmitters may result in neurologic and cognitive impairment. This is why so many of my patients tell me they feel better and think sharper after a B₁₂ shot. It is improving their neurotransmitter function, even if with a normal B₁₂ blood level!

Stomach Acid Blockers Block B₁₂ Absorption

Proton pump inhibitors (PPIs) are used to treat gastroesophageal reflux disease (GERD) and peptic ulcer disease. Examples of PPIs are Omeprazole (Prilosec-OTC) and Prevacid, Aciphex, Protonix, Nexium. H2 receptor antagonists are used to treat peptic ulcer disease. Examples are Tagamet, Pepcid AC, Axid and Zantac. PPIs and H2 medications can interfere with vitamin B₁₂ absorption from food by slowing the release of hydrochloric acid into the stomach. This is a concern because acid is needed to release vitamin B₁₂ from food prior to absorption.

Metformin And B₁₂ Deficiency

Metformin (Glucophage, Glumetza, Fortamet, or any diabetic medicine that has ‘Met’ in its name) normalizes glucose absorption and is a drug used to treat diabetes. Metformin may interfere with calcium metabolism. This may indirectly reduce vitamin B₁₂ absorption because vitamin B₁₂ absorption requires calcium. Surveys suggest that from 10% to 30% of patients taking Metformin have evidence of reduced vitamin B₁₂ absorption. In a study involving 21 subjects with type 2 diabetes, researchers found that 17 who were prescribed Metformin experienced a decrease in vitamin B₁₂ absorption. Researchers also found that using calcium carbonate supplements (1,200 mg/day) helped limit the effect of Metformin on vitamin B₁₂ absorption in these individuals.

So What Can I Do?

The route of administration of vitamin B₁₂, to void the IF pathway, can be nasally, under the tongue or under the skin via a shot. Initial recommended dosages for the shot route include 1,000 to 2,000 mcg per day for one week then 1,000 mcg per month for life. Nasal or under the tongue route include 1,000 to 5000 mcg every day or every other day for one to two weeks, followed by 1000 to 5,000 mcg every one to three months for individuals with B₁₂ deficiency syndrome. Taking high dose B₁₂ by mouth will not usually replace depleted B₁₂ levels because of your faulty mechanism of absorption that caused you to be deficient in the first place. *HC is also known as transcobalamin I (TC I) and transcobalamin III (TC III).

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