“Vitamin B12 Deficiency: Are You Missing This Key Nutrient?”

Introduction

Vitamin B12 is a water-soluble vitamin that is naturally present in food ( Meat, Fish, egg and dairy products). Vitamin B12 circulates in plasma bound to R-factor and transcobalamin II. Approximately 80 per cent of vitamin B12 is bound to haptocorrin and is functionally inactive. Vitamin B12 bound to transcobalamin II is the active form absorbed by cells. Vitamin B12 is required for the development, myelination, and function of the central nervous system; healthy red blood cell formation; and DNA synthesis 

Recommended Intake

1. Age > 14 years = 2.4 mcg /day
2. Pregnancy = 2.6 mcg /day
3. Lactating mother = 2.8 mcg /day

Sources of Vitamin B-12

1. Vitamin B12 is present in foods of animal origin, including fish, meat, poultry, eggs, and dairy products 
2. Plant foods do not naturally contain vitamin 
3. Breast milk of women = 0.44 mcg/L
4. Dietary supplements like

The most common form of vitamin B12 in dietary supplements is cyanocobalamin, other forms of vitamin B12 in supplements are adenosylcobalamin, methylcobalamin, and hydroxocobalamin, absorption rates of vitamin B12 in supplements is only1.3 – 2 % 

Vitamin B-12 Supplement available in 

1. IV /IM injection form
2. Nasal spray
3. Oral tablet

Vitamin B-12 Deficiency-Causes

Causes of vitamin B12 deficiency include 

1. Difficulty absorbing vitamin B12 from food, lack of intrinsic factor (e.g., because of pernicious anaemia), surgery in the gastrointestinal tract, prolonged use of certain medications (e.g., metformin or proton pump inhibitors
2. Dietary deficiency ( Vegan and Vegetarian diet)

The effects of vitamin B-12 deficiency can include

1. Megaloblastic anemia
2. Pancytopenia -Low haemoglobin,low White Cells and platelets
3. Glossitis of the tongue; fatigue; palpitations; pale skin
4. Dementia
5. Infertility 
6. Neurological changes, such as numbness and tingling in the hands and feet, can also occur These neurological symptoms can occur without anaemia 
7. In pregnant and breastfeeding women, vitamin B12 deficiency might cause neural tube defects, developmental delays, failure to thrive, and anaemia in offspring 

Store of vitamin B-12 in the body

Liver stores about 1 to 5 mg of vitamin B12 (or about 1,000 to 2,000 times as much as the amount typically consumed in a day)

Groups at Risk of Vitamin B-12 deficiency 

1. Older adults
2. Individuals with pernicious anemia
3. Individuals with gastrointestinal disorders- atrophic gastritis, H pylori infection.
4. Individuals who have had gastrointestinal surgery-Surgical procedures in the gastrointestinal tract, such as for weight loss or to remove all or part of the stomach, can cause a complete or partial loss of cells that secrete hydrochloric acid and cells that secrete intrinsic factor
5. Vegetarians-Vegans who consume no animal products and vegetarians who consume some animal products (e.g., dairy products, eggs, or both) but not meat have a higher risk of developing vitamin B12 deficiency because natural food sources of vitamin B12 are limited to animal foods ( Liver)
6. Infants of vegan women

Vitamin B-12 and Health

Cancer

1. Low Serum Vitamin B12 level is associated with
2. Lung Cancer in men
3. Colorectal cancer
4. Esophageal cancer
5. Pancreatic cancer. Gastric cancer
6. Cardiovascular disease and stroke
7. An elevated homocysteine level has been associated with an increased risk of CVD Vitamin B12 and other B vitamins are involved in homocysteine metabolism and supplementation with these micronutrients can reduce CVD risk by lowering homocysteine levels.
8. Dementia and cognitive function
9. elevated homocysteine levels and the incidence of both Alzheimer’s disease and dementia
10. Energy and endurance: Because of its role in energy metabolism, vitamin B12 is often promoted as an energy enhancer and an athletic performance and endurance booster

Health Risks from Excessive Vitamin B-12

No, Even at large doses, vitamin B12 is generally considered to be safe because the body does not store excess amounts.

Interactions with Medications

Vitamin B12 has the potential to interact with certain medications.

1. Proton pump inhibitors, such as omeprazole and lansoprazole and histamine 2-receptor antagonists, such  ranitidine (Zantac). They can interfere with vitamin B12 absorption from food by slowing the release of gastric acid into the stomach and thereby lead to vitamin B12 deficienc
2. Metformin

Diagnostic Evaluation

1. CBC and blood smear 
2. Anemia
3. Macrocytic red blood cells (RBCs; eg, mean corpuscular volume [MCV] >100 fL) or macro-ovalocytosis (picture 4)
4. Mild leukopenia and/or thrombocytopenia
5. Low reticulocyte count
6. Hypersegmented neutrophils on the peripheral blood smear (ie, >5 percent of neutrophils with ≥5 lobes or ≥1 percent of neutrophils with ≥6 lobes)
7. Serum Vitamin B12 Level  
8. Above 300 pg/mL-Normal
9. 200 to 300 pg/mL – Borderline; deficiency is possible and additional testing is useful.
10. Below 200 pg/mL (below 148 pmol/L) – Low; consistent with deficiency

Metabolite testing (MMA and homocysteine) 

1. MMA is elevated in vitamin B12 deficiency but not in folate deficiency. This is because vitamin B12 is a cofactor in conversion of methylmalonyl-CoA to succinyl-CoA, a reaction that occurs in mitochondria and is catalyzed by methylmalonyl-CoA mutase [59]. In the absence of vitamin B12, this reaction cannot proceed normally, and MMA accumulates 
2. Homocysteine is elevated in both vitamin B12 and folate deficiencies. This is because both vitamins are required for the metabolism of homocysteine to methionine (figure 3). In the absence of either vitamin, this process cannot occur normally, and homocysteine accumulates. Thus, a normal MMA and an increased homocysteine level are consistent with folate deficiency.

Vitamin B-12 rich Diets

1. Milk and milk products are good sources of vitamin B12 
2. Fish and red meat are excellent sources of vitamin B12. Poultry and eggs also contain vitamin B12.

Treatment of Vitamin B-12 deficeincy

Intramuscular injection 

1. 1000 mcg intramuscularly once per week until the deficiency is corrected and then once per month (cyanocobalamin) or once every other month (hydroxocobalamin) in individuals with impaired absorption of vitamin B12 ( atrophic gastritis , pernicious anemia, celiac disease ,IBD , bariatric surgery, gastrectomy, ileal loop syndrome,
2. If there are symptoms of anaemia or Hb. <8 g/dl and/or neurologic symptoms, 1000 mcg can be administered one to three times per week or daily, followed by once weekly

Oral tablet-Preferred for dietary deficiency

1. Equal efficacy to intramuscular therapy
2. In adults with normal absorption, oral dosing is equally effective as intramuscular dosing when given at a dose of 1000 mcg orally once per day. 
3. For individuals with impaired absorption of vitamin B12, therapy with very high oral doses of oral vitamin B12 (eg, 2000 mcg daily) will be effective as long as the dose is high enough to provide absorption via a mechanism that does not require intrinsic factor or a functioning terminal ileum (ie, passive diffusion/mass action) 

Routes that are not used

Vitamin B12 is not given intravenously; prescribing information notes that intravenous use will result in urinary excretion of most of the vitamin B12. Concerns about anaphylaxis have also been raised