Vitamin B12 Injections Not Necessary: How to Take Vitamin B12

There is no need to waste money on vitamin B12 injections when oral tablets are equivalent in the proper doses (2,6), even in those with pernicious anemia (30).

Introduction: Vitamin B12 Injections Not Necessary – How to Take Vitamin B12

Vitamin B12 (VB12), is a vitamin that belongs to the vitamin B complex group. Plants and animals are not capable of producing B12, and the exclusive source of this vitamin appears to be tiny microorganisms such as bacteria, yeasts, molds, and algae. Vitamin B12 is only found naturally in animal food products such as meat and fish but synthetic forms are widely available and added to many foods like cereals. Vegetarians are not able to obtain adequate amounts of vitamin B12 in their diet and may not know how to take vitamin B12. Vegetarians  and may be at risk of several health conditions due to B12 deficiency. Vitamin B12 is involved in the development of red blood cells and it protects the nervous system. It also might reduce cardiovascular disease risk by helping to control levels of homocysteine (an amino acid) in the blood. Learn about how to take vitamin B12 by reading further.

Vitamin B12 Injections are Needed for Symptoms of Deficiency

There are several conditions in which vitamin B12 injections should be provided over oral vitamin B12. Vitamin B12 deficiency, especially with concerning symptoms is necessary to replace with injections to deliver the vitamin more quickly into the body. Without enough vitamin 12, deficiency may result in permanent damage (e.g., blindness, deafness, dementia). Fatigue, and tingling in the hands or feet, can be early signs of deficiency. VB12 deficiency may lead to symptoms associated with anemia, low platelets, tongue inflammation, gastrointestinal complaints, jaundice, impaired cognition, neuropathy, gait disturbance, and changes in skin pigmentation.

Here is How to Take Vitamin B12

The first priority when considering how to take vitamin B12 supplements or injections is to obtain your level by a blood test. Vitamin B12 is promoted as an energy and nutritional enhancer in many clinics as an intramuscular injection. Weight loss clinics sell vitamin B12 injections, but these injections provide no benefit in weight loss or energy levels unless a deficiency or megaloblastic anemia is present. There is no need to waste money on vitamin B12 injections when oral tablets are equivalent in the proper doses (2,6), even in those with pernicious anemia (30).

Duyvendak M et al (6) outlined how to take vitamin B12 after a review of 2 randomized controlled trials. These trials which administered oral vitamin B12 at doses of 1000-2000 micrograms daily showed it to be equally effective in replenishing vitamin B12 levels as a vitamin B12 injection. The authors also found that the minimum oral dose was 647-1032 micrograms per day. Therefore, it is recommended that patients with vitamin B12 deficiency should be given 1000 micrograms of the vitamin orally daily for 90 – 120 days. If they are unable to take B12 by mouth, parenteral administration of at least 1000 mcg is indicated weekly and then reduced to monthly with monitoring.

What is a “good” vitamin B12 level?

The Institute of Medicine states that a vitamin B12 level of 350 pg per mL is protective against deficiency.

When is a vitamin B12 level too high?

Vitamin B12 levels over 1000 pg/mL are potentially dangerous. Cappello et al (31) found that hospitalized patients with a vitamin B12 level above this range not only had a higher risk of dying, but also was noted to have a significantly longer length of hospital stay. These findings were calculated independently from age, gender, weight, recent weight loss, kidney disease, C-reactive protein, prealbumin, cancer diagnosis and hospital unit location. Therefore, the ideal vitamin B12 level would be midway between 350 and 1000 pg per ml.

Institute of Medicine Recommendation for Vitamin B12:

The Institute of Medicine has outlined how to take vitamin B12. Healthy children and adults up to 50 years of age, excluding vegetarians, are generally able to absorb vitamin B12 from animal food sources. For adults over age 50, only about 50% of vitamin B12 is absorbed from food sources and 10-30% of these older adults may not be able to absorb enough from food sources. Crystalline formulations are absorbed better than food sources of vitamin B12 and therefore, vegetarians and adults over age 50 are recommended to consume B12 fortified food or B12 supplements. (1)

National Institutes of Health Vitamin B12 Recommendation:

Office of Dietary Supplements of the National Institutes of Health revealed how to take vitamin B12 in their recommendation: The Office of Dietary Supplements of the National Institutes of Health has established recommended daily intakes for vitamin B12 available here: http://ods.od.nih.gov/factsheets/VitaminB12-HealthProfessional/

Guidelines for Vitamin B12 Administration and Screening:

An article by Langan RC et al entitled “Update on vitamin B12 deficiency” published in the American Family Physician outlined how to take vitamin B12 and established guidelines on management of those suspected of vitamin B12 (VB12) deficiency. The following is adapted from this source: (2)

• A higher risk of VB12 Deficiency may occur in the following conditions: pernicious anemia (autoimmune-mediated chronic atrophic gastritis), postsurgical malabsorption, dietary deficiencies, malabsorption from food, gastric bypass, Crohn’s, tapeworm infection, low intrinsic factor, genetic, malnutrition, elderly, alcohol abuse, vegetarian, H2 blockers, metformin, and proton pump inhibitors.
• If a patient is at risk of VB12 deficiency, the first step is a complete blood count (CBC) and a serum VB12 level (cobalamin).
• This update stated that the majority of research cited a low VB12 level to be under 150 pg per mL (110.67 pmol per L) but some define it as under 200 pg per mL.
• Once the deficiency is established, no further testing is needed, and treatment with 1-2 mg of oral VB12 is as effective as an intramuscular dose.
• If a patient has a low normal level between 200 to 350 pg per mL, does not have symptoms, but has an increased risk of VB12 deficiency, a serum homocysteine and/or methylmalonic acid level (both precursors to VB12) should be obtained.
• A VB12 level of 350 pg per mL was noted to be protective from deficiency.
• An elevated homocysteine and/or methylmalonic acid level in the face of normal VB12 level defines subclinical VB12 deficiency. If they are at high risk of VB12 deficiency, they should be treated, but otherwise can be monitored and retested.
• Of note, this update stated that treating high serum homocysteine levels with VB12 in Alzheimer’s patients did not improve progression and did not reduce mortality in heart disease.
• Langan RC expressed that falsely low VB12 levels may be caused by gestation, multiple myeloma, folic acid deficiency and birth control pills.
• A falsely normal level may be seen in kidney disease, disease of the liver and diseases of the bone marrow.

Vitamin B12 Level at Which Deficiency May Occur:

According to Lindenbaum et al (3), the serum vitamin B12 level has a 100% sensitivity. Patients may show deficiency symptoms when levels are below 200 pg/ml. This may be manifested as mild anemia and/or neurologic symptoms.

Genetic Factors for Vitamin B12 Status:

Genetics may determine how to take vitamin B12. Methylenetetrahydrofolate (MTHFR) polymorphism is a genetic mutation which predisposes affected individuals to develop low vitamin B12 levels, low folate levels, elevated homocysteine levels, and an increase in cardiovascular risk (32, 33). Those individuals with this MTHFR genetic mutation are deficient in the methylenetetrahydrofolate reductase enzyme needed by the body to utilize vitamin B12 and folate. This MTHFR deficiency is present in about 20-30% of individuals. Shiran et al (33) suggested that “B12 deficiency be tested for MTHFR polymorphism in order to identify potential vascular abnormalities and increased cardiovascular risk.” Those testing positive for the MTHFR polymorphism should replace these vitamin deficiencies with methylated forms of vitamin B12 and folate. This may be done with with 0.4-1 mg daily of methyltetrahydrofolate (methylated folic acid) and 1-2 mg daily of methylcobalamin (methylated vitamin B12) instead of the traditional replacement method with folic acid and cyanocobalamin.

How to Lower Homocysteine Levels:

Adequate doses of vitamin B12, vitamin B6 and folic acid are required to lower methylmalonic acid and homocysteine levels. Naurath HJ, et al performed a prospective, multicentre, double-blind placebo controlled study on elderly patients with normal vitamin B12 levels. The authors found that a vitamin supplement containing 1 mg vitamin B12, 1.1 mg folate, and 5 mg vitamin B6 significantly lowered methylmalonic acid and homocysteine levels. The study concluded that methylmalonic acid and homocysteine levels may help identify elderly subjects who may benefit from these vitamin supplements. (4)

Vitamin B12 Requirement in Healthy Individuals:

Use of methylmalonic acid and homocysteine levels to obtain vitamin B12 dose recommendation: Levels of vitamin B12 and vitamin B12 biomakers (cobalamin, total transcobalamin, holo-transcobalamin, methylmalonic acid [MMA], total homocysteine [tHcy], autoantibodies against intrinsic factor [IF] and helicobacter pylori) were measured in 299 men and women aged 18 to 50. Bor et al. found that vitamin B12 intake ranged from 0.42-22.7 microg/d. Further analysis showed that a vitamin B12 intake of 4 to 7 mcg/day was associated with the lowest methylmalonic acid and homocysteine levels suggesting that this dose is associated with the presence of adequate levels of vitamin B12.  This suggests that current vitamin B12 recommendations of 2.4 microgram daily may be inadequate even for young people who have adequate absorption capability. (5)

Vegetarian Women and Vitamin B12:

In vegetarian women, supplementation of vitamin B12 is required due to the lack of this vitamin in vegetarian foods. (7)

Etiology of Vitamin B12 Deficiency:

Vitamin B12 deficiency has been attributed to a number of factors including low dietary intake of the vitamin, especially among individuals who do not consume animal products (vegetarians, vegans, lacto-ovo vegetarians) and persons in less-industrialized countries. Among the elderly, reduced vitamin B12 absorption is linked to lower stomach acid and H. pylori, a bacterial infection that is commonly found in the stomach. A common genetic polymorphism may affect the function of transcobalamine, the protein required for vitamin B12 cellular uptake and metabolism. (8)

Race and Vitamin B12 Deficiency:

Measures of iron, folate, vitamin B12 status, and anemia, socio-demographic data, and gender were analyzed in 1770 elderly subjects from the 2001–2002. Males were reported to have greater chances of not consuming enough folate and vitamin B12 than females. Whites were less deficient in vitamin B12 and folate than Hispanics and blacks and often exceeded nutrient intake as recommended by the Food and Nutrition Board. Incidence of iron and folic acid deficiency did not differ significantly among ethnic groups. Hispanics (non-Mexican American) were significantly more likely than whites and blacks to be vitamin B12 deficient. Blacks were significantly more likely to be folate deficient than other ethnicities. (9)

Vegetarian Children Need Vitamin B12:

Concern exists that vegetarian children may not be able to obtain enough vitamin B12 since adults tend to have low levels. Consider showing vegetarian children how to take vitamin B12 which is available in children’s multivitamins. On the other hand, one study in Poland did show that children aged 5-11 on vegetarian or omnivorous diets were found to have a normal vitamin B12 level (10).

Vitamin B12 in Risk of Stroke:

Homocysteine, vitamin B and risk of stroke: Researchers looked at the relationship between homocysteine, vitamin B and risk of stroke in patients with severe hyperhomocysteinemia in a meta-analysis. Lowering homocysteine with folic acid, vitamin B6, and vitamin B12 may improve a patient’s clinical outcomes. Results demonstrate that supplementation with these vitamins did in fact decrease homocysteine and showed a tendency toward lowering the risk of stroke. (11)

Vitamin B12, Vitamin B6, Folic Acid, Homocysteine and Stroke:

Lowering of homocysteine, an amino acid, with folic acid and vitamins B6 and B12 had a modest, but beneficial effect on stroke prevention or fatal stroke among a population at high risk for cardiovascular disease. Results from a five-year research trial that randomly assigned 5,522 adults with heart disease to either placebo or a daily combination regimen of 2.5 mg of folic acid (vitamin B9), 50 mg vitamin B6 and 1mg of vitamin B12 found that daily supplements of folic acid, vitamin B6, and B12 for 5 years reduced the risk of stroke by 25%. However, no noticeable effect was observed during the first 3 years of supplementation. During a five-year follow-up period, stroke occurred in 258 of the participants (4.7%). The risk was lower in those who followed the vitamin regimen. The average homocysteine concentration decreased by 2.2 micromol/L in the vitamin therapy group and increased by 0.80 micromol/L in the placebo group. Those who benefited the most from the vitamin treatment included people: younger than 69, with higher cholesterol and homocysteine levels at the start of the study, from areas where folic acid-fortified food isn’t available, who weren’t receiving anti-platelet drugs or cholesterol-lowering drugs at the start of the study. (12)

Lacunar Stroke and Vitamin B12:

Researchers discovered that lacunar stroke patients (n=40) who lack sufficient levels of B12 (n=13) are more likely to suffer from increased levels of fatigue and depression. Lacunar stokes are cause when a small branch of a larger blood vessel going to the brain becomes closed or obstructed.  In this study, lacunar stroke patients with vitamin B12 deficiency when compared to non-vitamin B12 deficient individuals reported significantly more fatigue (90.7% versus 59.4%) and depressive symptoms (6.62% versus 3.89%). (13)

B12 Deficiency Responsible for Cognitive Impairment:

Low serum vitamin B12 levels (<150 ρmol/L) are associated with neurodegenerative disease and cognitive impairment. This analysis of 17 studies (looking at the relationship between vitamin B12 and cognitive impairment) demonstrated that vitamin B12 supplements administered orally or injected at 1mg daily corrected the deficiency, and moreover, improved cognitive ability, though only among patients with pre-existing vitamin B12 deficiency. Vitamin B12 therapy was not shown to improve cognitive ability in patients without pre–existing vitamin B12 deficiency. (14)

Vitamin B12 and Homocysteine (Hcy) in Alzheimer’s Disease:

Inflammation is a protective response that elevates blood markers that are useful in predicting the onset of Alzheimer’s disease. They found that supplementation with with folic acid, vitamin B6, and vitamin B12 decreased homocysteine (Hcy). Since hyper-homocysteinemia is common among the elderly, the authors concluded that Hcy is a potential marker in age-related neurodegenerative diseases. Researchers expressed that that lowering homocysteine with folic acid, vitamin B6, and vitamin B12 may improve a patient’s clinical outcome. (15)

According to Langan RC et al, vitamin B12 supplement taken by Alzheimer’s disease patients with high serum homocysteine levels did not reverse the rate of cognitive decline and therefore they are not recommended. (2)

Vitamin B12 Deficiency Results in Megaloblastic Anemia (Abnormally Large Red Blood Cells)

Vitamin B12 is a necessary component in the creation of red blood cells. Researchers conducted a systematic review of studies looking at the relationship of vitamin supplementation on anemia. Vitamin B12 intake may prevent anemia with abnormally large red blood cells (megaloblastic anemia). (16)

Folic acid, vitamin B12, and anemia: A case study of a 49-year-old woman with anemia due entirely to folic and vitamin B12 deficiency was reported by Tschöp M. et al. After being hospitalized and put on a treatment of vitamin B12 also known as cobalamin (1 mg intramuscularly twice weekly for 6 weeks, then 300 micrograms daily by mouth for 4 weeks) and folic acid (5 mg twice daily for 10 weeks) plus a well-balanced diet, red blood cells increased to normal levels after 2 months. (17)

Vitamin B12 in Vegetarians with Coronary Artery Disease (CAD):

In a study involving 816 subjects (368 with CAD and 448 controls) in India, levels of vitamin B12 were found to be significantly lower in patients with CAD, as compared to controls. Vegetarians were found to have lower levels of vitamin B12 and a higher incidence of CAD compared to non-vegetarians in India. (18)

Vitamin B12 Deficiency Linked to Heart Disease:

A strong link was reported between vitamin B12 deficiency and heart disease, conditions that affect the circulation of blood to the brain, vascular risk factors and drugs used to prevent heart related events and strokes caused by reduced blood supply. B12 deficiency rates in semi-urban and rural areas were examined among older individuals (65 years old and older) between 2008-2010. Researchers found that 16.5% of the study sample suffered from low vitamin B12 levels. There was no evidence of folic acid deficiency in the study population. (19)

An association between heart disease and vitamin B12 deficiency has been established but does not necessarily imply the deficiency results in heart disease. Treating high serum homocysteine levels with vitamin B12 did not reduce mortality in heart disease (2).

Vitamin B12 Occurs in Hypothyroidism:

Jabbar et al. tested 116 hypothyroid patients (95 females and 21 males) and found 46 (39.6%) of them had low vitamin B12 levels. Of those hypothyroid patients with vitamin B12 deficiency, 24 received intramuscular vitamin B12 injections monthly. Improvement in symptoms was noted in 58.3% of these subjects. The authors conclude, that replenishing vitamin B12 leads to improvement in symptoms among hypothyroid patients and monitoring of vitamin B12 levels in this patient group is suggested. (20)

Low Vitamin B12 Risks Neural Tube Defects:

Results of a meta-analysis that included 1566 controls and 567 cases found that having a low maternal vitamin B12 status increased the risk of the fetus developing neural tube defects with an overall risk of 2.41. Neural tube defects (NTDs) are birth defects. They are disorders causing an opening in the spinal cord or brain during early pregnancy affecting the development of a baby and can cause life-long complications of varying severity. (21)

Low Vitamin B12 Level Linked to Higher Risk of Breast Cancer:

Researchers investigated whether breast cancer may, in part, be caused by a vitamin B12 deficiency. At Johns Hopkins University in Maryland, two large but separate blood sample donations were evaluated against cases of breast cancer. In 1974, 12,450 blood samples were donated by female volunteers. In 1989, another 14,625 women again voluntarily donated samples of their blood. Cases of breast cancer that occurred in these groups of women were then recorded and their blood samples examined. Researchers found that women who had the lowest levels of B12 in their blood, had the highest rates of breast cancer. Therefore, the authors concluded that there was a link between breast cancer risk and low B12 levels, mostly among postmenopausal women. (22)

Vitamin B12 Deficiency Correlated to Depression:

Vitamin B12 deficiency among depressive patients of Turkish (n=47) and Dutch (n=28) descent were examined to determine the relationship between the frequency of vitamin B deficiency and depression. Depression was diagnosed using the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders. The Beck Depression Inventory (BDI) and the 21-item Hamilton Depression Rating Scale (HAM-D-21) were used to determine severity of symptoms. Levels of vitamin B6 and B12, folic acid and homocysteine (tHcy) were measured at baseline. Results indicate patients with vitamin B12 deficiency and hyperhomocysteinaemia had significantly higher BDI scores than those with normal levels. (23)

Researchers in a cross-sectional study evaluated the relationship between vitamin B12 and folic acid and depressive symptoms in 669 Chinese adults age 55 and older.  Depressive symptoms were measured using the Geriatric Depression Scale (GDS) (score > or =5). Low folate was associated with symptoms of depression independent of homocysteine and B12 levels in subjects.  B12 deficiency was found by the study to be significantly associated with symptoms of depression independent of homocysteine and folic acid. (24)

Stroke patients were found to have higher rates of depression when vitamin B12 is deficient. Researchers discovered that stroke patients (n=40) who lack sufficient levels of B12 (n=13) are more likely to suffer from increased levels of fatigue and depression when compared to non-vitamin B12 deficient individuals. (13)

Medications Influence Vitamin B12 Status

Metformin Lowers Vitamin B12 Levels

The findings of a multi-center randomized controlled trial suggested that patients treated with long-term with metformin are at risk of developing vitamin B12 deficiency, which is likely to get progressively worse over time. 390 patients with type 2 diabetes received metformin (850 mg) or placebo three times daily for 4.3 years. Compared with placebo, metformin was associated with a significant 19% decrease in baseline VB12 concentration. The absolute risks for vitamin B12 deficiency and low vitamin B12 level were significantly higher in the metformin group than in the placebo group: 7% and 11% higher, with numbers needed to harm of 14 and 9 per 4.3 years, respectively. Blood homocysteine levels were also significantly elevated. (25)

Proton Pump Inhibitors May Lower Absorption Rates of Vitamin B12 :

A review of studies reports that omeprazole, a drug that blocks production of stomach acid and is used to treat diseases in which stomach acid causes damage, may reduce the absorption of vitamin B12. However, there is also data that drinking juice or other acid drinks can lessen this effect. There is currently a lack of data to determine how omeprazole affects vitamin B12 absorption over time. (26)

How to Take Vitamin B12 in Foods:

Adapted from: United States Department of Agriculture

Summary: Vitamin B12 Injections are Unnecessary – How to Take B12

• The Institute of Medicine has established that healthy children and adults up to 50 years of age, excluding vegetarians, are generally able to absorb vitamin B12 from animal food sources. For adults over age 50, only about 50% of vitamin B12 is absorbed from food sources and intake should be doubled. 10-30% of these older adults may not be able to absorb enough from food sources. Crystalline formulations are absorbed better than food sources of vitamin B12 and therefore, vegetarians of all ages and adults over age 50 are recommended to consume B12 fortified food or B12 supplements. (1)
• The office of dietary supplements of the National Institutes of Health has established recommended daily intakes for vitamin B12 available here: http://ods.od.nih.gov/factsheets/VitaminB12-HealthProfessional/
• An article by Langan RC et al entitled “Update on vitamin B12 deficiency” published in the American Family Physician established guidelines on management of patients suspected of vitamin B12 (VB12) deficiency: (2)
  • Consider testing those at risk of VB12 deficiency: vegetarians, pernicious anemia (autoimmune-mediated chronic atrophic gastritis), postsurgical malabsorption, dietary deficiencies, malabsorption from food, gastric bypass, Crohn’s, tapeworm infection, low intrinsic factor, genetic polymorphism, malnutrition, elderly, Helicobacter pylori infection, alcohol abuse, vegetarian, H2 blockers, metformin, and proton pump inhibitors.
  • If a patient is at risk of VB12 deficiency, the first step is a complete blood count (CBC) and a serum VB12 level (cobalamin).
  • This update stated that the majority of research cited a low VB12 level to be under 150 pg per mL (110.67 pmol per L) but some define it as under 200 pg per mL.
  • Once the deficiency is established, no further testing is needed, and treatment with 1-2 mg of oral VB12 is as effective as an intramuscular dose.
  • If a patient has a low normal level between 200 to 350 pg per mL, does not have symptoms, but has an increased risk of VB12 deficiency, a serum homocysteine and/or methylmalonic acid level (both precursors to VB12) should be obtained.
  • A VB12 level of 350 pg per mL was noted to be protective from deficiency.
  • An elevated homocysteine and/or methylmalonic acid level in the face of normal VB12 level defines subclinical VB12 deficiency. If they are at high risk of VB12 deficiency, they should be treated, but otherwise can be monitored and retested.
  • Of note, this update stated that treating high serum homocysteine levels with VB12 in Alzheimer’s patients did not improve progression and also did not reduce mortality in heart disease.
  • Langan RC expressed that falsely low VB12 levels may be caused by gestation, multiple myeloma, folic acid deficiency and birth control pills.
  • A falsely normal level may be seen in kidney disease, disease of the liver and diseases of the bone marrow.
• Patients may show deficiency symptoms when levels are above 200 pg/ml and may be manifested as mild anemia and/or neurologic symptoms (3).
• A vitamin supplement containing 1 mg vitamin B12, 1.1 mg folate, and 5 mg vitamin B6 significantly lowered methylmalonic and homocysteine levels (4).
• Vitamin B12 intake from the diet in the amount of 4 to 7 mcg/day was associated with the lowest methylmalonic acid and homocysteine levels suggesting that current vitamin B12 recommendations of 2.4 microgram daily may be inadequate (5).
• Patients with vitamin B12 deficiency should be given 1000 micrograms of the vitamin orally daily for 90 – 120 days unless they are unable to do so in which case weekly IM administration of  least 1000 mcg is indicated. The dose schedule may then be reduced to monthly with monitoring. (6)
• Vegetarians may require testing for deficiency and are either required to take a vitamin B12 supplement due to the lack of this vitamin in vegetarian foods (7), or consume adequate vitamin B12 in fortified foods such as cereals every day (1).
• Lowering homocysteine with folic acid, vitamin B6, and vitamin B12 may improve a patient’s clinical outcome and may lower the risk of stroke (11,12), especially within a population at high risk for cardiovascular disease (12). Those who benefited the most from the vitamin treatment included people: younger than 69, with higher cholesterol and homocysteine levels at the start of the study, from areas where folic acid-fortified food isn’t available, or who weren’t receiving anti-platelet drugs or cholesterol-lowering drugs at the start of the study (12).
• Lacunar stroke patients with vitamin B12 deficiency when compared to non-vitamin B12 deficient individuals reported significantly more fatigue (90.7% versus 59.4%) and depressive symptoms (6.62% versus 3.89%) (13).
• Vitamin B12 supplements improved cognitive ability among patients with pre-existing vitamin B12 deficiency, but not in patients without pre–existing vitamin B12 deficiency (14), and vitamin B12 supplement taken by Alzheimer’s disease patients with high serum homocysteine levels did not reverse the rate of cognitive decline and therefore they are not recommended by Langan RC et al (2). Other authors from recent research suggested that lowering homocysteine with folic acid, vitamin B6, and vitamin B12 may improve a patient’s clinical outcome (15).
• Adequate vitamin B12 intake prevents megaloblastic anemia due to deficiency of this vitamin.
• Kumar J et al found that coronary artery disease (CAD) incidence was higher in a vegetarian population from India which had significantly lower vitamin B12 levels suggesting that CAD was related to vitamin B12 deficiency (18). Other research has demonstrated that changing to a vegetarian diet leads to regression of CAD (29), but the vitamin B12 status was not determined. Treating high serum homocysteine levels with vitamin B12 did not reduce mortality in heart disease (2).
• About 40% of patients with hypothyroidism were found to have vitamin B12 deficiency (20).
• A low maternal vitamin B12 status increased the risk of the fetus developing neural tube defects with an overall risk of 2.41 (21).
• A link was found between breast cancer risk and low vitamin B12 levels, mostly among postmenopausal women (22).
• Results indicate patients with vitamin B12 deficiency and hyperhomocysteinemia had significantly worse depression scores than those with normal levels (13,23,24).
• Use of the medications metformin (25), and proton pump inhibitors (26) were found to be associated with vitamin B12 deficiency.
• How to take vitamin B12 with methylenetetrahydrofolate (MTHFR) polymorphism
  • Methylenetetrahydrofolate (MTHFR) polymorphism is a genetic mutation which predisposes affected individuals to develop low vitamin B12 levels, low folate levels, elevated homocysteine levels, and an increase in cardiovascular risk (32, 33).
  • Shiran et al (33) suggested that “B12 deficiency be tested for MTHFR polymorphism in order to identify potential vascular abnormalities and increased cardiovascular risk.”
  • In MTHFR polymorphisms, replace folate  and B12 with 0.4-1 mg of methyltetrahydrofolate (methylated folic acid) daily and 1-2 mg of methylcobalamin (methylated vitamin B12) daily.

References: Vitamin B12 Injections are Unnecessary – How to Take Vitamin B12

1.Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline. Institute of Medicine (US) Standing Committee on the Scientific Evaluation of Dietary Reference Intakes and its Panel on Folate, Other B Vitamins, and Choline. SourceWashington (DC): National Academies Press (US); 1998. http://www.ncbi.nlm.nih.gov/pubmed/23193625

2.Langan RC, Zawistoski KJ. Update on vitamin B12 deficiency. Am Fam Physician. 2011 Jun 15;83(12):1425-30. http://www.ncbi.nlm.nih.gov/pubmed/21671542

3.Lindenbaum J, Savage DG, Stabler SP, Allen RH. Diagnosis of cobalamin deficiency: II. Relative sensitivities of serum cobalamin, methylmalonic acid, and total homocysteine concentrations. Am J Hematol. 1990 Jun;34(2):99-107. http://www.ncbi.nlm.nih.gov/pubmed/2339684

4.Naurath HJ, Joosten E, Riezler R, Stabler SP, Allen RH, Lindenbaum J. Lancet. Effects of vitamin B12, folate, and vitamin B6 supplements in elderly people with normal serum vitamin concentrations. 1995 Jul 8;346(8967):85-9. http://www.ncbi.nlm.nih.gov/pubmed/7603218

5.Bor MV, von Castel-Roberts KM, Kauwell GP, Stabler SP, Allen RH, Maneval DR, Bailey LB, Nexo E. Daily intake of 4 to 7 microg dietary vitamin B-12 is associated with steady concentrations of vitamin B-12-related biomarkers in a healthy young population. Am J Clin Nutr. 2010 Mar;91(3):571-7. http://www.ncbi.nlm.nih.gov/pubmed/20071646

6.Duyvendak M, Veldhuis GJ. Oral better than parenteral supplementation of vitamin B12.[Article in Dutch]. Ned Tijdschr Geneeskd. 2009;153:B485. http://www.ncbi.nlm.nih.gov/pubmed/19900336

7.Hovdenak N, Haram K. Influence of mineral and vitamin supplements on pregnancy outcome. Eur J Obstet Gynecol Reprod Biol. 2012 Oct;164(2):127-32. http://www.ncbi.nlm.nih.gov/pubmed/22771225

8.Allen LH. Causes of vitamin B12 and folate deficiency. Food Nutr Bull. 2008 Jun;29(2 Suppl):S20-34; discussion S35-7. http://www.ncbi.nlm.nih.gov/pubmed/18709879

9.Hinds HE, Johnson AA, Webb MC, Graham AP. Iron, folate, and vitamin B12 status in the elderly by gender and ethnicity. J Natl Med Assoc. 2011 Sep-Oct;103(9-10):870-7. http://www.ncbi.nlm.nih.gov/pubmed/22364055

10.Laskowska-Klita T, Che?chowska M, Ambroszkiewicz J, Gajewska J, Klemarczyk W. The effect of vegetarian diet on selected essential nutrients in children. Med Wieku Rozwoj. 2011 Jul-Sep;15(3):318-25. http://www.ncbi.nlm.nih.gov/pubmed/22006487

11.Herrmann W, Obeid R. Homocysteine: a biomarker in neurodegenerative diseases. Clin Chem Lab Med. 2011 Mar;49(3):435-41. http://www.ncbi.nlm.nih.gov/pubmed/21388339

12.Saposnik G, Ray JG, Sheridan P, McQueen M, et al. Heart Outcomes Prevention Evaluation 2 Investigators. Homocysteine-lowering therapy and stroke risk, severity, and disability: additional findings from the HOPE 2 trial. Stroke. 2009 Apr;40(4):1365-72. http://www.ncbi.nlm.nih.gov/pubmed/19228852

13.Huijts M, Duits A, Staals J, van Oostenbrugge RJ. Association of vitamin B12 deficiency with fatigue and depression after lacunar stroke. PLoS One. 2012;7(1):e30519. http://www.ncbi.nlm.nih.gov/pubmed/22276208

14.Moore E, Mander A, Ames D, Carne R, Sanders K, Watters D. Cognitive impairment and vitamin B12: a review. Int Psychogeriatr. 2012 Jan 6:1-16. http://www.ncbi.nlm.nih.gov/pubmed/22221769

15.Van Dam F, Van Gool WA. Arch Gerontol Geriatr. Hyperhomocysteinemia and Alzheimer’s disease: A systematic review.2009 May-Jun;48(3):425-30. http://www.ncbi.nlm.nih.gov/pubmed/18479766

16.Fishman SM, Christian P, West KP. The role of vitamins in the prevention and control of anaemia. Public Health Nutr. 2000 Jun;3(2):125-50. http://www.ncbi.nlm.nih.gov/pubmed/10948381

17.Tschöp M, Folwaczny C, Schindlbeck N, Loeschke K. Megaloblastic anemia due to inadequate nutrition. German. Dtsch Med Wochenschr. 1997 Jun 20;122(25-26):820-4. http://www.ncbi.nlm.nih.gov/pubmed/9244670

18.Kumar J, Garg G, Sundaramoorthy E, Prasad PV, Karthikeyan G, Ramakrishnan L, Ghosh S, Sengupta S. Vitamin B12 deficiency is associated with coronary artery disease in an Indian population. Clin Chem Lab Med. 2009;47(3):334-8. http://www.ncbi.nlm.nih.gov/pubmed/19676146

19.Vazquez-Pedrazuela Mdel C, Canton-Alvarez MB, de la Fuente-Hontañon Mdel C, Soloaga-Morales A, Collazos-del Castillo JM, Sertal-Parcero R. [Vitamin B12 and folic acid deficiency in the population over 65 years: a descriptive study]. [Article in Spanish]. Rev Esp Geriatr Gerontol. 2012 Nov-Dec;47(6):259-61. http://www.ncbi.nlm.nih.gov/pubmed/22648085

20.Jabbar A, Yawar A, Waseem S, Islam N, Ul Haque N, Zuberi L, Khan A, Akhter J. Vitamin B12 deficiency common in primary hypothyroidism. J Pak Med Assoc. 2008 May;58(5):258-61. http://www.ncbi.nlm.nih.gov/pubmed/18655403

21.Wang, Z., X. Shang, and Z. Zhao, Low maternal vitamin B(12) is a risk factor for neural tube defects: a meta-analysis. J Matern Fetal Neonatal Med. 2012 Apr;25(4):389-94. http://www.ncbi.nlm.nih.gov/pubmed/21627554

22.Wu K, Helzlsouer KJ, Comstock GW, et al. A prospective study on folate B12 and pyridoxal 5′-phosphate (B6) and breast cancer. Cancer Epidemiol Biomarkers Prev 1999;8:209–17. http://www.ncbi.nlm.nih.gov/pubmed/10090298

23.Güzelcan Y, van Loon P. Vitamin B12 status in patients of Turkish and Dutch descent with depression: a comparative cross-sectional study. Ann Gen Psychiatry. 2009 Aug 13;8:18. http://www.ncbi.nlm.nih.gov/pubmed/19674486

24.Ng TP, Feng L, Niti M, Kua EH, Yap KB. Folate, vitamin B12, homocysteine, and depressive symptoms in a population sample of older Chinese adults. J Am Geriatr Soc. 2009 May;57(5):871-6. http://www.ncbi.nlm.nih.gov/pubmed/19484842

25.de Jager, J., Kooy, A., Lehert, P., Wulffele, M., van der Kolk, J., Bets, D., Verburg, J., Donker, A., & Stehouwer, C. Long term treatment with metformin in patients with type 2 diabetes and risk of vitamin B-12 deficiency: randomised placebo controlled trial. BMJ. 2010 May 20;340:c2181 http://www.ncbi.nlm.nih.gov/pubmed/20488910?dopt=Abstract

26.Bradford GS and Taylor CT. Omeprazole and vitamin B12 deficiency. Ann Pharmacother 1999 May;33(5):641-3. http://www.ncbi.nlm.nih.gov/pubmed/10369631?dopt=Abstract

27.Nutritive Value of Foods, United States Department of Agriculture, Agricultural Research Service, Home and Garden Bulletin Number 72. May be accessed at: https://www.ars.usda.gov/SP2UserFiles/Place/12354500/Data/SR25/nutrlist/sr25w418.pdf and http://www.nal.usda.gov/fnic/foodcomp/Data/HG72/hg72_2002.pdf

28.Office of Dietary Supplements of the National Institutes of Health has established recommended daily intakes for vitamin B12 available here: http://ods.od.nih.gov/factsheets/VitaminB12-HealthProfessional/

29.Singh RB, Rastogi SS, Verma R, Bolaki L, Singh R.Indian experiment with nutritional modulation in acute myocardial infarction. Am J Cardiol. 1992 Apr 1;69(9):879-85. http://www.ncbi.nlm.nih.gov/pubmed/1550016

30.Chan CQ, Low LL, Lee KH. Oral Vitamin B12 Replacement for the Treatment of Pernicious Anemia. Front Med (Lausanne). 2016 Aug 23;3:38. https://www.ncbi.nlm.nih.gov/pubmed/27602354

31.Cappello S, Cereda E, Rondanelli M, Klersy C, Cameletti B, Albertini R, Magno D, Caraccia M, Turri A, Caccialanza R. Elevated Plasma Vitamin B12 Concentrations Are Independent Predictors of In-Hospital Mortality in Adult Patients at Nutritional Risk. Nutrients. 2016 Dec 23;9(1). https://www.ncbi.nlm.nih.gov/pubmed/28025528

32.Ni J, Zhang L, Zhou T, Xu WJ, Xue JL, Cao N, Wang X. Association between the MTHFR C677T polymorphism, blood folate and vitamin B12 deficiency, and elevated serum total homocysteine in healthy individuals in Yunnan Province, China. J Chin Med Assoc. 2017 Jan 13. pii: S1726-4901(16)30217-9. https://www.ncbi.nlm.nih.gov/pubmed/28094233

33.Shiran A, Remer E, Asmer I, Karkabi B, Zittan E, Cassel A, Barak M, Rozenberg O, Karkabi K, Flugelman MY. Association of Vitamin B12 Deficiency with Homozygosity of the TT MTHFR C677T Genotype, Hyperhomocysteinemia, and Endothelial Cell Dysfunction. Isr Med Assoc J. 2015 May;17(5):288-92. https://www.ncbi.nlm.nih.gov/pubmed/26137654