Is it ok to take 1000 mcg of vitamin B12 a day?
Vitamins are organic nutrients that are highly essential for maintaining growth, reproduction and various metabolic functions in our body, therefore vitamins are required to be present in our diet.
Vitamin B is a class of water-soluble vitamins consisting of eight members (Vit B1, B2, B3, B5, B6, B7, B9 and B12) which together are referred to as B complex. Vitamin B12 is a vital nutrient required to produce red blood cells, regulate the formation of myelin sheaths that shield the nerve cells of the nervous system and facilitate the synthesis of DNA.
Of note, vitamin B12 helps in the prevention of pernicious anemia, hence, it is otherwise known as “anti-pernicious anemia factor”. Vitamin B12 acts as a cofactor in two enzymes such as methionine synthase and methylmalonyl-coenzyme A mutase, which are critical enzymes in the production of SAMe (or S-adenosyl methionine), hemoglobin and catalytic intermediate by-products involved in fat and protein metabolism.
Vitamin B12 exists in four different forms, 3 bioactive and easily absorbed forms (methylcobalamin, adenosylcobalamin, and hydroxocobalamin) and 1 not so easily absorbed. All of these forms contain cobalt metal atoms and thus collectively are referred to as cobalamins.
Cobalamin consists of a heme-like planar corrin ring structure where four pyrrole nitrogens are coordinated to the central cobalt atom. Methylcobalamin occurs naturally in the body and assists in producing red blood cells, DNA and takes part in other physiologic functions. It is found in injections and oral supplements of vitamin B12.
Adenosylcobalamin, an unstable molecule, exists naturally, is required for energy metabolism, and is hard to find in vitamin B12 supplements.
Another natural form of vitamin B12 is hydroxocobalamin (or hydroxocobalamin), it’s considered the most well-tolerated form of all the cobalamins.
It is produced by the bacteria present in the digestive tract and is also available in both injectable and oral forms. Hydroxycobalamin is readily converted into the active forms, adenosylcobalamin, and methylcobalamin, inside the body.
Many have genetic mutations like MTR (methionine synthase) and MTRR (methionine synthase reductase) genetic variants who can’t make this conversion very well and it affects the absorption of cobalamin in the body.
Cyanocobalamin is cheap and the most common form of B12 found in oral, intramuscular, and intravenous vitamin B12 supplements.
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Vitamin B12 is scarcely available in a vegetarian diet. Many bacteria and algae can synthesize cobalamins whereas plants do not absorb cobalamins from the soil and thus, there is little or no vitamin B12 in vegetable sources.
The presence of vitamin B12 is low in milk, dairy and soy products, so they must be consumed in large quantities to meet the daily requirement. Fortified foods are another way to get a source of vitamin B12 into one’s diet (however, it will be almost exclusively in the cyanocobalamin form, which is not well absorbed by most people).
And if we know anything in this day and age, it’s that a large majority of people have ‘gut dysbiosis’. Therefore, absorbing B12 can be almost impossible through the gut for many (especially for those who have genetic complications as well). This is why doctors recommend oral/sublingual routes with ‘active cobalamins’ – that way the mucous membrane under the tongue is leveraged as one of the most optimal ways to absorb cobalamin.
Estimated average requirement (mcg)
Recommended nutrient intake (mcg)
>14 years & Adults
A study has reported the high dose of 2,000 mcg daily oral cyanocobalamin is equal or superior to 1,000 mcg of cyanocobalamin IM injection administered every month for the treatment of vitamin B12 deficiency.
Another study has concluded that 1,000 mcg of oral cyanocobalamin each day in the beginning, later on the weekly dose and followed by monthly are equally effective as 1,000 mcg of IM cyanocobalamin.
Though with limited evidence for satisfactory haematological and neurological responses in patients with vitamin B12 deficiency, both the studies have shown equal efficacy of oral and IM injections.
It has been proved that 69% of 1,000 mcg IM cyanocobalamin has been recovered in the urine after 72 hours, whereas only 27% is found from the same dose of hydroxocobalamin IM injection.
It clearly explains the reason for the equal effectiveness of oral and IM injection of cyanocobalamin. However, a recent study demonstrated that 1,000 mcg sublingual cyanocobalamin preparations are sufficient and even superior to 1,000 mcg IM injections of cyanocobalamin.
The natural forms of vitamin B12- methylcobalamin, hydroxocobalamin, and adenosylcobalamin have been commercially available, and are preferred over cyanocobalamin because they are bioidentical forms occurring in human physiology and animal foods.
A comparative animal study on the effectiveness of methylcobalamin and cyanocobalamin supplementation has reported that urinary excretion of cyanocobalamin was 3 times higher than that of methylcobalamin.
Methylcobalamin supplementation also resulted in 13% more cobalamin storage in the liver than that of cyanocobalamin.
Another study has also reported lower tissue retention and higher urinary excretion from cyanocobalamin supplements as compared to methyl, hydroxy, and adenosylcobalamin.
Therefore, methylcobalamin is the least costly form of natural B12 available at present in most of the multivitamins and B-complex formulas.
The oral administration of 25 or 100 mcg of cyanocobalamin every day could only lower but did not normalize the MMA (mean methylmalonic acid) levels.
However, 1000 mcg daily dosing of cyanocobalamin was able to normalize the MMA concentrations in patients with pernicious anemia.
Another dose-finding trial study shows that the lowest daily dose of oral cyanocobalamin required to normalize the biochemical markers of mild vitamin B12 deficiency varies from 647-1,032 mcg in the elderly.
This dose is more than 200 times higher than the daily recommended dietary allowance for vitamin B12.
Megaloblastic anemia, a sign of either vitamin B12 and/or folate deficiency can be hidden by the ingestion of a large amount of folic acid, but the progressive damage to the nervous system may continue due to the ‘masked’ vitamin B12 deficiency.
High dosage of vitamin B12:
- Chan CQH, Low LL, Lee KH. Oral vitamin B12 Replacement for the Treatment of Pernicious Anemia. Front Med 2016;3:1-6.
- FAO/WHO expert consultation on human vitamin and mineral requirements. Vitamin B12. Chapter-5; 65-72 (http://www.fao.org/3/a-y2809e.pdf).
- Eussen SM, de Groot LM, Clarke R, et al. Oral Cyanocobalamin Supplementation in Older People with Vitamin B12 Deficiency: A Dose-Finding Trial. Arch Intern Med 2005;165:1167-1172.
- Langan RC, Goodbred AJ. Vitamin B12 Deficiency: Recognition and Management. Am Fam Physician 2017;96:384-389.
- Vitamin B12 Fact sheet for consumers. National Institutes of Health Office of dietary supplements; 1-3 (https://ods.od.nih.gov/pdf/factsheets/VitaminB12-Consumer.pdf).
- Shane B. Folate and vitamin B12 metabolism: Overview and interaction with riboflavin, vitamin B6, and polymorphisms. Food Nutr Bull 2008;29:S5-S16.
- Mahmood L. The metabolic processes of folic acid and Vitamin B12 J Health Res Rev 2014;1:5-9.
- Rizzo G, Lagana AS. (2020) A review of vitamin B12. In Patel VB. (Ed.) Molecular Nutrition: Vitamins 105-129 Academic Press.
- Stabler SP. Vitamin B12 N Eng J Med 2013;368:149-160.
- Berlin, H., Berlin, R. Brante, G. Oral Treatment of Pernicious Anemia With High Doses of Vitamin B12 Without Intrinsic Factor. Acta Medica Scandinavica, 1968;184: 247–258.
- Andres E, Goichot B, Schlienger JL. Food cobalamin malabsorption: a usual cause of vitamin B12 Arch Intern Med 2000;160:2061-2.
- Rajan S, Wallace JI, Brodkin KI, Beresford SA, Allen RH, Stabler SP. Response of elevated methylmalonic acid to three dose levels of oral cobalamin in older adults. J Am Geriatr Soc 2002;50:1789-1795.
- Paul C. Comparative Bioavailability and Utilization of Particular Forms of B12 Supplements With Potential to Mitigate B12-related Genetic Polymorphisms. Integr Med 2017;16:42-49.
- Vidal-Alaball J, Butler C, Cannings-John R, Goringe A, Hood K, McCaddon A, McDowell I, Papaionnou A. Oral vitamin B12 versus intramuscular vitamin B12 for vitamin B12 deficiency. Cochrane Database Syst Rev 2005;3: doi: 10.1002/14651858.CD004655.pub2.
- Bensky MJ, Ayalon-Dangur I, Ayalon-Dangur R, Naamany E, Gafter-Gvii A, Koren G, Shiber S. Comparison of sublingual vs. intramuscular administration of vitamin B12 for the treatment of patients with vitamin B12 deficiency. Drug Deliv Transl Res. 2019;9:625‐630.