Vitamin B12

Introduction

Vitamin B12 is usually consumed by food. Vitamin B12 only occurs in animal-based food in sufficient quantity. The risk of vitamin B12 deficiency mainly applies to people who either do not eat much animal based food (e.g. vegetarians) or who cannot absorb the eaten vitamin B12 appropriately (e.g. often occurs in elderly people)1. Vitamin B12 is also known under the name cobalamin1.

Not Enough

The body can store very much vitamin B12 compared to its usage. Therefore, it usually takes years until a deficiency starts showing up2. Vitamin B12 deficiency can lead to brain damage and memory difficulties as well as cognitive problems3. A multi-year chronic deficiency can lead to nerve disorders such as paresthesias, ataxias, reflex disturbances and other neurological problems4.

Too Much

In general, no negative effects of a too high consumption of vitamin B12 are known 5. Too much vitamin B12 is excreted with urine5. There are weak indications of a higher cancer risk and acne5. Even if a too high vitamin B12 dosage does not show negative effects, due to security concerns one should not consume unnecessarily high dosages of vitamin B12 without a reason.

A too high vitamin B12 concentration in the blood should be investigated, because it could be the result of other serious diseases.

Recommended Daily Intake (Total)

The Institute of Medicine (US) recommends around 2.4μg (microgram; one million μg are one gram) for an adult. The details by gender and age are available here. This means the total intake including normal food and supplements together.

Supplements

Often the vitamin B12 intake from food is sufficient.

If there is a deficiency or the risk of a deficiency, then the amount of recommended supplementation is very dependent on the cause of the deficiency.

If there is vitamin B12 deficiency because of insufficient consumption of vitamin B12 containing food (e.g. vegan), then a periodic (1-2x per day) consumption of a moderate amount of B12 can be sufficient.

If there is vitamin B12 deficiency due to malabsorption in the intestine, then much higher dosages of vitamin B12 might be required, because most of it will not be absorbed.

The following table shows the absorption of vitamin B122,6.
Single oral doseNormal absorptionAbsorption problems (e.g. PA)
1 μg0.56 μg (56%)0.01 μg (1.2%)
10 μg1.6 μg (16%)0.1 μg (1.2%)
50 μg1.5 μg (3%)0.6 μg (1.2%)
500 μg9.7 μg (2%)7.0 μg (1.3%)
1000 μg∼ 13 μg (1.3%)∼ 12 μg (1.2%)

As visible in the table, the healthy body can absorb small amounts of vitamin B12 very effectively with a large percentage (e.g. of 1 μg it absorbs 56%). If one gives the body higher doses at once, then the body cannot absorb all of it as well any more (e.g. of 10 μg only 1.6 μg or 16%). That means that possible supplementation is more effective if given often in smaller dosages (1x-2x a day) rather 1x a week.

Also visible is that with absorption issues a much larger quantity of supplementation is required because only around 1.2% is absorbed and the remainder is excreted.

If a person without absorption problems only wants to take a supplement 1x a week, then he also must use higher dosages, because as already discusses, the body can only absorb smaller quantities effectively at once.

Assessment of Status

There are different tests available. Currently, the best test seems to be the urinary methylmalonic acid test. In addition, a Holo-TC II blood test can be made to confirm the results of the urinary methylmalonic acid test.

Urinary Methylmalonic Acid Test
This seems to be the best test currently7. If there is a vitamin B12 deficiency then the values of methylmalonic acid in urine are often elevated.
The results can be interpreted the following way:

Urinary Methylmalonic Acid Test7
<3.6 mmol/mol creatine
(less than 3.6mmol urinary methylmalonic acid per mol creatine)
normal
>3.6 mmol/mol creatine
(more than 3.6mmol urinary methylmalonic acid per mol creatine)
Suspected vitamin B12 deficiency

The urinary test seems to be more accurate than the below also described methylmalonic acid blood test7.

Holo-TC II Blood Test
The Holo-TC II measures the vitamin B12 as Holo-TC II in the blood. This form of vitamin B12 can be used by cells in the body. The normal vitamin B12 blood tests measures all vitamin B12 in the blood, including Holo-TC I, which cannot be used by cells. The Holo-TC II blood tests seems to be better than the normal total vitamin B12 blood test8.

Methylmalonic Acid Blood Test
A high value of methylmalonic acid in the blood is an indication for a vitamin B12 deficiency. The results of this tests may also be elevated due to kidney problems9. It is also possible that the result is elevated due to intestinal bacterial overgrowth9.

Homocysteine Blood Test
A high homocysteine level in the blood if often one of the earliest symptoms of vitamin B12 deficiency4. An elevated value can also be the result of kidney issues9. To exclude kidney problems an additional blood test can be made (creatine)9. A high homocysteine value can also be the result of folate deficiency9.

Normal Vitamin B12 Blood Test
There is a blood test to measure the vitamin B12 in the blood serum. This test gives an indication, but is by itself insufficient. It is not accurate enough. It is possible to have normal vitamin B12 blood levels and deficiency symptoms as well as low blood levels without deficiency symptoms 4. A low-normal blood value (150-300 pmol/L) can, but does not have to, already be accompanied by cognitive problems3.

Other Test
Depending on the situation other tests can also be made that are related to vitamin B12 deficiency. A deficiency might also show up in a hemogram (blood exam). Or one can search for antibodies against the intrinsic factor (body's own helper to absorb vitamin B12).

Natural Sources

Vitamin B12 only occurs in animal-based food and some bacteria4. Meat and fish contain vitamin B12 as well as Milk and eggs4. Plants generally do not contain any4.

For vegetarians with milk and eggs a sufficient intake with food possible, but one should be mindful of it 10. For vegans (vegetarians without milk and without eggs) supplementation is needed or with vitamin B12 fortified food10.


In general plants and mushrooms do not contain any vitamin B12. There are a few special exceptions, for example certain fermented plants, certain mushrooms and algae. But these foods are not suitable to cover one's need for vitamin B12. Examples are:

  • Shiitake mushrooms in dried form contain 4-6μg B12 per 100g11. That would mean a person has to eat 50g of dried shiitake per day.
  • Nori seaweed (Porphyra sp.) contains relatively much B12 with around 25-32μg/100g12. The effects of a daily consumption of this algae are insufficiently researched9.
  • A study revealed that vitamin B-12 from nori or spirulina algae cannot or only ineffectively be used by the body (low bioavailability)13.
  • Sauerkraut can contain vitamin B124. If specific bacteria are added in the production then amounts up to 7.1μg/100g are possible9. That would mean a daily consumption of around 25-50g of this specially produced Sauerkraut.

The content of vitamin B12 can vary significantly depending on the region of the plant or mushroom. Is is also possibly that the vitamin B12 content can vary strongly depending on coincidental factors, for example, coincidentally present bacteria in the sauerkraut production. In addition, it is not known how well the body can absorb and use the vitamin B12 found in these foods. In addition, the recurring consumption of these foods may have unwanted side effects. Therefore, plants and mushrooms are not a realistic and reliable source for sufficient vitamin B12.


In conclusion, only animal-based food (meat, fish, eggs, milk, etc.) can supply the human body reliably with enough vitamin B12. If no animal-based foods are eaten, then supplementation or fortified food is appropriate.

Types of Supplements

Supplements are mainly produced by fermentation with bacteria14.

The following forms of vitamin B12 occur in supplements:

  • Methylcobalamin
  • Adenosylcobalamin
  • Hydroxocobalamin
  • Cyanocobalamin

Methylcobalamin, Adenosylcobalamin and Hydroxocobalamin also occur in natural food (meat, eggs, milk, milk products). Cyanocobalamin is produced synthetically. Which form is best is debated.

Biological Details

The body builds for the vitamin B12 absorption special helper substances with the name "Intrinsic Factor". These help to effectively absorb the small amounts of vitamin B12 contained in food. People with impaired intrinsic-factor-functionality have malabsorption issues.


References

1
Fiona O’Leary, Samir Samman. (2010). Vitamin B12 in Health and Disease. Nutrients, 2(3), 299-316. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3257642/ at 2018-06-25.

2
Carmel, Ralph. (2008). How I treat cobalamin (vitamin B12) deficiency. Blood, 112(6), 2214-2221. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2532799/ at 2018-06-25.

3
Smith, A.D. (2016). Hippocampus as a mediator of the role of vitamin B-12 in memory. The American Journal of Clinical Nutrition, 103(4), 959-960. Retrieved from https://academic.oup.com/ajcn/article/103/4/959/4564639 at 2018-06-25.

4
Eidgenössische Ernährungskommision [EEK]. (2007). Gesundheitliche Vor- und Nachteile einer vegetarischen Ernährung Expertenbericht der Eidgenössischen Ernährungskommission. Retrieved from https://www.eek.admin.ch/dam/eek/de/dokumente/publikation-und-dokumentation/expertenbericht-vegetarische-ernaehrung.pdf.download.pdf/Vegiernaehrung.pdf at 2018-06-22.

5
Institute of Medicine (US) Standing Committee on the Scientific Evaluation of Dietary Reference Intakes and its Panel on Folate, Other B Vitamins, and Choline. (1998). Cover of Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline. Retrieved from https://www.ncbi.nlm.nih.gov/books/NBK114310/ at 2018-06-26.

6
Hans Berlin Ragnar Berlin Gunnar Brante. (1968). ORAL TREATMENT OF PERNICIOUS ANEMIA WITH HIGH DOSES OF VITAMIN B12 WITHOUT INTRINSIC FACTOR . Journal of Internal Medicide, 184(1-6), 247-258. Retrieved from https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.0954-6820.1968.tb02452.x at 2018-06-26.

7
Norman, Eric J. (2004). Urinary Methylmalonic Acid Test May Have Greater Value than the Total Homocysteine Assay for Screening Elderly Individuals for Cobalamin Deficiency. (Letters to the Editor). Clinical Chemistry, 50(8). Retrieved from http://clinchem.aaccjnls.org/content/50/8/1482#ref-6 at 2018-07-22.

8
Carmel, Ralph. (2011). Biomarkers of cobalamin (vitamin B-12) status in the epidemiologic setting: a critical overview of context, applications, and performance characteristics of cobalamin, methylmalonic acid, and holotranscobalamin II. The American Journal of Clinical Nutrition, 94(1), 348-358. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3174853/ at 2018-07-22.

9
Gianluca Rizzo, Antonio Simone Laganà, Agnese Maria Chiara Rapisarda, Gioacchina Maria Grazia La Ferrera, Massimo Buscema, Paola Rossetti, Angela Nigro, Vincenzo Muscia, Gaetano Valenti, Fabrizio Sapia, Giuseppe Sarpietro, Micol Zigarelli, and Salvatore Giovanni Vitale. (2016). Vitamin B12 among Vegetarians: Status, Assessment and Supplementation. Nutrients, 8(12), 767. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5188422/ at 2018-07-17.

10
Eidgenössische Ernährungskommision [EEK]. (2007). Empfehlungen - Gesundheitliche Vor- und Nachteile einer vegetarischen Ernährung. (Eidgenössisches Departement des Innern EDI. Bundesamt für Gesundheit BAG. Direktionsbereich Verbraucherschutz). Retrieved from https://www.eek.admin.ch/dam/eek/de/dokumente/publikation-und-dokumentation/empfehlung-vegetarische-ernaehrung.pdf.download.pdf/Empfehlungen_Gesundheitliche_Effekte_einer_vegetarischen_Ern%C3%A4hrung.pdf at 2018-06-22.

11
Tomohiro Bito, Fei Teng, Noriharu Ohishi, ShigeoTakenaka, Emi Miyamoto, Emi Sakuno, Kazuhisa Terashima, Yukinori Yabuta, Fumio Watanabe. (2014). Characterization of vitamin B12 compounds in the fruiting bodies of shiitake mushroom (Lentinula edodes) and bed logs after fruiting of the mushroom. Mycoscience, 55(6), 462-468. Retrieved from https://www.sciencedirect.com/science/article/pii/S1340354014000102 at 2018-07-17.

12
Watanabe F, Takenaka S, Katsura H, Masumder SA, Abe K, Tamura Y, Nakano Y. (1999). Dried green and purple lavers (Nori) contain substantial amounts of biologically active vitamin B(12) but less of dietary iodine relative to other edible seaweeds. J Agric Food Chem., 47(6), 2341-2343. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/10794633 at 2018-07-17.

13
Dagnelie PC, van Staveren WA, van den Berg H. (1991). Vitamin B-12 from algae appears not to be bioavailable. The American Journal of Clinical Nutrition, 53(3), 695-697. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/2000824 at 2018-07-17.

14
Huan Fang, Jie Kang, and Dawei Zhang. (2017). Microbial production of vitamin B12: a review and future perspectives. Microb Cell Fact, 16. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5282855/ at 2018-07-17.