Vitamin B12 Analogs

Pseudovitamin B12  

Vitamin B12 Analogs

B12 Analogs: Foods like spirulina contain vitamin B12 analogs; pseudovitamin B12, which are similar to real B12 but actually useless and even dangerous.

Vitamin B12 and Vitamin B12 Analogs

Vitamin B12 analogs, also known as pseudovitamin B12, are molecules which have a very similar chemical structure to that of vitamin B12, but which shouldn’t be substituted for consumption. On the contrary, they are potentially harmful, since these molecules replace the important B12 transportmolecules within the body, thus hindering the absorption of actual vitamin B12.

During the initial research phase on vitamin B12, it was difficult to differentiate between vitamin B12 analogs and real vitamin B12, as the tests used were carried out using both forms. However, today it is unequivocally possible to identify B12 analogs in many foods through the use of paper chromatography. This spells the end for many foods which were previously thought to be rich in vitamin B12, but in fact have now been proven to actually contain nothing more than pseudovitamin B12.

This is particularly bad news for vegetarians and vegans, as a natural form of B12 would constitute excellent enrichment and would be a replacement for B12 compounds. Unfortunately, no such natural form could be verified before now. Foods which were reputed or assumed to contain vitamin B12, but which actually contain pseudo-vitamin-B12, include the following examples:

Spirulina1
Nori2
Miso3
Wakame4

In some cases, these are still being marketed as sources of vitamin B12, but experts have shown that they actually worsen a vitamin B12 deficiency in certain instances.5

What are Vitamin B12 Analogs?

Vitamin B12 (cobalamin) is a fairly large molecule which always binds with other molecule groups in the body. The different forms of vitamin B12 are named according to which molecule the B12 bonds to: methylcobalamin is simply cobalamin bound to a methyl group and similarly cyanocobalamin the bond of cobalamin and a cyano group, such as cyanide.

Vitamin B12 functions as a coenzyme in the body, enabling the effect of other enzymes. However, there are only two specific forms of vitamin B12 which are active within the body as such coenzymes:

  • Methylcobalamin 
  • Adenosylcobalamin

Two other cobalamins can be converted into these forms in the body: cyanocobalamin and hydroxocobalamin. They are therefore not directly in operation in the body, but represent good, functional precursors of the active coenzymes.

Moreover, there are some additional forms of cobalamin which the body cannot use, all of which in turn belong to the larger molecule group of corrinoids – molecules, which, like vitamin B12, have a cobalt atom in their nucleus.

Some of these corrinoids have a very similar chemical structure to vitamin B12, yet perform no meaningful functions in the body – on the contrary, they are potentially harmful.6

B12 analogs corrinoids

B12 Analogs: Not Only Useless, but Also Dangerous

Vitamin B12 analogs are so similar to the vitamin in question, that it causes confusion, not only for human research methods, but also for the body itself. The pseudovitamin B12 binds to specific transport molecules which are actually intended for the transport of vitamin B12, whereby they are in direct competition with one another.

Since the capacity of transport molecules is limited, the pseudo vitamin B12 molecules effectively take the places designed for the vitamin B12 molecules, making it more difficult for the body to obtain the real vitamin. Therefore, it stands to reason that the more vitamin B12 analogs we consume, the harder it is for us to obtain authentic vitamin B12.

Various studies show that the B12 analogs are able to bind to all known transport molecules, as well as to intrinsic factor, which is largely responsible for the absorption of B12 from food and even directly onto the corresponding receptors of the intestinal wall.7 Vitamin B12 analogs are thus not only useless, but also harmful.

Even conventional serum tests struggle to differentiate between some pseudo B12 and vitamin B12 in the blood. A deficiency can therefore be present even at very high serum levels. Consequentially, other tests, such as the MMA urine test, are increasingly preferred today.8, 9

Vitamin-B12 and its Analogs: Difficult to Differentiate

Various methods have been developed to measure the vitamin B12 content in a sample; however, almost all of them have failed to distinguish between B12 and its analogs.

Microbiological Assay

Measurement of the success of microorganisms whose growth is reliant on B12 

High
(only low in ochromonas malhamensis)

R Protein Assay

Observation of the amount of B12 which binds to the R protein

High

IF Assay

Observation of the amount of B12 which binds to the intrinsic factor

Low, but present

Radioisotope Dilution Assay (RIDA)

= IF Assay

Low, but present

Paper Chromatography

Analysis of the molecular structure

Analogs can be identified, but only on a molecule by molecule basis

As the table above shows, only paper chromatography can safely determine whether it is a B12 analog or a real vitamin in question, as it examines the molecules directly.

B12 Blood Tests and Pseudovitamin B12

Since the B12 serum test is based on an IF assay, there is no reliable information on the amount of biologically utilizable B12, as it also measures some B12 analogs.

Today there is a subsequent movement towards measuring particular metabolic products, as opposed to measuring vitamin B12 directly, in order to verify the vitamin B12 content of foods and and determine B12 efficiency. This allows for much more reliable information about the actual B12 activity in the body. The gold standard here is the MMA urine test: it can only be safely concluded that a food source contains mainly usable vitamin B12 if it successfully lowers MMA levels.

Vegan Vitamin B12 Sources and Vitamin B12 Analogs

Knowledge of vitamin B12 analogs holds particular importance for the discussion of vegan vitamin B12 sources. Almost all alleged botanical sources of vitamin B12 have been more or less proven to contain far more pseudovitamin B12. 

Algae also produce some interesting results, which show that the fresh plants contain real vitamin B12, but dried algae contain only pseudo-B12.2 The natural process that each plant goes through here as it dries seem to indicate chemical reactions which break down the vitamin B12.

Furthermore, since it is the microorganisms rather than the plants which produce vitamin B12, the ratio of vitamin B12 to analogs can be extremely varied depending on which bacteria are living in the plant’s environment. This can vary from year to year and is the reason why different studies can provide such different results regarding the B12 content of certain plants. The alga chlorella, as an example, can show a very high level of vitamin B12 in one study,10 where other studies can show no B12 whatsoever.11

So far, no natural source which effectively lowers MMA levels has been found. However, other relevant studies on different growing areas and conditions are missing here. Therefore, there is currently no recognized natural source of vitamin B12. On the contrary, scientists warn against using algae as a B12 source, because the pseudo-B12 which could be present could cause issues for the supply of B12 in the body.

Only chlorella, aphanizomenon flos-aquae, dulse and ciccilithophore algae are currently being tested as sources of real vitamin B12. All others have a higher B12 analog content, potentially causing a negative effect on existing vitamin B12 levels.

Sources

1 Watanabe F, Katsura H, Takenaka S, Fujita T, Abe K, Tamura Y, Nakatsuka T, Nakano Y. Pseudovitamin B(12) is the predominant cobamide of an algal health food, spirulina tablets. J Agric Food Chem. 1999 Nov;47(11):4736-41.

2 Yamada K, Yamada Y, Fukuda M, Yamada S. Bioavailability of dried asakusanori (porphyra tenera) as a source of Cobalamin (Vitamin B12). Int J Vitam Nutr Res. 1999 Nov;69(6):412-8

3 Treuesdell, D. D., Green, N. R. and Acosta, P. B. (1987), Vitamin B12 Activity in Miso and Tempeh. Journal of Food Science, 52: 493–494. doi: 10.1111/j.1365-2621.1987.tb06650.x

4 Yamada S, Shibata Y, Takayama M, Narita Y, Sugawara K, Fukuda M. Content and characteristics of vitamin B12 in some seaweeds. J Nutr Sci Vitaminol (Tokyo). 1996 Dec;42(6):497-505.

5 Dagnelie PC, van Staveren WA, van den Berg H. Vitamin B-12 from algae appears not to be bioavailable. Am J Clin Nutr. 1991;53:695-7.

6 Carmel R, Karnaze DS, Weiner JM. Neurologic abnormalities in cobalamin deficiency are associated with higher cobalamin ‘analogue’ values than are hematologic abnormalities. J Lab Clin Med. 1988 Jan;111(1):57-62

7 Bunge MB, Schilling RF. Intrinsic factor studies. VI. Competition for vit. B12 binding sites offered by analogues of the vitamin. Proc Soc Exp Biol Med. 1957 Dec;96(3):587-92. PubMed PMID: 13505799.

8 Murphy, M. F., Sourial, N. A., Burman, J. F., Doyle, D. V., Tabaqchali, S. and Mollin, D. L. (1986), Megaloblastic anaemia due to vitamin B12 deficiency caused by small intestinal bacterial overgrowth: possible role of vitamin B12 analogues. British Journal of Haematology, 62: 7–12. doi: 10.1111/j.1365-2141.1986.tb02894.x

9 J. Fred Kolhouse, M.D., Haruki Kondo, M.D., Nancy C. Allen, R.N., Elaine Podell, A.B., and Robert H. Allen, M.D. „Cobalamin Analogues Are Present in Human Plasma and Can Mask Cobalamin Deficiency because Current Radioisotope Dilution Assays Are Not Specific for True Cobalamin“ N Engl J Med 1978; 299:785-792October 12, 1978DOI: 10.1056/NEJM197810122991501

10 Kittaka-Katsura H, Fujita T, Watanabe F, Nakano Y. Purification and characterization of a corrinoid compound from Chlorella tablets as an algal health food. J Agric Food Chem. 2002 Aug 14;50(17):4994-7

11 Pratt R, Johnson E. Deficiency of vitamin B12 in Chlorella. J Pharm Sci. 1968 Jun;57(6):1040-1




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