B12 NonSoloVegan

By Doctor. Gianluca Rizzo - Nutritionist

One of the most discussed and now most commonly accepted aspects of vegetarian nutrition is the need for vitamin B12 supplementation and its potential risks in deficiency states.

Why is it necessary to integrate the B12?

Cobalamin, the full name of this vitamin, appears to be synthesized exclusively from single-celled organisms and for this reason its version in the form of supplement is called cyanocobalamin (an unequivocal indication of bacterial and non-animal origin), while natural forms are adenosylcobalamin and methylcobalamin. The molecular functions are: transfer of a hydrogen atom between two adjacent carbons, reduction of ribonucleotides in deoxyribonucleotides, intramolecular transfer of a methyl group; in mammals these reactions occur during the synthesis of methionine from homocysteine and in the isomerization of methylmalonyl CoA in SuccinylCoA (with neurological tissue damage in the case of accumulation of intermediates). The interesting thing is that this vitamin is necessary for different metabolic processes in the protist kingdom and in the animal kingdom (in the latter of great importance in nervous districts and red blood cells), but its synthesis is restricted to microorganisms only and this it implies that it cannot be found in plant tissues, let alone in fungi and yeasts, since they do not synthesize it, do not absorb it from the outside and do not use it. It seems, however, that large vegetarian apes, such as gorillas, do not suffer from the absence of this vitamin factor, even though they are unable to synthesize it independently. The most reliable explanation of this phenomenon concerns the use of fruit with its natural bacterial biofilm and therefore with an "invisible" source of cobalamin . This has led some vegetarians to think that the right daily ration of B12 can be obtained by simply not washing the fruit and eating it with the peel (possibly organic products and therefore safer in terms of the potential presence of nitrogen compounds and herbicides of the conventional agriculture). Unfortunately this is not feasible because it must be taken into consideration that the great frugivorous apes are able to eat a very high dose of fruit that allows the accumulation of the relative bacterial cobalamin. Furthermore, they have a much more efficient immune system than ours which allows them to cope with the potential charge of pathogenic microorganisms that can be found on fruit. A bacterial microbiota could populate gastric districts of these primates, representing an additional source of cobalamin. Let us not forget that hygiene standards have allowed humans, after the Middle Ages, to drastically reduce mortality rates and that today, in less well-off countries, the main causes of death are precisely infectious ones. We, like many other animals, have in spite of ourselves the need for a "tank" organism that accumulates B12 to allow us to take it at the concentrations necessary for our health. The organs richer in cobalamin will therefore be represented by liver, kidneys and spleen, districts in which there is a physiological tendency to accumulate vitamin factors, even if cooking will destroy most of them.

Another often proposed theory hypothesizes that, since there is indeed a conspicuous production of B12 within our intestine by the intestinal microbiota, our nutritional requirement is almost nil. Unfortunately this is also erroneous and the demonstration is inherent in the mechanism of absorption of the same vitamin. The B12 before being absorbed is bound by the salivary polypeptide R thanks to the acid pH of the stomach, afterwards it transfers the vitamin to Castle's intrinsic factor which mediates its intestinal absorption at the level of the small intestine. This implies that the cobalamin produced in the large intestine has no hope of being absorbed since there is no local availability of the relevant transport factors. Many animals have the strange behavior of eating stool, which would explain a strategy of recovery of minerals and vitamins synthesized in the terminal tracts of the intestine.

Another theory that must be dispelled is the presence of cyanobacteria associated with marine algae which, ingested by human beings, can be a food source of B12. Also in this case the rule of the tank is valid because only fish can absorb a sufficient amount of active vitamin through marine food (corrinoids), while algae-based foods do not have a high enough level to be a source of B12 for being human or may contain non-active analogues. The presence of plant analogues of cobalamin seems to have a potentially harmful effect because it causes the deactivation of active B12, decreasing its bioavailability, as happens with the analogues of many algae (PE spirulina).

All this absolutely does not want to discourage the vegetarian choice but, on the contrary, stimulate the attention towards the need for a correct integration. Cyanocobalamin supplements derived from bacterial biotechnologies are now available on the market that allow a correct integration program and an effective prevention of possible deficiencies.

Daily requirement of Vitamin B12

The daily requirement is 2-2.5 µg per day but for supplementation we generally recommend a dose of 10 µg from supplements or 2 µg total per day from fortified foods. Too high doses can significantly reduce the bioavailability due to the absence of intrinsic factor. In any case, the vitamin is highly thermolabile so even omnivores should not underestimate it in cases of potential shortage. Integration is fundamental at various stages of life and should never be underestimated. In pediatric age there is a strong need for this vitamin in order to allow a correct cell expansion during the growth phase. We must keep in mind that even in gestation and lactation, a correct balance of B12 in the mother allows the fetus or newborn to have a regular intake, not having in these phases another vitamin source outside the maternal one.

In adulthood, B12 participates in the removal of homocysteine, a potentially harmful molecule for the cardio-vascular system and the brain district.

Even in old age, but not only for vegetarians, cobalamin becomes a very important factor for a correct homeostasis since in this phase of life it is easy to manifest latent deficiencies or dependent on common senile malnutrition, and pathologies closely associated also to the same homocysteine, as recently discovered for Parkinson's. It seems that this molecule can disrupt the cerebral microvenous fitness while the hypomethylation of DNA due to B12 deficiency may favor alterations in the neurotransmitter inter-synaptic communication systems. In old age the subclinical deficiency can act subtly due to insufficient intake, alterations in absorption, achlorhydria or alterations in the production of intrinsic factor.

Obviously the more the vegetarian diet will be restrictive and the more attention must be paid to this possible deficiency; this is because vegan ovo-latto, having access to foods rich in B12 on average, may not need integration, while vegans, having no animal sources, will necessarily have to use supplements. This means that, while international publications have highlighted the advantages of a vegetarian diet for cardiovascular fitness, the shadow of hyperhomocysteinemia due to B12 deficiency could nullify them, increasing the risk of coronary heart disease.

Vitamin B12 deficiency: Diagnosis and blood test

Another aspect that can be useful to investigate is represented by the diagnostic systems available for detecting the possible deficiencies of cobalamin . The most commonly used method is the total cobalamin dosage but, for some time now, the scientific community has shown that this may be an index that is not very sensitive to the real condition of the disease. Added to this is the fact that the need for B12 in humans is very low and our body is able to effectively save the important vitamin so as not to require large quantities with the diet. This implies at the same time that the state of deficiency is subtle and with a slow action that can manifest itself with serious consequences in an unexpected and irreversible way even after 5 - 10 years of dietary deficiency. In fact, the lack of vitamin B12 is the first cause of megaloblastic anemia also known as pernicious due to its characteristics, as well as other important effects on central and peripheral neuronal demyelination that can lead to potential neuropsychiatric disorders.

Much more sensitive diagnostic targets are represented by the dosage of olotranscobalamina II, methylmalonic acid and homocysteine.

Holotranscobalamina II represents the active cobalamin fraction, linked to the transcobalamin II transport factor which aims to distribute the vitamin to the various districts. It has a short half-life (6 'versus 6 days of total B12), represents no more than 30% of all cobalamin and has been experimentally demonstrated that cellular membrane receptors for the incorporation of the complex are ubiquitous. Most of the absorbed cobalamin is bound to the aptocorrin, a transport protein that does not seem to have the function of distributing the vitamin to various districts but of mediating a scavenger function through theoretical retrograde transport to the liver, perhaps of harmful analogues, the hepatocytes being the only cells that have the relative membrane receptor for the internalization of the B12-aptocorrine complex. The detection of holotranscobalamina II (holoTCII) correlates much more effectively with vitamin deficiency than total B12.

Homocysteine (HCY) represents a metabolic intermediate of the synthesis pathway of methionine. For this conversion, the participation of vitamin factors such as folic acid (B9), pyridoxine (B6) and cobalamin (B12) is essential. In the absence of these vitamins, the biochemical pathway leads to accumulation of HCY which has been defined as an independent risk index for cardiovascular and coronary diseases. Homocysteine levels may increase both due to genetic predisposition and vitamin deficiency of the aforementioned factors and also in case of renal damage or unhealthy habits and use of drugs, but monitoring over time can exclude genetic origin. As for omnivores, high levels of HCY can probably depend on deficiencies of B6, B9 and B12 while in vegetarians, whose diet is very rich in folate and pyridoxine, HCY levels correlate much better with B12 levels (correlation reverse). On the other hand, the strong availability of B9 among vegetarians takes part in the phenomenon called the Folate Trap in which the metabolic pathway is pushed by the low availability of B12, decreasing the levels of HCY through conversion to cysteine. The large availability of folate acts as an acceptor of methyl groups, being transformed into methyltetrahydrofolate (5-MTHF) which, can no longer be reconverted due to the absence of cobalamin, accumulating in this form. The accumulation of MTHF inhibits the transmethylation of S-adenosylmethionine (SAM) which pushes further towards the synthesis of cysteine. In vegetarians, high levels of homocysteine can coexist in conjunction with high levels of folates that do not necessarily indicate adequate subcellular levels of b9 due to the aforementioned mechanism, but may partly compensate for hyperhomocysteinemia. In the case of kidney damage the homocysteine levels can be increased independently of vitamin deficiencies and a condition of hyperhomocysteinemia has been detected among smokers, due to the nitrites and cyanates derived from cigarette smoke that inactivate serum B12.

Methylmalonic acid (MMA) represents a by-product derived from the incomplete degradation of fatty acids to odd coals. This route is very important because β-oxidation, via the catabolism of fatty acids, manages to use only molecules with two carbon atoms. To completely degrade the odd chain fatty acids, one must necessarily follow the alternative pathway leading to the formation of succinyl-CoA from proprionyl-CoA through three steps, the last of which involves cyanocobalamin as a cofactor of the methylmalonyl-CoA mutase enzyme. In the absence of B12 the way is blocked and the MMA intermediate accumulates. Unfortunately the detection of methylmalonic acid cannot be carried out through cheap and rapid diagnostic systems but through complex mass spectrometry systems that make it unusable as a routine diagnostic system of choice. Furthermore, elevated levels may depend on possible kidney damage and intestinal bacterial overgrowth that can cause increased levels of MMA, as established in studies on Indian individuals from the Asian continent with high levels of MMA and normal levels of cobalamin and holoTCII.

From these data it is easy to see that the diagnosis must always be made by an informed medical staff who is able to interpret the picture described by the results, together with the anamnestic information such as eating habits, renal function with creatinine, correct intestinal function and overall cardiovascular risk.

The B12 deficiency stages have been divided into 4 degrees. The first two are characterized by mild plasma deficiency and decreased cellular reserves, but with total B12 levels in the physiological range, while it can be found in holoTCII levels. In the third stage a functional deficiency can already be detected with an increase in MMA and HCY. In the fourth stage a lowering of cobalamin levels below the physiological range is already noticeable but with the possible establishment of irreversible conditions affecting the nervous tissue and red blood cells, with lowering of hemoglobin levels and alteration of the erythrocyte volume. It is therefore understandable the importance of a diagnostic system that allows to detect the condition of deficiency before a situation that is difficult to recover is created. It can thus be easily deduced that low levels of holoTCII alone do not allow to distinguish between the 4 stages, while normal levels of MMA and HCY do not exclude the possibility of I or II stage; this clearly indicates that no single index can have the prognostic value of the complete picture of the relative levels .

In studies on the correlation between diet and B12 deposits, a gradual deficiency has been noted that increases from omnivores towards vegan ovo latto to vegans and raw foodists . For example, in one study, B12 levels of 1%, 26%, and 52% were found below the physiological values in vegan and vegan omnivores, ovo lattoos respectively, with holoTCII levels of 11%, 73% and 90 % below physiological values, and MMA levels increased by 5%, 61% and 86%. The correlation between the total B12 and holoTCII is greater at higher values while at lower values it loses significance; this implies that in the vegetarian individual a functional deficiency may already be present at medium-low levels of total cobalamin and for this reason some researchers propose to restrict the physiological range for vegetarians above 360 pmol / L of B12. Based on similar correlation curves, holoTCII levels above 50 pmol / L may be a good index of vitamin reserves while below this level in vegetarians, although in the physiological range, comparison with others would still be recommended indices.

The control of the early indices of cobalamin deficiency is fundamental for all asymptomatic subjects and with B12 levels in the norm but belonging to risk categories . These categories do not only concern vegan individuals but also elderly and smokers (as mentioned), as well as obese (altered vitamin absorption), women in estroprogestinica therapy (hormonal alteration), sports (increased metabolism), individuals with gastric resection (achlorhydria and malabsorption), celiacs, individuals with IBD and diseases affecting the gastro-intestinal tract, alcoholics and drug addicts or simply on continuous drug therapy (malabsorption).

Physiological ranges - Blood analysis

B12:> 135 pmol / L
holoTCII:> 35 pmol/L
MMA: <271nmol / L
HCY: <13 umo / L

Essential bibliography

Arch Neurol. 1998 Nov; 55 (11): 1449-55. Folate, vitamin B12, and serum total homocysteine levels in confirmed Alzheimer disease. Clarke R, Smith AD, Jobst KA, Refsum H, Sutton L, Ueland PM.
Clin Chim Acta. 2002 Dec; 326 (1-2): 47-59. Vegetarian lifestyle and monitoring of vitamin B-12 status. Herrmann W, Geisel J.
Am J Clin Nutr. 2003 Jul; 78 (1): 131-6. Vitamin B-12 status, particularly holotranscobalamin II and methylmalonic acid concentrations, and hyperhomocysteinemia in vegetarians. Herrmann W, Schorr H, Obeid R, Geisel J.
Clin Chem. 2003 Dec; 49 (12): 2076-8. Holotranscobalamin as an indicator of dietary vitamin B12 deficiency. Lloyd-Wright Z, Hvas AM, Møller J, Sanders TA, Nexø E.
Journal of clinical ligand assay. - ISSN 1081-1672. - 13: 3 (2008), pp. 243-249. Preclinical deficiency status of vitamin B12 in asymptomatic subjects: importance of olotranscobalamin dosage (active vitamin B12). Novembrino C, De Giuseppe R, Uva V, Bonara P, Moscato G, Galli C, Maiavacca R, Bamonti F.
Clinical Biochemistry 2009; 33 (5) 306. Determination of serum olotranscobalamina: analytical evaluation and role in asymptomatic smokers. De Giuseppe R, Uva V, Novembrino C, Accinni R, Della Noce C, Gregori D, Lonati S, Maiavacca R, Schiraldi G, Bonara P, Bamonti F.
Meat Sci. 2013 Mar; 93 (3): 586-92. doi: 10.1016 / j.meatsci.2012.09.018. Epub 2012 Oct 31. Meat nutritional composition and nutritive role in the human diet. Pereira PM, Vicente AF.