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Intestinal absorption and concurrent chemical changes of methylcobalamin

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Abstract

Intestinal absorption of 14CH3- and/or 57Co-methylcobalamin (CH3-B12) was studied with regard to chemical changes. It was found that absorption of a physiologic dose of CH3-B12-57Co in the rat was the same as that of cyanocobalamin (CN-B12) in quantity and speed, but more radioactivity accumulated in liver after 8 hours, indicating a gradual conversion of CH3-B12 to hydroxocobalamin and cobamide coenzyme. Schilling test with CH3-B12-57Co yielded urinary excretion about 1 3 that with CN-B12-57Co, and similar changes of CH3-B12 in human body were suggested. In the rat, expiration of 14CO2 following oral administration of 14CH3-B12 was small, as contrasted by quick and massive evolution of 14CO2 when photolyzed 14CH3-B12 was given. With supraphysiologic doses, more than 60 per cent of 14C disappeared from the gastrointestinal tract in 2 to 3 hours, suggesting instability of free CH3-B12, and there was a distinct difference in tissue distribution between 14C and 57Co following administration of 14CH3-B12-57Co. It seems, therefore, that cleavage of -CH3 in vivo is different in mechanism from that in vitro or after photolysis. Paper chromatography of digested ileal mucosa obtained after oral administration of a small dose of CH3-B12-57Co, demonstrated unchanged CH3-B12 and some other cobamides. It is concluded that in the alimentary tract, free CH3-B12 is labile and loses CH3 progressively. However, in a physiologic situation where intrinsic factor is operative, CH3-B12 may be partially protected by it from such chemical changes.

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... Although absorption in the blood of the 2 B 12 forms was similar, the study found that MeCbl supplementation caused 13% more cobalamin to be stored in the liver than did CNCbl supplementation. 7 Chalmers 8 reviewed the results of 3 human studies that also found lower tissue retention of B 12 as a result of supplementation with CNCbl rather than OHCbl, MeCbl, or AdCbl, together with increased urinary excretion of CNCbl. The researchers concluded that the lower bioavailability of CNCbl was due to its lower efficiency in cellular uptake and metabolic activation. ...
... 21 CNCbl absorption was also found to be similar to that of MeCbl in an animal study. 7 Unlike vitamin B 12 found in food, supplemental B 12 is not bound to protein; therefore, it readily binds to HC, and it is also available for direct absorption by diffusion. The supplement's delivery system may be a sublingual lozenge, a liquid, or a capsule or tablet that is meant to open up in the stomach or lower intestinal tract. ...
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Context: Three natural forms of vitamin B12 are commercially available: methylcobalamin (MeCbl), adenosylcobalamin (AdCbl), and hydroxycobalamin (OHCbl), all of which have been shown in clinical studies to improve vitamin B12 status. They are bioidentical to the B12 forms occurring in human physiology and animal foods. In contrast, cyanocobalamin (CNCbl), a synthetic B12 compound used for food fortification and in some supplements, occurs only in trace amounts in human tissues as a result of cyanide intake from smoking or other sources. Objective: This study had 3 objectives: (1) To summarize and compare assimilation pathways for 4 B12 forms; (2) to determine whether supplementation with a particular B12 form (or combination of forms) presents any advantages for the general population or for individuals with single nucleotide polymorphisms (SNPs) in B12-related pathways; and (3) to address misconceptions regarding B12 forms, methylation pathways, and various SNPs reported in commercially available tests. Design: PubMed was systematically searched for articles published up to June 2016 using specific key words. Human, animal, and in vitro studies that were published in English, French, and German were included. Other studies considered were found by selecting in PubMed the suggested "related studies" and also some referenced studies. Setting: The study occurred in Los Angeles, CA, USA. Results: The studies reviewed provide evidence that all supplemental or food-derived B12 forms are reduced to a core cobalamin molecule, which converts to the intracellular active forms: MeCbl and AdCbl, in a ratio not influenced by the form of B12 ingested. The methyl and adenosyl components of supplemental MeCbl and AdCbl are cleaved inside cells and are not used in the synthesis of intracellular MeCbl and AdCbl, respectively. However, the overall bioavailability of each form of supplemental B12 may be influenced by many factors such as gastrointestinal pathologies, age, and genetics. Polymorphisms on B12-related pathways may affect the efficiency of absorption, blood transport, cellular uptake, and intracellular transformations. Conclusions: Supplementing with any of the nature bioidentical forms of B12 (MeCbl, OHCbl, and/or AdCbl) is preferred instead of the use of CNCbl, owing to their superior bioavailability and safety. For the majority of the population, all B12 forms may likely have similar bioavailabilities and physiological effects; thus, it makes sense to employ the least-expensive form of B12, such as MeCbl. Individuals with particular single nucleotide polymorphisms (SNPs) affecting B12 assimilation may raise their B12 status more efficiently with 1 or more particular forms of vitamin B12. However, because those types of SNPs are not currently reported in commercial tests, individuals may require either a trial-and-error approach by supplementing with 1 particular form of B12 at a time, or they might simply use a supplement with a combination of all 3 naturally occurring forms of B12 that are commercially available for a better chance of achieving faster clinical results. That approach may or may not offset genetic polymorphisms involving B12 metabolism and related pathways.
... However, the use of a specific vitamin B 12 form, namely OHCbl, is advantageous in individuals with a genetic disorder of the intracellular vitamin B 12 metabolism [28,85]. Moreover, there is a growing body of research demonstrating lower tissue retention, higher urinary excretion, and, consequently, lower overall bioavailability of vitamin B 12 , supplemented in the form of CNCbl, compared to OHCbl, MeCbl, and AdoCbl [85,110,111]. Additionally, some researchers suggest the use of natural vitamin B 12 forms (OHCbl, MeCbl, or AdoCbl) instead of CNCbl for its long-term supplementations to avoid the accumulation of cyanide in human tissues, which is especially important for smokers, as tobacco smoke is one of the major sources of cyanide [85,[112][113][114]. Consequently, there is an evident trend of the replacement of CNCbl supplements, which were previously almost exclusively found on the market, with its natural forms, especially MeCbl, presumably because of its cost-effectiveness [85]. ...
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Vitamin B12, also known as the anti-pernicious anemia factor, is an essential micronutrient totally dependent on dietary sources that is commonly integrated with food supplements. Four vitamin B12 forms—cyanocobalamin, hydroxocobalamin, 5′-deoxyadenosylcobalamin, and methylcobalamin—are currently used for supplementation and, here, we provide an overview of their biochemical role, bioavailability, and efficacy in different dosage forms. Since the effective quantity of vitamin B12 depends on the stability of the different forms, we further provide a review of their main reactivity and stability under exposure to various environmental factors (e.g., temperature, pH, light) and the presence of some typical interacting compounds (oxidants, reductants, and other water-soluble vitamins). Further, we explore how the manufacturing process and storage affect B12 stability in foods, food supplements, and medicines and provide a summary of the data published to date on the content-related quality of vitamin B12 products on the market. We also provide an overview of the approaches toward their stabilization, including minimization of the destabilizing factors, addition of proper stabilizers, or application of some (innovative) technological processes that could be implemented and contribute to the production of high-quality vitamin B12 products.
... Several methods has been reported for estimation for individual drugs. Dulo can be quantified by spctrophotometric method [6 ],RP-HPLC including solid phase extraction , GC-NPD and GC-MS [7][8][9][10][11][12][13], Similarly literature are available for the quantification of methylcobalamin by HPLC [14][15][16][17][18][19][20][21][22][23][24][25][26].Though the combination of Dulo and CH 3 B 12 is available in the market, at present simultaneous determination is not yet reported in the literature. The developed analytical approaches were applied to the estimation of synthetic mixtures consisting of Dulo and CH 3 B 12. ...
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... One study identified that the percent of absorption of 1 mcg of cyanCbl was 49%, while the identical amount of methylCbl was 44% (28). In contrast, other studies have shown that cyanCbl is excreted 3 times more in the urine than meth-ylCbl, which may indicate that methylCbl is better retained in the body (29). There are also studies that showed that differences in bioavailability are insignificant and that, in fact, there are other factors involved (e.g., age or genetics) (7,30). ...
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Plant-based nutrition has become extremely popular in the contemporary era. Its positive effects are sustained by many studies, but one of its risks is that it is almost completely devoid of vitamin B12. In the present study, we analyzed the effects of two types of vitamin B12 supplements, cyancobalamin and methylcobalamin on the level of active serum vitamin (holotranscobalamin) in a group of Romanian individuals (n=42) following a (vegan) plant-based diet. The results revealed that cyancobalamin gives better results in maintaining B12, as quantified by the holotranscobalamin value (median=150 pcg/l) when compared with methylcobalamin (median=78.5 pcg/l). The frequency of administration, regardless of the quantity in one dose, is another important factor in maintaining the holotranscobalamin level within suitable limits. More frequent intakes give more optimal results. Vegans trying to supplement with alternative products (algae, kombucha, other fermented products), had the lowest levels of holotranscobalamin, always bellow the recommended level of 35 pcg/l (median=29 pcg/l). Vegans must be educated on B12 supplementation, about the pharmaceutical forms on the market and their performances and on choosing the optimal plan in order to avoid the onset of B12 deficiency.
... Cyanocobalamin is a man-made form of Vitamin B 12 that normally occurs only in trace amounts in human tissue, particularly in smokers (Paul and Brady, 2017). While all forms of vitamin B 12 -naturally occurring adenosylcobalamin and hydroxycobalamin and the man-made form cyanocobalaminare absorbed with similar efficiency (Paul and Brady, 2017), a potential concern with meeting B 12 requirements through cyanocobalamin is that its tissue retention rates, and subsequent metabolic activity, are reduced compared to naturally occurring forms of B 12 (Glass et al., 1961;Hertz et al., 1964;Okuda et al., 1973;Paul and Brady, 2017). Additionally, the B 12 found in animal foods is protein-bound and therefore partially protected from light degradation (Linnell and Matthews, 1984). ...
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There is wide scale concern about the effects of red meat on human health and climate change. Plant-based meat alternatives, designed to mimic the sensory experience and nutritional value of red meat, have recently been introduced into consumer markets. Plant-based meats are marketed under the premise of environmental and human health benefits and are aimed appeal to a broad consumer base. Meat production is critiqued for its overuse of water supplies, landscape degradation, and greenhouse gas emission, and depending on production practices, environmental footprints may be lower with plant-based meat alternatives. Life-cycle analyses suggest that the novel plant-based meat alternatives have an environmental footprint that may be lower than beef finished in feedlots, but higher than beef raised on well-managed pastures. In this review, we discuss the nutritional and ecological impacts of eating plant-based meat alternatives vs. animal meats. Most humans fall on a spectrum of omnivory: they satisfy some nutrient requirements better from plant foods, while needs for other nutrients are met more readily from animal foods. Animal foods also facilitate the uptake of several plant-derived nutrients (zinc and iron), while plant nutrients can offer protection against potentially harmful compounds in cooked meat. Thus, plant and animal foods operate in symbiotic ways to improve human health. The mimicking of animal foods using isolated plant proteins, fats, vitamins, and minerals likely underestimates the true nutritional complexity of whole foods in their natural state, which contain hundreds to thousands of nutrients that impact human health. Novel plant-based meat alternatives should arguably be treated as meat alternatives in terms of sensory experience, but not as true meat replacements in terms of nutrition. If consumers wish to replace some of their meat with plant-based alternatives in the diet (a “flexitarian approach”) this is unlikely to negatively impact their overall nutrient status, but this also depends on what other foods are in their diet and the life stage of the individual.
... Secondly, the conclusion assumes that the form of vitamin B,, ingested in food is the form which is presented to the absorbing site, and this is doubtful. There is evidence that crystalline methylcobalamin in supraphysiological amounts is converted to other cobalamins, at least in the rat intestine (Okuda, Yashima, Kitazaki & Takara, 1973) and the results of in vitro studies suggest that hydroxocobalamin can be converted to sulphitocobalamin in the upper region of the gastrointestinal tract (Farquharson & Adams, unpublished results). These points are relevant to the problem of estimating the capacity to absorb vitamin B,,. ...
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Current Clinical Management Guidelines of Diabetic Peripheral Neuropathy (DPN) are based on adequate glucose control and symptomatic pain relief. However, meticulous glycemic control could delay the onset or slow the progression of diabetic neuropathy in patients with DM type 2, but it does not completely prevent the progression of the disease. Complications of DPN as it continues its natural course, produce increasing pain and discomfort, loss of sensation, ulcers, infections, amputations and even death. In addition to the increased suffering, disability and loss of productivity, there is a very significant economic impact related to the treatment of DPN and its complications. In USA alone, it has been estimated that there are more than 5,000,000 patients suffering from DPN and the total annual cost of treating the disease and its complications is over $10,000 million dollars. In order to be able to reduce complications of DPN, it is crucial to improve or correct the metabolic conditions that lead to the pathology present in this condition. Pathophysiologic mechanisms implicated in diabetic neuropathy include: increased polyol pathway with accumulation of sorbitol and reduced Na+/K+-ATPase activity, microvascular damage and hypoxia due to nitric oxide deficit and increased oxygen free radical activity. Moreover, there is a decrease in glutathione and increase in homocysteine. Clinical trials in the last two decades have demonstrated that the use of specific nutrients can correct some of these metabolic derangements, improving symptom control and providing further benefits such as improved sensorium, blood flow and nerve regeneration. We will discuss the evidence on lipoic acid, acetyl-L-carnitine, benfotiamine and the combination of active B vitamins L-methylfolate, methylcobalamin and piridoxal-6-phosphate. In addition, we discuss the role of metformin, an important drug in the management of diabetes, and the presence of specific polymorphic genes, in the risk of developing DPN and how metabolic correction can reduce these risks.
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Article
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Article
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Article
A technique to prepare an intestinal loop in situ in rats is described for the study of the effect of intrinsic factor (IF) on the absorption of vitamin B 12 and of the site of absorption. It was found that a) the site of absorption of vitamin B 12 is the smal intestine and, particularly, the middle portion; b) a saline extract of rat stomach mucosa, as well as rat gastric juice, when mixed with a low test dose of vitamin B 12 , markedly increased the absorption of vitamin B 12 by the loop. A quantitative relationship was demonstrated between absorption and vitamin B 12 -binding power of such an extract. However, a purified hog IF did not enhance the absorption of vitamin B 12 and c) two different mechanisms for the absorption of vitamin B 12 are suggested. One operates when a small physiological dose is administered; the absorption can be enhanced by co-administration of IF and be inhibited by ethylenediaminetetraacetate (EDTA). The other operates when a high dose is given; the absorption under such conditions is not affected either way by the administration of IF or EDTA.
Article
Intestinal absorption of Co58-labeled vit. B12 coenzyme (5,6-dimethylbenzimidazolyl cobamide) was studied in comparison with Co60-cyanocobalamin in rats. The results indicate that (a) quantitatively, absorption of orally administered coenzyme is about the same as that of cyanocobalamin. (b) Absorption of the coenzyme from the small intestine as determined by the “loop” technic is markedly enhanced by rat intrinsic factor and to the same extent as with cyanocobalamin. (c) There is no demonstrable preference in absorption between the 2 compounds when both are mixed and coadministered. (d) Slightly less of the absorbed radioactive coenzyme is flushed out in the urine by a large parenteral dose of unlabeled compound as compared with radioactive cyanocobalamin. These findings show that coenzyme behaves much like cyanocobalamin in intestinal absorption, quantitatively as well as in mechanism.