B12 Deficiency And Hypothyroidism

Amazoniac

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- Vitamin B12 among Vegetarians: Status, Assessment and Supplementation

"A common mistake is to think that the presence of dairy products and eggs in the diet, as in LOV [Library of Virginia], can still ensure a proper intake of Cbl, despite excluding animal flesh. In reality, consumption of such foods, despite containing significant amounts of Cbl, would be sufficient neither on a daily basis nor in order to meet vitamin requirements [18].[*] A Dietary Reference Intake (DRI) of 2.4 μg/day for Cbl in adults is a common chosen value [19,20]. Such an amount is apparently exceeded by American adults, with a mean intake ranging from 4.6 to 6.3 μg/day [21]. However, it is not uncommon to see a moderate deficiency among omnivores in Western countries [22,23]. A recent report by the European Food Safety Authority (EFSA) Panel on Dietetic Products, Nutrition and Allergies established an Adequate Intake (AI) of 4 μg/day for adults, with a mean intake in European countries ranging between 4.2 and 8.6 μg/day [24]."

*This doesn't seem too unlikely given that milk is meant to be ingested as a sole food throughout the day in small amounts at a time.​
"The main source of consumption in the general population comes from animal foods with a significant contribution from milk and dairy products [25]. Losses of up to 50% can occur through food processing which involves cooking, pasteurization and exposure to fluorescent light. This limits its availability, together with a drop in absorption capacity and an increase in Cbl concentration in food [26]. Some researchers claim that the currently recommended intake levels may not be sufficient for an adequate daily intake, with particular regard to aging and the physiological reduction in absorptive capacity [27]. With senescence, the epithelial cells of the stomach reduce their ability to biosynthesize the transporter proteins of Cbl. The gastric secretion ability is necessary both for the dissociation of Cbl from foods and for the binding to the carriers [28]. For these reasons, the American Institute of Medicine recommends a supplementation of Cbl for people of 50 years of age and older [19]. The development of blood and cognitive disorders are rather common aspects found among the elderly population [29].

In the vegetarian diet, there are few sources of Cbl, whilst supplement use is frequently resisted.

Although some plant foods seem to represent a significant source of Cbl [30,31], data in the literature are still insufficient to determine whether Cbl is found in the active form, and whether regular consumption of these foods can be sustainable when the variability in the production processes is taken into account."

"In the cell, the Cbl isoforms are metabolized inside the peroxisome by the reactions of dealkylation, decyanation and reduction, and then released in the specific cell compartment as coenzyme Me-Cbl and Ado-Cbl, according to their cytosolic or mitochondrial fate, respectively [46]. This step is crucial in the activation of the provitamin forms. Other corrinoid compounds do not fulfill the vitamin functions, in all probability due to the binding power of the lower ligand with the cobalt, which does not allow peroxisome activation [45]. It seems that all isoforms, provitamins and coenzymes should follow a mandatory route before being assigned to the appropriate cell district. However, the H-Cbl form may be more reactive, and its use can be facilitated by a number of enzymatic processes through non-specific cellular reactions [47]. If this mechanism were confirmed, the use of already active Cbl cofactors would not represent any provitamin advantage [45]. In 1982, Gimsing et al. analyzed Cbl in tissues from patients with pernicious anemia. After administration of H-Cbl or Cn-Cbl, they found that detected plasma Cbl was dependent on the form administered, dominant in the blood pattern. Results from erythrocytes and liver biopsies showed no differences, irrespective of the Cbl form used, indicating that administered Cbl preparations are converted in vivo to the necessary coenzymes [48]. Although current studies have many limitations and altogether there are no significant differences, the retention percentage after oral ingestion may change between different forms [49]. Following the ingestion of 1 μg of Cbl, the retention of Ado-Cbl and H-Cbl is 34% and 56%, respectively. Following the ingestion of 5 μg of Cbl, the retention of Ado-Cbl and Cn-Cbl is 13% and 20%, respectively. Following the ingestion of 25 μg of Cbl, the retention of Cn-Cbl and Ado-Cbl is 6% and 8%, respectively [50]. Updated data are not currently available."

"Supplementation is often avoided due to preconceptions and aversion to products which are thought to be artificial, or due to the myth that the shortage will manifest itself only in rare cases after many years of ceased intake, an idea also supported by some researchers [115]. Although the shortage is documented in the macrobiotic community, many feel reluctant to use supplements, fortified foods, and more generally, processed foodstuffs [116]."

"The concomitant use of more specific markers enables a more detailed diagnosis. In adult German vegetarians, Cbl deficiency was present in 58%–66% or 61%–72% of participants if both criteria HTCII/MMA or HTCII alone were adopted, respectively [84,91,93,95]."

"Although in the past it was thought that only [vegans] were at risk of vitamin deficiencies, recent studies indicate that even the [lacto and ovo and vegetarians] are at risk [125,126,127]. Herrmann et al. found that deficiency rates among LOV/LV and VN were 32% and 43%, respectively [85]. Supplementation in LOV/LV was effective in reducing deficiency rates from 68% to 31%, but the amounts were still insufficient [18]. Also the increase of MCV and RDW, associated with the lack of Cbl, leads to the increased cardiovascular risk [128,129]. Neurological manifestations of vitamin deficiency can also occur in the absence of anemia [130]."

"Supplements have been demonstrated as efficient in the restoration of Cbl blood concentration [97,138]. Currently, the official position of associations and government agencies is categorical and unequivocal: in the case of a vegetarian diet, including LOV, LV and OV, supplementation of Cbl is required [11,13]. Cbl concentration per 100 g of cow’s milk, dairy products and chicken eggs ranged from 0.5 to 0.4 μg, from 4.2 to 3.6 μg, and from 2.5 to 1.1 μg, respectively [139,140]. Taking into account the losses during cooking and the specific absorption rate, these quantities are not sufficient to ensure the daily intake in a balanced diet [141]."

"Its safety has been demonstrated through the use of an ultra-high parenteral dose of 25 mg daily for 10 days followed by 25 mg monthly for five months [150]." :skull:

"The therapeutic administration of oral Cbl has proven to be as effective as intramuscular administration [152]. This is very useful, as intramuscular administration is far more expensive and rather painful for the patient, as well as not being free from complications [153]."

"Since the crystalline form of Cbl is not bound to food proteins, the bioavailability in supplements is equal, if not superior."

"The vegetarian diet is very high in fiber, which may reduce the ability to absorb some nutrients efficiently [156]. An excess of fiber in the diet could disrupt the re-absorption of the Cbl mechanism through enterohepatic circulation, although there is no evidence to confirm that this happens in humans [157]."

"The consumption of oral doses of 1 μg, 10 μg, 50 μg, 500 μg, 1000 μg, are absorbed with an efficiency of 56%, 16%, 3%, 2%, 1.3%, respectively [151]."

"Using multivitamins can be inefficient and counterproductive for the supplementation of Cbl. The Cbl can be degraded in the presence of vitamin C and copper with the formation of inactive by-products. These compounds can inhibit the transport system interacting with transporter proteins [172,173]. Nutritional yeast fortified with Cbl is available in the USA, though its use may be less effective than supplements, in the case of deficiency [97]."

"[..]an Italian study has shown that selected types of oyster mushrooms grown in the southern areas of Italy show a wide range of concentrations of Cbl from 0.44 to 1.93 μg/100 g, as detected by ELISA immunoassay. The highest concentration was found in the species Pleurotus nebrodalis, typical of the mountain areas in central Sicily [176]. Less common mushrooms such as Craterellus cornucopioides or Cantharellus cibarius may contain 1.09–2.65 μg/100 g [177]. Shiitake mushrooms, popular among vegetarians, can contain up to 5.61 ± 3.9 μg of Cbl per 100 g of dry weight (mostly in active form), although with great variability [178]. Even in this case, although a portion of 50 g of dried shiitake could be adequate to achieve the daily requirement, it is unlikely that this will happen daily. Among the most widely used edible seaweeds, Enteromorpha sp. and Porphyra sp. (also known as nori) contain relevant amounts of Cbl ranging from 32.3 to 63.6 μg/100 g [179]. In vitro tests are promising, but there are not enough human clinical trials to consider the use of seaweed as favorable in vitamin provision [180,181]. In a clinical trial of six vegan children, the daily use of nori seaweed seemed to prevent Cbl deficiency, measured via serum Cbl [182]. In disagreement with these data, Dagnelie et al. found no positive effects in using nori seaweed and spirulina on Cbl-deficient children [183]. The Cbl content of other edible macroalgae is negligible and approximately zero [184]."

"Some fermented vegetable foods, such as sauerkraut, natto and tempeh, can have significant amounts of Cbl. It is unlikely that their daily use in Western countries represents a stable source of Cbl. The presence of Cbl in these foods depends on environmental bacteria randomly present in the fermentative microorganism pool [194]. It is very difficult to standardize the content from one product to another as they are subject to wide variation. Tempeh, for example, during the fermentation of soy beans can develop Cbl in a range between 0.7 to 8 μg per 100 g [195]. Other fermented soy foodstuff has only trace amounts of Cbl [196,197]. In sauerkraut production, the addition of Proprionibacteria sp. to cabbage may boost Cbl concentration up to 7.2 μg/100 g [198]. The use of organic fertilizer can increase the content of Cbl in spinach leaves up to 0.14 μg/100 g. However, the quantity of spinach that needs to be ingested in order to satisfy the daily requirement would be prohibitive [199]."

"According to Carmel, a single oral dose of 50 μg, 500 μg or 1000 μg will be absorbed at an amount of 1.5 μg, 9.7 μg or 13 μg, respectively [151]."

"There were no apparent substantial differences between the absorption of sublingual and oral forms [152,206]. However, oral dissolution could be critical in the secretion of the salivary R-binder and its subsequent bond. Since the Cbl would not be dissolved, about 88% could be not absorbed [54]. Since the development of a Cbl deficiency can also be observed among the LOV, the use of a supplement is necessary, regardless of the type of vegetarian diet [110]."

"If rare genetic defects of cellular trafficking and processing proteins exist, the choice of alternative forms of Cbl, such as Me-Cbl or H-Cbl could improve the effectiveness of supplementation [154,208,209,210]."

"The current data do not support the theory that vitamin deficiency needs 20–30 years to be manifested [125]."

"[..]cobalamin displays other functions, not strictly metabolic, that could be lacking when deficient. A vitamin B12 deficiency could be related to oxidative stress markers like plasma glutathione, malondialdehyde and serum total antioxidant capacity, which could contribute to a neurophysiological disturbance [220]. Furthermore, Cbl, particularly H-Cbl, can act as a detoxifying agent, removing potentially dangerous cyanid molecules from the body [212]."​
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- Treatment of vitamin B12 deficiency–Methylcobalamine? Cyancobalamine? Hydroxocobalamin?—clearing the confusion

"In vitamin B12 deficiency, decreased MeCbl leads to the ‘folate trap’, that is, a functional deficiency of folate.4"

"Vitamin B12 has two active forms, methylcobalamin and adenosylcobalamin (AdCbl), formed as a result of two distinct metabolic cascades.1,6,7 Their metabolic fates and thereby their functions are also distinct. AdCbl is the major form in cellular tissues stored in the mitochondria. MeCbl is found in the cytosol, and it predominates in blood and in other body fluids.8"

"In vitamin B12 deficiency, decreased AdCbl leads to a decrease in the conversion of methylmalonyl-CoA to succinyl-CoA with a resultant increase in methylmalonyl-CoA, which disturbs the carbohydrate, fat, aminoacid and urea metabolism and thereby affects the synthesis of neuronal myelin.10"

I'm quoting these again to include images this time:

Mitochondrial encephalomyopathy with elevated methylmalonic acid is caused by SUCLA2 mutations
The-Krebs-cycle-and-methylmalonic-acid-metabolism.png

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"To summarize, the preferred formulation for vitamin B12 deficiency should be a combination of the active forms of vitamin B12, MeCbl and AdCbl, or HCbl[.]" "In case of the oral route, about 500–750 μg of each, MeCbl and AdCbl, would be required. A lower quantity may be required via the parenteral route. Only in the rare genetic disorders of conversion of vitamin B12 to its active coenzyme forms are the active forms to be used exclusively by the parenteral route."​
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- Vitamin B-12 status, particularly holotranscobalamin II and methylmalonic acid concentrations, and hyperhomocysteinemia in vegetarians | The American Journal of Clinical Nutrition | Oxford Academic
 

Elephanto

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Thanks, @Amazoniac! I get MMA tests regularly. Three years vegan without supplementation and so far so good. Hopefully this continues past the five year mark.

WOW. Just wow. *shakes head*

B12 can be synthesized in significant amounts by gut bacterias.
Vitamin B12 synthesis by human small intestinal bacteria. - PubMed - NCBI

A synthesis of scientific litterature on the influence of a vegan diet on gut microbiota actually shows that the microbiota thriving under a vegan diet favors the B12-producing ones (eating meat + lack of veggies will favor other types that will reduce their population by competition). I like to see it as an hint to intelligent design of our world and that people are not punished through ill health for refusing to kill animals. Algaes and some mushroom types can also be sufficient sources but I'm not a big fan of those.
 
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Amazoniac

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B12 can be synthesized in significant amounts by gut bacterias.
Vitamin B12 synthesis by human small intestinal bacteria. - PubMed - NCBI

A synthesis of scientific litterature on the influence of a vegan diet on gut microbiota actually shows that the microbiota thriving under a vegan diet favors the B12-producing ones (eating meat + lack of veggies will favor other types that will reduce their population by competition). I like to see it as an hint to intelligent design of our world and that people are not punished through ill health for refusing to kill animals. Algaes and mushrooms can also be a sufficient source but I'm not a big fan of those.
This often happens with various other nutrients in which the body has no other option but to allow the growth of bacteria that can provide what's missing. The question is: what's better, to rely on this or to supplement? Given its safety, my bet would be on supplementing, especially if the person is already stressed.
 

Elephanto

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This often happens with various other nutrients in which the body has no other option but to allow the growth of bacteria that can provide what's missing. The question is: what's better, to rely on this or to supplement? Given its safety, my bet would be on supplementing, especially if the person is already stressed.
Sure, I take one since I sometimes eat meat and I don't know how sugar or the use of natural antiseptics is going to affect these bacterias. You can at least sleep in peace with a supp if you can't get tested. I know that sometimes my posts sound like advices when I just want to share additional information, I probably should add a notice.
 

Jennifer

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B12 can be synthesized in significant amounts by gut bacterias.
Vitamin B12 synthesis by human small intestinal bacteria. - PubMed - NCBI

A synthesis of scientific litterature on the influence of a vegan diet on gut microbiota actually shows that the microbiota thriving under a vegan diet favors the B12-producing ones (eating meat + lack of veggies will favor other types that will reduce their population by competition). I like to see it as an hint to intelligent design of our world and that people are not punished through ill health for refusing to kill animals. Algaes and some mushroom types can also be sufficient sources but I'm not a big fan of those.
I had heard in the past that B12 can be synthesized by gut bacteria, but wasn't sure if it was true so thank you for sharing this, Elephanto. :) And the bolded — I like how you see it. I totally agree!

Thank you for that perspective, @Amazoniac.

So far so good but in case my levels drop too low in the future, do you guys know if cyanocobalamin is an okay form? Years back I supplemented with hydroxycobalamin, then tried methylcobalamin and adenosylcobalmin and they all caused me migraines. The supps. were even free of excipients.
 

Amazoniac

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I had heard in the past that B12 can be synthesized by gut bacteria, but wasn't sure if it was true so thank you for sharing this, Elephanto. :) And the bolded — I like how you see it. I totally agree!

Thank you for that perspective, @Amazoniac.

So far so good but in case my levels drop too low in the future, do you guys know if cyanocobalamin is an okay form? Years back I supplemented with hydroxycobalamin, then tried methylcobalamin and adenosylcobalmin and they all caused me migraines. The supps. were even free of excipients.
For how long did you try? Such experience is common during repletion, it tends to disappear. It might have worked as expected and maybe it's a clue that you could've sticked with the form that gave you the worst initial effect (tut).

Since the various reports on more serious troubles with supplements involve people insisting with the belief that they were cleansing the body, I guess what you could do to prevent this is to adjust its use in a way that the symptoms are only mild, but eventually discontinuing if they don't start to improve. Making sure that other B-vitamins aren't missing to avoid distortions should also be reasonable.

The cyanid is harmful, but perhaps not as much if you choose to use tiny amounts at a time, 10 mcg or so.

--
Vitamin B12 Deficiency In Chronic Kidney Disease
 

Jennifer

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For how long did you try? Such experience is common during repletion, it tends to disappear. It might have worked as expected and maybe it's a clue that you could've sticked with the form that gave you the worst initial effect (tut).

Since the various reports on more serious troubles with supplements involve people insisting with the belief that they were cleansing the body, I guess what you could do to prevent this is to adjust its use in a way that the symptoms are only mild, but eventually discontinuing if they don't start to improve. Making sure that other B-vitamins aren't missing to avoid distortions should also be reasonable.

The cyanid is harmful, but perhaps not as much if you choose to use tiny amounts at a time, 10 mcg or so.

--
Vitamin B12 Deficiency In Chronic Kidney Disease
Thank you, Amazoniac! This is very interesting.

The first time I supplemented with B12 was about a year into doing 80/10/10 and I supplemented for a year. The second time was while Peating so close to two years. My previous diets were animal based so I would think that I would of had enough stores unless I wasn't absorbing it from my food.

If it does ever come to me needing it, I'll try as you say and dose it so that symptoms are only mild and see if they eventually resolve, and make sure I'm getting plenty of the other B vitamins. Based on what Elephanto said, I think I'll also look into which mushrooms are a good source of it.

Thanks again! :)
 

Amazoniac

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Vitamin B12 – Vegan Health

Fernijen, I forgot to add that it can be an allergic reaction too. If you ever supplement again and have a bad reacta, it's worth trying different brands that use the same form.

There's the possibility that the disappearance of such symptom after using the supplement for a while being due to the body adapting somehow to its poor quality.

EFSA on 5’-deoxyadenosylcobalamin and methylcobalamin as sources for Vitamin B12 added as a nutritional substance in food supplements (manufacturing process)
 
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haidut

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Amazoniac

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Possible interrelationship between vitamins E and B12 in the disturbance in methylmalonate metabolism in vitamin E deficiency.

"The results of the present investigation demonstrate that the increased production of methylmalonate in the livers of vitamin E-deficient animals is due to an impairment in methylmalonyl-CoA mutase activity arising out of a limited availability of the adenosylcobalamin."​

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The comment that B12 needs calcium for absorption doesn't make much sense in practice because I guess significant impairment can only happen on extreme calcium deficiency or (usually) induced by drugs that affect calcium metabolism.

Effect of calcium deficiency on vitamin B12 absorption in rats. - PubMed - NCBI

"The influence of calcium on vitamin B12 absorption was investigated in two experiments. In the first we investigated whether B12 malabsorption in rats with biliary diversion through choledochocolic fistula is caused by deficiency of calcium in the small intestine. Calcium concentrations were measured in 10 fistula- and 10 sham-operated rats. Fistula rats had steatorrhea, but the concentration of calcium in the intestinal lumen was increased. In the second experiment we studied the effect of calcium deficiency on B12 absorption. Ten young rats were fed a low-calcium diet and 10 rats a control diet for 4 weeks. Rats on the low-calcium diet had moderately reduced calcium concentration in the blood and in the intestinal juice but unaltered calcium concentration in the cytosol fraction of intestinal mucosal scrapings. The absorption of 57CoB12 was unimpaired. This suggests that moderate calcium deficiency does not influence the intestinal absorption of vitamin B12 in the rat."​
 

Amazoniac

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Vitamin B12 as a regulator of bone health

"Bone histology and histomorphometry analysis revealed that B12 deficiency [in mice] profoundly affected osteoblast numbers and bone formation, but had no effect on bone resorption parameters[6]. These results suggested that B12 deficiency may directly affect osteoblast cells."

"Unbiased metabolomics analysis of B12-deficient mice liver led to the identification that these animals have a major reduction in a variety of metabolites[6]. Further downstream analysis of the metabolomics data, which included variable importance in projection analysis, showed that taurine was the most highly dysregulated molecule in B12-deficient livers and that it could separate wild-type (WT) animals from B12-deficient animals with the highest accuracy."

"[..]taurine is an essential factor that can rescue B12 deficiency-induced growth retardation and low bone mass. Taurine does so by increasing IGF1 synthesis from the liver and promoting IGF1 action on the osteoblasts. In the osteoblasts taurine promotes IGF1R signalling by increasing the phosphorylation of IGF1R and other downstream signalling proteins. Together, these studies revealed that one mechanism through which B12 regulates growth and bone mass is through the regulation of IGF1 and taurine production from the liver downstream of GH (Figure 3)[38]."

"The demonstration of taurine as a factor downstream of B12 that regulates osteoblasts functions in a mouse model of B12 deficiency begged the question whether this axis is operational in humans. This was addressed in a small cohort of patients that had B12 deficiency either due to maternal insufficiency of B12 or due to age-related decline in B12 absorption. Correlation analysis between serum levels of B12, taurine and osteocalcin showed that like the B12-deficient mouse model, patients had a significant positive correlation between these parameters. These clinical studies provided evidence that B12–taurine–bone axis is as operational in humans as it is in mice[6]."

"Multiple evidences point towards the fact that the manipulation of [the] gut–liver–bone axis has the potential to increase bone mass in low bone mass disorders. First, B12 and taurine specifically regulate bone formation and therefore have the potential to increase bone formation in diseases that specifically affect this process. Second, both these products are naturally derived and therefore use of these molecules will likely pose no safety issues. For instance, taurine is produced in the body and B12 is stored in the body in high amounts in the liver. However, as in other discoveries of novel pathways, we have a long way to go before the true potential of B12–taurine axis in the treatment of bone and other metabolic disorders will be realized."
 

Amazoniac

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'Advanced Nutrition and Human Metabolism' (978-1-133-10405-6):

"Vitamin B12 deficiency can be produced in several situations, such as with:

- Inadequate intake, which is most likely to occur in a strict vegetarian (vegan), especially in an infant or young child with minimal stores of the vitamin.
- Impaired pancreatic exocrine function, which decreases the pH of the intestinal tract (due to insufficient release of bicarbonate) and impairs the release of vitamin B12 from R proteins.
- Impaired gastric function, which may result from pernicious anemia or other gastric conditions and alters vitamin release and/or binding needed for absorption. Pernicious (which refers to death) anemia is an autoimmune condition in which the body produces antibodies that attack the gastric parietal and mucosal cells, causing destruction and atrophy in the body and fundus regions of the stomach. The destruction of the parietal cells causes diminished (hydrochlorhydria) or absent (achlorhydria) hydrochloric acid production and insufficient IF synthesis. Without IF, vitamin B12 cannot be absorbed. Further, with insufficient hydrochloric acid (as may also result from the use of some medications—H2 blockers and proton pump inhibitors—for the treatment of ulcers and gastroesophageal reflux disease), vitamin B12 release from food protein is impaired, causing food cobalamin malabsorption. These conditions are especially prevalent in older individuals; the incidence of vitamin B12 deficiency in the elderly may be as high as 15%. Atrophic gastritis, characterized by a loss and inflammation of gastric cells, also diminishes acid production to impair vitamin absorption. Conversely, people with Zollinger-Ellison syndrome produce excessive quantities of gastric acid, which results in diminished intestinal pH and impaired release of vitamin B12 from R-proteins.
- Impaired intestinal function, especially if affecting the ileum, such as occurs with celiac disease and Crohn’s disease, may decrease the absorptive surface and thus the vitamin receptors in the ileum to limit vitamin absorption.
- Competition. People with parasitic infections such as tapeworms may develop a vitamin B12 deficiency because the parasite uses the vitamin and consequently limits the vitamin’s availability to the infected person. Similarly, the prolonged use of H2 blockers and proton pump inhibitors (used to treat ulcers and gastroesophageal reflux disease) is associated with diminished absorption of vitamin B12 because of bacterial overgrowth. The intestinal bacteria over-grow in the more alkaline intestinal environment created when the medication diminishes acid production. Further, the bacteria use the vitamin B12 for their own growth, which limits its availability to and use by the individual.
- Use of nitrous oxide (an anesthetic agent), primarily in people who have poor vitamin B12 status, may result in deterioration of nervous system function, especially demyelination problems. Mechanisms by which nitrous oxide alters vitamin B12 metabolism and induces deficiency are under investigation [13]."​


- Comparative Bioavailability and Utilization of Particular Forms of B12 Supplements With Potential to Mitigate B12-related Genetic Polymorphisms

"Animals store bioavailable vitamin B12 compounds in their milk, eggs, muscles and organs, and especially in the liver.11 AdCbl is the predominant B12 form found in meats, at 68%, with the rest occurring as OHCbl and MeCbl.12 MeCbl is the predominant form in milk and eggs."

"[..]a 2010 study assessed B12 status versus B12 intake by measuring homocysteine and methylmalonic acid and concluded: “In persons with normal absorption, our data indicate that an intake of 4–7 μg of vitamin B12/d is associated with an adequate vitamin B12 status, which suggests that the current RDA of 2.4 μg of vitamin B12/d might be inadequate for optimal biomarker status, even in a healthy population between 18 and 50 years of age.”16"

"Vitamin B12 occurs in foods bound in a protein matrix, from which it needs to be liberated during digestion, unlike B12 added as fortification. The bioavailability of foodderived B12 depends on adequate chewing and on the levels of stomach acid and proteolytic enzymes. After liberation from the food matrix, B12 binds to haptocorrin (HC), also called R factor, which is a protein secreted in the saliva and stomach fluids and which carries B12 along the gastrointestinal tract. Subsequently, proteolytic enzymes are needed to liberate B12 from HC to make it available for 2 distinct routes of absorption, either (1) binding to the intrinsic factor (IF) protein or (2) being taken into the gastrointestinal mucosa by diffusion. IF facilitates B12 absorption by the endocytosis route in the ileum, but it gets saturated at the level of 2 μg of B12 per meal."

"All conditions that involve impaired production of IF, such as autoimmune pernicious anemia or atrophic gastritis, and/or a compromised intestinal absorptive function, as in celiac disease, ulcerative colitis, Crohn’s disease, or tropical sprue, may greatly impair B12 absorption by endocytosis."

"Unlike vitamin B12 found in food, supplemental B12 is not bound to proteid; 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. It is not clear if or how much absorption occurs by the oral mucosa route owing to inadequate studies comparing sublingual with encapsulated B12.3,4 The sublingual formulations may achieve partial absorption directly through the oral mucosa, but it is conceivable that part of the B12 may be bound by HC immediately in the saliva and then carried down to be absorbed in the GI tract by IF or by diffusion. B12 bioavailability from a nutritional supplement is not impaired in cases of low stomach acidity."

"All forms of B12 that are absorbed in the blood are transported by transcobalamin-I (TC-I) and transcobalamin- II (TC-II).5 One study observed that AdCbl seems to be the preferred form for binding to TC-II, whereas MeCbl is bound by both TC-II and TC-I.22 Because only TC-II delivers B12 inside cells, owing to specialized receptors, it appears that the AdCbl form of B12 may be delivered more efficiently to body cells than the MeCbl form."

"Two forms of B12, MeCbl and AdCbl, are recognized as active forms of B12 in human and animal physiology because they act as cofactors in important metabolic reactions. However, numerous studies have shown that those forms of B12 are not retained intact in their active form when they are ingested from foods or supplements because they go through intracellular metabolism.2,23,24"

"Numerous studies and reviews of B12 metabolism have shown that CNCbl, MeCbl, OHCbl, and AdCbl are reduced to the core cobalamin molecule inside the cytosol. It is important to note that the ligands specific to the ingested B12 form—methyl and adenosyl—are removed during that process and not used inside cells during the conversion of cobalamin to the 2 active forms of B12 (Figure 1).6,25-30 Activation of cobalamin occurs in very specific cellular environments; cobalamin is converted into MeCbl inside the cytosol and to AdCbl inside mitochondria. The final amounts and ratios of MeCbl and AdCbl produced do not depend on the initial form of B12 that had entered the cells.25 However, those amounts might vary based on cell type, specific cellular conditions, and genetic polymorphisms of those metabolic pathways."

"A cellular study has clarified that the methyl group brought inside cells by supplementation with MeCbl is not used in any methylation reactions and that supplementation with that form of B12 does not produce more methionine as compared with supplementation hydroxycobalamin.25"

"Another cellular study showed that the lysosomal reduction to cobalamin, when B12 is supplemented as AdCbl, was 67 times slower than the reduction of MeCbl to cobalamin. Thus, AdCbl supplementation may result in a slower synthesis of intracellular AdCbl and MeCbl compared with MeCbl supplementation.31"

"Intracellular synthesized SAMe derives its methyl component either from 5-methyl-tetrahydrofolate, with cobalamin acting as an intermediate carrier of the methyl group, or from intake of methionine, betaine, or choline. Thus, intracellular levels of SAMe are not influenced by the form of B12 ingested."

"It is clear that the form of B12 entering the body does not differentially influence the metabolite levels in any methylation reactions. However, the amount of vitamin B12 ingested at one time and its bioavailability, reflected by the portion converted to cobalamin inside cells, is relevant. Those factors can influence the extent to which 5-MTHF, available inside cells, will be used for methylation reactions and DNA synthesis.32,33"

"Inside the mitochondria, a portion of available cobalamin is converted to AdCbl, a cofactor for the conversion of methylmalonyl CoA (MMCoA) to Succinyl-CoA, which enters the Krebs cycle."

"All B12 forms [can be] converted to AdCbl, because they are all broken down to cobalamin first while the adenosyl group that is used to assemble AdCbl is synthesized from adenosine triphosphate inside the mitochondria.26,29 Consequently, if supplemental B12 is in the AdCbl form, it is unlikely that the total AdCbl produced inside the mitochondria would be higher compared with that derived from other supplemental B12 forms.6"

"Glutathionylcobalamin (GSHCbl) is an intermediate in cobalamin metabolism. GSHCbl is a newly proposed active form of B12, a cofactor affecting nitric oxide production, protection, and action in reactions associated with cell membranes.34,35 Those effects may have profound implications for vascular and immune health, but the results of those studies are preliminary.36-39"

[39] The gorilla link above.​
.
"Supplementation with AdCbl has been shown to modulate the immune response by downregulating excess inflammatory processes that are mediated by inducible nitric oxide.37 That fact may explain why B12 supplementation has been shown to reduce the severity of autoimmune conditions, such as rheumatoid40 and atopic dermatitis.41 It is likely that all forms of B12 may have those effects, because they are all converted to intracellular GSHCbl."

For less details:

"All forms of B12—CNCbl, MeCbl, OHCbl, and AdCbl—seem to be absorbed with similar efficiency in the blood stream but differ in overall bioavailability, as reflected by their tissue retention rates. That fact may be due to different affinities for the blood-transport binding proteins, cell receptors for B12 uptake, and intracellular enzymes involved in their conversion to intracellular cobalamin. All of the B12 forms are reduced to the core cobalamin molecule inside the cytosol and then converted to the 2 active forms of B12—MeCbl and AdCbl—irrespective of the form of B12 ingested. It is important to understand that the conversions to active B12 forms do not employ the methyl or adenosyl ligand from supplemental MeCbl or AdCbl, respectively. The methyl group is derived from other molecules—5-MTHF, SAM-e, or betaine— while the adenosyl group is synthesized inside cells."

"As a result, the form of ingested B12 may influence how much cobalamin is produced inside cells but not how it is converted to MeCbl, AdCbl, or various active metabolites involved in methylation reactions. Genetics may affect the activity of enzymes involved in absorption, binding to B12 blood transport or intracellular proteins and/or B12 metabolism. However, no polymorphisms are analyzed through commercially available clinical tests that justify the use of any particular form(s) of B12."

"The current review shows that claims, such as “supplemental OHCbl delivers fewer methylating metabolites than supplemental MeCbl” are not scientifically substantiated. Supplemental OHCbl may deliver more, less, or the same amount of cobalamin inside cells as other B12 forms, thus resulting in the production of higher, lower, or equal amounts of intracellular MeCbl, respectively."

"Ingestion of CNCbl results in lower tissue retention of active vitamin B12 than the naturally occurring forms of B12, which may be particularly problematic in individuals with SNPs on B12 metabolic pathways. Researchers also have expressed concerns of potential cyanide accumulation in human tissues after long-term supplementation and/or intake from foods fortified with CNCbl. Thus, the CNCbl form of B12 seems to be an inferior choice despite its lower cost."

"One animal study compared the effects of supplementation with MeCbl versus CNCbl and showed that CNCbl urinary excretion that was 3 times higher than that of MeCbl. Although absorption in the blood of the 2 B12 forms was similar, the study found that MeCbl supplementation caused 13% more cobalamin to be stored in the liver than did CNCbl supplementation.7"

"Based on the considerations discussed in the current article, it is possible that individuals with particular SNPs [Scottish National Parties] affecting B12 assimilation might 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 one 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. The injectable form of B12 hydroxocobalamin is a justifiable choice when high dose oral B12 is not successful. This administration route may overcome severe absorption impairments due to pathologies or SNPs.6"

@Blossom @Sheila
..
- Cobalamin coenzyme forms are not likely to be superior to cyano- and hydroxyl-cobalamin in prevention or treatment of cobalamin deficiency (but the effects still differ depending on the form)
- Differences in Tissue Distribution of Cyano–B12 and Hydroxo–B12 One Week after Oral Intake: An Experimental Study in Male Wistar Rats

- A new 13C breath test to detect vitamin B12 deficiency: a prevalent and poorly diagnosed health problem

- Vitamin B12 and Semen Quality
Duh, everyboodeeeeeeh wants deeh good boo sack, rhye? @DaveFoster
 
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CrystalClear

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In Australia, the low end of the normal range for B12 in a female is 150. I was 275 in 2016 - age 57. This month I was tested again and it was 297. I was hoping for a much better improvement. I even mentioned to the young GP that their ranges just aren't accounting for my symptoms and that I had read that Europe and Japan had lifted their lower end of range to 500. So to him I am fine.
Lately, Ive had worsening sciatica and numbness showing up in my right thigh. I also get a sharp jabbing sensation in my feet, toes and sometimes lower leg. I really wonder how well I absorb B12 now, although been Peating for nearly 3 years. I do well with B1 and have recent very good improvements in temperature, making me think my liver is doing better ( although I don't think test results reflected it which has me confused.)
 

Birdie

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In Australia, the low end of the normal range for B12 in a female is 150. I was 275 in 2016 - age 57. This month I was tested again and it was 297. I was hoping for a much better improvement. I even mentioned to the young GP that their ranges just aren't accounting for my symptoms and that I had read that Europe and Japan had lifted their lower end of range to 500. So to him I am fine.
Lately, Ive had worsening sciatica and numbness showing up in my right thigh. I also get a sharp jabbing sensation in my feet, toes and sometimes lower leg. I really wonder how well I absorb B12 now, although been Peating for nearly 3 years. I do well with B1 and have recent very good improvements in temperature, making me think my liver is doing better ( although I don't think test results reflected it which has me confused.)
This is so interesting because long ago I used B12 injections for sciatica. I was pregnant and could barely walk. Friends recommended a doctor who gave me B12 injections which cured the sciatica.

Through the years, if sciatica returned, I'd use B12 injections. Now, I use it twice a week. When I go too long between injections, I get foot pain...
 

Birdie

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Thanks @Amazoniac. Good information. Another reason to stay away from nitrous oxide too. Parasites good to know about....
 

CrystalClear

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It's very interesting having read previous posts about dealing with sciatica with B12, I thought I would start taking some leftover lozenges I had.
Bought and took some ages ago but gave up due to no discernible effect.
In recent months though, sciatica (or maybe piraformus problems) has become worse, setting in after a few minutes of light activity. (Further diminishing quality of life). I have dissolved a couple of lozenges under the tongue everyday for a week or so now, and realised the sciatica has decreased a fair bit. (Maybe it's a placebo effect?) lol
I've actually been able to spend some productive time in my front garden pruning back shrubs without having to quit after five minutes.
I was doing some stretching exercises previously which worked up to a point, but the B12 seems to have helped.
I also heard Ray say, I believe it is related, about compressed nerves, that the tissue of hypothyroid people can swell (edema?) and press on nerves. Correct me if I am wrong.
 

Birdie

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It's very interesting having read previous posts about dealing with sciatica with B12, I thought I would start taking some leftover lozenges I had.
Bought and took some ages ago but gave up due to no discernible effect.
In recent months though, sciatica (or maybe piraformus problems) has become worse, setting in after a few minutes of light activity. (Further diminishing quality of life). I have dissolved a couple of lozenges under the tongue everyday for a week or so now, and realised the sciatica has decreased a fair bit. (Maybe it's a placebo effect?) lol
I've actually been able to spend some productive time in my front garden pruning back shrubs without having to quit after five minutes.
I was doing some stretching exercises previously which worked up to a point, but the B12 seems to have helped.
I also heard Ray say, I believe it is related, about compressed nerves, that the tissue of hypothyroid people can swell (edema?) and press on nerves. Correct me if I am wrong.
Glad to hear it's been improving and able to prune shrubs.

It sounds like your body is able to use the B12 from the lozenges sublingually.
Others, like me, can't absorb B12 even sublingually and need injections. Much easier to use a lozenge!
It makes sense though that using one daily would give you a better chance at absorption than, say using it just once in a while.

My husband takes a liquid under the tongue every morning.

I learned in school and have often heard or read that extra B12, since it is water based not oil based, will be flushed out in the urine.
That could be wrong. But, I don't worry about whatever level comes up for me in tests.

Anyway, whenever I get blood work done, it seems I've just done an injection, so it's high!

Hope you keep improving. We must be able to garden! My big pruning effort this year has been a little maple tree in front of our dining room window.
Now that I think of it, pretty amazing I could do it and not end up a wreck.
 

Birdie

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- Impaired intestinal function, especially if affecting the ileum, such as occurs with celiac disease and Crohn’s disease, may decrease the absorptive surface and thus the vitamin receptors in the ileum to limit vitamin absorption.
- Competition. People with parasitic infections such as tapeworms may develop a vitamin B12 deficiency because the parasite uses the vitamin and consequently limits the vitamin’s availability to the infected person. Similarly, the prolonged use of H2 blockers and proton pump inhibitors (used to treat ulcers and gastroesophageal reflux disease) is associated with diminished absorption of vitamin B12 because of bacterial overgrowth. The intestinal bacteria over-grow in the more alkaline intestinal environment created when the medication diminishes acid production. Further, the bacteria use the vitamin B12 for their own growth, which limits its availability to and use by the individual.
- Use of nitrous oxide (an anesthetic agent), primarily in people who have poor vitamin B12 status, may result in deterioration of nervous system function, especially demyelination problems. Mechanisms by which nitrous oxide alters vitamin B12 metabolism and induces deficiency are under investigation [13]."

Thanks to Amazoniac.
 
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