What is it? Why do we need it? Where can I find it? What? Eat my poo?!?!?
Vitamin B12 is cobalamin. Cobalamin is an unusual vitamin in that it is not made by plants or humans and instead is synthesized exclusively by bacteria and archaea.
There are multiple forms of cobalamins.
- Methylcobalamin and adenosylcobalamin are the two co-enzyme forms of B12. Methylcobalamin is coenzyme for methionine synthase involved in methione and subsequent SAM production for methylation processes. Adenosylcobalamin are coenzymes for and methylmalonyl-CoA mutase.
- Cyanocobalamin and hydroxocobalamin are synthetic forms frequently used for supplementation if the naturally occurring coenzyme forms are deficient. The cobalamin used in clinical studies, cyanocobalamin, is an artefact of the cobalamin isolation procedure.
By definition vitamins are not synthesized in sufficient quantities by humans.
In the case of cobalamin we have a symbiotic relationship with our gut microbes; whereby we feed the gut flora with enough plant material and they synthesise vitamin B12 for us. As this is a symbiotic relationship the bacteria that make the vitamin B12 will also use some for themselves. It is a precious resource in the gut and the host (us) will not get all of the vitamin B12 made.
Why supplement? Vitamin B12 cannot be synthesised by mammalian species, but only by microorganisms.
In humans, bacterial synthesis of B12 mainly takes place in the large bowel and the caecum. From these sites absorption, cannot take place. Absorption occurs further upstream in the small intestine and not from the large intestine and cecum and therefore humans are predominately dependent on dietary sources of vitamin B12 to deliver the cobalamin into the small intestine for absorption.
There is however a % of our B12 supplied from oral bacteria, recycled enterocystes and recycled bile salts reabsorbed and delivered back to the liver and subsequently via the gall bladder back into the digestive tract.
B12 is absorbed with active transporters
Intrinsic Factor (IF) is secreted within the stomach; it is a glycoprotein that is necessary to transport B12 through part of the absorption process.
Other cobalamin transporters: In addition to IF, there are 3 more substances known as transcobalamins, which also transport cobalamins within the body; TCI, TCII, and TCIII.
Or B12 is absorbed via passive diffusion
“Because of the highly polar nature of cobalamin(s), only 1% of an oral intake can traverse plasma membranes by passive diffusion.”
This shows the dose required to force enough of a concentration gradient to force the B12 into cells via passive diffusion. To force high levels in to cells the B12 levels in the gut must be significantly higher than the enterocyctes to force it from areas of high concentration to areas of low concentration and then the concentration gradient from the cells to the blood stream and then from the blood stream to our body target cells.
Other cobalamins and B12 analogues may have opposite effect and be “antinutrients”
There are other forms of cobalamin however that we cannot use, but these antinutrient forms are capable of competing with other forms of vitamin B12 cobalamin. As our testing methods and technology improve we have better ability to test and discriminate between cobalamins which are relevant, and those which are not.
However, some papers, products and protocols are based on data from older, less discriminatory tests published before they discovered how to differentiate between the various forms of cobalamins.
e.g. 1 – claims that your oral bacteria produce enough B12 to sustain life is false as it was based on old faulty science. We now know that they don’t; they produce other B12 Analogues, cobalamins which closely resemble B12, but which your body cannot use.
e.g. 2 – Spirulina contains cobalamins, and marketing claims are made that these too are vitamin B12 but we now have the technology to distinguish between the different forms and the levels of useful B12 have been reduced significantly to negligible levels.
What is worse with these fraudulent or misleading or naïve claims is that in some cases the contained cobalamins may actually have a negative effect on the symptom picture which can lead people away from B12 supplements or further investigation into B12 deficiency state.
B12 analogues can block and / or compete with B12 for reaction sites within our cells, interfering with our assimilation and use of B12 itself.
Sources of B12
Animal sources – Meat, offal, organ meats, dairy
Vegan sources – Algae (purple laver Nori), mushrooms, fermented vegetable products
As mentioned many times previously vitamin B12 is not synthesized by plants. The technology to identify vitamin B12 in amongst other cobalamins has only been made sensitize / accurate enough in recent years; the research showing vegetable sources of B12 such as spirulina is outdated and follow up studies using the new technology has discovered that spirulina contains the antinutrient form of cobalamins instead of the beneficial B12. This new discovery has cast doubt over a lot of our existing dietary recommendations for correcting B12 deficiency in vegans.
It is well known that vegans regularly suffer from B12 deficiency based on epidemiological studies. But not all vegans are deficient. So where do the good guys get theirs?
Copraphagy is an option
Animals that practice copraphagy (eating of one’s own faeces) have the excellent blood levels of B12. As discussed previously most B12 is made in the large intestine but the best site for absorption is in the small intestine, the digestive tract only moves one way. Down and out; it can’t go backwards so it makes sense to get the most out of the nutrients made in the colon by bacteria to get a few more runs through the tract to get the most out of your waste and efficiently recycle.
Most of the B12 in faecal matter is freshly made from the bacteria in the last part of the bowel. Faecal matter also contains B12 from bile salts and from recycling old tissue and cells shed from the gut wall.
If we are not eating our own poo maybe, we should eat our own body parts?
“Villi are projections into the lumen covered predominantly with mature, absorptive enterocytes, along with occasional mucus-secreting goblet cells. These cells live only for a few days, die and are shed into the lumen to become part of the ingesta to be digested and absorbed.”
As our old tissues are digested they liberate nutrients, including vitamin B12 in the preferred form that can be reabsorbed and re-used.
B12 in protein
In animals, B12 is normally attached to a protein either for transport or storage.
Stomach acid is needed to liberate the B12 from the protein.
The stomach cells also produce a protein called intrinsic factor (IF), which travels to the small intestine. IF doesn’t work well in acid and needs an alkaline environment. Other transporters carry the B12 into the alkaline rich small intestine where pancreatic enzymes cleave away any other binding proteins. Of all of the liberated corrinoids, only the cobalamins attach to intrinsic factor. Intrinsic factor then carries the cobalamins to the last section of the small intestine, the ileum.
The cells lining the ileum contain receptors for the cobalamin-IF complex. The cobalamin-IF complex protects the cobalamin against bacterial and digestive enzyme degradation. The IF-receptor also ensures that cobalamins will be given priority for absorption over non-cobalamin corrinoids.
Passive diffusion is used to absorb any cobalamin that is not bound to IF (usually about 1-3% of the cobalamins are absorbed this way.)
Digestion and absorption of supplemental B12 (not bound to protein)
In supplements, B12 is not bound to protein, and therefore does not need digestive enzymes or stomach acid to be liberated from protein (only from the tablet / capsule / lozenge / spray matrix). When taken in large enough doses; large amounts of B12 can be absorbed through passive diffusion by manipulating the physics of concentration gradient. The B12 will move from area of high concentration to low concentration to create equilibrium.
Recycled B12 via enterohepatic circulation
About 60% of the total amount of B12 in the body is stored in the liver and 30% is stored in the muscles. The enterohepatic circulation links to digestive tract and liver.
Bile is made in the liver and is secreted into the beginning of the small intestine. It is then reabsorbed at the end of the small intestine (the ileum) and taken back to the liver where it is used again. This circuit is called enterohepatic circulation.
In some cases of low B12 intake, absorption increases which can delay overt B12 deficiency, sometimes for decades and make the symptoms appear gradually.
For vegans who do not supplement, the enterohepatic circulation may determine how long one can go before developing B12 deficiency symptoms.
- strange sensations, numbness, or tingling in the hands, legs, or feet
- difficulty walking (staggering, balance problems)
- a swollen, inflamed tongue
- yellowed skin (jaundice)
- difficulty thinking and reasoning (cognitive difficulties), or memory loss
- paranoia or hallucinations
Causes of deficiency
- no intrinsic factor e.g. pernicious anaemia
- proton-pump inhibitors (such as Nexium or Prevacid)
- H2 blockers (such as Pepcid or Zantac)
- metformin (diabetes, PCOS and other insulin resistant syndromes)
- common deficiency in vegans
- gastric surgery for weight loss
- Inflammatory bowel disorders
- Dietary inadequacy
Frequently people claim to be experiencing withdrawal symptoms from oral B12 supplementation when they miss a few days and do not want to stop taking it others will complain that they felt an initial surge in energy and feelings of wellbeing after a B12 injection followed by a slump and deterioration. The reason for this observation may be related to the passive diffusion of B12 into cells. Passive diffusion requires a steep concentration gradient, meaning the B12 gets loaded up really high in blood and because cells have significantly lower levels than blood, the B12 passes through the cell wall. Moving from high concentration to low concentration. The problem here is that the levels required to do this are thousands x the actual amount we need on a daily basis with the results being a sudden influx of B12 inside our cells. Subsequently this gradient slope needs to be maintained so as the levels inside and outside of cells come into balance the immediate wellbeing effects diminish. As the blood levels reduce post injection or supplementation the concentration gradients polarise to the opposite and B12 starts diffusing out of the cells to maintain balance and there is a period of withdrawals symptoms or deterioration of symptoms to be worse than prior to the initiation of supplementation.