Some 15 years ago I attended a seminar by Dr Steve Haltiwinger, a maverick U.S. doctor who had once specialised in a mental health clinic, one of several physicians in this facility. Disappointed with results, Dr Haltiwinger began experimenting with nutrients such as B12 and folic acid, much to the chagrin of his colleagues. As it turned out, many of the patients he treated responded well to these nutritional interventions, and his practise began to steadily build. Ultimately, his colleagues became envious of his success, ostracised him and had him challenged in court as practising in a medically unethical way with ‘unscientific’ methods. He was subsequently banned from practising medicine in the U.S. altogether, and moved to Mexico.
Dr Haltiwinger in his seminar explained that one of the first clinical signs of B12 deficiency was depression or mood disorder, well before blood levels of B12 indicated a problem with anaemia. In those days, the reasons for this were not all that well understood, though the New England Journal of Medicine as long ago as 1988 had reported that B12 addressed these same neurological symptoms in the absence of haematological abnormalities. Now we have a clear understanding that a low or sub-optimal B12 can mean defective or slowed methylation, with a reduction in SAMe production required for serotonin and dopamine synthesis, important neurotransmitters that maintain our mood and sense of well-being. Dr Haltiwingers’ colleagues were attempting to target this downstream neurotransmitter deficit with drugs, while he was treating the nutritional upstream cause. For that he got kicked out of the U.S. for unethical practise.
B12 in the Gut
The B12 story gets even more interesting. Bacteria in the gut of an animal like a sheep or cow, synthesise hydroxycobalamin, the natural form of B12 found in animal, but not vegetable foods. The forms of B12 that are found in plant foods such as spirulina, are not as well absorbed or utilised by the body, hence why vegans or vegetarians tend to become deficient in this nutrient. Hydroxycobalamin can be converted by the liver into two active forms, methylcobalamin used in methylation and adenosylcobalamin used in mitochondrial energy production and also playing a significant role in myelin synthesis. The synthetic form of B12 known as cyanocobalamin prescribed by doctors and found commonly on health food store shelves, is a stable and cheaper form of B12 with a long shelf life.
What the body first has to do with this synthetic form is get rid of the cobalt molecule that has been attached to hydroxycobalamin in a lab through treatment with activated charcoal that acts as a cobalt donator. Two things then need to happen for effective utilisation in the body. The first is absorption of the B12 in the gut, dependent on adequate Intrinsic Factor secretion in the stomach, which binds on to the B12 and transports it the terminal ileum, the last part of the small intestine where it is absorbed. Problems here that can limit absorption include low stomach acid and Intrinsic Factor secretion, an increasingly common problem due to the prevalence of chronic stress which inhibits vagal nerve supply to the GI tract. This can be compounded by a history of reflux and/or usage of anti-acid medications, which are often prescribed on the pretext that there is too much acid, when in fact there is mostly lowered acid production and defective mucosal barrier protection, both due to inhibited vagal nerve function. It just seems there is too much acid due to increased sensitivity of the stomach lining, the restoration and repair of which is then neglected. Inflammation in the upper bowel due to IBS, Chron’s, SIBO or food intolerance/sensitivity can also result in defective B12 absorption.
B12 and Cobalt
The second thing that is needed is effective removal of the cobalt molecule from synthetic B12. Assuming the gut is in good shape and the cyanocobalamin has been absorbed, the cobalt molecule will be removed in the liver. It is believed this step is dependent on effective phase 2 liver glutathionation. If you have low glutathione or are suffering from oxidative stress, this conversion may be compromised.
It can make much more sense then to supply either sub-lingual B12 that dissolves in the mouth and bypasses gut absorption completely, or hydroxycobalamin in a lozenge form that can also compensate for defective glutathionation. The body will then choose which active form it needs to convert to, adenosylcobalamin or methylcobalamin or both. Having explained the main absorption pathway above, it has been determined that high doses of standard oral cyanocobalamin if maintained for a few months, eventually results in an increase in B12, even in those with pernicious anaemia and defective production of Intrinsic Factor, suggesting that there may be some other route of absorption that might bypass the Intrinsic Factor pathway. However, why wait when you can get results immediately with either sub-lingual B12 or hydroxycobalamin lozenges.
What’s the Difference?
As well as the treatment of mood disorders or depression with hydroxycobalamin, the adeno and methyl forms of B12 can be individually taken in a capsule or lozenge form, and can be used alone or in tandem for treating a wide range of neurological conditions, that do not respond to ordinary B12 supplementation. Particularly if there is a concomitant liver disorder, the active forms should always be chosen as conversion to the active or co-enzyme forms may be compromised. Adenosylcobalamin is not that well absorbed through the gut (around 35%), so a lozenge is always preferred. Methylcobalamin is 100% absorbed so capsules or liquids are o.k. here.
Methylcobalamin appears to have the highest uptake in neurons of any form of B12 and current medical research reveals it has a significant role to play in improved nerve conduction and peripheral neuropathies. Conditions shown to respond well include Bells Palsy, paraesthesias , pain perception, nerve injury, diabetic neuropathy, deteriorating eyesight, sleep disturbances such as hypersomnia ( sleeping for too long) as well as a lowering of elevated homocysteine in defective methylation.
Adenosycobalamin is directly involved in porphyrin and heme synthesis and has been shown to normalise various haematological parameters such as hemoglobin, hematocrit, red cell count, mean corpuscular volume, iron, and transferrin iron binding capacity in pregnant women. If iron is being supplemented and the levels are not going up, co-incident adenosylcobalamin supplementation to help correct this would be advisable. Adenosylcobalamin activates myelin sheath repair and has been shown to help restore structure and function of the neocortex of anorexics, translating to an improvement in appetite regulation and also to improved gut function, possibly through increased myelination or restoration of function of the vagus nerve.
As well as adenosylcobabamin being involved in mitochondrial energy production, there appears to be a role for the concomitant use of both adeno and methyl B12 in many neurological conditions, where they may work synergistically in improved nerve conduction and myelin synthesis. As there is no known toxicity at a therapeutic range of up to 6000mcg/day of either, beyond which no benefit has been demonstrated, anyone with a neurological impairment or defect, resistant to conventional treatment, should consider their use. Care however has to be taken with a minority of ‘over- methylators’ with methylcobalamin , and a lower or pulsed dose protocol might be more appropriate, along with B3 to soak up some methyl groups. Consult with your wholistic G.P. or naturopath if you react to methylating nutrients such as methycobalamin, TMG or 5MTHF.
B12 and the Liver
With anyone with acute or chronic liver disease, there may be an impairment of synthesis of the active forms of B12, which can contribute to poor Phase 1 and 2 liver and systemic detoxification, impaired methylation and also cause secondary systemic issues such as fatigue or neurological symptoms. In practical terms, hormone residues, heavy metal, chemical and metabolic toxins may accumulate adding to fatigue. Adenosylcobalamin and methlycobalamin both appear to be hepatoprotective and restorative and have been used successfully in the treatment of liver disease. One possible pathway for this is improved Phase 1 detoxification as CYP450 enzymes require heme co-factors (adenosylcobalamin) while Phase 2 detoxification enzymes require methylation (methylcobalamin), reducing the toxic burden on the liver.
B12 and Nitric Oxide
Nitrous oxide, which is the ‘laughing gas’ your dentist or anaesthetist might offer you, limits or inactivates both coenzyme forms of B12 and at the same time interferes with methionine synthase in the methylation cycle. Vitamin B12 levels or methylation defects should be checked or evaluated in people with risk of vitamin B12 deficiency prior to using nitrous oxide anesthesia, such as vegans or those avoiding animal products, those with chronic stomach or gastro-intestinal distress, or those that show sub-clinical B12 deficiency signs such as mood disorders or depression. Significant neurologic dysfunction after a single anaesthetic dose of nitrous oxide has been reported in those with B12 deficiency which can last for weeks. Hydroxy B12 lozenges prior to anaesthesia might be an appropriate pre-nitrous oxide ‘buzz’ for many, short of checking B12 levels and methylation status.
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This article is for information purposes only. Please refer to our Medical Disclaimer policy for more information. The opinions expressed here represents the author’s and not necessarily those of Realize Health. In addition, thoughts and opinions change from time to time due to updates in research and as a necessary consequence of having an open mind. Views expressed in out-of-date posts may not be the same to those we hold today.