Vitamin B12 is almost the magic potion in my clinical practice. I see patients with chronic fatigue syndrome, chemical, electro or food sensitivities and environmental illness, Autism spectrum disorders, and neurological problems such as depression, delusion, multiple sclerosis, dementia, developmental delay, diabetic neuropathy, transient ischaemic attacks and dear old heart disease. Not to mention infertility. What do they all have in common? Functional B12 deficiency is a worldwide problem1
Doctors consider B12 deficiency anaemia an old person’s disease, but it can strike at any age, any culture or socioeconomic status. To the discerning eye it is easy to spot, easy to treat and easy to cure. If you are over 40 you have an elevated risk and over 60 means up to a 40% chance of potentially dangerously low B12 levels. This is in part due to the fact that digestive secretions diminish as part of the aging process so levels of stomach acid may be too low to be able to extract the B12 from foods. Hypothyroidism and gut bacteria imbalance may also impact, more so (but not exclusively) in females. Government statistics seriously underestimatetrueincidence.
While some specialists advocate that B12 can be gained from seaweed and algae this is in minimal amounts. The body needs to be able to eat and assimilate B12 from meat, fish, poultry, eggs and dairy so vegans fall short.
However the majority of people eat plentiful supplies of these foods and still develop B12 deficiency. This is because Hydrochloric acid and pepsin are required to split the B12 from the protein. Protease enzymes then help Intrinsic factor (IF) latch onto the B12, taking it to the last portion of the small intestine and into the bloodstream [see diagram right]. Without good levels of IF and stomach acid none of this can occur so digestion has to be optimal. That’s where your naturopathic doctor or registered nutritional therapist can be useful.
What does this mean?
Sadly for those who have a functionalB12deficiencytheymay never be diagnosed. This is because Western medicine only accepts B12 deficiency once pernicious anaemia has developed, which can take many years. Western medicine testing (from your doctor) only offers a
serum blood level, which is a pretty useless test, because we need to know about the function of B12. You can have high levels in serum without it going to the cells that need it.
You can see macrocytic (abnormally large) red blood cells on a basic haematology screen from your GP – (otherwise known as a full blood count) and this should lead your doctor to consider B12 and folate deficiency and that in turn should lead them to ‘poor methylation’. This is the key player in the top 5 killer diseases (heart disease, stroke, diabetes, cancer, Alzheimer’s/ dementia). Methylation is also one ofthekeyprocessesin detoxification. Unfortunately I n most cases when GPs see macrocytic blood cells they don’t necessarily consider B12 / folate deficiency, so patients are often left never knowing about Functional B12 deficiency. Instead patients are diagnosed with macrocytic or megaloblastic anaemia and given blood transfusions rather than B12. Together with Methylfolate (a type of folic acid), B12 is an essential co-factor required for DNA synthesis in rapidly dividing cells. This is where chromosomes are dividing, most notably bone marrow and myeloid cells but also rapidly growing and dividing foetal cells. (If a foetus is going to make it past 12 weeks gestation then methylation has to occur and sometimes we need to assist that process.)
As you become more deficient in B12 disease, fighting white blood cells diminish in number leaving you susceptible to viral (such as Herpes) and bacterial infections (such as streptococcus). Your gut lining begins to leak like a sieve because your body cannot make enough cells to replace your intestinal lining (this can lead to
food intolerance and auto- immune disease). You get weak and exhausted due to anaemia. Proton pump inhibitors, H2 blockers and antacids, or drugs that reduce stomach acid also increase the risk of functional B12 deficiency.
The best way to test for functional B12 deficiency is testing for Methylmalonic acid (MMA) in urine, Homocysteine CyanCobalamin
The common synthetic form of vitamin B12 is cyanocobalamin This form doesn’t occur in nature but is used in many pharmaceuticals and supplements, and as a food additive, because of its lower cost. In the body it is converted to the physiological forms, methylcobalamin and adenosylcobalamin, leaving very small amounts of the cyanide molecule.
Removing the cyanide molecule from the vitamin and then flushing it out of your body uses up “methyl groups” of molecules in your body that are needed to fight things like homocysteine (high levels cause heart disease). This means that by taking cyanocobalamin, you’re actually stealing methyl groups from your body and making it do more work at the biochemical level. This uses up substances such as glutathione that are often in short supply anyway, potentially worsening your overall health situation rather than helping it; if you are a hyper-sensitive individual the last think you need is to reduce your methylation capacity!
(Hcy) in plasma or Holotranscobalamin (holoTC) in serum (blood). HoloTC measures only the 20% active component of serum B12. However you can also test your genomes (your DNA) with a test by ‘23andme’, which would give you all the SNiPs (Single Nucleotide Polymorphisms) that require B12 as a co-factor. This is an amazing way to personalise your health prescription. SNiPs are small changes in your unique genetic code. They occur as an aspect of human evolution to aid survival of the species but we have changed the environment so much that some of these work against us so we need to change the way they express themselves. [Tests are available through your practitioner or support group members can use their discount code from Detox People, although the results will need to be interpreted by an experienced practitioner.]
Types of B12
There are four types of B12 or cobalamins and taking the correct type is crucial if you are to gain optimum benefit.
Cyanocobalalmin is more commonly used in the medical world as B12 shots for conditions such as pernicious anaemia and in many commercial vitamin supplements because it is the cheapest form. However studies2 suggest that the dose required to normalise mild vitamin B12 deficiency is 200 times more than the recommended dietary allowance (RDA). In addition, Cyanocobalalmin has a cyanide molecule attached.
Methylcobalamin (a coenzyme of B12) is a later introduction. A systematic review included three studies using a vitamin B complex, and three using pure methylcobalamin on patients with diabetic neuropathy. Methylcobalamin improved the neurological symptoms much more than the B complex but the authors note that only two of the studies were of good quality. We do still need to see good quality research in this field. A monograph3 in Alternative Medicines review advocates that methylcobalamin at dosages of 1500-1600mcg per day irrespective of the route of administration showed improvements in Bell’s palsy, Cancer, Diabetic neuropathy, Eye Function, Heart Rate variability, HIV, Homocysteinemia, Male impotence and sleep disturbances. As far as I am aware there are no studies supporting the use of Cyanocobalamin over methylcobalamin. Are there case studies of people with autism/ environmental illness able to metabolise methyl forms better that cyan? Studies debate the issue but have not concluded anything. Cyanocobalamin has to be converted to methylcobalamin in the liver but autists seem to have difficulty doing this.
Hydroxycobalalmin (a natural form/ vitaminer of B12) has been tested on cyanide poisoning4 and as a scavenger of Nitric oxide (NO). Martin Pall has done extensive work on th cycle) and its relevance to Chronic Fatigue syndrome. His book is quite complex but very informative.6
Finally Adenosylcobalalmin: Carmen Wheatley5 has focused on Adenosylcobalalmin being the principal Nitric oxide synthase catalyst. This is influential in regulating the immune and the pro/anti- inflammatory response. While some forms of B12 inhibit this enzyme, Adenosylcobalalmin doesn’t and it is the mitochondrial form of B12.
Which form to take?
I would never advocate Cyanocobalamin for any condition so that only leaves the three later forms. The methyl aspect of Methylcobalamin is not tolerated well by some people: taking methyldonors if you are COMT and VDR Taq can exacerbate your current neurological symptoms and here we come back to Nutrigenomics for the key issues. People who have a DNA test and find they have COMT V158M and VDR Taq polymorphisms (natural variations in a gene, DNA sequence, or chromosome ) or SNiPs (Single Nucleotide Polymorphisms, frequently called SNPs (pronounced “snips”), are the most common type of genetic variation among people. ) have to be very careful to take the correct form of B12, and they need to work with an experienced practitioner to get this right. This is because having a SNiP or two isn’t so cut and dry. Whether a SNiP is homozygous (from both parents) or Heterozygous (from one parent) or wildcard (normal) determines your type of B12. It is very complicated and all links in with other methylation SNiPs such as MTHFR (Methyltetrahydrofolate reductase – an enzyme that helps to convert synthetic folic acid to methylfolate, the body’s preferred form) so it needs careful handling and a systematic approach. That said, a couple of hours with a specialist MTHFR functional medicine practitioner following your ‘23andme’ genetic testing will generally get you this information much more easily than trying to work it out for yourself. This is real individualised medicine. Using the correct type of B12 for you means you probably need a lower dose so that can offset the practitioner fees against the cost of supplementing.
Modes of delivery
B12 can be delivered by a number of routes: Intramuscular (IM) or Subcutaneous (SC) injection.These need a doctor prescription although if you are deficient in B12, the results can be pretty dramatic. Sublingual (SL) is a tablet or liquid dissolved under the tongue and is said to be as effective as IM or SC injections so long as you have the correct type of B12. Personally I have found a 3- type combination sublingual B12 as effective as regular SC Methylcobalamin injections. Transdermal patches, which are applied to the skin as a plaster for 24 hours, are useful for those with malabsorption problems. Transdermal creams (ie skin creams) are also very useful in malabsorption syndromes, Coeliac Disease, Ulcerative colitis and Crohn’s disease. We use these for children where injections may cause distress.
Oral delivery. As this route goes via the stomach, the B12 will require intrinsic factor in order to be absorbed, so a capsule or tablet absorbed in the stomach is unlikely to be of much if any benefit.
Some practitioners advocate using injectable B12 to get a patient’s levels back up, and then switch to oral supplements, (2,000 mcg per day) but you do need a naturopathic doctor to prescribe it for you. However I find the right type of B12 at the right dose with the right delivery method is just as effective from the start.
1 Stabler, S.P. & Allen, R.H., 2004. Vitamin B12 deficiency as a worldwide problem. Annual review of nutrition, 24, pp.299– 326.
2 Eussen, S.J.P.M. et al., 2005. Oral Cyanocobalamin supplementation in older people with vitamin B12 deficiency: a dose- finding trial. Archives of internal medicine, 165(10), pp.1167–72. Available at: http://www.ncbi.nlm.nih.gov/ pubmed/15911731 [Accessed November 1, 2014
3 Sun, Y., Lai, M.-S. & Lu, C.-J., 2005. Effectiveness of vitamin B12 on diabetic neuropathy: systematic review of clinical controlled trials. Acta neurologica Taiwanica, 14 (2), pp.48–54. Available at: http:// www.ncbi.nlm.nih.gov/ pubmed/16008162 [Accessed November 1, 2014].
4 Dart, Richard C. (1 January 2006). “Hydroxocobalamin for Acute Cyanide Poisoning: New Data from Preclinical and Clinical Studies; New Results from the Prehospital Emergency Setting”. Clinical Toxicology 44 (s1): 1– 3. doi:10.1080/15563650600811607. PMID 16990188.
5 Wheatley, C. (2012) The Very Large Gorilla Sitting in the Room? Adenosylcobalamin is the Missing Link: its Radical and Tetrahydrobiopterin are the Principal in vivo Catalysts for Mammalian Nitric Oxide Synthases. Orthomolecular Oncology, (registered charity no. 1078066), 4 Richmond Road, Oxford, OX1 2JJ, and St Catherine’s College, Oxford, OX1 3UJ, UK.
6 Prof. Martin Pall PhD: Explaining Unexplained Illnesses, CRC Press; 23 April 2007. ISBN-10: 078902389X
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