B12 and fatigue exploring the nutrigenomics connection

Screenshot 2015-09-01 21.07.29

cam-mag.com I September 2015

B12 by supplement or injection, has become a controversial aspect of treatment for chronic fatigue. Orthodox medics dismiss the idea that anyone not in a frank B12 deficiency state can benefit. But both anecdotal and a few peer-reviewed studies suggest otherwise. In published papers, prof Marty Pall and colleagues have even proposed a mechanism, showing that the hydroxocobalamin form of B12 is a particularly potent nitric oxide (NO-) neutraliser, which is significant as CFS sufferers are said to display nitric oxide (NO-) and peroxynitrite (ONOO-) over-production. On top of that B12 status is can be hard to assess using conventional blood testing. CAM’s resident nutrigenomics expert, Anne Pemberton, here provides the genetic knowledge that is often overlooked when recommending B12 and other supplements.

With the explosion of information on Nutrigenomics and the addition of what appears to be an explosion of B12 deficiency syndromes it can be a nightmare to wade through what scanty evidence is available and address some of that effectively for the greater good of our clients. Supplement and testing companies are all on the bandwagon now, with an overwhelming amount of informaton for the purpose of selling products. Although these educational efforts may be well-meaning , what this increasingly means is that practitioners and patients are being encouraged to treat SNiPs, while everyone has a view and there is still widespread confusion. The information presented in this article is not for the purpose of SNP treating, it has to be taken in context with a full client history and analysis of the case alongside relevant functional tests as appropriate to the case. We all have many SNPs and some of those will be homozygous and / or heterozygous but that doesn’t mean they are expressing. Sometimes those with expressive SNPs are not “fixed” simply by adding in extra B vitamins and minerals. You can often exacerbate a poor metabolic status with this type of practice. We often need to look a lot deeper into the environmental causes for SNP expression and correct those first. The actual functionality is determined by a concert of multiple genes working together in an integrated network of interactions of their expressed protein products, the system behaviour is complicated. So clinicians fall back on the crutch of one or two homozygous mutations as being the culprit. This simply wrong. Screenshot 2015-09-01 21.48.05Having said that, some clients  may have reached a state due to metabolics, epigenetics, or many SNPs plus exposures to metals, toxins, infections, etc. that their chemical reactions are not properly coupled. They can then, for example reach much higher levels of ammonia or taurine, or lack the co-enzymes for adequate transulfuration and so on. The important thing is how to support this clinically.

Screenshot 2015-09-01 22.44.19*NB: Yasco says COMT +/- or +/- require these versions of B2 as opposed to methylcobalamin due to MEB12 increasing the number of methyl donors. This is very much dependent on your client. In clinical practice some function better on a combination of methylcobalamin and adenoslylcobalamin at lower doses.                               ** Nutritional cofactors for the individual SNPs.

 

It is not necessarily useful for example on seeing that a client has a heterozygous mutation in the CBS gene, to jump to the conclusion the person has a definite problem. We need to think in reverse. What are their symptoms? Find that out first and work back. Do not read the genome ticker tape and speculate forward.

Linking this to B12

So with the focus particularly on B12 there are certain things we do know. The overall incidence of B12 deficiency is unknown and certain groups have been identified as being high risk with rates of diagnosed deficiency around 15% (1). However most cases with neurological signs of B12 deficiency are not readily detected in blood due to the action of folate normalising blood cell abnormalities associated with B12 deficiency (2). With the above in mind it is still crucial to test and the gold standard is Methylmalonic acid in serum or urine (3). There are a number of polymorphisms associated with B12 deficiency (4). Assuming you have carried out appropriate testing AND taken a full history, we can define some possible recommendations. These are not mutually exclusive, nor is any /one brand likely to be the ultimate choice.

References:

  1. Bosque P. Vitamin B12 deficiency – Epidemiology. Medmerits [Internet]. 2014 [cited 2015 Aug 15]; Available from: http://www.medmerits.com/index.php/article/vitamin_b12_deficiency/P6
  2. Healton EB, Savage DG, Brust JC, Garrett TJ, Lindenbaum J. Neurologic aspects of cobalamin deficiency. Medicine (Baltimore) [Internet]. 1991 Jul [cited 2015 Aug 15];70(4):229–45. Available from: http://www.ncbi.nlm.nih.gov/pubmed/1648656
  3. Goringe A, Ellis R, McDowell I, et al. The limited value of methylmalonic acid, homocysteine and holotranscobalamin in the diagnosis of early B12 deficiency. Haematologica 2006;91:231-4.
  4. Mitchell ES, Conus N, Kaput J. B vitamin polymorphisms and behavior: evidence of associations with neurodevelopment, depression, schizophrenia, bipolar disorder and cognitive decline. Neurosci Biobehav Rev [Internet]. 2014 Nov [cited 2015 Aug 15];47:307–20. Available from: http://www.sciencedirect.com/science/article/pii/S0149763414002048

 

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