Testing a Relevant SNP?

A new study in Science Magazine by Simonti et al has linked this SNP to a rare condition known as protein-calorie malnutrition (PCM).  The study compared electronic health records (EHR) for 28,000 people with SNPs that are now known to derive from Neandertal DNA.

SNP rs12049593 is in an intron of SLC35F3, which means it does not change the actual structure of the protein, but instead alters the amount of protein produced.  SLC35F3 codes for a protein that helps transport vitamin B1 (thiamine) through the body to the mitochondria, where it can be used to generate and store energy from sugar. The linkage to PCM makes sense, because PCM is characterized by fatigue, malnutrition, and wasting even in the presence of adequate caloric intake.

"Humans depend on diet for their thiamine needs. Very little thiamine is stored in the body and depletion can occur within 14 days. Severe thiamine deficiency may lead to serious complications involving the nervous system, brain, muscles, heart, and stomach and intestines." (Mayoclinic)

"Thiamine is required for the assembly and proper functioning of several enzymes that are important for the breakdown, or metabolism, of sugar molecules into other types of molecules (i.e., in carbohydrate catabolism). Proper functioning of these thiamine–using enzymes is required for numerous critical biochemical reactions in the body, including the synthesis of certain brain chemicals (i.e., neurotransmitters); production of the molecules making up the cells’ genetic material (i.e., nucleic acids); and production of fatty acids, steroids, and certain complex sugar molecules.

Thiamine deficiency can lead to cell damage in the central nervous system through several mechanisms. First, the changes in carbohydrate metabolism, particularly the reduction in a–KGDH activity, can lead to damage to the mitochondria. Because the mitochondria produce by far the most energy required for cellular function, mitochondrial damage can result in cell death through a mechanism called necrosis. Altered carbohydrate metabolism can lead to oxidative stress, characterized by excess levels of highly reactive molecules such as free radicals and/or the presence of insufficient levels of compounds to eliminate those free radicals (i.e., antioxidants, such as glutathione). Oxidative stress can lead to various types of cell damage and even cell death."  (from Role of Thiamine Deficiency in Alcoholic Brain Disease)

Simonti et al state:
"Decreased expression of this transporter in the brain or GI tract could exacerbate malnutrition or its symptoms. It is possible that new dietary pressures may have caused changes in carbohydrate metabolism to be beneficial in early human migrants out of Africa; indeed, there is evidence suggesting that Neandertal-derived genes increase the efficiency of fat digestion. More recently, the reduction of thiamine present in foods from the grain-refining process, as well as an increased intake of simple carbohydrates, make this a potentially harmful allele, because it could reduce thiamine availability although modern diets increase demand."

I am homozygous for the recessive allele of SNP rs12049593.  I have a C where 95% of people have a G or T, courtesy of my Neandertal ancestry.  According to the Simnoti study, I may have some malnutrition symptoms if I do not express the B1 transporter gene.  According to my research, B1 can also passively diffuse if it is ingested at high enough concentrations.

I tested oral administration of 100mg/day of B1, which is more than 6000% of the US RDA but is the only size pill commercially available; apparently, this is a standard doze for supplementing B vitamins.  I weighed myself morning and night for 1 week and did not notice any change in weight.  Subjectively, I noticed some tiredness the first two times I took B1, then I noticed some energy, and after four or five days I do not notice any effect from supplementation.

UPDATE:  Figuring out what allele is variant and which is most common is difficult.  My information above was from 23andme raw data viewer, but when I loaded my data into the excellent Enlis Genome Personal software, I see that I actually have the reference allele, not the rare allele.  So that may explain why I don't respond to supplemental B1.

Trying to Expose Sham "Nutrigenomics Testing"

Denise Minger published a post about her genetic MTHFR status that convinced me to test mine, but now I'm writing to expose this for scam it is. It took me an embarrassingly long time to realize that there is simply no scientific evidence for the claims on geneticgenie.org, mthfrsupport.com, or any of the other websites that have sprung up around Dr. Yasko's unsupported claims about SNPs and the detox/methylation cycle.  I fell for, and many people are continuing to fall for it.

The idea of correlating individual genetic differences to different nutritional requirements seems scientifically plausible.  But searching Pubmed shows that the claims being made about specific SNPs are not backed up by published scientific research. This scam propagates on plausibility, confusion, and ultimately, apathy.  I was taken in and confused by the veneer of scientific credibility...and when it didn't make sense I assumed I just needed to spend more time on the research.

But there is no research backing up these claims. They can all be traced back to Amy Yasko, who runs a website promoting her personal interpretations and observations.  While she claims not to make any money from sharing her knowledge, she promotes products and testing sold by her husband's company.  Her bibliography appears to include extensive scientific work, but I was unable to locate any of the papers she claims to have published.  She states that she is now "too busy" to publish her results.  I also could not find any confirmation that she is a real doctor (JD or PhD).

The sad truth is that, whether she believes in her own theories or not, this is a classic snake oil supplement gimmick hiding behind a sheen of fake science.  Selling B vitamins as miracle drugs has a long history, because almost everyone feels better with a few B vitamins (that's why they put them in energy drinks).  If you try the more expensive supplements she promotes, you may or may not feel better.  If you do feel better, you're quite likely to promote the gimmick. Most of the people commenting write in to say that they are feeling better, or think that they will when they get their supplement combination dialed in.  If you don't fell better, you might be motivated to try a different high-priced supplement, or you might just give up and stop reading this (or other) blogs.  The result is a huge number of people who appear to have been helped by this approach, and a continuous supply of new customers.

While we all want personally-tailored miracle drugs, maybe the best we can say right now is to eat "whole foods, mostly plants, and not too much"...and skip the overpriced unscientific supplements.

More background on Amy Yasko's nutrigenomics scam.

A brief review of the state of the science for one of Yasko's claims.

My review of the complex problems involved in evaluating Yasko's incomplete metabolic diagrams.

How Many Great- (Great...) Grandparents Did I Have?

Ancestry studies based on mitochondrial or Y chromosome assays only detect a single path through our complicated family tree.  For example, my Y chromosome is inherited from my father, and my father's father, who got it from his father's father's (...) father.  A test based on my Y chromosome wouldn't take into account any of the rest of my ancestry contributed from, for example, my father's mother's father's (...) father).

So maternal and paternal lineage data is really about just two branches picked out of our entire family tree.  The results are presented using "haplogroups", which are unique patterns of mtDNA or Y DNA that can be traced back to a single mutation event.  But ancestry is exponential, not linear! Haplogroups only detect a single branch out of a very large number of branches.  And what if my family tree isn't a tree, but a bush?  The scientific term for this is "pedigree collapse".

Assuming a generation time of 20 years, 500 years ago (=25 generations) I could have had 33 million great [...] grandparents! But the population of Europe (I have European ancestry) was only around 60 million in A.D. 1500 (Jan de Vries, compilation of estimates). Assuming no interbreeding of ancestors in the last 500 years, I would have to be related to everyone with European ancestry a little over 25 generations ago. Clearly there must have been some interbreeding, which would imply that I did NOT have 33 million great [...] grandparents.

This probably explains the question better than I can.  

I think the key question is...How many great [...] grandparents did I have? THAT would tell us how informative mtDNA or Y-chromosome haplogroups are.  If I had more grandparents then these tests are less informative.  If I had fewer grandparents they could be quite informative.

I'd be curious just to know ballpark figures. Did I have 10 million or 10,000 great [...] grandparents in A.D. 1500?

I found a study that shed some light on this issue: The Geography of Recent Ancestry across Europe by Peter Ralph and Graham Coop.  According to their results, there was a genetic bottleneck in, for example, the Balkans, around A.D. 1400 and a much larger bottleneck around B.C.  100.  This means that, for example, two average unrelated people in Europe share almost all of the same ancestors as recently as 1,000 years ago!