[petejh]

Thought it would be interesting to start a thread about the effects our genes may have on performance and training.

Starter for 10.. Any geneticists here who could comment on the possible effect of BH4 on the body's ability to produce nitric oxide? Anybody think it may be possible that differing SNP's in MTHFR may impact production of BH4 which in turn may impact a person's aerobic or anaerobic exercise capacity?

Background for asking is I've been interested for years in learning more about MTHFR and COMT from a point of view of physical and mental health, and how diet/vitamins can help or hinder health and mood. As someone with a heterozygous mutation in MTHFR 1298 and 677 I've wondered if this could impact physical performance in any meaningful way? I notice that if I take a concentrated beetroot shot before climbing it noticeably improves my aerobic endurance and ability to shake off a forearm pump. I assume this is due to the increased level of nitric oxide in my body. And wonder if someone with (potentially) genetically-impaired ability to produce nitric oxide may benefit most from dietary supplements such as beetroot.

[Ru]

My wife is a doctor that specialises in this stuff. I read out your post to her and she talked at me for 15 minutes. I sort of zoned out after a couple of minutes though. I might try and pay more attention and do a reply later but I'm wading through a load of tax law at the moment.

[petejh]

 

Think she'd be interested in responding here? Or is my hypothesis about SNP's in MTHFR and/or COMT genes impacting nitric oxide which in turn impacts physical performance a blind ally?

[bigironhorse]

As someone with a heterozygous mutation in MTHFR 1298 and 677 I've wondered if this could impact physical performance in any meaningful way?

I don't know anything about these specific genes but the answer to this may be influenced by the nature of the heterozygosity. If both mutations are on the same allele then you may see haplosufficiency, where one normal allele is sufficient for normal function (again I don't know anything about these genes so not sure if this is likely to be the case). If you have one mutation on each allele (compound heterozygote) then you may see a greater effect. Obviously the nature of the mutant allele is also important e.g. loss of function, gain of function or neutral.

[Ru]

Or is my hypothesis about SNP's in MTHFR and/or COMT genes impacting nitric oxide which in turn impacts physical performance a blind ally?

From what I understand from what she said, (I have no background in genetics or any real knowledge so I may have got this wrong) there is an impact but quite what that impact is in a person is very difficult/impossible to tell just from SNP's in MTHFR and/or COMT. MTHFR/COMT aren't the only genes involved in these pathways and there are many other genes that code for similar things or provide different pathways to the same result. Genetic tests also tell you nothing about how a gene is expressed. She says diet changes /supplements can help. Sorry to be vague.

[bigironhorse]

Based on a very quick skim of this (https://omim.org/entry/607093) it sounds like the SNP's you describe have little effect on expression of the gene, but lead to production of altered protein products. In one study the 1298 SNP enzyme was found to have indistinuishable biochemical characteristics to the wild-type whereas the 677 produced an enzyme with reduced stability, however this may be controversial. No additive effect was reported when both SNPs were present in the same allele.

Alleles with both SNPs are considered rare (interestingly with increased incidence in the UK), so I guess you are more likely to be a compound heterozygote, but this may not be clear from a simple genetic screen.

PS: I am not spending any more time thinking abut this than it takes to type so may be wildly innaccurate!

[petejh]

Thanks both, interesting.
BIH, yes compound heterozygote. There's a good resource on the website 'foundmyfitness.com' where you can upload your 23andme raw file to get more detailed info on various SNPs that you may have. I also cross-referenced the uploaded raw data on 'genticgenie.org' to see if they give the same result.
Ru, yes understand that there are loads of different pathways, genes and even workarounds for various bodily processes. But it is interesting that reduced BH4 is implicated in a few of the various MTHFR and COMT SNPs, and BH4 is mentioned in various places as a rate-limiting cofactor in the body's production of nitric oxide - a substance essential for aerobic and anaerobic endurance.  But yeah massively complex no doubt. All I know is beet supplementation greatly increases my forearm aero capacity like I say, presumably due to the increased production of nitic oxide.

[TobyD]

Thanks both, interesting.
....  But yeah massively complex no doubt. All I know is beet supplementation greatly increases my forearm aero capacity like I say, presumably due to the increased production of nitic oxide.

Again,  purely subjectively,  beetroot makes no perceptible difference to me, but I tend to develop and maintain endurance easily.
However,  strength training and protein intake also don't seem to have that much impact on strength or power. 

[Will Hunt]

Is this what Montgomery meant when he told his men to find favours in the beetroot fields?

[Stu Littlefair]

Ru, yes understand that there are loads of different pathways, genes and even workarounds for various bodily processes...

Let me preface this by saying I know less than nothing about this topic. But whenever anyone asks about the effect of a single gene or supplement and tries to work out the effect from first principles I go and have a little look at these posters and then have a 5 minute lie down.

http://biochemical-pathways.com/#/map/1
http://biochemical-pathways.com/#/map/2

[Johnny Brown]

All I know is beet supplementation greatly increases my forearm aero capacity like I say, presumably due to the increased production of nitic oxide.

'Know' is a big claim. How are you controlling for the placebo effect?

[petejh]

Haha! Yes it's a complex subject but that doesn't mean it's not possible to ascertain some general principles and good practices, which are based on solid evidence. And for people with mutations of one or other of the MTHFR genes there's plenty of good quality evidence out there for the positive impacts on health following supplementation with various of the B-vitamins. (as well as negative ones, e.g. clear association with increased risk of cancer in men from high B12 doses, i.e. over 1mg/day). 

Your post could be taken as suggesting 'it's too complicated to be worth caring about'. I don't agree. 747s are complicated to build but pilots don't need to be able to build a 747 or know it's wiring diagram in detail to know how to fly one safely. They require an overall working knowledge of its various systems.

[petejh]

JB: yes of course I'm cloning myself and not allowing my clone to take the beetroot, and then setting off against me on the beacon lead wall 

For 'know' accept my apologies and read as 'feel'. But I know when I'm pumped and not able to shake it off versus when I am able to shake it off. And the evidence for concentrated beetroot being having beneficial impact on exercise capacity is pretty well-established.

[teestub]

Was the mechanism for beetroot increasing exercise performance to do with handling lactate? I thought the best results were for more aerobic exercise but I’m too lazy to look.

With how invested ( 😄 ) you are in dietary supplementation I bet you’re going to have an even better placebo effect than others would, so it’s win win!

[petejh]

Quite. Not only do I not get as pumped I also get richer.

[Stu Littlefair]

Your post could be taken as suggesting 'it's too complicated to be worth caring about'. I don't agree.

Nor do I. My meaning is really that the complexity of the system is such that approaching from the bottom up - i.e "it's plausible that gene X has effect Y and therefore Z" - is too likely to create explanations that possess truthiness but are wrong.

It makes me feel that the way to tackle this kind of issue is through the analysis of population level data and the results of very large trials, which is merely extremely hard rather than completely impossible.

So to use this specific issue, discussions along the lines of "there's good evidence for beetroot, and I feel it works for me" are interesting and useful to fellow climbers, whereas discussions along the lines of "maybe this is because gene X has effect Y" are probably not, and are potentially misleading and (in some cases but not this one) dangerous.

[petejh]

Yep.
But that should be obvious to anyone with a brain, it's no reason not to discuss this sort of topic on here. Only a fool would read something on the internet and then think 'magic bullet, simple' - and there are no shortage of people and companies willing to take your money in relation to spurious health claims to do with this stuff. Hasn't that always been so?


So, going back to my original question about BH4 in particular, and my question about it possibly having some impact on climbing (or any athletic) performance.

1. The evidence is established that BH4 is an important co-factor in the production of Nitric Oxide. source

2. The evidence is established that people with particular SNP's of the most well-researched MTHFR genes (1298 and 677) have varying reduced levels of BH4. source

3. Therefore it's reasonable to ask, and the evidence suggests it is so, if those people with SNPs of 1298 - a mutation that's quite common in the population - also have some level of impaired production of Nitric Oxide? Especially under conditions of high demand. As in heart attack for e.g. source

4. Another condition of high demand for Nitric Oxide is when we're asking our muscles to perform efficiently during hard climbing. Surely I don't need a source for this but you can DYOR.

5. It's well established that supplementation with high-nitrate concentrated beetroot temporarily boosts production of Nitric Oxide compared with placebo. source

6. Therefore, can supplementation aimed at improving the function of the two most well-researched MTHFR genes 1298 and 677 also improve production of nitric oxide in people with impairment as a consequence of BH4? And as a result does this affect how pumped you get trying to onsight left wall?

I only ask because I find it interesting that there may be a genetic component in propensity to forearm pump that is to do with a part of genetics that's already relatively well-researched (relative to other pathways that is), due to it being to do with the Methylation pathway. (but certainly nothing conclusive).


Or we could just discuss non-controversial safe topics like kneepads spoiling Sheffield climber's most highly-cherished route, why BoJo's a cunt, and Shark's endless pushing the stone up the hill of the Oak.

[Johnny Brown]

JB: yes of course I'm cloning myself and not allowing my clone to take the beetroot, and then setting off against me on the beacon lead wall 

Well that's not going to work either. You need to prepare an identical potion in appearance and taste but no beetroot, and then give them to a trusted third party to randomly administer to you and your clone. Preferably repeatedly.

[teestub]

This meta analysis only discusses improved cardio respiratory endurance and VO2max which isn’t much use unless you’re actually redpointing Alps not sport routes. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5295087/

Have you got any papers where beetroot is show to increase anaerobic performance or reduce lactate levels?

And more importantly were you using a knee pad when you were trying Mecca, or just the heel spurs?

[petejh]

I was using a kneepad and Anasazi Whites on Mecca,  so both 

Research away regards high-nitrate beetroot. 'Examine.com' is a good place to find a load of papers.

There are 57 references to get through.

Also - isn't it well accepted that anaerobic capacity is impacted by aerobic capacity? Barrows?

edit: to quote Barrows' Ancap/Aerocap/AnPow/AeroPow document -'in reality the tanks are linked together in a number of ways, expanding one aspect will affect the others and no doubt there are other flaws with the analogy I've not thought of!'.

[petejh]

Stuff like this makes people suspicious because it can seem like 'hacking' the body and potentially dangerous (as Stu mentions). But there are all sorts of ways of 'hacking' the body for improved health that could, if looked from a certain angle, seem like playing around with our ancient software.. Just today there was a report on the news about how researchers have discovered a latent mechanism in the body that can be triggered by cold-water swimming. The latent system comes from a time when our ancestors used to go into 'hibernation mode' at times of hardship, and which produces a protein researchers have suggested may be potentially beneficial in reducing risk Alzheimers.

I suggest that if 'cold water swimming' was replaced with 'cold water stress therapy' and offered by companies with 'special therapy pools' then it'd be viewed suspiciously, quite rightly.

But it's just the cold-stress reaction in the body triggering certain genes. The same for 'heat-stress gene-triggering treatment'... aka saunas, a related reaction to cold-stress is likely being triggered.