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Genetic Testing Consistent with Neurotyping?

I’ll try to keep this as short as I can because I feel like this is a very new topic - reviewed in May 2019 and published on June 4th, 2019 - of course warranting further exploration and discussion. I’m hoping that some of this site’s contributors can add some thoughts to these findings.

It appears that “extra” glucose tolerance is a recently acquired trait (500-50k years according to the study) just like Lactose tolerance was acquired, and that this tolerance has spread to some populations but not all races obv. In fact, SNPedia here lists massive differences from one region to another.

https://www.snpedia.com/index.php/Rs1061325

What I’m getting at is that I’m a type 1A. I’ve had HbA1c up to 6.2% while at my peak physique, embracing the frequent carb meals life. Turns out that I’m part of the 18% Europeans who’s also a T,T “hunter gatherer” homozygote. Somewhat unexpected tbh.

What’s Thib’s nutritional recommendations (and they’re spot on for me) = less carbs as in pretty much post workout only, not a whole lot of fat either, tons of protein. Eggs and nuts for breakfast. Multiple snacks, nothing that would push me off the sympathetic mode. This is quite consistent with Ori Hofmekler’s idea of a “Warrior Diet” who’d have the ancient genetics to “trap” glucose in the cell and fast / undereat, then feast - except that humans have evolved a lot, which is to say that neither paleo advocates nor vegans are inherently right or wrong. At least according to this very recent publication. Rhonda Patrick often mentions fructose “ATP trapping” and I think that this isn’t much different.

From there it would seem consistent to view type 2s as “farmer-hunter” heterozygotes maybe? and type 3s as the “farmer” homozygote type?

I think that this place is more open minded than your Reddit’s typical “just do 5x5 and eat whole grains” hive mind - I tried debating the topic on r/nutrition, to no avail . It would be great if there was a correlation between saliva testing and your neurotype.

Hopefully some people who’ve done both can chime in and add their results? If anyone here has done 23andme or ancestry or myheritageDNA testing, the gene you’re looking for should be in the raw data somewhere. Ctrl+F “Rs1061325”

@Chris_Colucci why move this to T replacement? I understand that Thibs forum might have not been the proper place for this but the Nutrition or Bigger Stronger forums sound more appropriate don’t they?

Im waiting on my genetic testing from 23 and me as we speak. Should have it in a few days…

Was that information front and center? Or did you have to look it up and research yourself?

Will this give me a better idea of what my diet should look like? I have always suspected I do better on lower carbs, but have kept them fairly high recently. In good shape, could lose some pounds to be more cut though for sure.

I don’t see that it was moved, but Supps & Nutrition would seem like a more appropriate place, so… yeah.

At this point, neurotype seems to be a) polygenic and b) modulated by developmental environment, probably during gestation. I say this first because we can not identify a single human gene that would control all of the factors determining neurotype, because individuals with the same primary neurotype have different secondary type dominance (indicating independent assortment of traits) and because I have known identical twins who clearly exhibit different neurotypes.

I will also mention that glucose utilization depends DRAMATICALLY on glucose intake as a percentage of calories. Individuals who eat <30% carbs at maintenance will make 300% more fat burning enzymes than individuals who eat 60% carbs, and will make less than half as much glycolytic enzymes, will burn more fat at all workload levels and will require 2-3x as much insulin to dispose of the same amount of glucose as someone eating 60% carbs because muscle cells get fat loaded and downregulate glycolytic enzyme synthesis. This effect can be shifted over the course of 3-14 days.

Also, glucose disposal/utilization is genetically independent from the ability to tolerate starch anti-nutrients. In other words, one person can use glucose very well, but be sensitive to grain/legume proteins and lectins, while someone else can tolerate them, but not run on glucose. There are independent proteins involved in glucose utilization and in gut permeability that are on different chromosomes.

Still, there seems to be a link in glucose tolerance and neurotype, so glucose tolerance is certainly one of many of the polygenic traits that determines neurotype.

I don’t understand why C.T.'s forum would be wrong for this discussion. He has written about genetics and neurotype and glucose metabolism, and responded to almost identical threads before with no issue.

Well I posted there unless I misclicked and then I saw the discussion pop up on T replacement. I must’ve goofed idk. I’m sorry to be annoying @Chris_Colucci May we move that thread there again? If CT’s fine with it of course. I’m just thinking that it would be nuts if we could combine some gene results and his work on neurotypes. Not dead on exact science but the more info you’ve got pointing to the same direction…

I don’t perceive the switch towards fat oxidation as beneficial considering that mitochondrial CO2 and ATP output should be better on glucose, hence the “ancestral” glucose “trapping” (to reiterate Rhonda’s wording on fructose). I agree that there other factors potentially at play yet if you have a permissive vs efficient GLUT4 transporter you’re going to have a strong hint at what your diet should look like, at least that’s the leap I’m taking from reading this paper? FYI I quoted a bunch of relevant parts on that Reddit thread

@alphagunner you do have to manually type the RS on the raw data. Just extract the .txt document from 23andme and you’ll get that sorted out easily

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Thanks, maybe ill tag you in a few weeks when I get it because some of that sounded like gibberish to me.

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Interesting. The glut 4 receptor may be a key. If I remember right, it is insulin independent and can be used to clear fructose and galactose from the blood too. If some individuals have a much more pronounced NIMGU (non insulin mediated glucose uptake) even without significant activity.

Also, some cell types can convert fructose into glucose. The prevalence of these enzymes in different cells could be important. Fructose is very toxic in the blood and can only be used by cells that can turn it into glucose/glycogen.

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FYI

https://www.ncbi.nlm.nih.gov/pubmed/9801136

The glucose transport proteins (GLUT1 and GLUT4 ) facilitate glucose transport into insulin -sensitive cells. GLUT1 is insulin-independent and is widely distributed in different tissues. GLUT4 is insulin -dependent and is responsible for the majority of glucose transport into muscle and adipose cells in anabolic conditions.

I think that the ancestral vs modern GLUT4 could make (blood) glucose excess as toxic as (blood) fructose. The “carb-phobics” might have had a point since day 1, if it turns out that their genetics indeed were the most efficient for glucose/fructose “trapping”. Eat carbs every blue moon, make the most of it within the cell. Sounds quite consistent with the paleo way of life. Obviously not true for people who are very well adapted to eating high glucose - independently of anti nutrients and such, which require extensive soaking, fermenting and all that jazz. I do very bad on those foods, no surprises.

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https://www.sciencedirect.com/topics/neuroscience/glucose-transporter

Double checking but I think it may be the glut 3 that moves fructose and primarily in non-insulin dependent tissues like some of the gut organs, nerves, eye, panceas. Also, people may vary in their gut organs’ capacity to absorb and transform fructose into glucose.

Also fructose causes glycosylation by a seperate mechanism-backing up the pylol or “sorbitol” pathway https://www.ncbi.nlm.nih.gov/pubmed/18224243 which makes 1 mg/dl of fructose in the blood equivalent to 10 mg/dl or glucose in terms of glycosylation effects.

Also, I seem to remember Paleo author Wolf found that as his carb intake dropped from 40 to 30 to 20 to 10% carbs, his fasting blood sugar crept up to around 120. This phenomenon is known as physiological insulin resistance but some people do not experience a profound increase in fasting blood sugar on low carbs while others do. Physiological insulin resistance appears to be due primarily to muscle cells filling up with fatty acids instead of glycogen and making fat burning rather than glucose burning enzymes, and also a degree of perpetual mild gluconeogenesis from protein. Ketones can also raise fasting blood sugar and even push glycosylation. Since burning glucose during activity upregulates glucose burning enzymes in muscles, peri-workout carbs may actually lower A1C, and since most peri-workout glucose is taken into muscles by NIMGU peri-workout carbs should not result in developmental insulin resistance. The main reason why people become more insulin sensitive when cutting calories is because fatty acids are depleted from muscle cells creating more space for glucose to move into after a meal, but people who easily produce cortisol in a calorie deficit can increase insulin output when reducing calories because of the effects of cortisol, glucagon, adrenaline and GH.

Fructose transporters are GLUT2 and GLUT5

GLUT3 was also shown to transport mannose, galactose, and xylose but is unable to transport fructose .

While we’re at it discussing fructose v glucose and glucose polymorphism, have you ever heard of something resembling fructose genetic polymorphism?

It would make sense that, unlike glucose, the abundance of fructose is so recent - pretty much mid 20th century according to USDA databases - that very few humans would be adapted to the amounts routinely eaten or drunk in the West. Even if most short term studies (wards or questionnaires) show that 30-100ish grams a day don’t disrupt blood lipids, I think they’re poorly designed.

  1. There are definitely people who experience frutosemia, but its not due to lack of uptake, but that the liver, gut and kidneys lack an enzyme that turns it into a usable form. As a result, glucose levels back up. It can result in high A1C and general glycosylation despite normal glucose levels. I do not know if the enzyme blocks an intermediate needed to turn fructose into glucose.

  2. Fructose was present in the primitive human diet because fructose composes approximately half of the sugar in fruit and honey, mostly in the form of the sucrose disaccharide. While I have not seen studies that show that increasing sugar raises triglycerides in the short run, my wife, as a cardiologist has found that patients with high triglycerides almost universally lower them by eliminating most sugar, and most high triglyceride patients consume a lot of sugar, especially juice and soda. Also, alcohol competes for enzymes that turn fructose into glycogen which is the healthiest outcome. Galactose may also work similarly.

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