Significant improvement in quality of life by hacking glucose metabolism

[sb4]

Something that I forgot to mention is that chris masterjohn is always banging on about how insulin is needed to build glutathione, thyroid hormones (I think) and some other stuff. Perhaps that urge for carbs is your body crying out for glutathione or something similar.

That good thing about MCTs though, if I am correct with there mechanism of action, is that you can have high insulin without the negative effects of glucose on PDH.

 

[gregh286]

Yeah I have heard that you should eat vegetables with high long chain fat as like you say, the high fat increases inflammatory effects of the immune system and short chains (created by bacteria for veg) reduce that inflammation.

In my reading I found that MCTs can potentially cause allergies and increase Th2 although I think this is from oral consumption as the effects happen in the intestines. It was recommended to take away from food but that obviously can cause GI issues.

If I were you @leokitten I would purchase some regular MCT oil and use it transdermally with your normal keto meals and see what effects. If no or minimal sides then progress to using it with some carbs. I would cup my hand and poor some in my hand then apply it to my skin 3/4 times, which is probably equal to 6-7tbsps. I apply it to my torso and face and sit shirtless for a good 6hrs. Apply it 15-30mins before eating. I would also buy some C8 (in my very limited experience C6/8/10/12 containing ones cause worse GI response) and take 1/2tbsp at first but see how far you can build up to over the coming weeks, assuming of course, that it has helped you.

I am still tinkering with this at the moment as I am experiencing a little too fast GI. I think the thing with MCT is, even small amounts can cause big symptoms. You may not need as much as me however as I am eating like 200g carbs in my morning meal, with some butter and cheese, and then a fairly low carb evening meal.

If you just do 100g carbs +MCT like once or twice a week you may be filling up some nutritional deficiencies that you might be encountering on the keto diet. Hopefully if this is true it will stop your urge for carbs followed by a crash, but there is a lot of if's and but's before then. I choose potatoes because they are nutrient dense, particularly in magnesium and potassium which I find hard to get on keto. Also I have a weird thing going on with me where I have an aversion to salt despite having POTS and high salt does me no favours. I seem to crave foods with higher Mg and K.

Yea get that too low cell mineral status. All over muscle twitches...specially chest muscles. Have to start tanking mineral and electrolyte drinks till it stops.

 

[tyson oberle]

Something that I forgot to mention is that chris masterjohn is always banging on about how insulin is needed to build glutathione, thyroid hormones (I think) and some other stuff. Perhaps that urge for carbs is your body crying out for glutathione or something similar

That good thing about MCTs though, if I am correct with there mechanism of action, is that you can have high insulin without the negative effects of glucose on PDH.

I wonder if metformin with the combination of carbohydrates and mct oil would be beneficial?

 

[sb4]

I wonder if metformin with the combination of carbohydrates and mct oil would be beneficial?

Very interesting thought. As far as I understand it, metformin destroys complex 1 in mitochondria, forcing the electrons to go in at complex 2 but does this stop the upstream usage of pyruvate through PDH?

What mechanism did you have in mind @tyson oberle?

 

[SherDa]

Would taking a ketone supplement increase allergies? Or is that specific to MCTs?

 

[sb4]

Would taking a ketone supplement increase allergies? Or is that specific to MCTs?

The mechanism I was talking about earlier I am pretty sure is specific to MCTs.

 

[tyson oberle]

Very interesting thought. As far as I understand it, metformin destroys complex 1 in mitochondria, forcing the electrons to go in at complex 2 but does this stop the upstream usage of pyruvate through PDH?

What mechanism did you have in mind @tyson oberle?

I do not have a specific mechanism in mind, except that metformin is supposed to improve insulin sensitivity.

 

[sb4]

I have recently had a new idea on how to eat carbs and bypass PDH. Alcohol.

Ethanol gets converted mainly in the liver to acetaldehyde the acetone and then to acetyl CoA. As far as I understand it, this is very much like MCTs, in that they are preferentially oxidized immediately, unlike LCTs.

This means that with sufficient alcohol, the liver and other tissues via the blood will have lots of acetyl CoA from alcohol whilst also having a lot of pyruvate from carbs. This will mean the pyruvate will be forced down though pyruvate carboxylase instead of PDH and into oxaloacetate. Indeed you can get ketoacidosis if you drink excessive amounts of alcohol.

Now the obvious problem with this is acetaldehyde which is know to be a major cause of alcohol related health issues. So how much would we have to drink to get the equivalent effect of MCT oil?

100ml of vodka is 276kcal (0 carbs 0 fats 0 protein). 1 tbsp of MCT oil is 126kcal. A small shot glass of vodka is 25ml and 1 unit. So 2 shots of vodka should = 1 tbsp of MCT oil. So 4 shots a day would be like drinking 2 pints a day.

This is quite a lot, especially considering how sick we already are, also considering that many of us can't handle alcohol well anymore. Indeed I haven't drank in 6yrs+ after finding my symptoms got way worse the next day. However this is when I was still going out down town and drinking many units. Perhaps a lower level spread out more evenly through the week wouldn't be so bad.

men and women are advised not to drink more than 14 unitsa week on a regular basis. spread your drinking over 3 or more days if you regularly drink as much as 14 units a week.

So if I where to drink my equivelant amount of MCT oil a week I would be hitting 28 units, double the limit, however it would be spread out. If I had half this dose and the equivilant to 1tbsp mct a day it would be right on the limit.

It should be noted that alcoholics go way way over this limit. I know my dad does, and I just saw an article saying Adrian Chiles was at 100 units per week.

The recommended limits for men are 3-4 units a day and for women it’s 2-3 units a day. It’s also recommend that everyone has at least 2 or 3 days off alcohol a week.

Perhaps transdermal MCT oil, oral exogenous ketones, and a shot of vodka with carbs is the way to go?

@Hip

 

[leokitten]

@sb4 I don’t know the mechanism, but for me any amount of alcohol contributes to PEM and worsening symptoms.

When I got ME I got sudden strong alcohol intolerance from one day to the next where before I could drink without any issues. Even a fraction of a glass made me feel like I had alcohol poisoning and had drank way too much, I would vomit and feel intensely ill.

For about the first 6 months to a year it was like that and then it slowly started improving, though it was like a few other gradual symptom improvements that mistakenly made me feel like my ME was getting better in general when in reality was it was going from acute to chronic phase. I could drink a little after a couple years. But even then and to this day, one glass causes eventual symptom worsening, it’s just not as severe as before and if I want to have a glass or wine or two with a dinner once in a blue moon I just know and deal with the consquences.

 

[sb4]

@leokitten Dammit. Punches a hole in my theory. You do better on ketosis so I am guessing you have problems with PDH so this should help you but doesn't. I will probably give it a try myself in the near future although like I say, I also remember alcohol causing me problems.

So the problems that alcohol could cause that spring to mind are:
1) Acetaldehyde. This is a problematic molecule that needs to be quickly turned into acetone. If you drink too much and cause a bottle neck you could have problems.

2) The ethanol handling organs are low in energy thanks to CFS meaning they cannot facilitate the reactions quick enough and cannot deal with negative effects of accumulating acetaldehyde as well.

3) Thiamine deficiency. This could be a big one as thiamine was a big help to me at one time. Alcohol causes thiamine deficiency.

4) Folate deficiency. Alcohol also blocks the absorption, or something similar, of folate. Quite a few CFSers have a lack of folate. Interestingly one of the symptoms I do remember from when drinking with this illness is I would get a very painful achy feeling in the bones of one of my arms the next day. It was really unpleasant. I have also got this same achy bone feeling multiple times from messing around with higher dose methylfolate. These are the only times I have gotten this problem so I am pretty sure it is related to folate.

Of these things there is not much you can do about the first 2 other than spread the dose out through the day. However the last 2 can be corrected with supplementation. I am currently supplementing allithiamine and methylfolate daily as well as other methylation support. So perhaps this will allow me to avoid the negative effects?

 

[sb4]

Here is the paper on MCTs potentially causing allergies via oral consumption. I have yet to read through it.

Here is alcohol blocking thiamine absorption.

Here is a study suggesting other methylation B vits are reduced in alcoholism.

Here is a study showing folate deficiency in alcoholism induced in various ways.

Ethanol‐associated folate deficiency can develop because of dietary inadequacy, intestinal malabsorption, altered hepatobiliary metabolism, enhanced colonic metabolism, and increased renal excretion. Ethanol reduces the intestinal and renal uptake of folate by altering the binding and transport kinetics of folate transport systems. Also, ethanol reduces the expression of folate transporters in both intestine and kidney, and this might be a contributing factor for folate malabsorption, leading to folate deficiency.

 

[sb4]

Okay so going through the MCT inducing alergies paper it appears that the mechanism is through lack of chylomicrons.

Basically, LCTs require chylomicrons to be absorbed from the small intestine, MCTs do not. If you supply LCTs but blocks chylomicrons with drugs then you get more or less the same results as using MCTs in regards to increasing allergy sensitivity.

With chylomicrons you get more antigens in the blood and less in the lymph tissue. For whatever reason, this is good and doesn't cause antigen sensitivity. Without chylomicrons you get less antigens in the blood and more in the lymph, this leads to more IgG and IgE.

Apparently feeding antigen plus LCT a week before feeding antigen + MCT means that MCTs are fine and don't produce allergies.

So far it seems that if you eat enough LCTs with your MCTs then you will release chlymicrons and thus be protected against the antigen effect. This should work if they chylomicrons work by absorbing antigens and thus minimizing antigen interaction with immune cells in Peyers Patches. If the problem however is antigens somehow attaching themselves to non chylomicron bound fats, and if MCTs don't absorb into chylomicrons or the MCTs exit the stomach before LCTs, then eating LCT with MCT may not make a difference.

It then goes on to say MCTs promote TH2 response in intestinal epithilia and again this seems to depend on chylomicrons.

 

[SherDa]

@sb4
In attempting to stimulate PDH:

From Wikipedia: In humans, CoA biosynthesis requires cysteine, pantothenate, and adenosine triphosphate (ATP).

Also, does lysine play a role? For a long time, I had a sticky note on my laptop that said "lysine degrades to acetyl CoA." It was there so long that I'm not sure where I picked up on this, but I'm positive it was the idea of someone much smarter than I in the realm of biochemistry.

It seems like lysine and cysteine are present in damn near every important peptide or protein in human metabolism. Like any protein or peptide that relies on disulfide bonds for its structure will have cysteine. (This includes the peptide hormones like vasopressin. I'm assuming any hormone that helps regulate fluid and electrolytes is of interest.)

So here it seems are 2 amino acids that are necessary for PDH but also potentially cause a lot of systemic systems when depleted?

I know that's not super-helpful, but when I get obsessed with trying to figure things out, it's always nice to have other avenues to explore when I hit a dead-end, so maybe there is something in the amino acid world that can help stimulate PDH?

Lysine and cysteine both make me feel better, but it's short-lived. Cysteine (and other sulfur supplements like glucosamine sulfate) depletes my copper pretty quickly, which is manifests as anemia and boils in less than 2 weeks (every time!). I'm unsure if I should continue the cysteine/sulfates but increase copper intake or back off the sulfur. I love the way sulfur supps make me feel, at least until my copper gets depleted. I have no idea if this is from acetyl CoA production or something to do with iron-sulfur complexes or some other reason.

I'm interested in your glucose metabolism experiments. If one cannot burn glucose well, then hopefully symptomatic relief can come from fat or ketone burning. I guess at this point I'm worried that inflammation upregulating IDO wastes tons of B6 and alters protein metabolism, so I try to look for responses to amino acid supplements to try to confirm this, but I also understand the complexity of human metabolism so I accept that it's unlikely I'll figure it out.

 

[sb4]

@SherDa Yeah I too am interested in amino acids effects on PDH and would be interested in knowing what you find out.

Lysine is an interesting one as, as far as I understand it, it is crucial for the use of B6. I think the B6 binds to the lysine on molecules to cause an effect.

Interestingly I think Glycine also might have helped my glucose metabolism though I am not 100% sure. It has been shown to help diabetes but I was thinking that since it can be turned into pyruvate, perhaps glycine or an intermediate sends the signal to turn on PDH that is otherwise being blocked by glucose.

 

[pamojja]

Also, does lysine play a role? For a long time, I had a sticky note on my laptop that said "lysine degrades to acetyl CoA." It was there so long that I'm not sure where I picked up on this, but I'm positive it was the idea of someone much smarter than I in the realm of biochemistry.

Not any smarter, but searching usually does find something again: https://www.google.com/search?q=lysine degrades to acetyl CoA&ie=utf-8&oe=utf-8&client=firefox-b

Cysteine (and other sulfur supplements like glucosamine sulfate) depletes my copper pretty quickly, which is manifests as anemia and boils in less than 2 weeks (every time!)

Interesting, because I do have higher serum, whole blood and unbound copper, but all the NAC, MSM, DMSO, glucosamine-, chondroitin-, and Mg-sulfate (from Mineral water) I took wasn't helpful to bring it down at all. At least for the last 10 years.

I guess at this point I'm worried that inflammation upregulating IDO wastes tons of B6 and alters protein metabolism, so I try to look for responses to amino acid supplements to try to confirm this,

Would explain why I need so much B6 (only 200 mg/d brought dream-recall back). I do supplement lysine at 6 g/d.

 

[sb4]

@gregh286 I found this paper that suggests that ME/CFS patients have higher levels of malondialdehyde. Malondialdehyde is detoxified using the enzyme ALDH1A1 and similar enzymes. These same enzymes are used to detoxify acetaldehyde and formaldehyde (which is what alcohol gets broken down into).

So if we already have higher levels of malondialdehyde and other aldehydes that use ALDH1A1 / etc then adding ethanol on top of this is just adding fuel to the fire, potentially explaining why people with CFS feel terrible after drinking.

 

[Peyt]

@sb4 or anyone that might know the answer to this question:
Is MCT oil is a vasodialator?
I have Orthostatic Hypotension and can not take anything the dilates blood vessels any further because it gives me low blood pressure and headaches. I remember trying L-carnitine a while back for the same purpose of breaking down fats and got really bad headaches due to L-carnitine's vasodilating effects, so just wondering if MCT oil is in the same class as far as vasodilation ?

 

[Peyt]

This article suggests that coconut oil helps lower blood pressure and increase N.O. which is exactly what a person with POTS or Orthostatic Hypotension would not want, and since MCT oil is derived from Coconut I am wondering if the same would be true?
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3687594/

 

[sb4]

@Peyt I am not sure if MCT is a vasodialator or not. I apply it just before food and I get hot soon after but that is most likely the food.

I have trouble also with heat and vasodialation yet MCT overal helps my symptoms by reducing postprandial carb symptoms.

I would say to buy some, it's fairly cheap and see how you feel. If gut symptoms then apply transdermally.