Coconut Oil Leads To Dementia?

[SB4]

So...are you saying that basically no matter what we eat it will jam up TCA and ETC? Or is it just synthetic fats that do that?

Well, from what I've read, some foods and water are naturally more deuerium depleted than others. Fats are, carbs are deuterium loaded, protein in the middle, but obviously it varies. Water, in general, the higher up it is, further inland, and colder it is, is more deuterium depleted. This is because deuterium freezes at a higher temp.

Deuterium seems to be pro growth, so kids need more deuterium, and cancer likes more D.

So if you eat high carbs and it is summer time, the sun helps you deplete the higher D levels from your body. How it does this I'm sketchy on but something to do with sugars having D on there second(???) carbon bond and UV light helps brake it off (deuterium is harder to break as its heavier and reactions are slower as its held more closesly to molecules vs H). If you have decent mito function it seems you could also get away with high carb as the mitochondrial matrix contains DDW so you can get D out of the TCA cycle when it swaps H/D ions inside the mito.

Then when winter rolls round. You eat high fat and have cooler (DDW) water so you dont need much help from the sun to deplete D.

So perhaps why these synthetic fat are bad is decause during hydrogenation (???) they remove the DD hydrogens of fat (say at 125ppm) and replace them with regular tap water at 155ppm. This would be a big change in how much D cytochrome 2 sees and will slow down all reactions D is involved with resulting in less energy and the bad effects we see from these fats.

I don't know, I'm just speculating here but it seems reasonable.

 

[shepherdgirl]

"RP: In the 1930s when they first made isotopically heavy water with deuterium replacing hydrogen, they found that it slowed biological processes - daily rhythm, nerve conduction - and in 1950 they showed in mouse experiments that it tremendously accelerated the aging process and all of the features of aging, slowing metabolism and dying prematurely were produced but it took about 50 years after that before people started experimenting with the light water from which the heavy water has been removed and they found that - for example, they were experimenting with it in Russian space vehicles and they found the condensed sweat had been filtered and it was a very light water resembling glacier water."
from:
KMUD Herb Doctors: Inflammation (Jan 2011)

 

[SB4]

@shepherdgirl Interesting, thanks. So ray peat knew about deuterium, huh.

 

[nbznj]

this whole topic is such a gem, however this completely blew my mind

But cardiovascular disease appears to have little to do with lipids (Pauling, 1991).

especially knowing that modern fruits and vegetables are pretty damn poor in vitamins, especially C. I read somewhere that our grandparents got 50x more vitamin C from an apple. I know there's more to fruits than ascorbate but it's definitely back to my supplements staple.

 

[Travis]

...But probably not as interesting as kinetic isotope effects in biochemistry. As early as 1934, it had been predicted by Michael Polanyi that molecules incorporating H², or deuterium, would have different rates of metabolism within the body—compared of course to those containing hydrogen. The heavier tritium, having one proton and two neutrons, would be expected to be slower than both:

'It is obvious that this new discovery opens up a wide and important field of work, but I shall leave my chemical colleagues to deal adequately with this question. On account of its greater mass, it is to be expected that the rate of diffusion and the rate of chemical reaction will differ when H² is substituted for H¹, while the compounds formed with the new isotope are to be expected in some cases to exhibit rather different properties from the normal hydrogen compounds. Similarly, this new discovery opens up interesting questions on the effect of heavy water in altering the normal physical and chemical processes in animal and plant life. A certain amount of information is already available in this interesting field of enquiry.' ―Polanyi⁽¹⁾ (1934)​

I only mention this somewhat trivial fact because Michael Polanyi is a Peat‐approved biochemist, mentioned in three of his articles. Ray Peat had even made clear that he'd read Polanyi's book—entitled 'Personal Knowledge'—in his article Physiology texts and the real world. So like Gilbert Ling, Thomas Kuhn, Joseph Needham, and Linus Pauling, the books and articles of chemist Michael Polanyi should perhaps be considered worth reading.

Since deuterium is not radioactive or dangerous in any other conceivable way, all metabolic changes must result from kinetic isotope effects. Polanyi's prediction had come true, and chemists routinely measure these effects primarily to determine specific information about a reaction mechanism. The anti‐metabolic effects of heavy water (D₂O) could stem mostly from deuterium's relatively slow enzymatic kinetic rates compared to water (H₂O). The rate of pyruvate decarboxylation in the enzyme pyruvate decarboxylase—I hate those tautological formulations yet they are inescapable—of Zymomonas mobilis was found to be greatly influenced by the heavy water concentration of the solution.⁽²⁾

The overall isotope effects of pyruvate decarboxylase of both species was on the order of ~1.25–1.30, meaning that deuterated water slowed the metabolic rate of this enzyme by ~25–30%. Since there was little interspecies rate variation between enzymes of Zymomonas mobilis and Saccharomyces cerevisiae, you'd probably expect the human enzyme to be similarly effected.

But most interesting about this study is that the observant reader will note that this drives another dagger into the Breslow Mechanism for thiamine action. The Breslow Mechanism relies on the #2 carbon being deprotonated and reprotonated, an event that kinetic isotope effects this small would preclude serious consideration of. When a hydrogen bond is broken or formed in an enzymatic reaction, kinetic isotope effects between 8 and 20 are generally observed.

The Breslow Mechanism⁽³⁾ would require a higher kinetic isotope ratio than observed.

Instead of acting like Breslow seems to imagine, the open‐ring Knell Mechanism⁽⁴⁾ is more realistic and is not contradicted by the above kinetic isotope data; this mechanism involves the shifting of a methylene bridge (think folate) with the now exposed thiolate group attacking pyruvate's α-carbon. Many thiols are acidic and become deprotonated in solution, so the Knell Mechanism doesn't require any proton transfer with water or deuterium.

Knell draws a protonated thiol above, yet also draws the thiolate when depicting a similar reaction (shown below). This thiolate would be stabilized both by intramolecular resonance and by an intermolecular hydrogen bond to ³⁸⁸threonine within the enzyme's binding pocket. So this thiol(ate) could be expected to exist in the deprotonated state, making the Knell Mechanism compliant with the kinetic isotope data of pyruvate decarboyxlase since the Knell Mechanism involves no proton transfer with solution.

click to embiggen: Catalytic domain of pyruvate decarboxylase and open‐ring thiamine (deprotonated)

And besides all the lines of evidence already compiled by Knell against the prevailing Breslow Mechanism, there is more recent evidence that thiamine exists in the open‐ring configuration discovered by X‐ray structural analysis!

[1] Rutherford, Lord. "Discussion on Heavy Hydrogen: Opening Address." Proceedings of the Royal Society of London. Series A, Containing Papers of a Mathematical and Physical Character (1934)
[2] Sun, S. "Carbon isotope effects, solvent isotope effects, and proton inventories for the unregulated pyruvate decarboxylase of Zymomonas mobilis." Journal of the American Chemical Society (1995)
[3] Breslow, Ronald. "The mechanism of thiamine action: predictions from model experiments." Annals of the New York Academy of Sciences (1962)
[4] Knell, Alan. "Thiamine: a study of its chemistry, biochemistry and mechanism of action." Dissertation: University of Warwick(1970)​

 

[SB4]

@Travis Maybe you will be interested in this Submolecular regulation of cell transformation by deuterium depleting water exchange reactions in the tricarboxylic acid substrate cycle
I haven't read it yet.

How it affects the TCA and then mitochondria is key. What happens if the NADH is actually NAD(2)H. Will this deterium slow down electron delivery? What if D gets gets pumped across the inner mitochondrial membrane? Will it jam up the ATPase?

Why are raypeaters able to eat a ***t ton of deuterium (carbs) yet appear to be healthy? Is it because their mitochondrias water is deuterium depleted and they are very good at recycling it?

 

[Such_Saturation]

Why are raypeaters able to eat a ***t ton of deuterium (carbs) yet appear to be healthy?

You mean 155ppm versus 140ppm?

 

[SB4]

You mean 155ppm versus 140ppm?

Yeah, although if its keto it would be more like 120-130 I think.

It appears a small amount change but considering how much water is in the body and how much its used, small changes could be very signicant.

Also, I cant find it now but I read somewhere that even 1 deuterium can affect something crazy like 72 surrounding hydrogen ions proton tunneling. So could have effects a lot bigger than its ppm.

 

[Such_Saturation]

Yeah, although if its keto it would be more like 120-130 I think.

It appears a small amount change but considering how much water is in the body and how much its used, small changes could be very signicant.

Also, I cant find it now but I read somewhere that even 1 deuterium can affect something crazy like 72 surrounding hydrogen ions proton tunneling. So could have effects a lot bigger than its ppm.

The effect on water of those extra oxygens is likely even more important.

 

[Travis]

@Travis Maybe you will be interested in this Submolecular regulation of cell transformation by deuterium depleting water exchange reactions in the tricarboxylic acid substrate cycle
I haven't read it yet.

How it affects the TCA and then mitochondria is key. What happens if the NADH is actually NAD(2)H. Will this deterium slow down electron delivery? What if D gets gets pumped across the inner mitochondrial membrane? Will it jam up the ATPase?

Why are raypeaters able to eat a ***t ton of deuterium (carbs) yet appear to be healthy? Is it because their mitochondrias water is deuterium depleted and they are very good at recycling it?

I know. I was actually looking for an article on H²‐labeled pyruvate when I found the one on heavy water; and since this was related to @shepherdgirl's comment, I had kept reading despite it being on heavy water and not pyruvate. But to my surprise, that article had provided a rather strong argument against my favorite biochemical unicorn: the Breslow Mechanism. While not as important as Na⁺/K⁺‐ATPase, it is interesting to ponder how something so obviously wrong can be maintained as fact for over 50 years. If you read the Knell Dissertation, I think you will agree that the Breslow Mechanism is less realistic than the open‐ring explanations. Even simply looking at the Breslow scheme can give a person uneasy feelings, and the Knell Mechanism is so cool that you want it to be true.

I was thinking that kinetic isotope effects of the enzymes could play a small role; all of the dehydrogenases, and all the NAD⁺ hydrogen transfers, would be expected to contribute to the differential kinetic isotope effects between the relatively H²‐enriched fatty acids and the carbohydrates. But then I got to thinking that this would likely be overshadowed by the proton migration occurring in the mitochondria, just as you say. I did read a classic Mitchell article or two almost a year ago, and his explanations are generally considered correct to this day. Although many criticisms can be made against many things in biochemistry, I found the Mitchell articles rather solid. After all, ADP does need a proton to becomes ATP. It's not that these protons add to ADP; what happens is that H⁺ adds to a hydroxyl (–OH) on phosphate, catalyzing its removal as it leaves as H₂O. So this H⁺ migration across the mitochondrial wall seems completely necessary, both for this reason and you have to account for all the hydrogens stripped‐off of glucose somehow. The carbons and the oxygens become carbon dioxide, and perhaps even water at times, but the hydrogens do need to go somewhere. They seem to be transported from glucose, to NAD⁺, to ADP/ATP, and then this 'hydrogen potential' on ATP is probably transferred to the cell membrane and beyond. When ATP becomes ADP, the converse reaction occurs: this reaction liberates H⁺, instead of neutralizing it. Some of these H⁺s must eventually be funneled to the urine since this fluid is always excreted at low pH.

Kinetic isotope effects can be as high as 20, meaning that a 100% deuterium‐enriched fatty acid could be metabolized over 20× slower that the corresponding pure hydrogen analogue; there are many enzymatic steps, and enzymatic rate of each step would compound. But as you had said, the difference in isotopic enrichment is only 140‧ppm vs 155‧ppm: Finding out if this would make a significant difference appears somewhat difficult because I haven't seen one study focused on this. A person wanting to put realistic numbers behind this appears to be on their own.

And I was wondering why sugar and fatty acids have different isotopic enrichment? Is this because the hydrogens of one come from water, while the hydrogens from another come from atmospheric H₂?

Mitchell, Peter. "Chemiosmotic coupling in oxidative and photosynthetic phosphorylation." Biological Reviews (1966)​

 

[Travis]

Oh god [sniffles]. I didn't realize that Ronald Breslow had just died three months ago [blots tear].

I suppose then I'll should give him a few seconds' of silence . . . right before I stealth‐edit the Wikipedia page on thiamine!

 

[shepherdgirl]

wish i could add more to this conversation, but I'm currently not a biochemist... i have a question though - would it be worth buying, or diy-ing, light water? For example:
I googled low deuterium water and found this.
I think Ray talked about high altitude sugar beets and their derivatives having light water - does anyone perhaps know how to buy alpine beet sugar?

 

[SB4]

I was thinking that kinetic isotope effects of the enzymes could play a small role; all of the dehydrogenases, and all the NAD⁺ hydrogen transfers, would be expected to contribute to the differential kinetic isotope effects between the relatively H²‐enriched fatty acids and the carbohydrates. But then I got to thinking that this would likely be overshadowed by the proton migration occurring in the mitochondria, just as you say. I did read a classic Mitchell article or two almost a year ago, and his explanations are generally considered correct to this day. Although many criticisms can be made against many things in biochemistry, I found the Mitchell articles rather solid. After all, ADP does need a proton to becomes ATP. It's not that these protons add to ADP; what happens is that H⁺ adds to a hydroxyl (–OH) on phosphate, catalyzing its removal as it leaves as H₂O. So this H⁺ migration across the mitochondrial wall seems completely necessary, both for this reason and you have to account for all the hydrogens stripped‐off of glucose somehow. The carbons and the oxygens become carbon dioxide, and perhaps even water at times, but the hydrogens do need to go somewhere. They seem to be transported from glucose, to NAD⁺, to ADP/ATP, and then this 'hydrogen potential' on ATP is probably transferred to the cell membrane and beyond. When ATP becomes ADP, the converse reaction occurs: this reaction liberates H⁺, instead of neutralizing it. Some of these H⁺s must eventually be funneled to the urine since this fluid is always excreted at low pH.

Okay so just so I got this:
ATP is used in the cytosol with H2O to form ADP, in doing so a cytosolic H2O is split into a -OH given to ADP and a H+ which is urinated out.
This ADP then travels into the mito where it combines with a H+ from NADH to make ATP + H2O.
This H2O is important and is made from one glucose / fat Hydrogen and one Cytosolic water Hydrogen.
We know mito water is Deuterium depleted or at least should be so the hydrogen from glucose / fat needs to be D depleted as the hydrogen from the cytosol will be around 150ppm. So the TCA must select the H+ in glucose/fat that are Deuterium depleted to be sent to the NADH wheras the D rich ones get sent to NADPH in the cytosol.
But wait, doesn't the mitochondria recycle the DDW H+ in the TCA. Now I'm confused.
It appears the slowing of the TCA cycle in mitochondria means more cytosolic glucose is used to make DNA, etc and this would mean the DNA would be deuterium loaded at the wrong places.

Also this is probably a dumb question but if we are peeing out H+ then the electron that gets passed through the ETC, where does this negative charge end up. Is it something to do with O2 being in a triplet state and 2 electrons get used up to make CO2?

wish i could add more to this conversation, but I'm currently not a biochemist... i have a question though - would it be worth buying, or diy-ing, light water? For example:
I googled low deuterium water and found this.
I think Ray talked about high altitude sugar beets and their derivatives having light water - does anyone perhaps know how to buy alpine beet sugar?

I am currently mixing 1/3 preventa 25ppm with 2/3 standard water. Too early to notice anything yet. Waiting for salivary deuterium test.

 

[SB4]

Here's another one for you.

This diagram (Submolecular regulation of cell transformation by deuterium depleting water exchange reactions in the tricarboxylic acid substrate cycle) talks of removing deuterium from the Carbons in the TCA through CO2.
Now is it suggesting that the Carbons being removed have 2H isotope (deuterium) attatched to them and these leave with the CO2. Or is he suggesting that the carbon itself is Deuterated (C13???) and so the carbon is ejected as CO2?

 

[shepherdgirl]

I am currently mixing 1/3 preventa 25ppm with 2/3 standard water.

Interesting. How did you come up with that ratio?
Is it only UV light that removes deuterium? Or could red light help?
So if one is doing the peaty thang and drinking 2 quarts each of (sea level) milk and oj, plus lots of deut-heavy carbs, would 1/2 liter of light water make a difference?
Where can one buy a salivary deuterium test?

 

[shepherdgirl]

O chemists, what do you think of this simple diy method for light water?

 

[Travis]

Here's another one for you.

This diagram (Submolecular regulation of cell transformation by deuterium depleting water exchange reactions in the tricarboxylic acid substrate cycle) talks of removing deuterium from the Carbons in the TCA through CO2.
Now is it suggesting that the Carbons being removed have 2H isotope (deuterium) attatched to them and these leave with the CO2. Or is he suggesting that the carbon itself is Deuterated (C13???) and so the carbon is ejected as CO2?

That's a neat article, and it's about ²H only. Carbon‐13 is much less abundant but has less kinetic isotope effects because it only weighs ~8% more than ¹²carbon (¹³⁄₁₂ = 8.333%), while deuterium weighs 100% more than hydrogen. The kinetic isotope effects of carbon‐13 can be measured but they are negligible relative to hydrogen's.

The most interesting thing about the article, in my opinion, is this passage:

'More specifically, natural glucose source isolated from leaf starch of common bean (Phaseolus vulgaris) or spinach (Spinacia oleracea) is depleted in deuterium in the C(2) position. Carbon specific deuterium depletion in fatty acids from plants [42] and other sources [43,44] is also evident, which generate deuterium depleted matrix water in mitochondria during complete oxidation in complex-IV.' ―László G Boros​

You would think that ²H and ¹H would exist throughout the entire glucose molecule at random: ~155‧ppm everywhere, with the odds of any one hydrogen having a neutron being .0155%—completely without carbon‐to‐carbon variation. But the carbon #2 of the bean‐derived glucose is apparently deuterium‐depleted on just that one carbon [?], which is puzzling. Perhaps gravity is working opposite capillary action in the bean stalk? separating the lighter ¹H₂O from the deuterated water as its pulled down by gravity, producing a distribution in which ²H₂O is tending more towards the lower half of the stem?

And it looks as though the NADH ⟶ NAD⁺ kinetic isotope effects are considerable; this is the main cofactor for these hydride [:H] transfer reactions. At body temperature (94.73°F; 308‧K), the hydride transfer reaction of an NADH analogue was measured as having kinetic isotope effect of 14:

The cofactor NADH has two hydrogen atoms on its catalytic carbon—despite only one being written there—so it could potentially exist as a mixed species having one ²H and one ¹H. In this case, a person could be interested in knowing if it would just selectively transfer the lighter ¹H at the very same rate as an NADH molecule would having two light hydrogens. This would be a fair question, and I think the answer would be 'no.'

Since the catalytic carbon of NADH is sp³‐hybridized, the hydrogens stay to one side of the molecule—they do not interconvert. The hydrogen on one face of the molecule must remain in that position until either itself or the other hydrogen is removed—after which that carbon becomes sp²‐hybridized, non‐optically‐active, symmetrical, and planar. And since NADH exists in enzymatic binding sites in only one orientation, you would expect only one hydrogen on that carbon to be 'active'—or transferable—since only one hydrogen would be facing the substrate. So an NADH molecule with only one deuterium, as long as its on the correct side of the ring, would be expected to transfer at a slower rate (~14×); there is no need to assume that NADH needs both hydrogens to be deuterium—a statistically improbably event. At normal enrichment, the chance of both NADH hydrogens being deuterium is only .0000024%.

So the kinetic isotope effect of about 14 seems to be a fair number for NADH hydride transfers; but considering the fact that NADH is often stabilized inside of an enzyme could change this number. Perhaps we need to look for at a kinetic isotope study on NADH metabolic enzymes . . . if there is one?

Lu, Yun. "Hydride-exchange reactions between NADH and NAD⁺ model compounds under non-steady-state conditions. Apparent and real kinetic isotope effects." Organic & biomolecular chemistry (2003)​

 

[Travis]

Also this is probably a dumb question but if we are peeing out H+ then the electron that gets passed through the ETC, where does this negative charge end up. Is it something to do with O2 being in a triplet state and 2 electrons get used up to make CO2?

Not all of the hydrogens exit as acidic protons (H⁺), or as proton–neutrons in the case of ionized deuterium (D⁺). Some of these end‐up as H₂O, being transferred to O₂ by heme‐catalyzed enzymes at the very end of the 'electron transport chain.' The electrons flow through microtubules to distant places where they eventually should flow through a heme complex and then discharged; they flow to the center of a porphyrin ring, convert Fe³⁺ to Fe²⁺, and this heme‐ligated iron(II) atom then adsorbs an O₂ molecule:

[1] Fe²⁺–Ö–Ö:⁻ ​

This then attracts a proton (H⁺) from solution—likely from hydronium (H₃O⁺):

[2] Fe²⁺–Ö–Ö:H​

And more electrons are then collected by the heme complex and funneled to iron, electrons (e⁻) which are then donated to the oxygen species adsorbed onto iron. This sequential reduction eventually ends with two H₂O molecules for every one O₂:

[3] Fe³⁺–Ö:⁻ + ⁻Ö:H

[4] Fe²⁺–Ö:H + H:Ö:H

[5] Fe³⁺ + ⁻Ö:H + H₂O

[6] Fe³⁺ + H:Ö:H + H₂O

[7] Fe³⁺ + H₂O + H₂O

[8] Fe²⁺ + 2‧H₂O ​

 

[Travis]

O chemists, what do you think of this simple diy method for light water?

I think someone needs to have a look at the freezing points. I can see this happening, and would provide a good explanation for how glacial water becomes deuterium‐rarified: through sequential freeze–thaw cycles and sublimation; the light water evaporating until it hits a cooler elevation where it recondenses to becomes ice again. This could be the overlooked wild card that authors like Herbert Shelton had overlooked when attempting to explain the longevity of the Hunzas, ascribing their long lives merely to the 'mineral richness' of the glacial water and diet. Little did he know that mountains could act like hydrogen distilleries, and these atoms have kinetic isotope effects which translate to kinetic metabolic effects, aging, and cancer (if you believe the study above).

I think a few iterations of freeze–draining would tend towards lighter water, but I don't see how UV light could do anything.

 

[DaveFoster]

me:
Hi Ray,
I don't know if other people warned you about it but there's a concern of aluminium contamination with hydrogenated CO:

Coconut Oil Leads To Dementia?


And more information here:

Coconut Oil Leads To Dementia?

[I posted the two posts in the mail to make sure he would see them]

Ray:
Neurology. 1985 Feb;35(2):193-8.
Disappearance of high-incidence amyotrophic lateral sclerosis and parkinsonism-dementia on Guam.
Garruto RM, Yanagihara R, Gajdusek DC.
The high incidence rates of amyotrophic lateral sclerosis (ALS) and parkinsonism-dementia (PD) occurring among the Chamorros of Guam have declined to rates only slightly higher than those observed in the continental United States. This decline has occurred principally among males, especially those born after 1920 and living in areas where calcium and magnesium levels are low in soil and water. The male-to-female ratio among affected patients now approaches unity, compared with ratios of 2 to 1 for ALS and 3 to 1 for PD three decades ago. These changes are consistent with the hypothesis that the previously high incidence resulted from defects in mineral metabolism and secondary hyperparathyroidism, provoked by nutritional deficiencies of calcium and magnesium, with resultant deposition of calcium and aluminum in neurons.

J Occup Environ Med. 2014 May;56(5 Suppl):S73-9.
Is the Aluminum Hypothesis dead?
Lidsky TI.
The Aluminum Hypothesis, the idea that aluminum exposure is involved in the etiology of Alzheimer disease, dates back to a 1965 demonstration that aluminum causes neurofibrillary tangles in the brains of rabbits. Initially the focus of intensive research, the AluminumHypothesis has gradually been abandoned by most researchers. Yet, despite this current indifference, the Aluminum Hypothesis continues to attract the attention of a small group of scientists and aluminum continues to be viewed with concern by some of the public. This review article discusses reasons that mainstream science has largely abandoned the Aluminum Hypothesis and explores a possible reason for some in the general public continuing to view aluminum with mistrust.
Free PMC Article

Uh... way to be cryptic. I wish he'd give a straight answer in this context.