The Travis Corner

[Travis]

Travis, what are the benefits of raw goat milk/cheese compared to pasteurized? Just curious, as I'm doing really well on my near-daily half gallon of pasteurized goat milk, and certainly would not be able to afford the same amount of raw goat milk.

I don't think that should matter much unless you're a die-hard raw foodist. The criticisms I levy against the common brands of milk have more to do with its prior homogenization and the cow's genetics, and even goat milk that'd been pasteurized should still be far less immunogenic if not more so. Milk from goats and sheep also have a lower opiate activity, and the fact they'd hadn't been injected with Monsanto's rBGH also means lower IGF-1. I do believe that raw cow's milk is better than common processed varieties, but that's only because this proves that it hadn't been homogenized. Since homogenization traps milk proteins into small liposomes, the fact that cow's milk is raw also means that it should be less immunogenic. If goat's milk were also homogenized I think it would be more problematic, yet the naturally small size of it's liposomes precludes the necessity for such. What is said about goat milk applies equally well to sheep, whose milk goes into making the popular pecorino Romano—perhaps the easiest to find non-cow cheese.

 

[Arrade]

Vitamin K prevents calcification by creating γ-carboxyglutamate domains on proteins, binding free Ca²⁺ thereby preventing its precipitation with free pyrophosphate. This effect is best demonstrated in animals taking Warfarin, those whose arteries and veins so calcified as to become 'chalk-like' within weeks.⁽²⁾ Brain calcification is best reversed by carbon dioxide because it's the substrate for neuronal carbonic anhydrase, an enzyme that creates acidity by converting it into carbonic acid. Magnesium also antagonizes calcification and fibrosis,⁽¹⁾⁽⁴⁾ and pineapples would be expected to as well because they contain both bromelain and ascorbic acid: The former is absorbed whole and can degrade damaged collagen and scar tissue,⁽⁵⁾ while the latter induces new procollagen synthesis over fourfold at only 100 μM.⁽³⁾

[1] Meema, H. "Serum magnesium level and arterial calcification in end-stage renal disease." Kidney international (1987)
[2] Price, P.A. "Warfarin causes rapid calcification of the elastic lamellae in rat arteries and heart valves." Arteriosclerosis, thrombosis, and vascular biology (1998)
[3] Geesin, J.C. "Ascorbic acid specifically increases type I and type III procollagen messenger RNA levels in human skin fibroblasts." Journal of Investigative Dermatology (1988)
[4] Heggtveit, H. "Cardiac necrosis and calcification in experimental magnesium deficiency: a light and electron microscopic study." The American journal of pathology (1964)
[5] Castell, J. V. "Intestinal absorption of undegraded proteins in men: presence of bromelain in plasma after oral intake." American Journal of Physiology-Gastrointestinal and Liver Physiology (1997)​

Ascorbic adic without bromelain is useful, then? Or do you need bromelain to allow its benefits?

 

[Travis]

@Travis How does the delivery of tobacco's components change with vaporization as compared to combustion?

I like smoking hand rolled American Spirits but I can't handle more than a couple puffs before the buzz becomes overwhelming. I want to try vaporization of the leaf instead of combusting it, so that hopefully I have a more controlled inhalation with a less drastic physiological effect, but I'm struggling to find information on this. Most search results pop up with vaping of nicotine juice which I have no interest in.

As far as I can tell, the nicotine we inhale from cigarettes had been volatilized by the high-temperature flame front preceding the flame itself. The nicotine that becomes combusted is inactive on acetylcholine receptors, and combusted ammonia becomes carcinogenic nitric oxide (ṄO) and nitrogen dioxide (ṄO₂). Vaporized ammonia is simply ammonia, and although not carcinogenic it does have its own problems. My understanding of ammonia toxicity lies in its ability to displace the potassium ion (K⁺) from the cytosol around mitochondria, as the ammonium ion (NH₄⁺), which lowers oxidative phosphorylation and the same time it induces osmotic swelling. In peripheral tissues this is no huge deal, yet because the brain is constrained by the skull this increases cerebral pressure. Hyperammonemia always reduces cognition, and the manner in which it can induces fatality appears indistinguishable from cerebral edema. There is also some indication that ammonia increases plasma nitric oxide, which I imagine it does by increasing substrate cycling: ornithine ⟶ citrulline ⟶ arginine ⟶ iNOS/eNOS.

Vaporizing should be a tarless process, and I don't even think it'd produce the carcinogenic ṄO and ṄO₂ species. Lowering ammonia is relatively easy by comparison, which can be accomplished by adding substrates to the urea cycle—arginine, citrulline, ornithine—and diverting waste nitrogen towards the hippurate pathway via benzoate or cinnamaldehyde. In my opinion: citrulline is the best urea substrate because it can detoxify ammonia in states of low ornithine carbamoyltransferase activity, the enzyme most commonly found impaired in hyperammonemic states. I am lowering ammonia right now using cinnamon and watermelons, yet I do have citrulline in the mail for post-watermelon season ammonia detoxification. Salicylates can induce liver damage and hyperammonemia, even to the point of smelling it in the urine (personal observation).

Zimmerman, H.J. "Effects of aspirin and acetaminophen on the liver." Archives of Internal Medicine (1981)
Yoshida, I. "Sudden onset of ornithine carbamoyltransferase deficiency after aspirin ingestion." Journal of inherited metabolic disease (1993)​

 

[energyandstruct]

Vitamin D does lower metabolism, which it does by downregulating uncoupling protein. Thyroid hormone does the opposite and strongly induces uncoupling protein, a mitochondrial protein that increases metabolism by coupling ATP production with cAMP. I interpret this effect as a device to prevent overheating in the sun, and believe the only way to lower endogenous heat production is through lowering the metabolic rate.

Wong, K.E. "Involvement of the vitamin D receptor in energy metabolism: regulation of uncoupling proteins." American Journal of Physiology-Endocrinology and Metabolism (2009)​

Interesting, and yet lowered vitamin D seems to be responsible for fatigue and pain (or at least danny keeps sending me articles suggesting this, and ray always tells me thyroid, vitamin D, calcium, and progesterone, are the main things). This is confusing me

 

[Travis]

Interesting, and yet lowered vitamin D seems to be responsible for fatigue and pain (or at least danny keeps sending me articles suggesting this,

I could see how someone could get that impression from epidemiological studies, those where 'low vitamin D' is more-or-less synonymous with 'high melatonin.' We have two hormones correlated with both latitude and ultraviolet light exposure

[...] and ray always tells me thyroid, vitamin D, calcium, and progesterone, are the main things). This is confusing me

And yet, vitamin D directly antagonizes triiodothyronine's main function: to transcribe-for uncoupling protein:

Larkin, Sarah. "Regulation of the third member of the uncoupling protein family, UCP3, by cold and thyroid hormone." Biochemical and biophysical research communications (1997)

​

de Lange, Pieter. "Uncoupling protein-3 is a molecular determinant for the regulation of resting metabolic rate by thyroid hormone." Endocrinology (2001)

'In both tissues, the maximal (12-fold) increase in uncoupling protein-3 density was reached at 65 h. The resting metabolic rate showed the same time course, and at 65 h the increase vs. time zero was 45%. [...] The results reported here provide the first direct in vivo evidence that uncoupling protein-3 has the potential to act as a molecular determinant in the regulation of resting metabolic rate by T3.' ―de Lange
​

Shi, Hang. "1α, 25-dihydroxyvitamin D₃ inhibits uncoupling protein 2 expression in human adipocytes." The FASEB Journal (2002)

​

Wong, Kari. "Targeted expression of human vitamin D receptor in adipocytes decreases energy expenditure and induces obesity in mice." Journal of Biological Chemistry (2011)

[Fig 1: These Western blot images prove that that the human VDR vector that'd previously been microinjected into developing rat embryos is now truly being expressed in the 'transgenic group,' and not the 'wild type' group, as intended. This had been a successful and stable dNA implantation, now implying the 'transgenic' mice would be expected to have an accentuated response to vitamin D₃ as compared to the 'wild type' mice.]​

[Fig 2: This image speaks for itself, and is another demonstration that vitamin D can lower the metabolic rate.]​

[Fig 3: The mRNA concentrations determined, from left to right, had been those encoding: carnitine palmitoyl transferase-1, carnitine palmitoyl transferase-2, hexokinase, pyruvate kinase, uncoupling protein-1, uncoupling protein-2, uncoupling protein-3.]​

[Fig 4: Results of glucose injection at 2 mg/kg body weight after a six-hour fast. Note the reduced capacity to metabolize glucose in the mice having additional vitamin D receptors, an effect fully consistent with their reduced expression of hexokinase and pyruvate kinase. Since these mice also had a reduced expression of carnitine palmitoyl transferase-1 and -2, it could be rightly anticipated that they would also metabolize long-chained fatty acids at a reduced rate.]​

[Fig 5: Despite both groups eating the same amount of food and sharing identical conditions, the oxygen utilization rate had been significantly attenuated in the mice having the extra vitamin D receptors. Since the ability to enhance the oxygen utilization rate is thyroid hormone's classic function, vitamin D can be seen as antagonizing T₃ directly if it can also be assumed that vitamin D can indeed transcribe through its eponymous receptor.]​

 

[haidut]

Salicylates can induce liver damage and hyperammonemia, even to the point of smelling it in the urine (personal observation).

Salicylic acid is excreted primarily by conjugation with glycine, and this is the same mechanism through which benzoic acid reduces ammonia. The drug Ucephan for lowering ammonia due to liver damage is just benzoic acid. Salicylic acid is just 2-OH-benzoic acid, and given the mechanism in the post below it should lower ammonia, not raise it.
Aspirin reduces ammonia?

If there is higher ammonia due to aspirin it could be due to aspirin uncoupling in high doses and not some organic ammonia-raising effects. The liver "damage" is probably just lower ATP if aspirin is taken in high enough doses. Btw, most of the time this "damage" from aspirin and other uncouplers has been measures simply by looking at liver enzynes. Cell analysis from anima liver did not show damage, just swollen cells due to chronic uncoupling and giant mitochondria. Some elevation of liver enzymes is not pathologica. Both Pauling and St. Gyorgi said elevations up to 2 times the upper limit of normal actually indicate the liver is doing its job. If you look at people with true liver disease, their ALT and GGT are usually 8-10 times above normal. Acetominphen can cause such damage, but not aspirin. Hence the suicide attempts with acetominophen and nor aspirin. Incidentally, DNP has many of the same effects as aspirin on liver and ammonia, so the issue here is likely too much uncoupling and thus low ATP, and not some organic liver-toxic effects. In fact, aspirin (in moderate doses equivalent to 15mg/kg-20mg/kg for a human) has been shown to protect the liver from a number of toxins such as cadmium and CCl4.
Hepatic ATP content and hyperammonemia induced by CCl4 in rats. - PubMed - NCBI
Liver Disease Is Caused By Low ATP Driven By Fat (PUFA) Oxidation

Just my 2c.

 

[raypeatclips]

I could see how someone could get that impression from epidemiological studies, those where 'low vitamin D' is more-or-less synonymous with 'high melatonin.' We have two hormones correlated with both latitude and ultraviolet light exposure


And yet, vitamin D directly antagonizes triiodothyronine's main function: to transcribe-for uncoupling protein:

Larkin, Sarah. "Regulation of the third member of the uncoupling protein family, UCP3, by cold and thyroid hormone." Biochemical and biophysical research communications (1997)

View attachment 10792
​

de Lange, Pieter. "Uncoupling protein-3 is a molecular determinant for the regulation of resting metabolic rate by thyroid hormone." Endocrinology (2001)

'In both tissues, the maximal (12-fold) increase in uncoupling protein-3 density was reached at 65 h. The resting metabolic rate showed the same time course, and at 65 h the increase vs. time zero was 45%. [...] The results reported here provide the first direct in vivo evidence that uncoupling protein-3 has the potential to act as a molecular determinant in the regulation of resting metabolic rate by T3.' ―de Lange
​

Shi, Hang. "1α, 25-dihydroxyvitamin D₃ inhibits uncoupling protein 2 expression in human adipocytes." The FASEB Journal (2002)

View attachment 10793
​

Wong, Kari. "Targeted expression of human vitamin D receptor in adipocytes decreases energy expenditure and induces obesity in mice." Journal of Biological Chemistry (2011)

View attachment 10794

[Fig 1: These Western blot images prove that that the human VDR vector that'd previously been microinjected into developing rat embryos is now truly being expressed in the 'transgenic group,' and not the 'wild type' group, as intended. This had been a successful and stable dNA implantation, now implying the 'transgenic' mice would be expected to have an accentuated response to vitamin D₃ as compared to the 'wild type' mice.]​

View attachment 10795

[Fig 2: This image speaks for itself, and is another demonstration that vitamin D can lower the metabolic rate.]​

View attachment 10796

[Fig 3: The mRNA concentrations determined, from left to right, had been those encoding: carnitine palmitoyl transferase-1, carnitine palmitoyl transferase-2, hexokinase, pyruvate kinase, uncoupling protein-1, uncoupling protein-2, uncoupling protein-3.]​

View attachment 10797

[Fig 4: Results of glucose injection at 2 mg/kg body weight after a six-hour fast. Note the reduced capacity to metabolize glucose in the mice having additional vitamin D receptors, an effect fully consistent with their reduced expression of hexokinase and pyruvate kinase. Since these mice also had a reduced expression of carnitine palmitoyl transferase-1 and -2, it could be rightly anticipated that they would also metabolize long-chained fatty acids at a reduced rate.]​

View attachment 10798

[Fig 5: Despite both groups eating the same amount of food and sharing identical conditions, the oxygen utilization rate had been significantly attenuated in the mice having the extra vitamin D receptors. Since the ability to enhance the oxygen utilization rate is thyroid hormone's classic function, vitamin D can be seen as antagonizing T₃ directly if it can also be assumed that vitamin D can indeed transcribe through its eponymous receptor.]​

Do you avoid the sun? Why do you think so many people are vitamin D deficient with major issues which improve with the addition of vitamin D?

 

[Travis]

Salicylic acid is excreted primarily by conjugation with glycine, and this is the same mechanism through which benzoic acid reduces ammonia. The drug Ucephan for lowering ammonia due to liver damage is just benzoic acid. Salicylic acid is just 2-OH-benzoic acid, and given the mechanism in the post below it should lower ammonia, not raise it.
Aspirin reduces ammonia?

Well certainly; but aspirin has been shown to cause a net hyperammonemia by lowering the expression of ornithine carbamoyltransferase, a urea cycle enzyme needed to efficiently detoxify ammonia. The urea cycle detoxifies far more ammonia than the hippurate pathway, the one in which benzoic acid and cinnamaldehyde serve as substrates. Thousands of cases of Reye's syndrome demonstrate that aspirin can cause hyperammonemia to the point of cerebral edema, coma, and death. There is so much evidence for this that I am surprised that someone would contest it.

If there is higher ammonia due to aspirin it could be due to aspirin uncoupling in high doses and not some organic ammonia-raising effects. The liver "damage" is probably just lower ATP if aspirin is taken in high enough doses. Btw, most of the time this "damage" from aspirin and other uncouplers has been measures simply by looking at liver enzynes. Cell analysis from anima liver did not show damage, just swollen cells due to chronic uncoupling and giant mitochondria. Some elevation of liver enzymes is not pathologica. Both Pauling and St. Gyorgi said elevations up to 2 times the upper limit of normal actually indicate the liver is doing its job. If you look at people with true liver disease, their ALT and GGT are usually 8-10 times above normal.

I am talking about reduced activity of liver specific urea cycle enzymes, not the increased activity of alanine transaminase and aspartate transaminase often released into the circulation:

Snodgrass, Philip. "Urea-cycle enzyme deficiencies and an increased nitrogen load producing hyperammonemia in Reye's syndrome." New England Journal of Medicine (1976)

​

Yoshida, I. "Sudden onset of ornithine carbamoyltransferase deficiency after aspirin ingestion." Journal of inherited metabolic disease (1993)

'A 15-year-old boy was admitted to Kurume University Medical Center because of deep coma. Initially he was diagnosed as Reye syndrome by the referring physician. After the admission and biochemical investigations including enzymatic study, the diagnosis of this patient was confirmed as OCT deficiency (Mizoguchi et al 1990). Careful history taking revealed that this patient had begun to take aspirin at the onset of prodromal symptoms' ―Yoshida​

'Recently Yamamoto and colleagues (1987) reported that salicylate inhibited mitochondrial OCT processing in vitro. The sudden onset in this patient immediately after taking aspirin suggests that aspirin may have some relation to the onset of OCT deficiency. This hypothesis complicates interpretation of the epidemiological linkage between aspirin and Reye syndrome (Hurwitz et al 1987). It is well known that OCT deficiency is sometimes misdiagnosed as Reye syndrome (Mizoguchi et al 1990). If OCT deficiency were included in patients who were reported as Reye syndrome, it would be important to re-evaluate the linkage between aspirin and Reye syndrome.' ―Yoshida​

Zimmerman, H.J. "Effects of aspirin and acetaminophen on the liver." Archives of Internal Medicine (1981)

'Despite this recent authoritative reassurance, there is now ample evidence that aspirin is capable of producing liver damage.⁽²⁾⁽⁵⁾⁽⁶⁻⁸⁾⁽⁹⁾⁽³⁾⁽⁴⁾⁽⁵⁾⁽¹³⁻²¹⁾⁽²⁷⁾ Indeed, there have been more than 50 articles describing aspirin-induced hepatic injury, most of them published during the past five years.⁽²⁾⁽⁵⁾⁽⁶⁾⁽⁹⁾⁽¹³⁻²¹⁾⁽⁶⁸⁾ How can one reconcile the long period of unawareness of aspirin-induced hepatic injury with the rapid accumulation of evidence that aspirin does have hepatotoxic potential? A partial explanation would seem to be that, in the past, instances of hepatic injury have been overlooked because jaundice rarely accompanies aspirin-induced hepatic injury, and there have been few other overt manifestations of liver damage. Instances of serious injury that may have surfaced in the past were presumably attributed to other factors.' ―Zimmerman​

Acetominphen can cause such damage, but not aspirin. Hence the suicide attempts with acetominophen and nor aspirin.

That's certainly not what the specialists appear to think. I am convinced that were anyone else to actually read the Zimmerman article cited above, they'd conclude that both acetaminophen and aspirin have similar hepatotoxic potential yet the former is infamous in that regard simply because it'd been a popular suicide drug in England at one time. Hence, acetaminophen had caused many more cases of liver damage than aspirin had simply due to the higher doses employed.

'Within a few years of its entry into popular use, reports of suicidal overdoses leading to hepatic necrosis began to appear; before long, acetaminophen overdose became one of the most popular means of attempting suicide and the most prominent cause of severe hepatic necrosis in the United Kingdom.' ―Zimmerman​

'Total single doses exceed 15 g in about 80% of cases;' ―Zimmerman​

Incidentally, DNP has many of the same effects as aspirin on liver and ammonia, so the issue here is likely too much uncoupling and thus low ATP, and not some organic liver-toxic effects. In fact, aspirin (in moderate doses equivalent to 15mg/kg-20mg/kg for a human) has been shown to protect the liver from a number of toxins such as cadmium and CCl4.
Hepatic ATP content and hyperammonemia induced by CCl4 in rats. - PubMed - NCBI
Liver Disease Is Caused By Low ATP Driven By Fat (PUFA) Oxidation

Just my 2c.

So I get the a .pdf file of your first citation in the original typeset, namely this one here:

Yamamoto, Hiro-Aki. "Hepatic ATP content and hyperammonemia induced by CCl₄ in rats." Toxicology (1988)

And the words 'aspirin,' 'acetylsalicylate,' '2-acetoxybenzoic acid,' nor salicylate appear not once in the document. How exactly can this article be cited as proof that aspirin protects against carbon tetrachloride-induced hyperammonemia when aspirin hadn't even been used?

 

[Wagner83]

@Travis which food do you get your zinc from and do you notice a difference in well-being or brain function when you stop eating goat cheese?

 

[Travis]

Do you avoid the sun? Why do you think so many people are vitamin D deficient with major issues which improve with the addition of vitamin D?

I am talking about only one specific effect, and that is the basal metabolic rate. Can you cite a case where a person's basal metabolic rate had actually increased by taking vitamin D?

 

[energyandstruct]

I am talking about only one specific effect, and that is the basal metabolic rate. Can you cite a case where a person's basal metabolic rate had actually increased by taking vitamin D?

You said "I see how you could get that idea from epidemiological studies", and my question is still--if a lot of epidemiological studies show pain and fatigue and depression from vitamin D deficiency, yet it seems that it lowers basal metabolic rate, what's the deal... Is there another mechanism for fatigue beyond basal metabolic rate? is there a curve effect in which optimal vitamin D levels raise metabolic rate but high enough levels lower it?

 

[Travis]

@Travis which food do you get your zinc from and do you notice a difference in well-being or brain function when you stop eating goat cheese?

Well I don't notice much from goat cheese besides maybe a slight opiate effect, which is certainly not a big deal as long as you don't eat it before very demanding tasks. The amino acid ratio is just like leaf protein, and this is about what I'm used to anyway. I see goat and sheep cheese as somewhat inert, certainly less influential on psychology and health than quickly drinking soda or honey-water. Yet zinc is practically the only thing not at 100% RDA, or over, when I cronometer what I eat. Even though the sodium intake is often under the RDA, I fell this is completely natural because the only way to achieve it is through using salt—this must either be mined or made from evaporated seawater. The selenium is often under the RDA as well yet this is unique in that it's the only protein-bound mineral, meaning that the methods employed to detect minerals fail to detect most selenium in most foods. The selenomethionine and selenocysteine found in foods is discarded in the protein/cellulose fraction when determining minerals—via flame spectroscopy—in the supernatant. For this reason I'd assume that nearly everyone's diet provides the RDA for selenium despite the USDA database saying otherwise. And naturally: vitamin D is always at 0% percent yet this isn't technically a vitamin anyway since it comes from the sun. A similar thing can be said about vitamin B₁₂: an enzymatic cofactor which now has been proven to be synthesized by enteral bacteria and absorbed by transcobalamin, completely independent of intrinsic factor. Thus, zinc is the only think that I'd consider to be legitimately under the RDA when I cronometer what I normally eat. I realize that this is involved in steroid synthesis, and perhaps I may look for some high-zinc foods. I have eaten before pumpkin seeds in the past for their high zinc content yet I now avoid those due to their high composition of linoleic acid. Yet I would imagine that there's something out there, and I do think coconuts actually do supply the RDA for zinc when I have those. I am certainly not afraid of steroids or cholesterol, and zinc appears generally beneficial as far as I know.

 

[Travis]

You said "I see how you could get that idea from epidemiological studies", and my question is still--if a lot of epidemiological studies show pain and fatigue and depression from vitamin D deficiency, yet it seems that it lowers basal metabolic rate, what's the deal... Is there another mechanism for fatigue beyond basal metabolic rate? is there a curve effect in which optimal vitamin D levels raise metabolic rate but high enough levels lower it?

Well serotonin can certainly help depression, yet is this the best way to go about it? I would be interested in seeing what Ray Peat and Danny Roddy cita as evidence of vitamin D's ability to decrease fatigue, which I assume would be related to the basal metabolic rate.

 

[Wagner83]

Well I don't notice much from goat cheese besides maybe a slight opiate effect, which is certainly not a big deal as long as you don't eat it before very demanding tasks. The amino acid ratio is just like leaf protein, and this is about what I'm used to anyway. I see goat and sheep cheese as somewhat inert, certainly less influential on psychology and health than quickly drinking soda or honey-water. Yet zinc is practically the only thing not at 100% RDA, or over, when I cronometer what I eat. Even though the sodium intake is often under the RDA, I fell this is completely natural because the only way to achieve it is through using salt—this must either be mined or made from evaporated seawater. The selenium is often under the RDA as well yet this is unique in that it's the only protein-bound mineral, meaning that the methods employed to detect minerals fail to detect most selenium in most foods. The selenomethionine and selenocysteine found in foods is discarded in the protein/cellulose fraction when determining minerals—via flame spectroscopy—in the supernatant. For this reason I'd assume that nearly everyone's diet provides the RDA for selenium despite the USDA database saying otherwise. And naturally: vitamin D is always at 0% percent yet this isn't technically a vitamin anyway since it comes from the sun. A similar thing can be said about vitamin B₁₂: an enzymatic cofactor which now has been proven to be synthesized by enteral bacteria and absorbed by transcobalamin, completely independent of intrinsic factor. Thus, zinc is the only think that I'd consider to be legitimately under the RDA when I cronometer what I normally eat. I realize that this is involved in steroid synthesis, and perhaps I may look for some high-zinc foods. I have eaten before pumpkin seeds in the past for their high zinc content yet I now avoid those due to their high composition of linoleic acid. Yet I would imagine that there's something out there, and I do think coconuts actually do supply the RDA for zinc when I have those. I am certainly not afraid of steroids or cholesterol, and zinc appears generally beneficial as far as I know.

Thanks, I do enjoy feta cheese, usually later in the day. Have you considered adding infrequent seafood to your diet?

 

[HDD]

Well serotonin can certainly help depression, yet is this the best way to go about it? I would be interested in seeing what Ray Peat and Danny Roddy cita as evidence of vitamin D's ability to decrease fatigue, which I assume would be related to the basal metabolic rate.

HD: [...] How do you see fibromyalgia in terms of vitamin D3 deficiency?

RP: I think, it's parallel, almost identical to the hypothyroid condition. All of the inflammations that you get with low thyroid function are structurally and functionally similar to those you get from a vitamin D deficiency. And the thyroid stimulating hormone is an agent of those inflammatory processes, actually more than the direct effect of thyroxin which lowers TSH. The TSH directly activates and causes tissue to release the inflammatory cytokines, interleukins and so on, and parathyroid hormone does that. And just by taking vitamin D or increasing your calcium intake or decreasing your phosphate relative to the calcium: all of these cases in your diet will lower both TSH and parathyroid hormone. And both of these hormones are directly involved in things such as mast cell activation, releasing histamine and serotonin, increasing all of the cytokines, tumor necrosis factor, nitric oxide: all of the things that promote degenerative inflammatory processes. And so functionally vitamin D and thyroid are really parallel. You can't quite separate them.

 

[Diokine]

Unregulated increases in basal metabolic rate will result in excessive accumulation of cyclic-AMP and endoplasmic reticulum stress, misfolded proteins and gross defects in cellular organization. This also results in nervous fatigue in muscles and an inability to oxidize fats and insulin resistance. This generally results in fatigue. Vitamin D is critical in maintaining proper feedback between metabolic drive and recovery from the byproducts of such drive.

 

[energyandstruct]

Well serotonin can certainly help depression, yet is this the best way to go about it? I would be interested in seeing what Ray Peat and Danny Roddy cita as evidence of vitamin D's ability to decrease fatigue, which I assume would be related to the basal metabolic rate.

"I have only had a couple of abnormal things show up on tests. I have very low cortisol and high DHEA. I have low vitamin D. My thyroid panels were all normal, including parathyroid. I have extremely low chymotrypsin."

Hey ______, can you post the tests? I think deficiencies of thyroid and vitamin D can cause CFS. Also, what have you been eating? And do you lean towards constipation or diarrhea?
Robert K. Naviaux. Metabolic features of chronic fatigue syndrome. July 13, 2016. "Metabolomics showed that chronic fatigue syndrome is a highly concerted hypometabolic response to environmental stress that traces to mitochondria and was similar to the classically studied developmental state of dauer."
Holick, M.F., et al. Vitamin D deficiency. N Engl J Med. 2007 Jul 19;357(3):266-81. "One study showed that 93% of persons 10 to 65 years of age who were admitted to a hospital emergency department with muscle aches and bone pain and who had a wide variety of diagnoses, including fibromyalgia, chronic fatigue syndrome, and depression, were deficient in vitamin D.”
Kevin Johnson and Maryam Sattari. Vitamin D deficiency and fatigue: an unusual presentation. Springerplus. 2015; 4: 584.
Fatigue is a vague but common complaint that is poorly characterized by physicians as well as patients. While fatigue may result from a number of different etiologies, at the present time, a comprehensive approach to each patient with fatigue does not include routine measurement of serum vitamin D levels. A 61-year-old man was evaluated for excessive daytime fatigue. No features characteristic for depression, sleep apnea, or narcolepsy were present. A comprehensive work-up, including thyroid function tests and testosterone levels, did not reveal any abnormalities. However, serum 25-hydroxyvitamin D level was low, at 18.4 ng/mL. Vitamin D supplementation was initiated. At follow-up in 3 and 12 months, the patient reported complete resolution of daytime fatigue, corresponding to an increase in his vitamin D levels. Possible mechanisms for clinical improvement include effects of vitamin D on components of inflammatory cascades, including tumor necrosis factor-alpha and prostaglandin D2, which result in decrease in central nervous system homeostatic sleep pressure. While more research is needed to determine if patients presenting with fatigue should be routinely screened for vitamin D deficiency, clinicians should consider obtaining vitamin D levels in patients with unexplained fatigue, nonspecific musculoskeletal pain, and risk factors for vitamin D deficiency.
Sharpe M, Hawton K, Clements A, Cowen PJ. Increased brain serotonin function in men with chronic fatigue syndrome. BMJ. 1997 Jul 19;315(7101):164-5. "Raised brain serotonin activity might explain the excessive fatigue experienced by patients with the chronic fatigue syndrome. Increased prolactin release mediated by serotonin in the chronic fatigue syndrome…."





This is the first email from danny where he cites some research, later I found something about vitamin D in naviaux's paper on the CDR (not the one about CFS specifically)

I don't recall ray citing specific research on vitamin d, he usually just advises taking it. but he may have written about it in his articles (so much stuff to comb through, it's endless)

 

[energyandstruct]

Well serotonin can certainly help depression, yet is this the best way to go about it? I would be interested in seeing what Ray Peat and Danny Roddy cita as evidence of vitamin D's ability to decrease fatigue, which I assume would be related to the basal metabolic rate.

also danny says he uses high doses of vitamin D on skin and thinks it's very similar to thyroid in effects:
"If the thyroid is low, and the liver can't store sugar well, I imagine any mild stress could cause hypoglycemia and a rise in adrenaline, cortisol, etc. I've noticed that vitamin D and thyroid have had similar effects, which isn't surprising given they're close proximity to each other."

 

[haidut]

So I get the a .pdf file of your first citation in the original typeset, namely this one here:

Sorry, should have clarified. That article points out that DNP also causes hyperammonemia and excerbates hepatic encephalopathy caused by CCL4. Something aspirin can also do in high doses, and the symptoms are similar to the Reye syndrome as you mentioned.

I don't think the mechanism of aspirin vs. acetaminophen hepatotoxicity has been clarified. It is known that their toxicity profile on liver is different, with the acetaminophen being clearly cytotoxic in almost any dose/concentration while aspirin only being indirectly toxic and only so when blood levels exceed 30mg/dL.
Effects of aspirin and acetaminophen on the liver. - PubMed - NCBI

And here is an actual study of aspirin in HED 15mg/kg protecting the liver against CCl4-induced damage.
Effects of acetyl salycilic acid and ibuprofen in chronic liver damage induced by CCl4. - PubMed - NCBI

 

[Travis]

HD: [...] How do you see fibromyalgia in terms of vitamin D3 deficiency?

RP: I think, it's parallel, almost identical to the hypothyroid condition. All of the inflammations that you get with low thyroid function are structurally and functionally similar to those you get from a vitamin D deficiency. And the thyroid stimulating hormone is an agent of those inflammatory processes, actually more than the direct effect of thyroxin which lowers TSH. The TSH directly activates and causes tissue to release the inflammatory cytokines, interleukins and so on, and parathyroid hormone does that. And just by taking vitamin D or increasing your calcium intake or decreasing your phosphate relative to the calcium: all of these cases in your diet will lower both TSH and parathyroid hormone. And both of these hormones are directly involved in things such as mast cell activation, releasing histamine and serotonin, increasing all of the cytokines, tumor necrosis factor, nitric oxide: all of the things that promote degenerative inflammatory processes. And so functionally vitamin D and thyroid are really parallel. You can't quite separate them.

Well I would say in response to that:

Travis: Yes but parathyroid hormone is released independently of vitamin D. Parathyroid hormone is synthesized by the parathyroid gland in response to calcium levels, which it can sense using a specific Ca²⁺-binding peptide. Calcium is also absorbed passively regardless of circulating vitamin D, and VDR-knockout rodents live just fine—albeit skinnier with a higher metabolic rate—with a just a little extra calcium. Vitamin D deficient rats do often have total alopecia, yet this is not fatal and could occur simply because calcitriol transcribes for keratin 19—which is a hair keratin. Of course nobody outside of a laboratory could possibly get that low in vitamin D, yet the fact it antagonizes triiodothyronine by under-expressing uncoupling protein should be noted. Even though increased calcium can be argued as tending towards reversing fatigue in a number of ways, rodent models imply that its non-calcemic effects could trump its ability to enhance calcium absorption. Vitamin D could have the net effect of inducing fatigue by under-expressing uncoupling protein:

Nemeth, Edward. "Calcimimetics with potent and selective activity on the parathyroid calcium receptor." Proceedings of the National Academy of Sciences (1998)

'Parathyroid hormone (PTH) secretion is regulated by a cell surface Ca²⁺ receptor that detects small changes in the level of plasma Ca²⁺.' ―Nemeth​

Mathieu, Chantal. "In vitro and in vivo analysis of the immune system of vitamin D receptor knockout mice." Journal of Bone and Mineral Research (2001)

'A major observation in this study is that by restoring the metabolic defects, especially hypocalcemia, caused by vitamin D resistance, the immune defects disappeared. Feeding VDR-KO mice a lactose or corn oil–rich diet succeeded not only in correcting calcium and bone homeostasis—most probably through stimulation of intestinal calcium uptake via vitamin D-independent pathways—but also in restoring all observed immune abnormalities in vitro as well as in vivo.' ―Mathieu
​

Weber, K. "Differences in triglyceride and cholesterol metabolism and resistance to obesity in male and female vitamin D receptor knockout mice." Journal of Animal Physiology and Animal Nutrition (2013)

'Although VDR knockout mice of both sexes consumed more food than wild-type and heterozygous littermates, their body weight and the weight of fat depots was lower after 6 months on a diet with 5% crude fat content. When adult animals were challenged with a high-fat diet containing 21% crude fat content for 8 weeks, VDR knockout mice of both sexes had a significantly higher food intake but gained less weight than their wild-type littermates. Cholesterol levels were higher after 2 days on the high-fat diet in both sexes, but in the VDR knockout mice, less cholesterol was detected in the serum after 8 weeks. Wildtype male mice showed signs of fatty liver disease at the end of the experiment, which was not detected in the other groups. In conclusion, lack of the VDR receptor results in reduced fat accumulation with age and when adult mice are fed a high-fat diet, despite a higher food intake of VDR knockout mice relative to their wild-type littermates. These effects can be detected in both sexes. Wild-type male mice react with the highest weight gain and cholesterol levels of all groups and develop fatty liver disease after 8 weeks on a high-fat diet, while male VDR knockout mice appear to be protected.' ―Mathieu
​

Certainly vitamin D has beneficial function, yet humans have never taken such high amounts orally before the practice of irradiating lanolin. Using theoretical approximations of skin secosteroidal synthesis as the basis for daily oral intake may not be physiologically appropriate, and the visceral organs could be exposed to log orders more vitamin D than evolutionarily encountered by our species. Taking high dose vitamin D could be tricking the body into assuming it's warmer than it actually is, inducing the downregulation of uncoupling protein to reduce metabolism and hence heat production. During the autumn months, the declining vitamin D levels would naturally allow the thyroid receptor to transcribe dNA with greater accessibility, thereby increasing the metabolic rate in anticipation for the winter months. Vitamin D is molecular signal for direct sunlight, one that our bodies' had evolved to use to partially determine metabolic rate:

Lovegrove, B. G. "The influence of climate on the basal metabolic rate of small mammals: a slow-fast metabolic continuum." Journal of Comparative Physiology. B, Biochemical, Systemic, and Environmental Physiology (2003)

'The overall model revealed that the BMR of Indomalayan, Afrotropical and Australian mammals was lower than that of Holarctic mammals and that, in addition, the BMR of Palaearctic mammals was higher than that of mammals from all other zones.' ―Lovegrove​

Tired people could be low in vitamin D because they are too tired for outdoor activity, and also because low ultraviolet light means high melatonin. Now what happens when people actually take vitamin D orally? Well it makes me tired, and it makes a good deal of other people tired as well:

Case 1: Why does vitamin d make me so tired
Case 2: Does vitamin D supplementing make you tired ?
Case 3: Feeling Tired and Imbalanced Since Taking Vitamin D
Case 4: Vitamin D3 supplementation and fatigue
Case 5: FATIGUE WITH VITAMIN D3
Case 6: Severe Fatigue after Taking Vitamin D
Case 7: Why does taking vitamin D tablets make me incredibly tired?​