The Travis Corner

[HDD]

@Travis Did you have your vitamin D measured prior to supplementing?

After a quick google, I found that bone pain is not indicative that you shouldn’t supplement but the pain indicates that you need vitamin D. The other thing I found was magnesium may need to be increased when supplementing.

“However, if you are experiencing pain while taking vitamin D, then your bone mineral status is definitely not normal and your pain proves it. You see, when your bones are seriously depleted of minerals, and you begin to take vitamin d, the vitamin d will help you start absorbing minerals and depositing them into the bones where it is needed. But water always attaches to minerals, and when your bones begin to remineralize, it will also draw water with those minerals.

Unfortunately for many, when this happens, the periosteum, a thin layer of tissue that surrounds the bones, will swell with the water, causing pain similar to the pain of a bone bruise. This pain is ‘temporary’, meaning that it can last weeks to months, sometimes even up to 6 months or longer, depending upon how long it takes for your bones to stop remineralizing at such a high rate. “

“One other cause of the pain, or at least that might be contributing to your problems is a deficiency of vitamin D cofactors such as:

• Magnesium
• Vitamin A
• Vitamin K
• Vitamin B2 (riboflavin)
• Zinc

Pain While Taking Vitamin D? What Can You Do?

This site sells supplements so I’m not sure how legit the info is, however, I did find similar info on other sites.

 

[HDD]

On Reye Syndrome/aspirin -

“Early in the 20th century, people were told that fevers were very bad, and that aspirin should be used whenever there is a fever.

In the 1980s, there was a big publicity campaign warning parents that giving aspirin to a child with the flu could cause the potentially deadly Reye syndrome. Aspirin sales declined sharply, as sales of acetaminophen (Tylenol, etc.) increased tremendously. But in Australia, a study of Reye syndrome cases found that six times as many of them had been using acetaminophen as had used aspirin. (Orlowski, et al., 1987)”
Aspirin, brain, and cancer

From referenced abstract-
A catch in the Reye. - PubMed - NCBI

“Twenty-six cases of Reye syndrome from The Children's Hospital, Camperdown, Australia, occurring between 1973 and 1982 were reviewed. Of these, 20 cases met the US Public Health Service Centers for Disease Control criteria for the diagnosis of Reye syndrome. Aspirin or salicylate ingestion had occurred in only one of the 20 cases (5%), and paracetamol (acetaminophen) had been administered in only six of the cases (30%). Pathologic confirmation of the diagnosis of Reye syndrome was accomplished in 90% of the cases.”

“In Australia, the pediatric usage of aspirin has been extremely low for the past 25 years (less than 1% of total dosage units sold), with paracetamol (acetaminophen) dominating the pediatric analgesic and antipyretic market. Reye syndrome may be disappearing from Australia despite a total lack of association with salicylates or aspirin ingestion, since there were no cases found at The Children's Hospital in 1983, 1984, or 1985.”

 

[Amazoniac]

@Travis Did you have your vitamin D measured prior to supplementing?

After a quick google, I found that bone pain is not indicative that you shouldn’t supplement but the pain indicates that you need vitamin D. The other thing I found was magnesium may need to be increased when supplementing.

“However, if you are experiencing pain while taking vitamin D, then your bone mineral status is definitely not normal and your pain proves it. You see, when your bones are seriously depleted of minerals, and you begin to take vitamin d, the vitamin d will help you start absorbing minerals and depositing them into the bones where it is needed. But water always attaches to minerals, and when your bones begin to remineralize, it will also draw water with those minerals.

Unfortunately for many, when this happens, the periosteum, a thin layer of tissue that surrounds the bones, will swell with the water, causing pain similar to the pain of a bone bruise. This pain is ‘temporary’, meaning that it can last weeks to months, sometimes even up to 6 months or longer, depending upon how long it takes for your bones to stop remineralizing at such a high rate. “

“One other cause of the pain, or at least that might be contributing to your problems is a deficiency of vitamin D cofactors such as:

• Magnesium
• Vitamin A
• Vitamin K
• Vitamin B2 (riboflavin)
• Zinc

Pain While Taking Vitamin D? What Can You Do?

This site sells supplements so I’m not sure how legit the info is, however, I did find similar info on other sites.

It might have something to do with a faster rate of deposition with supplementation, making it disordered; it's unusual for the body to obtain a lot of ingested vit D at once and without preformed vitamin A. This should be eased or disappear with a fat-soluble vitamin complex, such as Zeus' Estroban. I guess it can also be eased by taking much less at a time to prevent this. A paragraph that reads like Wikipedia.

Vitamin D Really Toxic?

I have tried supplemental vit D before and I couldn't make it work right (but much better when part of a complex). It seemed to increase my need for magnesium, vit C, taurine, and possibly other nutrients in a way that it was difficult to keep up.

People taking vit D should be careful with extra calcium, especially if the metabolism is weak and the person is prone to calcification.

The skin production from sun exposure also increases or drops depending on needs, so being able to produce 10000 IU from a single exposure can't be used as reference for what happens on consecutive exposures.

 

[HDD]

Ray Peat —

“In addition to a few quarts of milk with added vitamin D, and eating liver, I rub several drops of the vitamin D oil onto my skin, and occasionally use an ultraviolet light.”

Q. I noticed you mention eating liver, could I ask the relationship between liver and vitamin D?

Ray Peat —

“The liver catalyzes the hydroxylation of cholecalciferol to 25-OH-colecalciferol, and many nutritional deficiencies can effect the liver's functions. I've known several liver-avoiders whose serum 25-OH-Vitamin D stays low despite big doses, and I suspect their general nutrition is responsible. It's reasonable to feed their liver optimally.”

 

[HDD]

@Amazoniac

Caller: Did you say that you need added calcium for the vitamin D to work better?

RP: You need a good ratio of calcium to phosphate, and I think it's really protective to take in well over a thousand. I try to get about 2,500 mg of calcium per day.

RP: Thyroid works in many ways similarly to vitamin D and regulates calcium and magnesium in particular.

Vitamin D - KMUD, 2016-11-18


The calcium/phosphate ratio is emphasized.

 

[haidut]

You had clearly cited an article as proof that aspirin could protect against carbon tetrachloride poisoning that hadn't even used aspirin.

Is that right? You know that I had read that article and had also cited it twice, and I don't think you are giving a fair summary of the situation. This is what the article says:

'The mechanism for aspirin-caused liver injury is not clear. Aspirin produces hepatotoxic reactions as a cumulative phenomenon, requiring days or weeks to develop. Patients with active rheumatic or collagen disease, as well as children, are especially susceptible. Blood levels of salicylate higher than 25 mg/dL are particularly likely to lead to hepatic injury.' ―Zimmerman ​

'The mechanism for acetaminophen liver damage is quite clear. It produces hepatic injury as a result of a large single overdose, usually suicidal in intent. Patients with acetaminophen blood levels higher than 300 mg/dL at four hours after intake are most likely to develop hepatic damage; when N-acetylcysteine is used within the first ten hours after ingestion of an overdose, the recovery rate is reported to be virtually 100%. The conditions of patients receiving long-term full doses of either aspirin or acetaminophen should be intermittently monitored for hepatic injury.' ―Zimmerman ​

You see: he had stated that aspirin is hepatotoxic at over 25 mg/dL, and also that acetaminophen is hepatotoxic at over 300 mg/dL. Yet, you implied the exact opposite and had claimed that acetaminophen is 'clearly cytotoxic in almost any dose.' If you'd read that article you'd know that 90% of all acetaminophen hepatotoxicity had occurred with doses over 15 grams, and you might even get the impression that it's only notorious for such on account of it's use as a popular suicide drug in the United Kingdom. Have you actually seen any evidence at all of acetaminophen causing liver damage at plasma concentrations under 25 mg/dL like you had implied?

This appears to demonstrate the role 2-series prostaglandins have in liver fibrosis, yet as far as I can discern Reye syndrome has caused more fatalities and cases and irreversible brain damage than has carbon tetrachloride. I would imagine that simply avoiding ω−6 fatty acids would lower the carcinogenic potential just the same, which it could do by lowering arachidonic acid and increasing Mead acid. There are many other COX-2 inhibitors that don't cause hyperammonemia by inhibiting ornithine carbamoyltransferase.

Sorry, I disagree on this one. In fact, there is a study (below) showing aspirin can protect the liver from the toxicity of acetaminophen. The toxicity of APAP is multifaceted and not limited to glutathione depletion. It involves serotonergic mechanisms as well as direct toxicity (activation of TLR family), resulting in cells spilling ATP, LDH and other intracellular components into the blood. To my knowledge, aspirin does not do that even in high doses, except for raising the GSSG/GSH by lowering GSH. Human trials with 3g aspirin daily noted no side effects except ototoxicity. The clinically relevant dose of APAP for humans is 3g-4g daily. According to the study below, at presumably safe doses (HED ~36mg/kg) APAP can apparently cause serious hepatoxocity. And APAP was given just once. Imagine what happens with chronic exposure. The study even goes as far as to suggest formulating aspirin and APAP together to protect from the hepatotixicity in cases of (usually intentional) APAP overdose. Given that this study did not use an APAP dose that qualifies as overdose, the aspirin/APAP combo should be even more relevant considering the millions of people around the world that consume such APAP doses on a daily basis.

JCI - Acetaminophen-induced hepatotoxicity in mice is dependent on Tlr9 and the Nalp3 inflammasome
'Aspirin a day' for the liver

"...We have identified a 2-signal requirement for amplification of APAP-induced liver toxicity. Tlr9 provides a signal for the transcription of pro–IL-1β and pro–IL-18, and the Nalp3 inflammasome provides the signal for cleavage and activation of these pro-cytokines. In addition we have demonstrated the biologicalsignificance of mammalian DNA from apoptotic cells in activating Tlr9, expanding its known role as a stimulus for the development of autoimmunity to include induction of sterile inflammation (19, 23, 31)."

"...The signals required for activation of the Nalp3 inflammasome are not as well defined as those for Tlr9, with uric acid and ATP from dying hepatocytes being candidates (34, 35). The relative importance of these for Nalp3 activation in APAP hepatotoxicity needs to be established. Our model builds on the known mechanism of APAP-induced toxic injury to hepatocytes and identifies DNA from apoptotic cells as a signalforimmune activation (Figure 7)."

"...The requirement of Nalp3 inflammasome–mediated inflammation in APAP-induced hepatotoxicity and the ability of aspirin to inhibit this pathway to the degree that it reduces liver injury and improves survival have significant clinical implications. If these findings are confirmed in humans, coformulation of aspirin with APAP may reduce hepatoxicity from APAP overdoses. Furthermore the Nalp3 inflammasome may have an importantrole in otherforms ofsterile inflammation, such as ischemic and nonalcoholic steatohepatitis."

Now, there are much more troubling implications from the study above. As you know TLR9 activation is implicated in many autoimmune conditions and several cancers. Considering the boom in autoimmune hepatitis cases over the last 2 decades, I am beginning to wonder if these are not linked to the strong medical propaganda to push people away from aspirin and towards "safer" alternatives like APAP.

No need to argue. I am not trying to convince you of anything. Just something to think about.

 

[Amazoniac]

@Amazoniac

Caller: Did you say that you need added calcium for the vitamin D to work better?

RP: You need a good ratio of calcium to phosphate, and I think it's really protective to take in well over a thousand. I try to get about 2,500 mg of calcium per day.

RP: Thyroid works in many ways similarly to vitamin D and regulates calcium and magnesium in particular.

Vitamin D - KMUD, 2016-11-18


The calcium/phosphate ratio is emphasized.

The higher your calcium intake, the more careful you have to be with vitamin D supplementation, especially so in the cases mentioned above. Supplemental vit D is very effective is suppressing metabolism depending on how much you need and can handle, I have experienced this many times and I'm certainly not alone based on frequent reports that include headaches, cold body, palpitations, bad body odor, concerning hair analysis patterns, and so on. People with plenty of vit D can get away with much lower calcium intakes, and it almost seems that one has to compensate for the other to keep a good balance.

Milk Alkali Syndrome (explicit)

 

[HDD]

@Amazoniac
I find it odd that Ray Peat has not discussed these issues, don’t you? I would be interested in his take on it.

Edit: Ray is very conservative in regards to supplementation and I don’t believe he writes/speaks about anything without having thorough knowledge of the subject.

 

[Amazoniac]

@Amazoniac
I find it odd that Ray Peat has not discussed these issues, don’t you? I would be interested in his take on it.

Edit: Ray is very conservative in regards to supplementation and I don’t believe he writes/speaks about anything without having thorough knowledge of the subject.

He does acknowledge that once one is decreased, you can compensate with the other:

East West: Serotonin And Endotoxin

"Eating excess calcium is very helpful for regulating the parathyroid hormone. It tends to rise in the winter. So I think we need more calcium during the winter."​

--
Unrelated but interesting:

"95% of [serotonin] roughly is produced in the intestine and that biggest concentration in the digestive system is in or around the appendix." "[..]there is a gradient through increasing as you go down the small intestine and normally the upper part starting at your stomach almost everyone has a sterile upper small intestine and as you go down, the likelihood of having bacteria increases. And as the person's thyroid function decreases, their intestinal secretion are reduced, peristalsis is reduced, bacteria tend to creep farther and farther up. A really healthy person has almost sterile whole small intestine and the sicker you are, the lower your thyroid function, the more bacteria live in your small intestine, and that means that foods that are slower to digest are going to feed bacteria and encourage them to live more abundantly higher up in your intestine. But ordinarily the gradient of bacteria is very concentrated towards the appendix, the lower end of the small intestine, and it happens that the gradient of bacterial infection increases parallel to the gradient of serotonin and is probably that the toxins from the bacteria interacting with the physiology of the person are stimulating the production of serotonin because the function of serotonin is to cause contraction of the intestinal muscles, get rid of what is in there cause diarrhea and get rid of the irritant."​

 

[CLASH]

@Amazoniac
With this calcium/ vit d3 info in mind (I have read some of the studies you posted and others because vit d3 tends to make me tired), what do you find to be safe intake for either?

I’ve found from reading/ experience that taking calcium in a 1:1 ratio with phosphorous is helpful but with certain stipulations:
1) calcium should be taken with a meal and magnesium
2) calcium should be less than 500mg per dose (i shoot for 300mg)
3) calcium should be taken with magnesium and vit K2

As for vit D3, I’m not entirely sure. I have no issues with the sun. So far I’ve kept doses at or under 2000iu but I still get fatigue/ sleepiness from it. I may consider splitting the dosages up to get smaller boluses to stimulate food intake (topical made me feel worse than oral). What are your thoughts?

 

[Arrade]

@Amazoniac
With this calcium/ vit d3 info in mind (I have read some of the studies you posted and others because vit d3 tends to make me tired), what do you find to be safe intake for either?

I’ve found from reading/ experience that taking calcium in a 1:1 ratio with phosphorous is helpful but with certain stipulations:
1) calcium should be taken with a meal and magnesium
2) calcium should be less than 500mg per dose (i shoot for 300mg)
3) calcium should be taken with magnesium and vit K2

As for vit D3, I’m not entirely sure. I have no issues with the sun. So far I’ve kept doses at or under 2000iu but I still get fatigue/ sleepiness from it. I may consider splitting the dosages up to get smaller boluses to stimulate food intake (topical made me feel worse than oral). What are your thoughts?

I take 30,000 iu Vit D and haven't gone above median range

 

[Amazoniac]

@Amazoniac
With this calcium/ vit d3 info in mind (I have read some of the studies you posted and others because vit d3 tends to make me tired), what do you find to be safe intake for either?

I’ve found from reading/ experience that taking calcium in a 1:1 ratio with phosphorous is helpful but with certain stipulations:
1) calcium should be taken with a meal and magnesium
2) calcium should be less than 500mg per dose (i shoot for 300mg)
3) calcium should be taken with magnesium and vit K2

As for vit D3, I’m not entirely sure. I have no issues with the sun. So far I’ve kept doses at or under 2000iu but I still get fatigue/ sleepiness from it. I may consider splitting the dosages up to get smaller boluses to stimulate food intake (topical made me feel worse than oral). What are your thoughts?

You have to take into consideration what sun and diet provide, and if you really need supplementation, I suggest you to familiarize with a lower dose first (such as 400 IU) and only then start to work your way up slowly. In publication #2 here it was estimated that diet provides about 1300-1600 IU depending on its composition (animal fats especially); and the average of sun exposure was 1500 IU.

Then you have on publication #1 there a mad graph that makes you realize the generalized recommendations are nearly useless: the same dose that can turn someone into a statue might not be enough to bring the other out of a deficiency. But of course the more you take, the greater your levels.

In terms of nutritional support, the comments above apply: trying it as part of a fat-soluble vitamins complex and increase magnesium, B-vitamins, taurine and vit C along.

For magnesium it's better to supplement up to 120 mg or so multiple times instead of more at once. The efficiency of absorption starts to decrease markedly as the doses increase much beyond that.

It's worth considering adding vit D to orange juice since this way it might help in reducing the dose needed to achieve the same benefit. For some reason I have the impression that such combination is safer than with milk. If you're prone to calcification it's better to take it away from meals that are higher in calcia.

Testing or praying is also useful.

 

[Amazoniac]

When in need, the absorption can double (Lancaster, 2016):

Magnesium supplementation and microelement homeostasis
"In general, 30-40% of the daily dietary magnesium intake is absorbed in the small intestine. In case of low magnesium intake, absorption rate may be as high as 75%, while in case of high intake it may be reduced to 25%."​

If vit D supplementation creates a sudden shortage of magnesium [or encourages its absorption (Agathos, 2018)], you can perhaps take advantage of that by increasing the dose from 120 to 200 mg or so without much wastage.

Magnesium absorption in the human small intestine. Results in normal subjects, patients with chronic renal disease, and patients with absorptive hypercalciuria.

"In the present experiments water movement was near zero. Contraction or expansion of luminal volume would tend to increase or decrease luminal Mg concentration. Since Mg absorption rate is highly dependent on luminal Mg concentration (up to 10 mM [1 mM = 2 mEq = molecular weight (Mg is about 24 g/mol) in mg]), Mg absorption under normal physiologic conditions (i.e., after a meal) would probably be influenced to an important degree by water movement."

"One interesting result of our experiments is that Mg absorption is reduced in the jejunum of patients with chronic renal disease. It is known that these patients have a deficiency of the active metabolite of vitamin D, 1,25-dihydroxycholecalciferol (31, 32) and that vitamin D stimulates Mg absorption in vitamin D-deficient animals (10, 11). Most likely, the malabsorption of Mg in patients with renal disease is due to vitamin D deficiency. The fact that Mg absorption in renal disease patients is so markedly depressed suggests that Mg absorption is exquisitely dependent on vitamin D. Of course, renal insufficiency per se might also depress Mg absorption, but if so, the defect would have to be quite specific since most ions and solutes (divalent cations excluded) are absorbed normally in the jejunum and ileum of patients with chronic renal disease (33). Whatever its cause, it seems likely that Mg malabsorption helps protect renal disease patients from the hazards of magnesium overload (34)."
@yerrag (it should be evident that you're one of my favorite fishes)

"If Mg as well as Ca absorption depends on vitamin D, the question arises whether these two divalent cations are absorbed by the same transport mechanism. If so, they might compete for the common diffusion site or transport carrier in the membrane. Our results reveal that Ca has no effect on Mg absorption in the jejunum, even when the Ca concentration in the lumen is eight-fold higher than the luminal Mg concentration. This strongly suggests that the Ca and Mg transport systems are separate. On the other hand, the presence of 5 mM Mg in the lumen resulted in a 40% inhibition of Ca absorption. (However, increasing the Mg concentration to 10 mM did not cause a further depression of Ca absorption.) Assuming that the Ca and Mg transport mechanisms are separate, the reason why Mg depresses Ca absorption is not clear. Since Mg has been shown to reduce passive cation movement via shunt pathways in gallbladder mucosa (35, 36), one possibility is that Mg may depress Ca absorption by reducing the passive component (25) of jejunal Ca absorption."

"According to the data shown in Fig. 1, the half-maximal absorption rate of Mg by the human small bowel occurs when the luminal Mg concentration is about 5 mM [120 mg]."

Similar to another experiment.​

.
"Assuming a maximum transport capacity for Mg of 0.2 mmol [5 mg]/30 cm per h (Fig. 1), and a 300-cm length of small intestine (37), the absorptive capacity of the human small bowel is 2 mmol/h or 48 mmol/day (about 1,100 mg/day). This compares with an average dietary intake of 500 mg/day, of which about 170 mg is absorbed [35%] according to balance techniques (38) (which may underestimate absorption somewhat due to secretion of Mg in the digestive juices)."

"Of course, it must be kept in mind that the test solutions used in our experiments did not contain glucose or other nutrients and that they were designed to result in near zero movement of water. Therefore, our results may not be directly applicable to normal physiological conditions within the gastrointestinal tract."​

 

[yerrag]

Whatever its cause, it seems likely that Mg malabsorption helps protect renal disease patients from the hazards of magnesium overload (34)."
@yerrag (it should be evident that you're one of my favorite fishes)

Thanks. The author has a nice way of putting. Painting mg malabsorption as helping renal disease patients rom the hazards of magnesium overload. But why would there be an overload if there is magnesium overload? There seems to be some circular logic in that statement. I'm not getting it.

 

[yerrag]

Thanks. The author has a nice way of putting. Painting mg malabsorption as helping renal disease patients rom the hazards of magnesium overload. But why would there be an overload if there is magnesium overload? There seems to be some circular logic in that statement. I'm not getting it.

Let me rephrase: Why would there be an overload if there is magnesium malabsorption? It seems to be an obvious case of cause and effect that does need to be stated. It's like saying defecating all you eat keeps you from getting obese. Am I getting this wrong? The argument isn't circular (my mistake) and.the only thing that's noteworthy is it's exceedingly banal.

 

[Amazoniac]

Let me rephrase: Why would there be an overload if there is magnesium malabsorption? It seems to be an obvious case of cause and effect that does need to be stated. It's like saying defecating all you eat keeps you from getting obese. Am I getting this wrong? The argument isn't circular (my mistake) and.the only thing that's noteworthy is it's exceedingly banal.

They're not speculating that the malabsorption is intentional, but that it could help to prevent an overload in the disease.

 

[Ritchie]

That seems safe, but from now on I'm going with this.

Cheers, thanks for that travis

 

[yerrag]

They're not speculating that the malabsorption is intentional, but that it could help to prevent an overload in the disease.

Still having difficulty with the logic. If the malabsorption were the result of magnesium overload, then I can see it being helpful. But if magnesium overloading never happened, then malabsorption would simply be a problem finding its own silver lining.

 

[Travis]

Any speculation as to why oral vitamin D would cause these symptoms in some people but not others? I once took 10,000 IU orally of Thorne Vitamin D liquid every day until the 30 ml bottle was empty and then 5,000 IU daily after that until another bottle was empty. During that time 25-hydroxyvitamin D rose from 40 ng/mL to 80 ng/mL and I didn’t notice any bone pain or tiredness. Could VDR polymorphisms have an impact on this?

Joint pain seems to be a common finding in hypercalcemia, so perhaps my vitamin D receptors in the intestines were unusually responsive or very highly expressed.

 

[Travis]

from what you say there is no vitamin A in his diet.

Beta-carotene is very often considered dietary vitamin A, and for good reason. Beta-carotene is essentially two retinol molecules joined at their methyl ends, yet is safer to consume because it's cleavage is regulated under reverse feedback from retinoic acid.