75 replies to this topic

[nowayout]

Also bear in mind cholecalciferol is not the active form of D3. It is not even the precursor to the active form of D3. It is the precursor to the precursor of the active form, and basically inert.

I am still curious: In which tissue(s) does the conversion to the active form take place during oral supplementation, and how, if at all, is this different from what happens during photosynthesis?

The only meaningful questions are: 30ng or 45ng/ml 25(OH)D? Higher levels are associated with lower mortality, even if oral supplementation did negatively affect the gut it could be worth it.

Isn't the response-curve supposed to be U-shaped, though? Having the "right" serum levels won't help you if the wrong tissues are oversaturated and therefore in the wrong part of the U.

The question may seem silly to you guys, but D3 in the doses mentioned does not have a lot of track record and it is not so unusual for the route of administration to make a big difference to the safety of a drug. For an extreme example, just look at that woman who just won her case in the U.S. supreme court against a drug maker. She got gangrene because the drug was infused into an artery instead of a vein. In her case having the right plasma concentration was pretty much irrelevant.

Edited by andre, 09 March 2009 - 04:37 PM.

[FunkOdyssey]

Cholecalciferol is inert until it is hydroxylated in the liver to 25OHD. Normally, cholecalciferol is transported from the skin to the liver by Vitamin D binding protein. If you eat the cholecalciferol then you deliver it to the liver more directly. The output (25OHD released from the liver) is the same either way.

Is this the same guy that gave me a hard time about not combining blueberries with casein?

Edited by FunkOdyssey, 09 March 2009 - 04:47 PM.

[nowayout]

Cholecalciferol is inert until it is hydroxylated in the liver to 25OHD. Normally, cholecalciferol is transported from the skin to the liver by Vitamin D binding protein. If you eat the cholecalciferol then you deliver it to the liver more directly. The output (25OHD released from the liver) is the same either way.

Thanks, that mitigates my concern somewhat.

Is this the same guy that gave me a hard time about not combining blueberries with casein?

Yes, I am sorry, and now in turn you must think I'm nuts. I do tend to go overboard on safety issues.

[FunkOdyssey]

Nah, you are asking good questions. To be honest, I did not have a firm grasp of cholecalciferol transportation and metabolism until you voiced your concerns and now we all understand it better as a result.

[kismet]

25(OH)D is converted to calcitriol in the kidney, known as the active form of vitamin D, it suppresses PTH blood levels (and thus bone resorption) in an endocrine fashion. The 25(OH)D levels can serve as a substrate for local (autocrine) calcitriol synthesis, which can reach higher levels than present in the blood. It is thought that the autocrine calcitriol synthesis is of paramout importance to most of the health benefits of vitamin D.

[FunkOdyssey]

Yeah, that's why andre's concerns would have been valid if we were orally supplementing with 25OHD, because perhaps that would result in 1,25OHD concentrations in/around the GI tract higher than normal.

[davidd]

Really great discussion here. And thanks, Krillin, for your post. A lot of good information to be had there. I still haven't even gotten through it all yet.

If people haven't read it yet (I haven't even completed it yet myself), one of the links he gave has some very interesting information in it about hypervitaminosis of vitamin D. Some of the information that article that struck me as important was that some people have had "good" levels of Vitamin D, but for some reason, their body excreted calcium, thus resulting in bone loss. And that was *with* calcium supplementation. The answer was to reduce vitamin D, oddly enough.

And, of course, the mention of heart disease at higher levels (>90ng/ml, I believe) was important.

Lastly, I must have missed it in other Vitamin D reading I've done, but the author points out that studies have shown that if you are getting Vitamin D from the sun, your body will shut down production after a point. However, if you are supplementing *and* getting it from the sun, your body will continue to produce as much as it would have if you hadn't been supplementing. This is important when going from winter to spring/summer if you are going to be exposed to more sun in the spring/summer months.

To be clear, I'm not saying chronic deficiency is good -- not at all. But all this other information makes me believe that periodic testing is extremely important to be positive that you aren't raising your concentration too high. The other thing mentioned was that you can be on the same dose for months and your blood concentration may not increase, but after being on for years, it can. If true, that would seem to indicate some sort of change in the body after prolonged exposure to significant amounts of vitamin D.

The other mental note I'm making for myself is that you can go from a "good" level to "too high" in a short period of time as well, so if I'm going to supplement in the 2000+mg/day category, then I'm going to get tested every few months to be on the safe side. $240-$260/year seems like a reasonable cost to make sure I'm not over doing it. Of course, that adds up a bit if you count every member of the family.

Let's say 60 ng/ml is the perfect level (just for the sake of my point). If certain situations (sun exposure, unintended supplementation due to products not listing all the vitamin D they have, etc., etc.) cause your level to jump up, then you could be in the danger zone. However, if 40 ng/ml is still pretty good, then that still gives you the potential for increased lifespan/fewer diseases, yet also gives you an extra buffer and might allow you to catch the problem before you are in the danger category. Just something to ponder. It is that "perfect in theory" vs "perfect in reality" issue.

These U-shaped situations are a real pain, aren't they??

Anyone have any links to tests a person can order to measure calcium in urine?


David

[davidd]

Yeah, that's why andre's concerns would have been valid if we were orally supplementing with 25OHD, because perhaps that would result in 1,25OHD concentrations in/around the GI tract higher than normal.

Can you expound upon this? I thought you shot down the potential GI tract issue due to the fact that it isn't converted until after digestion??

Thanks,
David

[FunkOdyssey]

We are taking cholecalciferol, which is converted to 25OHD in the liver. We do not supplement with 25OHD. Cholecalciferol is biologically inert until it is metabolized by the liver. This is why the original source of the cholecalciferol is seemingly unimportant -- all roads lead to the liver.

[krillin]

Some of the information that article that struck me as important was that some people have had "good" levels of Vitamin D, but for some reason, their body excreted calcium, thus resulting in bone loss. And that was *with* calcium supplementation. The answer was to reduce vitamin D, oddly enough.

It makes sense if you consider vitamin D's mission to be the elevation of blood calcium, from both increased intestinal absorption and bone resorption. K2 is the vitamin that directs the calcium into the proper tissues.

[kismet]

And, of course, the mention of heart disease at higher levels (>90ng/ml, I believe) was important.

As pointed out vitamin D regulates calcium homeostasis. High doses of vitamin D are used in the VD(N) (vit D+nicotine) model to induce vascular calcification. I did not read the article, but I think I know what they were talking about. There was a study which showed very high vitamin D levels in "south Indian patients with ischemic heart disease"

Lastly, I must have missed it in other Vitamin D reading I've done, but the author points out that studies have shown that if you are getting Vitamin D from the sun, your body will shut down production after a point. However, if you are supplementing *and* getting it from the sun, your body will continue to produce as much as it would have if you hadn't been supplementing. This is important when going from winter to spring/summer if you are going to be exposed to more sun in the spring/summer months.

I guess so. The feedback only takes place in the skin, after some ten thousands of IUs are produced in the skin, further vitamin D is destroyed by the UV radiation in your skin - so blood levels of 25(OH)D/supplemental cholecalciferol won't affect the feedback mechanism.

The other thing mentioned was that you can be on the same dose for months and your blood concentration may not increase, but after being on for years, it can. If true, that would seem to indicate some sort of change in the body after prolonged exposure to significant amounts of vitamin D.

Vitamin D metabolism is a mystery, sometimes.

The other mental note I'm making for myself is that you can go from a "good" level to "too high" in a short period of time as well, so if I'm going to supplement in the 2000+mg/day category, then I'm going to get tested every few months to be on the safe side. $240-$260/year seems like a reasonable cost to make sure I'm not over doing it. Of course, that adds up a bit if you count every member of the family.

Are you talking about vitamin D? (it is not measured in mg, btw)
Being too high is not an issue, it all depends on the chronic exposure. Having blood levels of 80-90ng/ml all year long, could be detrimental. (1) It's only one study, though.
Generally levels of >32ng/ml offer very strong protection from heart disease.

(1) Eur J Epidemiol. 2001;17(6):567-71.
Serum 25-hydroxyvitamin D3 levels are elevated in South Indian patients with ischemic heart disease.
Rajasree S, Rajpal K, Kartha CC, Sarma PS, Kutty VR, Iyer CS, Girija G.
"When controlled for age and selected variables using the multivariate logistic regression, the adjusted OR relating elevated serum 25-hydroxyvitamin D3 levels (> or = 222.5 nmol/l, > or = 89 ng/ml) and IHD is 3.18 (95% CI: 1.31-7.73). "

Edit:
In a letter Reinhold Vieth questions their methodology, but even assuming that this result (which I have pointed out is an outlier) is irrelevant, there's no reason to go for such high levels (as there's zero proof of any benefits beyond 50ng/ml).

Edited by kismet, 10 March 2009 - 10:16 AM.

[davidd]

We are taking cholecalciferol, which is converted to 25OHD in the liver. We do not supplement with 25OHD. Cholecalciferol is biologically inert until it is metabolized by the liver. This is why the original source of the cholecalciferol is seemingly unimportant -- all roads lead to the liver.

Okay, that's what I thought you were saying. Just wanted to make sure.

Thanks,
David

[davidd]

Some of the information that article that struck me as important was that some people have had "good" levels of Vitamin D, but for some reason, their body excreted calcium, thus resulting in bone loss. And that was *with* calcium supplementation. The answer was to reduce vitamin D, oddly enough.

It makes sense if you consider vitamin D's mission to be the elevation of blood calcium, from both increased intestinal absorption and bone resorption. K2 is the vitamin that directs the calcium into the proper tissues.

Are you suggesting that they may not have taken enough K2?

David

[davidd]

And, of course, the mention of heart disease at higher levels (>90ng/ml, I believe) was important.

As pointed out vitamin D regulates calcium homeostasis. High doses of vitamin D are used in the VD(N) (vit D+nicotine) model to induce vascular calcification. I did not read the article, but I think I know what they were talking about. There was a study which showed very high vitamin D levels in "south Indian patients with ischemic heart disease"

Are you suggesting that it may have been due to nicotine use by the south Indian patients?

Lastly, I must have missed it in other Vitamin D reading I've done, but the author points out that studies have shown that if you are getting Vitamin D from the sun, your body will shut down production after a point. However, if you are supplementing *and* getting it from the sun, your body will continue to produce as much as it would have if you hadn't been supplementing. This is important when going from winter to spring/summer if you are going to be exposed to more sun in the spring/summer months.

I guess so. The feedback only takes place in the skin, after some ten thousands of IUs are produced in the skin, further vitamin D is destroyed by the UV radiation in your skin - so blood levels of 25(OH)D/supplemental cholecalciferol won't affect the feedback mechanism.

Yes, it does make sense. I just never really thought about it in that way.

The other mental note I'm making for myself is that you can go from a "good" level to "too high" in a short period of time as well, so if I'm going to supplement in the 2000+mg/day category, then I'm going to get tested every few months to be on the safe side. $240-$260/year seems like a reasonable cost to make sure I'm not over doing it. Of course, that adds up a bit if you count every member of the family.

Are you talking about vitamin D? (it is not measured in mg, btw)
Being too high is not an issue, it all depends on the chronic exposure. Having blood levels of 80-90ng/ml all year long, could be detrimental. (1) It's only one study, though.
Generally levels of >32ng/ml offer very strong protection from heart disease.

Yes, I'm talking about D3. I meant 2000+ IU/day. Just a typo.
I'm not sure there are enough studies to show that 1 or 2 months at 100 ng/ml is not detrimental in some way.

David

[kismet]

Are you suggesting that it may have been due to nicotine use by the south Indian patients?

No, but nicotine certainly could increase CVD risk together with very high 25(OH)D levels. Just wanted to point out that vitamin D (-poisoning) both with and without nicotine is used as a model of vascular calcification, while at the correct doses vitD is protective.

Yes, I'm talking about D3. I meant 2000+ IU/day. Just a typo.
I'm not sure there are enough studies to show that 1 or 2 months at 100 ng/ml is not detrimental in some way.

David

We definitely can exclude acute toxicity in most populations. I would not expect any long term damage, neither would I expect anyone to maintain such high levels for months... I don't think that is an issue.

[krillin]

Some of the information that article that struck me as important was that some people have had "good" levels of Vitamin D, but for some reason, their body excreted calcium, thus resulting in bone loss. And that was *with* calcium supplementation. The answer was to reduce vitamin D, oddly enough.

It makes sense if you consider vitamin D's mission to be the elevation of blood calcium, from both increased intestinal absorption and bone resorption. K2 is the vitamin that directs the calcium into the proper tissues.

Are you suggesting that they may not have taken enough K2?

David

Probably, based on the fringe status of K2 supplements and the difficulty in getting it through diet. I'm not willing to say that K2 would've prevented the toxicity, but it's possible.

Med Hypotheses. 2007;68(5):1026-34.
Vitamin D toxicity redefined: vitamin K and the molecular mechanism.
Masterjohn C.
Weston A. Price Foundation, 4200 Wisconsin Ave., NW, Washington, DC 20016, United States. ChrisMasterjohn@gmail.com

The dose of vitamin D that some researchers recommend as optimally therapeutic exceeds that officially recognized as safe by a factor of two; it is therefore important to determine the precise mechanism by which excessive doses of vitamin D exert toxicity so that physicians and other health care practitioners may understand how to use optimally therapeutic doses of this vitamin without the risk of adverse effects. Although the toxicity of vitamin D has conventionally been attributed to its induction of hypercalcemia, animal studies show that the toxic endpoints observed in response to hypervitaminosis D such as anorexia, lethargy, growth retardation, bone resorption, soft tissue calcification, and death can be dissociated from the hypercalcemia that usually accompanies them, demanding that an alternative explanation for the mechanism of vitamin D toxicity be developed. The hypothesis presented in this paper proposes the novel understanding that vitamin D exerts toxicity by inducing a deficiency of vitamin K. According to this model, vitamin D increases the expression of proteins whose activation depends on vitamin K-mediated carboxylation; as the demand for carboxylation increases, the pool of vitamin K is depleted. Since vitamin K is essential to the nervous system and plays important roles in protecting against bone loss and calcification of the peripheral soft tissues, its deficiency results in the symptoms associated with hypervitaminosis D. This hypothesis is circumstantially supported by the observation that animals deficient in vitamin K or vitamin K-dependent proteins exhibit remarkable similarities to animals fed toxic doses of vitamin D, and the observation that vitamin D and the vitamin K-inhibitor Warfarin have similar toxicity profiles and exert toxicity synergistically when combined. The hypothesis further proposes that vitamin A protects against the toxicity of vitamin D by decreasing the expression of vitamin K-dependent proteins and thereby exerting a vitamin K-sparing effect. If animal experiments can confirm this hypothesis, the models by which the maximum safe dose is determined would need to be revised. Physicians and other health care practitioners would be able to treat patients with doses of vitamin D that possess greater therapeutic value than those currently being used while avoiding the risk of adverse effects by administering vitamin D together with vitamins A and K.

PMID: 17145139