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Could magnesium help also?jaa said:post 110731 The paper states that the renal-potassium wasting is caused by hypercalciema. Seems like supplementing vitamin k2 could help.
milk_lover said:post 110734Could magnesium help also?jaa said:post 110731 The paper states that the renal-potassium wasting is caused by hypercalciema. Seems like supplementing vitamin k2 could help.
milk_lover said:Could magnesium help also?
@tyw, what are your thoughts on vitamin d from supplements or from sun?
If you search for this on the forum, you'll notice how there's still a lot of confusion on this.
For reasons that I don't understand, it seems easier to overdose with much less when people take supplements, the effects are also very different. Why?
Thanks! @SuikerbuikSun exposure is preferred. Fixing of sulfation pathways along with adequate sulfur supply is needed in this case.
Efficacy of supplementation is going to be dependent on liver and kidney function and overall storage and mobilisation capacity. Storage is a hit or miss, and conversion is a hit or miss. Regulation is less controlled with supplemental form. I will support use of supplements during cases of tested deficiency and low sunlight, but that requires the appropriate testing and personal supervision of a medical practitioner.
More details below.
Image for reference: https://www.nap.edu/read/5776/chapter/9#251
View attachment 5192
----
Active Form
As basic background information, the active form of Vitamin D3 is called calcitriol. This is the compound that will be responsible for vitamin D3's effects, and therefore any disruptions along the pathway to synthesise this compound, or some problem with response to this compound, will prevent the expected effects from Vitamin D3.
----
Supplements vs Natural Synthesis. Sulfation vs not
When we refer to vitamin D3 supplements, we are talking about cholecalciferol, also, we are usually talking about un-sulfated cholecalciferol.
When we make cholecalciferol in the skin, it is made from 7-dehydrocholesterol, and this is usually a sulfated compound. The main difference with sulfation, is that the the sulfated cholecalciferol product from skin production is both water and fat soluble, while most cholecalciferol supplements are not sulfated, and only fat soluble.
We can already see that if a person fails to create enough 7-dehydrocholesterol, or doesn't have enough sulfur, or fails in the needed sulfation pathways, then skin production of cholecalciferol is going to be reduced.
----
Storage and Conversion of Cholecaliferol
In any case, once we have cholecalciferol, much of it is stored, and some of it sent to the liver to be converted to calcifediol / 25(OH)D3.
Storage of cholecalciferol is largely (>70%) in adipose tissue, and I personally think this is even more likely if cholecalciferol is taken through supplements in the un-sulfated, fat-soluble-only form. This means that body fat is a store of cholecalciferol, and the more body fat one has, the more one has potential active Vitamin D3 production from stored precursors. Whether or not this can lead to excess vitamin D3 is unknown, but I have seen cases of people saying that their measured 25(OH)D3 levels shot up dramatically after losing significant levels of body fat.
Another risk here with supplementing in people with lots of body fat, is that supposed high dose supplementation doesn't change 25(OH)D3 levels, and prompts the person to supplement even more, even to the point of overdose. It is storage of cholecalciferol that is causing the lack of impact on 25(OH)D3 levels.
----
25(OH)D
And now we get to 25(OH)D / calcifediol, which is what is usually measured on "Vitamin D serum tests" -- Calcifediol - Wikipedia
This is made in the liver from cholecalciferol, using the enzyme cytochrome P450 2R1 / Vitamin D 25-hydroxylase. Instantly we see potentials for failure ... The liver is yet again the bottleneck for active Vit D3 function, and the CYP450 system is particular dependent on good reducing function -- most of these enzymes have a heme iron center, and require NADPH for function. NAPDH levels need to be constantly replenished by the Pentose Phosphate Pathway.
I speculate that any excessive xenobiotic burden on the liver will also compromise production of 25(OH)D3, but in any case, both supplemental and endogenously synthesis cholecalciferol needs to go through this phase, and if the liver isn't functioning well, then there will be no active Vitamin D3.
In any case, 25(OH)D3 seems to be distributed pretty evenly between all tissues, and can be mobilised at will. Most kinetic studies will say that we have a couple of days, to a week's worth, of 25(OH)D3 ready to be converted to calcitriol.
----
Active D3
The active form of D3 is then calcitriol / 1,25(OH)2D3 -- Calcitriol - Wikipedia
This happens in the kidneys, and note again that the conversion from 25(OH)D to active calcitriol requires another CYP450 family enzyme, 25-Hydroxyvitamin D3 1-alpha-hydroxylase / cytochrome p450 27B1. The same caveats about apply (just substitute kidney over liver).
This conversion is a dynamic process, and as we already know, is tied heavily to calcium metabolism, and thus is expected to vary acutely.
====
At the end of all of that, we can see that endogenous vs exogenous cholecalciferol largely differs in their sulfation characteristics, which has definite implications for storage of cholecalciferol.
As far as I know, it is unknown whether or not the un-sulfated supplementatl cholecalciferol can escape regulation. For example, it may be possible that sulfated, water-soluble, skin-produced cholecalciferol, is capable of signalling to the rest of the system that, "hey, we have enough cholecalciferol", and prevent accumulation of excess.
In any case, it is clear that cholecalciferol synthesis in the skin is regulated, but exogenous supplies are not. In that sense, it is probably wise to supplement only if one is sure that 25(OH)D3 tests continue to come back at deficient levels, where there is no access to sunshine, and that one is relatively weight stable through the period of supplementation.
SIDENOTE: I personally do not like the idea of tanning beds. EMF emission is unknown, and intensity of lights has to be well-known (need to pester the business offering the service to give you all the details).
Taking care not to overload the liver is something that everyone should already do. Vitamin D3 production is just yet another system that is heavily dependent on this organ.
....
Great reply. I'm on the same side of the fence. D is fairly well regulated. "More" can often turn into "less".Sun exposure is preferred. Fixing of sulfation pathways along with adequate sulfur supply is needed in this case.
Efficacy of supplementation is going to be dependent on liver and kidney function and overall storage and mobilisation capacity. Storage is a hit or miss, and conversion is a hit or miss. Regulation is less controlled with supplemental form. I will support use of supplements during cases of tested deficiency and low sunlight, but that requires the appropriate testing and personal supervision of a medical practitioner.
More details below.
Image for reference: https://www.nap.edu/read/5776/chapter/9#251
View attachment 5192
----
Active Form
As basic background information, the active form of Vitamin D3 is called calcitriol. This is the compound that will be responsible for vitamin D3's effects, and therefore any disruptions along the pathway to synthesise this compound, or some problem with response to this compound, will prevent the expected effects from Vitamin D3.
----
Supplements vs Natural Synthesis. Sulfation vs not
When we refer to vitamin D3 supplements, we are talking about cholecalciferol, also, we are usually talking about un-sulfated cholecalciferol.
When we make cholecalciferol in the skin, it is made from 7-dehydrocholesterol, and this is usually a sulfated compound. The main difference with sulfation, is that the the sulfated cholecalciferol product from skin production is both water and fat soluble, while most cholecalciferol supplements are not sulfated, and only fat soluble.
We can already see that if a person fails to create enough 7-dehydrocholesterol, or doesn't have enough sulfur, or fails in the needed sulfation pathways, then skin production of cholecalciferol is going to be reduced.
----
Storage and Conversion of Cholecaliferol
In any case, once we have cholecalciferol, much of it is stored, and some of it sent to the liver to be converted to calcifediol / 25(OH)D3.
Storage of cholecalciferol is largely (>70%) in adipose tissue, and I personally think this is even more likely if cholecalciferol is taken through supplements in the un-sulfated, fat-soluble-only form. This means that body fat is a store of cholecalciferol, and the more body fat one has, the more one has potential active Vitamin D3 production from stored precursors. Whether or not this can lead to excess vitamin D3 is unknown, but I have seen cases of people saying that their measured 25(OH)D3 levels shot up dramatically after losing significant levels of body fat.
Another risk here with supplementing in people with lots of body fat, is that supposed high dose supplementation doesn't change 25(OH)D3 levels, and prompts the person to supplement even more, even to the point of overdose. It is storage of cholecalciferol that is causing the lack of impact on 25(OH)D3 levels.
----
25(OH)D
And now we get to 25(OH)D / calcifediol, which is what is usually measured on "Vitamin D serum tests" -- Calcifediol - Wikipedia
This is made in the liver from cholecalciferol, using the enzyme cytochrome P450 2R1 / Vitamin D 25-hydroxylase. Instantly we see potentials for failure ... The liver is yet again the bottleneck for active Vit D3 function, and the CYP450 system is particular dependent on good reducing function -- most of these enzymes have a heme iron center, and require NADPH for function. NAPDH levels need to be constantly replenished by the Pentose Phosphate Pathway.
I speculate that any excessive xenobiotic burden on the liver will also compromise production of 25(OH)D3, but in any case, both supplemental and endogenously synthesis cholecalciferol needs to go through this phase, and if the liver isn't functioning well, then there will be no active Vitamin D3.
In any case, 25(OH)D3 seems to be distributed pretty evenly between all tissues, and can be mobilised at will. Most kinetic studies will say that we have a couple of days, to a week's worth, of 25(OH)D3 ready to be converted to calcitriol.
----
Active D3
The active form of D3 is then calcitriol / 1,25(OH)2D3 -- Calcitriol - Wikipedia
This happens in the kidneys, and note again that the conversion from 25(OH)D to active calcitriol requires another CYP450 family enzyme, 25-Hydroxyvitamin D3 1-alpha-hydroxylase / cytochrome p450 27B1. The same caveats about apply (just substitute kidney over liver).
This conversion is a dynamic process, and as we already know, is tied heavily to calcium metabolism, and thus is expected to vary acutely.
====
At the end of all of that, we can see that endogenous vs exogenous cholecalciferol largely differs in their sulfation characteristics, which has definite implications for storage of cholecalciferol.
As far as I know, it is unknown whether or not the un-sulfated supplementatl cholecalciferol can escape regulation. For example, it may be possible that sulfated, water-soluble, skin-produced cholecalciferol, is capable of signalling to the rest of the system that, "hey, we have enough cholecalciferol", and prevent accumulation of excess.
In any case, it is clear that cholecalciferol synthesis in the skin is regulated, but exogenous supplies are not. In that sense, it is probably wise to supplement only if one is sure that 25(OH)D3 tests continue to come back at deficient levels, where there is no access to sunshine, and that one is relatively weight stable through the period of supplementation.
SIDENOTE: I personally do not like the idea of tanning beds. EMF emission is unknown, and intensity of lights has to be well-known (need to pester the business offering the service to give you all the details).
Taking care not to overload the liver is something that everyone should already do. Vitamin D3 production is just yet another system that is heavily dependent on this organ.
....
----
Active Form
As basic background information, the active form of Vitamin D3 is called calcitriol. This is the compound that will be responsible for vitamin D3's effects, and therefore any disruptions along the pathway to synthesise this compound, or some problem with response to this compound, will prevent the expected effects from Vitamin D3.
----
Storage and Conversion of Cholecaliferol
In any case, once we have cholecalciferol, much of it is stored, and some of it sent to the liver to be converted to calcifediol / 25(OH)D3.
Another risk here with supplementing in people with lots of body fat, is that supposed high dose supplementation doesn't change 25(OH)D3 levels, and prompts the person to supplement even more, even to the point of overdose. It is storage of cholecalciferol that is causing the lack of impact on 25(OH)D3 levels.
....