266 replies to this topic

[AstralStorm]

Chemical properties such as solubility in polar acyclic solvents. (such as fatty acids)
Also whether said chemical attaches to lipids (proteins transporting fats) and if there is a specific transporter through the gut wall or it can diffuse through.
These depend on both structure and electrochemistry.

Whether the substance is a powder, crystal or solution might have some effect on absorption, but is usually less important.
It becomes important for substances only marginally absorbable.
For example, vitamin D is fat soluble, but you can make a powder containing it and medium chain triglycerides. Those are also a powder, yet dissolve the vitamin.

Edited by AstralStorm, 02 July 2014 - 10:46 AM.

[eon]

so a powdered vitamin D becomes water soluble but not the liquid form?

[AstralStorm]

No, it is still fat soluble. Just the fats are a powder or taken separately.

[eon]

So I must do a google search to determine if the supplement is fat or water soluble then? I can't take a lucky guess if it is or isn't? Usually the bottles will say to take with or without food which tells you it is water soluble. If it says take with a meal, it had to be fat soluble.

[Darryl]

Water and fat solubility are not absolute binary categories.

 

A common way of measuring their propensity to disolve in water or lipids is their partition coefficient (which will vary depending on the solvents, temperature, and salinity/pH etc of the water).

 

Some examples (octanol / water partition coefficients at 25 C and pH 7, reported in log Kow), with the more hydrophobic (fat soluble) compounds at the top. Note the log Kow, its not a linear scale.

 

alpha-tocopherol (E): 12

cholecalcipherol (D): 10.2

retinol (A): 5.68

biotin: 0.39

ethanol: -0.30

riboflavin (B2): -1.46

pantothenate (B5): -1.69

ascorbate ©: -2.15

nicotinic acid (B3): -2.34

folic acid: -2.81

choline bitartrate: -4.99

 

Among essential nutrients, only A, D, E, the longer K2 forms of K, and of course the essential fatty acids alpha-linolenic acid and linoleic acid, are highly fat soluble. Biotin is a borderline case. Everything else, including the dissociated ionic forms of minerals, will partition mostly to the water phase.

 

A good source for partition coefficients, when known, is the Hazardous Substances Data Bank (HSDB), which also includes non-hazardous substances like those above.

 

 

 

Edited by Darryl, 03 July 2014 - 05:49 PM.

[eon]

that's interesting. where does DHA or fish oils fall under? Does it dissolve in itself since it is "fatty"? Is it water or fat soluble then? I would think it is fat soluble but it's already fatty so why take a fatty substance with it? I have taken it with fatty substance such as oysters. I would eat oysters then take the DHA pill (algae based) and feel the sharpness in my head. As if it's working or maybe I simply upped the ante since I think oysters would also have DHA?

[timar]

I would eat oysters then take the DHA pill (algae based) and feel the sharpness in my head.

 

Great. Do more of that and you might have to ask fewer questions.
 

[AstralStorm]

that's interesting. where does DHA or fish oils fall under? Does it dissolve in itself since it is "fatty"? Is it water or fat soluble then? I would think it is fat soluble but it's already fatty so why take a fatty substance with it? I have taken it with fatty substance such as oysters. I would eat oysters then take the DHA pill (algae based) and feel the sharpness in my head. As if it's working or maybe I simply upped the ante since I think oysters would also have DHA?

"Dissolving in itself" is silly. Those do dissolve in other fats, fatty acids and most other non-polar solvents. That said, they already come solvated and absorbable, so there's no need unless you're really trying to devise a dry form.

Adding extra fats might improve absorption.

 

The last part is pure placebo effect. Neither of the above should have such effects. If it happens again, you might actually have found a migraine trigger or have a mild allergy to one of the constituents.

[ironfistx]

 

No multivitamins exclude all the micronutrients I'm avoiding supplementing.

Well it all depends on the dose, doesn't it? I couldn't think of a single micronutrient I wouldn't take at all (after all, they are nutrients), but there are many I wouldn't take more than a RDAish dose of. The only exeption would be iron and copper, for which there is strong evidence of adverse effects even at normal dietary levels, so I try to generally limit my intake of them.
 

 

What is wrong with copper?  I have taken it for tendonitis and it seems to help.

[Darryl]

Mostly associations with cancer, all-cause mortality, and of most recent scientific interest, Alzheimer's.

 

Wu, T., Sempos, C. T., Freudenheim, J. L., Muti, P., & Smit, E. (2004). Serum iron, copper and zinc concentrations and risk of cancer mortality in US adults.Annals of epidemiology, 14(3), 195-201.

Leone, N., Courbon, D., Ducimetiere, P., & Zureik, M. (2006). Zinc, copper, and magnesium and risks for all-cause, cancer, and cardiovascular mortality.Epidemiology, 17(3), 308-314.

Morris, M. C., Evans, D. A., Tangney, C. C., Bienias, J. L., Schneider, J. A., Wilson, R. S., & Scherr, P. A. (2006). Dietary copper and high saturated and trans fat intakes associated with cognitive decline. Archives of Neurology, 63(8), 1085-1088.

Squitti, R., Bressi, F., Pasqualetti, P., Bonomini, C., Ghidoni, R., Binetti, G., ... & Rossini, P. M. (2009). Longitudinal prognostic value of serum “free” copper in patients with Alzheimer disease. Neurology, 72(1), 50-55.

Brewer, G. J. (2009). Risks of copper and iron toxicity during aging in humans.Chemical research in toxicology, 23(2), 319-326.

Kitazawa, M., Cheng, D., & LaFerla, F. M. (2009). Chronic copper exposure exacerbates both amyloid and tau pathology and selectively dysregulates cdk5 in a mouse model of AD. Journal of neurochemistry, 108(6), 1550-1560.

Brewer, G. J. (2012). Copper toxicity in Alzheimer's disease: Cognitive loss from ingestion of inorganic copper. Journal of Trace Elements in Medicine and Biology, 26(2), 89-92.

Squitti, R. (2012). Copper dysfunction in Alzheimer's disease: From meta-analysis of biochemical studies to new insight into genetics. Journal of Trace Elements in Medicine and Biology, 26(2), 93-96.

Loef, M., & Walach, H. (2012). Copper and iron in Alzheimer's disease: a systematic review and its dietary implications. British Journal of Nutrition,107(01), 7-19.

Yin, J. J., Fu, P. P., Lutterodt, H., Zhou, Y. T., Antholine, W. E., & Wamer, W. (2012). Dual role of selected antioxidants found in dietary supplements: crossover between anti-and pro-oxidant activities in the presence of copper.Journal of agricultural and food chemistry, 60(10), 2554-2561.

Singh, I., Sagare, A. P., Coma, M., Perlmutter, D., Gelein, R., Bell, R. D., ... & Deane, R. (2013). Low levels of copper disrupt brain amyloid-β homeostasis by altering its production and clearance. Proceedings of the National Academy of Sciences, 110(36), 14771-14776.

Squitti, R., Siotto, M., & Polimanti, R. (2014). Low-copper diet as a preventive strategy for Alzheimer’s disease. Neurobiology of Aging.

 

The situation is not unlike that of iron, where supplements can easily push us into too much of a good thing.

 

Some of the effects may be mediated by impairing zinc absorption, and conversely zinc supplementation appears to be an attractive approach to moderating copper uptake.

 

A shame because supplemental copper was promising for inducing collagen production.

Edited by Darryl, 05 July 2014 - 04:58 AM.

[AstralStorm]

About iron, wasn't that mostly related to the heme (blood/meat), but not ferric oxide (plants) form? Specifically GI cancers.

I know the latter can in principle be reduced, but this does not happen often.

 

Thanks about info on copper. Are the effects there also when zinc is supplemented in a higher amount?

I have a strong suspicion it's not the copper itself, it's the interaction with zinc absorption. Zinc is quite a potent immunomodulator.

 

There's a potent confounder in epidemiological analysis of both of these elements: meat intake.

Choice quote here from the systematic AD review above: "In contrast, Cu intake was not associated with

cognitive change when the diet was not high in saturated fats."

This seems to imply that copper is a bystander and probably not the cause. The randomized controlled trials were way too small and inconclusive for my liking.

 

I do not trust the ROS theories for these, since they have been evaluated only in a Petri dish. Lipid peroxidation theory has much more merit.

The mouse study is also quite interesting, but 0.13 mg/L is not a low level of copper at all. It's a pretty large amount for a rodent - that said, it is less than EPA recommendations.

Comparing this to supplement levels: RDA for people is around some 1-2 mg depending on the source. This copper sulfate level in water alone could provide an estimated 0.25-0.5 mg daily.

Edited by AstralStorm, 05 July 2014 - 09:18 AM.

[timar]

@eon: Please don't take my last comment as a personal insult. It was just this particular post of you - the question whether fish oil is lipid soluble combined with the comment about instant mental sharpness after taking DHA - that was a bit too much for me to take

 

I agree with Darryl regarding copper (adding this cross-sectional study on serum copper and inflammatory markers). Don't supplement it. As it is the case with iron, there may be significant differences in the bioavailability of dietary copper between animal and plant sources. Cocoa, nuts, seeds and legumes all contain relatively high levels of copper, yet higher intakes of those foods have been consistently associated with positive health outcomes, which is not true for organ meats rich in copper, regardless of its glorification as a super-food by the WAPF and some Paleo advocates.

 

There is indeed an intricate relationship between copper and zinc metabolism and some of the adverse effects of an excessive intake of each mineral are due to an induced deficienty state in the competing one (see this review on zinc toxicity). An ideal copper-zinc probably falls between 1:12 and 1:8, the lower end for men and the higher for women, but this is a somewhat speculative ratio derived from healthy dietary patterns and their relation to serum levels and not based on hard evidence from RCTs.

Edited by timar, 05 July 2014 - 10:19 AM.

[eon]

I read of someone saying niacin causes cataracts, not sure how if that is fact.

 

Anyway, does anyone here know if using 50mg of zinc picolinate have any adverse effects? I can't pinpoint if this has anything to do with my (right) eye feeling as if there is hair in it. There is no hair, there's a bit of a tiny bump on the white part of the eye though and some redness. I'm suspecting my use of zinc had something to do with this but I'm not sure. I am cutting back on it to see if the eye issue disappears. I took this zinc about 2 weeks ago daily and this is when the eye issue started I think week later after use. I use niacin like once or twice a week (100mg).

[AstralStorm]

That high zinc intake might interact with copper absorption and a small bit of it is required. Why would you take that much anyway?

Niacin should be fine, I've seen higher levels used in treating dyslipidemia (as in cholesterol).

But neither should cause such effects at these doses. Really huge doses of niacin could do it maybe - measured in grams.

 

What you're experiencing is likely some kind of eye or eyelash infection. Maybe a foreign body, take a peek in the mirror. See a doctor if the problem doesn't go away soon. (like, in a day or two)

A much more distant possibility could be neuropathy. There are many reasons for that. The ones which could perhaps be tied to supplements are high chronic B6 overdose (messing up the supplementation) or lack of B12 (possible) or B1 (very unlikely with a normal diet). However those tend to show up in extremities first, rather than eyes, and as numbness, rather than weird irritation/pain sensation.

Edited by AstralStorm, 02 August 2014 - 04:12 PM.

[eon]

well the capsule came as 50mg dosage. I stopped it for 2 days and seems like the eye irritation disappeared. Not sure if eating those baby carrots (high in vitamin A) helped or eating cucumbers helped but the problem disappeared. Adding some asthaxanthin as well may have done the job. Maybe I should take the zinc every other day and not daily.

[niner]

IMHO, 50 mg of zinc is too much as a daily dose.  Some people react badly to picolinate; I happen to be one of them, but have no problem with other forms of zinc.  I doubt that the carrots or cucumbers had anything to do with the eye irritation clearing up.  Time heals all.

[timar]

eon, you seem to stubbornly relate every little change you observe in your mind or body to supplements you have taken or foods you have eaten. This way you are bound to get lost in the maze of placebo effects and cognitive biases. The things you observe are often not the meaningful signal you take them to be but mostly background noise entirely unrelated to your observations. There are many things going on in your body irrespective of the supplements you take or specific foods you eat (e.g. some itch in the eye that would have eased anyway), or they are related to them on an entirely different timescale, usually too long to observe any direct cause-effect relation (e.g. long-term intake of DHA may well cause subtle improvements in brain function, but certainly not immediately after you pop a pill). You should practice some critical thinking and self-reflection, it would save you a lot of hassle (and probably money as well).

Edited by timar, 06 August 2014 - 09:25 AM.

[eon]

I agree. There's a note on the bottle that it's not for long term use. I was fine when I was using 15mg of it (another brand). The eye irritation is all gone now ever since I stopped taking the 50mg zinc picolinate. I might use this every other day or 2x a week only.

 

IMHO, 50 mg of zinc is too much as a daily dose.  Some people react badly to picolinate; I happen to be one of them, but have no problem with other forms of zinc.  I doubt that the carrots or cucumbers had anything to do with the eye irritation clearing up.  Time heals all.

 

[eon]

is it best to avoid magnesium during the day as it is a muscle relaxant? Maybe I'm using it wrong when I should be using it before bedtime? Is it best to use it before bedtime rather than first thing in the morning? I read that this mineral makes people tired as it is a relaxant.

Edited by eon, 03 September 2014 - 07:30 AM.

[eon]

is it possible and effective to take vitamins sublingually even though it isn't manufactured to be used sublingually? I'm talking about vitamin B12 for example. I have tried the sublingual version but am now using a lozenge version that is directed to be used as chewable and or dissolve in mouth. Could I use this or any vitamin of this type sublingually? Another thing is if I want a quick energy pre workout can I use glucose sublingually as well rather than swallowing with water? Well might as well name some vitamins that could be highly effective when used sublingually? I could think of B12. I notice a difference when taking it this way rather than chewing and swallowing it. 

 

Chime in everyone...

Edited by eon, 19 September 2014 - 09:14 AM.

[pamojja]

is it possible and effective to take vitamins sublingually even though it isn't manufactured to be used sublingually?..

 

Chime in everyone...

 

My anecdotal experience: from 2010 to '11 took for the first time about 20mg/d of Germanium orally, Hair-tissue-mineral anaysis showed its level still declined. The next year I added the same amount to Resveratrol with some drops of high percentage alcohol for buccal delivery. After which HTMA levels of Germanium shoot up from 0.4 to 0.19 ug/g (0.06 - 0.11 normal range). Back to my low 0.4 since discontinuation the year after.
 

 

is it best to avoid magnesium during the day as it is a muscle relaxant?

 

Do you feel disturbed by any muscle relaxant effects? - In my case I still even need this effect from 1.8 g of elemental Magnesium per day due to a severe mg deficiency for avoiding cramps. Because of the laxative effect I couldn't take that all at once before bedtime.

[eon]

I've been taking magnesium before bedtime from now on. Before it was first thing in the morning which I feel makes me too relaxed to get going through the day. So for me it's best to take at the end of the day not at the start.

 

 

is it possible and effective to take vitamins sublingually even though it isn't manufactured to be used sublingually?..

 

Chime in everyone...

 

My anecdotal experience: from 2010 to '11 took for the first time about 20mg/d of Germanium orally, Hair-tissue-mineral anaysis showed its level still declined. The next year I added the same amount to Resveratrol with some drops of high percentage alcohol for buccal delivery. After which HTMA levels of Germanium shoot up from 0.4 to 0.19 ug/g (0.06 - 0.11 normal range). Back to my low 0.4 since discontinuation the year after.
 

 

is it best to avoid magnesium during the day as it is a muscle relaxant?

 

Do you feel disturbed by any muscle relaxant effects? - In my case I still even need this effect from 1.8 g of elemental Magnesium per day due to a severe mg deficiency for avoiding cramps. Because of the laxative effect I couldn't take that all at once before bedtime.

 

 

[eon]

“Iron is important for several processes of brain development and function,” Schmidt noted. “In the brain, iron contributes to neurotransmitter production, myelination, and immune function; [impairment] of all three of these pathways has been associated with autism.” Still, she said, there is much work to be done before scientists get to the root causes of autism."

 

https://www.yahoo.co...8163648242.html

 

Yet why people say to avoid supplementing with iron (and vitamin A)? I would think there are better versions of iron by now?

 

Also to those saying 5000 IU of vitamin D is too much, Thorne Research sells a 25,000 IU vitamin D for short term use. What you people think of it? I believe it's suggested use is once a week dose but is it still too much to take in 25,000 IU in that one dose? 

[timar]

Yet why people say to avoid supplementing with iron (and vitamin A)? I would think there are better versions of iron by now?

 

It really wouldn't have taken you much own research and reasoning to answer that question yourself. It is because a) more is not always better but sometimes worse and b) because men and non-menstruating women eating a mixed diet are already getting plenty - if not too much - of preformed vitamin A and iron. I suspect that you already know the answer but that you are (I'm judging from your posts here so far) somewhat addicted to constantly buy and try new supplements and now have you read some positive things about the physiological importance of iron and would like to find a justification to try an iron supplement. Be warned that unless you are a menstruating vegetarian it will most likely do more harm than good to you. That is by the way true for almost any supplement taken indiscriminately.

 

Also to those saying 5000 IU of vitamin D is too much, Thorne Research sells a 25,000 IU vitamin D for short term use. What you people think of it? I believe it's suggested use is once a week dose but is it still too much to take in 25,000 IU in that one dose?

 

Please understand, as a general rule: just because something is offered on the market and advertised in some way it doesn't mean that it is a good idea for most people or even anybody to take it. Heck, thousands of people are happily poisoning themselves with chlorine dioxide just because some batshit crazy Texan quack is promoting it as a cure-all unicorn piss!

 

That said, a high-dose vitamin D supplement is suitable for people having been diagnosed with a vitamin D deficiency in order to quickly get them out of the deficient range. As vitamin D is fat-soluble and has a long physiological half-life it can also be taken on a weakly or even monthly basis instead of a lower dose daily supplement. I take a 20.000 IU pill once a week during wintertime myself (in addition to the 2000 IU I get from my daily supplements) but I do so after having monitored my blood levels of vitamin D for several years and figured out that this is the amount I need to be around 40 ng/ml by the end of winter (the optimum range is thought to be 40-60 ng/ml). Don't supplement more than an avarage of 4000 IU per day without monitoring your serum vitamin D and calcium levels.

Edited by timar, 23 September 2014 - 10:58 AM.

[krillin]

Intermittent vitamin D use is controversial so I would stick to daily. I think the theory is that the temporarily-high blood level before it gets stored away is enough to cause harm.

[timar]

Not really. This is a fringe opinion (Sanders is well known as a fierce "vitamin D skeptic") not supported by dozens of clinical trials and long-standing clinical practise having shown bolus high-dose oral vitamin D to be perfectly safe. The only side effect mentioned in the leaflet of the prescription D3 Dekristol 20,000, which is available in Germany since the 1960s and has been taken by hundreds of thousands of patients since then is hypercalcaemia if overdosed (note that as a prescription medicine it is subject to strict surveillance). Just like it is done with vitamin K today, millions of newborn infants have been given a "welcome shot" of 5 mg D3 (200,000 IU) in Germany between the 1950 and 1970s. This practise was only ended because it was finally deemed an unecessary high dose - not because any adverse effects would have been reported! A recent review found no adverse events from bolus doses up to 500,000 in adults.

 

Moreover, cholecalciferol (D3) and ergocalciferol (D2) are both biologicaly inactive form of vitamin D. The become somewhat biologically active only after conversion to 25(OH)D in the liver, which is quickly saturated. Hence there is no transient increase in 25(OH)D (let alone the most active form 1,25(OH)₂D, the conversion of which in the kidney and peripheral tissues is tightly regulated) after bolus doses of D3 or D2.

 

While 200,000 IU of D3 may not be physiological, 20,000 IU certainly are because it is the amount synthesized in the skin after 0.5 MED of whole-body sun-exposure in lean and fair skinned people. There is no metabolic difference between oral D3 and that synthesized in the skin.

 

The U-shaped curve found in some but not all observational studies is most probably due to confounding factors: improved synthesis in the skin due to high levels of cholesterol which after all is the substrate to vitamin D synthesis (ApoE4 carriers tend to have higher levels of 25(OH)D), polymorphisms in certain cytochrome P450 enzymes or other enzymes involved in vitamin D metabolism, leading to higher retention of vitamin D but also some toxic compounds, last but not least people suffering from frailty and other conditions having been prescribed or recommended D3 supplementation by a practitioner, which is particularly common in Scandinavian countries (being fond of their cod liver oil) where U-shaped curves have been reported.

Edited by timar, 24 September 2014 - 10:31 AM.

[krillin]

That review finding no problems must have been pretty selective. Sanders' paper listed several examples, including this one, this one, and this one. In the third one, 25-OH D tripled in three days from 22 ng/ml to 67 ng/ml and bone turnover markers spiked. 67 ng/ml is enough to reduce bone density in older adults and some races of younger adults. It would furthermore be worse than a steady value of 67 ng/ml, because the 1-alpha-hydroxylase is expecting 22 ng/ml so excessive 1,25-OH D will be produced until the enzyme can be downregulated.

 

This is speculation on my part, but if vitamin D is like 25-OH D and can displace 1,25-OH D from the vitamin D binding protein, then high amounts could have some "activity" mediated through an increase in free 1,25-OH D.

 

 

[timar]

That review finding no problems must have been pretty selective. Sanders' paper listed several examples, including this one, this one, and this one. In the third one, 25-OH D tripled in three days from 22 ng/ml to 67 ng/ml and bone turnover markers spiked. 67 ng/ml is enough to reduce bone density in older adults and some races of younger adults. It would furthermore be worse than a steady value of 67 ng/ml, because the 1-alpha-hydroxylase is expecting 22 ng/ml so excessive 1,25-OH D will be produced until the enzyme can be downregulated.

 

Now wait a moment! I wrote that the review by Kearns et al. found "no adverse events from bolus doses up to 500,000 in adults". That was sloppy. I should have written: from oral bolus doses below 500,000 IU vitamin D3, as that is what the review found. The first reference you provided found a slightly increased risk of fracture (RR 1.26) in elderly woman receiving a bolus dose of 5000,000 IU D3. The second study found an increased risk of fracture from an intramuscular injection of 300,000 IU vitamin D2. Besides the fact that it was injected, ergocalciferol is a non-physiological form of vitamin D which has only recently been shown to increase muscle damage in athletes even at a daily dose below the UL. The third study observed a dose-dependend effect of D3 on a marker of bone turnover (sCTX). The effect was sustained with a bolus dose of 600,000 IU, transient (lasting only 3 days) with 300,000 IU and entirely insignificant with 100,000 IU.

 

The observational association between 25(OH)D and bone mineral density is subject to confounding factors (such as those I mentioned above) and hence not very suggestive regarding a causative role of high levels of vitamin D in reduced bone mineral density, which is not supported but rather contradicted by mechanistic animal studies and well-conducted RCTs (which didn't use non-physiological bolus doses or forms of vitamin D). A level of 67 ng/ml (168 nmol/l) would be to the extreme right of the graph, far above the reference range where you can easily see that there are hardly any data points remaining. No confidence intervals are shown, but I would be surprise if this association even bore any significance.

 

This is speculation on my part, but if vitamin D is like 25-OH D and can displace 1,25-OH D from the vitamin D binding protein, then high amounts could have some "activity" mediated through an increase in free 1,25-OH D.

 

That is speculation indeed, with next to no evidence to support it. Usually, 1,25(OH)₂D decreases after supplementation of D3 within the physiological dose range. The adverse effects from the above mentioned studies on cholecalciferol are all related to bone health and can be explained, as you already mentioned, by a disregulation of PTH and/or 1-alpha-hydroxylase caused by such high, non-physiological bolus doses. The study by Rossini et al. is very suggestive in this regard and also shows that this effect is unlikely to occur at doses well below 300,000 IU. Given those results and that, as stated above, physiological sun exposure can easily produce 20,000-30,000 IU of cholecalciferol which is quickly released into the blood stream and hydroxilated in the liver exactly the same way as orally absorbed D3, plus the vast amount of positive clinical experience with doses up to 100,000 IU, a single oral dose within this range can reasonably be considered as safe.

 

To make absolutely sure to be on the safe side, though, one should limit a single dose to 50,000 IU (twice the endogenous production but half the NOAEL from the above study and a commonly administered dose) of vitamin D3 and avoid vitamin D2.

 

Edited by timar, 25 September 2014 - 01:50 PM.

[krillin]

The observational association between 25(OH)D and bone mineral density is subject to confounding factors (such as those I mentioned above) and hence not very suggestive regarding a causative role of high levels of vitamin D in reduced bone mineral density, which is not supported but rather contradicted by mechanistic animal studies and well-conducted RCTs (which didn't use non-physiological bolus doses or forms of vitamin D). A level of 67 ng/ml (168 nmol/l) would be to the extreme right of the graph, far above the reference range where you can easily see that there are hardly any data points remaining. No confidence intervals are shown, but I would be surprise if this association even bore any significance.

 

This is speculation on my part, but if vitamin D is like 25-OH D and can displace 1,25-OH D from the vitamin D binding protein, then high amounts could have some "activity" mediated through an increase in free 1,25-OH D.

 

That is speculation indeed, with next to no evidence to support it. Usually, 1,25(OH)₂D decreases after supplementation of D3 within the physiological dose range. The adverse effects from the above mentioned studies on cholecalciferol are all related to bone health and can be explained, as you already mentioned, by a disregulation of PTH and/or 1-alpha-hydroxylase caused by such high, non-physiological bolus doses. The study by Rossini et al. is very suggestive in this regard and also shows that this effect is unlikely to occur at doses well below 300,000 IU. Given those results and that, as stated above, physiological sun exposure can easily produce 20,000-30,000 IU of cholecalciferol which is quickly released into the blood stream and hydroxilated in the liver exactly the same way as orally absorbed D3, plus the vast amount of positive clinical experience with doses up to 100,000 IU, a single oral dose within this range can reasonably be considered as safe.

 

To make absolutely sure to be on the safe side, though, one should limit a single dose to 50,000 IU (twice the endogenous production but half the NOAEL from the above study and a commonly administered dose) of vitamin D3 and avoid vitamin D2.

 

 

Excessive vitamin D reducing bone density is easy to imagine. It increases bone resorption, and it's possible that it depletes vitamin K. On that bone mineral density graph, the ~35 ng/ml which is suggested in other papers as optimal for all-cause mortality will also keep most people from going over the top of the U-curve, so it seems believable to me. I'm not sure I get your point about 67 ng/ml being beyond most of the data points. Are you suggesting that it's possible the curve turns upwards again? Even if it does, the highest justifiable level is 55 ng/ml, and that's only worth it if you're at high risk of beast cancer or MS.

 

Single oral doses of 300,000 IU or 200,000 IU can send you above 50 ng/ml. In this 70,000 IU study, they show individual data points and one person shot up to ~65 ng/ml in just 2 days and then it fell, demonstrating that you can get a transient increase in 25D from a big bolus of D.

 

Could you provide a reference for 0.5 MED = 20,000 IU? According to Holick (Figure 11), 1 MED is between 10,000 and 25,000 IU. Depending on what kind of relationship you use for interpolation, I estimate between 13,000 and 16,000 IU, so 20,000 cannot be considered physiological. (Another estimate comes in at sun = 8,000-10,000 IU.)

 

Vitamin D and 1,25D have the same affinity for the vitamin D binding protein, so I'm retracting the displacement speculation. (Click on "look inside". Fortunately, the infomation is in the free preview.)

[eon]

what's a good combo to take with potassium citrate? it is said to be a diuretic but I take it for arrythmias. Works. I think I've seen it sold in combo with taurine and magnesium. Is it a bad combo to take it with ascorbic acid (vit C) or not?