Levels Of Vitamin-D Metabolites After Supplementation And After UV Radiation

[Giraffe]

I found two studies that checked levels of vitamin-D metabolites after supplementation or after UV radiation. Both studies confirm that 1,25(OH)2D is tightly regulated. As it is substrate depending during vitamin-D deficiency, an increase is seen in those subjects that were vitamin D-deficient before supplementation or radiation.

The Effect of Vitamin D Supplementation on Vitamin D Status and Parathyroid Function in Elderly Subjects

In this Dutch study, people living in nursing homes and aged people's homes were either supplemented for one year with 400 or 800 IU vitamin D3 daily or served as controls. The supplemented group reached levels in the vicinity of what by the majority of researchers is considered as needed to suppress PTH levels.

The next figure shows the individual serum 1,25-(OH)2D responses after 3 months of treatment with vitamin D3 (400 or 800 IU daily). Please note that this study was published in 1988; what they call "adequate" is just enough to prevent rickets and osteomalacia. **

Vitamin-D Synthesis and Metabolism after Ultraviolet Irradiation of Normal and Vitamin-D-Deficient Subjects

Eight healthy, white, paid volunteers received whole-body exposure equal to one to four times the minimal erythemal dose of UVR, and three vitamin-D-deficient white women received one minimal erythemal dose.

Interesting here is that 25(OH)D raises only moderately and slowly in the vitamin-D replete subjects although the vitamin D3 levels spike after UV radiation, especially in those who received a sunburn dose.

open triangles, dashed line = 3 vitamin-D deficient patients exposed to 1 MED (minimum erythemal dose)
solid squares, solid line = 3 healthy subjects exposed to 3 MED
solid circle, solid line = 1 healthy control exposed to 1 MED

_____

** Epidemic influenza and vitamin D (2006)

The critical question of ‘What is an ideal 25(OH)D level?’ must be answered, ‘In regard to what?’ Levels needed to prevent rickets and osteomalacia (10 ng/ml) are lower than those that dramatically suppress parathormone levels (20 ng/ml) [105]. In turn, those levels are lower than those needed to increase intestinal calcium absorption maximally (34 ng/ml) [106]. In turn, neuromuscular performance in 4100 elderly patients steadily improved as 25(OH)D levels increased and maximum performance was associated with levels of 50 ng/ml [107]. If levels of 50 ng/ml are associated with further benefits, such as preventing viral respiratory infections, we are only now learning about it. Until more is known, it may be prudent to maintain wintertime 25(OH)D at concentrations achieved in nature by summertime sun exposure (50 ng/ml).

_____

A paper written by several renowned researchers:

Estimates of optimal vitamin D status (2005)

Abstract
Vitamin D has captured attention as an important determinant of bone health, but there is no common definition of optimal vitamin D status. Herein, we address the question: What is the optimal circulating level of 25-hydroxyvitamin D [25(OH)D] for the skeleton? The opinions of the authors on the minimum level of serum 25(OH)D that is optimal for fracture prevention varied between 50 and 80 nmol/l. However, for five of the six authors, the minimum desirable 25(OH)D concentration clusters between 70 and 80 nmol/l. The authors recognize that the average older man and woman will need intakes of at least 20 to 25 mcg (800 to 1,000 IU) per day of vitamin D(3 )to reach a serum 25(OH)D level of 75 nmol/l. Based on the available evidence, we believe that if older men and women maintain serum levels of 25(OH)D that are higher than the consensus median threshold of 75 nmol/l, they will be at lower risk of fracture.

 

[paymanz]

Very interesting data,thanks.:)

 

[Amazoniac]

Why is that vit D from supplements only lasts a day or so, yet from the sun it can last months?

 

[Giraffe]

Why is that vit D from supplements only lasts a day or so, yet from the sun it can last months?

What makes you think that vitamin D from supplements only lasts a day?

I was trying to find the answer for myself if I could save enough vitamin D during Summer to get me through the Winter. *)

When searching for information, I found this study. I remember that there was another study discussing storage of vitamin D, but I can't find it right now.

*) Answer is: Probably not.

 

[Amazoniac]

What makes you think that vitamin D from supplements only lasts a day?

I was trying to find the answer for myself if I could save enough vitamin D during Summer to get me through the Winter. *)

When searching for information, I found this study. I remember that there was another study discussing storage of vitamin D, but I can't find it right now.

*) Answer is: Probably not.

I think it was @haidut that commented. However it might be simply due to a lower dose per day for being risky to supplement much more than what's currently regarded as safe.
On the other hand, I still don't understand how can you get much more through the sun and not run into the same problems, at least not as fast or to the same degree. What am I missing?

 

[Giraffe]

Effects of Above Average Summer Sun Exposure on Serum 25-Hydroxyvitamin D and Calcium Absorption | The Journal of Clinical Endocrinology & Metabolism | Oxford Academic

In this study 25(OH)D levels in outdoor workers were measured at the end of summer and again at the end of winter. One takeaway is that the extent of sun exposure (= how much of the body) matters more than total hours. A few of the participants did not even reach sufficient levels at the end of summer.

Moreover, even rather intensive sun exposure did not regularly protect against a winter deficit (and, in some participants, not even a summer one), defined as serum 25(OH)D levels below 75 nmol/liter. Based on the average rate of decline observed in our subjects, it can be estimated that in individuals for whom summer sun exposure is the principal source of vitamin D, a late summer 25(OH)D level of approximately 127 nmol/liter is needed to avoid levels falling to less than 75 nmol/liter by late winter. Without another substantial source of vitamin D, it is unlikely that occasional sun exposure by persons who spend most of their daylight hours indoors can support vitamin D repletion, a conclusion congruent with that reached by Glerup et al. (22).

Figure 1 displays individual changes in serum 25(OH)D.

 

[Giraffe]

I do not want to derail the thread were this study was posted originally.

"[Our] data imply that high doses of supplemental vitamin D3 are sufficient to markedly induce the expression of 24-hydroxylase, leading to the negative control of 1,25[OH]2D activity."

One group was supplemented with 5,000 IU and the other one with 10,000 IU, each for 12 weeks. Just looking at the graphs...

In both groups 1,25[OH]2D first increased, but at week 18 it had returned to baseline, while serum 24,25[OH]D was still higher than at baseline. The peak value of 1,25[OH]2D was about the same in both groups. How do they explain that it was later in the group with the higher dose?

This makes no sense. I bet that the individual values were completely random as in the Dutch study I posted above.

- Efficacy of High-Dose Vitamin D Supplements for Elite Athletes

With the equivalent of 5000 or 10000 IU a day for 12 months, their vit D levels ended up at about 150 and the others something close to 200 nmol/L.

But the interesting part..

"[Our] data imply that high doses of supplemental vitamin D3 are sufficient to markedly induce the expression of 24-hydroxylase, leading to the negative control of 1,25[OH]2D activity."

"Serum responses of the major vitamin D metabolites with treatment of either 35,000 or 70,000 IU/wk vitamin D3 25-hydroxyvitamin D (25[OH]D) (A), 1>,25-dihydroxyvitamin D3 (1>,25[OH]2D3) (B), 24,25-hydroxyvitamin D (C), and intact PTH (D). Samples were collected before supplementation (basal) and then at weeks 6, 12, and 18 of supplementation. At week 12, supplementation was stopped in both groups. *Significance for both groups compared with basal. #Significance for the 70,000 IU/wk compared with basal."
"The fact that the concentration of serum 24,25[OH]2D3 did not show a decline along with 1,25[OH]2D after the withdrawal of supplementation has practical implications. The finding suggests that the activity of 24-hydroxylase is sustained after large increases in 1,25[OH]2D and may persist and decrease both the concentration and the subsequent biological activity of 1,25[OH]2D."

"Evidence is now emerging that the 24,25[OH]2D metabolite may act at the VDR as a ‘‘blocking molecule’’ binding to the VDR decreasing 1,25 [OH]2D activity (5). Because 24,25[OH]2D is present in the circulation in nanomole per liter concentration compared with picomole per liter for 1,25[OH]2D, the significantly higher prevailing 24,25[OH]2D concentrations are liable to contribute to a significant decrease in the activity of the biologically active 1,25[OH]2D. Thus, a dual regulation would appear to be present in subjects receiving high-dose vitamin D supplementation preventing possible toxic effects, namely, 1) the positive stimulation of 24-hydroxylase and 2) the negative control of the VDR activity."

"These findings may explain reported observations of deterioration in skeletal muscle function, increased risk of falls, and increased fracture risk in individuals supplemented with extreme dose vitamin D3 to correct for severe vitamin D deficiency."

"Furthermore, in a retrospective observational cohort study, very low (<10 nmol/L) and high (>140 nmol/L) concentrations of 25[OH]D showed an increased risk of all-cause mortality, indicating not only a lower limit but also an upper limit for serum 25[OH]D (7). This hypothesis also lends an explanation for the inconsistency in positive outcomes related to supplemental vitamin D reported by large-scale meta-analyses (4). It is reasonable to suggest that mega dose vitamin D supplements are detrimental to vitamin D target tissues by increasing the production of 24,25[OH]2D, which may act to block the activity of the VDR."

 

[Amazoniac]

I do not want to derail the thread were this study was posted originally.

"[Our] data imply that high doses of supplemental vitamin D3 are sufficient to markedly induce the expression of 24-hydroxylase, leading to the negative control of 1,25[OH]2D activity."

One group was supplemented with 5,000 IU and the other one with 10,000 IU, each for 12 weeks. Just looking at the graphs...

In both groups 1,25[OH]2D first increased, but at week 18 it had returned to baseline, while serum 24,25[OH]D was still higher than at baseline. The peak value of 1,25[OH]2D was about the same in both groups. How do they explain that it was later in the group with the higher dose?

This makes no sense. I bet that the individual values were completely random as in the Dutch study I posted above.

If you were to taste a toxin, smaller doses would make you think that you can handle it, so detoxification would be put on hold, with larger doses it must be triggered earlier and the greater contamination confounds with the degree of decontamination. It was dosed once a week, the surprising aspect is how they survived, maybe it's because they're athletes.

 

[Giraffe]

If you were to taste a toxin, smaller doses would make you think that you can handle it, so detoxification would be put on hold, with larger doses it must be triggered earlier and the greater contamination confounds with the degree of decontamination. It was dosed once a week, the surprising aspect is how they survived, maybe it's because they're athletes.

In so-called Stoss therapy much higher doses have been given to patients, even to children, and it's considered to be safe. I personally prefer smaller daily doses though.

I feel that the study you posted is weird:

1,25(OH)2D does not only have a role in calcium and bone homeostasis. It also regulates responses of the immune and cardiovascular system. If it is elevated something is out of whack.

According to many studies 1,25(OH)2D is not affected by circulating 25(OH)D. In some studies based on small samples or specific patient groups there was an inverse relationship. In the study you linked they do not even mention that their results are contrary to the results of all the other studies. This is unscientific!

They seem to assume that the role of 24,25(OH)2D is solely to deactivate or counteract 1,25(OH)2D. This is disputable.

Normally 1,25(OH)2D and 24,25(OH)2D are maintained in relative proportion. Only if vitamin D status is insufficient 1,25(OH)2D is favored over 24,25(OH)2D by the body. -- Figure 3C (ratio 1,25(OH)2D : 24,25(OH)2D) and figure 2D (PTH) suggest that the lower dose of vitamin D may have been insufficient. They do not discuss it.

.....

The dynamic relationships between the active and catabolic vitamin D metabolites, their ratios, and associations with PTH​

Despite a direct enzymatic conversion of 25(OH)D to 1,25(OH)2D, we showed no correlation in serum concentrations between these two vitamin D metabolites (Fig. 1b). This finding is consistent with published studies; 1,25(OH)2D is able to directly inhibit the expression of 1α-hydroxylase, and indirectly inhibit by suppressing PTH and stimulating FGF23 production11,12. This negative feedback system provides an essential safeguard mechanism against hypercalcaemia, hence 1,25(OH)2D concentration is unaffected by the circulatory concentration of 25(OH)D.

[...]when vitamin D status is sufficient, serum concentrations of 1,25(OH)2D and 24,25(OH)2D are maintained in relative proportion and showed no significant change beyond the sufficient threshold. In contrast, when vitamin D status is insufficient, a progressive and highly significant increase in 1,25(OH)2D:24,25(OH)2D VMR is evidence that the production of serum 1,25(OH)2D is favoured over 24,25(OH)2D as the availability of vitamin D precursors in circulation diminishes.

Editorial: 24, 25-Dihydroxyvitamin D—Active Metabolite or Inactive Catabolite?​

Evidence gathered in vivo also supports a physiological role for 24,25(OH)2D during embryogenesis and in processes regulating bone growth, development, and repair.

 

[Amazoniac]

In so-called Stoss therapy much higher doses have been given to patients, even to children, and it's considered to be safe. I personally prefer smaller daily doses though.

I feel that the study you posted is weird:

1,25(OH)2D does not only have a role in calcium and bone homeostasis. It also regulates responses of the immune and cardiovascular system. If it is elevated something is out of whack.

According to many studies 1,25(OH)2D is not affected by circulating 25(OH)D. In some studies based on small samples or specific patient groups there was an inverse relationship. In the study you linked they do not even mention that their results are contrary to the results of all the other studies. This is unscientific!

They seem to assume that the role of 24,25(OH)2D is solely to deactivate or counteract 1,25(OH)2D. This is disputable.

Normally 1,25(OH)2D and 24,25(OH)2D are maintained in relative proportion. Only if vitamin D status is insufficient 1,25(OH)2D is favored over 24,25(OH)2D by the body. -- Figure 3C (ratio 1,25(OH)2D : 24,25(OH)2D) and figure 2D (PTH) suggest that the lower dose of vitamin D may have been insufficient. They do not discuss it.

.....

The dynamic relationships between the active and catabolic vitamin D metabolites, their ratios, and associations with PTH​

Editorial: 24, 25-Dihydroxyvitamin D—Active Metabolite or Inactive Catabolite?​

It can be consistent with the idea of a dose that's sufficiently high to boost protective measures earlier and delay the rise of killcitriol. The weird thing in their argument would be why the 24,25 metabolite wasn't elevated when circulating killcitriol peaked in the victims that were less intoxicated (week 6 in Fig. 2C). If such metabolite was regulating or inhibiting something adverse from excess killcitriol, that should've happened according to them.

---

- Dose-response effects of supplementation with calcifediol on serum 25-hydroxyvitamin D status and its metabolites: A randomized controlled trial in older adults

Spoiler

 

[Amazoniac]

Another strange thing is the basal killcitriol values being relatively high. It is short-lived, I tried to find if they dosed killciol close to testing to explain the differences between it and the one above, but couldn't. I'm aware of Mike's publication, the fact that these two had most readings above that of baseline (compare before and after) might have been a coincidence.

 

[Giraffe]

Another strange thing is the basal killcitriol values being relatively high. It is short-lived, I tried to find if they dosed killciol close to testing to explain the differences between it and the one above, but couldn't. I'm aware of Mike's publication, the fact that these two had most readings above that of baseline (compare before and after) might have been a coincidence.

Calcitriol [1,25(OH)2D] is short lived and difficult to interpret. If it is unusally high or low you know that something is not right, but it is normaly not a marker of vitamin D status. The studies with stoss therapy I have seen did measure blood calcium, but never calcitriol. -- What I am trying to say is ... I too wondered if megadoses of vitamin D as the ones given in stoss therapy could cause a transient increase in calcitriol, but I could not find a study where calcitriol was measured and reported.