Intra-subject variability in Serum 25-D
Thursday, October 29, 2009 at 8:53PM Dr. Daniel Riemer has very kindly supplied me with the full text of the paper by Rejnmark et al I referenced in the last post.
Thank you Dr. Riemer!
The study is of women who were studied to see the effects of hormone replacement therapy (estrogen) on a variety of paramers, including temporal changes in levels of Vitamin D binding protein and on levels of 25 (OH) D3, which I will continue to abbreviate as 25-D.
It turns out there were no significant effects of estrogen replacement on D status. Of interest to us, they measured 25-D at 0, 1, 2 and 5 years. The assay used at time zero was different from the one used subsequently, so analysis of 25-D variability was only assessed between times 1 and 2 and 2 and 5. The methods section relates that they drew these levels at the same time of the year for each subject to attempt to minimize the effect of seasonal variation. That's good. They also say that about 40% of the subjects were taking D supplements. No comment about how static the levels of supplementation were.
So the shortest interval was a one year interval from time 1yr to time 2 yr. The intra-individual variability here averaged 13% with a range of 6% to 26%.
The three-year interval from time 2 yr to time 5yr had average variabilty of 16% with range of 7% to 29%.
The maximum interval of 4 years from time 1yr to time 5yr was 19% with a range of 12% to 27%.
What can we conclude and what is the relevance to those of us testing ourselves while supplementing?
I think we can say that up to 20% variation in two values obtained a year apart in someone who is presumed to be at equilibrium in their dosing regime could be basically "physiologic drift" - a real change in 25-D levels but not unexpected and not pathologic. Yet another reason to etiher test frequently (like twice a year) or to bias your level to the high side in case you drift lower a year later.
For those with variations over shorter periods of time, like one month, it seems reasonable to expect smaller amounts of variability due to this "physiologic drift" and if large differences are seen and you think you have been at equilibrium for a while (not changed your dosing regime for many months) one should probably look at lab error as the most likely cause, as miscalibration seems to be give the largest "delta" among the causes for variation at presumed equilibrium we have seen.
Who really knows, though? It is still possible that there could be high physiologic variability over short periods like one month. It simply has not been studied enough to say for sure to the best of my knowledge.
Reader Comments (3)
Nice post!
I would like you to comment on a couple of Vitamin D studies I found.
Your post about the effects of vitamin D on the immune system was fascinating. However, I found this study, which reports that "There was no benefit of vitamin D3 supplementation in decreasing the incidence or severity of symptomatic URIs during winter." Could it be that there is no significant benefit to the immune system increasing your levels beyond 63.0+/-25.8 nmol/l? But since some people had 63.0-25.8 nmol/L, shouldn't the study have found at least a small benefit of vitamin D on URI cases? Is this the only direct study looking at the effects of vitamin D on upper respiratory infection symptoms?
This study found that a multivitamin supplement with 400 IU increased 25(OH)D levels from 77 to 100 nmol/L. Could it be that the numbers are simply false, given that you have discussed about the accuracy of vitamin D testing? Or is it perhaps possible that a multivitamin supplement really is more efficient at increasing vitamin D levels?
Mike
63 nm/l is less than 25 ng/dl which is about 15 ng/dl short of what it takes to optimize immune function IMO. So yes, lack of an effect at these levels is plausible
Not sure if I am understanding your second question. Again, 100 nm/l is 40 ng/dl. Supplementation with only 400iu/day seems a small amount to get up to 40 ng/dl, but it might take an additional 4000 to get from there to 60 ng/dl as the effect is non-linear. As you suggest, though there may be a calibration issue as well as 400 is not much, or their other sources of D may have been high. Sorry I do not have time to read both papers right away. I hope that answers your questions
I am enrolled in a 5 year study on the effects of maintaining serum levels of vitamin D between 100 and 150 nmol/L. The study is sponsored by a consortium of scientists and concerned parties operating under the umbrella of the GrassRoots Health/Vitamin D Action organization (www.grassroots.net). The participants are supposed to attain and maintain serum levels of between 100 and 150 nmol/L (40 to 60 ng/ml). Blood spot 25-OH-D tests are performed every 6 months for every participant. So far out of approximately 1000 participants less than half are within the specified range (i.e. they are below 100 nmol/L)
I live above the 49th parallel. The sun's rays are only strong enough for 4 to 5 months to synthesize vitamin D on the skin. In order to maintain serum levels within the specified range I need to average about 8,000 IU of D3 supplement per day on a year round basis. My last 25-OH-D test result was 126 nmol/L. Another person in the study who is even farther north than I am barely gets above 100 nmol/L with regular use of a sun bed but only 400 IU per day of D3. So it is probably possible to attain serum levels of 63 nmol/L with a combination of sun and 400 IUs of D3 per day. But 63 nmol/L is too low.
According to vitamin scientists storage of vitamin D does not begin until a threshold of 80 nmol/L is reached. Reliable, consistent storage does not begin until a threshold of 100 nmol/L is reached. Without storage any vitamin D available is immediately used. Considering that the skin can produce 10,000 IUs of vitamin D with 20-30 minutes of sun exposure when the rays are strong enough 10,000 IUs appears to be close to the normal intake from both sun and diet/supplements.