Monday, December 13, 2010

What is a reasonable vitamin D level?

The figure and table below are from Vieth (1999); one of the most widely cited articles on vitamin D. The figure shows the gradual increase in blood concentrations of 25-Hydroxyvitamin, or 25(OH)D, following the start of daily vitamin D3 supplementation of 10,000 IU/day. The table shows the average levels for people living and/or working in sun-rich environments; vitamin D3 is produced by the skin based on sun exposure.


25(OH)D is also referred to as calcidiol. It is a pre-hormone that is produced by the liver based on vitamin D3. To convert from nmol/L to ng/mL, divide by 2.496. The figure suggests that levels start to plateau at around 1 month after the beginning of supplementation, reaching a point of saturation after 2-3 months. Without supplementation or sunlight exposure, levels should go down at a comparable rate. The maximum average level shown on the table is 163 nmol/L (65 ng/mL), and refers to a sample of lifeguards.

From the figure we can infer that people on average will plateau at approximately 130 nmol/L, after months of 10,000 IU/d supplementation. That is 52 ng/mL. Assuming a normal distribution with a standard deviation of about 20 percent of the range of average levels, we can expect about 68 percent of those taking that level of supplementation to be in the 42 to 63 ng/mL range.

This might be the range most of us should expect to be in at an intake of 10,000 IU/d. This is the equivalent to the body’s own natural production through sun exposure.

Approximately 32 percent of the population can be expected to be outside this range. A person who is two standard deviations (SDs) above the mean (i.e., average) would be at around 73 ng/mL. Three SDs above the mean would be 83 ng/mL. Two SDs below the mean would be 31 ng/mL.

There are other factors that may affect levels. For example, being overweight tends to reduce them. Excess cortisol production, from stress, may also reduce them.

Supplementing beyond 10,000 IU/d to reach levels much higher than those in the range of 42 to 63 ng/mL may not be optimal. Interestingly, one cannot overdose through sun exposure, and the idea that people do not produce vitamin D3 after 40 years of age is a myth.

One would be taking in about 14,000 IU/d of vitamin D3 by combining sun exposure with a supplemental dose of 4,000 IU/d. Clear signs of toxicity may not occur until one reaches 50,000 IU/d. Still, one may develop other complications, such as kidney stones, at levels significantly above 10,000 IU/d.

See this post by Chris Masterjohn, which makes a different argument, but with somewhat similar conclusions. Chris points out that there is a point of saturation above which the liver is unable to properly hydroxylate vitamin D3 to produce 25(OH)D.

How likely it is that a person will develop complications like kidney stones at levels above 10,000 IU/d, and what the danger threshold level could be, are hard to guess. Kidney stone incidence is a sensitive measure of possible problems; but it is, by itself, an unreliable measure. The reason is that it is caused by factors that are correlated with high levels of vitamin D, where those levels may not be the problem.

There is some evidence that kidney stones are associated with living in sunny regions. This is not, in my view, due to high levels of vitamin D3 production from sunlight. Kidney stones are also associated with chronic dehydration, and populations living in sunny regions may be at a higher than average risk of chronic dehydration. This is particularly true for sunny regions that are also very hot and/or dry.

Reference

Vieth, R. (1999). Vitamin D supplementation, 25-hydroxyvitamin D concentrations, and safety. American Journal of Clinical Nutrition, 69(5), 842-856.

72 comments:

soiltosustenance said...

Ned,

Thanks for this great article (as well as your comments at Free The Animal http://freetheanimal.com/2010/12/the-institute-of-medicine-vitamin-d-fail.html). I think that between your article and the article from Chris, we have an idea of what the sweet spot may be.

Do you have any thoughts regarding skin pigmentation changes in response to sun exposure as a way for the body to regulate vitamin D intake?

Jenny said...

At 55.8 ng/ml I developed a high blood calcium level that came down only after I stopped supplementing with Vitamin D. I been taking 2000 IU a day for a year. Before that I was taking 1000 IU for several years and did fine.

There are reports of an increase in Milk Alkali Syndrome which can cause a medical crisis with very high blood pressure caused by over-supplementation of Vitamin D. It was after reading about this that I connected my rise in blood calcium with the Vitamin D supplementation.

People need to be clear that the results of studies are reported in nanomole units but their labs report nanogram units. The nanomole units are much larger, and I suspect this makes people think their levels are low when they are not.

In any case, there is still no decent data pointing to reversal of the conditions associated with low Vitamin D through supplementation. Making major changes to components of a system you don't understand is a great way to damage it.

We don't understand Vitamin D's interaction with the body well at all.

qualia said...

what is your data for saying "and the idea that people do not produce vitamin D3 after 40 years of age is a myth."?

i certainly know that it's true for me and a relative. also, no one said "do not produce" - most sources say significantly decrease (like 50% at 40y), which is true in my experience.

Anonymous said...

The very high levels of vitamin D that are often recommended by doctors and testing laboratories — and can be achieved only by taking supplements — are unnecessary and could be harmful, an expert committee says. It also concludes that calcium supplements are not needed.

https://www.nytimes.com/2010/11/30/health/30vitamin.html


Biochemist Proposes Worldwide Policy Change to Step Up Daily Vitamin D Intake

http://www.sciencedaily.com/releases/2010/08/100809133325.htm

http://www.npr.org/2010/11/30/131699479/new-guidelines-for-taking-vitamin-d


Low and High Vitamin D Levels in Older Women Associated With Increased Likelihood of Frailty

http://www.sciencedaily.com/releases/2010/12/101208083047.htm


Are Some People Pushing Their Vitamin D Levels Too High?
http://www.westonaprice.org/blogs/are-some-people-pushing-their-vitamin-d-levels-too-high.html

Ned Kock said...

Below is a comment by Chris Kresser that Blogger doesn't seem to accept, and was stuck in the spam folder.

***

Ned,

Great post on an important topic. I test all of my patients' 25D levels. I've seen several with levels >100 ng/dL. Interestingly, these folks are not taking huge amounts of D3 (usually around 10,000 IU/d).

Since they're more than 3 SD above the mean you mentioned in the article, I wonder if there may be something else going on in these cases.

In any event, I think levels that high are too high. Melamed et al found that mortality increases at both high and low levels of 25D. Michaelsson found that in elderly men the mortality rates were increased at both high and low vitamin D levels, and the lowest mortality was seen with vitamin D between 24 and 34 ng/mL.

http://www.ncbi.nlm.nih.gov/pubmed/18695076?dopt=abstract

http://www.ncbi.nlm.nih.gov/pubmed/20720256?dopt=abstract

Anonymous said...

The Nutrition Source
Comment on the IOM Vitamin D and Calcium Recommendations

http://www.hsph.harvard.edu/nutritionsource/what-should-you-eat/vitamin-d-fracture-prevention/index.html


Federal Government-Funded Study Fails to Recognize Value of Vitamin D

http://www.lef.org/featured-articles/Federal-Government-Funded-Study-Fails-to-Recognize-Value-of-Vitamin-D_01.htm

Ned Kock said...

Hi soiltosustenance, thanks. Sunlight has a range of frequencies; called the spectrum of electromagnetic radiation from the sun. There is a theory that the suntan is to protect us from the most harmful ones. Some people believe that UVA is more harmful than UVB. Still, even UVB is harmful in excess, and the suntan may protect us from it as well, without blocking vitamin D production. In fact, getting a tan is a sign that you are producing vitamin D.

Ned Kock said...

Hi Jenny, thanks for sharing your experience. Yes, the confusion of the two units is widespread.

Ned Kock said...

Hi qualia. That comes from the Vieth (1999) article. Vitamin D production from sunlight goes down 20 percent in healthy seniors (65 and older). Still, that is about 8,000 IU/d, enough to keep the vitamin D battery fully charged.

Ned Kock said...

Hi Chris, thanks. Here is something interesting. Since production of vitamin D from sunlight goes down 20 percent in seniors, that would shift the normal distribution to the left. The new range would be roughly 33 to 50 ng/mL. Not very far from the numbers in the Michaëlsson et al. study, where the range with the lowest mortality seems to be 19 and 40 ng/mL. They studied older men. The mean age was 71, so for that age, the bell curve could have shifted even further to the left. Well, maybe the reduction in vitamin D production with age happens for a reason.

Ned Kock said...

I suspect that vitamin D levels go down for people with high circulating insulin, which is often a pre-diabetic condition. Vitamin D is stored in body fat, and abnormally high insulin levels may prevent their release. This may be why so many people think that once one turns 40 no more vitamin D is produced from sunlight. Once one turns 40 there is a greater chance that one will developed the metabolic syndrome, which often leads to abnormally high serum insulin levels.

TedHutchinson said...

Excellent summary.
May I encourage readers to also consider the early history of Vitamin D discovery by reading The Dental Essentials post
Prevention of Cavities with a Single “Massive” Dose of Vitamin D
and then download chapter 2 of the 1934 book Nutritionand disease Edward Mellanby
Bear in mind the Vitamin D research was done his wife May Mellanby who discovered the benefits of Vitamin A (cod liver oil)and they recommended a quart of milk daily This menu would supply more Vitamin D cofactors than currently found in SAD.

Kindke said...

Ted really interesting links thanks.

Can we conclude then that intermittent large doses of fat soluble vitamins are as effective as regular smaller doses ( of matched total dosage ) ?

It would be nice to only have to take vitamin D once per week rather than religiously taking it everyday.

I would also like to add that in my own experience my very bad dandruff cleared up once I started supplementing D3.

Ned Kock said...

Hi Ted, thanks for the links. The main problem that I see with that massive dose study is that it has no middle ground. The conditions were a no vitamin D condition, and two massive supplementation treatment conditions. Having one or two middle ground treatment conditions with modest supplementation would have been very useful.

Ned Kock said...

Having said that, there is indeed anecdotal evidence that a single high dose of vitamin D can keep the flu away, even after the first symptoms appear. This has been discussed on Freetheanimal.com, with various people talking about their positive experiences.

David Isaak said...

"In any case, there is still no decent data pointing to reversal of the conditions associated with low Vitamin D through supplementation."

Not entirely correct. For example, there are some double-blind, placebo-controlled studies that have shown Vitamin D supplementation to improve seasonal affective disorder. But those are short-term studies that are not designed to interevene is any life-threatening condition--i.e. studies that are cheap to do and don't require the participation of a major hospital.

It is true that most of the studies pointing to beenfits of Vitamin D are correlations rather than supplementation interventions. This is true of most nutritional research--and is likely to remain so. Vitamin D can't be patented.

The association of low Vitamin D status with any number of chronic diseases seems pretty clear at this point. It is certainly possible that such diseases cause low Vitamin D status rather than the other way round...but I'd consider that hypothesis more likely if low Vitamin D weren't associated with such a wide range of different conditions.

David Isaak said...

And, as to the recednt IOM results-well, I take them about as seriously as I take The Food Pyramid.

David Isaak said...

I can't get at more than the abstract on this one, but there is also a double-blind, supplement-vs-placebo study showing that Vitamin D supplementation educes insulin resistance:

http://www.ncbi.nlm.nih.gov/pubmed/19781131

People definitely respond differently to supplemental D3 intake. Supplementing with 5,000 IU daily put me at 85 ng/ml.
I've since lowered my intake, and my latest test (Dec 6) has me down at 53.

Chris Masterjohn said...

Hi Ned,

Heaney did some research, cited in my Seafood to Sunshine article, indicating that 60 ng/mL corresponds to something closer to 4,000 IU being supplemented in the coldest 6 mo of the year and no supplementation during the other 6 mo of the year for free-living people in Nebraska over two years.

Vieth's study was conducted in Canada, which is more north, but it was also shorter and it probably would have taken more northern people with lower baseline levels longer to equilibrate. I think that 60 ng/mL is probably closer to 4-5K IU over the long-haul than to 10K IU.

Also, there is no evidence whatsoever that 60 ng/mL is ideal. I used this as a *hypothetical* best guess in my Seafood to Sunshine article and that was several years ago. There is so much hoopla about vitamin D right now that frankly I expect them to poor money and resources into dose-finding randomized controlled trials with clinical endpoints instead of this endless and nearly useless barrage of epidemiological studies. These are useful for hypothesis generation and we already have the hypothesis.

Lifeguards have elevated risk of kidney stones, as even Dr. Cannell has cited; therefore, it is entirely reasonable that, at least assuming a certain context (maybe low A and K2 status is involved), 60 ng/mL might have toxic effects.

I will be reponding to the 999-page IOM report soon, but I have to read it first and 999 pages is a lot. :)

Chris

Chris Masterjohn said...

I should add that the 4,000 IU dose did not seem to completely plateau, so over the long-haul I would say 60 ng/mL is likely to reflect somewhere between 3,000 and 5,000 IU/d from all sources including food, supplement, and sunshine. It is confounded by inability to quantify sunlight input.

Chris

Ned Kock said...

Hi David, thank you. Interesting the study by von Hurst et al. They say that: “Optimal vitamin D concentrations for reducing IR were shown to be 80-119 nmol/l”. That is 32-48 ng/ml. However, it doesn’t seem like they tried higher doses than 4000 IU/d, so I don’t know how they came up with the upper end of the range (i.e., the 119 nmol/l).

Ned Kock said...

Hi Chris, thanks. The lifeguards in Israel were the ones with kidney stones, not the ones in St. Louis. Yet, the latter had significantly higher levels of 25D. (So high that I suspect that they were also supplementing orally or eating foods rich in vitamin D, in addition to getting a lot of sun.) I think it is possible, if not likely, that the kidney stones in the Israeli lifeguards were due to chronic dehydration.

Chris Masterjohn said...

Hi Ned,

I agree with you that chronic dehydration could have been a cause, but kidney stones are a more sensitive indicator of vitamin D toxicity than hypercalcemia and can occur in response to vitamin D in the absence of the latter, so it is entirely plausible that vitamin D could also be responsible. When it comes down to it, there is just no way to differentiate whether 60 ng/mL is helpful or harmful from available data.

I suspect that if one gets enough vitamin A and K and whatever other cofactors may be important that I might be overlooking, levels this high might be harmless and perhaps very beneficial, but at the moment that's not anything more than a suspicion. It would be pretty awesome to see some experimental work in this area.

Perhaps the encouragement that the IOM just gave to testing doses above 4,000 IU will help stimulate that type of research.

Chris

Chris Kresser said...

It's really time to get the word out about the harm that vitamin D can do at higher levels. I had two patients this week with levels above 100 ng/mL. They were supplementing at 10,000 IU for several months, which according to the data, should not raise their levels that high. But I've seen this in 3-4 patients now, so it seems unlikely to be extremely rare.

Everyone has got the memo that D is important, but unfortunately few understand that it can also be harmful in excessive amounts. I guess it's that American attitude: if a little bit of something is good, a lot must be better!

Ned Kock said...

Hi Chris (Kresser). Those high levels may well be due to them supplementing and still getting enough sun to produce a good amount of vitamin D. Even sun exposure of neck and arms only can lead to a significant amount of endogenous vitamin D production.

Chris Masterjohn said...

Chris --

Why do you consider these values not predicted by the available data?

Heaney et al tested 10,000 IU here:

http://www.ncbi.nlm.nih.gov/pubmed/12499343

It was provided for the coldest six months of the year for two successive years. It yielded mean 25(OH)D of 89.6 ng/mL. By definition, some fell above this number and some below, despite *only* receiving supplementation for half the year.

So it would just be baffling if you *didn't* encounter people supplementing with 10,000 IU who didn't get levels over 100 ng/mL.

Chris

Chris Kresser said...

I hadn't seen that paper, but was under the impression from other papers that even at 10,000 IU levels wouldn't rise that high in most people. Clearly I was mistaken.

In any event, I'm glad there's more discussion about the potential harm of levels above 60 ng/mL now.

Chris Masterjohn said...

Thanks Chris. I greatly apologize if my tone has sounded frustrated in any of these posts. I hope not. I'm glad, Chris K., that there is some discussion of this. I'm really happy that Tim Ferriss is brining the A/D/K interactions into public view and I think this might impact some in the research community, at least some of whom are starting to get interested in this area. I'm very happy to have guys like you and Ned who are very responsive to evidence within the paleo/traditional foods/wap/alternative health movement, and I'm happy Ned can offer his stats skills! I hope we can all straighten this out together!

Chris

Chris Kresser said...

No offense taken at all, Chris. I'm grateful for the collaboration and help in figuring this stuff out. As a practitioner it's great to have the support of folks like you, Ned, Jenny, Stephan and others who are looking closely and critically at the research.

Chris Masterjohn said...

Also Ned, do you really think 10,000 IU has plateaued in the graph you show? It looks to me like a best-fit line should be drawn straight through points 3,4, 5, and 6. It doesn't look like it's even close to plateauing.

Chris

Ned Kock said...

Hi Chris (M.). That is clearly a nonlinear, capacitor-charging-type relationship. Something like a: K*(1 – exp(-t/C)). It is hard to tell, but I think that if you were to draw a best-fitting curve defined by this type of function through the points, it would converge to somewhere around 130 nmol/l; maybe a bit higher, but not by much. The average of those averages for sun-rich environments is 137.75; but I think it is biased upwards by those lifeguards in St. Louis.

Chris Masterjohn said...

Ned,

When I look at these lines, rather simply without nearly the understanding of linear analysis that you have, I see that the slope between points 3 and 4 looks almost exactly the same as the slope between points 5 and 6, while the slope between points 4 and 5 is much steeper. This instinctively makes me want to draw a straight line through the whole thing to average the slope out, and in any case gives me no confidence that if we carried the line out to point 7, we would not see another big jump with a steep slope.

I find it implausible that 10,000 IU would plateau here at 130 nmol/L in any case when in 2-year study I posted in response to Chris K, 10,000 IU plateaued at ~225 nmol/L.

In any case why use Vieth's 2-month study when we have a much longer 2-year study composed of 2 six-month supplementation periods? I think, if we use Vieth's study at all, we should interpret the ambiguity of the line in the light of what Heaney et al found in their much longer study.

Chris

Anne said...
This comment has been removed by the author.
Anne said...

1500 IU D3 per day over the past two years has kept me in the range 50 to 80 ng/ml (125 to 200 nmol/L) depending on the time of year. I'm in my late 50's and live in the UK where we don't get that much sun. I get my levels of 25(OH)D tested every few months because I once went up to 154 ng/ml (384 nmol/L) on 4,000 IU D3 per day for only four months and in the winter ! Getting 25(OH)D tested is the most important thing in this because everyone is obviously very different.

Ned Kock said...

Hi Chris (M.).

I took a look at the Heaney et al. study; very interesting.

The function that they derive from the data is exactly a capacitor-charging one.

But, indeed, levels go up higher over time with a possible plateau at 225 nmol/l (89 ng/ml). They make it sound as if the skin production and other supplementation were insignificant, but I am not so sure. It is hard to reconcile this plateau with those averages for people living/working in sun-rich environments.

Anyway, here is the full version PDF, if anyone else is interested:

http://www.direct-ms.org/pdf/VitDGenScience/Heaney%20Vit%20D%20kinetics%2025D.pdf

Ned Kock said...

Hi Anne, thanks for sharing your experience. People are different, and some are more different than others. I was recently analyzing some medical data for a WarpPLS user and there were data points that were 7 standard deviations from the mean!

Chris Masterjohn said...

Ned,

They did it during the coldest six months of the year in Nebraska. I doubt the contribution of the sun was zero, but it couldn't have been very substantial compared to 10,000 IU from diet. Regardless, no one is supplementing in a sun-deprived bubble, so it's not an enormous interpretive confounder.

In any case, why do you find this hard to reconcile with data from people living in sun-rich conditions? I think the reconiliation is straightforward: these people are getting the equivalent of 3-5,000 IU/d from sun and not >10,000 IU.

Chris

Anonymous said...

Hi Ned
Thanks for this interesting article. My experience may serve as a datum point for older persons (I'm 71yo). As a trial I supplemented with 10,000IU of D3 for 4 weeks and in addition I took in about 15-20min of sun to 60% of body. The trial period was Jun-Nov and part of the motivation was to estimate the degree of infection (gums mainly). The result of D3(OH) test was a surprise; 183nmol/L or 73 in US units. The lab indicated that at 130nmol/L, 1 SD=19 and results are accurate to 2 SD's. So the test result is very approximate. However I do think it is plausible as I tanned very easily w/o burning. I have reduced D3 to 3000IU.
Morris

Ned Kock said...

Chris (M.), the reason I find those two pieces of data hard to reconcile is because I tend to assume that people living/working in sun-rich environments (e.g., farmers in Puerto Rico) would make 10,000 IU/d frequently enough to have levels equivalent to those taking oral supplementation of 10,000 IU/d. But I am keeping an open mind; skeptical, but open. I like the Heaney et al. study, and it is widely cited.

On a related note, I think skin production is frequently underestimated. Often people will spend a little time in the sun, with only legs and arms exposed, and their blood levels will go up significantly. This seems to also happen in the winter, as long as exposure is not too early or late in the day.

Btw, there are many fewer days with precipitation in Nebraska during the winter (about 7/mo, in Omaha) than during the rest of the year (about 13/mo, also in Omaha). Nebraska is high in terms of latitude, but not nearly as high as most of Canada.

Ned Kock said...

Hi Morris, thanks much for sharing your experience. Yours is a good example of the point made in the post that vitamin D production does not cease at age 40, as long as one doesn’t have any complication that itself suppresses vitamin D levels (such as hyperinsulinemia).

Ned Kock said...

By the way, perhaps I am wrong, but I wouldn’t expect a full-blown diabetic state to depress vitamin D levels; I would expect a pre-diabetic hyperinsulinemic state to do so. This is the state that often precedes the onset of diabetes type 2.

Chris Masterjohn said...

Ned,

Thanks. I think you are definitely keeping an open mind, and I appreciate that tremendously.

I think the data clearly indicate that you are overestimating sun production. If it were, on average, 10,000 IU, then people in sun-rich environments would have levels similar to those supplemented with 10,000 IU in the Heaney study. They do not.

I think the Vieth study clearly did not allow enough time for equilibration. Sure, Canada does have less sun, but this makes a much bigger difference in absence of supplementation and probably becomes close to negligible in the presence of sun. Thus, baseline 25OHD might be lower and equilibration might take longer. This is especially true because the 25OHD response to vitamin D input is not linear and becomes steadily decreased at higher inputs. Also, while Nebraska may provide some sun, the lifeguards in Israel no doubt had some dietary D.

The idea that 10,000 IU would be average input seems to be based on data showing that 10,000 IU is the *maximal* input. Sun input steadily declines the more one is exposed to sun, in large part due to the melanin response but probably for other reasons as well.

Chris

Ned Kock said...

Chris you are clearly in the wrong profession. Your future lies, I assure you, in civil litigation. There is still time to make the career shift :)

Chris Masterjohn said...

Ned,

I'm sorry, did I offend you? I didn't mean to. I greatly apologize if I carried an overly argumentative tone. :(

Chris

David Isaak said...

Chris M: "There is so much hoopla about vitamin D right now that frankly I expect them to poor money and resources into dose-finding randomized controlled trials with clinical endpoints instead of this endless and nearly useless barrage of epidemiological studies."

I sincerely hope you're right.

But low-carb, higher-fat diets also caused a lot of hoopla without much in the way of resources being directed toward intelligent and impartial studies of them.

My background is physics and chemistry. I haven't lost faith in American science per se. But I have lost faith in anything connected with medical research. I expect a flurry of poorly designed studies deliberately biased to show that there is no benefit to supplementation...but that significant benefits can be had from some patented chemicals...

BigWhiskey said...

this theory about Vitamin D has an interesting narrative, so, I thought I would call your attention to it.
http://healthjournalclub.blogspot.com/2010/12/sulfur-and-your-health.html

David Isaak said...

"By the way, perhaps I am wrong, but I wouldn’t expect a full-blown diabetic state to depress vitamin D levels; I would expect a pre-diabetic hyperinsulinemic state to do so. This is the state that often precedes the onset of diabetes type 2."

An interesting conjecture. It ought to be looked into.

Chris Masterjohn said...

David,

Volek is doing good low-carb studies at UConn.

For vitamin D, there's lots of research going on, and the new IOM report will stimulate dose-finding RCTs as well as funding for them.

I agree about underfinding and underresourcing of nutritional research in general.

Chris

Ned Kock said...

Hey Chris. Of course you didn’t offend me. You always present your points of view in a very polite and convincing way. I was just joking. I like challenging arguments.

By the way, I studied law for a while (for about year, eons ago) and almost decided to pursue that career at some point; maybe I would have been a good litigator myself.

And I am a big fan of the old "Law & Order" series, with Sam Waterston playing the role of ADA Jack McCoy. You remind me of him a bit :)

Ned Kock said...

Hi David. One of the reasons why I like to look at old medical/nutrition studies is that they often address much more fundamental questions than newer ones.

Ned Kock said...

Thanks for the link BigWhiskey.

David Isaak said...

Chris--

I've read Volek's stuff, and it's good. But the low-carb vs low-fat debate has been at high volume since the 1970s, and we are only now beginning to get a handful of studies done on the topic.

I don't think that nutrition research studies are particularly underfunded overall. But I think the money is allocated largely to attempts to find proof for the pre-existing belief systems of a coterie of researchers who have dominated the field since the days of Ancel Keys--pretty much the opposite of the way science is supposed to be done.

David Isaak said...

As long as we're on the topic, does anyone think that sunlamps might be better than supplements?

TedHutchinson said...

@ does anyone think that sunlamps might be better than supplements?
Depends I'm not keen on UVA and many commercial Tanning studios have high UVA outputs. The Vitamin D council offer Mercola's and Sperti so they may be worth considering. At least at home you can keep track of usage, most UVB tubes decline in UVB output over 500~800hrs.
Do bear in mind Vitamin D is made from cholesterol near surface of skin. Low cholesterol means potential for making Vit d is limited, partly why vitamin D production from sun/uvb declines with age.
Also remember the damage to skin by UVA may be increased by iron see also Iron Behaving badly
So before UVA exposure it's worth improving your natural sunscreen photoprection potential by increasing anti-oxidant status with natural iron chelators such as Curcumin, Quercetin, resveratrol, melatonin, green tea, lycopene but remember it takes time for these approaches to become effective so take the UV exposure very slowly and carefully.
I don't have to remind you to NEVER GET BURNT.
Don't give up on some oral D3.
I think it's possible vitamin d may have a direct impact on pathogenic, obesogenic gut flora.
Amid the Murk of 'Gut Flora,' Vitamin D Receptor Emerges as a Key Player

Chris Masterjohn said...

Vitamin D is not made from cholesterol; it is made from 7-dehydrocholesterol, a precursor to cholesterol. As far as I know, the 7-DHC is believed to be made locally in the skin, so I'm not sure what low blood cholesterol would tell you.

Chris

TedHutchinson said...

Vitamin D production after UVB exposure depends on baseline vitamin D and total cholesterol but not on skin pigmentation.

Chris Masterjohn said...

Thanks, Ted. I hadn't seen that paper. They cite a biochemistry textbook for their explanation that cholesterol is oxidized in the gut to 7-DCH, which is transported to the skin and converted to vitamin D. This does not make much sense in explaining a relationship to circulating total cholesterol rather than circulating 7-DCH. In any case, the letter by Glossman explains why this theory is completely implausible and to their knowledge not supported by any evidence, whereas they cite numerous pieces of evidence of why it is almost certainly not the case.

For lack of time, I did not read the whole paper, but I keyword searched the pdf for "cholesterol" and I could not find any place where they indicated they looked for a correlation between 25(OH)D and cholesterol or performed any statistical analysis to see if the relationship they found between baseline total cholesterol and 25(OH)D production was independent of baseline 25(OH)D. That makes me skeptical that the relationship is meaningful. However, if it is meaningful, it almost certainly reflects a third factor influencing HMG CoA reductase activity or LDL receptor activity in the liver and also influencing 7-DCH production in the skin, and not an actual causal effect of blood cholesterol levels on vitamin D production.

The correlation is pretty modest, r^2=~25%. Although I find the study interesting, I do not find it very convincing evidence that blood cholesterol levels have a causal effect on the potential for vitamin D production.

Chris

Ned Kock said...

I generally agree with Ted regarding lamps. Very good points.

Ned Kock said...

Assuming that 7-dehydrocholesterol and cholesterol levels are correlated, one would expect low cholesterol levels to also reflect low 7-dehydrocholesterol levels. But that’s a guess on my part.

Ned Kock said...

Ted, thanks for the link to the Bogh et al. article. Very interesting. Supports your point, and also confirmed some of my suspicions.

I’ve always felt that skin pigmentation was a protection that was not supposed to limit vitamin D production from the sun.

I thought it was funny that the authors used the term “non-sun worshippers”.

Ned Kock said...

Chris (M.), I was going to ask you for your take on the Bogh et al. article (linked by Ted), but I see you provided it above. We cannot blame the study for lack of addressing fundamental issues eh?

The full text PDF is here, for anyone interested:

http://www.nature.com/jid/journal/v130/n2/pdf/jid2009323a.pdf

The correlation between total cholesterol and 25D is reasonably strong and clearly statistically significant. It is 0.515, based on the R-squared of 0.265 that they provided.

The journal where the article was published (Journal of Investigative Dermatology) has a fairly solid citation impact – on average, a little over 120 citations per article. It doesn’t seem like the type of outlet that would publish implausible nonsense … but one never knows.

Chris Masterjohn said...

Hi Ned,

I agree the correlation is clearly statistically significant, but it is not clear to me whether the correlation is independent of other factors. In other words, if it largely dependend on baseline 25(OH)D then all it would mean would be that the less D you need, the less you make.

I agree the journal is not likely to publish nonsense, and I think that is why they published a letter extensively refuting the interpretation.

They also published another letter extensively refuting the lack of connection to skin pigmentation, showing that these authors used shorter-length UV than is found in daylight, and for physiological reasons their results differ from those of previous studies and from what occurs during exposure to true sunlight.

So, while this study may be well conducted and provide controversial findings, and thus be of interest to publish, the interpretation is challenged by the letters published alongside it and the strong evidence contained therein.

Chris

David Isaak said...

I'm not an albino, but I could easily play one on TV. I never tan. Burn, yes, quite easily, but the skin promptly peels off to reveal skin any Victorian girl would have killed for. (Well, if it weren't so hairy.)

But I digress. Ted, Chris, Ned--thanks for all the brainfood.

There's two reasons I asked about lamps. One is that there appears to be a feedback mechanism in sun exposure that seems to be absent from dietary supplements.

The second is that I read the post BigWhiskey listed:

http://healthjournalclub.blogspot.com/2010/12/sulfur-and-your-health.html

To tell the truth, I can't tell if the points made in that post really hold water. But it made me wonder if there is a real difference between endogenous and exogenous Vitamin D...

Anne said...

"The correlation between total cholesterol and 25D is reasonably strong and clearly statistically significant. It is 0.515, based on the R-squared of 0.265 that they provided."

I wasn't able to access the full study and it would be interesting to know the figures. As I wrote before my 25(OH)D is always between 125 and 200 nmol/L on only 1500 IU D3 per day and went up to 384 nmol/L on 4,000 IU per day. My total cholesterol is high !

Ned Kock said...

Hi David.

There are researchers who think that vitamin D production from sunlight comes with a few co-factors that are fairly important for health. The co-factors are also produced endogenously based on the same stimulus, namely sunlight.

Dr Holick is one of those researchers. Two blog posts reviewed his research (published in a book) below, by Dr. Eades:

http://www.proteinpower.com/drmike/supplements/sunshine-superman/

http://www.proteinpower.com/drmike/supplements/heliophobe-madness/

Ned Kock said...

Hi Anne. The participant with the highest 25D increase also had one of the highest TC levels in the group: approximately 5.5 mmol/. (As you can see, the TC levels were not that high in this group.) That person had an increase of 50 nmol/l in 25D.

Anne said...

Hi Ned - my TC levels are normally in the 7's (HDL is upper 2's and now 3, trigs 0.6) so I wonder if that's an explanation for the easy way I make 25(OH)D.

I should add that when my 25(OH)D went up to 384 nmol/L it did not cause any problems at all, everything else, calcium etc, stayed absolutely normal.

David Isaak said...

Here's a provocative article just published that suggests optimum breast-cancer prevention requires both sunlight and supplementation. Strictly observational, of course:

http://cebp.aacrjournals.org/content/early/2010/12/01/1055-9965.EPI-10-1039.abstract?sid=14f3ca06-f78f-4f8d-b169-5fbe7f2f62be

Can't get to more than the abstract. There are some quotes from the main text embedded in this pop-sci article:

http://www.nutraingredients-usa.com/Research/Supplements-and-sunlight-give-optimal-protection-from-breast-cancer-Study?utm_source=AddThisWeb&utm_medium=SocialAddThis&utm_campaign=SocialMedia

Neonomide said...

A Cochrane Review found that vitamin A supplements increased total mortality rate by 16%, perhaps through antagonism of vitamin D

http://www.ncbi.nlm.nih.gov/pubmed/18425980


Of course, supplements are not food.

My reasonable vitamin D level seems to be around 100 nmol/l and 50-100 µg day, at the moment. My Crohn's is simply almost symptomless at that dose.

McGill unversity researchers found that the vitamin D has a direct impact on two genes that have been linked to Crohn’s disease, beta-defensin and NOD2. Vitamin D directly impacts the beta defensin 2 gene, which then encodes a specific peptide, and the NOD2 gene that lets cells know that invading microbes are present. If NOD2 is deficient or defective, it cannot fight the invaders in the intestinal tract. If patients have an adequate amount of vitamin D, this breakdown may be prevented and inflammation may be reduced.

http://www.sciencedaily.com/releases/2010/01/100127104904.htm


Of course, Vitamin D has already prevented flare ups in a small controlled study (P = 0.06):

http://www.ncbi.nlm.nih.gov/pubmed/20491740

My guess is that 96 nmol/l is not enough and base levels were a LOT higher than Crohn's patients normally have. Also, as a clinical dose, 50 µg is a joke. Much larger doses have been used in Multiple Schlerosis patients and generally D3 rocked.

Sorry Jenny, I'm a believer. My BP also dropped like a stone, to around 115/65 first time in my life. I get periodical serum calcium tests too, and I had normal calcium even when taking 200 µg a day. As a semi-paleo, my calcium intake wasn't a lot I must say.

I happen to be finnish (62 degrees north, a bit south from Fort Yukon in Alaska by comparison), so my/our base values were around 20-25 nmol/l less than US ones, which should be taken into account.

As an anecdote, I tried to get a tan several 4-6 times a week during (a very hot) summer full frontal during mid-day, yet still my Crohn's reacted clearly better to D3 supplements in spring & autumn.

Neonomide said...

Oh and here is one interesting paper on vitamin D & vitamin K synergy:

http://www.thorne.com/altmedrev/.fulltext/15/3/199.pdf

Chris Masterjohn said...

By the way, Chris K and others, one of the contributors to interindividual variation in response of 25(OH)D to dietary D is going to be adiposity. People with more adipose tissue will require more D to lead to the same increase in 25(OH)D.

Chris

viagra online said...

Good information I like it so much.....


Smith ALan