25 replies to this topic

[DaffyDuck]

Would love to hear some comments about this study.

http://www.renalandurologynews.com/high-vitamin-d-levels-may-increase-prostate-cancer-risk/article/208624/

Dr. Albanes' group measured blood levels of 25-hydroxyvitamin D—a reliable biomarker of vitamin D status—in 1,000 PCa patients (cases) and 1,000 matched controls who were cancer free at the time of the case patients' cancer diagnosis. All subjects had participated in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study, which was conducted in Finland.
Compared with subjects in the first quintile of 25-hydroxyvitamin D blood levels, subjects in the fourth and fifth quintiles had a significant 26% and 56% increased risk of PCa, respectively, after adjusting for season of blood collection, the researchers reported in Cancer Epidemiology, Biomarkers & Prevention (published online ahead of print).

[niner]

This is a disturbing result. Not only was pCa higher in the upper quintiles, but aggressive disease is worse:

When the investigators considered aggressive and non-aggressive PCa separately, they found that higher vitamin D levels were not significantly associated with the risk of non-aggressive PCa but were significantly associated with aggressive disease. Subjects in the fourth and fifth quintiles had a significant 59% and 70% increased risk of aggressive PCa, respectively.

Here are some possible problems with the study:

Dr. Albanes' team noted that their study was limited by the inclusion of only Caucasian men who smoked. They also pointed out that their ability to find a protective effect of vitamin D may have been limited by the study population's relatively low vitamin D levels—owing at least in part to the high latitude of the study location—and a paucity of blood samples collected in the summer, when blood vitamin D levels would be higher than in other seasons.

These are non-trivial issues, though I have a hard time figuring out how you get a protective effect from a D deficiency. I hope that these paradoxical results are an artifact of smoking.

I would say that this deserves a harder look. As it happens, this article also mentions:

“The results of this study add to existing observations that higher levels of serum vitamin D increase an individual's risk of prostate cancer,” said Eric A. Klein, MD, Chairman of the Glickman Urological and Kidney Institute at Cleveland Clinic. “

There's more? I'd like to see them. I have a strong family history of pCa, so this could get me to move my target levels down significantly, if the effect holds up.

[leha]

I don't understand how everyone can make the leap that blood levels = utilization levels--of anything. Maybe the people with the aggressive pCa have some problem utilizing vitamin D, and therefore it is building up in their blood, un-utilized. Am I missing something?

The other problem I have with the findings of this study is the concluding paragraph:

“Together, these observations underscore the need for consumers and health care providers to use caution in using or recommending unregulated over-the-counter products unless clinical trials show they are beneficial,” Dr. Klein said.

This is a problem for me because there is a big push by pharmaceutical companies right now to get OTC supplements outlawed. We are in fact very close to this. All they need are a few more BS studies citing the supposed "dangers" of taking "unregulated" supplements. I would look very carefully at who funded the study in the first place before taking any stock in the findings. And then, once again, I question the whole premise that you can simply equate blood levels of a compound with its utilization by the body. The human body is incredibly complex, with many interdependent cofactors. Were this not the case, we would be able to create living, breathing Frankenstein's monsters by now--or at least administer perfect nutrition to every living human. We can't do any of that, because we don't know very much. We don't even know what the results of studies mean. </rant>

[leha]

Okay, not quite done. One more point to note is that the study does not even cite any of the subjects actually *taking* vitamin D supplements, and yet the doctor draws the conclusion that taking supplements is the risk factor. This makes no sense.

[kilgoretrout]

I am pretty sure there are numerous studies that correlate lower-than-optimal blood levels of vitamin D with higher levels of various health issues. Just use google and I bet you can find all kinds of pointers to the actual studies. Sorry but I am too lazy to look them up and post them here for you... practice makes perfect.

[Robert C]

I wonder how high the vit D levels were in the various quintiles? The fact that the study only included smokers (if I understand it correctly) is an obvious shortcoming to extrapolating this info to the general population. I also wonder what the purpose of this study was? It must have been something related to smoking???

Still, I also find this info disturbing. It does seem to me that high dose micronutrient supplementation is unproven and risky in many cases.

[9H}@}C\%kmFHOB#?X]

I will say this as clearly and succinctly as I can: To infer that what holds in the case of smokers will hold in the case of non-smokers is to commit a logical fallacy.

As with the beta-carotene/lung cancer study, all this shows is that in smokers (which should not necessarily be taken to imply all smokers), high vitamin D appears to be correlated with aggressive pCa. If you smoke, you should probably reconsider beta-carotene and vitamin D supplementation. But then again, you probably shouldn't smoke. If you don't smoke, then the evidence is overwhelming that supplementation with both beta-carotene and vitamin D at an individual-appropriate dosage is likely to be beneficial to you.

[nameless]

A couple of odd things I notice at first glance.

First, yeah, they were all smokers. But also this:
All subjects had participated in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study, which was conducted in Finland.

So, some questions I have: were the participants taking alpha tocopherol/beta carotene at the same time their D serum levels were measured? Would alpha-tocopherol or beta carotene skew the results at all? There doesn't seem to be any difference in D serum levels in those who took beta carotene, however:
http://www.ncbi.nlm....pubmed/10613346

But perhaps there was some other interaction going on?

We really need to see the quintile data and serum levels though. Assuming they weren't taking supplements, I wonder how the high quintile groups were getting their D... sun exposure or diet?

And on the Pauling site I see they mention this:

Although a prospective study of Finnish men found that low serum 25-hydroxyvitamin D levels were associated with earlier and more aggressive prostate cancer development (81), another prospective study of men from Finland, Norway and Sweden found a U-shaped relationship between serum 25-hydroxyvitamin D levels and prostate cancer risk. In that study serum 25-hydroxyvitamin D concentrations of 19 nmol/L or lower and 80 nmol/L or higher were associated with higher prostate cancer risk (82). Further research is needed to determine the nature of the relationship between vitamin D nutritional status and prostate cancer risk.

So it may be a U-based curve thing.

[9H}@}C\%kmFHOB#?X]

And on the Pauling site I see they mention this:

Although a prospective study of Finnish men found that low serum 25-hydroxyvitamin D levels were associated with earlier and more aggressive prostate cancer development (81), another prospective study of men from Finland, Norway and Sweden found a U-shaped relationship between serum 25-hydroxyvitamin D levels and prostate cancer risk. In that study serum 25-hydroxyvitamin D concentrations of 19 nmol/L or lower and 80 nmol/L or higher were associated with higher prostate cancer risk (82). Further research is needed to determine the nature of the relationship between vitamin D nutritional status and prostate cancer risk.

So it may be a U-based curve thing.

Uh-oh. This is much, much lower than the 50 ng/ml most of us aim for. 80 nmol/L = 32 ng/mL for vitamin D, I believe.

I don't know why I never looked this up before:

The Institute of Medicine committee concluded that a serum 25-hydroxyvitamin D level of 20 ng/mL is desirable for bone and overall health. The Dietary Reference Intakes for vitamin D are chosen with a margin of safety and 'overshoot' the targeted serum value to ensure that the specified levels of intake achieve the desired serum 25-hydroxyvitamin D levels in almost all persons. It is assumed there are no contributions to serum 25-hydroxyvitamin D level from sun exposure and the recommendations are fully applicable to people with dark skin or negligible exposure to sunlight.[34]
The Institute of Medicine found that serum 25-hydroxyvitamin D concentrations above 30 ng/mL are "not consistently associated with increased benefit". Serum 25-hydroxyvitamin D levels above 50 ng/mL may be cause for concern.[34]

Maybe I shouldn't have increased my D-3 dose when my 25(OH)D test came back at 21 ng/mL after all...

On the other hand, there does appear to be evidence that concentrations above 30 ng/mL are beneficial.

Edited by Watson, 30 July 2011 - 06:50 PM.

[Invariant]

And on the Pauling site I see they mention this:

Although a prospective study of Finnish men found that low serum 25-hydroxyvitamin D levels were associated with earlier and more aggressive prostate cancer development (81), another prospective study of men from Finland, Norway and Sweden found a U-shaped relationship between serum 25-hydroxyvitamin D levels and prostate cancer risk. In that study serum 25-hydroxyvitamin D concentrations of 19 nmol/L or lower and 80 nmol/L or higher were associated with higher prostate cancer risk (82). Further research is needed to determine the nature of the relationship between vitamin D nutritional status and prostate cancer risk.

So it may be a U-based curve thing.

Uh-oh. This is much, much lower than the 50 ng/ml most of us aim for. 80 nmol/L = 32 ng/mL for vitamin D, I believe.

I don't know why I never looked this up before:

The Institute of Medicine committee concluded that a serum 25-hydroxyvitamin D level of 20 ng/mL is desirable for bone and overall health. The Dietary Reference Intakes for vitamin D are chosen with a margin of safety and 'overshoot' the targeted serum value to ensure that the specified levels of intake achieve the desired serum 25-hydroxyvitamin D levels in almost all persons. It is assumed there are no contributions to serum 25-hydroxyvitamin D level from sun exposure and the recommendations are fully applicable to people with dark skin or negligible exposure to sunlight.[34]
The Institute of Medicine found that serum 25-hydroxyvitamin D concentrations above 30 ng/mL are "not consistently associated with increased benefit". Serum 25-hydroxyvitamin D levels above 50 ng/mL may be cause for concern.[34]

Maybe I shouldn't have increased my D-3 dose when my 25(OH)D test came back at 21 ng/mL after all...

On the other hand, there does appear to be evidence that concentrations above 30 ng/mL are beneficial.

The IOM report is very controversial: http://www.hsph.harv.../#iom-vitamin-d

Nevertheless, this is a very concerning study. It wouldn't be the first time everyone got all excited over a supplement that later turned out to be dangerous.. I would keep blood levels relatively low (though maybe a little above the levels recommended by the IOM), and wait for the randomized controlled trials to come in, especially if you're young.

[k10]

I would keep blood levels relatively low (though maybe a little above the levels recommended by the IOM), and wait for the randomized controlled trials to come in, especially if you're young.

This.

I think people jumped on to the mega-dose vitamin D bandwagon far too quickly with primarily preliminary research. Many studies are now showing harmful long-term effects of mega-dosing vitamin D. Some believe it can be harmful for both the immune system over a long period of time, and in regards to cancer pathogenesis.

I think we should keep a conservative approach in regards to supplementing Vit. D. I personally don't supplement it at all as I'm young and want to wait for more research into this. There are just too many unknowns about Vitamin D supplementation. It has profound effects on the body and the immune system and I believe that over-supplementation of this hormone may do more harm than good for some in the long run

[nupi]

But where does oversupplementation begin? 400IU? 1000 IU? 5000? Or is oversupplementation defined by going over a certain serum level? I am quite certain that some supplementation for those of us who do not get sun exposure is required (cf. fortified milk / rickets, nb I also don't drink milk)

Advising to avoid oversupplementation (without giving serum levels) is frankly a tautology....

Edited by nupi, 30 July 2011 - 08:42 PM.

[Robert C]

From what I understand the bone density issue is maxed out at about 30 ng/ml. It would seem resonable to me to aim to keep one's blood levels at or just above this level. I'm 52 now and my first vit D labs I had done were 3 years ago while I was taking 600 iu's contained in my multi. I live in sunny Houston, TX and at that time I was doing a lot of outdoor activities and I'm not "good" at all about covering up, wearing sun screen, taking care of my skin, etc.

Labs at that time at the end of summer showed a total vit D level of 44 ng/ml. Using the rule-of-thumb that every 1000 iu's of D increases one's levels about 10 ng/ml, I would estimate that my natural sun tanned state was about 38. So, shooting for a level at or slightly above 30 ng/ml year around passes the common sense smell test with me. Trying for a year around level well above one's natural sun tanned state maybe seems a bit risky and unproven.

I remember seeing a study that measured healthy young surfboarders' D levels in Hawaii some time ago but can't place it. I do remember the levels were well above 30 ng/ml tho.

I also wonder if taking a D supp is truly the same as getting sun exposure.

[cathological]

They probably all got their vitamin D from cod liver oil, which comes with lots of vitamin A. And vitamin A could be causing the prostate cancer risk. Or maybe something else is causing it that they didn't bother to measure. This study is stupid. No reason here to use less vitamin D if you ask me.

Edited by cathological, 30 July 2011 - 09:28 PM.

[nameless]

But where does oversupplementation begin? 400IU? 1000 IU? 5000? Or is oversupplementation defined by going over a certain serum level? I am quite certain that some supplementation for those of us who do not get sun exposure is required (cf. fortified milk / rickets, nb I also don't drink milk)

Advising to avoid oversupplementation (without giving serum levels) is frankly a tautology....

Dose by serum, not Vit D amounts. I have been aiming for around 40ng/ml, but 35-40 may be safer. Or perhaps even 30-35 ng/ml.

I wouldn't suggest jumping off of the D bandwagon just because of this study, but then again, I wouldn't advise super high D levels either (60-70+) as some members here have been using as their target.

One tricky thing with most D studies is they aren't based on supplementation, so other factors could be in play too. Such as dietary sources of D... if they study a population, let's say they have high-ish D serum and find a correlation to cancer. Maybe that population also consumes lots of eggs and dairy, so is it the D that is the problem, or eggs and dairy?

And even if this study is accurate regarding prostate cancer, would higher serum D levels decrease risks of other cancers or heart disease? Does Vit A or K play a role, as they sort of go hand in hand with D. A lot of questions remain to be answered.

Edited by nameless, 30 July 2011 - 09:46 PM.

[9H}@}C\%kmFHOB#?X]

I remember seeing a study that measured healthy young surfboarders' D levels in Hawaii some time ago but can't place it. I do remember the levels were well above 30 ng/ml tho.

Here is a discussion of the study you are remembering:

The above graph shows results from 93 healthy 24-year-old Hawaiian surfers. The authors of this paper concluded that: "the goal of vitamin D replacement therapy should be no greater than the maximum that appears attainable, a serum 25(OH)D concentration of approximately 60 ng/ml." However, many laboratories currently have listed their "sufficient" range as 32-150 ng/ml. There is no evidence that levels above 50 ng/ml are beneficial.

---

I also wonder if taking a D supp is truly the same as getting sun exposure.

Everything I have read states that vitamin D-3 as cholecalciferol is identical to the vitamin D that is produced by the human body when exposed to sunlight under normal conditions. Here is an example (Harvard School of Public Health):

What type of vitamin D supplement is best?
Two forms of vitamin D are used in supplements: vitamin D2 (“ergocalciferol,” or pre-vitamin D) and vitamin D3 (“cholecalciferol”). Vitamin D3 is chemically indistinguishable from the form of vitamin D produced in the body, and there’s evidence that it may be more effective than vitamin D2 at raising vitamin D levels in the blood. That’s why some scientists recommend looking for vitamin supplements that contain vitamin D3. Other scientists believe that vitamin D2 and vitamin D3 are similarly effective. Indeed, high dose vitamin D2 is available by prescription, and doctors regularly prescribe it to restore vitamin D levels in people who are deficient. As it turns out, the marketplace may answer the vitamin D question for you: More and more supplement makers offer vitamin D3 in their products.

Edited by Watson, 31 July 2011 - 02:23 AM.

[niner]

Here is a published critique of the earlier case control study. The full text is available here.

Dermatoendocrinol. 2009 Nov;1(6):289-93.
Critique of the U-shaped serum 25-hydroxyvitamin D level-disease response relation.
Grant WB.

Sunlight, Nutrition and Health Research Center (SUNARC); San Francisco, CA USA.

Previous work has suggested an optimal serum 25-hydroxyvitamin D [25(OH)D] level near 20-30 ng/mL, above which disease risk may increase. Although based primarily on a prostate cancer study in Nordic countries, examples include esophageal, and pancreatic cancer, cardiovascular disease, and all-cause mortality rate. However, these studies apparently are not representative of the findings in the literature for these diseases or disease outcome in general. The prostate cancer study was from Nordic countries and used serum 25(OH)D levels from more than 15 years prior to cancer diagnosis for about half of the cases. Most studies of prediagnostic serum 25(OH)D find no significant correlation with risk of prostate cancer. Many risk-modifying factors for prostate cancer exist that observational studies generally do not include. The esophageal cancer data were from a region of China with high incidence of esophageal cancer. The pancreatic study was conducted on smokers in Finland. Both the esophageal and pancreatic studies are at odds with many ecological and observational studies in various countries. When several studies for cardiovascular disease, and all-cause mortality rate are combined in preliminary meta-analyses, the best fits to the data show a monotonic decrease of hazard ratio with increasing logarithm of serum 25(OH)D. Thus, little support exists for the U-shaped serum 25(OH)D level-disease response relation, and the few studies that do should not be used in forming public health policies regarding vitamin D and ultraviolet-B irradiance.

PMID: 21572873

So we now have two flawed studies from Nordic countries, looking at individuals who may have gotten their vitamin D from cod liver oil, as cathological pointed out. The above critique pulls together other anti-vitamin D papers. Looking at the affiliation of the author of the critique, I'd guess he might be a vitamin D evangelist, so that's another thing to take into account. Be that as it may, he has some good points; the full paper is worth a look. I've been basing my 25-OH-D3 level target on Melamed's paper, where he sees a shallow minimum in all-cause mortality around 50. I've never been a fan of going for really high levels, although you can get well over 50 from sun alone. There's too much positive vitamin D data to run from D on the basis of these somewhat-shaky observations. Since I have a family history of pCa, I'm definitely going to keep an eye on this issue. I might lower my target a little. I'd like to see a study from somewhere farther from the arctic circle.

Edited by niner, 31 July 2011 - 06:37 AM.

[Robert C]

Thanks Watson for that info. My common sense tells me not to push D levels above what the sun can provide. From an evolution standpoint, I wonder if maybe that could even be a bit high for a caucasian? I think most darker people lived near the equator and most light skinned people lived nearer the poles. Light skinned people living near the poles could get D in the summer from sun and I guess could get it year-around from sea food. A white person living in a very sunny place maybe is a more recent thing? I guess what I'm saying here is maybe from a "what's natural" standpoint, looking at the max D levels of very sun tanned fair skinned people might not be entirely natural. I would love to see what dark skinned peoples' D levels are that live/work outside in very sunny areas.

I forgot to menion that I'm a white male with normal complextion. At the time of the above mentioned lab work I was healthy but 49. Maybe a bit old for peak D values from sun. I did not lay around outside tanning per say but I was very active outside and did not tend to wear sun screen. Based upon my personal easily attainable D levels from sun, and the various studies, I think I'll shoot for D levels in the 30 to 40 ng/ml range. It would seem natural to me to let it drift to the low side in winter and the high side in summer.

One other factor to complicate things. In the past people probably did not live long enough to have to worry and bone strength in old age. So, maybe we have a different set of challanges today.

[John2009]

Regarding the study on the surfers, by looking at the graph, it seems that the majority of surfers had blood levels between 30 and 45 ng/ml. Therefore, why would anyone want to go beyond 45 ng/ml in the absence of good data supporting higher levels ? It looks like only a small percentage of the surfers had levels above 50 ng/ml. There were only 93 people in the study, but if you have people wearing nothing but shorts who are out in the sun all day in Hawaii, and the majority of levels are 30 to 45 ng/ml, then it seems that is the place to start looking for an optimum level, unless there is good sound data supporting higher levels.

Edited by John2009, 31 July 2011 - 11:25 PM.

[Robert C]

Hi John. Actually if my eyes are reading the graph correctly, the two highest bars represent 20 to 30 ng/ml. Strange, but maybe they wear alot of suncreen???

[John2009]

Hey Robert,

Yea, I glanced at the chart & I guess my brain focused on the colored bars, I guess they were trying to show a cutoff point or something by using clear and colored bars in the graph.

Sunscreen would be a factor, but you would think they would have talked to these people at the start of the study and either had them not use sunscreen (if they already had good protective tans) or had them all use the same type and amount of sunscreen, perhaps the weakest possible. I did not read the full study, does it say anything about sunscreen ? I also think sunscreen use might make a study like this meaningless, since a decent sunscreen will block out most of the rays that create vitamin D.

In any event, it seems like low levels for people who spend practically all day in the sun, but perhaps these levels are actually ideal and our estimates of optimal levels are a bit high ?

[Invariant]

Hey Robert,

Yea, I glanced at the chart & I guess my brain focused on the colored bars, I guess they were trying to show a cutoff point or something by using clear and colored bars in the graph.

Sunscreen would be a factor, but you would think they would have talked to these people at the start of the study and either had them not use sunscreen (if they already had good protective tans) or had them all use the same type and amount of sunscreen, perhaps the weakest possible. I did not read the full study, does it say anything about sunscreen ? I also think sunscreen use might make a study like this meaningless, since a decent sunscreen will block out most of the rays that create vitamin D.

In any event, it seems like low levels for people who spend practically all day in the sun, but perhaps these levels are actually ideal and our estimates of optimal levels are a bit high ?

I surf sometimes, and have quite a few surfer friends. It is not very surfer-esque to be concerned with things like using sunscreen for protection. Except when the sun is very harsh or one isn't tanned yet, surfers generally don't bother using sunscreen. When they do use it, it's generally on the face and back, and it's very thick, water resistant stuff that is clearly visible, like white paint.

Of course, this is all generalization and there will be exceptions. Anyone care to look at the full study to see if they mention sunscreen?

[Invariant]

I looked up the study:


Low vitamin D status despite abundant sun exposure.
Binkley N, Novotny R, Krueger D, Kawahara T, Daida YG, Lensmeyer G, Hollis BW, Drezner MK.
Source
University of Wisconsin Osteoporosis Research Program, Madison, WI 53705, USA. nbinkley@wisc.edu


http://www.grc.com/h...un_Exposure.pdf

On average, the 93 subjects reported being outside for 22.4 h/wk (1.6) with no sunscreen,
and 28.9 h/wk (1.5) with and without sunscreen (Fig. 1). Of
subjects, 40% (37 of 93) reported never using sunscreen. The
resultant mean sun exposure index score, indicating hours
per week of total body skin exposure with no sunscreen used,
was 11.1 +/-  0.7 (range 1.0 –38.4). Only two subjects reported
use of tanning booths; as such, the skin darkening noted
previously reflects natural sunlight exposure.

Edited by Novotropic, 01 August 2011 - 10:04 AM.

[buck1s]

Hi John. Actually if my eyes are reading the graph correctly, the two highest bars represent 20 to 30 ng/ml. Strange, but maybe they wear alot of suncreen???

Maybe wetsuits?

[mikeinnaples]

I surf sometimes, and have quite a few surfer friends. It is not very surfer-esque to be concerned with things like using sunscreen for protection. Except when the sun is very harsh or one isn't tanned yet, surfers generally don't bother using sunscreen. When they do use it, it's generally on the face and back, and it's very thick, water resistant stuff that is clearly visible, like white paint.

Of course, this is all generalization and there will be exceptions. Anyone care to look at the full study to see if they mention sunscreen?

I don't surf sometimes. I live 50 yards from the waters edge and I surf every day there is a rideable wave. I AM a surfer.

1. Nearly every surfer I know between the ages of 20 and 50 wears sunscreen before paddling out.

2. Most surfers (barring the groms) think you are stupid not to wear sunscreen. I guess this comes with age and experience compared to the groms.

3. Every single surfing forum I frequent has sunscreen and skin cancer threads to rival anything we have going on here at imminst.

4. Not only can you get sunscreen that performs good in the water WITHOUT it being white and pasty ...you can get some that is environmentally safe to sea life.

5. Many surfers wear UV protective clothing as well, such as rashies ...though admittedly this isn't as wide spread (probably 10%). (the older guys out there will wear them more).

Speaking from first hand experience as a member of the surfing community of course.

Edited by mikeinnaples, 02 August 2011 - 04:08 PM.

[mikeinnaples]

Hi John. Actually if my eyes are reading the graph correctly, the two highest bars represent 20 to 30 ng/ml. Strange, but maybe they wear alot of suncreen???

Maybe wetsuits?

Not in Hawaii ....

I would suspect there is a huge difference in D absorption between natives and transplants though. The skin tone is certainly different naturally. Was that accounted for in the study?

Edited by mikeinnaples, 02 August 2011 - 04:07 PM.