HealingWell
Search Close Search
☰

OT: RCT/pooled cohort shows significant drop in breast cancer group+ Vit D(level 1 evidence?)

Support Forums
>
Prostate Cancer
✚ New Topic ✚ Reply
❬ ❬ Previous Thread |Next Thread ❭ ❭
Posted 7/23/2018 5:16 PM (GMT -5)
We have all recently read the recent RCT showing no advantage for anything after once a month huge megadoses of vitamin D. I was disappointed with that result, and questioned the methods, but let the chips fall where they may.

However, I have just found first an RCT showing benefits for diabetics who are given Vitamin D, and posted that in another thread.

But here is a “Pooled analysis of two randomized trials and a prospective cohort“ related to breast cancer.( Allen, please opine: does this qualify as an RCT? or not? I may be too ignorant of research methods to really know, hence I ask you)

/www.ncbi.nlm.nih.gov/pmc/articles/PMC6003691/

“Methods
Analyses used pooled data from two randomized clinical trials (N = 1129, N = 2196) and a prospective cohort (N = 1713) to examine a broad range of 25(OH)D concentrations……………..
Women in the 2007 Lappe et al. cohort (hereafter termed 2007 Lappe cohort) participated in a four year, population-based, double-blind, placebo-controlled trial of vitamin D and calcium supplementation in a 9-county area in Eastern Nebraska. Participants were randomly assigned to: 1) calcium plus vitamin D3 (1400–1500 mg/day of calcium plus 1100 IU/day of vitamin D3), 2) calcium (calcium as mentioned previously plus vitamin D placebo), or 3) control (calcium and vitamin D placebos). This trial was registered at clinicaltrials.gov as NCT00352170.
In another study, women in the 2017 Lappe et al. cohort (hereafter termed 2017 Lappe cohort) participated in a four year, population-based, double-blind, placebo-controlled trial of vitamin D and calcium supplementation in a 31-county area in Eastern Nebraska. Participants were randomly assigned to: 1) intervention (1500 mg/day of calcium and 2000 IU/day of vitamin D3) or 2) control (calcium and vitamin D placebos). This trial was registered at clinicaltrials.gov as NCT01052051.
For both Lappe cohorts, inclusion criteria included women aged 55 years or older who were free of known cancer at enrollment and within the prior 10 years. As described previously [19–22], supplement intake by bottle weight and health status were assessed at 6-month intervals….”


Another thing is: I guess you can not know how much vitamin D these ladies were actually taking unless you are watching them take it, which would be needed for a true intervention? However, no one has blood levels over 40 ng(and for sure 60ng/ml) unless they are supplementing or getting large amounts of sunshine. I also doubt many women have less than 20ng/ml if taking 2000 ius/day. So by the blood level results, you can pretty well figure out if they have been taking their supplements or not. Allen, you know way more than me about research. Would you say the above is correct statement, or not?


Please look at the charts and notice that the HR for breast cancer dropped in a straight line for each 20 ng increase in blood levels of vitamin D above reference <20ng(762 cases per 100,000 person-years). Presumably every increase in blood levels is due to intervention with supplements. Please look at figure 1 and it’s graph. Notice how without fail, another 20 ng increase(more supplements?) is associated with a further decrease in breast cancer HR, starting with 762 cases per 100,000 person-years for 20ng/ml, and fewer cases with EACH increase in vitamin D. With the largest drop seen going from 40-60 ng/ml(367 cases) to the >60ng group(134 cases). Notice also in the upper right part of figure 1 where it says “82% LOWER RATE for >60ng/ml vs <20 ng/ml (p=.006).



I realize we now have RCTs showing that a massive megadose of vitamin D once a month was helpful for exactly nothing. And maybe it is not, though at least it did not make the HRs for cancer worse, apparently. Still, studies such as this one, as well as the RCT showing impressive benefits for the diabetics, leave me feeling that “more research is needed”, as they say.

Allen, what is your opinion of this study? Is it worth considering, despite conflicting studies elsewhere? Thank you for your opinion.

Post Edited (BillyBob@388) : 7/27/2018 11:43:18 AM (GMT-6)

Posted 7/23/2018 5:52 PM (GMT -5)
I also saw this down in this discussion of this study:

Somebody said...
The Women’s Health Initiative (WHI) trial did not find an association between assigned vitamin D treatment group and breast cancer risk [34]; however, low dosage (400 IU/day) and poor compliance (~50%) likely contributed to the lack of effect. A subsequent re-analysis of the WHI data showed a significant reduction in breast cancer risk among women not taking a vitamin D or calcium supplement before enrollment [35]

I realize many here are convinced that all vitamins, and maybe even all diets are worthless, possibly even harmful. I am still not so sure. To me, though I don't know how well it qualifies as a true RCT ( it says "RCT"), but regardless, the results get my attention and at least shout "more studies are needed". However, is it as it says, an RCT? If so, then this along with the diabetes RCT, will keep me taking my vitamin D for now. YMMV.
Posted 7/23/2018 8:12 PM (GMT -5)
You are aware that the study you cited was in post-menopausal women and had nothing to do with prostate cancer? Here's what the authors say about that study:

"Participants received vitamin D alone rather than with calcium. It is possible that both medications, acting separately or synergistically, had a greater influence than vitamin D alone, although a reduction in cancer incidence was not seen in the Women’s Health Initiative which also gave both supplements."

/www.nejm.org/doi/full/10.1056/NEJMoa055222

The mean baseline Serum Vitamin D level was 25 mg/ml. In the Nebraska study, baseline vitamin D was 33 ng/ml. Importantly, in the Nebraska study of post-menopausal women, supplements containing vitamin D were regularly taken by 59% of the cohort, whereas only 8% of the people in the NZ study were already taking Vitamin D supplements.Baseline Vitamin D was found to be predictive of treatment effect.

Also calcium supplementation has been associated with increased risk of prostate cancer.

You criticize studies that give what you consider to be too-low doses and then turn around and criticize studies for giving what you consider to be too-high doses. Dose effect is one of the criteria by which we judge efficacy.

So, although the Nebraska study was an RCT, it was not confirmed by another similar study. And you cannot take the results of a study in post-menopausal women to give men with prostate cancer any direction.

I suggest you take metformin or other blood sugar-lowering drug for diabetes, rather than Vitamin D. It has a much better effectiveness against diabetes, and may help with PC too.
Posted 7/23/2018 9:03 PM (GMT -5)

Tall Allen said...
You are aware that the study you cited was in post-menopausal women and had nothing to do with prostate cancer?................

Certainly, I am aware of that. I did not post these 2 studies to make a statement about PC, which is why they are OT. I believe it has been said here recently that the RCTs now show that Vitamin D was not good for PC, any other cancer, heart disease, bones or anything else. Hence the 2 recent studies that seem to indicate it might be good for something.

Post Edited (BillyBob@388) : 7/23/2018 8:31:18 PM (GMT-6)

Posted 7/23/2018 9:19 PM (GMT -5)

Tall Allen said...


I suggest you take metformin or other blood sugar-lowering drug for diabetes, rather than Vitamin D. It has a much better effectiveness against diabetes, and may help with PC too.

Well, I don't have diabetes or pre-diabetes. I try to stay on top of that with intermittent fasting and or low carb eating. And Metformin is known to have some SEs for some people. But the point of posting the study on Vit D given to the folks with diabetic foot ulcers was to show that vitamin D- rather than being not helpful for PC, any other cancer, heart disease or anything else, was actually quite helpful(in this small RCT anyway) for the diabetic ulcers and all of the blood work normally associated with heart disease stemming from diabetes. Most importantly insulin and insulin resistance. IOW, maybe good for something.

"So, although the Nebraska study was an RCT, it was not confirmed by another similar study. "
I'm not sure: was the NZ study on PC/Vit D a follow up study, or has there been a follow up study?

"You criticize studies that give what you consider to be too-low doses and then turn around and criticize studies for giving what you consider to be too-high doses.". I only questioned such a truly massive dose, far beyond what has been recommended, being given as a 1 day dose and then nothing else for a month, as maybe not working in the same way as smaller consistent doses. Who can say if the results would be the same, and why do it that way anyway, rather than how it is usually done. As you said, "One can argue that a consistent daily Vitamin D3 intake might have had an effect". I agree.

Post Edited (BillyBob@388) : 7/23/2018 8:29:44 PM (GMT-6)

Posted 7/23/2018 9:27 PM (GMT -5)
Allen, thank you for confirming that the Nebraska study was an RCT, although it lacks a follow up. I did not want to falsely claim RCT status if it was not. What do you think about the graphs showing a consistent decrease in cancer rates for each increase in Vit D blood levels, with the single largest increase occurring at the >60ng/ml level? With an incidence 82% lower than the reference level of <20ng/ml.

Is that meaningful in your opinion? I mean, it seems very meaningful to me, and for sure if it is ever repeated. But I make no claims to being an expert at interpreting studies. But that is wondering what your opinion is on that chart in figure 1.

Post Edited (BillyBob@388) : 7/23/2018 8:30:12 PM (GMT-6)

Posted 7/23/2018 9:37 PM (GMT -5)
Since the post-menopausal women have one RCT that shows a benefit to getting calcium + Vitamin D and two that doesn't, the results are equivocal, but in favor of no benefit in terms of effect on cancers in post-menopausal women. I guess if I were a post-menopausal woman I'd be interested in keeping a normal level of Vitamin D and calcium.

However, we have no equivocal results for prostate cancer - the only RCT showed there was no benefit.

"I only questioned such a truly massive dose, far beyond what has been recommended, being given as a 1 day dose and then nothing else for a month, as maybe not working in the same way as smaller consistent doses."

As I explained, it was for compliance purposes, and to give a dose that moved the needle. Because Vitamin D is stored in fat and the liver, it should not make a difference - but if you want to believe it does make a difference - you would have to answer why it should.
Posted 7/23/2018 10:06 PM (GMT -5)

Tall Allen said...
Since the post-menopausal women have one RCT that shows a benefit to getting calcium + Vitamin D and two that doesn't, the results are equivocal, but in favor of no benefit in terms of effect on cancers in post-menopausal women. I guess if I were a post-menopausal woman I'd be interested in keeping a normal level of Vitamin D and calcium.

However, we have no equivocal results for prostate cancer - the only RCT showed there was no benefit.

"I only questioned such a truly massive dose, far beyond what has been recommended, being given as a 1 day dose and then nothing else for a month, as maybe not working in the same way as smaller consistent doses."

As I explained, it was for compliance purposes, and to give a dose that moved the needle. Because Vitamin D is stored in fat and the liver, it should not make a difference - but if you want to believe it does make a difference - you would have to answer why it should.

Thank you. So are you considering "Pooled analysis of two randomized trials and a prospective cohort" as 1 RCT? If so, fine, I don't know how those things work.

I do NOT believe giving a massive 1st day dose and then nothing for a month will make a dif, I simply do not know, I have no clue, but do wonder. Again as you said, " One can argue that a consistent daily Vitamin D3 intake might have had an effect". And I have argued that it MIGHT have had an effect. If I must give a reason, I can only guess at some reasons. Maybe the initial blood levels- before going into storage- shoot up to some level that has a negative effect? You used to talk about the U shaped curve for vitamin D and PC, right? If that exists, then thet could end up with a week or so where the very high levels work against them.

If that averages out to 3333 per day, then maybe they have levels that are high enough to work against you followed by a week or 2 where levels are not high enough to have an optimal effect? But I have no idea, I am just guessing. There would be no question if they had just done the study in a way simulating how it is done in real life. But, probably it make no dif. Probably.

Was this a follow up study? EDIT: never mind, I see you said "we have no equivocal results for prostate cancer - the only RCT showed there was no benefit."

Post Edited (BillyBob@388) : 7/24/2018 8:03:22 AM (GMT-6)

Posted 7/23/2018 11:04 PM (GMT -5)
As I read over this study again, I am more impressed. And left saying "more studies are needed, but while I wait I think I and the women in my family will continue with reasonable intake of vitamin D". I suppose many here will disagree with me. Maybe I'm crazy, but I am seeing possible reasons to supplement(pills or sunshine) and virtually none not to. Especially when this study is combined with the study on diabetics, and since the study with the huge once a month megadoses did not worsen cancer rates at all.

But this was no small study with N=5038. It was in fact 3 different studies, all with similar results:

Somebody said...
Analyses used pooled data from two randomized clinical trials (N = 1129, N = 2196) and a prospective cohort (N = 1713) to examine a broad range of 25(OH)D concentrations. The outcome was diagnosis of breast cancer during the observation periods (median: 4.0 years). Three analyses were conducted: 1) Incidence rates were compared according to 25(OH)D concentration from <20 to ≥60 ng/ml (<50 to ≥150 nmol/L), 2) Kaplan-Meier plots were developed and 3) multivariate Cox regression was used to examine the association between 25(OH)D and breast cancer risk using multiple 25(OH)D measurements.
Go to:
Results

Within the pooled cohort (N = 5038), 77 women were diagnosed with breast cancer (age-adjusted incidence: 512 cases per 100,000 person-years). Results were similar for the three analyses.

And results were quite good. And consistently less BC with each rising level of vitamin D ( 25(OH)D ). Am I crazy, or is that potentially important? And finally, the best group by far was the group with the very highest blood level, a level that many of us might have worried was too high. No sign of U shaped curve when it comes to this cancer, even if that tells us nothing about PC.

Somebody said...
Comparing incidence rates, there was an 82% lower incidence rate of breast cancer for ≥60 ng/ml vs <20 ng/ml (Rate Ratio = 0.18, 95% CI: 0.04–0.62, P = 0.006).".

One negative: I wish they had not included the calcium. Because, was it the calcium, the vitamin D, or both working together? A question to be settled later, I guess. However, while some got calcium, and some didn't, the chart in figure 1 clearly shows a big difference between all levels of vitamin D, so I suspect that was the main variable. "with the highest proportion breast cancer-free at 4 years in the ≥60 ng/ml group (99.3%) and the lowest proportion breast cancer-free in the <20 ng/ml group (96.8%). The proportion with breast cancer was 78% lower for ≥60 ng/ml vs <20 ng/ml (P = 0.02) in the Kaplan-Meier analysis.". I should point out that those in the GrassrootsHealth cohort (1700) did not have an intervention, as far as I can tell. They apparently simply measured their vitamin D levels and cancer rates, and they took whatever they took. But I guess one can ask how anyone can have a level >60ng without supplementing?

Also, I guess in table 2 they adjusted for calcium and several other variables, and concluded

Somebody said...
Women with 25(OH)D concentrations ≥60 ng/ml had an 80% lower risk of breast cancer compared to women with concentrations <20 ng/ml (HR = 0.20, P = 0.03), adjusting for age, BMI, smoking status, calcium supplement intake, and study of origin.....a continuous variable revealed consistently lower risk of breast cancer with higher 25(OH)D concentration, with no evidence of increased risk in the higher 25(OH)D concentrations".

Post Edited (BillyBob@388) : 7/24/2018 8:10:16 AM (GMT-6)

Posted 7/23/2018 11:12 PM (GMT -5)
Finally, one last thing adds to how promising this study is for the ladies in our lives(and who knows, maybe even men with other types of cancers): it is likely that out of 5038 post menopausal women, some already had breast cancer(BC) before they entered the study, right? So how did it look after they adjusted for that possibility by excluding women diagnosed during the 1st year: Behold:

Somebody said...
Whether our findings reflect prevention of the primary tumor or treatment of early stage, undiagnosed cancer by vitamin D is not clear. Of interest, the results for women who were followed and free of breast cancer at the end of the first year revealed a stronger association between 25(OH)D concentration and breast cancer risk (HR: 0.07, P = 0.02 for ≥60 vs <20 ng/ml). There was only one case of breast cancer diagnosed after one year among those with 25(OH)D concentrations ≥60 ng/ml.

HR .07. Man, if that was a drug, it would be head line news, breaking news, don't you think?

Here is hoping that it is even 1/2 as helpful for us PC guys, even if there is now one RCT now indicating it is not helpful at all. May there never be a follow up study confirming that one! yeah But, time will tell, and the chips will fall where they will.

Post Edited (BillyBob@388) : 7/24/2018 8:17:57 AM (GMT-6)

Posted 7/23/2018 11:44 PM (GMT -5)
This included some of the studies already included here, with some RCTs and some not, but "The study included all invasive cancers excluding skin cancer.". But I guess not PC, since I think they were still only studying women. All types of cancer then EXCEPT PC, dang it! The results are similar to what has already been quoted in earlier posts in this thread.

/www.ncbi.nlm.nih.gov/pmc/articles/PMC4822815/

Somebody said...
Conclusions

25(OH)D concentrations ≥40 ng/ml were associated with substantial reduction in risk of all invasive cancers combined...............proportion with cancer was 71% lower for ≥40 ng/ml vs. <20 ng/ml, P = 0.02). The ≥40 ng/ml group diverged early from the other groups and the 20–39 ng/ml diverged from the <20 ng/ml group at approximately 2 years................................
Spline regression revealed a sharp decrease in the risk of cancer with increased 25(OH)D concentration in the lower range of 25(OH)D and a gradual decline as serum concentrations neared 40 ng/ml and above, with no evidence of increased risk in the upper 25(OH)D concentrations (Fig 4). The reduction in risk from 20 ng/ml to 40 ng/ml was approximately 70%.............................
Note in Fig 4 the smallness in the reduction in risk as 25(OH)D exposure increases from 25 to 35 ng/ml. To the extent that Fig 4 adequately represents the association of risk and vitamin D status, this small effect size in the mid exposure range may explain why many treatment studies, particularly those that did not raise mean 25(OH)D concentration into the range above 40 ng/ml, failed to detect an association of serum 25(OH)D with cancer. This illustrates the importance of dosing in a manner calculated to span an appreciable portion of the sigmoid response curve.................
The findings from this analysis support the inverse association between 25(OH)D and risk of cancer and highlight the importance for cancer prevention of achieving a concentration substantially above 20 ng/ml, the concentration recommended by the IOM for bone health [21]. Increasing 25(OH)D concentrations to a minimum of 40 ng/ml could substantially reduce cancer incidence and associated mortality in the population based on these findings as well as other studies [22–26]. Primary prevention of cancer, rather than solely expanding early detection or improving treatment, will be essential for reversing the current upward trend of cancer incidence worldwide; this analysis suggests that improving vitamin D status is a key prevention tool.

OK, I realize many of us here at least suspect that all vitamins are just expensive urine, and are not good for anything, not PC or any other cancer or heart disease or diabetes not even bone health. But are you really that certain of that? I am not so sure of that.

Post Edited (BillyBob@388) : 7/23/2018 10:50:08 PM (GMT-6)

Posted 7/24/2018 9:16 AM (GMT -5)
I concluded the previous post with:

Somebody said...
OK, I realize many of us here at least suspect that all vitamins are just expensive urine, and are not good for anything, not PC or any other cancer or heart disease or diabetes not even bone health. But are you really that certain of that? I am not so sure of that.

I should have included diet along with the various vitamins among things that many feel are worthless, at least when it comes to cancer. In both cases though, I still ask: are you sure of that?
Posted 7/25/2018 9:13 PM (GMT -5)
OK, I'd like to bump or repeat something: after excluding diagnoses within the first year(IOW, preexisting cancers) there was this:

Somebody said...
Whether our findings reflect prevention of the primary tumor or treatment of early stage, undiagnosed cancer by vitamin D is not clear. Of interest, the results for women who were followed and free of breast cancer at the end of the first year revealed a stronger association between 25(OH)D concentration and breast cancer risk (HR: 0.07, P = 0.02 for ≥60 vs <20 ng/ml). There was only one case of breast cancer diagnosed after one year among those with 25(OH)D concentrations ≥60 ng/ml.

1:A hazard ratio of 0.07 for those in the highest vit D category of >60 ng/ml, or 93% less risk for the highest vitamin D group. (what can touch that for any cancer?)
2: risk is lowered fairly proportionately(See the chart in figure 1 in the RCT) as blood levels of vit D rise. Each and every rise of Vit D = a lowered risk
3: once you get to the final and highest vit D group of > 60 ng/ml of vit D, there is a larger drop in risk compared to all of the lower groups
4: out of 77 cases of cancer diagnosed, ONE was in the > 60 ng/ml group. ONE The vast majority were in the 1st and 2nd lowest vit D group.

Now, what I am really hoping for is to hear some comments from other than 1 guy giving an opinion on:

Do we now have RCT evidence of strong benefit(or any benefit) to giving Vit D to post menopausal women to lower breast cancer odds?

Or not?

The answer is an unequivocal YES, seems to me. ( and we can add the benefits in diabetes from the 2 other RCTs also, but the big one is the BC RCT ) But are there folks here who are of the opinion that the above RCT does NOT provide evidence that vit D is other than expensive(well, not that expensive) urine?

Also, who knows what level of evidence this is?

Either way, I'd love to know your thoughts.

Post Edited (BillyBob@388) : 7/25/2018 8:41:05 PM (GMT-6)

Posted 7/25/2018 9:22 PM (GMT -5)
There are two RCTs that show no benefit to post-menopausal women You fail to mention those, giving an unbalanced impression. So the bulk of the evidence is that there is no benefit.
Posted 7/25/2018 9:46 PM (GMT -5)

Tall Allen said...
There are two RCTs that show no benefit to post-menopausal women You fail to mention those, giving an unbalanced impression. So the bulk of the evidence is that there is no benefit.

I don't want to, but I must respond. Are you talking about one of these being the study I mentioned earlier, that used low dose and had poor compliance and that showed a significant reduction anyway after adjusting for women already taking a vitamin D or calcium supplement before enrollment? Is that one? If so, what was the other one?

From the discussion in the linked study:

Somebody said...
The Women’s Health Initiative (WHI) trial did not find an association between assigned vitamin D treatment group and breast cancer risk [34]; however, low dosage (400 IU/day) and poor compliance (~50%) likely contributed to the lack of effect. A subsequent re-analysis of the WHI data showed a significant reduction in breast cancer risk among women not taking a vitamin D or calcium supplement before enrollment [35]

Also, would you mind telling me what level of evidence this(Nebraska) study is? Thank you.

Post Edited (BillyBob@388) : 7/25/2018 8:50:24 PM (GMT-6)

Posted 7/25/2018 9:57 PM (GMT -5)
Re: the Women's Health Initiative that showed no benefit:
/www.hsph.harvard.edu/nutritionsource/vitamin-d-cancer-trials/

Somebody said...
The randomized controlled trial evidence on vitamin D supplementation and cancer prevention has been mixed to date. The Women’s Health Initiative trial, which followed roughly 36,000 women for an average of seven years, failed to find any reduction in colon or breast cancer risk in women who received daily supplements of 400 IU of vitamin D and 1,000 mg of calcium, compared to those who received a placebo. (1, 2) But that study had several limitations, chief among them the relatively low dose of vitamin D. (3, 4) Also, some people in the placebo group decided on their own to take extra calcium and vitamin D supplements, minimizing the differences between the placebo group and the supplement group, and about one third of the women assigned to vitamin D did not take their supplements. (5)

A more recent trial among nearly 1,200 postmenopausal women found significant reductions in overall cancer incidence among those randomized to receive 1,100 IU of vitamin D plus 1400-1500 mg calcium............................

So, this study was useless as far as telling us anything about what effect 1000-4000 iu/day of vitamin D might have on cancer. Sounds like it was almost designed to fail, or at least was poorly done. What was the other study?

Post Edited (BillyBob@388) : 7/25/2018 9:01:06 PM (GMT-6)

Posted 7/25/2018 10:28 PM (GMT -5)
Actually, Allen, never mind about what that other study was, or what level of evidence this Nebraska study is. I'm wore out thinking and writing about it. You will probably end up being right anyway. If you say "Megadoses of Vitamin D have no effect on prostate (or any other) cancer ", then it must be so. If others(or myself) want to read other studies that seem to call into question the results of that RCT , then we can do so and make our own conclusions. But for the moment, it just doesn't seem worth arguing about for any longer.
Posted 7/25/2018 10:52 PM (GMT -5)
Hey Guys, I just saw this. It is a great explanation, in less technical terms, of this RCT, or at least one segment of this pooled study, the Grassroots segment. This is good, look at the graphs. Impressive to me is that raising the vitamin D levels from an already higher than average of 29 to a mere 38 reduced cancer rates by 77%!

I love the question it asks about where on the graph would you want your vit D to be. Personally, I choose somewhere way on the right:

/grassrootshealth.net/blog/vitamin-d-and-cancer-research/

Somebody said...
The population was white, lived around 41 degrees latitude, and had an average vitamin D level of 29 ng/ml (72 nmol/L) which is higher than the normal US population average of 24 ng/ml (60 nmol/L).
Treatment and control

The treatment group took 1100 IU vitamin D and 1400-1500 mg calcium daily. There was a second group that received calcium and a placebo for vitamin D and a third group that received only placebo – no active supplements at all.
Results

The results with cancer surprised the researchers. They were expecting the primary outcome to be what was important, especially since up to this point most research on vitamin D had been for skeletal health. This was the first intervention trial that showed that vitamin D can reduce cancer incidence. Unfortunately, since it was not the primary outcome many people in the research community discounted the cancer results of this study...............There are always different ways to interpret data, and if you want to read all the charts view the paper here, but one of the most relevant was the reduction in cancers after one year on the treatment. They did this computation because you could assume that if a participant got cancer within the first year, then it most likely had been incubating in her body – and was not affected by the short vitamin D exposure.................For those diagnosed with cancer after the first year, there was a 77% lower risk of cancer in the vitamin D and calcium group than placebo alone. This group had an average vitamin D serum level of 38 ng/ml (96 nmol/L).......Where would you want your vitamin D level to be? On the left or the right side of this graph?

Analyzed by serum level, the data showed that participants with a vitamin D level of 55 ng/ml were 35% less likely to get cancer as compared to those with a vitamin D level of 30 ng/ml (P value = .03).
Why was this paper not well received?

The abstract, or summary of the paper, is often all that people see unless they subscribe to the journal or pay for the paper. In the abstract to this paper, it states

“Conclusions and Relevance – Among healthy postmenopausal older women with a mean baseline serum 25-hydroxyvitamin D level of 32.8 ng/ml, supplementation with vitamin D3 and calcium compared with placebo did not result in a significantly lower risk of all-type cancer at 4 years. Further research is necessary to assess the possible role of vitamin D in cancer prevention.”

“Significantly”

When a layman reads this text, it can be understood to mean that there wasn’t a meaningful reduction in risk – or that the vitamin D + calcium group did not have fewer cancers than the placebo group. However, this is not true.

“Significance” in scientific research terms is a computation done during data analysis to evaluate the strength of the evidence. It is also called the P-value. In this paper, it was reported as such (from the results section of the abstract)

“A new diagnosis of cancer was confirmed in 109 participants, 45 (3.89%) in the vitamin D + calcium group and 64 (5.58%) in the placebo group (difference, 1.69% [95% CI, -0.06% to 3.46%]; P=.06).”

The P-value is a probability, it is a percentage. In this calculation, the P-value was .06, which means that there is a 6% chance that this result (30% reduction in cancer in the vitamin D + calcium group) was due to chance – not the actual treatment. In a different wording, that means you are 94% sure it was NOT chance! The scientific community has agreed that P=.05 or less is an accepted amount for study results to have “significance” and anything higher than P=.05 is “not statistically significant.” There is no middle ground, it is black or white.......................................................
You will notice in the results reported above, many of them had P-values much lower than .05.
We ask you this

What is the cost of NOT taking vitamin D to achieve a serum level between 40 and 60 ng/ml?

References

Vitamin D and calcium supplementation reduces cancer risk: results of a randomized trial
Joan M. Lappe et al.
The American Journal of Clinical Nutrition
June 2007

Posted 7/26/2018 9:18 AM (GMT -5)
For those who prefer videos, here is one by one of the authors of the Nebraska study. It includes several interesting details, such as the fact that the participants were allowed to take their own vit D and calcium up to a certain amount. This explains what I think I already commented on: that this population already had ( at base line ) blood levels higher than average based on older studies. It also explains how some of them got levels above 40 and even 60 with only 2000 IU/day, or even in the first study(this was a follow up) with only 1100/day. I was really curious about that. For example, notice in the RCT that showed no benefit for PC, the whopping SINGLE dose of 200K(1st dose, then 100K once per month) only resulted in a level greater(how much greater) than 46 in 400 men randomly sampled. So I was curious how any of these women could end up > than 60 or even 70 with such relatively modest doses.

Also of interest(chart about 15 minutes in) is how most of the action took place at levels above 50 ng/ml, which had a reduction of risk 70% greater than a level of 30 ng/ml or less. Also, >50 was a noticeable improvement over 40 to 50 and even more so compared to 30-40.

Also of interest is how the differences in 30 ng and higher levels is accelerating once you approach 4 years into the trial.

/www.youtube.com/watch?v=y31zJEUPeOI

Post Edited (BillyBob@388) : 7/26/2018 8:22:50 AM (GMT-6)

Posted 7/26/2018 11:19 AM (GMT -5)
Allen, I seek your expert advice, if any one here knows the answer to this, you do. I have asked it previously several times but I have not seen the answer. Is the Nebraska RCT re: vitamin D vs breast cancer- or individual segments of that study as it was a pooling of 3 studies- level 1 evidence or level 2? Seems level 1 to me but I obviously am no expert. Thanks in advance

From another thread:

TA said...

Tall Allen said...
Levels of evidence include both the precedence of one type over another - a large well-done randomized clinical trial (RCT) takes precedence over an observational study. But it also includes a grading system that evaluates how well done the study was. In this case, the RCT was extremely well done.

It is important to acknowledge that there are problems even in many RCTs, but to take the paranoid point of view that they are all worthless leaves one in a no-man's-land. How then does one evaluate any study - other than by whether one personally likes it or not? JAMA has a reputation for only publishing the most important studies, and they get the top peer-reviewers in the world. It is the peer-review process that assures the quality of the published study. Does it ever fail? Of course. But we can be reasonably well assured hat a trial published in JAMA is both important and well done.

/www.elsevier.com/__data/promis_misc/Levels_of_Evidence.pdf

Somebody said...
Level I:
High quality randomized trial or prospective study; testing of
previously developed diagnostic criteria on consecutive patients;
sensible costs and alternatives; values obtained from many studies
with multiway sensitivity analyses; systematic review of Level I
RCTs and Level I studies.
Level II:
Lesser quality RCT; prospective comparative study; retrospective
study; untreated controls from an RCT; lesser quality prospective
study; development of diagnostic criteria on consecutive patients;
sensible costs and alternatives; values obtained from limited stud-
ies; with multiway sensitivity analyses; systematic review of Level
II studies or Level I studies with inconsistent results. ..............

Post Edited (BillyBob@388) : 7/26/2018 2:36:08 PM (GMT-6)

Posted 7/30/2018 3:08 PM (GMT -5)
I would like to reemphasize something about this RCT which showed strong benefits against breast cancer when vitamin D was given. It may give us some indicator what kind of blood level vit D we should shoot for(or at least the women in our lives should shoot for, although the Grassroots study looked at all cancers in women, so not PC obviously). This study showed nothing but improving odds as vit D increased to above 60.

By far the greatest benefits were seen as the blood levels exceeded 50 ng/ml, even more so above 60 ng/ml.

Also, people vary widely in their response to oral vitamin D, regarding how high their blood levels go. Some people here take 10K-15K per day, and still have levels that are only in the middle, if I understand them correctly. OTOH, I had no trouble reaching 80ng/ml when I was taking 10K per day of Walmart vitamin D. I had previously reached 30 when taking 2000/day. When I saw that 80ng, I cut back to 5000. I'm now not sure that # was really something to be concerned about.

So, these higher levels can be reached, just as they were by some in this RCT. And the higher levels- even the very highest- appear to be a plus against breast cancer. Though there were 77 cases of BC diagnosed in the group as a whole, with the vast majority in the lowest vit D groups, "There was only one case of breast cancer diagnosed after one year among those with 25(OH)D concentrations ≥60 ng/ml. This woman’s diagnosis occurred 2 months into year two. Since there is a time delay between cancer initiation and diagnosis, many undiagnosed cancers that existed at enrollment would be diagnosed during the first year. ".

That is worth re-reading: Only ONE out of 77 total cases of breast cancer occurred in the very highest level of vit D after 1 year(thus highly suspect of an already existing cancer at beginning of the study), and even that one occurred at 14 months, barely out of the 1st 12 month window.

Post Edited (BillyBob@388) : 7/30/2018 2:14:04 PM (GMT-6)

✚ New Topic ✚ Reply