Vitamins found to slash risk of cancer, including PC

The answer, in practical terms, is "they don't know". Everyone is looking at everything and getting mixed results..it happens in science all the time. :)

Sensationalism and controversy sell news papers.
Boring facts from double blind studies don't.

The SELECT trial is one of the few designed to detect a cause and effect relationship. And it alerted us to a real danger of supplementation. Incidental findings (as with Vitamin D, or omega-3s) are only hypothesis generating, and prove nothing (indeed, they are almost always disproved when real RCTs are done)
- other than alerting us to possible safety concerns.

The are Rules of Evidence that evidence-based medicine adheres to. Certainly the FDA does - and for good reason. Self medicating based on "junk medicine" is potentially dangerous, and none of us (including Dr. Oz and the media) should be advocating things that may harm others.

In case anyone missed it, the most recent supplement/dietary intervention to bite the dust is pomegranate juice and extract. Take the money saved on all such junk and send it to me.

- Allen

It was an abstract presented at the recent AUA conference. Interestingly, from the same folks who first raised interest by noting the increase in PSADT. Maybe this link will work:

A Randomized, Double-Blind, Placebo-Controlled Study of the Effects of Pomegranate Extract on Rising Prostate Specific Antigen (PSA) Levels in Men following Primary Therapy for Prostate Cancer

It was a well-done RCT sponsored by Roll International Corp., the makers of POM Wonderful. I'm sure they are not pleased.

It is a good case study about the problematic nature of self-medicating before the RCTs are in (in this case, ineffectual, rather than harmful). Earlier studies attempted to use PSADT prolongation as an endpoint, rather than proving a cause/effect relationship by using a placebo. Researchers at Johns Hopkins last year showed why that shouldn't be done.

By the way, the only other placebo-controlled study of pomegranate that I’m aware of, a Swiss study in men with prostate cancer (mostly who failed treatment and/or on ADT) also found no benefit to pomegranate.

BillyBob-
You seem to have missed my point, which is that all studies are not equivalent. Most studies are useful only for hypothesis generation. I have dozens of files on Vitamin D - many show a negative association, many show a positive association, and many show no association. Note that I used the word "association" and not "causation." That means that all of those studies prove nothing. They are useful only insofar as they raise questions for other studies, hopefully RCTs that can prove causation.

The SELECT study proving the deleterious effect of high levels of Vitamin E and Selenium, and the Pomegranate study I just linked, are examples of studies that provide proof rather than hypotheses. Even then, not all RCTs are equivalent - one must examine methodology closely for biases, it has to be powered to prove what it is trying to prove, and it should ideally be confirmed by other RCTs.

- Allen

Tall Allen said...
BillyBob-
You seem to have missed my point, which is that all studies are not equivalent. Most studies are useful only for hypothesis generation. I have dozens of files on Vitamin D - many show a negative association, many show a positive association, and many show no association. Note that I used the word "association" and not "causation." That means that all of those studies prove nothing. They are useful only insofar as they raise questions for other studies, hopefully RCTs that can prove causation.

The SELECT study proving the deleterious effect of high levels of Vitamin E and Selenium, and the Pomegranate study I just linked, are examples of studies that provide proof rather than hypotheses. Even then, not all RCTs are equivalent - one must examine methodology closely for biases, it has to be powered to prove what it is trying to prove, and it should ideally be confirmed by other RCTs.

- Allen

I did not miss your point because I did not see your post before I posted again. However, you might be missing mine. My point is that studies that don't show good- or which are even negative- are routinely broadcast. And these are not always RCT.

Like the study in the current thread about vitamins causing cancer, from the CDS news. For example, it says: "Dr. Tim Byers, director for cancer prevention and control at the University of Colorado Cancer Center, conducted a meta-analysis of two decades worth of research -- 12 trials that involved more than 300,000 people -- and found a number of supplements actually made a person much more likely to develop certain types of cancer. ". Is that an RCT?

"Byers began his investigation on the association between supplements and cancer risk 20 years ago. He and many other researchers observed that people who ate more fruits and vegetables cut their risk for cancer. ". RCT?

"Through his analysis, Byers found that people who took high doses beta carotene supplements had an increased risk for lung cancer. Selenium supplements were associated with skin cancer. Men who took vitamin E had an elevated risk for prostate cancer. Folic acid, a B vitamin, taken in excess could lead to an increased risk for colon cancer.". Is he basing this on RCTs? Maybe he is, I don't know. But whether he is or not, this stuff always seems to make the headlines. And if so, people should be dropping like flies considering how many vitamins they swallow, and don't forget herbs and minerals.

RCT? I have not seen this reported on any network news yet. Like I said, it is common to hear of any negative reports. Sorry, I have linked to this previously but- including another study by these folks in SC where repeat Bx's were improved after 1 year of Vitamin D(only 60 days this time). I am linking to it again to ask why I don't hear these things on the news? You can count on it that if the tumors were unchanged or worse, I would have heard about it, don't Y'all think?

Anyway, I find this interesting, take it FWIW if anything:
www.acs.org/content/acs/en/pressroom/newsreleases/2015/march/vitamin-d-may-keep-low-grade-prostate-cancer-from-becoming-aggressive.html

Somebody said...
DENVER, March 22, 2015 Taking vitamin D supplements could slow or even reverse the progression of less aggressive, or low-grade, prostate tumors without the need for surgery or radiation, a scientist will report today...........................................However, knowing that they have even low-grade prostate cancer can cause patients and their families excessive anxiety, which prompts some of the men to undergo an elective prostatectomy, despite the risk of complications such as infection, urinary incontinence and erectile dysfunction. But a man must wait 60 days from the time of his biopsy before he can undergo a prostatectomy, so that inflammation from the biopsy can subside.

Hollis wondered if giving these men vitamin D supplements during the 60-day waiting period would affect their prostate cancer. His previous research had shown that when men with low-grade prostate cancer took vitamin D supplements for a year, 55 percent of them showed decreased Gleason scores or even complete disappearance of their tumors compared to their biopsies a year before (J. Clin. Endocrinol. Metab., 2012, DOI: 10.1210/jc.2012-1451).

In a new randomized, controlled clinical trial, his team assigned 37 men undergoing elective prostatectomies either to a group that received 4,000 U of vitamin D per day, or to a placebo group that didn't receive vitamin D. The men's prostate glands were removed and examined 60 days later.

Preliminary results from this study indicate that many of the men who received vitamin D showed improvements in their prostate tumors, whereas the tumors in the placebo group either stayed the same or got worse. Also, vitamin D caused dramatic changes in the expression levels of many cell lipids and proteins, particularly those involved in inflammation. "Cancer is associated with inflammation, especially in the prostate gland," says Hollis. "Vitamin D is really fighting this inflammation within the gland."

The protein most strongly induced by vitamin D was one called growth differentiation factor 15 (GDF15). Previous studies by other groups showed that GDF15 dials down inflammation, and many aggressive prostate cancers make little or no GDF15.

The new research suggests that vitamin D supplementation may improve low-grade prostate cancers by reducing inflammation, perhaps lessening the need for eventual surgery or radiation treatment. "We don't know yet whether vitamin D treats or prevents prostate cancer," says Hollis. "At the minimum, what it may do is keep lower-grade prostate cancers from going ballistic."

Hollis notes that the dosage of vitamin D administered in the study , 4,000 U , is well below the 10,000-20,000 U that the human body can make from daily sun exposure. "We're treating these guys with normal body levels of vitamin D," he says. "We haven't even moved into the pharmacological levels yet."

The researchers acknowledge funding from Gateway for Cancer Research, the Department of Veterans Affairs, National Institutes of Health and South Carolina Clinical and Translational Research Institute.

Post Edited (BillyBob@388) : 4/23/2015 3:05:00 PM (GMT-6)

Tall Allen said...
I find the opposite of your assertion to be true - media, and particularly media personalities like Dr. Oz, routinely tout miraculous cures based on junk medicine. .....

I am only talking about what is reported in the news and network news programs, not what is done by various TV or internet personalities. I'm pretty sure I see a lot more of the negative reported. I certainly have not seen reported anything I have posted here.

PDA,

I think the MnSOD AA genotype subanalysis was a Hail Mary play. This is probably a very rare genotype and it is more than likely that if they had tested other antioxidants, soy isoflavones, smoking cessation, or even just exercise, they may have had similar findings. Pantuck's lab has been trying to prove this since 2006, and when POM Wonderful tried to make claims about their pomegranate juice, they were challenged to come up with a placebo-controlled trial. This is the result, unfortunately for them. I had always wondered why they didn't have placebo controls in their earlier studies -- it would have been so easy.

Those were not all controlled studies of pomegranate. When you used the word "placebo" in the search, it brought up abstracts where they made statements like "placebo-controlled studies are warranted." When you actually look at the studies it brings up, one had no placebo, one was randomized to two dose levels only, one (in two publications) concludes "Our primary endpoint in this modest-sized short-term trial was negative.", one was a test of Pomi-T with multiple ingredients (I would guess the broccoli is the good stuff), and the last one was the Swiss RCT I referenced that also showed no benefit.

Everything seems to cure the darn mice!

- Allen

BillyBob, I think the reason there are so few positive results reported has two parts:

One part is that in reality, the most common answer to scientific inquiry is "no".

The other is that the popular press is in the business of selling magazines and newspapers, and trumpeting headlines that scream bad news sell better. The bigger the bad news, the better. Good news doesn't sell.

Tudpock18 said...

compiler said...


Maybe we see so many negative articles because most of the stuff doesn't work??? We wish it did.

Mel

...wins my award for quote of the day.

Jim

Well, possibly, except for the fact of the studies I have linked to, which are NOT usually reported, and many others, which just as well show a positive effect for whatever substance as do many of the other studies show negative. For instance, the study I link to that shows a linear decrease in G8-10s with increasing blood levels of D, and a hazard ratio reduction to 0.4, and the one in which the path reports were improved with just 2 months of only 4000 IU prior to surgery. Not positive about that last one yet as the only place I can find it is at that one link. But I did find this earlier by the same folks:
www.ncbi.nlm.nih.gov/pubmed/22508710

Somebody said...
Abstract

Send to:
J Clin Endocrinol Metab. 2012 Jul;97(7):2315-24. doi: 10.1210/jc.2012-1451. Epub 2012 Apr 16.
Vitamin D3 supplementation at 4000 international units per day for one year results in a decrease of positive cores at repeat biopsy in subjects with low-risk prostate cancer under active surveillance.
Marshall DT1, Savage SJ, Garrett-Mayer E, Keane TE, Hollis BW, Horst RL, Ambrose LH, Kindy MS, Gattoni-Celli S.
Author information
Abstract
CONTEXT:

We wanted to investigate vitamin D in low-risk prostate cancer.
OBJECTIVES:

The objective of the study was to determine whether vitamin D(3) supplementation at 4000 IU/d for 1 yr is safe and would result in a decrease in serum levels of prostate-specific antigen (PSA) or in the rate of progression.
DESIGN:

In this open-label clinical trial (Investigational New Drug 77,839), subjects were followed up until repeat biopsy.
SETTING:

All subjects were enrolled through the Medical University of South Carolina and the Ralph H. Johnson Veterans Affairs Medical Center, both in Charleston, SC.
PATIENTS AND OTHER PARTICIPANTS:

All subjects had a diagnosis of low-risk prostate cancer. Fifty-two subjects were enrolled in the study, 48 completed 1 yr of supplementation, and 44 could be analyzed for both safety and efficacy objectives.
INTERVENTION:

The intervention included vitamin D(3) soft gels (4000 IU).
MAIN OUTCOME MEASURES:

Adverse events were monitored throughout the study. PSA serum levels were measured at entry and every 2 months for 1 yr. Biopsy procedures were performed before enrollment (for eligibility) and after 1 yr of supplementation.
RESULTS:
No adverse events associated with vitamin D(3) supplementation were observed. No significant changes in PSA levels were observed. However, 24 of 44 subjects (55%) showed a decrease in the number of positive cores or decrease in Gleason score; five subjects (11%) showed no change; 15 subjects (34%) showed an increase in the number of positive cores or Gleason score.
CONCLUSION:
Patients with low-risk prostate cancer under active surveillance may benefit from vitamin D(3) supplementation at 4000 IU/d.

I have not seen any of these on network news, have Y'all? But I can nearly guarantee that if the results had shown zero positive results or heaven forbid actually shown a hint of harm, I would have seen it on both network news and it would have shown up on my ATT home page which scrolls Yahoo News.

Also re: the above study, more details: www.ncbi.nlm.nih.gov/pmc/articles/PMC3387395/

Somebody said...
This clinical trial was approved by the Institutional Review Board of the Medical University of South Carolina (MUSC) and the Veterans Affairs Medical Center (www.ClinicalTrials.gov Identifier: NCT01045109).
Objectives

The objectives of this study were to determine whether vitamin D3 (4000 IU/d for 1 yr) would be safe and result in a measurable decrease of serum PSA levels in a significant number of enrolled subjects and be associated with a stabilization or improvement of their disease assessed through histological examination of repeat biopsy specimens (Gleason score and number of positive cores), obtained at the end of the study as part of the standard medical care for active surveillance.
Study medication
Food and Drug Administration Investigational New Drug no. 77,839 was granted for clinical studies designed to assess the effect of vitamin D3 (4000 IU/d for 1 yr) on subjects with early-stage prostate cancer. The vitamin D3 (cholecalciferol) was manufactured by J. R. Carlson Laboratories, Inc. (Arlington Heights, IL)............ Clinical trial study design

The open-label study enrolled 52 eligible subjects. Forty-eight subjects completed the study and were included in the safety analysis; these subjects had complete PSA laboratory results for inclusion in the evaluation of changes in PSA. Forty-four subjects had both baseline and repeat biopsy (as part of their standard of care) to compare the number of positive cores and Gleason score with baseline, after completing vitamin D3 supplementation..................
Historical control subjects
From an institutional (MUSC) database of more than 700 patients diagnosed with prostate cancer within the last 5 yr, we identified 19 control subjects who were under active surveillance, underwent repeat biopsies, and met all eligibility criteria of the open-label clinical trial, except that they received no vitamin D3 supplementation. We selected only patients who had their follow-up biopsy at 10 months or later after their initial positive biopsy to ensure comparability with the timing of the follow-up visit of the patients in the open-label trial. All subjects who met eligibility criteria were included. From these control subjects, we abstracted information on their serum PSA levels and assessment of tissue biopsy specimens.

By these criteria, 34% of these subjects progressed (Fig. 2A), defined as an increase in the number of positive cores or in Gleason score; one of the subjects progressed due to an increase in Gleason score (from 6 to 8 in one core), despite a decrease in the number of positive cores (from five to two), and was classified as having had a progression. Five subjects (11%) showed no change. However, more than half of the subjects (55%) showed improvement (Fig. 2B), defined as a decrease in positive cores and no increase in Gleason score at repeat biopsy.....................
Using the same criteria, 63% of the subjects in the control group progressed (because of an increase in the number of positive cores or in Gleason score), compared with 34% in the supplementation group (P = 0.05), as seen in Fig. 3A. Furthermore, in the historical control group, four patients (21%) had improvements in biopsy results

So here it is yet once again. In this case people treated with a measly 4000 IU for only one year while on AS had 34% progress while 63% in the control group progressed. 55% in the Vit D group actually showed improvement, compared to 21 % in the control group! 55% vs 21%! # 24 to 4! Come on! Is this not worthy of reporting to counter at least some of the negative reports? Would any of us know of this without research to dig it up? But I will bet you $1000 bucks that if it had shown the results reversed, with the Vit D group being worse, it would have been headline news.

OK, I know, this is not quite up to the standard of a large scale, RCT where live patients are in the control group getting fake Vit D as placebo. And Allen will no doubt say "proves nothing". But also like- I think- Allen said, we are unlikely to ever see those big RCT studies for a variety of reasons. But all of these studies from all of these different universities and med centers seem to be very promising to me, and are just as good as the studies that show less promising results and make the headlines.

I have not seen negative evidence that looks as strong, to me, as many of these positive studies. There should be a study out there where one group is given 4000+ Vit D, and a historical control group gets zero, and the control group has 30% get worse and 55% get better(OK that won't happen) while the Vit D group has 66% get worse and 19% get better. Is that study out there?

BTW, did any of you notice the humorous line from above? Food and Drug Administration Investigational New Drug no. 77,839 was granted Just like Vit C:K 100:1(Apatone), somebody wants to get this declared a prescription only FDA approved drug at $50 a pill!

EDIT: AHHHHHHH! I can not get ris of thre BOLD of that entire last section! Sorry, only a couple of lines are supposed to be bold. Edit #2: OK, maybe I fixed it.

Post Edited (BillyBob@388) : 4/23/2015 8:45:48 PM (GMT-6)

I'm not sure what I'm trying to say below, just working out ideas based on this interesting thread, so please bear with me :)

Just to keep things in perspective, it is very true that cancer in humans poses complexities that are currently at the threshold of scientific comprehension. Even evidence-based medications that are accepted after Phase III trials to "work" for PC, don't really "work" when compared to other medications treating simpler conditions.

Tylenol and Advil have efficacy rates far, far superior to Zytiga, in their own areas of deployment (i.e. when treating fever due to the a sever cold), yet both classes of medications are deemed to be "effective" in humans.

WIth Zytiga's response rate being around 50% and with Taxotere hovering around 35%, are we justified in accepting those Phase III results as evidence-based science? What should be an appropriate threshold for labelling a drug to be medially effective? Would we consider a computer that has a failure rate at 65% during its first boot-up an example of a successfully functioning computer? Or, if Tylenol failed to lower the temperature in half the people that took it, would that be considered an effective medication?

I realize that treating cancer is much more complex than tackling the common cold symptoms, and given the dire nature of cancer it is very logical and rational to accept any medication which shows any demonstrated effectiveness in a subground of patients. But if I were taking a drug that had a demonstrated efficacy in ~35% of the people taking it at any given time, I think I'd be taking my pomegranate supplements, along with my metformin as well. Since they don't do harm (as far as we know), and if they do show some metabolic activity (as is the case with Metformin), then in absolute terms, I lose nothing, given the less-than-exciting statistics offered me by the evidence-based Taxotere.

As I read through various recent papers on cancer research, more and more scientists are talking about combination therapies, combining different agents to achieve more lasting remissions. The last one is a recent paper on melanoma. Yervoy alone was pathetically ineffective, <10% efficacy, however when it was taken together with another drug (which had different mechanism of action), the results were dramatically exciting. Prominent PC oncologists like F. Strum, Drs. Lam and Myers, and others have been harping for years about combination therapies in PC. So, again, we have these studies which test supplements, Metformin, etc. as single agents, when even top-of-the-line immunotherapies like Yervoy show little success as mono-therapies in cancer.

If one takes 4 medications, all acting along different mechanisms, each with low (or even non-existent) rates of activity, isn’t it reasonable to expect more effective outcomes, than throwing individual drugs one at a time?