Diabetes drugs fuel cancer spread....

Metformin is chemically quite different from the diabetes drugs studied here (on 9 mice--not a robust finding).

I wish otherwise intelligent science writers would stop extrapolating out from specific results from specific studies to generalities: "All antioxidants bad!" Not very responsible or helpful, or scientific.

my oncologist told me if everything they found worked or didn't work in mice worked for humans, there would be a cure for cancer. I don't put much stock in things until the testing has been done on human bodies

Amen as to mouse studies vs. double-blind trials or even retrospective human studies. Remember the panic over cyclamates, causing Sucaryl to be reformulated? A few rats sated with cyclamate got bladder tumors, but not so humans (to the point where Canada quietly began allowing sales of cyclamate-Sucaryl). And much later, the studies in which thin mice injected with the hormone leptin stayed thin, fat mice injected with it got thin, and mice bred with defective production of leptin got massively obese? When obese humans were given leptin......nothing happened. Mice and rats are used as test subjects for practical reasons (they’re mammals, cheap, have shorter lifespans and thus produce faster results, don’t require scientists using them to hold medical licenses. don’t arouse the outrage triggered by using larger mammals that are viewed as more sentient, and don’t raise complex moral and ethical issues that testing on humans does). But not all mammals are alike in all respects.

I stopped taking antioxidant supplements during radiation--I don’t even take Vit. C for colds (nor echinacea, which can have estrogenic effects)--but I do take a gummy-vitamin, which has levels of A, C, and E too low to affect tumor cell proliferation. And metformin is a different type of non-insulin anti-diabetic, which may even prevent recurrence as well as bisphosphonates or biological anti-osteoporosis drugs do.

There is a genetic disease that runs in my husband's family. 20 years ago we were told researchers were a few years away from a cure. Two decades later not a single substance that worked in the mice has been effective in humans, and there have been many. For that reason I am also very skeptical of mouse studies, but here's the dilemma: once something has been found to be harmful in mice, it becomes understandably unethical to test it in humans so we never get the proof that it does or doesn't do harm. They are not going to do a follow up study in cancer patients based on these results so we will never know. Doctors will recommend against a drug or supplement based on a mouse study, but will rarely recommend for something just because it worked in mice. For that reason we're told to avoid just about everything, and that frustrates me because I believe there is more I can be doing to reduce risk of recurrence, but I'll never know for sure what it is.

Damned if you do, damned if you don't. This kind of research is apparently not so new. Here's a review from 2008:

Dual Roles of Nrf2 in Cancer

Abstract

"In response to oxidative stress, the transcription factor NF-E2-related factor 2 (Nrf2) controls the fate of cells through transcriptional upregulation of antioxidant response element (ARE)-bearing genes, including those encoding endogenous antioxidants, phase II detoxifying enzymes, and transporters. Expression of the Nrf2-dependent proteins is critical for ameliorating or eliminating toxicants/carcinogens to maintain cellular redox homeostasis. As a result, activation of the Nrf2 pathway, by naturally-occurring compounds or synthetic chemicals at sub-toxic doses, confers protection against subsequent toxic/carcinogenic exposure. Thus, the use of dietary compounds or synthetic chemicals to boost the Nrf2-dependent adaptive response to counteract environmental insults has emerged to be a promising strategy for cancer prevention. Interestingly, recent emerging data has revealed the "dark" side of Nrf2. Nrf2 and its downstream genes are overexpressed in many cancer cell lines and human cancer tissues, giving cancer cells an advantage for survival and growth. Furthermore, Nrf2 is upregulated in resistant cancer cells and is thought to be responsible for acquired chemoresistance. Therefore, it may be necessary to inhibit the Nrf2 pathway during chemotherapy. This review is primarily focused on the role of Nrf2 in cancer, with emphasis on the recent findings indicating the cancer promoting function of Nrf2 and its role in acquired chemoresistance."

And then later, a limited list of dietary Nrf2 inducers, otherwise considered chemopreventive unless, as "new emerging data" suggests, Nrf2 is overexpressed by a particular cancer:

"Examples of potent Nrf2 inducers from plants include sulforaphane (cruciferous vegetables) [62], curcumin (a widely used spice) [70–72], epigallocatechin-3-gallate (EGCG) (green tea) [73, 74], resveratrol (grapes) [75, 76], caffeic acid phenethyl ester (conifer trees) [70], wasabi (Japanese horseradish) [77], cafestol and kahweol (coffee) [78, 79], cinnamonyl-based compounds (cinnamon) [80], zerumbone (ginger) [81], garlic organosulfur compounds (garlic) [82, 83], lycopene (tomato) [84], carnosol (rosemany) [85, 86], and avicins (Bentham plant) [87].... This list of Nrf2 inducing chemopreventive compounds and synthetic chemicals is continuously growing."

If the cancer doesn't kill me, eating, drinking and breathing will. I had very expensive gene testing done on my cancer, but they didn't even look at Nrf2. On one hand it sounds like it would be good to know, but on the other hand what are you going to do about it? If you gave up everything that could induce Nrf2 you would end up with other health problems, maybe even another type of cancer.

Kayb - I don't think I'd heard that about radiation possibly leading to diabetes. When you have time could you elaborate on that? I did have RT (7 weeks) so try to stay abreast of such issues. Thanks!

It's disconcerting to think that ALA could possibly support metastasis. I've been taking it on the recommendation of my survivorship nurse practitioner and just bought another bottle of it but will have to delve into it further before continuing on it.

Fallleaves, I wish it was as simple as adding vitamin C for me. I have the tamoxifen to contend with, and there are so many substances that can possibly interfere with tamoxifen that it boggles the mind. Most of the problems come from interference with the metabolism of tam in the liver, but in the case of vitamin C it might block the cytotoxic and apoptotic effects of tam. I try to get plenty of C in my diet, but maybe I will add a low dose ascorbic acid supplement.

I'm a healthy person except for the cancer, but I do have a few issues that have been identified by my naturopath that could put me at higher risk of recurrence. Since I have been on the tamoxifen my cortisol, ceruloplasmin and copper levels have skyrocketed, which is maybe caused by the tam, maybe not. Cortisol is a stress hormone and high ceruloplasmin/copper contributes to angiogenesis.

I have to deal with these problems to reduce my risk, but almost everything I need to take for that purpose seems to either interfere with the tam, or increase risk of some other problem. I do a lot of research and weighing of risks vs. benefits. I stopped taking most supplements, but there are some that I decided are worth the risk. Ashwagandha for example. I need to reduce the cortisol, and ashwagandha was the only thing known to do that without interfering with the tam. But it's an anti-oxidant, and as I found out yesterday, also a potent nrf2 inducer. I'm not going to stop taking it because I think reducing the effect of stress on my body is more important than any possible effect on nrf2 at this time. However, I will continue to avoid huge doses. Time will tell if the lower-end dose I'm on is enough to lower the cortisol.

Kayb, Fallleaves and Solfeo, thank you for the additional materials and your comments. It certainly is a lot to sort out and be aware of, as we all know.

I believe that RT was a useful part of my treatment and I don't regret it but will be aware of the possible link to diabetes. As for ALA, well, who knows!

Curcumin is one of the things that may interfere with tamoxifen. I used to take it (didn't prevent my cancer either after over a decade on it), and want to take it again, but I've been counting the days until I can switch to an aromatase inhibitor. Unfortunately I just started my damn period a few days ago after 7 months without it, so I have to start the countdown to menopause all over again. Piperine, the black pepper extract that has to be taken with curcumin for absorption, might also interfere with tam. Women on these boards have received conflicting info from their doctors. Some more knowledgeable MOs say no because it could interfere, but there are some whose doctors are allowing the combination of tam and curcumin. As far as I have been able to tell none of them who are giving it the OK are taking the problem with tamoxifen and CYP450 enzymes into consideration, because a lot of doctors don't know much about it. I've tried to warn people but no one is going to listen to me over their doctor. I'm not willing to take the chance since I didn't have chemo or rads and tam is all I have.

My copper went up 70% over 6 months, and was quite a bit higher than the reference range. A spike in copper level has been seen in the year before recurrence so we're using the big guns. I'm taking tetrathiomolybdate, which is a strong copper chelator currently under study in women with a high risk of recurrence or Stage IV disease. It is expensive and insurance doesn't cover it, but it's working. It has to be compounded at a special pharmacy.

Hi Fallleaves - I have seen that study, but it's an in vitro study that doesn't take metabolism in the human body by the liver into consideration. There was another one in rats that showed that curcumin inhibited CYP3A4 and lowered the level of tamoxifen's active metabolites:

Effects of curcumin on the pharmacokinetics of tamoxifen and its active metabolite, 4-hydroxytamoxifen, in rats: possible role of CYP3A4 and P-glycoprotein inhibition by curcumin.

I hesitate to get into a discussion about this particular science here because I have seen this study misinterpreted by others as supportive of concurrent tam/curcumin use, because it showed increased bioavailability of tamoxifen. Well that is not necessarily a good thing because that means the production of the active metabolites that actually do the job was inhibited. Of course it was a rat study so it doesn't prove anything. It's also a weak inhibitor of CYP2D6 (the really important one).

There was this one study that showed no likely interaction, but it was done with a synthetic version of curcumin and it's not clear that natural curcumin would have the same effect. Is that what you are referring to when you mentioned "analogs?"

Evaluation of liposomal curcumin cytochrome p450 metabolism.

Fallleaves, I definitely don't know (and neither does anyone else I don't think) so erring on the side of caution is exactly what I'm doing. Regarding the study on liposomal curcumin, I am not sure how much more reliable a study is in an "ex vivo model of cryopreserved human hepatocytes," than in rats, and I haven't been able to get a clear answer from anyone. I mean, at least they are human liver cells, but it's still in a lab and not in the body. Is there anything more you know about this? Still, I'm like you and once I read something negative about a supplement interaction I'm afraid to take it.

I really just want off the tamoxifen with all of its interactions that are not really clearly understood by anyone. I didn't want to do oophorectomy or ovarian suppression because I am so close to menopause, but maybe I should re-think the ovarian suppression so I can get on an AI sooner. But that opens another can of worms with trying to figure out when I'm actually in menopause.

Thanks Fallleaves. What I've noticed in my travels is that studies of most supplements never make it past the rodent stage. I'm starting to wonder why they even bother.

ChiSandy, I agree there should be more regulation of supplements, if only to ensure that they are not contaminated and contain what they say they do. Most would probably be considered "generally recognized as safe" by the FDA, since they are largely non-toxic plant compounds, but they should be comprehensively looked at for health effects beyond toxicity. You're right about the funding not being there. The National Center for Complementary and Integrative Health, which is part of the NIH, gets $124 million a year, which is not really much to study all the supplements currently being taken by Americans for a wide variety of illnesses. I've seen estimates of from 48 to 87% of breast cancer patients using supplements, so really there should be more research dollars going towards finding out which ones interfere with/enhance conventional treatment. I remember back in the early 90's an attempt in Congress to have supplements treated like drugsf, and it being blocked by Sen. Orrin Hatch from Utah (where many supplements were made, at least at that time). He's still around, so I doubt there will be any tougher standards any time soon.

I believe you, solfeo. Lots of natural remedies have antibacterial properties. Glad they worked for your family!

On the subject of antioxidants though, there have been other studies linking them with cancer. Here's one:

https://www.sciencedaily.com/releases/2015/10/1510...

"The idea that antioxidants are good for you has been so strong that there have been clinical trials done in which cancer patients were administered antioxidants," added Dr. Morrison, who is also a CPRIT Scholar in Cancer Research and a Howard Hughes Medical Institute Investigator. "Some of those trials had to be stopped because the patients getting the antioxidants were dying faster. Our data suggest the reason for this: cancer cells benefit more from antioxidants than normal cells do."

Here's a Nobel Prize winner's thoughts on the matter:

http://www.theguardian.com/society/2014/feb/28/dna...

I don't take antioxidant supplements, but do try to stuff myself with fruits and veggies, ate lots of curries when I was on an AI (but cut down on that while on Tam), drink tea and coffee. At some point I had seen studies that said antioxidant supplements blunt the beneficial effects of exercise. So I said no when my personal trainer then tried to sell me some antioxidants. I told him the body produces its own antioxidants as an adaptive response to the stress of exercise. There might be a reason to take supplements when doing intense exercise and the body can't keep up but it's hard to know when that would be. And I probably would not have been in that situation for the most part.