I leave my computer for a few hours & suddenly Bill48162 has 31 replies & Nalakrats is up to 64.
I doubt that this post will be as popular, & some will view it as a downer, but I intend it as a manifesto for the use of supplements.
When I immediately failed "curative" treatment at age 56, I assumed the worse. I thought of moving to Colorado, so that my widow would be close to our daughter & grandchildren. That idea was a downer to my wife when she figured out how I was thinking. Instead, we moved to Asheville, NC, which we both saw as a life-affirming move, as it was.
My new doctor assured me that he could keep me alive - as long as I didn't get mets - "Those folk don't do well."
The current PCa mortality rate in the U.S. is ~18% of cases. One has to be unlucky to die of it. But, of course, I did get metastatic disease, so that statistic is no longer useful to me.
In the UK, the mortality rate is ~25%. The U.S. rate looks better because of the spurious Gleason score = 3+3 cases that over-screening detects.
The US PCa mortality rate per 100,000 lives is quite good at ~20 deaths per year [2], while the UK rate is above 50 [3]. This was my first lesson. Lattitude matters. London is 51.5074° N; New York is 40.7128° N. Sunlight strength & vitamin D is important. No surprise that Medierranean countries have better stats than Nordic countries.
When I took a look at worldwide statistics over a dozen years ago, it looked as though deaths in unscreened populations were running at ~35% of cases. (I can't find a U.S. statistic for men who never had a PSA test or a DRE.) It seems that even in the most unpromising circumstances, with perhaps poor access to standard care, two-thirds of men do not die of it.
Anyway, the numbers spurred me into looking at complementary approaches. One can take an optimistic view, become a vegan, get religion & so on, but the numbers are sobering once primary reatment has failed. Something more is needed to boost the odds of survival.
Back in 2005 the conventional options were Lupron & Taxotere (FDA approved only in 2004) for when Lupron failed. But I kept reading that Lupron mostly failed within 18-24 months. Why rush into a drug that is merely palliative & with a less than impressive mean time to failure? Particularly when still in one's 50's. & when CRPC is more aggressive?
& so I have spent some time on PubMed almost every day these past 14 years.
Along the way, I discovered that the smart money was also interested in supplements. Or rather, in tweaking natural substances to be more bioavailable & more cytotoxic.
There are 259 PubMed hits for <curcumin analog>. The following is the intro to a 2017 paper [1] (You can safely skip the paragraph when you get to "1,5-Diheteroarylpenta-1,4-dienones" - I'm sure that you'll get the point.):
"Curcumin is the major chemical component of well-known turmeric (Curcuma longa) that has long been used as a yellow spicy curry ingredient and as a traditional Ayurvedic, Chinese, and Hindu medicine. Curcumin is a well-established lead compound for the development of new anti-prostate cancer agents due to its safety profiles in human and its demonstrated potential in treating prostate cancer. Several strategies have been applied to optimize curcumin in the hope of improving its potency and/or bioavailability. Chemical manipulations on curcumin have been established as a meaningful approach to the development of curcumin-based anti-prostate cancer agents with more drug-like properties. 1,5-Diheteroarylpenta-1,4-dienones, 1,7-diheteroarylhepta-1,4,6-trienones, and 1,9-diheteroarylnona-1,4,6,8-tetraenones have been identified by us as potential scaffolds for developing curcumin-based anti-prostate cancer agents because of their apparently improved potency as compared with curcumin. Among them, the 1,4,6-trienone motif was envisioned and illustrated as a good bioisostere of the keto-enol central spacer in curcumin due to the indistinguishable shape and size. Our previous study demonstrates that 1-alkyl-1H-imidazol-2-yl in compounds 2–6 and 1-alkyl-1H-benzo[d]imidazole-2-yl in compounds 7–11 are significantly beneficial to the in vitro antiproliferative potency in three prostate cancer cell models. All 1,7-diheteroaryl-1,4,6-trienones investigated in our previous study have two identical nitrogen-containing terminal aromatic rings."
Phew!
One doesn't need to read the research history for the analogs WZ35, EF24, ca27, etc. to understand that curcumin might be worth looking at.
Turmeric is not a good source of curcumin & many curcumin brands deliver less of the polyphenol than one might suppose. LongVida has been proven to cross the blood-brain barrier. That is either very scary to you or comforting, of course.
Perhaps more impressive has been the smart money effort to find a calcitriol analog (715 hits).
Calcitriol (1,25-D) is the active form of vitamin D. Calcidiol (25,D) is the inactive reservoir. Cholecalciferol is the natural supplement & it gets converted to calcidiol. There are maybe two studies that claim that PCa cells can use calcidiol directly, but the smart money is on calcitriol-like drugs.
Calcitriol can be used directly via a drip, but it can quickly raise blood calcium levels, so it is a problematic drug. Hence the search for a less calcemic solution. When I was diagnosed, less than 200 hundred analogs had been looked at. The number is now huge. But no luck so far. Even so ...
It once seemed to me that everyone with PCa was taking vitamin D & many were testing 25-D levels & aiming for 50-75 ng/mL. I never saw any discussion of 1,25-D (except as the test one should not ask for). PCa suppresses the conversion within the cancer cells. We therefore need to fool the kidneys to maintain calcitriol production. We can do that by avoiding calcium supplements, excess phosphorus/phosphates (from large portions of meat/fish, phosphates in deli meats & soft drinks) & by judicious use of fructose every day.
I seem to need 7,000 IUs cholecalciferol in an oil base to maintain 25-D above 50 ng/mL. I use fructose in my coffee.
These are just two examples of supplements with pharma back stories.
I have posted extensively on vitamins, minerals & other supplements, so I'm looking to cover them all here.
If I had low-risk PCa & had been cured, I would be far less inclined to use supplements. As an advanced PCa case, I feel that I don't have that luxury.
My doctor told me 4-5 years ago that he was sure that I would be dead by now (then). I laughed & he said "No, really." But I never expected at age 56 to reach 70, & I think that supplements must have played a role.
When the new generation of drugs came out, doctors seemed to get excited by these game changers. I remember being puzzled by Dr. Myers being enthusiatic about a drug that might be good for an extra 6-12 months.
Within the past year, I watched a panel discussion where Johann de Bono (Royal Marsden), reflecting on two drugs he had been deeply involved with - Zytiga & Xtandi - worrying that doctors were ill-prepared to manage the changes that occur in cancer that becomes resistant to those drugs.
One begins using a palliative drug when one must, but I am not eager. I am fascinated by the studies that are looking at earlier use of drug combinations, but there needs to other drugs to block the signaling pathways that PCa use for resistance, IMO.
So far, I have avoided short-term palliation. I have had ups & down in my n=1 trials, but I'm still here & I never miss my 5 am coffee pills, my breakfast pills & my bedtime pills. Nalakrats thinks I'm a cissy for skipping lunch & dinner pills.
-Patrick
[1] ncbi.nlm.nih.gov/pmc/articl...
[2] seer.cancer.gov/statfacts/h...
"The number of deaths was 19.5 per 100,000 men per year. These rates are age-adjusted and based on 2011-2015 cases and deaths."
[3] cancerresearchuk.org/health...
"Mortality rates for prostate cancer are projected to fall by 16% in the UK between 2014 and 2035, to 48 deaths per 100,000 males by 2035."
Overcoming Drug Resistance in Advanced Prostate Cancer by Drug Repurposing
