#21

@RapAdmin How much Astaxanthin do you currently take and where do you buy it from? I still am taking 10 mg NOW brand daily. I’d like more if I could find a bulk source.

#22

This is a good read about prostate cancer prevention;

Prostate Cancer Prevention: What Can Be Done to Prevent Prostate Cancer & Risk Factors - Cleveland OH | University Hospitals.

Personnaly because I am under 50 years old and I get my PSA checked every 4 months, I don’t take a 5-AR blocker, even though I am on TRT. But if I would see a significant rise of my PSA levels that’s not caused by an infection , I would probably start taking a low dose of dutasteride

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#23

Dutasteride capsules cannot be split though?

#24

@RapAdmin This paper is magnificent. Thanks.

Everyone else:
Anyone interested in prostate health should read this…get to the list of well known plant compounds (polyphenols) that support prostate health. Eat a diverse plant based diet or find supplements.

I’m on this as I am looking to avoid the harsh chemicals for as long as I can.

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#25

If supplements really worked that well there’d be no need for medication in the first place. As long as the “Harsh chemicals” don’t affect all-cause mortality and you’re not part of the small minority who get side effects from dutasteride/finasteride/tamsulosin/tadalafil/etc., I don’t see why you shouldn’t take them.

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#26

Correct, on a podcast I heared that you can start with 0,5mg every 2 weeks as a starting dose, because of the very long half life (4-5 weeks…)

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#27

The lowest dose that supposedly works for hairloss is 0.5mg once a week. I don’t know if taking it once every two weeks suppressed enough DHT in the prostate’s tisue.

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#28

Aspirin and other nsa seem to have a profound impact on prostate health. It was covered a bit in the article above.

Another citation… shows the following conclusion “After adjustment for age, NSAID use was significantly inversely associated with onset of moderate/severe urinary symptoms.”

I had dropped low dose aspirin given recent negative findings, but I am back on it given the above sources.

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#29

@Bettywhitetest Thanks. I had stopped aspirin some time ago but now it’s back.

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#30

Interesting point, thank you for sharing!

Study reported that daily aspirin consumption led to a long-term reduction of 29% in PCa risk compared to non-consumers.

In the same time: several aspects render aspirin a double-edged sword for preventative measures:

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#31

The Aspree study (see below) influenced my recent thinking to drop aspirin at my age (69). But counter to this study, it seems aspirin can be protective against colon cancer if taken before 65. So I thought at my age it wise to give it up as I already received the benefit. But the studies given above make aspirin (and other nsa) as almost miracle drugs against prostate cancer and prostate growth. It seems to me that this boils down to aspirin effectively combating low grade inflammation - inflammation being the main contributor to the aging prostate problem.

The ASPREE trial enrolled older adults (70 and older; African-Americans and Hispanics 65 and older). Both trials showed that low dose aspirin (at 100 milligrams per day) did not prevent subsequent heart attacks or strokes over a period of approximately five years. However, aspirin did increase the risk for major bleeding. Furthermore, in the ASPREE trial, there were more deaths attributed to aspirin use. Michos finds the new results “alarming” and says that most adults without known heart disease should not take aspirin routinely for heart attack and stroke prevention.

The risks you cite give pause, particularly the McNeil 2018 paper about bleeding. But I am wondering if the risk can be mitigated with enteric coating, taking aspirin with food, etc. Right now I am thinking that combating low grade inflammation is of utmost importance at my age, and I am back on the aspirin train. I will look into risk management with its use though.

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#32

I find piperlongumine very interesting.I have read quite a lot of studies that show fascinating results. Piperlongumine seems to be bioavailable and effective at rather low dosing. But should not be combined with antioxidants.

" Metastatic castration-resistant prostate cancer (CRPC) is the leading cause of death among men diagnosed with prostate cancer… The results showed that PL exhibited stronger anticancer activity against CRPC compared to that of taxol, cisplatin (DDP), doxorubicin (Dox), or 5-Fluorouracil (5-FU), with fewer side effects in normal cells. Importantly, PL treatment significantly decreased cell adhesion to the extracellular matrix and inhibited the migration of CRPC cells"

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#33

Thanks for posting this article!

The main question for me revolves around making the information about polyphenols and their role in inflammation actionable, particularly in the context of cancer prevention. Polyphenols, known for their antioxidant and anti-inflammatory properties, are considered beneficial in this regard. However, determining the appropriate amount of polyphenols or supplements to take is complex.

For example, engaging the NRF2-ARE pathway is considered today crucial for cancer prevention. This pathway plays a key role in cellular defense against oxidative stress. However, as highlighted in the article from PubMed (The Effects of Dietary Supplements that Overactivate the Nrf2/ARE System - PubMed), overactivation or constant activation of the Nrf2/ARE antioxidant system can potentially contribute to various diseases, including certain types of cancer, autoimmune, neurodegenerative, and cardiovascular diseases. This paradox indicates that while activation of this pathway can be beneficial, its overstimulation can be detrimental.

Given this complexity, the idea of cycling the intake of polyphenols or related NRF2-ARE supplements might be feasible. This could mean limiting intake to certain days of the week, such as 2 days a week, or perhaps on a weekly cycle. However, there isn’t a definitive answer yet on the optimal cycling pattern today. :frowning:

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#34

Good find.
Being as old as I am this might be a supplement to consider.
What is the effective dosage?
Also, you should take NAC with PL.

One of the papers you reference says: PL “induced cell death in a concentration-dependent manner.”

One of the papers says: “Cells were treated with increasing concentrations of PL alone or concomitantly with a well-established antioxidant, N-Acetyl-L-Cysteine (NAC). Expectedly, the increase in ROS production in PL-treated cells was observed in a dose-dependent manner and was blocked by the addition of NAC to the cellular medium”

It looks like Piperlongumine raises ROS levels which is not a good thing.
“Indeed, the addition of PL causes a marked rise in ROS levels in LNCaP cells”

You should take NAC with PL to prevent the rise of ROS.

“Tumor cells are characterized by a high level of ROS. ROS overproduction can result from changes in many processes, such as oxidative phosphorylation (OXPHOS), transition metal ions, oxidase activity, protein folding, thymidine, and polyamine catabolism”

“N-acetyl-L-cysteine (NAC) is an anti-oxidant known to lower cellular ROS levels. Co-administration of NAC and PL reversed PL-mediated increase of ROS”

1 Like
#35

My father died of metastatic PCA at age 63 in 1984. I was 35 at the time and was shocked as I had always been told it was a disease you die with not from. That lead to a 10 year search at a local medical library as to what causes aggressive PCA in some men whereas most have the benign form that is not life threatening. This was in the mid-1980’s before there was an Internet.

That reseach lead to finding those men with the lowest Free Testosterone levels were the ones at highest risk of metastatic PCA along with a lack of dietary zinc and gamma tocopherols by 1995. At that point I was feeling a significant loss of strength in my weight training workouts and also of loss libido and no morning wood.

A measurement of my Free T level at that time was 1.0! I then started on a program of T. Cypionate injections, 200 mg/wk which I have maintained for the last 29 years continuously along with 50 mg of a chelated zinc and a mixed tocopherol supplement. My Free T level has remained in the 20 - 40 range since then and my most recent PSA was 2.5 at age 74.

In the bioidentical hormone program I have been the Clinical Coordinater of, and the Cardiac Rehab program I have directed over the last 23 years I have several hunded men on TRT. Only one man out of hundreds has developed PCA and it is the benign form as he has continued on T therapy with a PSA of 8.0 which has not changed in several years.

I believe PCA can be prevented (and possibly/probably arrested) with TRT, zinc, gamma tocopherol and other supplements. I am an Omnivore although I gravitate towards more meat and less vege’s and fruits than most. I do take a lot of other supplements ( Vits C, D3, fish oil, DHEA, a high potency MVM, Melatonin with L-threanine, Glucosamine, hydrolyzed whey protein, creatine, Lugol’s Solution, Magnesium Glycinate and a beet root extract Nitric Oxide supplement made by Berkeley Life.

I take 25 mcg of T3 for energy and hair growth as well as a low dose of generic Tadafil twice daily for additional BP lowering and arterial wall protection effects. Recently I have added Vitamin B17 to my cancer prevention protocol.

A large randomized trial of Finasteride published several years ago found a bit less PCA in the treatment group, however there were more cases of metastatic PCA compared to the placebo. It was bust in other words and attackinig DHT is a failed approach IMHO. I tried it back when it first came out in the 90’s and saw immediate negative erection effects causing its abandonment way back then.

Randy Ice PT, CCS

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#36

Observational studies are not to be trusted as reverse causality or other factors can’t be accounted for.

A large randomized trial of Finasteride published several years ago found a bit less PCA in the treatment group, however there were more cases of metastatic PCA compared to the placebo. It was bust in other words and attackinig DHT is a failed approach IMHO.

Later studies didn’t confirm that effect.

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#37

No, I don’t think so - for what its worth, I’ve asked my doctor about this, and he said its a property of the aspirin in your system, not the stomach.

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#38

ROS is a cellular signal. Antioxidants are supposed to reduce the effect of exercise. At least on elite level. Some anticancer treatments work through increased ROS. ROS start processes that lead to apoptosis in cancerous cells.

Adaptation to cellular stress is not a vital function of normal cells but is required of cancer cells, and as such might be a sensible target in cancer therapy. Piperlongumine is a naturally occurring small molecule selectively toxic to cancer cells. This study assesses the cytotoxicity of piperlongumine and its combination with cisplatin in head-and-neck cancer (HNC) cells in vitro and in vivo. The effect of piperlongumine, alone and in combination with cisplatin, was assessed in human HNC cells and normal cells by measuring growth, death, cell cycle progression, reactive oxygen species (ROS) production, and protein expression, and in tumor xenograft mouse models.

Piperlongumine killed HNC cells regardless of p53 mutational status but spared normal cells. It increased ROS accumulation in HNC cells, an effect that can be blocked by the antioxidant N-acetyl-L-cysteine. Piperlongumine induced selective cell death in HNC cells by targeting the stress response to ROS, leading to the induction of death pathways involving JNK and PARP. Piperlongumine increased cisplatin-induced cytotoxicity in HNC cells in a synergistic manner in vitro and in vivo. Piperlongumine might be a promising small molecule with which to selectively kill HNC cells and increase cisplatin antitumor activity by targeting the oxidative stress response

And similar effects are seen here. I don’t take NAC with Piperlongumine or senolytic protocolls aiming at bringing senescent cells into a cascade of events leading them to apoptosis. .

Piperlongumine (PL), a natural alkaloid from Piper longum L., possesses the highly selective and effective anticancer property. However, the effect of PL on ovarian cancer cells is still unknown. In this study, we firstly demonstrate that PL selectively inhibited cell growth of human ovarian cancer cells. Furthermore, PL notably induced cell apoptosis, G2/M phase arrest, and accumulation of the intracellular reactive oxidative species (ROS) in a dose- and time-dependent manner. Pretreatment with antioxidant N-acety-L-cysteine could totally reverse the PL-induced ROS accumulation and cell apoptosis. In addition, low dose of PL/cisplatin or paclitaxel combination therapies had a synergistic antigrowth effect on human ovarian cancer cells. Collectively, our study provides new therapeutic potential of PL on human ovarian cancer.

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#39

@BikeIce, thank you for your detailed and informative response regarding the relationship between circulating free testosterone (cFT) and prostate cancer (PC).

As referenced in a study from the National Institutes of Health (NIH) here, a γ-tocopherol-rich mixture of tocopherols has been shown to inhibit tumorigenesis in various cancers, including prostate cancer, in animal models. This suggests potential avenues for cancer prevention that may intersect with hormonal pathways. Since today it is on my watchlist: thank you!

The topic of free testosterone’s role in cancer risk remains somewhat controversial and complex. For instance, one NIH study found here indicates that men with low circulating free testosterone may have a lower overall risk of prostate cancer, which could be attributed to a direct biological effect or detection bias.

In the same time, research presented at the American Society of Clinical Oncology available here suggests that biochemically low cFT might be a risk factor for high-grade and high-stage cancer.

I respect the early findings you referenced → food for thoughts!

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#40

The following research is something I can not properly digest. I wonder about the net effect of high doses of glycine is, on the prostate? Of course the cancer prone mice were fed glycine for a long time, but mice or not men, and they showed improved lifespan, but still?

"Glycine restriction and supplement
Although glycine might be important for rapid cancer cell proliferation by supporting de novo purine nucleotide biosynthesis [6], glycine restriction alone didn’t have the same detrimental effect on cancer cells as serine starvation, which might be explained by the inter-conversion between serine and glycine in one-carbon metabolism by serine hydroxymethyl transferase (SHMT) [7, 16, 17], especially the mitochondrial glycine synthesis enzyme SHMT2 [6]. Interestingly, the consumption and release profiles of the NCI-60 cancer cell lines demonstrated that glycine among AAs had the most heterogeneous pattern either consumed or released, whereas serine showed relatively homogenous consumption [6]. Beyond the potential role of glycine restriction in blocking the rapid growth of certain cancer cells, the dietary supplement of glycine was also reported to inhibit the growth of certain types of tumors, such as liver tumors [29] and melanoma tumors [30]. Therefore, the heterogeneous metabolism of glycine in cancer cells might account for its paradoxical effects."

“After correcting for multiple testing, two lysophosphatidylcholines (LPCs) were positively associated with risk of overall prostate cancer (all ages and in older subjects). The strongest association was for LPC C17:0 in older subjects (OR = 2.08; 95% CI 1.45–2.98; p < 0.0001, significant also after the Bonferroni correction). Observed associations with risk of overall prostate cancer in younger subjects were positive for glycine and inverse for pyruvate.”

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