TorontoTRT
Active Member
Yup. I got the green theraband
DIM - Anti-androgen Clarification
- Thread starter TorontoTRT
- Start date
What's interesting about DIM's potential anti-androgen capabilities is that there is very little research on the topic.
However, this study is very interesting. "DIM Competes with Androgen for Binding to the AR in LNCaP Cells and in Recombinant AR Protein—Because our results strongly implicate the AR as the focus of the DIM mode of action in prostate cells, we assessed directly the ability of DIM to bind to this receptor. Our results of competitive binding assays with both the mutant AR of LNCaP cells and a wild-type recombinant human AR demonstrate that DIM, in the micro-molar concentration range, competes with labeled DHT for binding to the AR (Fig. 6). Cyproterone acetate and Casodex, two well known antiandrogens, were used as positive controls. DIM and Casodex exhibited similar binding affinity for the AR."
My takeaway from the results of the study are that DIM has the potential to compete with DHT for AR activity. So while the dosage of testosterone you take is what is going to directly affect muscle size and recovery, the level of DHT does not play a role in muscular development or recovery. The proposed idea behind DIM reduces muscle hypertrophy and recovery, speculative as it may be, does bring about cause for concern. However, it doesn't appear, from this study, that DIM's anti-androgen capabilities interfere with anything beside DHT binding at the AR, which may be a good thing for many males who suffer from acne and oily skin while on TRT.
@TorontoTRT @Gman86
However, this study is very interesting. "DIM Competes with Androgen for Binding to the AR in LNCaP Cells and in Recombinant AR Protein—Because our results strongly implicate the AR as the focus of the DIM mode of action in prostate cells, we assessed directly the ability of DIM to bind to this receptor. Our results of competitive binding assays with both the mutant AR of LNCaP cells and a wild-type recombinant human AR demonstrate that DIM, in the micro-molar concentration range, competes with labeled DHT for binding to the AR (Fig. 6). Cyproterone acetate and Casodex, two well known antiandrogens, were used as positive controls. DIM and Casodex exhibited similar binding affinity for the AR."
My takeaway from the results of the study are that DIM has the potential to compete with DHT for AR activity. So while the dosage of testosterone you take is what is going to directly affect muscle size and recovery, the level of DHT does not play a role in muscular development or recovery. The proposed idea behind DIM reduces muscle hypertrophy and recovery, speculative as it may be, does bring about cause for concern. However, it doesn't appear, from this study, that DIM's anti-androgen capabilities interfere with anything beside DHT binding at the AR, which may be a good thing for many males who suffer from acne and oily skin while on TRT.
@TorontoTRT @Gman86
So the results of the study determine that DIM competes with DHT for AR activity in LNCaP cells and in Recombinant AR Protein. The reported downstream effect on that being reduced risk of prostate cancer in men. The study does not indicate that all ARs are affected by DIM, nor does it suggest that skeletal muscle is negatively affected due to competitive binding at the AR in skeletal muscle.
When I have reviewed the small amount of research available, DIM's competitive activity has been discussed in regard to reduced risk of prostate cancer and estrogen-dependent cancers. I haven't found anything suggesting that all ARs throughout the body are affected by DIM.
I'n addition to effects on proliferation and apoptosis, DIM acts as an antiandrogen in prostate cancer cell lines. This study characterized the effects of prostatic DIM on the androgen receptor (AR) in patients with prostate cancer."
I am questioning whether DIM has specific anti-androgenic activity (specific ARs as previously mentioned) versus broad-spectrum competitive-binding at the AR.
What are your thoughts?
Vince
Super Moderator
This is one of my favorite threads. Even though I've never used DIM.
www.excelmale.com
Huge increase in libido with DIM
I started taking DIM (2 capsules a day - DIM plus from Nature’s way) and my libido went through the roof (it was already good before starting DIM). So i stopped and resumed a few times to see if it was the DIM responsible for the boost in libido and it seems like it is. So if you have your lab...
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Do you have anything tangible to go from to form a position either way or just speculation? Is there data?
I don't see anything in the available research that suggests decreased T levels, Free T, decreased muscular hypertrophy as a result, or anything resembling this. The research suggests focused anti-androgenic activity within the prostate.
So, as an example, we know that 3a-hydroxysteroid-dehydrogenase readily inactivates DHT within muscle tissue, significantly limiting DHT's effect in skeletal muscle.
What we don't know is whether or not DIM is inactivated in a similar fashion (not via the same enzyme) within muscle tissue, rendering its anti-androgenic properties ineffective. So, could DIM produce anti-androgenic effects in the prostate and other DHT-specific sites (hair, skin) yet produce little to no effect in muscle tissue? Or does DIM bind significantly to the AR in muscle tissue as it does in the prostate and negatively impact TRT outcomes?
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This study is very interesting. No human studies related to this.
onlinelibrary.wiley.com
"In conclusion, DIM (i) had side effect on some sperm characteristics, (ii) increased the MDA levels and (iii) led to histological degeneration of testicular tissues and apoptosis in a dose‐dependent manner."
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"In conclusion, DIM (i) had side effect on some sperm characteristics, (ii) increased the MDA levels and (iii) led to histological degeneration of testicular tissues and apoptosis in a dose‐dependent manner."
@Cataceous Maybe you can read this a see what you think its implications are, if any. This type of study is over my head but seems it may have some implications in this discussion.
"whereas all three decreased the 16α- and 2α-testosterone hydroxylation (DIM to 60%, CTI and BII to a mere 5% of the control cells)."
www.sciencedirect.com
academic.oup.com
"whereas all three decreased the 16α- and 2α-testosterone hydroxylation (DIM to 60%, CTI and BII to a mere 5% of the control cells)."
Acid reaction products of indole-3-carbinol and their effects on cytochrome P450 and phase II enzymes in rat and monkey hepatocytes
The effects of three acid condensation products of indole-3-carbinol (I3C), i.e. 3,3'-diindolylmethane (DIM), 5,6,11,12,17,18-hexahydrocyclonona[1,2-b…
www.sciencedirect.com
3,3′-Diindolylmethane and Genistein Decrease the Adverse Effects of Estrogen in LNCaP and PC-3 Prostate Cancer Cells
Abstract. Evidence suggests that 17β-estradiol (E2) contributes to the risk of prostate cancer (PCa), whereas the phytochemicals genistein from soy and 3,3′-dii
TorontoTRT
Active Member
DIM acts as an anti androgen and interferes with muscle hypertrophic, not because it competes with DHT, but because it inhibits mTor.
“DIM blocks the effects of testosterone. Higher doses (greater than 100mg) of isolated pure DIM can saturate tissues and block androgen (e.g. testosterone and dihydrotestosterone) receptors and inhibit the protein synthesis induced by the anabolic effects of androgens. This is one of the ways DIM can help in cases of prostate cancer ; the other way is by inhibiting mTOR pathways that lead to cell growth and division but we will discuss mTOR in greater detail later when we discuss muscle hypertrophy.”
“DIM blocks the effects of testosterone. Higher doses (greater than 100mg) of isolated pure DIM can saturate tissues and block androgen (e.g. testosterone and dihydrotestosterone) receptors and inhibit the protein synthesis induced by the anabolic effects of androgens. This is one of the ways DIM can help in cases of prostate cancer ; the other way is by inhibiting mTOR pathways that lead to cell growth and division but we will discuss mTOR in greater detail later when we discuss muscle hypertrophy.”
TorontoTRT
Active Member
“
Diindolylmethane blocks mTOR
Higher doses of DIM act systemically to block anabolic androgens and mTOR pathways. mTOR is necessary for cell growth and for this mechanism DIM is currently being researched as a potential tool for reducing growth of cancer and tumours; this research is still a long way from being able to make any solid anti-cancer claims for DIM. However, it is important for athletes using DIM as part of a muscle building campaign to know that mTOR is the main anabolic pathway necessary for muscle hypertrophy and DIM will also block mTOR stimulation of cell growth.”
Diindolylmethane blocks mTOR
Higher doses of DIM act systemically to block anabolic androgens and mTOR pathways. mTOR is necessary for cell growth and for this mechanism DIM is currently being researched as a potential tool for reducing growth of cancer and tumours; this research is still a long way from being able to make any solid anti-cancer claims for DIM. However, it is important for athletes using DIM as part of a muscle building campaign to know that mTOR is the main anabolic pathway necessary for muscle hypertrophy and DIM will also block mTOR stimulation of cell growth.”
This is the source you are citing.
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This article is based on speculation and not based on research. The recommended reading at the end of the article cites studies related to DIMs benefits on the prostate and estrogen-dependent cancers. Nothing related to mTor inhibition.
Analyzing the source of data in an article is important when determining the validity and reliability of an article's content.
TorontoTRT
Active Member
Just google DIM mTor and you’ll get plenty of medical papers. I can tell you from personal experience it presents muscle growth. All that to take for something it doesn’t even do. Lower estrogen. Better alternative is calcium d-glucarate which actually lowers estrogen and eliminates bad estrogen metabolites.
"Cumulative evidence indicates that mTOR acts as a ‘master switch’ of cellular anabolic and catabolic processes, regulating the rate of cell growth and proliferation by virtue of its ability to sense mitogen, energy and nutrient levels [3,4]."
"Dysregulation of mTOR and other proteins in the signaling pathway often occurs in a variety of human malignant diseases and the tumor cells have shown higher susceptibility to mTOR inhibitors than normal cells. For example, activation of the mTOR pathway was noted in squamous cancers [5], adenocarcinomas [6], bronchioloalveolar carcinomas [7], colorectal cancers [8], astrocytomas [9] and glioblastomas [10]."
"These findings indicate a potential role of dysregulated mTOR signaling in tumorigenesis and support the currently ongoing clinical development of mTOR inhibitors as a potential tumor-selective therapeutic strategy."
"Dysregulation of mTOR and other proteins in the signaling pathway often occurs in a variety of human malignant diseases and the tumor cells have shown higher susceptibility to mTOR inhibitors than normal cells. For example, activation of the mTOR pathway was noted in squamous cancers [5], adenocarcinomas [6], bronchioloalveolar carcinomas [7], colorectal cancers [8], astrocytomas [9] and glioblastomas [10]. A recent immunohistochemical study performed in tissue arrays containing 124 tumors from 8 common human tumor types revealed that approximately 26% of tumors (32/124) are predicted to be sensitive to mTOR inhibition [11]. These findings indicate a potential role of dysregulated mTOR signaling in tumorigenesis and support the currently ongoing clinical development of mTOR inhibitors as a potential tumor-selective therapeutic strategy."
"Increasing studies have demonstrated that some diet-derived natural products, including curcumin, resveratrol, epigallocatechin gallate (EGCG), genistein, 3, 3-diindolylmethane (DIM) and caffeine, may inhibit mTOR signaling directly or indirectly (Table 1) [140-147]."
I appreciate you pointing this out @TorontoTRT. From this study, it would appear that the potential anti-tumor/anti-cancer potential of DIM, as well as curcumin, resveratrol, EGCG, caffeine, and a few other agents, is based on their ability to inhibit mTOR signaling; mTOR signaling being responsible for (current thought in science) to act as the master switch of cellular anabolic and catabolic processes. So while mTOR inhibition may raise concern in bodybuilders or guys on TRT wanting to maximize body composition effects of testosterone, evidence doesn't suggest that cellular proliferation is significantly reduced in skeletal muscle as a result of mTOR inhibition. The evidence does, however, point to the reason why mTOR inhibitors (natural such as DIM or synthetic) act with potent anti-tumor, anti-cancer effects.
"Currently, all natural products tested, such as EGCG, curcumin and resveratrol, inhibit mTOR signaling at considerably high levels (micromolar ranges) in vitro."
I would hypothesize that the dosage of DIM or any natural supplement that reduces mTOR signaling would need to be used considerably higher dosages than are used in supplemental form (100-500 mg daily). So it would hypothesize that any reduction is muscle gain while using DIM would be nil.
For example, the study below shows how high of a dosage researchers are using to elicit harmful side effects from DIM (the equivalent of 900 mg to 9000 mg in a 200 lb male are used in the following study w/ 900 mg not eliciting harmful effects).
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Updates of mTOR inhibitors
Mammalian target of rapamycin (mTOR) is a central controller of cell growth, proliferation, metabolism and angiogenesis. mTOR signaling is often dysregulated in various human diseases and thus attracts great interest in developing drugs that target mTOR. ...
www.ncbi.nlm.nih.gov
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The claim for DIM has not been about estradiol reduction, but about steering metabolism in a safer direction. The effectiveness of CDG at typical doses is suspect:
However, a problem occurs when humans take this as an oral supplement. Although it appears to be safe even at high doses, very high doses are required for its effects (100mg/kg minimum, near maximal effects at 200mg/kg) and this would even only theoretically assure some protection against toxins that are glucuronidated. If a toxin is subject to another detoxification pathway (such as conjugation by glutathione) then Glucaric acid will serve no benefit.
...
Furthermore, all steroid hormones in the body (testosterone, estrogen, DHEA, etc.) are also glucuronidated. If using an oral dose that reduces the toxin, these hormones will also all be reduced for a short time.
...
Using calcium-D-glucarate as a daily preventative supplement does not appear to be a prudent idea, due to its lack of reliability even in theory and high doses used. However, a single acute dose of this supplement prior to known exposure to toxins that are glucuronidated (such as both benzopyrene and polyaromatic hydrocarbon compounds produced in the cooking of meat products) might be more prudent and potentially useful.
[1]TorontoTRT
Active Member
I was suspect about CDG until I did 3000 mg a day. What I saw was drastic changes. My acne on chest and shoulders disappeared. I wasn’t able to control acne under any protocol. From 80 mg a week to 125 mg a week. Injecting from once a week to every 3 days I had acne.
I was also hesitant due to cdg possibly eliminating testosterone and dhea due to Glucuronization.
But I ran multiple blood tests for before and after using it 3 months and what it showed is that E2 was cut by almost 25% even though test dosage was higher, and testosterone and dhea levels did not change or stayed appropriate to dosage: (trough numbers)
I was also hesitant due to cdg possibly eliminating testosterone and dhea due to Glucuronization.
But I ran multiple blood tests for before and after using it 3 months and what it showed is that E2 was cut by almost 25% even though test dosage was higher, and testosterone and dhea levels did not change or stayed appropriate to dosage: (trough numbers)
Dr. Crisler always contended that DIM helps TRT patients metabolize E2 into estrone, and CDG aids the body in eliminating estrogen. So his contention was that these two supplements work synergistically.
I hadn't heart of anyone taking that much. Interesting. But it's puzzling that you don't see a proportional effect on other hormones.
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