DIM & Arimistane: In Search of a Natural AI or SERM

Arimistane - legal dead end

I originally started out by reading up on Arimistane. It's commonly available, and my expectation was that it was perfectly legal. Apparently not so much:

“Arimistane” is represented as a dietary supplement on its label and other labeling; however, the product does not meet the definition of a dietary supplement in section 201(ff) of the FD&C Act [21 U.S.C. § 321(ff)]. To be a dietary supplement, a product must, among other things, “bear or contain one or more dietary ingredients'... (such) as a vitamin; mineral; amino acid; herb or other botanical; dietary substance for use by man to supplement the diet by increasing the total dietary intake; or a concentrate, metabolite, constituent, extract or combination of any dietary ingredient from the preceding categories.

The “Arimistane” ingredient listed on your product label, Androsta-3,5-Diene-7,17-Dione, is an aromatase inhibitor and does not constitute a dietary ingredient under section 201(ff)(1) of the FD&C Act...

Moreover, the product is a “new drug,” as defined by 201(p) of the FD&C Act [21 U.S.C. § 321 (p)], because it is not generally recognized as safe and effective for its labeled uses. The introduction or delivery for introduction, or causing the introduction or delivery for introduction, of any new drug lacking an FDA-approved new drug application (NDA) is a violation of sections 301(d) and 505(a) of the FD&C Act [21 U.S.C. §§ 331(d) and 355(a)]. Your sale of the new drug “Arimistane” in interstate commerce without an approved NDA violates these provisions of the FD&C Act.

Furthermore, your product is a “prescription drug” under section 503(b)(1)(A) of the FD&C Act [21 U.S.C. § 353(b)(1)(A)], in that because of its toxicity or other potentiality for harmful effect, or the method of its use, or the collateral measures necessary to its use, it is not safe for use except under the supervision of a practitioner licensed by law to administer it. Adverse events associated with the use of FDA-approved aromatase inhibitors include the following: decreased rate of bone maturation and growth, decreased sperm production, infertility, aggressive behavior, adrenal insufficiency, kidney failure, and liver dysfunction. Indeed, all aromatase inhibitor drugs which have been approved for marketing by the FDA are limited by an approved new drug application to use under the professional supervision of a practitioner licensed by law to administer such drug.

Source.

Who knew that Arimistane was of such danger? Won't somebody think of the children?

Funnily, this actually makes me more likely to use it: the FDA banned a compound? It must be effective.

DIM

So given this dead end in my quest to find a compound or stack that could serve either as a replacement for AI or SERM, I moved on to DIM. As with many compounds in this area, the science is fuzzy, but there is a key study that is indicative.

38 rats, split into 4 groups - control, DIM-10 which received 10mg kg, DIM-50 which received 50mg kg, DIM-100 which received 100mg/kg for 53 days.

  • DIM-10 lowered e2 to about 43% of control, and lowered test by 34%
  • DIM-50 increased e2 to 180% of control, and lowered test by 64%
  • DIM-100 increased e2 to 200% of control, and had no statistical impact to test

The authors make speculation on the causes, but it's mostly an unknown. What is known is that DIM is anti-androgenic, and at relatively high doses has undesirable effects to e2. The HED of DIM-10 for a 100kg male is 135mg daily and I wouldn't exceed it unless you're trying to further lower test and spike e2 for some reason.

Human Study

In a study using a specific altered form of DIM (BR-DIM, a more bio available form, 225mg x 2 daily), median plasma testosterone level prior to treatment was 280 ng/mL (range 77-557 ng/mL). In the 26 patients evaluable, plasma testosterone levels increased post-BR-DIM therapy in 15 patients, decreased in six patients and were unknown in five patients. The mean difference between pre- and post-BR-DIM testosterone levels was an increase of 76 ng/mL (range -107 ng/mL to 359 ng/mL).

Applications

Based on the human & rat studies, I see three applications for DIM:

  1. controlling e2 when an individual is already in a highly suppressed state (i.e. low test) and e2 is a major concern
  2. increasing e2 (such as if it was accidentally crashed, marginal use case)
  3. controlling e2 when an individual is using exogenous testosterone

So What?

The latter (i.e. controlling e2) is the best use for it. DIM impacts the testes directly, increasing oxidative stress. At low doses, this has a desired effect. At higher doses, the body has an apparent protection mechanism that kicks in that is, at this point in time, an unknown. As an antiandrogen / e2 agonist, it will have an impact to test and therefore e2 through negative feedback. It also prevents AR translocation (probably not desirable over the long term).

Ofc, there's no studies using men to measure its effect on e2. I'm going to cautiously suggest that, based on the study that we do have, DIM at 13.5mg / kg is effective in lowering e2. There's better (not legal) choices for e2 control, however, so the only real advantage I see with DIM is that it's easily obtainable.

  • Happily, I wrote this up before I checked Examine.com and they seem to agree with me: A supplemental dose of approximately 100mg DIM has been noted to alter urinary estrogens in a manner thought to reflect less estrogenicity (https://examine.com/supplements/diindolylmethane/#interactions-with-hormones_estrogen).
  • A quick Amazon search shows this commonly available at 200-300mg per cap. Imo this is too high for our purposes - look around for the 100mg (or less) caps, since they are also available but further down the results pages.

https://www.reddit.com/r/PEDsR/comments/bldng0/dim_arimistane_in_search_of_a_natural_ai_or_serm/