Is TMG really necessary when using DIM?

[frankwhardy]

Can anyone direct me to the studies indicating that DIM increases 4-OHE? Thanks!
Frank

I initially posted the above on another thread but never had a response, so I thought I would make it its own thread, still hoping for a response. I'm wondering if the idea that DIM might increase 4-OHE was started because some studies may have shown that its parent compound, indole-3-carbinol (I3C), may increase 4-OHE, but I can't find where DIM has been shown to do this. Just the opposite in fact (see the study abstract I quote below). Therefore, I'm doubting the need to use TMG with DIM for purposes of removing excess 4-OHE . . . I would love to see any studies on DIM showing that it actually increases 4-OHE.
Frank

Published in Cancer Detection and Prevention 2004; 28(1).

Differences in the hepatic P450-dependent metabolism of estrogen and tamoxifen in response to treatment of rats with 3,3?-diindolylmethane and its parent compound indole-3-carbinol

Daniel R. Parkin, BAa, Danuta Malejka-Giganti, PhD

Veterans Affairs Medical Center, Minneapolis, MN 55417, USA Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55455, USA

Indole-3-carbinol (I3C), present in cruciferous vegetables, and its major in vivo product 3,3?-diindolylmethane (DIM), have been reported to suppress estrogen-responsive cancers. This effect may be mediated through the modification of cytochrome P450 (CYP) complement and activities leading to estrogen detoxification. We examined the effects of a 4-day treatment of female Sprague*Dawley rats with DIM at 8.4 and 42 mg/kg body weight (bwt), on the hepatic CYP protein level, CYP1A1, 1A2, 2B1/2 and 3A1/2 probe activities and CYP-dependent metabolism of 17?-estradiol (E2) and estrone (E1). At 42 mg/kg bwt, DIM effected a small increase (2.8-fold) in CYP1A1 activity, and at both dose levels it reduced CYP3A1/2 activity by ~40%. At the higher dose level, DIM decreased the rates of oxidation of E2 to 4-OH-E2, 4-OH-E1, 6?-OH-E2 and 6(? + ?)-OH-E1 by 39, 44, 71 and 60%, respectively, and E1 to 6(? + ?)-OH-E1 by 39%. These effects were considerably different from those of I3C reported by us previously. We also examined the effects of DIM and I3C on the hepatic microsomal metabolism of tamoxifen (TAM). Whereas metabolism of TAM was unaffected by DIM, formation of N-desmethyl-TAM (and its presumed derivative) was increased ~3-fold by I3C at 250 mg/kg bwt. Since N-desmethyl-TAM is transformed to a genotoxic metabolite, dietary exposure to I3C may enhance hepatic carcinogenicity of TAM in the rat. The differences between I3C and DIM in CYP-mediated activities and metabolism indicate that DIM is not a proximate intermediate in the mechanism of action of I3C.

 

[jawbone]

remember these are rats(SD rats too boot) so I would not be quick to draw any conclusion

 

[frankwhardy]

Yes, I know, but if the studies (if they exist) that show DIM increasing 4-OH estradiol/estogen also use rats, then it will be an apples to apples comparison. Swale had said that he has seen information that indicated DIM can raise 4-OH-E. To quote him:

I have seen several studies which showed that while DIM improves the 2-OHE/16-a-OHE ratio, it also increases the bad 4-OHE. TMG, or its child DMG (although TMG is much better because it has already donated a valuable methyl group by the time it becomes DMG) will help flush the 4-OHE downstream.

Taking TMG/DMG is important on its own, even in absence of DIM supplementation. But I would not take DIM without it.

from the thread entitled "SWALE - DIM, TMG and Estrogens" found here:
https://thinksteroids.com/community/posts/432311

I'm just wondering if Swale was looking at I3C studies in which the researchers mistakenly *believed* that DIM was the active agent causing an increase in 4-OH-E, when the study I cited above found otherwise.

 

[jawbone]

Swale( with N. Delgado Phd.--not sure of spelling)) is very versed on this matter. I think he was doing a study on some of his pts using I3C by monitoring the E metabolites using urine testing. You might want to ck with him.