Leon Bradlow, Ph.D. writes...
Letter to the Editors of the
Townsend Letter for Doctors and Patients
A pseudo controversy concerning Indole-3-Carbinol (I3C) and
Diindolylmethane (DIM) is being promoted by the Life Extension
Foundation in response to an article comparing I3C to DIM in
the Sept/Oct 2001 Townsend Letter (1).
As one of the original investigators of the role of I3C in
hormonally-related cancers, I am disturbed by the distortions
made by Life Extension in their January 2002 magazine. There
is no evidence that I3C is active in its own right, while there
is abundant evidence that I3C is a "pro-nutritional"
which is converted by stomach acid to DIM, ICZ, LTR, CTR, ASB
and other polymers in varying amounts. The exact mix depends
upon the acidity of the stomach. This unpredictable process is
modulated by achlorhydria, and consumption of proton-pump inhibitors
or antacids. The higher the pH, the greater the relative formation
Contrary to the claims made in the Life Extension article,
the trimers (triple molecules from I3C) and ICZ (dioxin-like
double molecule from I3C), in addition to any beneficial effects
that they may induce, also induce a series of undesirable side
effects, including induction of estrogen receptor activity, inhibition
of apoptosis, etc.
In addition, ascorbigen (ASB) induces 4-hydroxylation to yield
the known carcinogenic 4-hydroxyestrogens, as noted by Sepkovic
et al. almost 10 years ago (2). Any compound, capable of inducing
4-hydroxylation is hardly desirable, as incorrectly implied in
It should also be noted that all of the responses to I3C in
cell culture studies, actually reflect the actions of Diindolylmethane,
since I3C is almost quantitatively converted to Diindolylmethane
in cell culture media at 37 C in about 24 hours.
Most importantly, the implication made by Life Extension that
Diindolylmethane promotes breast cancer is inaccurate and misleading.
In fact, Diindolylmethane has been recently shown by leading
investigators to inhibit the growth and potential spread of breast
cancer in vivo (3).
In comparison to I3C, Diindolylmethane is a more stable compound
which exhibits beneficial effects at lower doses, and without
the undesirable side effects of I3C. Diindolylmethane's stability
and potency at lower doses are evidence of its greater benefits,
in contrast to the undesirable responses observed with I3C products.
In view of the demonstrated safety benefits of Diindolylmethane
versus I3C, it is clear that Diindolylmethane is the compound
H. Leon Bradlow, Ph.D.
1. Zeligs MA. "The Cruciferous Choice: DIM or I3C?"
Townsend Letter for Doctors and Patients; August/September 2001;
2. Sepkovic DW, Bradlow HL, Michnovicz J, Murtezani S, Levy
I, Osborne MP. "Catechol estrogen production in rat microsomes
after treatment with indole-3-carbinol, ascorbigen, or beta-naphthaflavone:
a comparison of stable isotope dilution gas chromatography-mass
spectrometry and radiometric methods." Steroids. 1994
3. Janet Tou, Chibo Hong and Leonard F. Bjeldanes. "The
Influence of 3'3-Diindolylmethane on Breast Tumor Growth, Invasion
and Metastasis," Experimental Biology 2001, March 31-April
4, 2001, Orlando, Florida.
Auborn, Ph.D. writes...
Dear Dr. Zeligs,
Indole-3-carbinol (I3C) and one of its proximal products,
Diindolylmethane, are supplements that show real promise for
treatment of certain conditions such as pre-cancerous lesions
of the cervix.
Until recently, most in vitro, animal and clinical studies
only used I3C. However, in the stomach I3C is converted into
a variety of compounds, including Diindolylmethane, and it is
clear that I3C itself is not one of the active compounds.
Many experiments, including clinical studies, suggest that
Diindolylmethane is significantly more active than I3C for the
desired effects. At a minimum, the use of Diindolylmethane avoids
problems associated with I3C, such as the production of unknown,
poorly-characterized and potentially harmful products.
Since undesirable effects of I3C have been reported, such
as promotion of liver cancer in fish, I believe that the effects
of I3C products need to be evaluated and compared for their individual
and combined actions.
From my researcher's perspective, the ideal indole compound
would promote beneficial effects, be stable, inexpensive, and
not have any adverse effects. Based on the data, absorbable Diindolylmethane
is the only I3C-derived indole currently being marketed that
comes close to meeting the requirements for such a "designer
Karen Auborn, Ph.D.