The Cruciferous Choice: DIM or 13C? Phytonutrient Supplements for Cancer Prevention and Health Promotion

Townsend Letter for Doctors and Patients,  August, 2001  by Michael A. Zeligs

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Abstract

Cruciferous vegetable phytonutrients include natural substances whose supplemental use has great potential for the prevention of human cancer. The additional discovery that the cruciferous indoles, diindolyl-methane (DIM [R]) and indole-3-carbinol (13C), also promote healthy estrogen metabolism has expanded their usefulness as dietary supplements for many estrogen-related conditions. Beyond cancer prevention, effective uses of absorbable DIM have included benefits for perimenopausal women, in premenstrual syndrome (PMS), in endometriosis, and in cervical dysplasia. Also benefited from supplementation are women on estrogen replacement (HRT), as well as men with estrogen-related conditions including prostate hypertrophy. In choosing dietary supplement formulations containing DIM or 13C, it is important to understand basic differences in their phytochemical characteristics and interaction potential. These differences have important implications as to their relative safety for long-term use.

Introduction to the Cruciferous, Indole Phytonutrients

Cruciferous vegetables (broccoli, cabbage, cauliflower, Brussels sprouts, bok choy) are in the news as powerful sources of cancer-preventive phytonutrition. A recent study of Seattle men showed that three or more servings of cruciferous vegetables a week can reduce prostate cancer risk almost by half. [1] For women however, the news is not so clear. In a large prospective study of 350,000 women, no protection from breast cancer could be attributed to dietary fruits and vegetables, or to the highest intake of cruciferous vegetables. [2] Since other controlled studies in women have documented clear, beneficial action from cruciferous dietary supplements, [3] there is a growing basis for adding cruciferous phytonutrients to the fruits and vegetables of a healthy diet. The active substances in cruciferous vegetables benefiting estrogen-related disorders have proven to be absorbable diindolylmethane (DIM [R]) and its precursor indole-3-carbinol (13C). [4] Supplemental use of these substances has a long history in cancer prevention research. With expanding applications in preventive nutrition, their use in women has actually been shown to reduce risk status for breast cancer, [5] and cause the regression and disappearance of advanced cervical dysplasia. [6] The supplemental use of DIM and 13C are under active investigation. [7] These natural products are increasingly available as dietary supplements for healthier estrogen metabolism, perimenopause, men's health and cancer risk-reduction

Significant amounts of DIM are found in cruciferous plants following crushing. [8] This is unlike 13C which, due to its unstable nature, is only transiently present, primarily during digestion. [9] 13C is the natural precursor to DIM, which is formed from a "condensation reaction" in which one 13C molecule combines with another. The resulting DIM is a "di-indole" or double molecule formed from two 13C molecules. Release of active DIM is facilitated by enzymes in the plant and is also due to the action of gastric acid on 13C released during digestion. Pure forms of these natural substances derived from plant-based precursors are now available as dietary supplements. The choice of precursor 13C, or active DIM as a supplement requires an understanding of their relative merits and safety as phytonutrients. This review will compare and contrast the important differences between DIM and 13C.

DIM and 13C -- Different Physical and Phytochemical Characteristics

Based on well known physical characteristics, DIM is very stable in water and acid but highly insoluble. 13C is soluble but highly reactive, resulting in over 20 condensation products, including DIM, after 13C is exposed to stomach acid. [10] When 13C is kept dissolved in water, or buffered in weakly acidic solutions, a greater conversion to DIM occurs. DIM requires a special dietary supplement formulation to provide for improved solubility and complete gastrointestinal absorption. 13C requires careful storage, avoiding heat, moisture and light to slow its rapid breakdown on the shelf. Taken as a dietary supplement, 13C requires gastric acid for conversion to active products. 13C is more irritating to the stomach than DIM, due to its chemical reactivity. [11] 13C is much more sensitive to interaction with components of food, especially vitamin C, which limit its conversion into DIM and other condensation products. Conversion from 13C into DIM not only requires a precise acidity it requires time. This conversi on may proceed slowly, requiring more than a typical intestinal transit time to be complete.

A compelling study favoring the use of DIM over I3C demonstrated the fact that following an oral dose of I3C in humans only DIM and no I3C was found circulating in the bloodstream of test subjects. [12] This finding confirms that I3C disappears after entry into our stomachs, and since a highly sensitive detection method was used, no direct benefits can be attributed to absorbed I3C. Based on this study it is also documented that over 90% of an oral dose of I3C goes unaccounted for in the form of non-DIM "condensation products" of uncertain structure, uptake and activity.