Humble but Powerful: Cruciferous Vegetables Detoxify via a Potent Molecule Called DIM

Wherever you are on your health crusade, you will want to know about a potent, health-promoting compound called diindolylmethane, commonly known as DIM. You are undoubtedly familiar with the vegetable family known as the cruciferous, and its many satisfying, crunchy, often green constituents – kale, collard greens, cabbage, broccoli, and brussels sprouts – to name a few. Cruciferous vegetables seem to be on every menu now – whether it is the taqueria down the street or the invitation-only new trending restaurant in your city. And with good reason! In addition to the flavors and textures they bring to a meal, crucifers have many health benefits.

Unique Health Benefits of Cruciferous

Dietary consumption of cruciferous vegetables has been observed to benefit health and overall longevity in many ways. Higher intakes of cruciferous have been associated with a reduction of inflammation, particularly in women,^1,2 decreased risk of heart attack and cardiovascular disease-related mortality,^3,4 as well as a lower risk of certain types of cancer.^5,6,7 DIM is derived from the cruciferous and may be one of the primary contributors to these benefits. DIM is readily formed during the digestive process when indole-3-carbinol (I3C), a somewhat unstable compound directly derived from cruciferous, is exposed to stomach acid.⁸ It is also increased in crucifers by cooking, which activates an enzyme (myrosinase) responsible for its conversion.⁹

One of the mechanisms by which this vegetable family may have a positive impact on health is by supporting the body in detoxification.¹⁰ There are different estrogen metabolites in the body, some of which are more estrogenic and potentially harmful, while others are more protective.¹¹Increased intake of the cruciferous vegetables has been observed to shift estrogen metabolism, increasing the balance of the forms of estrogen which may be more protective and reduce risk of hormonal cancers such as breast cancer.⁵

What is Detoxification?

Unfortunately, the concept of detoxification has been oversimplified in many health-related circles, where fasting, juicing and yoga retreats are often emphasized. Although these approaches may have benefits, they don’t fully encompass the complexities of the larger process and the necessary steps by which detoxification occurs in the body. Thus, to enter in to a discussion of detoxification, some basic higher-level concepts of physiology and biochemistry are necessary to introduce.

Perhaps the most important molecule in detoxification is glutathione. Glutathione is the body’s main antioxidant and is necessary for cellular detoxification throughout your body.¹² Glutathione is necessary to protect the cell’s delicate machinery and to transport toxins out of the cell. One of the steps of detoxification involves the binding of toxins to glutathione, creating larger, inactive, water soluble molecules. These water-soluble molecules can easily be transported out of the cell, into the bile, and out of the body via stool.¹³ Because glutathione is utilized in the process of removing mercury and many other toxins from the cell, it also can become depleted in settings of increased toxicity.¹⁴

Arguably as important as glutathione for the process of detoxification is a protein known as Nrf2 (short for nuclear factor E2-related factor). Nrf2 is a cellular switch that orchestrates antioxidant, de­toxification, and cellular defenses. When activated, Nrf2 can switch on over 200 genes that help the cell generate its own highly pro­tective molecules.^15,16

Along with Nrf2 is its cellular helper and teammate, known as the antioxidant response element (ARE). Nrf2 is present in the cytosol of the cell, and responds to oxidative stress by translocating to the nucleus and binding to ARE, the promoter region of genes that encode the transcription of critical components of detoxification: antioxidant elements, detoxification enzymes, and proteins required for glutathione synthesis and recycling.¹⁷ This includes the phase II detoxification enzymes glutathione S-transferase (GST), glutathione reductase (GSR), and glutathione peroxidase (GPX).^18,19,20 The Nrf2/ARE pathway serves a protective role in the body, and is activated by elevated levels of reactive oxygen species (ROS) as well as exposures to air pollution and heavy metals.^21,22

Studies have also shown that the ability to upregulate Nrf2 and its antioxidant supporting action declines with age, which may be one reason the elderly are more susceptible to damage from environmental pollutants.²³ Additionally, some of the toxic substances which we are exposed to such as ochratoxin A, one of the most common mold toxins found in foods and water-damaged houses, and indoxyl sulfate, a uremic toxin that is increased with exposure to some toxic heavy metals, act as Nrf2 inhibitors, further contributing to toxicity and impaired detoxification.^24,25,26,27

Fortunately, there are natural substances that appear to induce Nrf2 and effectively switch on our detoxification pathways and antioxidant defenses. This includes DIM and other favorites such as lycopene (found in tomatoes) and epigallocatechin gallate, or EGCG (found in green tea).^28,29Increasing intake of these substances in the diet definitely can be helpful, but for many who struggle with things such as hormonal imbalance, mold exposure, and other environmental toxicities, dietary intake is usually not enough.

DIM and Hormones

Many integrative healthcare providers utilize DIM to support the body in the metabolism of hormones. The improved metabolism and elimination of the more dangerous forms of estrogen is proposed to be one of the reasons that DIM and cruciferous consumption may be protective against hormone-dependent cancers.³⁰ DIM induces the expression of cytochrome P450 enzymes that are responsible for metabolizing estrogen.³¹ By inducing these enzymes, DIM helps modify estrogen balance, increasing levels of 2-hydroxy-estrone, a metabolite of estrogen which has been suggested to be protective against breast cancer.³²

DIM and Nrf2

Because mold toxins (mycotoxins) can inhibit Nrf2 and our body’s detoxification pathways, we need a strong Nrf2 inducing agent to restore the protective glutathione system, and the associated enzymes necessary for it to do its job as well as recycle it. DIM has a strong Nrf2 activating effect which is not seen with DIM’s precursor I3C.³³ By “turning on” the Nrf2 switch, DIM increases the body’s expression of many drug metabolizing enzymes, detoxification-dependent transporters (necessary to get toxins out of the cell), and other antioxidant enzymes.³⁴

The benefits of Nrf2 activation go beyond recovering from mycotoxin exposure and hormone balance. For instance, our skin cells produce Nrf2 to protect themselves from many conditions which increase oxidative stress, such as UVB exposure.³⁵ Improving Nrf2 activation in the skin may be a means to combat sun-related damage,³⁶ as well as immune-mediated conditions of the skin such as dermatitis and vitiligo.^37,38

Although DIM may offer a variety of health benefits, when taken in traditional oral formulations such as tablets and capsules it has poor absorption and relatively rapid clearance.⁴² Lipid-based formulations such as liposomes and nanoemulsions have been shown to dramatically improve bioavailability of DIM as well as a variety of substances.^43,44 Absorption of nanoemulsified DIM begins immediately in the oral cavity, as the tiny, nano-sized particles enter circulation, evading breakdown by digestive secretions. Studies have also show that nanoemulsified delivery formats also prolong the time a therapeutic agent is in circulation, leading to reduced need for dosing.⁴⁵

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