Detoxification is a multi-step process that involves not only clean eating, but also awareness of water sources, exposure to toxins (both environmental and food-borne), and proper elimination. One way to think of it is, “We are what we eat, breathe, touch, and sense, but cannot eliminate.” We cannot completely control our exposure to toxins in food, food packaging, and the air we breathe, but we can take steps to support our ability to eliminate the toxins from our bodies and reduce exposures in the first place.
Our main organs of detoxification are the digestive system, liver, and kidneys. But an often-neglected “organ” system is also intricately involved: the gut microbiome. Combined, these cellular systems help protect us from the harmful substances found in xenobiotics, pharmaceuticals, and even metabolites of our own hormones. When out of balance, they can be responsible for increasing toxicity within the body.
In addition, not all toxicity enters our bodies in physical form. We are bombarded with an assortment of external stimuli on a constant basis, from advertising to smartphones to social media notifications that overstimulate our nervous system and leave many of us in a state of wired anxiety. In my opinion, this is another very important type of toxicity that needs to be addressed with our patients.
Liver detoxification is traditionally discussed as divided into two phases: Phase I and Phase II. The Phase I pathway is primarily controlled by the cytochrome P450 iso-enzymes, which are highly inducible. The cytochrome P450 system is the first defense against potential toxic threats to the body because it helps biotransform xenobiotics, pharmaceuticals and steroid hormones. The iso-enzymes create a reactive site on the compound, making it even more potentially toxic, until the Phase II conjugation enzymes attach a water-soluble group to this now-reactive site. CYP450 enzymes work through hydrolysis, oxidation, and/or reduction to add a reactive group, such as a hydroxyl, carboxyl, or amino acid. Because these intermediate metabolites are highly reactive, they have the potential of causing oxidative damage within the cells that produce them if they do not move into the slower, very important Phase II detoxification process. For this reason, detoxification is a process that has a high demand for antioxidants.
The Phase II enzymes include UDP-glucuronosyl transferases, glutathione S-transferases, amino acid transferases, N-acetyl transferases, and methyltransferases. Whereas Phase I is highly inducible, Phase II is much slower and highly dependent on the patient’s nutrition status. Therefore, overactivity of the CYP450 enzyme system without adequate Phase II support may enhance the destructive effects of environmental procarcinogens. We know that enzyme activity in this family of enzymes is widely controlled by genetic polymorphisms. One group, the CYP1 enzymes, are important in estrogen metabolism. CYP1A1/1A2 enzymes catalyze the 2-hydroxylation of estrogens, while the CYP1B1 catalyze the 4-hydroxylation of estrogens.1 Since 4-hydroxyestradiol may play a role in estrogen-related cancers, for example, via the production of free radicals, overactivation of this pathway may be involved in carcinogenesis.
Estrogen-dominance is a condition where excess estrogen and estrogen-metabolites flood the body. It is not only related to liver detoxification, but can also be caused by dysbiosis. An excess of bacteria in the gut expressing the beta-glucuronidase enzyme leads to cleavage of the water-soluble anchor on estrogen metabolites that allows them to be secreted through the bile into the digestive tract for elimination, thereby allowing estrogen to be released and get reabsorbed into the body.
If we consider breast cancer a condition linked to estrogen-dominance, then it is easy to understand how supporting detoxification through the liver in these patients is of great benefit to re-establishing hormonal balance. Other conditions of estrogen-dominance (progesterone deficiency) that may benefit include prostate cancer, fibrocystic breast disease, a shortened menstrual cycle with spotting, female weight/water retention, and patients on hormone therapies (pharmaceutical estrogens or progestins, bio-identical hormone therapy, and oral contraceptives).
When looking at functional foods that can modulate these pathways, we find that cruciferous vegetables have been shown to act as inducers of the CYP1A1 and 1A2 pathways.2 3 Resveratrol is also a CYP1A1 inducer.4 Chrysoeriol, present in celery and rooibos tea, has been shown to inhibit CYP1B1 in vitro,5 which may help patients with excessive 4-hydroxylation of estrogens. There are many other foods that support detoxification enzymes, by either inducing them or inhibiting them. Let’s take a look at a few of them.6
- Fish oil
- Chicory root
- Rooibos tea
- Cruciferous vegetables
- Green tea
Surprisingly, some of the nutrients, like green tea and curcumin, can also act as inhibitors of certain cytochrome P450 iso-enzymes.
- Meat (especially liver)
- Plant-derived (apple, apricot, artichokes, arugula, asparagus, sweet potatoes, carrots–rich in provitamin A carotenes, like beta carotene)
- Cruciferous vegetables
- Resveratrol (grapes, wine, itadori tea)
- Rooibos tea
- Ellagic acid (berries, pomegranate, grapes, walnuts)
- Astaxanthin (salmon, trout, krill, shrimp)
Glutathione S-Transferases (GST)
- Cruciferous vegetables
- Fish oil
- Purple sweet potato
- Green tea, rooibos tea
- Ellagic acid
- Genistein (as in fermented soy, like miso or tempeh)
Aside from foods, there are also other vitamins and nutrients used in the process of detoxification. These assist in augmenting detoxification capacity.
- Vitamin B12
- Riboflavin (vitamin B2)
- Niacin (vitamin B3)
- Pyridoxine (vitamin B6)
- Branched-chain amino acids (leucine, isoleucine, valine)
2Hakooz N, Hamdan I. Effects of dietary broccoli on human in vivo caffeine metabolism: a pilot study on a group of Jordanian volunteers. Curr Drug Metab. 2007 Jan; 8(1):9-15.
3Walters D. G., Young P. J., Agus C., et al. Cruciferous vegetable consumption alters the metabolism of the dietary carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in humans. Carcinogenesis. 2004;25(9):1659–1669. doi: 10.1093/carcin/bgh164.
4Chow HH, Garland LL, Hsu CH, Vining DR, Chew WM, Miller JA, Perloff M, Crowell JA, Alberts DS. Resveratrol modulates drug- and carcinogen-metabolizing enzymes in a healthy volunteer study. Cancer Prev Res (Phila). 2010 Sep; 3(9):1168-75.
5Takemura H, Sakakibara H, Yamazaki S, Shimoi K. Breast cancer and flavonoids - a role in prevention. Curr Pharm Des. 2013; 19(34):6125-32.
6Guilliams T.G. Ph.D. Functional Strategies for the Management of Gastrointestinal Disorders: Principles and Protocols for Healthcare Professionals. The Standard Road Map Series. 2016; 68 – 80.
Dr. Vincent M. Pedre is the medical director of Pedre Integrative Health and founder of Dr. Pedre Wellness, medical advisor to two health-tech start-ups (MBODY360 and Fullscript), and a functional medicine-certified practitioner in private practice in New York City since 2004.
He is a clinical instructor at the Mount Sinai School of Medicine, and is certified in yoga and medical acupuncture. On faculty at The Institute for Functional Medicine, Dr. Pedre taught the first AFMCP in Lima, Peru in November 2017. Most recently, he joined the Lifestyle Matrix Resource Center as a Clinical Expert serving the Pillars of GI Health Program. He believes the gut is the gateway to excellent health. For this reason, he wrote the book, Happy Gut�The Cleansing Program To Help You Lose Weight, Gain Energy and Eliminate Pain, which helps people resolve digestive and gut-related health issues.