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The Science of Detoxification: Phase III & Detox Nutrients

Written by Biljana Novkovic, PhD | Reviewed by Ana Aleksic, MSc (Pharmacy) | Last updated:
Puya Yazdi
Medically reviewed by
Puya Yazdi, MD | Written by Biljana Novkovic, PhD | Reviewed by Ana Aleksic, MSc (Pharmacy) | Last updated:

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The human body has an amazingly efficient detoxification system, mostly located in the liver. It orchestrates complex detox reactions that remove drugs and toxins, and phase III is its final step. Read on to learn which nutrients support it to help you restore detox balance in the body.

Phase III Detoxification

Recap: Detox Phases

Our bodies process and remove these foreign chemicals (xenobiotics) thanks to our efficient detoxification mechanisms. These mechanisms also deal with metabolic products such as excess hormones (endobiotics).

“Enzymes of detoxification” are a big family of enzymes that alter foreign chemicals and metabolic waste either by making them more readily excretable or less pharmacologically active [1].

The detoxification process can be roughly divided into three phases [2]:

  • Phase I is governed by transformation enzymes – these enzymes oxidize, reduce and hydrolyze toxins/drugs
  • Phase II is managed by conjugation enzymes – these enzymes conjugate Phase I products
  • Phase III is carried out by transport proteins – these proteins transport the final products from the cell

detoxification2

Transporters Eliminate Toxins from Cells

ABC Transporters

Phase III of detoxification is responsible for eliminating toxins and metabolic products from cells.

Phase III transporters can be found in the liver, intestine, kidney, and brain, where they act as a barrier against drug entry, and manage endobiotic and xenobiotic absorption, distribution, and excretion [3].

These transporters are called ABC transporters (ATP-binding cassette transporters) [3], and they require ATP to transport a broad range of compounds across the cell membrane [4]. Some of these transporters are also called multidrug resistance proteins (MRPs), because of their involvement in multidrug resistance [4].

Bile Secretion

Note that, although not officially a part of the 3 -phase detoxification process, bile secretion is necessary for the elimination of toxic endo- and xenobiotics such as bilirubin, lipid bacteria products (endotoxin), and several inflammatory mediators. These products are removed through the intestines [5].

Impairment of bile flow may result in a buildup of liver toxins and liver injury.

Dietary Factors that May Improve Bile Flow

Yarrow (Achillea millefolium) and artichoke may stimulate bile flow [6, 7], as may potentially cumin, ajowan, garlic and ginger [8, 9].

Heavy Metals Detoxification

Metals of Concern

There are 23 heavy metals of concern for human health because of residential or occupational exposure: antimony, arsenic, bismuth, cadmium, cerium, chromium, cobalt, copper, gallium, gold, iron, lead, manganese, mercury, nickel, platinum, silver, tellurium, thallium, tin, uranium, vanadium, and zinc [10].

In small amounts, some of these metals, such as iron, copper, and zinc, are required for maintaining good health, but in larger amounts, they can become toxic and dangerous [10].

Heavy metal toxicity can lower energy levels and damage the functioning of the brain, lungs, kidney, and liver [10].

Should You Worry About Exposure?

Luckily, most people don’t have to worry about heavy metal exposure.

Heavy metal poisoning is extremely rare in the United States. It happens only when people are exposed to exceptionally high amounts of heavy metals in their environment, typically due to work-related conditions.

Despite this, various heavy metals tests and detox protocols are being promoted online as healthy for the general population or for people suffering from certain health issues.

Science goes against these approaches. Evidence suggests that people should be cautious about these unproven, potentially unsafe, and often costly treatments.

Proposed Mechanisms of Damage

Heavy metal poisoning can cause an increase in the production of reactive oxygen species (ROS). Enhanced generation of ROS can overwhelm cells’ intrinsic antioxidant defenses, and result in oxidative stress. Cells under oxidative stress display various dysfunctions due to lesions caused by ROS to lipids, proteins, and DNA [11].

Scientists think that, in excess, heavy metals can further inactivate glutathione, inhibiting its antioxidant activity [12].

The Body’s Natural Chelators

Natural chelators that bind metals in our bodies include metallothioneins, and glutathione [13].

Metallothioneins

Metallothioneins (MTs) are cysteine-rich, small metal-binding proteins. MTs both take care of the physiological balance (homeostasis) of essential metals such as zinc and copper and protect against other toxic metals, such as cadmium and lead, by binding them and scavenging free radicals generated in oxidative stress [14, 15, 16].

One molecule of metallothionein can bind 7 atoms of bivalent metals (zinc, cadmium) or a greater number (12 atoms) of univalent ones (e.g. silver) [17].

Factors that Influence Metallothioneins:

  • Conditions like irritable bowel disease (IBD) decrease metallothioneins [18].
  • Zinc supplementation can restore metallothionein concentrations [18].
  • Chromium may inhibit zinc-induced metallothionein expression [18].
  • Hops, pomegranate, prune skin, and watercress can increase metallothioneins. So can sulforaphane from cruciferous vegetables, quercetin and Cordyceps sinensis, a mushroom native to the Himalayan region [18].

Beware of OTC Chelation Agents

The FDA clearly advises consumers against using over-the-counter chelation agents, which can be dangerous. Chelation agents should only be used by prescription and for certain cases, under medical supervision [19].

If you are being treated for heavy metal toxicity, certain healthy dietary changes and complementary strategies might be an option.

You may try the additional strategies listed below if you and your doctor determine that they could be appropriate. Many are not backed by proper clinical trials. None of these strategies should ever be done in place of what your doctor recommends or prescribes.

In people diagnosed with heavy metal poisoning, the goal of chelation is to bind heavy metals, which allows metals to be excreted out of the body.

Foods

Some foods have been suggested to reduce absorption or reabsorption of toxic metals and to support natural detoxification pathways:

  • Dietary insoluble fibers, including bran from grains as well as fruit, reduced levels of mercury in the brain and blood. However, soluble fiber, such as flaxseed, resulted in increased intestinal absorption of cadmium [13].
  • The algal polysaccharides alginate and chlorella were researched for reducing lead and mercury [13].
  • In mice, diets consisting of 5% and 10% of chlorella increased urinary and fecal excretion of mercury, and decreased mercury levels in the brain and kidneys, without affecting glutathione levels. Human studies about this use are lacking [20].
  • Diets rich in sulfur-containing foods such as alliums (onion family) and brassicas (cruciferous veggies) may increase glutathione and, theoretically, heavy metal detoxification.
  • Garlic prevents cadmium-induced kidney damage and decreases the oxidative damage due to lead in rats [13].

Human data are lacking.

Cilantro (leaves of Coriandrum sativum), a popular culinary and medicinal herb, is suggested to enhance mercury excretion following dental amalgam removal. In animals, it decreases lead absorption into bone [13].

However, in a study (RCT) on 32 children aged 3 – 7 years with lead-exposed parents found that cilantro extract given for 14 days did not decrease lead concentration in blood or excretion in urine compared to the placebo group [21].

Cilantro has not been tested for other types of heavy metal poisoning. It’s safe in the amounts it’s commonly used in foods, but there’s not enough data to rate its effects on health. Further clinical trials are required.

Supplements

Detox supplements have not been approved by the FDA for medical use. The FDA has not approved any supplement for heavy metals detox.

Supplements generally lack solid clinical research. Regulations set manufacturing standards for them but don’t guarantee that they’re safe or effective. Speak with your doctor before supplementing.

Therefore, no clinical evidence supports the use of the supplements listed below in people with heavy metal poisoning.

Below is a summary of the existing research, which should guide further investigational efforts. However, the studies listed below should not be interpreted as supportive of any health benefit.

Additionally, supplements may interact with medications. Speak with your doctor before supplementing. If you are being treated for heavy metal toxicity and your doctor determines some of the supplements listed below may be appropriate, you may try them.

  • Taurine and methionine, sulfur-containing amino acids, hypothesized to decrease oxidative stress markers resulting from heavy metal exposure [13].
  • Alpha lipoic acid may have metal-chelating activity. However, clinical experience suggests that it must be used carefully as it poses a risk of redistribution of metals. Clinical trials are lacking [13].
  • N-acetyl-cysteine (NAC), an orally available precursor of cysteine, is considered by some to be a chelator of toxic elements. It can also stimulate glutathione synthesis, particularly in the presence of vitamins C and E [13].
  • Limited research suggests that selenium forms a stable, insoluble compound with mercury, potentially providing relief of mercurialism symptoms. Organic selenium supplementation was beneficial in a controlled trial among 103 mercury-exposed villagers where a selenium yeast product increased mercury excretion and decreased oxidative stress. More research is needed [13, 22].
  • Magnesium and zinc supplementation have been proposed to blunt the absorption of cadmium [13].
  • Calcium supplementation reduced lead mobilization from maternal bones during pregnancy and lactation, protecting the newborn and infant [13]. In animals, calcium deprivation enhances the absorption of lead and cadmium [13].
  • In children, iron supplementation blunted lead accumulation [13].

Read about other purported detox supplements here.

Vitamins, Minerals, and Nutrients Essential for Detox

For the detoxification reactions to run smoothly, it is important for the body to be nutrient sufficient, because many vitamins and minerals are required either for the reactions themselves or for the production of detoxification enzymes. Researchers think that vitamins also help with the removal of the toxic products of phase I detoxification [23].

Minerals and Vitamins

The essential detoxification vitamins and minerals include vitamins A, B2, B3, B5, B6, folate (B9), B12, C and E, iron, calcium, copper, zinc, magnesium and selenium [23].

Limited research suggests that nutrients like zinc, calcium, iron, and magnesium might also reduce the absorption of toxic heavy metals. According to some studies, their depletion results in enhanced toxic metal uptake from the gut [24, 25, 26, 27].

These nutrients can be found in many healthy foods you can include. They are also included in multivitamin supplements. Talk to your doctor before taking any supplements or making major dietary changes, especially if you are currently receiving treatment for heavy metal poisoning.

Summary of “Detox Foods”

Anecdotally, these are usually considered “detox foods.” Most are good for general health and wellness, but clinical data about their effects on detoxification are largely lacking. Here’s a summary of these foods:

  • Apiaceous vegetables (carrots, parsnips, celery, parsley)
  • Apples
  • Artichoke
  • Berries (raspberries, blueberries)
  • Black tea
  • Black pepper
  • Broccoli and other cruciferous vegetables (arugula, bok choy, Brussel sprouts, cabbage, kale)
  • Caffeic acid (found in plants, with especially high levels in thyme, sage, spearmint Ceylon cinnamon, star anise, and yerba mate)
  • Celery
  • Chili peppers
  • Cilantro
  • Cinnamon
  • Citruses
  • Curcumin/Turmeric
  • Dandelion
  • Ellagic acid (found in blackberries, cranberries, pecans, pomegranates, raspberries, strawberries, walnuts, wolfberries, and grapes)
  • Fish oil
  • Garden cress
  • Garlic
  • Ghee
  • Ginger
  • Ginkgo
  • Goldenseal
  • Grapefruit
  • Green tea
  • Honeybush tea
  • Kale
  • Licorice
  • Lycopene
  • Olives and olive oil
  • Pomegranate
  • Propolis
  • Purple sweet potato
  • Quercetin (found in many plants, high in red kidney beans and capers)
  • Resveratrol (found in peanuts, grapes, and red wines)
  • Rooibos tea
  • Rosemary
  • Soybean/Black soybean
  • Starfruit
  • Watercress
  • Yarrow

Probiotics

Probiotics have many health benefits. Some researchers think that they might also bind toxins and reduce their toxicity, but clinical trials haven’t been carried out.

In animals, probiotics seem to bind heavy metals and prevent their absorption. They have been proposed to prevent cadmium, lead [28, 29, 30] and copper toxicity [31], and to potentially help with aluminum toxicity [32].

Furthermore, some scientists hypothesize that probiotics may reduce the absorption and toxicity of organophosphate pesticides [33, 34, 35].

In animals, they appear to bind to and inactivate heterocyclic aromatic amines (HACs), the most abundant mutagens in fried red meat [34, 36].

In test tubes, probiotics reduce the level of aflatoxin, produced by fungi and found in crops [37, 38, 39, 40, 41, 42].

Additionally, probiotics produce butyrate, which might induce phase II GST enzymes [43].

Calorie restriction and intermittent fasting

No clinical evidence supports the practice of caloric restriction or intermittent fasting for detoxification. These dietary modifications may be recommended to some people with metabolic issues or obesity, however.

If you decide to fast, make sure to consume enough fruits and veggies. Also, fasting is not an option for some people (for example, if you need to take medications with food or have certain medical conditions). Consult your doctor before fasting to make sure it’s safe for you.

Why might fasting be beneficial?

According to one theory, various metabolic, microbiota-derived and environmental toxins accumulate in fat tissue [44] because most of them are fat-soluble. In that way, these toxins temporarily escape detoxification enzymes.

In turn, high levels of toxins in the adipose tissues may decrease the turnover of fats in order to protect other organs from toxins [44]. This means that toxins accumulated in fat tissue might hypothetically make it more difficult to lose weight.

The content of persistent organic pollutants (POPs) in adipose (fat) tissues has been reported to be 2-3 times higher in obese compared to lean persons [44].

The effects of calorie restriction, by reduction of the daily intake by 20-40% year around, or intermittent fasting have shown some beneficial health effects [44, 45].

Reduced calorie intake without malnutrition has been proposed to induce Nrf2. but human data are lacking [46].

What about Sweating and Saunas?

Throughout the world, sweating with heat and/or exercise has long been associated with “cleansing.” Sweating has been suggested to assist with the removal of toxic elements from the body, but evidence is lacking to support this approach [47].

Nonetheless, various cultures engaged in sweat-inducing activities periodically. Whether it’s a Roman bath, Aboriginal sweat lodge, Scandinavian sauna, Turkish bath or rigorous exercise, sweating was traditionally viewed as beneficial.

Moderate exercise is great for most people. Sauna is probably also good for the average healthy person – it supports overall wellness. But despite the popular claims, heat, infrared light – and any type of sauna, for that matter – will not help you “sweat out toxins.”

For example, researchers believe that sauna use increases circulation throughout the skin and induces sweating, with blood flow to the skin increasing from 5 – 10% and the amount of blood pumped through the heart at rest to 60 – 70% [48].

Limited studies suggest that sweating causes some minerals, such as zinc, copper, and manganese to be excreted via the skin. But it has never been shown that sweating – caused by exercise or sauna use or other means – increases the elimination of heavy metals or that it’s helpful for people with heavy metal poisoning. This is a myth [49, 50].

Learn More

About the Author

Biljana Novkovic

Biljana Novkovic

PhD
Biljana received her PhD from Hokkaido University.
Before joining SelfHacked, she was a research scientist with extensive field and laboratory experience. She spent 4 years reviewing the scientific literature on supplements, lab tests and other areas of health sciences. She is passionate about releasing the most accurate science and health information available on topics, and she's meticulous when writing and reviewing articles to make sure the science is sound. She believes that SelfHacked has the best science that is also layperson-friendly on the web.

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