ODX Supplement Series: Metabolic Detoxification

Over 86,000 chemicals are registered in the United States, and approximately 2,000 new chemicals come to market annually (Allen 2011, TSCA 2024).

Common toxicants include heavy metals, persistent organic pollutants (e.g., pesticides, industrial and technical chemicals, and by-products of industrial processes), electromagnetic radiation, fat metabolites, alcohol metabolites, pharmaceutical and recreational drugs, and bacterial endotoxins (Allen 2011, Ayyadurai 2023). Toxicant exposure comes from various environmental sources, such as soil, air, water, dust, or food, when they are breathed, consumed, or absorbed.

Adverse health effects from bioaccumulative toxicants may include but are not limited to, endocrine disruption, neurological dysfunction, reproductive effects, abnormal cell growth, and cardiovascular diseases (Allen 2011).

Detoxification involves the mobilization, biotransformation, and elimination of toxic substances. With the help of supportive nutritional compounds, toxins are metabolized through phase I cytochrome P450 enzymes. The resulting intermediary metabolites are further biotransformed and neutralized through phase II pathways. This processing of toxins occurs primarily in the liver. Processed toxins are then excreted through bile, stool, and urine (Cline 2015, Hodges 2015).

Supportive Supplements

Protein/Amino Acids

To prevent protein deficiency: ~0.8 to 0.9 g/kg. Optimal intakes vary based on age, weight, and activity level and can range between 1.2 g/kg up to 2.7 g/kg (Examine.com 2024).

• High-quality, bioavailable protein is an important source of amino acids for the activity of phase I and phase II enzymes (Cline 2015).
• Glycine, L-glutamine, methionine, L-cysteine, and taurine are particularly important for phase II conjugation enzymes (Cline 2015).

Chlorella

Common daily doses of chlorella range from 6 g/d to 10 g/d in the scientific literature. The optimal dose of supplemental chlorella is not known (Examine.com 2024).

• Chlorella is a rich source of micronutrients and imparts metal-chelating effects.
• Nutritional algae extract (Chlorella/Fucus sp) and aminosulphurate supplementation for 90 days in subjects with amalgam fillings reduced mercury, silver, tin, lead, and uranium levels as compared with basal levels (Merino 2019).
• A chlorella dose of 9 g/day for 90 days significantly reduced hair mercury levels in an open-label trial of 58 healthy subjects. Blood mercury levels were also reduced (Maruyama 2018).
• A lower dose of 100 mg/day supported the detoxification of carcinogenic heterocyclic amines in a small two-week, double-blind, placebo-controlled study (Lee 2015).

B vitamins

B vitamin support for detoxification should include 10-25 mg of B6, 500-10,000 mcg of B12, 1,500 mcg of folate, and a balance of other B vitamins (Noland 2020).

• B vitamins support energy generation and detoxification, an energy-dependent process.
• B vitamins, including riboflavin, niacin, pyridoxine, folate, and B12, are essential cofactors for the cytochrome P450 enzymes involved in phase I detoxification (Cline 2015).

Milk Thistle

Typical daily doses for hepatoprotection fall between 420 mg and 600 mg of silymarin per day in divided doses (Examine.com 2024).

• Milk thistle/silymarin can provide antioxidant protection against reactive intermediates produced during phase I detoxification (Cline 2015).
• Silymarin benefits liver diseases through antioxidant, antifibrotic, choleretic, and anti-inflammatory activities. It also stimulates hepatic regeneration (Abenavoli 2018).

Glutathione/N-Acetyl L-cysteine (NAC)

N-acetyl L-cysteine efficiently increases intracellular glutathione synthesis, a major detoxification antioxidant. NAC is most often given in the dosage range of 600 to 1,800 mg daily in divided doses (Examine.com 2024)

• Glutathione provides antioxidant defense against reactive intermediates produced during phase I detoxification and is needed for glutathione conjugation in phase II detoxification (Cline 2015).
• Glutathione directly scavenges diverse oxidants, facilitates toxin excretion from cells and the body, and directly neutralizes persistent organic pollutants (Pizzorno 2014).

References

Abenavoli, Ludovico, et al. "Milk thistle (Silybum marianum): A concise overview on its chemistry, pharmacological, and nutraceutical uses in liver diseases." Phytotherapy research 32.11 (2018): 2202-2213.

Allen, Jason, et al. "Detoxification in naturopathic medicine: a survey." The Journal of Alternative and Complementary Medicine 17.12 (2011): 1175-1180.

Ayyadurai, VA Shiva, Prabhakar Deonikar, and Christine Fields. "Mechanistic understanding of D-Glucaric acid to support liver detoxification essential to muscle health using a computational systems biology approach." Nutrients 15.3 (2023): 733.

Chlorella. Examine.com. Accessed August 29, 2024. https://examine.com/supplements/chlorella/

Cline, John C. “Nutritional aspects of detoxification in clinical practice.” Alternative therapies in health and medicine vol. 21,3 (2015): 54-62.

Hodges, Romilly E, and Deanna M Minich. “Modulation of Metabolic Detoxification Pathways Using Foods and Food-Derived Components: A Scientific Review with Clinical Application.” Journal of nutrition and metabolism vol. 2015 (2015): 760689. doi:10.1155/2015/760689

Lee, Inyeong et al. “Detoxification of chlorella supplement on heterocyclic amines in Korean young adults.” Environmental toxicology and pharmacology vol. 39,1 (2015): 441-6. doi:10.1016/j.etap.2014.11.015

Noland, Diana, Jeanne A. Drisko, and Leigh Wagner, eds. Integrative and functional medical nutrition therapy: principles and practices. Springer Nature, 2020.

Maruyama, Isao, et al. "Chlorella supplementation decreases methylmercury concentrations of hair and blood in healthy volunteers." Fundamental Toxicological Sciences 5.3 (2018): 117-122.

Merino, José Joaquín et al. “The Long-Term Algae Extract (Chlorella and Fucus sp) and Aminosulphurate Supplementation Modulate SOD-1 Activity and Decrease Heavy Metals (Hg++, Sn) Levels in Patients with Long-Term Dental Titanium Implants and Amalgam Fillings Restorations.” Antioxidants (Basel, Switzerland) vol. 8,4 101. 16 Apr. 2019, doi:10.3390/antiox8040101

Milk Thistle. Examine.com. Accessed August 29, 2024. https://examine.com/supplements/milk-thistle/

N-Acetyl L-Cysteine (NAC). Examine.com. Accessed August 29, 2024. https://examine.com/supplements/n-acetylcysteine/

Optimal Protein Intake Guide & Calculator. Examine.com. Accessed August 29, 2024. https://examine.com/guides/protein-intake/?srsltid=AfmBOornS5KKc85ZEh9JCbdAZt99gABrV5bz7TLl35g4ixB_gvdcGnkO

Pizzorno, Joseph. "Glutathione!" Integrative Medicine: A Clinician's Journal 13.1 (2014): 8.

TSCA chemical substance inventory. United States Environmental Protection Agency. Accessed March 12, 2024. https://www.epa.gov/tsca-inventory/about-tsca-chemical-substance-inventory