Detox IV

Full ingredient list

Exact amounts delivered in each size. Formulas are compounded per patient and can be adjusted by your provider.

Supporting studies

• 1

  Glutathione is the molecule liver enzymes attach to toxins during Phase II detoxification so they can be excreted.

  This Annual Review of Pharmacology and Toxicology review covers the three mammalian glutathione transferase (GST) families - cytosolic, mitochondrial, and microsomal. These Phase II enzymes conjugate glutathione onto electrophilic xenobiotics such as carcinogens and environmental pollutants, and also onto endogenous compounds including aldehydes, quinones, and lipid hydroperoxides generated during oxidative stress. The review also describes glutathione transferases' roles in leukotriene, prostaglandin, and steroid hormone biosynthesis, and in modulating gene expression through nuclear receptor pathways. Glutathione is the required cofactor for this entire conjugation system.

  Mechanistic review Hayes JD, Flanagan JU, Jowsey IR Glutathione transferases. Annual Review of Pharmacology and Toxicology. 2005. PMID 15822171 ↗

• 2

  Glutathione is the body's most abundant intracellular antioxidant and its central redox regulator.

  This widely cited review in Molecular Aspects of Medicine describes glutathione as the most abundant low-molecular-weight thiol compound synthesized in human cells. The authors detail its role in protecting cells from oxidative damage and from the toxicity of reactive xenobiotic electrophiles, and in maintaining the cell's overall redox balance. The paper covers where oxidants and electrophiles come from, how glutathione eliminates them (by reduction and by conjugation), and how glutathione synthesis is regulated - including therapeutic strategies for raising cellular glutathione content.

  Mechanistic review Forman HJ, Zhang H, Rinna A Glutathione: overview of its protective roles, measurement, and biosynthesis. Molecular Aspects of Medicine. 2009. PMID 18796312 ↗

• 3

  Glutathione levels fall sharply with age, and restoring glutathione synthesis returns older adults' oxidative stress markers to youthful levels within two weeks.

  Using stable-isotope infusion techniques, researchers compared eight older and eight younger adults. Older subjects had markedly lower red blood cell glutathione concentrations, a substantially reduced rate of glutathione synthesis, and elevated markers of oxidative stress and oxidant damage. After just two weeks of supplementation with the glutathione precursors cysteine and glycine, older subjects' glutathione synthesis rates and concentrations were fully restored and their oxidative stress markers fell to levels comparable with the young control group. Route: dietary/oral precursor supplementation; glutathione status measured directly in blood.

  Controlled clinical study with stable-isotope kinetics Sekhar RV, Patel SG, Guthikonda AP, et al. Deficient synthesis of glutathione underlies oxidative stress in aging and can be corrected by dietary cysteine and glycine supplementation. The American Journal of Clinical Nutrition. 2011. PMID 21795440 ↗

• 4

  Intravenous N-acetylcysteine is powerful enough to protect the liver in acetaminophen poisoning — in the landmark study, 40 of 40 patients treated within eight hours had virtually complete protection against liver damage.

  Prescott and colleagues treated 100 consecutive cases of severe paracetamol (acetaminophen) poisoning with intravenous N-acetylcysteine. There was virtually complete protection against liver injury in the 40 patients treated within 8 hours, and only 1 of 62 patients treated within 10 hours developed severe liver damage, compared with 33 of 57 (58%) historical patients given supportive care alone. IV NAC also prevented kidney impairment and death, and the authors described the infusion as noticeably free of adverse effects. This is the clinical work behind NAC's status as an FDA-approved intravenous antidote and the clearest human demonstration of its hepatic antioxidant action.

  Clinical trial (prospective case series with historical control) Prescott LF, et al. Intravenous N-acetylcystine: the treatment of choice for paracetamol poisoning. British Medical Journal. 1979. PMID 519312 ↗

• 5

  A systematic review of more than 5,000 patients found intravenous and oral acetylcysteine equally effective at protecting the liver, confirming the IV route delivers the full therapeutic effect.

  This systematic review and meta-analysis pooled 16 studies covering 5,164 patients treated with acetylcysteine for acetaminophen toxicity. Hepatotoxicity rates were essentially identical between routes — 12.6% for oral and 13.2% for intravenous — and earlier treatment was associated with better outcomes. For a clinic setting, this is direct human evidence that intravenously delivered NAC reaches tissue and performs the same antioxidant, liver-protective job as the oral form.

  Systematic review and meta-analysis Green JL, et al. Oral and Intravenous Acetylcysteine for Treatment of Acetaminophen Toxicity: A Systematic Review and Meta-analysis. Western Journal of Emergency Medicine. 2013. PMID 23687539 ↗

• 6

  In a randomized clinical trial, supplementing the glutathione building blocks glycine and N-acetylcysteine corrected glutathione deficiency in older adults and improved walking speed, muscle strength and mitochondrial function.

  Researchers at Baylor College of Medicine randomized 24 older adults (ages 61-80) to GlyNAC or placebo for 16 weeks, with 12 young adults as a comparison group. Older adults started out glutathione-deficient with high oxidative stress and impaired mitochondrial fuel oxidation; GlyNAC — and not placebo — improved or corrected those defects and also improved gait speed, muscle strength, 6-minute walk distance, waist circumference and blood pressure. Supplementation was oral, and was reported as safe and well tolerated.

  Randomized controlled trial Kumar P, et al. Supplementing Glycine and N-Acetylcysteine (GlyNAC) in Older Adults Improves Glutathione Deficiency, Oxidative Stress, Mitochondrial Dysfunction, Inflammation, Physical Function, and Aging Hallmarks: A Randomized Clinical Trial. The Journals of Gerontology: Series A, Biological Sciences and Medical Sciences. 2023. PMID 35975308 ↗

• 7

  An earlier clinical trial of the same NAC-based protocol restored red blood cell glutathione in older adults and improved inflammation, insulin sensitivity, blood vessel function, strength, gait speed and cognition.

  This 24-week pilot clinical trial supplemented older adults with glycine plus N-acetylcysteine and measured red-cell glutathione, oxidative stress, mitochondrial function and a broad panel of clinical outcomes. Supplementation corrected glutathione deficiency and improved inflammation, endothelial function, insulin resistance, genomic damage, cognition, muscle strength, gait speed and exercise capacity, while lowering body fat and waist circumference. Benefits declined after supplementation was stopped for 12 weeks, indicating the effects tracked with continued nutrient delivery. Route was oral.

  Clinical trial Kumar P, et al. Glycine and N-acetylcysteine (GlyNAC) supplementation in older adults improves glutathione deficiency, oxidative stress, mitochondrial dysfunction, inflammation, insulin resistance, endothelial dysfunction, genotoxicity, muscle strength, and cognition: Results of a pilot clinical trial. Clinical and Translational Medicine. 2021. PMID 33783984 ↗

• 8

  Vitamin C supplementation raised glutathione — the body's master antioxidant — inside red blood cells by nearly 50%.

  In this double-blind study, adults consumed vitamin C-restricted diets and took placebo for a baseline week, then 500 mg of L-ascorbate daily for two weeks, then 2,000 mg daily for two weeks, then placebo again. Mean red blood cell glutathione rose nearly 50% after the 500 mg period compared with baseline (p < 0.05), with individual increases ranging from +8% to +84%. The authors concluded that vitamin C supplementation maintains reduced glutathione concentrations in blood and improves the overall antioxidant protective capacity of blood. (Route: oral.)

  Double-blind human supplementation study Johnston CS, Meyer CG, Srilakshmi JC Vitamin C elevates red blood cell glutathione in healthy adults. The American Journal of Clinical Nutrition. 1993. PMID 8317379 ↗

• 9

  Methionine is an essential sulfur amino acid that feeds directly into glutathione production and activates the body's own antioxidant enzymes.

  This review characterizes methionine as an aliphatic, sulfur-containing essential amino acid that the body cannot synthesize and must obtain from outside sources. It describes methionine's role in lipid metabolism, in activating endogenous antioxidant enzymes such as methionine sulfoxide reductase A, and in the biosynthesis of glutathione to counteract oxidative stress. Methionine also serves as a precursor for other key metabolites and helps regulate immune and metabolic function in mammals. This links methionine and N-acetylcysteine to the same downstream antioxidant pathway.

  Mechanistic review Martínez Y, et al. The role of methionine on metabolism, oxidative stress, and diseases. Amino Acids. 2017. PMID 28929442 ↗

• 10

  Methionine is the raw material for SAMe, the body's principal methyl donor, which is made mainly in the liver and is central to healthy liver metabolism.

  This comprehensive Physiological Reviews article describes how the enzyme methionine adenosyltransferase converts methionine and ATP into S-adenosylmethionine (SAMe), the body's main biological methyl donor, with the liver as the primary site of production. The review details how adequate hepatic SAMe supports methylation reactions, antioxidant defense and normal liver homeostasis, while experimental models with reduced hepatic SAMe develop oxidative stress and steatohepatitis. It also notes SAMe's therapeutic promise in intrahepatic cholestasis of pregnancy. This is the mechanistic rationale for methionine's inclusion as a lipotropic, methyl-donor nutrient.

  Mechanistic review Lu SC, Mato JM S-adenosylmethionine in liver health, injury, and cancer. Physiological Reviews. 2012. PMID 23073625 ↗

• 11

  A controlled human feeding study proved choline is truly essential: most adults deprived of it developed fatty liver or muscle changes, which resolved once choline was restored.

  Fischer and colleagues fed healthy adults with normal folate and B12 status a choline-depleted diet under controlled conditions. Seventy-seven percent of men and 80% of postmenopausal women developed fatty liver or elevated muscle enzymes, compared with 44% of premenopausal women, and the organ dysfunction resolved when choline was added back to the diet. Some men developed changes even while consuming the current recommended adequate intake, showing individual choline requirements vary widely. This is the clearest human evidence for choline's role in hepatic fat handling.

  Controlled human feeding (clinical) study Fischer LM, et al. Sex and menopausal status influence human dietary requirements for the nutrient choline. The American Journal of Clinical Nutrition. 2007. PMID 17490963 ↗

• 12

  Choline — the head group of phosphatidylcholine — was formally recognized as an essential nutrient by the Institute of Medicine in 1998, yet most Americans fall well short of the recommended intake.

  Zeisel and da Costa's review documents that the Institute of Medicine designated choline an essential nutrient in 1998, setting Adequate Intakes of 550 mg/day for men and 425 mg/day for women, based in part on the liver damage observed at lower intakes. Because choline supports everything from cell membrane structure to neurotransmitter synthesis, inadequate intake is linked to liver disease and atherosclerosis. The authors note that mean intakes for older children, men, women and pregnant women fall far below the IOM's adequate intake, and call for dietary guidance to increase consumption of choline-rich foods.

  Narrative review / nutritional requirement analysis Zeisel SH, da Costa KA Choline: an essential nutrient for public health. Nutrition Reviews. 2009. PMID 19906248 ↗

• 13

  Toxic metals cause damage largely by generating free radicals and draining the body's antioxidant reserves — and chelation therapy is a recognized way to reverse that oxidative burden.

  This comprehensive review examines how arsenic, lead, cadmium and mercury produce reactive oxygen species that injure cells, concluding that the toxic effects of these metals are caused primarily by an imbalance between pro-oxidant and antioxidant homeostasis — that is, oxidative stress. The authors evaluate the established chelating agents EDTA, DMPS, DMSA and BAL as the therapeutic answer to that metal-driven oxidative load, and note that pairing antioxidant support with chelation produces better outcomes than chelation alone — a rationale for combining chelation with antioxidant-containing IV protocols.

  Mechanistic review Flora SJS, Mittal M, Mehta A Heavy metal induced oxidative stress & its possible reversal by chelation therapy. Indian Journal of Medical Research. 2008. PMID 19106443 ↗

References

• 1Hayes JD, Flanagan JU, Jowsey IR. Glutathione transferases. Annual Review of Pharmacology and Toxicology. 2005. PMID 15822171 ↗
• 2Forman HJ, Zhang H, Rinna A. Glutathione: overview of its protective roles, measurement, and biosynthesis. Molecular Aspects of Medicine. 2009. PMID 18796312 ↗
• 3Sekhar RV, Patel SG, Guthikonda AP, et al. Deficient synthesis of glutathione underlies oxidative stress in aging and can be corrected by dietary cysteine and glycine supplementation. The American Journal of Clinical Nutrition. 2011. PMID 21795440 ↗
• 4Prescott LF, et al. Intravenous N-acetylcystine: the treatment of choice for paracetamol poisoning. British Medical Journal. 1979. PMID 519312 ↗
• 5Green JL, et al. Oral and Intravenous Acetylcysteine for Treatment of Acetaminophen Toxicity: A Systematic Review and Meta-analysis. Western Journal of Emergency Medicine. 2013. PMID 23687539 ↗
• 6Kumar P, et al. Supplementing Glycine and N-Acetylcysteine (GlyNAC) in Older Adults Improves Glutathione Deficiency, Oxidative Stress, Mitochondrial Dysfunction, Inflammation, Physical Function, and Aging Hallmarks: A Randomized Clinical Trial. The Journals of Gerontology: Series A, Biological Sciences and Medical Sciences. 2023. PMID 35975308 ↗
• 7Kumar P, et al. Glycine and N-acetylcysteine (GlyNAC) supplementation in older adults improves glutathione deficiency, oxidative stress, mitochondrial dysfunction, inflammation, insulin resistance, endothelial dysfunction, genotoxicity, muscle strength, and cognition: Results of a pilot clinical trial. Clinical and Translational Medicine. 2021. PMID 33783984 ↗
• 8Johnston CS, Meyer CG, Srilakshmi JC. Vitamin C elevates red blood cell glutathione in healthy adults. The American Journal of Clinical Nutrition. 1993. PMID 8317379 ↗
• 9Martínez Y, et al. The role of methionine on metabolism, oxidative stress, and diseases. Amino Acids. 2017. PMID 28929442 ↗
• 10Lu SC, Mato JM. S-adenosylmethionine in liver health, injury, and cancer. Physiological Reviews. 2012. PMID 23073625 ↗
• 11Fischer LM, et al. Sex and menopausal status influence human dietary requirements for the nutrient choline. The American Journal of Clinical Nutrition. 2007. PMID 17490963 ↗
• 12Zeisel SH, da Costa KA. Choline: an essential nutrient for public health. Nutrition Reviews. 2009. PMID 19906248 ↗
• 13Flora SJS, Mittal M, Mehta A. Heavy metal induced oxidative stress & its possible reversal by chelation therapy. Indian Journal of Medical Research. 2008. PMID 19106443 ↗