Immune response and inflammation during chemo and radiation therapy

Biological half-lives – Links

Methodological basis for half-lives

To ensure clinical credibility, the specified values have been established through a hierarchical prioritization of data across four levels – under Biological half-lives – Links (at the bottom of the page) called Level of Evidence:

• Level 1 (white): Direct evidence from human pharmacokinetic studies (measured in human blood).
• Level 2 (green): Extrapolation from the most potent active ingredients in complex extracts.
• Level 3 (yellow): Pharmacological estimate based on biochemical degradation and enzymatic kinetics.
• Level 4 (orange): Conservative estimate based on preclinical data (in vitro/in vivo) with an integrated safety margin.

By respecting these intervals, biosupport can be applied strategically during the recovery phase to optimize the overall course of treatment and minimize side effects without compromising the therapeutic index.

AHCC (active hexose correlated compound)

Half-life: Estimated < 5 hours (plasma) / Enzymatic impact normalized within 48 hours.

Washout: 2 days.

Level of Evidence: 2 (green).

Documentation: AHCC is a fermented mushroom extract rich in acetylated alpha-glucans. A human Phase 1 study (Spierings et al., 2007) documents clinical safety at high doses. However, metabolic studies (Mach et al., 2008; Mathew et al., 2017) demonstrate that AHCC functions as both a substrate and inducer of the liver enzyme CYP2D6 (Phase 1) as well as an inducer of UGT 1A3 and 1A6 (Phase 2). Since these enzymatic pathways are responsible for the metabolism of many oncological drugs (e.g., tamoxifen and letrozole), there is a risk of reduced treatment efficacy. Based on this proven enzymatic impact in human tissue, the washout period is set at 2 days to ensure metabolic normalization before treatment.

Link:

[A] Spierings E. L. et al.: A Phase I study of the safety of AHCC in healthy volunteers (J Nutr Sci Vitaminol, 2007) – Human safety.

[B] Mathew L., Gaikwad A., Smith J. A. et al.: Evaluation of Active Hexose Correlated Compound (AHCC) in Combination With Anticancer Hormones in Orthotopic Breast Cancer Models (Integrative Cancer Therapies, 2017)

[C] Coffer L. W. et al.: Evaluation of Active Hexose Correlated Compound (Ahcc) on Phase II Drug Metabolism Pathways and the Implications for Supplement-Drug Interactions (Semantic Scholar / ResearchGate, 2015)

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Akkermansia (muciniphila)

Half-life: 3–5 days (based on fecal washout).

Washout: 2 weeks (deviation: based on persistence in the gut and stabilization of the intestinal barrier).

Level of Evidence: 3 (yellow).

Documentation: Since this involves a bacterium, measurement is not based on a traditional biological half-life in the blood, but rather on its presence in the gut. The documentation is based on a clinical study (Depommier et al., Nature Medicine, 2019), which demonstrates the metabolic impact of the bacterium. Washout studies of probiotic bacteria show that levels in the gut typically return to baseline within one week after supplementation ends. The washout period is therefore set at 1–2 weeks to ensure that the bacterium’s production of metabolic byproducts (postbiotics) and its influence on the intestinal barrier have ceased before the initiation of oncological treatment.

Link:

[A] Depommier et al.: Supplementation with Akkermansia muciniphila in overweight and obese human volunteers: a proof-of-concept exploratory study (Nature Medicine, 2019)

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Activated charcoal

Half-life: Not relevant (not systemically absorbed).

Washout: 1 day (deviation: based exclusively on gastrointestinal passage).

Level of Evidence: 1 (white).

Documentation: Since activated charcoal is not absorbed into the blood but remains in the gastrointestinal tract, its presence is governed exclusively by gastrointestinal transit time. According to the clinical status report (Silberman et al., 2023), the substance is most effective within 1 hour after ingestion, and its excretion follows the body’s natural passage (typically 12–24 hours). As there is no systemic half-life to account for, the washout period is based solely on ensuring complete passage through the gut before oncological treatment.

Link:

[A] Activated Charcoal (NIH, 2023)

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Alpha-Lipoic Acid (ALA)

Half-life: 15–20 minutes (R-isomer) / up to 1 hour (racemate).

Washout: 2 days.

Level of Evidence: 1 (white).

Documentation: ALA is a sulfur-containing fatty acid that functions as a potent antioxidant in both aqueous and lipid phases. Human Phase 1 studies (Zárate et al., 2025) and randomized clinical trials (Yoon et al., 2016) unequivocally document that ALA is rapidly absorbed (tmax < 1 hour) and promptly eliminated from plasma with a half-life of less than 20 minutes for the biologically active R-form. Previous assumptions of long terminal elimination (based on preclinical models) have not been reproduced in human pharmacokinetic measurements over 36 hours. Since ALA effectively regenerates other antioxidants such as vitamins C and E, the washout period is conservatively set at 2 days to ensure that the enhanced antioxidant status is normalized before oncological treatment.

Link:

[A] Zárate E., Bravo-Lamicq C. et al.: Pharmacokinetics and safety of a fixed-dose combination of pregabalin and thioctic acid in healthy volunteers (Frontiers in Pharmacology, 2025) – Human safety. Latest human Phase 1 data.

[B] Yoon J., Moon S. J. et al.: Comparison of R(+)-α-lipoic acid exposure in healthy Korean male subjects (Translational and Clinical Pharmacology, 2016) – Documentation for the very short human half-life.

[C] Superti F. & Russo R.: Alpha-Lipoic Acid: Biological Mechanisms and Health Benefits (Antioxidants, 2024) – Systematic review of mechanisms of action.

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Amygdalin (B17)

Half-life: 45–120 minutes (for the substance itself), but with a risk of cyanide accumulation.

Washout: 2 days (deviation: requires time for elimination of toxic cyanide metabolite).

Level of Evidence: 1 (white).

Documentation: The clinical study (Moertel et al., 1982) conducted on 178 patients documents that amygdalin has no therapeutic effect on cancer but instead carries a significant risk of cyanide poisoning. The study showed that several patients had blood cyanide levels measured close to the lethal range. Since the substance is directly toxic and affects cellular oxygen uptake, the washout period is set at 2 days to ensure that cyanide levels have normalized before oncological treatment.

Link:

[A] A Clinical Trial of Amygdalin (Laetrile) in the Treatment of Human Cancer (The New England Journal of Medicine, 1982)

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Andrographis paniculata

Half-life: 2–7 hours.

Washout: 2 days.

Level of Evidence: 2 (green).

Documentation: Since the preparation is a complex extract, the evidence is based on extrapolation from the active driver, andrographolide. According to the systematic review (Raman et al., 2022), the plant contains active diterpene lactones (including andrographolide), which have a wide range of biological effects, including anti-inflammatory and antioxidant activity. As these constituents have low water solubility and undergo extensive metabolism in the body, the half-life varies but has been measured at approximately 6.67 hours. The washout period is set at 2 days to ensure that the plant’s influence on the cellular antioxidant balance and the liver’s enzyme systems has ceased before oncological treatment.

Link:

[A] Subashini Raman, Vikneswaran Murugaiyah et al.: Andrographis paniculata Dosage Forms and Advances in Nanoparticulate Delivery Systems: An Overview (PubMed, 2022)

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Apigenin

Half-life: 2.5 hours (plasma) / 12 hours (human excretion) / 91.8 hours (terminal phase).

Washout: 19 days. (3 days for short-term use)

Level of Evidence: 4 orange (preclinical data and metabolic clearance).

Documentation: Apigenin is a flavonoid with complex pharmacokinetics. Systematic reviews of human data (Wang et al., 2019) report an average excretion half-life of approximately 12 hours, while the plasma half-life for free apigenin has been measured as low as 2.5 hours (DeRango-Adem et al., 2021). However, the classic kinetics study (Gradolatto et al., 2005) demonstrated a very slow elimination with a terminal half-life of 91.8 hours due to enterohepatic recirculation. Latest research (Sato et al., Nature 2024) confirms that modern nano-delivery systems significantly increase bioavailability, potentially increasing the risk of tissue accumulation. To ensure complete clearance during regular use, a safety interval of 19 days is maintained, while 3 days is considered sufficient for short-term use.

Link:

[A] Wang M., Firrman J. et al.: A Review on Flavonoid Apigenin: Dietary Intake, ADME, Antimicrobial Effects, and Interactions with Human Gut Microbiota (NIH, Biomed Res Int., 2019)

[B] Sato V. H., Sato H. et al.: Enhancement of in vitro transcellular absorption and in vivo oral bioavailability of apigenin by self-nanoemulsifying drug delivery systems (Scientific Reports, Nature, 2024)

[C] DeRango-Adem et al.: Does Oral Apigenin Have Real Potential for a Therapeutic Effect in the Context of Human Gastrointestinal and Other Cancers? (Frontiers in Pharmacology, 2021)

[D] Gradolatto et al.: PHARMACOKINETICS AND METABOLISM OF APIGENIN IN FEMALE AND MALE RATS AFTER A SINGLE ORAL ADMINISTRATION (Science Direct, 2005)

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Artemisinin

Half-life: 1–5 hours.

Washout: 1 day.

Level of Evidence: 1 (white).

Documentation: A randomized controlled study ([A] Gordi, 2002) shows that artemisinin has a short half-life and exhibits time-dependent pharmacokinetics, where the substance induces its own metabolism, thereby increasing the rate of excretion over time. Another study ([B] Benakis, 1997) determines the average elimination phase to be between approximately 2.6 and 4.3 hours (distribution and elimination half-life, respectively). Since the substance is rapidly excreted from the body and does not accumulate with repeated dosing, the washout period is set at 1 day to ensure that the active ingredients are out of the system before oncological treatment.

Link:

[A] Gordi: Artemisinin Pharmacokinetics and Efficacy in Uncomplicated-Malaria Patients Treated with Two Different Dosage Regimens (ASM Journals, 2002)

[B] Benakis: Pharmacokinetics of Artemisinin and Artesunate after Oral Administration in Healthy Volunteers (1997)

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Ashwagandha

Half-life: 1–5 hours.

Washout: 2 days.

Level of Evidence: 3 (yellow).

Documentation: A comprehensive study (Modi et al., 2022) has mapped the pharmacokinetics of the central constituents (withanolides). The results show rapid absorption via the gastrointestinal tract (tmax of less than 1 hour) and fast turnover in the blood. Although the individual components have short half-lives, they exhibit the ability to cross the blood-brain barrier and affect central body functions. Due to this systemic impact and documented interactions with the hormonal system and liver metabolism, the washout period is set at 2 days to ensure metabolic normal conditions before oncological treatment.

Link:

[A] Modi et al.: Pharmacokinetic Study of Withanosides and Withanolides from Withania somnifera Using Ultra-High Performance Liquid Chromatography-Tandem Mass Spectrometry (UHPLC-MS/MS) (PubMed, 2022)

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Astragalus

Half-life: 2.1–2.7 hours (human measurements).

Washout: 1 day.

Level of Evidence: 1 (white).

Documentation: Astragalus contains saponins, with Astragaloside IV being the primary active marker. A comprehensive review (Stępnik et al., 2025) summarizes the substance’s anti-inflammatory and immunomodulatory effects. A human Phase 1 study (Xu et al., 2013) documents rapid and linear elimination in humans with a half-life of 2.1–2.7 hours and confirms that no accumulation occurs with daily dosing. The mathematical elimination (5 x t½) is thus completed in less than 14 hours. Preclinical models have shown half-lives of up to 5.5 hours (Tan et al., 2020), but these have not been reproduced in human trials. Since Astragalus has a low oral bioavailability of approximately 2.2% (ResearchGate, 2018) and the substance is excreted rapidly, a 24-hour washout ensures full elimination of the active components and a good margin for normalization of biological processes before oncological treatment.

Link:

[A] Xu M., Yin J. et al.: Pharmacokinetics and tolerance of total astragalosides after intravenous infusion in healthy Chinese volunteers (Phytomedicine, 2013) – Primary source for human kinetics.

[B] Stepnik et al.: In Vivo Insights into the Role of Astragaloside IV in Preventing and Treating Civilization Diseases: A Comprehensive Review (MDPI, 2025)

[C] Tan Y. Q. et al.: Astragaloside IV: An Effective Drug for the Treatment of Cardiovascular Diseases (Drug Des Devel Ther., 2020) – Preclinical data and comparison.

[D] Qing, et al.: Pharmacokinetics Comparison, Intestinal Absorption and Acute Toxicity of LS-102 (Research Gate, 2018) – Documentation for low oral absorption (2.2%) of AGS-IV.

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Baicalin

Half-life: 6–15 hours.

Washout: 4 days.

Level of Evidence: 3 (yellow).

Documentation: A clinical study (Liu et al., 2019) conducted on 16 volunteers investigated the pharmacokinetics of baicalin and its potential for interactions with medications metabolized via CYP3A and P-glycoprotein. The study shows that baicalin has an average elimination half-life of approximately 6.4 hours, but with significant individual variation. Since the substance binds strongly to plasma proteins (86–92%) and its active metabolite, baicalein, has the potential to inhibit important enzyme systems in the liver, the washout period is set at 4 days. This ensures that the substance is completely excreted so that it does not affect the metabolism of the oncological treatment.

Link:

[A] Liu et al.: A Single Dose of Baicalin Has No Clinically Significant Effect on the Pharmacokinetics of Cyclosporine A in Healthy Chinese Volunteers (Frontiers, 2019)

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Berberine

Half-life: 12–15 hours (in the excretion phase).

Washout: 3 days.

Level of Evidence: 1 (white).

Documentation: Comprehensive systematic reviews ([A] Ai, 2021) and a clinical study ([B] Solnier, 2023) conducted on 10 healthy volunteers document the pharmacokinetics of berberine. Although standard berberine has a very low bioavailability (less than 1%) due to P-glycoprotein-mediated efflux, modern formulations show up to 6 times higher absorption. The terminal half-life is established at approximately 12–15 hours, reflecting elimination from tissue stores in the liver and kidneys, among others. Since berberine affects multiple signaling pathways (including AMPK and NF-κB) and can interact with the liver’s enzyme systems, the washout period is set at 3 days to ensure complete clearance before oncological treatment.

Link:

[A] Ai: Berberine: A Review of its Pharmacokinetics Properties and Therapeutic Potentials in Diverse Vascular Diseases (Frontiers 2021)

[B] Solnier: Characterization and Pharmacokinetic Assessment of a New Berberine Formulation with Enhanced Absorption In Vitro and in Human Volunteers (MDPI, 2023)

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Boron

Half-life: Approximately 21 hours.

Washout: 5 days.

Level of Evidence: 1 (white).

Documentation: According to a comprehensive analysis by Health Canada (2007/2013) [A], orally ingested boron is rapidly and completely absorbed (over 90%) and passes through the body without being metabolized. It is excreted via the kidneys with a half-life of 21 hours, and most is eliminated within four days, although a very small amount may temporarily accumulate in bone tissue. Recent research ([B] Bartusik-Aebisher, 2025) indicates that boron can interact with the metabolism of steroid hormones and vitamin D, potentially extending their half-life in the body. Since boron does not accumulate in soft tissue and is excreted predictably, the washout period is set at 5 days to ensure complete clearance before oncological treatment.

Link:

[A] Boron as a Medicinal Ingredient in Oral Natural Health Products (Natural Health Canada, 2007)

[B] Bartusik-Aebisher: Boron in Diet and Medicine: Mechanisms of Delivery and Detection (MDPI, 2025)

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Boswellia

Half-life: approx. 6.8 hours (AKBA) / measurable in plasma up to 48 hours.

Washout: 4 days.

Level of Evidence: 1 (white).

Documentation: Boswellia serrata contains active boswellic acids (BA), including AKBA, which function as potent inhibitors of inflammatory mediators (Roy et al., 2019). A human Phase 1 study (Kulkarni et al., 2021) in healthy volunteers documents an initial elimination half-life for AKBA of 6.8 hours. However, recent clinical measurements of both raw extract and formulated particles (Schmiech et al., 2024) demonstrate residual plasma concentrations up to 48 hours after ingestion, due to the substance’s lipophilic nature and slow release from tissue stores. To comply with the pharmacological standard for complete elimination (5 \times t½ in the terminal phase), the washout period is set at 4 days (96 hours). This ensures full clearance of both plasma and tissue stores as well as normalization of inflammatory signaling pathways (5-LOX) before oncological treatment.

Links:

[A] Kulkarni:Pharmacokinetics of solid lipid Boswellia serrata particles in healthy subjects (PubMed, 2021) – Primary source for human kinetics (AKBA).

[B] Schmiech et al.: Single-dose comparative pharmacokinetic/pharmacodynamic study of a micellar formulation versus a native Boswellia serrata dry extract in healthy volunteers (Science Direct, 2024) – Documentation for terminal phase and 48-hour detection.

[C] Roy N. K. et al.: An Update on Pharmacological Potential of Boswellic Acids against Chronic Diseases (Int. J. Mol. Sci., 2019) – Review of molecular targets and bioavailability.

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Butyric acid

Half-life: 0.5–14 minutes.

Washout: 1 day.

Level of Evidence: 1 (white).

Documentation: Pharmacokinetic measurements in humans (Daniel et al., 1989) show that butyric acid is eliminated extremely rapidly from the blood. The elimination curve is divided into two phases, with an initial half-life of only 0.5 minutes followed by a phase of 13.7 minutes. Although preclinical models (Jung et al., 2021) utilize tributyrin (TB) as a “prodrug” to create a more stable release in the gut, human data confirm that the systemic presence is very short-lived. Due to this lightning-fast metabolic turnover, the washout period is set at 1 day to ensure complete elimination before oncological treatment.

Link:

[A] Daniel et al.: Pharmacokinetic study of butyric acid administered in vivo as sodium and arginine butyrate salts (ScienceDirect, 1989)

[B] Jung et al.: An efficient system for intestinal on-site butyrate production using novel microbiome-derived esterases (Springer Nature, 2021)

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Cannabis (THC/CBD)

Half-life: 20 hours (THC) / >134 hours (CBD).

Washout: 28 days (exception: based on slow release from adipose tissue and influence on CYP450).

Level of Evidence: 1 (white).

Documentation: The pharmacokinetics of cannabis are complex due to the substances’ high lipid solubility, which leads to extensive storage in the body’s adipose tissue. For THC, review studies (Huestis, 2007) document that the terminal half-life is between 20 and 30 hours, as the substance is slowly released from tissue stores into the blood. For CBD, recent pharmacokinetic modeling (Kolli et al., 2025) demonstrates that the terminal elimination half-life in humans is extremely long, exceeding 134 hours (>5.5 days), meaning it can take over 70 days to reach a steady state in the body. Since both substances affect the liver’s enzyme systems (especially CYP450) and have prolonged biological activity, the washout period is conservatively set at 4 weeks (28 days) to ensure complete elimination from tissue stores before oncological treatment.

Link:

[A] Lucas et al.: The pharmacokinetics and the pharmacodynamics of cannabinoids (British Journal of Clinical Pharmacology, 2018)

[B] Huestis: Human Cannabinoid Pharmacokinetics (Chemistry & Biodiversity, 2007)

[C] Kolli et al.: Cannabidiol Bioavailability Is Nonmonotonic with a Long Terminal Elimination Half-Life (Cannabis and Cannabinoid Research, Mary Ann Liebert, 2025)

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CoQ10

Half-life: 33–57 hours.

Washout: 12 days.

Level of Evidence: 1 (white).

Documentation: CoQ10 is a fat-soluble molecule with a high molecular weight, resulting in slow and limited absorption. Systematic reviews (Bhagavan, 2006) establish an average plasma half-life of approximately 33 hours. This is supported by clinical reviews (Raizner, 2019), which confirm a half-life of over 30 hours and point out that peak concentrations are only reached 6–8 hours after ingestion. Other pharmacokinetic assessments (Bolt Pharmacy, 2026) indicate a range of up to 57 hours. Since CoQ10 accumulates in tissue stores and has a significant antioxidant effect, the washout period is set at 10–12 days to ensure that plasma levels are normalized before oncological treatment.

Link:

[A] Bhagavan & Chopra: Coenzyme Q10: absorption, tissue uptake, metabolism and pharmacokinetics (Free Radical Research, 2006)

[B] Raizner: Coenzyme Q10 (Methodist Debakey Cardiovasc J., PubMed, 2019)

[C] Bolt Pharmacy: How Long Does CoQ10 Stay in Your System? UK Guide (Bolt, 2026)

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DCA (dichloroacetat)

Half-life: 1 hour (initial) to over 10 hours (with repeated dosing).

Washout: 14 days (exception: due to irreversible inactivation of the GSTZ1 enzyme).

Level of Evidence: 1 (white).

Documentation: DCA exhibits completely unique and dose-dependent pharmacokinetics in humans. Initially, the substance has a short half-life of approximately 1 hour (James et al., 2016). However, DCA inactivates the enzyme (GSTZ1-1) responsible for its own metabolism in the liver. This causes the half-life to increase significantly with repeated dosing—often to approximately 10 hours, but in certain cases considerably longer (Curry et al., 1991). Recent reviews (Koltai et al., 2024) point out that DCA’s ability to inhibit pyruvate dehydrogenase kinase (PDK) and alter cellular bioenergetics makes precision in dosing and washout crucial, especially since the substance can have unpredictable effects upon accumulation. Studies show that it can take from one week up to 3 months for enzyme capacity to normalize. Due to this accumulation and enzyme inhibition, the washout period is conservatively set at 14 days to ensure metabolic normalcy before oncological treatment.

Link:

[A] Curry et al.: Disposition and pharmacodynamics of dichloroacetate (DCA) and oxalate following oral DCA doses (Biopharm Drug Dispos, 1991)

[B] James & Stacpoole: Pharmacogenetic considerations with dichloroacetate dosing (Pharmacogenomics, 2016)

[C] Koltai & Fliegel: Dichloroacetate for Cancer Treatment: Some Facts and Many Doubts (Pharmaceuticals, 2024)

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DIM (diindolylmethane)

Half-life: 4–8 hours.

Washout: 3 days.

Level of Evidence: 2 (green).

Documentation: DIM is the primary acid-condensation product of Indole-3-carbinol (I3C). Phase 1 clinical trials (Reed et al., 2006) document that I3C cannot be measured in plasma after ingestion but is rapidly converted to DIM, which reaches its maximum concentration (tmax) after approximately 2 hours. Although most subjects have low levels after 12–24 hours, significant inter-individual variation has been observed, with some individuals still having measurable levels after 12 hours. Recent systematic reviews (Srikanth et al., 2025) confirm a half-life of 4–8 hours and point out DIM’s impact on estrogen metabolism and xenobiotic processes. Furthermore, clinical studies (Castañon et al., 2012) show that while DIM is well tolerated with daily dosing, a stable period is required to ensure elimination. The washout period is set at 3 days to ensure complete clearance of all active metabolites before oncological treatment.

Link:

[A] Srikanth et al.: Unveiling the Multifaceted Pharmacological Actions of Indole-3-Carbinol and Diindolylmethane: A Comprehensive Review (Plants, 2025)

[B] Reed et al.: Single-Dose and Multiple-Dose Administration of Indole-3-Carbinol to Women: Pharmacokinetics Based on 3,3′-Diindolylmethane (Cancer Epidemiol Biomarkers Prev, 2006)

[C] Castañon et al.: Effect of diindolylmethane supplementation on low-grade cervical cytological abnormalities (British Journal of Cancer, 2012)

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EGCG (Green Tea)

Half-life: 3-5 hours.

Washout: 2 days.

Level of Evidence: 1 (white).

Documentation: EGCG (Epigallocatechin-3-gallate) is rapidly absorbed from the gut, with peak plasma concentrations occurring after approximately 1.5 hours. A randomized controlled phase 1 trial (Lee et al., 2002) shows an elimination half-life of 3.4 hours, with the substance primarily found in free form in plasma, while its metabolites are excreted rapidly via the urine. Another randomized, double-blind, and placebo-controlled phase 1 trial (Ullmann, 2004) confirms that with repeated dosing over 10 days, dose-dependent saturation of excretory pathways occurs at high doses (800 mg), which can slightly prolong the half-life. Due to EGCG’s ability to inhibit specific transport proteins (OATP) and influence drug metabolism, the washout period is set at 2 days to ensure complete elimination before oncological treatment.

Link:

[A] Ullmann et al.: Plasma-kinetic characteristics of purified and isolated epigallocatechin gallate (EGCG) after 10 days repeated dosing in healthy volunteers (Int J Vitam Nutr Res, 2004)

[B] Lee et al.: Pharmacokinetics of tea catechins after ingestion of green tea and (-)-epigallocatechin-3-gallate by humans: Formation of different metabolites and individual variability (Cancer Epidemiol Biomarkers Prev, 2002)

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Genistein

Half-life: 3.8–10.2 hours (in the elimination phase).

Washout: 4 days.

Level of Evidence: 1 (white).

Documentation: Genistein is an isoflavone that is rapidly absorbed but undergoes extensive metabolism. A randomized phase 1 clinical trial (Bloedon et al., 2002) in postmenopausal women showed a terminal half-life for free genistein of 3.8 hours, while the total amount (including conjugated metabolites) had a “pseudo-half-life” of approximately 10.1 hours. Another prospective, randomized phase 1 trial (Ullmann et al., 2005) with synthetic genistein confirms terminal half-lives between 7.7 and 10.2 hours depending on the dose. Although certain mechanistic studies (Yang et al., 2012) point to the possibility of low bioavailability and recirculation, clinical data indicate that progressive accumulation does not occur with daily dosing. The washout period is set at 4 days to ensure complete elimination of both free genistein and its metabolites.

Link:

[A] Bloedon et al.: Safety and pharmacokinetics of purified soy isoflavones: single-dose administration to postmenopausal women (American Journal of Clinical Nutrition, 2002)

[B] Ullmann et al.: Safety, tolerability, and pharmacokinetics of single ascending doses of synthetic genistein (Bonistein™) in healthy volunteers (Advances in Therapy, 2005)

[C] Yang et al.: Bioavailability and Pharmacokinetics of Genistein: Mechanistic Studies on its ADME (Anticancer Agents Med Chem., 2012)

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Shark Liver Oil

Half-life: Not precisely established (incorporated into cell membranes and transformed into plasmalogens).

Washout: 14 days (exception: based on lipid remodeling in immune cells).

Level of Evidence: 3 (yellow).

Documentation: Shark liver oil is a rich source of alkylglycerols (AKG). Unlike many other preparations that merely circulate in plasma, AKG functions as building blocks incorporated into cell membranes. A phase 1 clinical trial (Paul et al., 2021) shows that shark liver oil supplementation for 3 weeks leads to a significant enrichment of plasmalogens in both plasma and white blood cells. The alkylglycerols themselves undergo extensive metabolic “remodeling” in the body. Review articles (Pugliese et al., 1998 & Iannitti & Palmieri, 2010) describe AKG as multifunctional with stimulating effects on macrophages and the immune system that can persist after ingestion. Since the preparation alters the lipid composition of immune cells over a prolonged period, and precise data for terminal elimination are lacking, the washout period is conservatively set at 14 days.

Link:

[A] Pugliese et al.: Some biological actions of alkylglycerols from shark liver oil (J Altern Complement Med, 1998)

[B] Iannitti & Palmieri: An Update on the Therapeutic Role of Alkylglycerols (Marine Drugs, 2010)

[C] Paul et al.: Shark liver oil supplementation enriches endogenous plasmalogens and reduces markers of dyslipidaemia and inflammation (Med-Life Discoveries, 2021)

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Honokiol

Half-life: 2.5–5 hours (in the elimination phase).

Washout: 3 days.

Level of Evidence: 1 (white).

Documentation: Honokiol is a polyphenol from the magnolia tree that exhibits a biphasic kinetic profile. Review articles (Arora et al., 2012) describe an initial rapid distribution in the body followed by a slower elimination phase. A randomized phase 1 clinical trial (Sarrica et al., 2018) indicates an average half-life in this phase of approximately 2.33 hours in humans. Although honokiol is generally considered safe, preclinical studies (Kim et al., 2018) show that the substance can inhibit important liver enzymes (especially CYP1A and CYP2C). Since this enzyme interaction can alter the metabolism of other drugs, the washout period is set at 3 days to ensure that normal liver function is restored.

Link:

[A] Arora et al.: Honokiol: a novel natural agent for cancer prevention and therapy (Current Molecular Medicine, 2012)

[B] Sarrica et al.: Safety and Toxicology of Magnolol and Honokiol (Planta Medica, 2018)

[C] Kim et al.: Modulation of Rat Hepatic CYP1A and 2C Activity by
Honokiol and Magnolol: Differential Effects on
Phenacetin and Diclofenac Pharmacokinetics In Vivo (Molecules, 2018)

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I3C (Indol-3-carbinol)

Half-life: Less than 1 hour (extremely rapid conversion).

Washout: 3 days (exception: follows the elimination of the active metabolite DIM).

Level of Evidence: 1 (white).

Documentation: I3C is an unstable molecule that is immediately converted into condensation products in stomach acid. A phase 1 clinical trial (Reed et al., 2006) documents that I3C itself is not detectable in plasma after oral ingestion, as it functions as a “pro-drug” primarily for DIM. A follow-up phase 1 clinical trial (Reed et al., 2008) examined the absorption of the active metabolite directly and demonstrated a safe profile at doses up to 200 mg. A systematic review (Srikanth et al., 2025) confirms that the pharmacological effect in humans is primarily mediated via these metabolites. Since I3C is converted instantaneously but leaves behind active substances with longer elimination times, the washout period is set at 3 days.

Link:

[A] Srikanth et al.: Unveiling the Multifaceted Pharmacological Actions of Indole-3-Carbinol and Diindolylmethane: A Comprehensive Review (PubMed, Plants, 2025)

[B] Reed et al.: Single-Dose and Multiple-Dose Administration of Indole-3-Carbinol to Women: Pharmacokinetics Based on 3,3′-Diindolylmethane (Cancer Epidemiol Biomarkers Prev, 2006)

[C] Reed et al.: Single-dose pharmacokinetics and tolerability of absorption-enhanced 3,3′-diindolylmethane in healthy subjects (Research Gate, Cancer Epidemiol Biomarkers Prev, 2008)

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Ginger

Half-life: 0.6–2.4 hours (in the elimination phase).

Washout: 2 days.

Level of Evidence: 1 (white).

Documentation: Ginger contains several active components, including gingerols and 6-shogaol. A phase 1 clinical trial (Zick et al., 2008) documents that these substances are absorbed rapidly but are primarily found as conjugated metabolites in plasma with a half-life of less than 2 hours. Another clinical trial (Zhang et al., 2022) confirms that the half-life for both the free substances and their metabolites remains stable between 0.6 and 2.4 hours, even with long-term use. A review article (Biomedicine & Pharmacotherapy, 2023) defines 10-gingerol as a central phenolic compound with significant anti-inflammatory properties and describes its role in managing complex physiological responses. Since the substances are metabolized and excreted rapidly without accumulation, the washout period is set at 2 days.

Link:

[A] Zick et al.: Pharmacokinetics of 6-, 8-, 10-Gingerols and 6-Shogaol and Conjugate Metabolites in Healthy Human Subjects (Cancer Epidemiol Biomarkers Prev, 2009)

[B] Zhang et al.: Pharmacokinetics of Gingerols, Shogaols, and Their Metabolites in Asthma Patients (J Agric Food Chem, 2023)

[C] ScienceDirect: 10-Gingerol – an overview (Biomedicine & Pharmacotherapy, 2023)

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L-Carnitin / ALC

Half-life: 25.7–60.3 hours (plasma) / 38–119 hours (total body turnover).

Washout: 13 days.

Level of Evidence: 1 (white).

Documentation: L-Carnitine and its acetylated form, ALC, are strictly regulated in the body through diet, endogenous production, and efficient renal reabsorption. A clinical trial (Cao et al., 2009) shows that L-carnitine has a longer half-life in plasma (60.3 hours) than ALC (35.9 hours) after oral ingestion. A comprehensive review article (Rebouche, 2004) points out that the total body turnover time is up to 119 hours, as the substance is stored in tissues such as muscle, and that ALC is partially hydrolyzed during absorption. Data from Wikipedia/DrugBank (2024) confirm that ALC in the blood is rapidly broken down by plasma esterases into carnitine, which then transports fatty acids into the mitochondria for energy production. Due to the slow tissue turnover and the significance for mitochondrial metabolism, the washout period is set at 13 days.

Link:

[A] Cao et al.: Comparison of pharmacokinetics of L-carnitine, acetyl-L-carnitine and propionyl-L-carnitine after single oral administration of L-carnitine in healthy volunteers (PubMed, 2009)

[B] Rebouche: Kinetics, pharmacokinetics, and regulation of L-carnitine and acetyl-L-carnitine metabolism (Ann N Y Acad Sci, 2004)

[C] Wikipedia: Acetylcarnitine – Clinical data and Biochemical production (2024)

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LDN (Low Dose Naltrexone)

Half-life: 4 hours (naltrexone) / 13 hours (6-beta-naltrexol).

Washout: 3 days.

Level of Evidence: 1 (white).

Documentation: Naltrexone is a well-documented drug that is rapidly absorbed upon oral ingestion (Tmax 1 hour). A clinical review (Toljan et al., 2018) describes naltrexone as an opioid antagonist that, in low doses (phase 1 trial), triggers a temporary receptor blockade. According to official pharmacokinetic data in DrugBank (2024), naltrexone has a plasma half-life of 4 hours but is converted in the liver to the primary active metabolite, 6-beta-naltrexol, which has a significantly longer half-life of approximately 13 hours. The clinical profile from Renew Health (2026) supports that although the substance and its metabolite are eliminated from plasma after approximately 72 hours, the secondary biological effect of increased endorphin production lasts for up to 24 hours after each dose. Since LDN interacts with the body’s opioid system and can block the effect of pain medication, the washout period is set at 3 days.

Link:

[A] Toljan et al.: Low-Dose Naltrexone (LDN)—Review of Therapeutic Utilization (Medical Sciences, 2018)

[B] DrugBank: Naltrexone – Identification, Pharmacokinetics and Mechanism of Action (2024)

[C] Renew Health: How Long Does Low Dose Naltrexone Stay in Your System (2026)

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L-Glutamine

Half-life: 1–2 hours.

Washout: 2 days.

Level of Evidence: 1 (white).

Documentation: L-Glutamine is the most abundant amino acid in the body and serves as a central energy source for intestinal and immune cells, among others. A population pharmacokinetic analysis (Sadaf et al., 2024) shows that the substance has very rapid absorption and elimination with a Tmax of approximately 1.2 hours, and no accumulation is observed with repeated dosing. Official data from DrugBank/FDA (2024) confirm that the terminal elimination half-life is approximately 1 hour, while technical overviews (Protocol for Life Balance, 2018) report an average half-life of 110 minutes in human trials (phase 1). Since glutamine is metabolized extremely rapidly through the body’s natural metabolic pathways and excreted efficiently, the washout period is set at 2 days.

Link:

[A] Sadaf et al.: A Population Pharmacokinetic Analysis of l-Glutamine Exposure in Patients with Sickle Cell Disease: Evaluation of Dose and Food Effects (Clin Pharmacokinet, 2024)

[B] DrugBank: L-Glutamine – Identification, Pharmacology and Pharmacokinetics (2024)

[C] Protocol for Life Balance: L-Glutamine Pure Powder – Technical Summary and Naturokinetics (2018)

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Liposomal Curcumin

Half-life: 6–42 minutes (plasma) / up to 2 hours (tissue).

Washout: 2 days.

Level of Evidence: 1 (white).

Documentation: Curcumin is characterized by extremely low water solubility and rapid metabolism. The liposomal formulation is developed as a delivery system that protects the molecule and significantly increases bioavailability compared to standard curcumin extract (Prasad et al., 2014). However, a clinical pharmacokinetic phase 1 trial (Bolger et al., 2017) of the liposomal form (Lipocurc™) shows that the substance is still rapidly eliminated from the bloodstream with a plasma half-life of between 24 and 42 minutes in humans following infusion. Although the substance is effectively distributed to tissues such as the liver and lungs, it is rapidly converted by reductases into the metabolite tetrahydrocurcumin (THC) and undergoes phase II conjugation into glucuronide and sulfate forms (Li et al., 2024). Since the active curcuminoids are rapidly metabolized and excreted, the washout period is set at 2 days.

Link:

[A] Bolger et al.: Distribution and Metabolism of Lipocurc™ (Liposomal Curcumin) in Dog and Human Blood Cells: Species Selectivity and Pharmacokinetic Relevance (Anticancer Research, 2017)

[B] Li et al.: Comparative Pharmacokinetic Assessment of Curcumin in Rats Following Intratracheal Instillation Versus Oral Administration: Concurrent Detection of Curcumin and Its Conjugates in Plasma by LC-MS/MS (Pharmaceutics, 2024)

[C] Prasad et al.: Recent Developments in Delivery, Bioavailability, Absorption and Metabolism of Curcumin: the Golden Pigment from Golden Spice (Cancer Research and Treatment, 2014)

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Luteolin

Half-life: 5–9 hours.

Washout: 2 days.

Level of Evidence: 4 (orange).

Documentation: Luteolin is a natural flavonoid with antioxidant and anti-inflammatory properties being investigated for its ability to modulate signaling pathways in cancer cells (Wang et al., 2024). Human studies show that the substance is absorbed rapidly, with peak concentrations occurring after 1–2 hours, but it has low bioavailability of the free aglycone at approximately 17.5% due to extensive metabolism in the gut and liver (Lv et al., 2025). As specific human curve data for elimination are lacking, data from pharmacokinetic animal models (phase 1) (Sarawek et al., 2008) are utilized, showing a half-life for free luteolin of 8.94 hours and approximately 5–7 hours for the conjugated metabolites. Based on the moderate metabolic rate and documented metabolism, the washout period is set at 2 days.

Link:

[A] Wang et al.: Progress, pharmacokinetics and future perspectives of luteolin modulating signaling pathways to exert anticancer effects: A review (Medicine (Baltimore), 2024)

[B] Lv et al.: Luteolin: exploring its therapeutic potential and molecular mechanisms in pulmonary diseases (Frontiers in Pharmacology, 2025)

[C] Sarawek et al.: Pharmacokinetics of Luteolin and Metabolites in Rats (Natural Product Communications, 2008)

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Lysine

Half-life: 15–16 hours.

Washout: 4 days.

Level of Evidence: 1 (white).

Documentation: L-Lysine is an essential amino acid crucial for protein synthesis and collagen formation, as detailed in a comprehensive review article (Holeček, 2025), which describes the latest insights into the substance’s physiological significance in humans. Clinical pharmacokinetic phase 1 studies (Capparelli, 2007) have demonstrated an average plasma elimination half-life of 15.72 ± 3.76 hours. Lysine is actively transported into cells, resulting in tissue concentrations significantly higher than those in plasma. The assessment of the amino acid’s safety profile and metabolic adaptation relies on toxicokinetic review studies (Bier, 2003), which define the framework for safe intake. Since lysine has a relatively long half-life and influences immune and growth processes via lysine-arginine antagonism, the washout period is set at 4 days.

Link:

[A] Holeček: Lysine: Sources, Metabolism, Physiological Importance, and Use as a Supplement (International Journal of Molecular Sciences, 2025)

[B] Capparelli: Pharmacologic, Pharmacodynamic, and Pharmacokinetic Considerations with Intravenous Ibuprofen Lysine (The Journal of Pediatric Pharmacology and Therapeutics, 2007)

[C] Bier: Amino Acid Pharmacokinetics and Safety Assessment (The Journal of Nutrition, 2003)

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Magnesium

Half-life: 5.2 hours (plasma) / approx. 40 days (biological/tissue).

Washout: 2 days.

Level of Evidence: 1 (white).

Documentation: Magnesium is a vital cation and an essential cofactor for over 300 enzymatic reactions, including energy production via ATP metabolism and DNA synthesis. A comprehensive review article (Gröber, 2019) highlights how the substance shares transport and metabolic pathways with numerous drugs, creating a risk for interactions. Clinical pharmacokinetic phase 1 studies (Okusanya et al., 2015) of magnesium sulfate have established a plasma half-life of approximately 5.2 hours, which contrasts with the total biological half-life of approximately 42 days reported in DrugBank (2018). This marked difference is due to the fact that over 50% of the body’s magnesium is deposited in bone tissue, which acts as a slow exchange reservoir. Since magnesium in the bloodstream is excreted exclusively via the kidneys in proportion to serum concentration, the washout period is set at 2 days.

Link:

[A] Gröber et al.: Magnesium and Drugs (PubMed, International Journal of Molecular Sciences, 2019)

[B] Okusanya et al.: Clinical pharmacokinetic properties of magnesium sulphate in women with pre‐eclampsia and eclampsia (BJOG, 2015)

[C] DrugBank: Magnesium – Summary, Mechanism of Action and Pharmacokinetics (2018)

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Milk Thistle (Silymarin/ Silybin)

Half-life: 1–3 hours (free) / 3–8 hours (conjugated).

Washout: 2 days.

Level of Evidence: 1 (white).

Documentation: Milk thistle contains the silymarin complex, in which silybin is the primary active component with antioxidant and anti-inflammatory properties. Clinical pharmacokinetic phase 1 studies (Wen, Dumond et al., 2008) show that silymarin-flavonolignans are absorbed rapidly but are also eliminated promptly. After absorption, the substance undergoes extensive phase II metabolism (glucuronidation and sulfation), resulting in the majority being found in conjugated form with a half-life of up to 8 hours. Xie et al. (2019) further document that silybin undergoes enterohepatic recirculation (reabsorption from the gut), which extends the substance’s presence in the organism. Efflux transporters such as MRP2 contribute to limiting systemic availability. Since silybin and its metabolites are excreted via bile and kidneys but are recirculated in the process, the washout period is set at 2 days to ensure complete clearance.

Link:

[A] Wen Z., Dumond J et al.: Pharmacokinetics and metabolic profile of free, conjugated, and total silymarin flavonolignans in human plasma after oral administration of milk thistle extract (NIH, Drug Metabolism and Disposition, 2008)

[B] Xie et al.: Metabolism, Transport and Drug–Drug Interactions of Silymarin (Molecules, 2019)

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Melatonin

Half-life: 40–60 minutes.

Washout: 1 day.

Level of Evidence: 1 (white).

Documentation: Melatonin is an endogenous hormone that regulates the body’s circadian rhythm via interaction with MT1 and MT2 receptors in the brain. In a clinical cohort crossover phase 1 study (Andersen et al., 2016), the pharmacokinetics of both oral and intravenous melatonin were investigated in healthy volunteers. The study demonstrated that melatonin undergoes extremely extensive “first-pass” metabolism in the liver, resulting in a very low oral bioavailability averaging 2.5% to 3%. The elimination half-life was measured at 54 minutes after oral ingestion and 39 minutes after intravenous infusion, respectively. The primary metabolic pathway is through the liver’s CYP1A2 enzymes, where the hormone is converted to 6-hydroxymelatonin, which is subsequently conjugated and excreted in the urine (Savage et al., 2024). While standard formulations have a short duration of action, prolonged-release formulations (e.g., Circadin) have an extended half-life of 3.5 to 4 hours (Wikipedia, 2024). Due to the rapid metabolic turnover, the washout period is set at 1 day.

Link:

[A] Andersen et al.: Pharmacokinetics of oral and intravenous melatonin in healthy volunteers (BMC Pharmacology and Toxicology, 2016)

[B] Savage et al.: Melatonin – StatPearls (NCBI Bookshelf, 2024)

[C] Wikipedia: Melatonin as a medication and supplement – Pharmacokinetics

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Metformin

Half-life: 1.5–6.2 hours (plasma) / approx. 17.6–23.4 hours (erythrocytes).

Washout: 5 days.

Level of Evidence: 1 (white).

Documentation: Metformin is a biguanide that lowers blood sugar by inhibiting hepatic glucose production and improving insulin sensitivity. A comprehensive review of metabolic pathways (Gong et al., 2012) states that metformin does not undergo hepatic metabolism at all but is excreted 100% unchanged via the kidneys. The oral bioavailability is approximately 40–60%, and absorption is dependent on specific transporters such as OCT1 and OCT2. Clinical pharmacokinetic phase 1 studies (Xie et al., 2015) explain the significant difference in half-lives by the fact that metformin distributes into erythrocytes (red blood cells). While elimination from plasma occurs rapidly (half-life approx. 6.2 hours), the repartitioning from blood cells back into plasma is very slow (half-life approx. 32–39 hours), resulting in a terminal half-life in whole blood of up to 23.4 hours. Since the substance is exclusively excreted renally and persists in the blood cells, the washout period is set at 5 days.

Link:

[A] Gong et al.: Metformin pathways: pharmacokinetics and pharmacodynamics (Pharmacogenetics and Genomics / PMC, 2013)

[B] Xie et al.: Metformin’s Intrinsic Blood-to-Plasma Partition Ratio (B/P) (Journal of Pharmacology and Experimental Therapeutics, 2015)

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Lactic acid bacteria (Probiotic)

Half-life: N/A – excreted continuously during passage (Transit time: approx. 24–48 hours / Persistence: 3–6 days).

Washout: 2 days (based on normal intestinal transit).

Note: In cases of risk for severe neutropenia or specific immunotherapy, 6 days is recommended to ensure complete fecal washout.

Level of Evidence: 1 (white).

Documentation: Lactic acid bacteria are living microorganisms whose effects depend on their ability to survive passage through the gastrointestinal tract. A clinical pilot phase 1 study (Tremblay et al., 2023) investigated the correlation between total whole gut transit time (WGTT) and bacterial persistence. The study documents that the bacteria are detected in the stool 1–2 days after ingestion and that most strains are washed out 3–6 days after discontinuation. Transit time varies individually, but the study confirms that the bacteria do not colonize the gut permanently but are excreted continuously. A review article (Bezkorovainy, 2001) supports this, estimating that only 20–40% of the ingested bacteria survive the passage to the colon. Since the bacteria do not accumulate systemically and are washed out rapidly in accordance with intestinal transit, the washout period is set at 2 days. For patients with severely compromised immune systems (neutropenia) or those undergoing treatment with checkpoint inhibitors, the period is extended to 6 days to eliminate any metabolic or immunological interaction.

Link:

[A] Tremblay et al.: Total Transit Time and Probiotic Persistence in Healthy Adults (PubMed, Journal of Neurogastroenterology and Motility, 2023)

[B] Bezkorovainy: Probiotics: determinants of survival and growth in the gut (The American Journal of Clinical Nutrition, 2001)

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NAC (N-acetylcysteine)

Half-life: 2.0–6.3 hours (plasma) / approx. 15–19 hours (terminal/tissue).

Washout: 4 days.

Level of Evidence: 1 (white).

Documentation: N-acetylcysteine (NAC) is a thiol-containing compound that serves as a central precursor for the synthesis of glutathione (GSH), the body’s primary intracellular antioxidant. A comprehensive review article (dos Santos Tenório et al., 2021) describes how NAC exerts its effects by both restoring cellular redox balance and inhibiting inflammation through the suppression of NF-κB and reduction of cytokines such as IL-6 and TNF-α. Clinical pharmacokinetic phase 1 studies (Olsson et al., 1988) have demonstrated low oral bioavailability of free NAC (approx. 4–9%) due to extensive first-pass metabolism, where the substance is rapidly deacetylated to cysteine. A more recent phase 1 study (Papi et al., 2020) has established that while the plasma half-life is short (approx. 2 hours), the terminal half-life for total NAC is significantly longer (approx. 15–19 hours), reflecting protein binding and the formation of disulfides. Since NAC is primarily excreted renally and metabolized into natural amino acids, the washout period is set at 4 days.

Link:

[A] Pharmacokinetics and Safety of Single and Multiple Doses of Oral N-Acetylcysteine in Healthy Chinese and Caucasian Volunteers: An Open-Label, Phase I Clinical Study (Adv Ther, 2020)

[B] Olsson et al.: Pharmacokinetics and bioavailability of reduced and total N-acetylcysteine (Eur J Clin Pharmacol, 1988)

[C] dos Santos Tenório et al.: N-Acetylcysteine (NAC): Impacts on Human Health (PubMed, Antioxidants, 2021)

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Niacin (B3)

Half-life: 20–45 minutes (niacin) / approx. 4.3 hours (the metabolite nicotinamide).

Washout: 2 days.

Level of Evidence: 1 (white).

Documentation: Niacin (nicotinic acid) is an essential B-vitamin used in gram doses as a lipid-regulating agent through conversion to the coenzyme NAD. A pharmacokinetic phase 1 study (Menon et al., 2007) of extended-release (ER) niacin shows that niacin undergoes rapid and extensive metabolism via two primary pathways: conjugation with glycine to nicotinuric acid (NUA) and the formation of nicotinamide (NAM). While niacin itself has a very short plasma half-life of under one hour, the metabolite nicotinamide persists significantly longer (half-life approx. 4.3 hours). Clinical investigations of patients with impaired renal function (Reiche et al., 2011) indicate that although certain metabolites like NUA accumulate in dialysis patients, no dose adjustment is required as niacin kinetics themselves remain stable. FDA documentation confirms that approximately 60–70% of a dose is excreted renally within 96 hours, primarily as metabolites, and that only about 3% is excreted as unchanged niacin. Since both the active substance and its primary metabolites have a rapid turnover and do not accumulate systemically to a significant degree in healthy individuals, the washout period is set at 2 days.

Link:

[A] Menon et al.: Plasma and urine pharmacokinetics of niacin and its metabolites from an extended-release niacin formulation (PubMed, Int J Clin Pharmacol Ther, 2007)

[B] Reiche et al.: Pharmacokinetics of extended-release nicotinic acid in patients with chronic kidney disease (Nephrology Dialysis Transplantation, 2011)

[C] FDA: Advicor (niacin extended-release/lovastatin) – Clinical Pharmacology (AccessData FDA)

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Nigella Sativa (Black Cumin)

Half-life: Not detectable in human serum (due to immediate protein binding and instability). However, note reaction during chemotherapy.

Washout: 4 days.

Level of evidence: 3 (yellow).

Documentation: Nigella Sativa contains thymoquinone (TQ). A comprehensive review of clinical trials up to March 2025 (Gouda et al., 2025) shows potential, but also limitations due to low bioavailability. A human trial (Tekbaş et al., 2023) has confirmed that TQ is not measurable in the blood after oral ingestion due to immediate protein binding (>99%). Although human data for elimination are limited, a study in rats (Ahmad et al., 2025) demonstrates that TQ is a potent inhibitor of CYP3A4, which increased the exposure of oncological medicine (Dasatinib) by over 200%. Due to this strong enzymatic impact seen in animal models, and the uncertainty of transferring this to humans, a precautionary washout of 4 days (96 hours) is established to ensure full enzymatic normalization before oncological treatment.

Link:

[A] Ahmad A. et al.: Drug Interaction of Dasatinib with Thymoquinone: A
Pharmacokinetic Study in Rats (Int. J. Med. Sci., 2025) – Documentation for 200% increase in drug concentration in rats

[B] Tekbaş A. et al.: Gas Chromatography–Mass Spectrometry Detection of Thymoquinone in Oil and Serum for Clinical Pharmacokinetic Studies (MDPI, Int. J. Mol. Sci., 2023) – Human source proving rapid binding and elimination from serum.

[C] Gouda Y. A. et al.: Thymoquinone and therapeutic potentials: Updated evidences from clinical trials (Pharmacological Research, 2025) – Compilation of clinical evidence up to March 2025.

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Omega-3 (EPA/DHA)

Half-life: 37–79 hours (EPA) / approx. 46 hours (DHA).

Washout: 21 days (deviation: incorporation into platelet membranes requires full replacement of cells).

Level of evidence: 1 (white).

Documentation: Omega-3 fatty acids (EPA and DHA) are well-investigated through direct evidence from human studies. A randomized phase 1 trial (Braeckman et al., 2013) conducted on healthy volunteers has measured the terminal half-lives for EPA to an average of 79 hours with regular intake. Another phase 1 trial (Lapointe et al., 2019) confirms the kinetic profile of the fatty acids and demonstrates that they achieve steady-state after 7–10 days of treatment. FDA documentation (FDA, 2014) and data from DrugBank (DrugBank, 2024) state that DHA has a half-life of approx. 46 hours. Although the mathematical elimination from plasma is faster, the washout period is conservatively set at 21 days because the fatty acids are physically incorporated into the phospholipids of the cell membranes and affect platelet function long after they are out of the blood. This ensures complete clearance from both plasma and tissue stores before oncological treatment.

Link:

[A] Braeckman et al.: Pharmacokinetics of Eicosapentaenoic Acid in Plasma and Red Blood Cells After Multiple Oral Dosing With Icosapent Ethyl in Healthy Subjects (Clin Pharmacol Drug Dev., 2013)

[B] Lapointe et al.: Evaluation of OM3-PL/FFA Pharmacokinetics After Single and Multiple Oral Doses in Healthy Volunteers (Clinical Therapeutics, 2019)

[C] DrugBank: Fish Oil – Identification, Pharmacology and Pharmacokinetics (DrugBank Online, 2024)

[D] FDA: Epanova (omega-3-carboxylic acids) – Clinical Pharmacology and Biopharmaceutics Review (AccessData FDA, 2013)

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Pao Pereira

Half-life: 12–24 hours (based on preclinical models).

Washout: 5 days.

Level of evidence: 4 (orange).

Documentation: The preparation is extracted from the bark of Geissospermum vellosii and contains beta-carboline alkaloids. A preclinical study ([A] Bemis et al., 2009) conducted on mice demonstrates tumor-inhibiting effects, and another preclinical study ([B] Yu & Chen, 2014) shows that the extract potentiates the effect of carboplatin. As only preclinical data and no human measurements for elimination exist, an increased safety margin is used (Level 4). The half-life is estimated at 12–24 hours based on metabolic indicators in animal models. The washout period of 5 days serves as a deliberate “over-insurance” to eliminate the risk of interaction with oncological treatment.

Link:

[A] Bemis et al.: beta-carboline alkaloid-enriched extract from the amazonian rain forest tree pao pereira suppresses prostate cancer cells (PubMed, 2009)

[B] Yu & Chen: The plant extract of Pao pereira potentiates carboplatin effects against ovarian cancer (PubMed, 2014)

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Papaya leaf extract

Half-life: 24–48 hours (based on preclinical excretion rate).

Washout: 10 days.

Level of evidence: 1 (white).

Documentation: Papaya leaf extract (Carica papaya) has been clinically investigated for its ability to increase platelet counts. A randomized, placebo-controlled pilot study ([C] Sathyapalan et al., 2020) conducted on adult patients with dengue fever and severe thrombocytopenia documents that the extract is safe, well-tolerated, and effective in accelerating the recovery of platelet counts. The study further indicates potential immunomodulatory and antiviral activity through influence on cytokine levels (e.g., IL-6 and TNFα). Since clinical data in humans confirm safety and biological effect, but pharmacokinetic animal studies ([A] ResearchGate, 2025) demonstrate a very slow elimination phase, where only 4.73% of the substance was excreted after 48 hours, the preparation is placed at Level 1 for clinical evidence, while the washout period is kept conservative. The washout period is set at 10 days to ensure complete elimination of the active metabolites before oncological treatment.

Link:

[A] Nugrahaningsih Wh et al.: Pharmacokinetic aspect of Carica papaya leaf extract after oral administration (ResearchGate, 2025)

[B] Sharma et al.: Carica papaya L. Leaves: Deciphering Its Antioxidant Bioactives, Biological Activities, Innovative Products, and Safety Aspects (PMC, 2022)

[C] Dipu T. Sathyapalan et al.: Papaya ved trombocytopæni: Efficacy & safety of Carica papaya leaf extract (CPLE) in severe thrombocytopenia (≤30,000/μl) in adult dengue – Results of a pilot study (Plus One, 2020)

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Pau D’Arco

Half-life: 24–48 hours (based on clinical toxicity data).

Washout: 10 days.

Level of evidence: 1 (white).

Documentation: Pau D’Arco (Tabebuia impetiginosa) contains the active naphthoquinones lapachol and beta-lapachone. The preparation has been the subject of extensive clinical investigations, including trials under the auspices of the National Cancer Institute (NCI) in the 1970s ([A] de Almeida, 2009). Although lapachol exhibited antitumor activity in human clinical phase 1 trials, further development was halted due to toxicity at therapeutic doses. A review of the biological mechanisms ([B] Castellanos et al., 2009) confirms that the substance interferes with the vitamin K cycle, which affects coagulation. Recent evaluations of human and animal studies ([C] Almeida, 2013) demonstrate that lapachol has the ability to reduce tumor pain and induce remission, but also emphasize the complex metabolic interactions. Since the clinical trials in humans document both efficacy and significant systemic impact (Level 1), the half-life is estimated at 24–48 hours. The washout period is conservatively set at 10 days to ensure that the impact on coagulation factors and DNA enzymes has ceased before oncological treatment.

Link:

[A] de Almeida: Preclinical and Clinical Studies of Lapachol and Beta-Lapachone (The Open Natural Products Journal, 2009)

[B] Castellanos et al.: Red Lapacho (Tabebuia impetiginosa)–a global ethnopharmacological commodity? (PubMed, 2009)

[C] Almeida: Lapachol and its derivatives as potential drugs for cancer treatment (ResearchGate, 2013)

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Quercetin

Half-life: Approx. 11 hours (terminal elimination phase).

Washout: 3 days.

Level of evidence: 1 (white).

Documentation: Quercetin is a well-investigated flavonoid with extensive human data. A randomized crossover study ([A] Graefe et al., 2001) of 12 healthy volunteers documents that the terminal elimination half-life is approximately 11 hours, regardless of whether the substance is ingested as isolated glycosides or via a plant matrix (e.g., onion or buckwheat). The study further demonstrates that free quercetin cannot be measured in plasma, as it is rapidly converted into glucuronides. Recent randomized clinical trials ([C] Joseph et al., 2022) confirm the rapid biotransformation and show that modern delivery systems can significantly increase bioavailability, but without fundamentally changing the metabolic clearance. A systematic review ([B] Frenț et al., 2024) emphasizes the many biological effects, including the influence on inflammatory signaling pathways. Since elimination is primarily hepatic and the half-life is clinically verified in humans, the washout period is set at 3 days to ensure complete elimination before oncological treatment.

Link:

[A] Graefe et al.: Pharmacokinetics and bioavailability of quercetin glycosides in humans (PubMed, 2001)

[B] Frenț et al.: A Systematic Review: Quercetin—Secondary Metabolite of the Flavonol Class (MDPI, 2024)

[C] Joseph et al.: Enhanced Bioavailability and Pharmacokinetics of a Natural Self-Emulsifying Reversible Hybrid-Hydrogel System of Quercetin (ACS Omega, 2022)

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Resveratrol

Half-life: 2–5 hours (at single dose) / up to 9.7 hours (at sustained intake).

Washout: 3 days.

Level of evidence: 1 (white).

Documentation: Resveratrol has been extensively clinically investigated in humans. Systematic reviews and clinical phase 1 trials ([A] Patel et al., 2011; [B] Muñoz et al., 2015) show that the substance is absorbed effectively (approx. 70%), but has a low bioavailability of around 1% due to rapid and extensive metabolism in the liver (cytochrome P450) and the gut microbiota. At a single dose, the half-life is short (approx. 2–5 hours), but with daily administration over 21 days, an accumulation effect is observed where the half-life increases to 9.7 hours ([B] Muñoz et al., 2015). Recent pharmacokinetic evaluations from 2025 ([C] Wang et al., 2025) confirm that modern formulations can significantly increase the absorption rate and bioavailability, but that the overall elimination pathways remain rapid. As the substance in high doses (over 2.5 g) can cause gastrointestinal side effects and affects growth factors such as IGF-1, the washout period is set at 3 days to ensure complete clearance of both the parent compound and the dominant sulfate and glucuronide metabolites before oncological treatment.

Link:

[A] Patel et al.: Clinical trials of resveratrol (Annals of the New York Academy of Sciences, 2011)

[B] Muñoz et al.: Pharmacological Properties of Resveratrol. A Pre-Clinical and Clinical Review (Biochemistry & Pharmacology, 2015)

[C] Wang et al.: Pharmacokinetic evaluation of two oral Resveratrol formulations in a randomized, open-label, crossover study (Scientific Reports/Nature, 2025)

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Rhodiola rosea

Half-life: 4–6 hours (for the active main component salidroside).

Washout: 3 days.

Level of evidence: 1 (white).

Documentation: Rhodiola rosea is clinically verified through a phase III randomized, double-blind, and placebo-controlled trial ([A] Olsson et al., 2009) of the standardized extract SHR-5, which demonstrated a significant effect on stress-related fatigue and a reduction in the cortisol response. A comprehensive review article ([D] Bertollo et al., 2026) emphasizes the plant’s therapeutic potential in psychiatric care through modulation of neurotransmitters and the HPA axis, but simultaneously warns of the risk of herb-drug interactions. Pharmacokinetic overviews ([B] Fan et al., 2020) and clinical reviews indicate that the terminal half-life for the active component salidroside is approx. 4–6 hours in humans. Since the preparation has a direct biological impact on the body’s stress hormones (cortisol) and neuroinflammatory signaling pathways, the washout period is set at 3 days to ensure complete clearance and stabilization of the hormonal systems before oncological treatment.

Link:

[A] Olsson et al.: A randomised, double-blind, placebo-controlled, parallel-group study of the standardised extract shr-5 of the roots of Rhodiola rosea in the treatment of subjects with stress-related fatigue (PubMed, 2009)

[B] Fan et al.: Salidroside as a potential neuroprotective agent: a review of pharmacokinetics and safety (ScienceDirect, 2020)

[C] Bertollo et al.: Medicinal Plants for Major Depressive Disorder (MDPI / Brain Sciences, 2026)

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Mushrooms (medicinal)

Half-life: 0.5–1 hour (triterpenes)/ up to 24 hours (for beta-glucan interaction).

Washout: 5 days (deviation: based on immunological interaction from beta-glucans).

Level of evidence: 1 (white).

Documentation: Medicinal mushrooms such as Ganoderma lucidum (Reishi) are clinically well-documented through several randomized controlled trials (RCTs) and meta-analyses ([A] Lucius, 2025; [B] Jin et al., 2016). A study ([A] Lucius, 2025) demonstrates that the active triterpenes (ganoderic acids) are absorbed and eliminated very rapidly with a terminal half-life of only 0.66 hours. The beta-glucans have a low direct bioavailability (0.5–5%) but exert their primary immunomodulatory effect through sustained interaction with the gut microbiota and immune cells ([C] Kirdeeva et al., 2026). Clinical evidence shows that Reishi improves quality of life and immune status (CD3, CD4, NK cells) in cancer patients without negatively affecting liver or kidney function ([A], [B]). Since the mushrooms contain complex polysaccharides that can interact with the immune system over a longer period, the washout period is set at 5 days to ensure that the immunological and enzymatic impact (CYP450) is normalized before oncological treatment.

Link:

[A] Lucius: Clinical Evidence for the Use of Ganoderma lucidum Medicinal Mushroom (Sage Journals, Integrative and Complementary Therapies, 2025)

[B] Jin et al.: Ganoderma lucidum (Reishi mushroom) for cancer treatment (Cochrane Database, 2016)

[C] Kirdeeva et al.: The Inclusion of Dietary and Medicinal Mushrooms into Translational Oncology: Pros and Cons at the Molecular Level (MDPI / IJMS, 2026)

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Sulforaphane

Half-life: 2–3 hours.

Washout: 3 days (72 hours) (deviation: based on persistence of active nitrile metabolites).

Level of evidence: 1 (white).

Documentation: Sulforaphane is clinically verified in humans through randomized clinical trials ([A] Egner et al., 2011; [B] Bouranis et al., 2023). Human pharmacokinetics establish a terminal half-life of 2–3 hours for free sulforaphane. Recent human data ([B]), however, show that the metabolite sulforaphane-nitrile has a significantly slower excretion profile and can be traced in the body for up to 72 hours after ingestion. Since this sustained presence of metabolites affects the liver’s detoxification enzymes (phase 2 enzymes), which are critical for the metabolism of oncological medicine ([C] Yagishita et al., 2019), the washout period is set at 3 days to ensure complete elimination and normalization of enzyme activity before treatment.

Link:

[A] Egner et al.: Bioavailability of sulforaphane from two broccoli sprout beverages: Results of a short term, cross-over clinical trial in Qidong, China (Cancer Prevention Research, 2011)

[B] Bouranis et al.: Sulforaphane and Sulforaphane-Nitrile Metabolism in Humans Following Broccoli Sprout Consumption: Inter-individual Variation, Association with Gut Microbiome Composition, and Differential Bioactivity (Molecular Nutrition & Food Research, 2023)

[C] Yagishita et al.: Broccoli or Sulforaphane: Is It the Source or Dose That Matters? (MDPI / Molecules, 2019)

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TUDCA (tauroursodeoxycholsyre)

Half-life: 3.5–5.8 days.

Washout: 4 weeks (28 days). (Deviation to ensure complete clearance from the enterohepatic circulation).

Level of evidence: 1 (white).

Documentation: TUDCA is a hydrophilic bile acid that is clinically verified through randomized crossover studies ([A] Invernizzi et al., 1999) and recent pharmacokinetic phase I trials ([B] Pena et al., 2026). TUDCA exhibits higher bioavailability and less conversion to toxic metabolites than regular UDCA. Since bile acids are part of a closed circuit between the gut and the liver (enterohepatic recirculation), systemic elimination is slow. The latest clinical measurements ([B]) establish the terminal half-life at up to 5.8 days. As TUDCA affects bile secretion, cholesterol metabolism, and possesses chaperone activity in the cells, the washout period is set at 4 weeks to ensure complete elimination before oncological treatment.

Link:

[A] Invernizzi et al.: Differences in the Metabolism and Disposition of Ursodeoxycholic Acid and of its Taurine-Conjugated Species (Hepatology, 1999)

[B] Pena et al.: Pharmacokinetic Evaluation of Ursodeoxycholic Acid, Unconjugated and Conjugated, within Two Oral Formulations in Healthy Male Subjects (Journal of Biosciences and Medicines, 2026)

[C] Kusaczuk: Tauroursodeoxycholate—Bile Acid with Chaperoning Activity: Molecular and Cellular Effects and Therapeutic Perspectives (MDPI / Cells, 2019)

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Vitamin A (retinyl-palmitat/retinol)

Half-life: 13.5 hours (plasma) / 128 days (biological in liver stores).

Washout: 3 days (72 hours).

Note: Although plasma levels normalize quickly, liver stores persist for up to 4 months. In case of suspected hypervitaminosis A (overdose), the oncologist should be consulted regarding specific interactions.

Level of evidence: 1 (white).

Documentation: Pharmacokinetic studies ([A] Davis et al., 2000) document a plasma half-life of approx. 13.5 hours, which means that the circulating amount of Vitamin A is eliminated after approx. 3 days. This is the primary washout period to avoid acute interactions in the blood during oncological treatment. It should be noted, however, that Vitamin A is stored in the liver’s stellate cells with an extremely long biological half-life of 128 days ([C] Furr et al., 1989). Although the patient can start treatment after 3 days of cessation of supplementation, liver stores will remain saturated for up to 4 months, which requires attention in case of suspected hypervitaminosis A or when using drugs with high liver metabolism.

Link:

[A] Davis et al.: Pharmacokinetics of retinyl palmitate and retinol after intramuscular retinyl palmitate administration in severe malaria (Clin Sci, 2000)

[B] Reinersdorff et al.: Plasma kinetics of vitamin A in humans after a single oral dose of [8,9,19-13C]retinyl palmitate (PubMed, J Lipid Res, 1996)

[C] Furr et al.: Vitamin A concentrations in liver determined by isotope dilution assay with tetradeuterated vitamin A (PubMed, Am J Clin Nutr, 1989)

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Vitamin B complex

Half-life: 1–2 hours (for B1, B2, B3, B5, B7, B9)/ 15–25 days (for B6).

Washout: 3 days for the complex generally/ 4 weeks (28 days) for B6.

Level of evidence: 1 (white).

Documentation: The Vitamin B complex consists of eight water-soluble vitamins that are primarily excreted rapidly via the kidneys. For most of these, including thiamine (B1) and riboflavin (B2), the renal clearance is so rapid that toxicity and accumulation are rarely a problem ([D] FAO, 2001). The plasma half-life for these is very short, and they are washed out after 3 days ([C] Ali et al., 2022). Vitamin B6 (pyridoxine), however, differs significantly by having a terminal elimination phase of up to 25 days. An expert consensus ([B] Schellack et al., 2025) states that complete clearance of B6 requires 20–40 days, which is supported by clinical findings of persistently elevated levels after cessation ([A] Lindschinger et al., 2019). Since an excess of B6 is associated with a risk of peripheral neuropathy, the washout period for preparations containing B6 must always be 4 weeks before oncological treatment.

Link:

[A] Lindschinger et al.: A Randomized Pilot Trial to Evaluate the Bioavailability of Natural versus Synthetic Vitamin B Complexes (PubMed, Oxid Med Cell Longev, 2019)

[B] Schellack et al.: Expert Consensus on Vitamin B6 Therapeutic Use: Guidance on Safe Dosage and Clinical Management (Drug Healthc Patient Saf, 2025)

[C] Ali et al.: Dietary Vitamin B Complex: Orchestration in Human Nutrition throughout Life (Nutrients, 2022)

[D] FAO: Chapter 3. Thiamin, riboflavin, niacin, vitamin B6, pantothenic acid and biotin (Human Vitamin and Mineral Requirements, 2001)

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Vitamin D3 (Cholecalciferol)

Half-life: 12–24 hours (initial distribution phase from blood to tissue)/ 15–25 days (terminal elimination).

Washout: 3 days (72 hours). Note: 72-hour clearance time for the free, circulating amount in the blood to avoid acute interactions, although the body’s total stores are emptied much more slowly.

Level of evidence: 1 (white).

Documentation: Vitamin D3 is extremely fat-soluble and exhibits a significant storage effect. While the circulating form in the blood (25(OH)D) has a half-life of approx. 2–3 weeks, recent research ([B] Uçar et al., 2025) documents that the Vitamin D3 molecule itself is actively absorbed and retained in the body’s fat cells (adipocytes). From there, it is only slowly released into the bloodstream. Clinical trials ([A] Charoenngam et al., 2021) confirm that this is particularly pronounced in patients with a higher BMI, where Vitamin D is rapidly drawn out of circulation and deposited. The 3-day washout period is targeted at removing the acute amount in plasma before oncological treatment, while the systemic stores in adipose tissue will persist for months after cessation ([C] Fassio et al., 2020).

Link:

[A] Charoenngam et al.: A pilot-randomized, double-blind crossover trial to evaluate the pharmacokinetics of orally administered 25-hydroxyvitamin D₃ and vitamin D₃ in healthy adults with differing BMI and in adults with intestinal malabsorption (Am J Clin Nutr, 2021)

[B] Uçar et al.: Vitamin D3, 25-Hydroxyvitamin D3, and 1,25-Dihydroxyvitamin D3 Uptake in Cultured Human Mature Adipocytes (Nutrients, 2025)

[C] Fassio et al.: Pharmacokinetics of Oral Cholecalciferol in Healthy Subjects with Vitamin D Deficiency: A Randomized Open-Label Study (Nutrients, 2020)

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Vitamin E (alpha-tocopherol)

Half-life: 20 hours (plasma)/ >2 years (biological in adipose tissue).

Washout: 4 days (96 hours). Note: 72-96 hours ensures elimination of excess circulating tocopherol and normalization of liver output. Deposition in adipose tissue persists for years.

Level of evidence: 1 (white).

Documentation: Vitamin E exhibits complex pharmacokinetics governed by rapid hepatic uptake and re-excretion. Clinical isotope-labeling studies ([A] Violet et al., 2020) show that 85% of a dose is cleared from plasma within 20 minutes, after which it is redistributed via lipoproteins from the liver, peaking after 3–4 hours. This process is inhibited in hepatosteatosis (fatty liver), where the vitamin is sequestered in liver fat. While the plasma half-life is approx. 20 hours ([D] Zaffarin et al., 2020), Vitamin E is extremely persistent in adipose tissue, where it takes up to 2 years to reach new steady-state levels after cessation ([B] Handelman et al., 1994). Since high doses (>300 mg) interact with oncological drugs such as tamoxifen and anticoagulants ([C] Podszun et al., 2014), the washout is set at 4 days to ensure the elimination of excess circulating levels.

Link:

[A] Violet et al.: Vitamin E sequestration by liver fat in humans (JCI Insight, 2020)

[B] Human adipose alpha-tocopherol and gamma-tocopherol kinetics during and after 1 y of alpha-tocopherol supplementation (Am J Clin Nutr, 1994)

[C] Podszun et al.: Vitamin E–drug interactions: molecular basis and clinical relevance (Nutr Res Rev, 2014)

[D] Zaffarin et al.: Pharmacology and Pharmacokinetics of Vitamin E: Nanoformulations (Int J Nanomedicine, 2020)

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Vitamin K2 (menaquinone)

Half-life: 72 hours for MK-7 – (1 hour for MK-4)

Washout: 2 weeks (14 days) for MK-7 – (Approx. 1 day for MK-4)

Level of evidence: 1 (white).

Documentation: Vitamin K2 primarily exists as the homologs MK-4 and MK-7, which exhibit fundamentally different pharmacokinetics. MK-4 has a very short half-life of approx. 1 hour and rarely reaches measurable levels in the blood at nutritional doses ([A] Sato et al., 2012). Conversely, MK-7 has a long half-life of approx. 72 hours ([C] CRN, 2025), which leads to accumulation with daily intake and sustained circulation in the blood for several days after cessation ([B] Du et al., 2023). Since Vitamin K2 directly counteracts the effects of certain types of medicine and affects the coagulation cascade, the washout period for MK-7 is set at 14 days to ensure complete elimination (5 x t½), while MK-4 is washed out after 24 hours.

When a patient mentions they are taking “Vitamin K2,” it can be assumed with high probability that it is MK-7. Therefore, the long washout of 14 days is the most relevant safety precaution in this context.

Link:

[A] Sato et al.: Comparison of menaquinone-4 and menaquinone-7 bioavailability in healthy women (Nutr J, 2012)

[B] Du et al.: The study of bioavailability and endogenous circadian rhythm of menaquinone-7, a form of vitamin K_2, in healthy subjects (Br J Nutr, 2023)

[C] Council for Responsible Nutrition: Vitamin K2 – Menaquinone-7 (Vitamin and Mineral Safety, 4th Ed., 2025)

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Zink

Half-life: 5 hours (plasma)/ >300 days (biological in tissue).

Washout: 3 days (72 hours). Note: 72 hours ensures complete clearance of the free plasma concentration and interrupts the enterohepatic recirculation before oncological treatment.

Level of evidence: 1 (white).

Documentation: Zinc exhibits a distinct biphasic kinetics. The circulating amount in plasma has a half-life of approx. 5 hours ([C] Ranasinghe et al., 2018), and the zinc concentration typically peaks 5–6 hours after ingestion ([A] Salhab et al., 1999). A special characteristic of zinc is the enterohepatic recirculation, where zinc is excreted via the bile and reabsorbed in the intestine, which can lead to secondary peaks in the plasma level up to 24 hours after cessation. Since free-circulating zinc can act as an effective chelator and potentially interact with chemotherapeutics such as cisplatin, the washout period is set at 3 days to ensure stable plasma levels. It is noted that the body’s total stores in muscles and bones have a biological half-life of over a year, but these pools do not participate in the acute interaction risk ([B] Study 2).

Link:

[A] Salhab et al.: The bioequivalence study of Folifer-Z: sustained-release iron and zinc (Int J Pharm, 1999)

[B] Vale, Leite et al.: Zinc pharmacokinetic parameters in the determination of zinc status (ResearchGate/Journal of Trace Elements, 2025)

[C] Ranasinghe et al.: Pharmacokinetics of zinc in pre-diabetes: a pilot study (J Diabetes Metab Disord Control, 2018)

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March 06, 2026

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