CoChat
Sign Up
Cited by 296Sulfur Compounds in BiologyAntioxidant Activity and Oxidative StressSelenium in Biological Systems

The biology of ergothioneine, an antioxidant nutraceutical

Open access
Borodina, Irina, Kenny, Louise C., McCarthy, Cathal M., Paramasivan, Kalaivani, Pretorius, Etheresia, Roberts, Timothy J., van der Hoek, Steven A., Kell, Douglas B.·2020·Nutrition Research Reviews
DOI 10.1017/s0954422419000301PMC PMC7653990
Open this paper in CoChat — free accountOpen PDF

Abstract

Ergothioneine (ERG) is an unusual thio-histidine betaine amino acid that has potent antioxidant activities. It is synthesised by a variety of microbes, especially fungi (including in mushroom fruiting bodies) and actinobacteria, but is not synthesised by plants and animals who acquire it via the soil and their diet, respectively. Animals have evolved a highly selective transporter for it, known as solute carrier family 22, member 4 (SLC22A4) in humans, signifying its importance, and ERG may even have the status of a vitamin. ERG accumulates differentially in various tissues, according to their expression of SLC22A4, favouring those such as erythrocytes that may be subject to oxidative stress. Mushroom or ERG consumption seems to provide significant prevention against oxidative stress in a large variety of systems. ERG seems to have strong cytoprotective status, and its concentration is lowered in a number of chronic inflammatory diseases. It has been passed as safe by regulatory agencies, and may have value as a nutraceutical and antioxidant more generally.

AI snapshot

Written from the paper’s full text.

TL;DR

Ergothioneine (ERG) is a diet-derived thio-histidine betaine antioxidant synthesised mainly by fungi and actinobacteria, not by plants or animals, and taken up in animals by the selective transporter SLC22A4/OCTN1. The review argues ERG is a promising nutraceutical with broad cytoprotective and antioxidant actions, but that definitive clinical benefit remains mostly circumstantial.

Key findings

  • ERG is not biosynthesised by plants or animals; humans and other animals acquire it via diet and a highly selective transporter, SLC22A4 (OCTN1), a 551-amino-acid transporter coupled in humans to influx of 2 or 3 Na+ per ERG. In engineered HEK293 cells, ERG was taken up about 100 times more quickly than tetraethylammonium.
  • Mushrooms are the prime dietary source. Reported amounts include oyster mushrooms (*Pleurotus* spp.) up to 4 mg/g DM, golden oyster *Pleurotus citrinopileatus* 10·65 mg/g DM, shiitake about 1 mg/g DM, porcini/ceps >7 mg/g DM, and button mushrooms *Agaricus bisporus* about 0·4 mg/g DM.
  • ERG is metabolised and excreted slowly: after 5–25 mg daily doses for 7 d in humans, urinary excretion was <4%, with hercynine and lesser S-methyl-ERG as main metabolites. It has been declared safe by bodies such as the European Food Standards Agency and lacks detectable mutagenicity or genotoxicity in high-dose assays.
  • In a 3236-participant Swedish study, ERG was associated with lower risk of coronary disease (HR per 1 sd increment = 0·85; P = 0·01), cardiovascular mortality (HR = 0·79; P = 0·002) and overall mortality (HR = 0·86; P = 4 × 10−5). Observational data also linked 1·5 mushroom servings/week to halving of mild cognitive impairment incidence and nine servings/week to a five-fold decrease.

Methods

  • Narrative review synthesising published literature on ERG discovery, structure, biosynthesis, phylogenetics, SLC22A4 biology, oxidative stress, nutritional sources, safety, analytics, serum concentrations, metabolism, bioactivities and mechanisms.
  • Includes compiled tables of ERG concentrations in human serum, fermentative production in recombinant micro-organisms, and biological properties altered by ERG or SLC22A4 modulation, plus references to phylogenetic and structural analyses.
  • No systematic search strategy, inclusion criteria or meta-analysis is stated; the synthesis is qualitative and literature-based.

Limitations

  • The authors state that evidence for ERG as a preventive or palliative nutraceutical in inflammatory diseases is “mostly circumstantial rather than definitive,” and that they lack examples where ERG is both low in a syndrome and exogenous administration produces functional improvement. They note that randomised controlled trials are only beginning, with one pure-ERG trial registered.
  • The authors state that mechanisms are often unclear and studies “rather descriptive in nature”; effects on host microbiomes “do not yet seem to have been studied”; mitochondrial expression remains uncertain because antibody evidence is hazardous; and old animal ERG-deprivation experiments need repeating with modern lower-detection-limit techniques.
  • Evident from the text: as a narrative review without systematic search or quantitative pooling, it may be subject to selection and interpretation bias, and many cited findings come from animal, cell-culture or observational studies rather than definitive human trials.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1017/s0954422419000301

Cites

589 of 589 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 262 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    Fed-batch cultivation of engineered S. cerevisiae produced 598 (sd 18) mg/l ERG after an 84-h fermentation.

    “Fed-batch cultivation resulted in 598 (sd 18) mg/l ERG after an 84-h fermentation.”
    Quote in the paperSubstantial claim
  • Findingcitation

    SLC22A4 transcript expression varies more than 4000-fold between different cell lines.

    “Fig. 4 shows the expression of the transcript for SLC22A4 in fifty-six cell lines using previous data(119) taken from the human protein atlas(186), indicating a range in expression levels between different cell lines of more than 4000-fold, a number not atypical for human transporters(119).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [119] O’Hagan S, Wright Muelas M, Day PJ, et al. (2018) GeneGini: assessment via the Gini coefficient of reference “housekeeping” genes and diverse human transporter expression profiles. Cell Syst 6, 230– 244. 29428416 PMC5840522

      Not checked in the free run.

    • cites [186] Thul PJ, Åkesson L, Wiking M, et al. (2017) A subcellular map of the human proteome. Science 356, eaal3321. 28495876

      Not checked in the free run.

  • Interpretationreasoning

    ERG may have value as a nutraceutical and antioxidant more generally.

    “It has been passed as safe by regulatory agencies, and may have value as a nutraceutical and antioxidant more generally.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: ERG classes as a nutraceutical.
  • Premisecitation

    ERG is synthesised by a variety of microbes, especially fungi and actinobacteria.

    “The chief organisms capable of its synthesis are fungi and certain yeasts(59,60), though actinobacteria and certain other micro-organisms(60–66), including the slime mould Physarum polycephalum (65), cyanobacteria(67–71) and methylotrophs(72) are also naturally capable of its production.”
    Quote in the paperNot a substantial claim0 of 9 sources checked
    • cites [59] Melville DB, Genghof DS, Inamine E, et al. (1956) Ergothioneine in microorganisms. J Biol Chem 223, 9– 17. 13376573 source

      Not checked in the free run.

    • cites [60] Jones GW, Doyle S & Fitzpatrick DA (2014) The evolutionary history of the genes involved in the biosynthesis of the antioxidant ergothioneine. Gene 549, 161– 170. 25068406 source

      Not checked in the free run.

    • cites [61] Newton GL, Arnold K, Price MS, et al. (1996) Distribution of thiols in microorganisms: mycothiol is a major thiol in most actinomycetes. J Bacteriol 178, 1990– 1995. 8606174 PMC177895 source

      Not checked in the free run.

    • cites [62] Dosanjh M, Newton GL & Davies J (2008) Characterization of a mycothiol ligase mutant of Rhodococcus jostii RHA1. Res Microbiol 159, 643– 650. 18832026 source

      Not checked in the free run.

    • cites [63] Genghof DS & Van Damme O (1964) Biosynthesis of ergothioneine and hercynine by mycobacteria. J Bacteriol 87, 852– 862. 14137624 PMC277104 source

      Not checked in the free run.

    • cites [64] Genghof DS & Van Damme O (1968) Biosynthesis of ergothioneine from endogenous hercynine in Mycobacterium smegmatis. J Bacteriol 95, 340– 344. 5644441 PMC252023 source

      Not checked in the free run.

    • cites [65] Genghof DS (1970) Biosynthesis of ergothioneine and hercynine by fungi and Actinomycetales. J Bacteriol 103, 475– 478. 5432011 PMC248105 source

      Not checked in the free run.

    • cites [66] Trivedi A, Singh N, Bhat SA, et al. (2012) Redox biology of tuberculosis pathogenesis. Adv Microb Physiol 60, 263– 324. 22633061 source

      Not checked in the free run.

    • cites [72] Alamgir KM, Masuda S, Fujitani Y, et al. (2015) Production of ergothioneine by Methylobacterium species. Front Microbiol 6, 1185. 26579093 PMC4621440 source

      Not checked in the free run.

  • Premisecitation

    Mushroom or ERG consumption seems to provide significant prevention against oxidative stress in a large variety of systems.

    “Mushroom or ERG consumption seems to provide significant prevention against oxidative stress in a large variety of systems.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites 125,271,318–351

      Not checked in the free run.

  • May combine two claims. 41
  • Classified as probably not a substantial claim. 9

  • May combine two claims.

    Findingown data

    About 60% of measured ERG from engineered S. cerevisiae was extracellular and the rest accumulated in cells.

    “Some 60 % of the measured ERG was extracellular and the rest accumulated in the cells.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Just two drugs marketed for human consumption and no endogenous genome-encoded metabolites from Recon2 contain the imidazole-2-thione substructure.

    “From a pharmaco-chemical point of view ERG is also unusual, since – using our standard substructure analysis(53,54) in KNIME(55) – we note that just two drugs marketed for human consumption (the anti-thyroxine-production drug methimazole and its pro-drug carbimazole, Fig. 1), and no endogenous genome-encoded metabolites from Recon2(56) contain the imidazole-2-thione substructure(57).”
    Quote in the paperNot a substantial claim0 of 4 sources checked
    • cites [53] O’Hagan S & Kell DB (2017) Analysis of drug-endogenous human metabolite similarities in terms of their maximum common substructures. J Cheminform 9, 18. 28316656 PMC5344883

      Not checked in the free run.

    • cites [54] O’Hagan S & Kell DB (2016) MetMaxStruct: a Tversky-similarity-based strategy for analysing the (sub)structural similarities of drugs and endogenous metabolites. Front Pharmacol 7, 266. 27597830 PMC4992690

      Not checked in the free run.

    • cites [55] O’Hagan S & Kell DB (2015) The KNIME workflow environment and its applications in genetic programming and machine learning. Genetic Progr Evol Mach 16, 387– 391.

      Not checked in the free run.

    • cites [56] Thiele I, Swainston N, Fleming RMT, et al. (2013) A community-driven global reconstruction of human metabolism. Nat Biotechnol 31, 419– 425. 23455439 PMC3856361

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Premisenone given

    ERG concentration is lowered in a number of chronic inflammatory diseases.

    “ERG seems to have strong cytoprotective status, and its concentration is lowered in a number of chronic inflammatory diseases.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    ERG has emerged as an important nutrient and possible vitamin with widespread occurrence and commonly a functional undersupply.

    “Recently, however, l-(+)-ergothioneine, hereafter ergothioneine (ERG), has emerged(3–10) as an important nutrient, and indeed possible vitamin(3), that has precisely these properties of a very widespread occurrence coupled, commonly, to a functional undersupply.”
    Quote in the paperSubstantial claim0 of 8 sources checked
    • cites [3] Paul BD & Snyder SH (2010) The unusual amino acid l-ergothioneine is a physiologic cytoprotectant. Cell Death Differ 17, 1134– 1140. 19911007 PMC2885499

      Not checked in the free run.

    • cites [4] Cheah IK & Halliwell B (2012) Ergothioneine; antioxidant potential, physiological function and role in disease. Biochim Biophys Acta 1822, 784– 793. 22001064

      Not checked in the free run.

    • cites [5] Halliwell B, Cheah IK & Drum CL (2016) Ergothioneine, an adaptive antioxidant for the protection of injured tissues? A hypothesis. Biochem Biophys Res Commun 470, 245– 250. 26772879

      Not checked in the free run.

    • cites [6] Halliwell B, Cheah IK & Tang RMY (2018) Ergothioneine – a diet-derived antioxidant with therapeutic potential. FEBS Lett 592, 3357– 3366. 29851075

      Not checked in the free run.

    • cites [7] Ames BN (2018) Prolonging healthy aging: longevity vitamins and proteins. Proc Natl Acad Sci U S A 115, 10836– 10844. 30322941 PMC6205492

      Not checked in the free run.

    • cites [8] Kerley RN, McCarthy C, Kell DB, et al. (2018) The potential therapeutic effects of ergothioneine in pre-eclampsia. Free Radic Biol Med 117, 145– 157. 29284116

      Not checked in the free run.

    • cites [9] Anonymous (2015) l-Ergothioneine. http://www.tetrahedron.fr/products/research/l-ergothioneine (accessed August 2019).

      Not checked in the free run.

    • cites [10] Beelman RB, Kalaras MD, John P, et al. (2019) Micronutrients and bioactive compounds in mushrooms: a recipe for healthy aging? Nutr Today 54, 16– 22.

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationreasoning

    ERG may have the status of a vitamin.

    “ERG may even have the status of a vitamin.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Plants and animals do not biosynthesise ERG.

    “Thus higher plants contain it but do not biosynthesise it(74); instead they and other organisms(68,75) take it up from fungal production in the soil(76–79), and possibly via actinobacterial(80) or fungal(80,81) symbionts.”
    • Also stated in: § Biosynthesis and phylogenetic distribution · hedged
      “Animals are also considered not to biosynthesise it(82,83), and accumulate it using a particular transporter, detailed below, via the plants and animals that they eat.”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [74] Melville DB & Eich S (1956) The occurrence of ergothioneine in plant material. J Biol Chem 218, 647– 651. 13295219

      Not checked in the free run.

    • cites [82] Melville DB, Otken CC & Kovalenko V (1955) On the origin of animal ergothioneine. J Biol Chem 216, 325– 331. 13252032

      Not checked in the free run.

    • cites [83] Melville DB, Horner WH, Otken CC, et al. (1955) Studies on the origin of ergothioneine in animals. J Biol Chem 213, 61– 68. 14353906

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Plants acquire ERG from soil, and animals acquire it via their diet.

    “Thus higher plants contain it but do not biosynthesise it(74); instead they and other organisms(68,75) take it up from fungal production in the soil(76–79), and possibly via actinobacterial(80) or fungal(80,81) symbionts.”
    • Also stated in: § Biosynthesis and phylogenetic distribution · plain
      “Animals are also considered not to biosynthesise it(82,83), and accumulate it using a particular transporter, detailed below, via the plants and animals that they eat.”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [74] Melville DB & Eich S (1956) The occurrence of ergothioneine in plant material. J Biol Chem 218, 647– 651. 13295219

      Not checked in the free run.

    • cites [82] Melville DB, Otken CC & Kovalenko V (1955) On the origin of animal ergothioneine. J Biol Chem 216, 325– 331. 13252032

      Not checked in the free run.

    • cites [83] Melville DB, Horner WH, Otken CC, et al. (1955) Studies on the origin of ergothioneine in animals. J Biol Chem 213, 61– 68. 14353906

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Ergothioneine (ERG) is an unusual thio-histidine betaine amino acid that has potent antioxidant activities.

    “Ergothioneine (ERG) is an unusual thio-histidine betaine amino acid that has potent antioxidant activities.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [32] Servillo L, Castaldo D, Casale R, et al. (2015) An uncommon redox behavior sheds light on the cellular antioxidant properties of ergothioneine. Free Radic Biol Med 79, 228– 236. 25483556

      Not checked in the free run.

    • cites [33] Franzoni F, Colognato R, Galetta F, et al. (2006) An in vitro study on the free radical scavenging capacity of ergothioneine: comparison with reduced glutathione, uric acid and trolox. Biomed Pharmacother 60, 453– 457. 16930933

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    SLC22A4 and its homologues have significant specificity for ERG and weak activity for various drugs.

    “Subsequent work(87,169–172) has confirmed and reinforced this view of SLC22A4 and its homologues(173) as having significant specificity for ERG, and weak activity for various drugs(174–177).”
    Quote in the paperSubstantial claim0 of 10 sources checked
    • cites [87] Tucker RAJ, Cheah IK & Halliwell B (2019) Specificity of the ergothioneine transporter natively expressed in HeLa cells. Biochem Biophys Res Commun 513, 22– 27. 30929922 source

      Not checked in the free run.

    • cites [169] Bacher P, Giersiefer S, Bach M, et al. (2009) Substrate discrimination by ergothioneine transporter SLC22A4 and carnitine transporter SLC22A5: gain-of-function by interchange of selected amino acids. Biochim Biophys Acta 1788, 2594– 2602. 19814996 source

      Not checked in the free run.

    • cites [170] Grigat S, Harlfinger S, Pal S, et al. (2007) Probing the substrate specificity of the ergothioneine transporter with methimazole, hercynine, and organic cations. Biochem Pharmacol 74, 309– 316. 17532304 source

      Not checked in the free run.

    • cites [171] Gründemann D (2012) The ergothioneine transporter controls and indicates ergothioneine activity – a review. Prev Med 54, Suppl., S71– S74. 22182480 source

      Not checked in the free run.

    • cites [172] Tschirka J, Kreisor M, Betz J, et al. (2018) Substrate selectivity check of the ergothioneine transporter. Drug Metab Dispos 46, 779– 785. 29530864 source

      Not checked in the free run.

    • cites [173] Shimizu T, Masuo Y, Takahashi S, et al. (2015) Organic cation transporter OCTN1-mediated uptake of food-derived antioxidant ergothioneine into infiltrating macrophages during intestinal inflammation in mice. Drug Metab Pharmacokinet 30, 231– 239. 26003890 source

      Not checked in the free run.

    • cites [174] Yabuuchi H, Tamai I, Nezu J, et al. (1999) Novel membrane transporter OCTN1 mediates multispecific, bidirectional, and pH-dependent transport of organic cations. J Pharmacol Exp Ther 289, 768– 773. 10215651 source

      Not checked in the free run.

    • cites [175] Akamine T, Koyanagi S, Kusunose N, et al. (2015) Dosing time-dependent changes in the analgesic effect of pregabalin on diabetic neuropathy in mice. J Pharmacol Exp Ther 354, 65– 72. 25962390 source

      Not checked in the free run.

    • cites [176] Shimizu T, Kijima A, Masuo Y, et al. (2015) Gene ablation of carnitine/organic cation transporter 1 reduces gastrointestinal absorption of 5-aminosalicylate in mice. Biol Pharm Bull 38, 774– 780. 25947923 source

      Not checked in the free run.

    • cites [177] Tamai I (2013) Pharmacological and pathophysiological roles of carnitine/organic cation transporters (OCTNs: SLC22A4, SLC22A5 and Slc22a21). Biopharm Drug Dispos 34, 29– 44. 22952014 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    SLC22A4 is concentrative, coupled in humans to influx of 2 or 3 Na+ ions per ERG transported.

    “It is concentrative, coupled in humans to influx of 2 or 3 Na+ ions per ERG transported(130).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [130] Gründemann D, Harlfinger S, Golz S, et al. (2005) Discovery of the ergothioneine transporter. Proc Natl Acad Sci U S A 102, 5256– 5261. 15795384 PMC555966

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    ERG biosynthesis proceeds from histidine via hercynine and hercynylcysteine sulfoxide, with an alternative route via γ-glutamylhercynylcysteine sulfoxide.

    “Thus (Fig. 2), histidine is trimethylated using S-adenosyl methionine to form trimethyl histidine, also known as hercynine(95,96). This reacts oxidatively with cysteine to form hercynylcysteine sulfoxide(97), which is converted to ERG. In some organisms, hercynine takes a more convoluted route via γ-glutamylhercynylcysteine sulfoxide (Fig. 2)(94).”
    Quote in the paperNot a substantial claim0 of 4 sources checked
    • cites [95] Reinhold VN, Ishikawa Y & Melville DB (1970) Conversion of histidine to hercynine by Neurospora crassa. J Bacteriol 101, 881– 884. 5438052 PMC250405

      Not checked in the free run.

    • cites [96] Melville DB, Ludwig ML, Inamine E, et al. (1959) Transmethylation in the biosynthesis of ergothioneine. J Biol Chem 234, 1195– 1198. 13654346

      Not checked in the free run.

    • cites [97] Ishikawa Y, Israel SE & Melville DB (1974) Participation of an intermediate sulfoxide in the enzymatic thiolation of the imidazole ring of hercynine to form ergothioneine. J Biol Chem 249, 4420– 4427. 4276459

      Not checked in the free run.

    • cites [94] Naowarojna N, Cheng R, Chen L, et al. (2018) Mini-review: ergothioneine and ovothiol biosyntheses, an unprecedented trans-sulfur strategy in natural product biosynthesis. Biochemistry 57, 3309– 3325. 29589901 PMC6008215

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    SLC22A4 transports ERG about 100 times more quickly than tetraethylammonium, leading to its designation as the ERG transporter.

    “Incubating the cells just with ERG showed that it was taken up about 100 times more quickly than was tetraethylammonium, leading to the designation of SLC22A4 as ‘the’ ERG transporter(130).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [130] Gründemann D, Harlfinger S, Golz S, et al. (2005) Discovery of the ergothioneine transporter. Proc Natl Acad Sci U S A 102, 5256– 5261. 15795384 PMC555966

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Tissue levels of ERG depend on exogenous supply and are well correlated with expression levels of SLC22A4.

    “Tissue levels of ERG depend on an exogenous supply(179), but are then well correlated with the expression levels of SLC22A4(3,180).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [179] Darghouth D, Giarratana MC, Oliveira L, et al. (2016) Bio-engineered and native red blood cells from cord blood exhibit the same metabolomic profile. Haematologica 101, e220– e222. 26969083 PMC5013952 source

      Not checked in the free run.

    • cites [3] Paul BD & Snyder SH (2010) The unusual amino acid l-ergothioneine is a physiologic cytoprotectant. Cell Death Differ 17, 1134– 1140. 19911007 PMC2885499 source

      Not checked in the free run.

    • cites [180] Taubert D, Lazar A, Grimberg G, et al. (2006) Association of rheumatoid arthritis with ergothioneine levels in red blood cells: a case control study. J Rheumatol 33, 2139– 2145. 17086603

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Enantiopure l-ERG has been synthesised chemically and by fermentation of genetically engineered micro-organisms.

    “In addition, enantiopure l-ERG has been synthesised chemically(76,110–112), and by fermentation of genetically engineered micro-organisms (Table 2).”
    Quote in the paperNot a substantial claim0 of 4 sources checked
    • cites [76] Melville DB (1959) Ergothioneine. Vitam Horm 17, 155– 204.

      Not checked in the free run.

    • cites [110] Daunay S, Lebel R, Farescour L, et al. (2016) Short protecting-group-free synthesis of 5-acetylsulfanyl-histidines in water: novel precursors of 5-sulfanyl-histidine and its analogues. Org Biomol Chem 14, 10473– 10480. 27759126

      Not checked in the free run.

    • cites [111] Xu JZ & Yadan JC (1995) Synthesis of l-(+)-ergothioneine. J Org Chem 60, 6296– 6301.

      Not checked in the free run.

    • cites [112] Khonde PL & Jardine A (2015) Improved synthesis of the super antioxidant, ergothioneine, and its biosynthetic pathway intermediates. Org Biomol Chem 13, 1415– 1419. 25467279

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Egt1 from N. crassa is 876 amino acids long, while egtD from M. tuberculosis is 321 amino acids long; conserved N-terminal sequences imply an extra C-terminal domain catalysing production of hercynylcysteine sulfoxide from hercynine.

    “Egt1 from N. crassa is 876 amino acids long(108), while egtD (from Mycobacterium tuberculosis (109)) is just 321 amino acids long; since the N-terminal sequences are well conserved (Fig. 3), this implies an extra C-terminal domain catalysing the production of hercynylcysteine sulfoxide from hercynine.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [108] Uniprot (2019) Neurospora crassa EGT1. https://www.uniprot.org/uniprot/Q7RX33 (accessed August 2019).

      Not checked in the free run.

    • cites [109] Uniprot (2019) Mycobacterium tuberculosis EGTD. https://www.uniprot.org/uniprot/P9WN46 (accessed August 2019).

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The thione tautomer of ERG is predominant at physiological pH, making it unusually resistant to autoxidation.

    “Although it is a thiol, and hence an antioxidant(32,33), the thione tautomer is predominant at physiological pH(34,35), and this makes it unusually resistant to autoxidation, i.e. simple oxidation by molecular O2 (32,36–38).”
    Quote in the paperSubstantial claim0 of 6 sources checked
    • cites [34] Hand CE, Taylor NJ & Honek JF (2005) Ab initio studies of the properties of intracellular thiols ergothioneine and ovothiol. Bioorg Med Chem Lett 15, 1357– 1360. 15713386

      Not checked in the free run.

    • cites [35] Hand CE & Honek JF (2005) Biological chemistry of naturally occurring thiols of microbial and marine origin. J Nat Prod 68, 293– 308. 15730267

      Not checked in the free run.

    • cites [32] Servillo L, Castaldo D, Casale R, et al. (2015) An uncommon redox behavior sheds light on the cellular antioxidant properties of ergothioneine. Free Radic Biol Med 79, 228– 236. 25483556

      Not checked in the free run.

    • cites [36] Fahey RC (2013) Glutathione analogs in prokaryotes. Biochim Biophys Acta 1830, 3182– 3198. 23075826

      Not checked in the free run.

    • cites [37] Sheridan KJ, Dolan SK & Doyle S (2015) Endogenous cross-talk of fungal metabolites. Front Microbiol 5, 732. 25601857 PMC4283610

      Not checked in the free run.

    • cites [38] Fahey RC (2001) Novel thiols of prokaryotes. Annu Rev Microbiol 55, 333– 356. 11544359

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    ERG reacts virtually instantaneously with hydroxyl radicals, and more slowly with H2O2 and/or O2•−.

    “Its reaction with hydroxyl radicals (OH•) is virtually instantaneous, while it reacts only more slowly with H2O2 and/or O2 •− (38).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [38] Fahey RC (2001) Novel thiols of prokaryotes. Annu Rev Microbiol 55, 333– 356. 11544359

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In mushrooms, ERG is typically the main antioxidant, and it may also inhibit tyrosinase.

    “This also seems true of mushrooms(271,272), where ERG is typically the main antioxidant(273–275), and where it may also inhibit the oxidative enzyme tyrosinase(276).”
    Quote in the paperNot a substantial claim0 of 6 sources checked
    • cites [271] Savoie J-M, Minvielle N & Largeteau ML (2008) Radical-scavenging properties of extracts from the white button mushroom, Agaricus bisporus. J Sci Food Agric 88, 870– 875. source

      Not checked in the free run.

    • cites [272] Yokota ME, Frison PS, Marcante RC, et al. (2016) Iron translocation in Pleurotus ostreatus basidiocarps: production, bioavailability, and antioxidant activity. Genet Mol Res 15. 26909996 source

      Not checked in the free run.

    • cites [273] Kozarski M, Klaus A, Jakovljevic D, et al. (2015) Antioxidants of edible mushrooms. Molecules 20, 19489– 19525. 26516828 PMC6331815 source

      Not checked in the free run.

    • cites [274] Zhao H, Zhang M, Liu Q, et al. (2018) A comprehensive screening shows that ergothioneine is the most abundant antioxidant in the wild macrofungus Phylloporia ribis Ryvarden. J Environ Sci Health C 36, 98– 111. 29667505 source

      Not checked in the free run.

    • cites [275] Dubost NJ, Ou B & Beelman RB (2007) Quantification of polyphenols and ergothioneine in cultivated mushrooms and correlation to total antioxidant capacity. Food Chem 105, 727– 735. source

      Not checked in the free run.

    • cites [276] Liao WC, Wu WH, Tsai PC, et al. (2012) Kinetics of ergothioneine inhibition of mushroom tyrosinase. Appl Biochem Biotechnol 166, 259– 267. 22068690 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    ERG can react with and detoxify, or prevent the formation of, hydroxyl radicals, singlet oxygen, ozone, superoxide, peroxide, hypochlorite and peroxynitrite.

    “Although the literature is somewhat scattered and heterogeneous, it seems clear that as well as hydroxyl radicals(228–232), ERG can also react with and detoxify, or prevent the formation of, singlet oxygen(233–242), ozone(243), superoxide(231,241,244–246), peroxide(32,124,247,248), hypochlorite(32,232,249) and peroxynitrite(224,231,250,251).”
    Quote in the paperSubstantial claim0 of 10 sources checked
    • cites [228] Akanmu D, Cecchini R, Aruoma OI, et al. (1991) The antioxidant action of ergothioneine. Arch Biochem Biophys 288, 10– 16. 1654816 source

      Not checked in the free run.

    • cites [229] Asmus KD, Bensasson RV, Bernier JL, et al. (1996) One-electron oxidation of ergothioneine and analogues investigated by pulse radiolysis: redox reaction involving ergothioneine and vitamin C. Biochem J 315, 625– 629. 8615839 PMC1217242 source

      Not checked in the free run.

    • cites [230] Motohashi N & Mori I (1986) Thiol-induced hydroxyl radical formation and scavenger effect of thiocarbamides on hydroxyl radicals. J Inorg Biochem 26, 205– 212. 3009712 source

      Not checked in the free run.

    • cites [231] Jang JH, Aruoma OI, Jen LS, et al. (2004) Ergothioneine rescues PC12 cells from β-amyloid-induced apoptotic death. Free Radic Biol Med 36, 288– 299. 15036348 source

      Not checked in the free run.

    • cites [232] Chaudière J & Ferrari-Iliou R (1999) Intracellular antioxidants: from chemical to biochemical mechanisms. Food Chem Toxicol 37, 949– 962. 10541450 source

      Not checked in the free run.

    • cites [233] Oumari M, Goldfuss B, Stoffels C, et al. (2019) Regeneration of ergothioneine after reaction with singlet oxygen. Free Radic Biol Med 134, 498– 504. 30721726 source

      Not checked in the free run.

    • cites [234] Devasagayam TPA, Sundquist AR, Di Mascio P, et al. (1991) Activity of thiols as singlet molecular oxygen quenchers. J Photochem Photobiol B 9, 105– 116. 1907641 source

      Not checked in the free run.

    • cites [235] Hartman PE, Hartman Z & Ault KT (1990) Scavenging of singlet molecular oxygen by imidazole compounds: high and sustained activities of carboxy terminal histidine dipeptides and exceptional activity of imidazole-4-acetic acid. Photochem Photobiol 51, 59– 66. 2304979 source

      Not checked in the free run.

    • cites [236] van den Broeke LT & Beyersbergen van Henegouwen GM (1993) Thiols as potential UV radiation protectors: an in vitro study. J Photochem Photobiol B 17, 279– 286. 8492245 source

      Not checked in the free run.

    • cites [237] Egorov S, Kurella EG, Boldyrev AA, et al. (1997) Quenching of singlet molecular oxygen by carnosine and related antioxidants. Monitoring 1270-nm phosphorescence in aqueous media. Biochem Mol Biol Int 41, 687– 694. 9111930 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In M. tuberculosis and other mycobacteria, other actinobacteria and fungi, ERG can have a role as an antioxidant and act as a buffer against reductive stress.

    “In M. tuberculosis and other mycobacteria(254), and also in other actinobacteria(255) and in fungi(247,256,257), it is clear that ERG can have a role as an antioxidant(66,258–260) and also act as a buffer against reductive stress(261).”
    Quote in the paperNot a substantial claim0 of 5 sources checked
    • cites [254] Sao Emani C, Williams MJ, Wiid IJ, et al. (2013) Ergothioneine is a secreted antioxidant in Mycobacterium smegmatis. Antimicrob Agents Chemother 57, 3202– 3207. 23629716 PMC3697313 source

      Not checked in the free run.

    • cites [255] Nakajima S, Satoh Y, Yanashima K, et al. (2015) Ergothioneine protects Streptomyces coelicolor A3(2) from oxidative stresses. J Biosci Bioeng 120, 294– 298. 25683449 source

      Not checked in the free run.

    • cites [247] Bello MH, Barrera-Perez V, Morin D, et al. (2012) The Neurospora crassa mutant NcΔEgt-1 identifies an ergothioneine biosynthetic gene and demonstrates that ergothioneine enhances conidial survival and protects against peroxide toxicity during conidial germination. Fungal Genet Biol 49, 160– 172. 22209968 source

      Not checked in the free run.

    • cites [256] Liu H, Zhao X, Guo M, et al. (2015) Growth and metabolism of Beauveria bassiana spores and mycelia. BMC Microbiol 15, 267. 26581712 PMC4652391 source

      Not checked in the free run.

    • cites [257] Sheridan KJ, Lechner BE, Keeffe GO, et al. (2016) Ergothioneine biosynthesis and functionality in the opportunistic fungal pathogen, Aspergillus fumigatus. Sci Rep 6, 35306. 27748436 PMC5066259 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    SLC22A4 is known to express in the intestinal lumen, taking up ERG and some xenobiotics including pyrilamine, quinidine and verapamil, and having multiple known but weak inhibitors.

    “SLC22A4 is known to express in the intestinal lumen(185), acting to take up ERG, as well as some xenobiotics including pyrilamine, quinidine and verapamil, and having multiple known but weak inhibitors.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [185] Wolf KK & Paine MF (2018) Metabolic barrier of the gastrointestinal tract In Comprehensive Toxicology, 3rd ed, pp. 74– 98 [ C McQueen, editor]. Amsterdam: Elsevier.

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Oxidative stress is widespread to the point of ubiquity in chronic, inflammatory diseases.

    “Oxidative stress is widespread to the point of ubiquity in chronic, inflammatory diseases(206,207), with over fifty papers having the words ‘oxidative’, ‘stress’ and ‘review’ in their titles at PubMed in 2018 alone!”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [206] Kell DB & Pretorius E (2018) No effects without causes. The iron dysregulation and dormant microbes hypothesis for chronic, inflammatory diseases. Biol Rev 93, 1518– 1557. 29575574 PMC6055827

      Not checked in the free run.

    • cites [207] Butterfield DA & Halliwell B (2019) Oxidative stress, dysfunctional glucose metabolism and Alzheimer disease. Nat Rev Neurosci 20, 148– 160. 30737462 PMC9382875

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    ERG is unusually stable, with anhydrous ERG decomposing only at 275-276°C, allowing isolation at temperatures close to boiling water.

    “A useful feature is that ERG is unusually stable, in that anhydrous ERG decomposes only at 275–276°C(76), allowing its isolation at temperatures close to that of boiling water(72).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [76] Melville DB (1959) Ergothioneine. Vitam Horm 17, 155– 204.

      Not checked in the free run.

    • cites [72] Alamgir KM, Masuda S, Fujitani Y, et al. (2015) Production of ergothioneine by Methylobacterium species. Front Microbiol 6, 1185. 26579093 PMC4621440

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    ERG is present in seminal fluid and human breast milk.

    “Interestingly, ERG is also present in seminal fluid(394–396) and human breast milk(6).”
    Quote in the paperNot a substantial claim0 of 4 sources checked
    • cites [394] Leone E, Mann T (1951) Ergothioneine in the seminal vesicle secretion. Nature 168, 205– 206. 14875049

      Not checked in the free run.

    • cites [395] Strzeżek R, Koziorowska-Gilun M, Kowalowka M, et al. (2009) Characteristics of antioxidant system in dog semen. Pol J Vet Sci 12, 55– 60. 19459440

      Not checked in the free run.

    • cites [396] Strzeżek R, Koziorowska-Gilun M, Kielczewski K, et al. (2015) Effect of dialysis of dog semen on sperm characteristics and some biochemical components of seminal plasma. Pol J Vet Sci 18, 447– 448. 26172197

      Not checked in the free run.

    • cites [6] Halliwell B, Cheah IK & Tang RMY (2018) Ergothioneine – a diet-derived antioxidant with therapeutic potential. FEBS Lett 592, 3357– 3366. 29851075

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Serum ERG concentration varies with diet, starvation, age and other factors, including diseases of oxidative stress, with typical values of 20-100 μg/ml.

    “Unsurprisingly it varies with diet(388,389), starvation(390), age(391,392) and other factors, including diseases of oxidative stress(393), with typical values of 20–100 µg/ml.”
    Quote in the paperNot a substantial claim0 of 5 sources checked
    • cites [388] Baldridge RC & Lewis HB (1953) Diet and the ergothioneine content of blood. J Biol Chem 202, 169– 176. 13061442

      Not checked in the free run.

    • cites [389] Baldridge RC (1955) Blood ergothioneine and dietary oats. J Nutr 56, 107– 113. 14368376

      Not checked in the free run.

    • cites [390] Teruya T, Chaleckis R, Takada J, et al. (2019) Diverse metabolic reactions activated during 58-hr fasting are revealed by non-targeted metabolomic analysis of human blood. Sci Rep 9, 854. 30696848 PMC6351603

      Not checked in the free run.

    • cites [391] Cheah IK, Feng L, Tang RMY, et al. (2016) Ergothioneine levels in an elderly population decrease with age and incidence of cognitive decline; a risk factor for neurodegeneration? Biochem Biophys Res Commun 478, 162– 167. 27444382

      Not checked in the free run.

    • cites [392] Yan S, Wu B, Lin Z, et al. (2009) Metabonomic characterization of aging and investigation on the anti-aging effects of total flavones of Epimedium. Mol Biosyst 5, 1204– 1213. 19756310

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    A number of high-dose studies indicate ERG is safe for mammalian consumption at levels far in excess of those likely in foodstuffs, and it has been declared safe by EFSA.

    “Notwithstanding the highly variable intake between individuals(358), however, a number of high-dose studies have indicated that ERG is safe for mammalian consumption at levels far in excess of those likely to be encountered in foodstuffs(125,131,359,360), and it has been declared safe by relevant committees such as those of the European Food Standards Agency(361,362).”
    Quote in the paperNot a substantial claim0 of 6 sources checked
    • cites [125] Weigand-Heller AJ, Kris-Etherton PM & Beelman RB (2012) The bioavailability of ergothioneine from mushrooms (Agaricus bisporus) and the acute effects on antioxidant capacity and biomarkers of inflammation. Prev Med 54, Suppl., S75–S78. 22230474 source

      Not checked in the free run.

    • cites [131] Tang RMY, Cheah IK, Yew TSK, et al. (2018) Distribution and accumulation of dietary ergothioneine and its metabolites in mouse tissues. Sci Rep 8, 1601. 29371632 PMC5785509 source

      Not checked in the free run.

    • cites [359] Marone PA, Trampota J, Weisman S (2016) A safety evaluation of a nature-identical l-ergothioneine in Sprague Dawley rats. Int J Toxicol 35, 568– 583. 27306320 source

      Not checked in the free run.

    • cites [360] Cheah IK, Tang RMY, Yew TSZ, et al. (2017) Administration of pure ergothioneine to healthy human subjects: uptake, metabolism, and effects on biomarkers of oxidative damage and inflammation. Antioxid Redox Signal 26, 193– 206. 27488221 source

      Not checked in the free run.

    • cites [361] Turck D, Bresson JL, Burlingame B, et al. (2016) Safety of synthetic l-ergothioneine (Ergoneine (R)) as a novel food pursuant to Regulation (EC) No 258/97. EFSA J 14, 4629. source

      Not checked in the free run.

    • cites [362] Turck D, Bresson JL, Burlingame B, et al. (2017) Statement on the safety of synthetic l-ergothioneine as a novel food – supplementary dietary exposure and safety assessment for infants and young children, pregnant and breastfeeding women. EFSA J 15, 5060. PMC7010164 32625352 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    ERG has been proposed as a nutritional biomarker for mushroom consumption, but different mushrooms contain different amounts that can vary with physiological or environmental conditions.

    “Indeed, ERG has been proposed as a nutritional biomarker for mushroom consumption(296,297), albeit that different mushrooms typically contain different amounts(275,298–300), and these can vary with physiological or environmental conditions(301–305).”
    Quote in the paperNot a substantial claim0 of 10 sources checked
    • cites [296] Wang Y, Gapstur SM, Carter BD, et al. (2018) Untargeted metabolomics identifies novel potential biomarkers of habitual food intake in a cross-sectional study of postmenopausal women. J Nutr 148, 932– 943. 29767735

      Not checked in the free run.

    • cites [297] Pallister T, Jennings A, Mohney RP, et al. (2016) Characterizing blood metabolomics profiles associated with self-reported food intakes in female twins. PLOS ONE 11, e0158568. 27355821 PMC4927065

      Not checked in the free run.

    • cites [275] Dubost NJ, Ou B & Beelman RB (2007) Quantification of polyphenols and ergothioneine in cultivated mushrooms and correlation to total antioxidant capacity. Food Chem 105, 727– 735.

      Not checked in the free run.

    • cites [298] Dubost NJ, Beelman RB, Peterson D, et al. (2005) Identification and quantification of ergothioneine in cultivated mushrooms by liquid chromatography–mass spectroscopy. Int J Med Mush 8, 215– 222.

      Not checked in the free run.

    • cites [299] Dubost NJ, Beelman RB & Royse DJ (2007) Influence of selected cultural factors and postharvest storage on ergothioneine content of common button mushroom Agaricus bisporus (J. Lge) Imbach (Agaricomycetideae). Int J Med Mush 9, 163– 176.

      Not checked in the free run.

    • cites [300] Kalaras MD, Richie JP, Calcagnotto A, et al. (2017) Mushrooms: a rich source of the antioxidants ergothioneine and glutathione. Food Chem 233, 429– 433. 28530594

      Not checked in the free run.

    • cites [301] Tepwong P & Ohshima T (2009) Biosynthesis of ergothioneine during different stages of submerged fermentation of “Shiitake” (Lentinus edodes) mushroom and their bioactive properties. J Biosci Bioeng 108, S4– S5.

      Not checked in the free run.

    • cites [302] Tepwong P, Giri A & Ohshima T (2012) Effect of mycelial morphology on ergothioneine production during liquid fermentation of Lentinula edodes. Mycoscience 53, 102– 112.

      Not checked in the free run.

    • cites [303] Tepwong P, Giri A, Sasaki F, et al. (2012) Mycobial enhancement of ergothioneine by submerged cultivation of edible mushroom mycelia and its application as an antioxidative compound. Food Chem 131, 247– 258.

      Not checked in the free run.

    • cites [304] Kalaras MD, Beelman RB & Elias RJ (2012) Effects of postharvest pulsed UV light treatment of white button mushrooms (Agaricus bisporus) on vitamin D-2 content and quality attributes. J Agric Food Chem 60, 220– 225. 22132934

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing). May combine two claims.

    Interpretationcitation

    Studies of the effects of ERG have in general been rather descriptive in nature and at the level of processes rather than mechanisms.

    “studies of the effects of ERG have in general(449) been rather descriptive in nature. Many have been at the level of processes rather than mechanisms”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [449] Kell DB & Oliver SG (2004) Here is the evidence, now what is the hypothesis? The complementary roles of inductive and hypothesis-driven science in the post-genomic era. Bioessays 26, 99– 105. 14696046 source

      Not checked in the free run.

    • cites [3] Paul BD & Snyder SH (2010) The unusual amino acid l-ergothioneine is a physiologic cytoprotectant. Cell Death Differ 17, 1134– 1140. 19911007 PMC2885499 source

      Not checked in the free run.

    • cites [360] Cheah IK, Tang RMY, Yew TSZ, et al. (2017) Administration of pure ergothioneine to healthy human subjects: uptake, metabolism, and effects on biomarkers of oxidative damage and inflammation. Antioxid Redox Signal 26, 193– 206. 27488221 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    NF-κB is redox-sensitive.

    “is itself redox-sensitive(455–458)”
    Quote in the paperNot a substantial claim0 of 4 sources checked
    • cites [455] Buelna-Chontal M & Zazueta C (2013) Redox activation of Nrf2 & NF-κB: a double end sword? Cell Signal 25, 2548– 2557. 23993959

      Not checked in the free run.

    • cites [456] Kaur U, Banerjee P, Bir A, et al. (2015) Reactive oxygen species, redox signaling and neuroinflammation in Alzheimer’s disease: the NF-κB connection. Curr Top Med Chem 15, 446– 457. 25620241

      Not checked in the free run.

    • cites [457] Lepetsos P, Papavassiliou KA & Papavassiliou AG (2019) Redox and NF-κB signaling in osteoarthritis. Free Radic Biol Med 132, 90– 100. 30236789

      Not checked in the free run.

    • cites [458] Gao G & Dudley SC Jr (2009) Redox regulation, NF-κB, and atrial fibrillation. Antioxid Redox Signal 11, 2265– 2277. 19309257 PMC2819799

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Polymorphisms in SLC22A4 are associated with ischaemic stroke, erythroid differentiation, hearing loss, rheumatoid arthritis, lupus, Crohn's disease, type 1 diabetes and diabetic embryopathy.

    “Polymorphisms in SLC22A4, of which there can be many(177,412–415), under selection(416), have also been associated with ischaemic stroke(417), erythroid differentiation(418), hearing loss(412), rheumatoid arthritis(126,180,419–427), lupus(428), Crohn’s disease(401,429–436), hearing loss(412), type 1 diabetes(437) and diabetic embryopathy(438).”
    Quote in the paperNot a substantial claim0 of 10 sources checked
    • cites [417] Yamase Y, Horibe H, Ueyama C, et al. (2015) Association of TOMM40 and SLC22A4 polymorphisms with ischemic stroke. Biomed Rep 3, 491– 498. 26171154 PMC4487021

      Not checked in the free run.

    • cites [401] Kato Y, Kubo Y, Iwata D, et al. (2010) Gene knockout and metabolome analysis of carnitine/organic cation transporter OCTN1. Pharm Res 27, 832– 840. 20224991

      Not checked in the free run.

    • cites [429] Taubert D, Grimberg G, Jung N, et al. (2005) Functional role of the 503F variant of the organic cation transporter OCTN1 in Crohn’s disease. Gut 54, 1505– 1506. 16162962 PMC1774715

      Not checked in the free run.

    • cites [430] Taubert D, Jung N, Goeser T, et al. (2009) Increased ergothioneine tissue concentrations in carriers of the Crohn’s disease risk-associated 503F variant of the organic cation transporter OCTN1. Gut 58, 312– 314. 19136526

      Not checked in the free run.

    • cites [431] Jung ES, Park HJ, Kong KA, et al. (2017) Association study between OCTN1 functional haplotypes and Crohn’s disease in a Korean population. Korean J Physiol Pharmacol 21, 11– 17. 28066136 PMC5214902

      Not checked in the free run.

    • cites [432] Lai Y, Xue J, Liu CW, et al. (2019) Serum metabolomics identifies altered bioenergetics, signaling cascades in parallel with exposome markers in Crohn’s disease. Molecules 24, 449. PMC6385106 30691236

      Not checked in the free run.

    • cites [433] Huff CD, Witherspoon DJ, Zhang Y, et al. (2012) Crohn’s disease and genetic hitchhiking at IBD5. Mol Biol Evol 29, 101– 111. 21816865 PMC3245542

      Not checked in the free run.

    • cites [434] Peltekova VD, Wintle RF, Rubin LA, et al. (2004) Functional variants of OCTN cation transporter genes are associated with Crohn disease. Nat Genet 36, 471– 475. 15107849

      Not checked in the free run.

    • cites [435] Newman B, Gu X, Wintle R, et al. (2005) A risk haplotype in the solute carrier family 22A4/22A5 gene cluster influences phenotypic expression of Crohn’s disease. Gastroenterology 128, 260– 269. 15685536

      Not checked in the free run.

    • cites [436] Leung E, Hong J, Fraser AG, et al. (2006) Polymorphisms in the organic cation transporter genes SLC22A4 and SLC22A5 and Crohn’s disease in a New Zealand Caucasian cohort. Immunol Cell Biol 84, 233– 236. 16519742

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In human volunteers given 5-25 mg daily doses of ERG for 7 d, urinary excretion was <4%, and main metabolites were hercynine and lesser amounts of S-methyl-ERG, correlated with ERG level and dose.

    “In a recent and detailed study, Cheah et al. (360) administered 5–25 mg daily doses of ERG to human volunteers for 7 d. There was little urinary excretion (<4 %), and the main metabolites were hercynine, plus lesser amounts of S-methyl-ERG, whose concentrations were well correlated with the level of ERG and the dose of ERG given.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [360] Cheah IK, Tang RMY, Yew TSZ, et al. (2017) Administration of pure ergothioneine to healthy human subjects: uptake, metabolism, and effects on biomarkers of oxidative damage and inflammation. Antioxid Redox Signal 26, 193– 206. 27488221 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Thiolurocanic acid can be further degraded to glutamate.

    “The thiolurocanic acid can be further degraded to glutamate(410).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [410] Booth JS, Appleman MD (1963) Degradation of ergothioneine by cell-free extracts of Alcaligenes faecalis. II. Production of glutamic acid. J Bacteriol 85, 654– 657. 14042946 PMC278197

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Various biomarkers of oxidative stress (e.g., 8-iso-PGF2α) were lowered concomitantly in the human study, attesting to antioxidant functions of ERG in vivo.

    “Various other biomarkers of oxidative stress (for example, 8-iso-PGF2α from lipid peroxidation) were lowered concomitantly in the human study, attesting to the antioxidant functions of ERG in vivo, although in this case the healthy young subjects were probably not suffering from oxidative stress.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    ERG is present in eye lens, where its concentration is lower in individuals with cataracts.

    “ERG is also present in eye lens, where its concentration is lower in individuals with cataracts(400).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [400] Shukla Y, Kulshrestha OP & Khuteta KP (1981) Ergothioneine content in normal and senile human cataractous lenses. Indian J Med Res 73, 472– 473. 7275246

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Mushrooms have substantial effects on cognitive function, mainly ascribed to their ERG content.

    “Mushrooms have been shown to have very substantial effects on cognitive function(341,348,510–513), and this is mainly ascribed to their ERG content”
    Quote in the paperSubstantial claim0 of 6 sources checked
    • cites [341] Mori K, Inatomi S, Ouchi K, et al. (2009) Improving effects of the mushroom Yamabushitake (Hericium erinaceus) on mild cognitive impairment: a double-blind placebo-controlled clinical trial. Phytother Res 23, 367– 372. 18844328

      Not checked in the free run.

    • cites [348] Feng L, Cheah IK, Ng MM, et al. (2019) The association between mushroom consumption and mild cognitive impairment: a community-based cross-sectional study in Singapore. J Alzheimers Dis 68, 197– 203. 30775990

      Not checked in the free run.

    • cites [510] Nurk E, Refsum H, Drevon CA, et al. (2010) Cognitive performance among the elderly in relation to the intake of plant foods. The Hordaland Health Study. Br J Nutr 104, 1190– 1201. 20550741

      Not checked in the free run.

    • cites [511] Zhang S, Tomata Y, Sugiyama K, et al. (2017) Mushroom consumption and incident dementia in elderly Japanese: the Ohsaki Cohort 2006 Study. J Am Geriatr Soc 65, 1462– 1469. 28295137

      Not checked in the free run.

    • cites [512] Phan CW, David P & Sabaratnam V (2017) Edible and medicinal mushrooms: emerging brain food for the mitigation of neurodegenerative diseases. J Med Food 20, 1– 10. 28098514

      Not checked in the free run.

    • cites [513] Thangthaeng N, Miller MG, Gomes SM, et al. (2015) Daily supplementation with mushroom (Agaricus bisporus) improves balance and working memory in aged rats. Nutr Res 35, 1079– 1084. 26475179

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    ERG does not have the pro-oxidant issue of ascorbate, partly because it can chelate Fe and Cu.

    “This is not an issue with ERG, however, partly because it can chelate them”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    In a 3236-participant Swedish study, ERG was the metabolite most strongly connected to a health conscious food pattern and was associated with lower risk of coronary disease, cardiovascular mortality and overall mortality.

    “in a 3236-participant Swedish study, ERG was the metabolite most strongly connected to a ‘health conscious food pattern’ and was associated with a lower risk of coronary disease (hazard ratio (HR) per 1 sd increment of ERG, HR = 0·85; P = 0·01), cardiovascular mortality (HR = 0·79; P = 0·002) and overall mortality (HR = 0·86; P = 4 × 10–5)(509).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [509] Smith E, Ottosson F, Hellstrand S, et al. (2019) Ergothioneine is associated with reduced mortality and decreased risk of cardiovascular disease. Heart 2019, heartjnl-2019-315485 (epublication ahead of print version 31 October 2019). PMC7229907 31672783

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Consuming 1.5 mushroom servings per week is associated with a halving of the incidence of mild cognitive impairment, and nine servings per week with a five-fold decrease.

    “consuming 1·5 mushroom servings per week was associated with a halving of the incidence of mild cognitive impairment (a precursor of Alzheimer’s dementia), while intake of nine servings per week was associated with a five-fold decrease(348).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [348] Feng L, Cheah IK, Ng MM, et al. (2019) The association between mushroom consumption and mild cognitive impairment: a community-based cross-sectional study in Singapore. J Alzheimers Dis 68, 197– 203. 30775990

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    ERG levels are decreased, or ERG has been proposed as a useful antioxidant, in diseases such as acute respiratory distress syndrome, CVD, chronic obstructive pulmonary disease, pre-eclampsia, overhydrated hereditary stomatocytosis, and certain leukaemias.

    “ERG levels are decreased, or ERG has been proposed as a useful antioxidant, in diseases such as acute respiratory distress syndrome(505), CVD(506,507), chronic obstructive pulmonary disease(223), pre-eclampsia(8) (see also Turner et al. (128)), overhydrated hereditary stomatocytosis(508), and is significantly lowered in others such as certain leukaemias(121,122).”
    Quote in the paperSubstantial claim0 of 4 sources checked
    • cites [505] Repine JE & Elkins ND (2012) Effect of ergothioneine on acute lung injury and inflammation in cytokine insufflated rats. Prev Med 54, Suppl., S79– S82. 22197759 PMC3355229

      Not checked in the free run.

    • cites [506] Martin KR (2010) The bioactive agent ergothioneine, a key component of dietary mushrooms, inhibits monocyte binding to endothelial cells characteristic of early cardiovascular disease. J Med Food 13, 1340– 1346. 21091247

      Not checked in the free run.

    • cites [507] Servillo L, D’Onofrio N & Balestrieri ML (2017) Ergothioneine antioxidant function: from chemistry to cardiovascular therapeutic potential. J Cardiovasc Pharmacol 69, 183– 191. 28375902

      Not checked in the free run.

    • cites [223] Rahman I (2012) Pharmacological antioxidant strategies as therapeutic interventions for COPD. Biochim Biophys Acta 1822, 714– 728. 22101076 PMC3295924

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    ERG has been shown to protect against a range of oxidative and toxic insults, including decreasing oxidative stress in rat liver and kidney, rescuing cells from β-amyloid-induced apoptotic death, protecting against palmitic acid-induced cell death, mercuric chloride-induced cellular dysfunction, and Cu-induced oxidative DNA damage.

    “ERG has been shown to decrease oxidative stress in the liver and kidney of rats(469), rescued cells from β-amyloid-induced apoptotic death(231), protected against palmitic acid-induced cell death(470), mercuric chloride-induced cellular dysfunction(471), and prevented Cu-induced oxidative damage to DNA(472,473).”
    Quote in the paperSubstantial claim0 of 4 sources checked
    • cites [469] Deiana M, Rosa A, Casu V, et al. (2004) l-Ergothioneine modulates oxidative damage in the kidney and liver of rats in vivo: studies upon the profile of polyunsaturated fatty acids. Clin Nutr 23, 183– 193. 15030958 source

      Not checked in the free run.

    • cites [231] Jang JH, Aruoma OI, Jen LS, et al. (2004) Ergothioneine rescues PC12 cells from β-amyloid-induced apoptotic death. Free Radic Biol Med 36, 288– 299. 15036348 source

      Not checked in the free run.

    • cites [472] Rai RK, Chalana A, Karri R, et al. (2019) Role of hydrogen bonding by thiones in protecting biomolecules from copper(I)-mediated oxidative damage. Inorg Chem 58, 6628– 6638 31067034 source

      Not checked in the free run.

    • cites [473] Zhu BZ, Mao L, Fan RM, et al. (2011) Ergothioneine prevents copper-induced oxidative damage to DNA and protein by forming a redox-inactive ergothioneine–copper complex. Chem Res Toxicol 24, 30– 34. 21047085 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Nominally antioxidant molecules such as ascorbate have complex, multi-electron redox chemistry and can act as pro-oxidants, especially in the presence of free Fe or Cu.

    “nominally antioxidant molecules such as ascorbate have complex, multi-electron redox chemistry, and can in fact act as pro-oxidants(502,503), especially in the presence of free Fe(208,213) or Cu(504).”
    Quote in the paperSubstantial claim0 of 5 sources checked
    • cites [502] Mendes-da-Silva RF, Lopes-de-Morais AA, Bandim-da-Silva ME, et al. (2014) Prooxidant versus antioxidant brain action of ascorbic acid in well-nourished and malnourished rats as a function of dose: a cortical spreading depression and malondialdehyde analysis. Neuropharmacology 86, 155– 160. 25008558 source

      Not checked in the free run.

    • cites [503] Zhang P & Omaye ST (2001) Antioxidant and prooxidant roles for β-carotene, α-tocopherol and ascorbic acid in human lung cells. Toxicol In Vitro 15, 13– 24. 11259865 source

      Not checked in the free run.

    • cites [208] Kell DB (2009) Iron behaving badly: inappropriate iron chelation as a major contributor to the aetiology of vascular and other progressive inflammatory and degenerative diseases. BMC Med Genomics 2, 2. 19133145 PMC2672098 source

      Not checked in the free run.

    • cites [213] Kell DB (2010) Towards a unifying, systems biology understanding of large-scale cellular death and destruction caused by poorly liganded iron: Parkinson’s, Huntington’s, Alzheimer’s, prions, bactericides, chemical toxicology and others as examples. Arch Toxicol 577, 825– 889. PMC2988997 20967426 source

      Not checked in the free run.

    • cites [504] Ullah MF, Khan HY, Zubair H, et al. (2011) The antioxidant ascorbic acid mobilizes nuclear copper leading to a prooxidant breakage of cellular DNA: implications for chemotherapeutic action against cancer. Cancer Chemother Pharmacol 67, 103– 110. 20213077 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    NF-κB increases the rates of SLC22A4 transcription.

    “NF-κB increases the rates of SC22A4 transcription(419).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [419] Maeda T, Hirayama M, Kobayashi D, et al. (2007) Mechanism of the regulation of organic cation/carnitine transporter 1 (SLC22A4) by rheumatoid arthritis-associated transcriptional factor RUNX1 and inflammatory cytokines. Drug Metab Dispos 35, 394– 401. 17142562

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    ERG has been widely used in cosmetics and is known as a skin protectant.

    “ERG has been widely used(543–547), since much skin damage is caused by UV-mediated reactive oxygen species production(548); indeed, ERG is known as a skin protectant(240–244,549–551).”
    Quote in the paperNot a substantial claim0 of 10 sources checked
    • cites [543] Taofiq O, González-Paramás AM, Martins A, et al. (2016) Mushrooms extracts and compounds in cosmetics, cosmeceuticals and nutricosmetics – a review. Industrial Crops Products 90, 38– 48.

      Not checked in the free run.

    • cites [544] Wu Y, Choi M-H, Li J, et al. (2016) Mushroom cosmetics: the present and future. Cosmetics 3, 22.

      Not checked in the free run.

    • cites [545] Linder J (2012) Cosmeceutical treatment of the aging face In Aesthetic Medicine, pp. 69– 84 [ PM Prendergast and MA Shiffman, editors]. Berlin: Springer.

      Not checked in the free run.

    • cites [546] Cronin H, Draelos ZD (2010) Top 10 botanical ingredients in 2010 anti-aging creams. J Cosmet Dermatol 9, 218– 225. 20883295

      Not checked in the free run.

    • cites [547] Souyoul SA, Saussy KP & Lupo MP (2018) Nutraceuticals: a review. Dermatol Ther (Heidelb) 8, 5– 16. 29411317 PMC5825326

      Not checked in the free run.

    • cites [240] Dong KK, Damaghi N, Kibitel J, et al. (2007) A comparison of the relative antioxidant potency of l-ergothioneine and idebenone. J Cosmet Dermatol 6, 183– 188. 17760697

      Not checked in the free run.

    • cites [241] Obayashi K, Kurihara K, Okano Y, et al. (2005) l-Ergothioneine scavenges superoxide and singlet oxygen and suppresses TNF-α and MMP-1 expression in UV-irradiated human dermal fibroblasts. J Cosmet Sci 56, 17– 27. 15744438

      Not checked in the free run.

    • cites [242] Stoffels C, Oumari M, Perrou A, et al. (2017) Ergothioneine stands out from hercynine in the reaction with singlet oxygen: resistance to glutathione and TRIS in the generation of specific products indicates high reactivity. Free Radic Biol Med 113, 385– 394. 29074402

      Not checked in the free run.

    • cites [243] He QC, Krone K, Scherl D, et al. (2004) The use of ozone as an oxidizing agent to evaluate antioxidant activities of natural substrates. Skin Pharmacol Physiol 17, 183– 189. 15258449

      Not checked in the free run.

    • cites [244] Markova NG, Karaman-Jurukovska N, Dong KK, et al. (2009) Skin cells and tissue are capable of using l-ergothioneine as an integral component of their antioxidant defense system. Free Radic Biol Med 46, 1168– 1176. 19439218

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Brain and serum ERG levels are markedly different in Parkinson's disease and in sudden infant death syndrome.

    “Brain and serum ERG levels are also markedly different in Parkinson’s disease(515), reviewed in Hang et al. (516), Shao & Le(517) and Shah & Duda(518), and even in sudden infant death syndrome(519)”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [515] Hatano T, Saiki S, Okuzumi A, et al. (2016) Identification of novel biomarkers for Parkinson’s disease by metabolomic technologies. J Neurol Neurosurg Psychiatry 87, 295– 301. 25795009

      Not checked in the free run.

    • cites [519] Graham SF, Chevallier OP, Kumar P, et al. (2017) Metabolomic profiling of brain from infants who died from sudden infant death syndrome reveals novel predictive biomarkers. J Perinatol 37, 91– 97. 27608295

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    The evidence that ERG may be a useful nutraceutical as a preventive or palliative for various inflammatory diseases is extensive but mostly circumstantial rather than definitive.

    “While the evidence that ERG may be a useful nutraceutical as a preventive or palliative for various inflammatory diseases is extensive, it is mostly circumstantial rather than definitive”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    ERG is a potent and effective antioxidant and seems to be an important nutraceutical.

    “ERG, a potent and effective antioxidant, seems to be an important nutraceutical”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    ERG is protective against β-amyloid-induced neuronal injury and cytotoxicity.

    “ERG has been shown to be protective against β-amyloid-induced neuronal injury(520) and cytotoxicity(521).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [520] Yang NC, Lin HC, Wu JH, et al. (2012) Ergothioneine protects against neuronal injury induced by β-amyloid in mice. Food Chem Toxicol 50, 3902– 3911. 22921351

      Not checked in the free run.

    • cites [521] Cheah IK, Ng LT, Ng LF, et al. (2019) Inhibition of amyloid-induced toxicity by ergothioneine in a transgenic Caenorhabditis elegans model. FEBS Lett 593, 2139– 2150. 31211853

      Not checked in the free run.

47 of 47

  • The paper relies on this without support.

    ERG classes as a nutraceutical.

    “Since ERG classes as a nutraceutical, it seems timely to bring together the extensive but widespread knowledge of its biology so that it may be made more widely available, and that is the purpose of this review.”

  • The paper relies on this without support.

    The chief source of ERG in the human diet is mushrooms.

    “The chief source of ERG in the human diet is mushrooms (usually the fruiting bodies of Basidiomycetes).”

  • The paper relies on this without support.

    SLC22A4 has evolved and been selected to effect ERG uptake in all known animals.

    “The fact that a specific transporter known as SLC22A4 has evolved and been selected to effect ERG uptake in all known animals”
3 of 3

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Red-blood-cell measurements are labeled serum concentrations

    Minor

    Table 3 presents the age-group values as serum concentrations, while its cited study is explicitly about levels in red blood cells.

  • Transporter distribution conflicts with claim about all animals

    Minor

    The conclusions say SLC22A4 evolved to effect uptake in all known animals, whereas the phylogenetic section says its homologues exist only in vertebrate animals.

  • Metal-affinity ordering places zinc both above and below cobalt

    Minor

    The same strict ordering places zinc above cobalt and cobalt above zinc, so it cannot hold as written.

  • Mouse data appear in a table labeled human serum

    Minor

    Table 3 is titled as concentrations in human serum, but one of its rows reports a measurement from mice.

4 of 4

Cites

Flagged first, then by citations

26 of the 615 references couldn’t be matched to a known paper.

Research works printed but not linked: 11

  1. 381. Bashir, R (2017) Bio-analytical screening and characterization of antioxidant compounds using online liquid chromatography techniques and mass spectrometry. Thesis for Doctor of Philosophy, Swinburne University of Technology.
  2. van der Hoek, 2019, Engineering the yeast Saccharomyces cerevisiae for the production of l-(+)-ergothioneine, bioRxiv, 2019, 667592
  3. Tanret, 1909, A new base taken from rye ergot, ergothioneine, Ann Chim Phys, 18, 114
  4. Rahman, 2017, Corroborative assessment of mushroom as the graceful ageing and lifespan promoting agent, Biointerface Res App, 7, 2072
  5. Hartman, 1986, Ergothioneine (2-thiol-l-histidine betaine = Et) as an antimutagen – interception of direct-acting mutagens formed from nitrosation of spermidine, Environ Mol Mutagen, 8, 36
  6. 10.1023/a:1006914028195 · DOI
  7. Logan, 2013, Lipid Oxidation: Challenges in Food Systems
  8. 403. Jose, JM (2011) Ergothioneine degradation and properties of ergothionase from Agrobacterium radiobacter. BSc Thesis, Penn State University.
  9. Tanret, 1909, The new base drawn from rye ergot, ergothioneine, Cr Hebd Acad Sci, 149, 222
  10. Hartman, 1986, Protection afforded by carnosine and by ergothioneine against bacteriophage-P22 inactivation by gamma-irradiation, Environ Mol Mutagen, 8, 35
  11. Kell, 2009, Proceedings of the International Beilstein Symposium on Systems Chemistry, 149

Cited by

Sorted by citations

Related

Authors
Borodina, I., Kenny, L. C., McCarthy, C. M., Paramasivan, K., Pretorius, E., Roberts, T. J., van der Hoek, S. A., & Kell, D. B.
Affiliations
  • Novo Nordisk Foundation (DK)
  • University of Liverpool (GB)
  • University College Cork (IE)
  • Stellenbosch University (ZA)
Corresponding author
Kell, Douglas B.
ORCID
Venue
Nutrition Research Reviews
Publisher
Cambridge University Press (CUP)
Published
2020-02-13
Volume
33
Issue
2
Pages
190-217
ISSN
  • 0954-4224 (ISSN-L)
  • 1475-2700
DOI
10.1017/s0954422419000301
PMC
PMC7653990
OpenAlex
W3006322261
Semantic Scholar
5524d0186c44a8298e41eefc7977e93586a821c5
Cited by
296
References
615
Citations by year
2026: 58 · 2025: 59 · 2024: 54 · 2023: 37 · 2022: 42 · 2021: 33 · 2020: 13
FWCI
3.02
Type
journal article
Language
en
Open access
Licence
Locations
  • Nutrition Research Reviews (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Technical University of Denmark, DTU Orbit (Technical University of Denmark, DTU) (submittedVersion, other-oa)
Funders
  • Novo Nordisk (NNF10CC1016517)
  • Novo Nordisk Fonden (NNF20OC0060809, NNF10CC1016517)
  • Directorate for Biological Sciences
  • Biotechnology and Biological Sciences Research Council (BB/P009042/1, BB/P009042/2, BB/R000093/1)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Sulfur Compounds in Biology
  • Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
  • Health Sciences › Nursing › Nutrition and Dietetics › Selenium in Biological Systems
Keywords
ergothioneine, antioxidants, nutraceuticals, SLC22A4, amino acid transporters, fungal biosynthesis, actinobacteria, mushroom fruiting bodies, dietary intake, erythrocytes, oxidative stress, cytoprotection, chronic inflammatory diseases, food safety
MeSH terms
Animals, Antioxidants, Biological Products, Ergothioneine, Fungi, Humans, Oxidative Stress, Dietary Supplements, Organic Cation Transport Proteins, Symporters, Actinobacteria

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-10.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-10.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review