CoChat
Sign Up
Cited by 1,924Animal Behavior and ReproductionAntioxidant Activity and Oxidative StressBird parasitology and diseases

No evidence that carotenoid pigments boost either immune or antioxidant defenses in a songbird

Open access
Koch, Rebecca E., Kavazis, Andreas N., Hasselquist, Dennis, Hood, Wendy R., Zhang, Yufeng, Toomey, Matthew B., Hill, Geoffrey E.·2018·Nature Communications
DOI 10.1038/s41467-018-02974-xPMC PMC5799171
Open this paper in CoChat — free accountOpen PDF

Abstract

Dietary carotenoids have been proposed to boost immune system and antioxidant functions in vertebrate animals, but studies aimed at testing these physiological functions of carotenoids have often failed to find support. Here we subject yellow canaries ( Serinus canaria ), which possess high levels of carotenoids in their tissue, and white recessive canaries, which possess a knockdown mutation that results in very low levels of tissue carotenoids, to oxidative and pathogen challenges. Across diverse measures of physiological performance, we detect no differences between carotenoid-rich yellow and carotenoid-deficient white canaries. These results add further challenge to the assumption that carotenoids are directly involved in supporting physiological function in vertebrate animals. While some dietary carotenoids provide indirect benefits as retinoid precursors, our observations suggest that carotenoids themselves may play little to no direct role in key physiological processes in birds.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1038/s41467-018-02974-x

Cites

2 of 2 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

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?

  • Surface expression changes of other receptors involved in Aβ recognition and uptake might have counteracted the effects of increased TREM2 signaling upon INPP5D haploinsufficiency.

    “Although TREM2 has been shown to bind to Aβ and facilitate its uptake80,81, the surface expression changes of other receptors involved in Aβ recognition and uptake might have counteracted the effects of increased TREM2 signaling upon INPP5D haploinsufficiency83,84.”

    From INPP5D/SHIP1 regulates endo-lysosomal function and cargo-selective phagocytosis in human microglia (2025) · cites this paper as [84]

    The cited paper’s Discussion concerns carotenoid pigmentation and physiological defenses in canaries; its Methods describe avian immune assays. Searches of our full-text copy for TREM2, INPP5D, Aβ uptake, and receptor surface expression found no passage addressing the proposed counteracting effect. (LLM, conf=0.79)

    Experimental — accuracy not yet measured

  • Aβ can bind to lipoproteins such as clusterin (ApoJ) and ApoE in the brain, which facilitates its clearance by microglia via TREM2.

    “However, Aβ can bind to lipoproteins such as clusterin (ApoJ) and ApoE in the brain82–84, which facilitates its clearance by microglia via TREM281.”

    From INPP5D/SHIP1 regulates endo-lysosomal function and cargo-selective phagocytosis in human microglia (2025) · cites this paper as [84]

    The Methods sections on LPS challenge and respiratory burst concern immune responses in songbirds, not amyloid-β clearance in the brain. Searches for TREM2, microglia, ApoE, and clusterin found no passage in our copy addressing the claim. (LLM, conf=0.79)

    Experimental — accuracy not yet measured

Self-check

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

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 45

  1. [1]Rao AV Rao LG Carotenoids and human health Pharmacol. Res. 2007 55 207 216 10.1016/j.phrs.2007.01.012 17349800 · DOI
  2. [2]Surai PF Speake BK Sparks NHC Carotenoids in avian nutrition and embryonic development. 2. Antioxidant properties and discrimination in embryonic tissues J. Poult. Sci. 2001 38 117 145 10.2141/jpsa.38.117 · DOI
  3. [3]Svensson PA Wong BBM Carotenoid-based signals in behavioural ecology: a review Behaviour 2011 148 131 189 10.1163/000579510X548673 · DOI
  4. [4]Perera CO Yen GM Functional properties of carotenoids in human health Int. J. Food Prop. 2007 10 201 230 10.1080/10942910601045271 · DOI
  5. [5]Chew BP Park JS Carotenoid action on the immune response J. Nutr. 2004 134 257S 261S 10.1093/jn/134.1.257S 14704330 · DOI
  6. [6]Costantini D Møller AP Carotenoids are minor antioxidants for birds Funct. Ecol. 2008 22 367 370 10.1111/j.1365-2435.2007.01366.x · DOI
  7. [7]Perez-Rodriguez L Carotenoids in evolutionary ecology: re-evaluating the antioxidant role BioEssays 2009 31 1116 1126 10.1002/bies.200900070 19705366 · DOI
  8. [9]Olson VA Owens IPF Costly sexual signals: are carotenoids rare, risky or required? Trends Ecol. Evol. 1998 13 510 514 10.1016/S0169-5347(98)01484-0 21238418 · DOI
  9. [10]Bertrand S Faivre B Sorci G Do carotenoid-based sexual traits signal the availability of non-pigmentary antioxidants? J. Exp. Biol. 2006 209 4414 4419 10.1242/jeb.02540 17079711 · DOI
  10. [11]Simons MJ Cohen AA Verhulst S What does carotenoid-dependent coloration tell? Plasma carotenoid level signals immunocompetence and oxidative stress state in birds—a meta-analysis PLoS ONE 2012 7 e43088 10.1371/journal.pone.0043088 22905205 PMC3419220 · DOI
  11. [12]Simons MJ Maia R Leenknegt B Verhulst S Carotenoid-dependent signals and the evolution of plasma carotenoid levels in birds Am. Nat. 2014 184 741 751 10.1086/678402 25438174 · DOI
  12. [14]Toomey MB High-density lipoprotein receptor SCARB1 is required for carotenoid coloration in birds Proc. Natl. Acad. Sci. USA 2017 114 5219 5224 10.1073/pnas.1700751114 28465440 PMC5441819 · DOI
  13. [18]Sild E Hõrak P Assessment of oxidative burst in avian whole blood samples: validation and application of a chemiluminescence method based on Pholasin Behav. Ecol. Sociobiol. 2010 64 2065 2076 10.1007/s00265-010-1076-z · DOI
  14. [19]Harmon BG Avian heterophils in inflammation and disease resistance Poult. Sci. 1998 77 972 977 10.1093/ps/77.7.972 9657606 · DOI
  15. [20]Maney DL Davis AK Goode CT Reid A Showalter C Carotenoid-based plumage coloration predicts leukocyte parameters during the breeding season in northern cardinals (Cardinalis cardinalis) Ethology 2008 114 369 380 10.1111/j.1439-0310.2008.01476.x · DOI
  16. [21]Gross WB Siegel HS Evaluation of the heterophil/lymphocyte ratio as a measure of stress in chickens Avian Dis. 1983 27 972 979 10.2307/1590198 6360120 · DOI
  17. [22]Costantini D Møller AP Does immune response cause oxidative stress in birds? A meta-analysis Comp. Biochem. Physiol. A Mol. Integr. Physiol. 2009 153 339 344 10.1016/j.cbpa.2009.03.010 19303455 · DOI
  18. [24]Ilmonen P Taarna T Hasselquist D Experimentally activated immune defence in female pied flycatchers results in reduced breeding success Proc. R. Soc. Lond. Ser. B 2000 267 665 670 10.1098/rspb.2000.1053 PMC1690582 10821610 · DOI
  19. [25]Hasselquist D Marsh JA Sherman PW Wingfield JC Is avian humoral immunocompetence suppressed by testosterone? Behav. Ecol. Sociobiol. 1999 45 167 175 10.1007/s002650050550 · DOI
  20. [26]Koch RE Hill GE An assessment of techniques to manipulate oxidative stress in animals Funct. Ecol. 2017 31 9 21 10.1111/1365-2435.12664 · DOI
  21. [27]Tella JL Ecological, morphological and phylogenetic correlates of interspecific variation in plasma carotenoid concentration in birds J. Evol. Biol. 2004 17 156 164 10.1046/j.1420-9101.2003.00634.x 15000658 · DOI
  22. [28]Simons MJP Groothuis TGG Verhulst S An appraisal of how the vitamin A-redox hypothesis can maintain honesty of carotenoid-dependent signals Ecol. Evol. 2015 5 224 228 10.1002/ece3.1364 25628879 PMC4298449 · DOI
  23. [29]Hill GE Johnson JD The vitamin A-redox hypothesis: a biochemical basis for honest signaling via carotenoid pigmentation Am. Nat. 2012 180 E127 E150 10.1086/667861 23070328 · DOI · Paper page
  24. [30]Hill GE Condition-dependent traits as signals of the functionality of vital cellular processes Ecol. Lett. 2011 14 625 634 10.1111/j.1461-0248.2011.01622.x 21518211 · DOI
  25. [31]Weaver RJ Koch RE Hill GE What maintains signal honesty in animal colour displays used in mate choice? Philos. Trans. R. Soc. Lond. Ser. B 2017 372 20160343 10.1098/rstb.2016.0343 28533460 PMC5444064 · DOI
  26. [32]Koch RE Josefson CC Hill GE Mitochondrial function, ornamentation, and immunocompetence Biol. Rev. 2017 92 1459 1474 10.1111/brv.12291 27455896 · DOI
  27. [33]Johnson JD Hill GE Is carotenoid ornamentation linked to the inner mitochondria membrane potential? A hypothesis for the maintenance of signal honesty Biochimie 2013 95 436 444 10.1016/j.biochi.2012.10.021 23131590 · DOI
  28. [34]Hill GE Cellular respiration: the nexus of stress, condition, and ornamentation Integr. Comp. Biol. 2014 54 645 657 10.1093/icb/icu029 24791751 · DOI
  29. [35]García-de Blas E Mateo R Alonso-Alvarez C Specific carotenoid pigments in the diet and a bit of oxidative stress in the recipe for producing red carotenoid-based signals PeerJ 2016 4 e2237 10.7717/peerj.2237 27635308 PMC5012267 · DOI
  30. [36]Weaver RJ Santos ESA Tucker AM Wilson AE Hill GE Carotenoid metabolism strengthens the link between feather coloration and quality Nat. Commun. 2018 9 73 10.1038/s41467-017-02649-z 29311592 PMC5758789 · DOI
  31. [37]Lopes RJ Genetic basis for red coloration in birds Curr. Biol. 2016 26 1427 1434 10.1016/j.cub.2016.03.076 27212400 PMC5125026 · DOI
  32. [38]Mundy NI Red carotenoid coloration in the Zebra Finch is controlled by a cytochrome P450 gene cluster Curr. Biol. 2016 26 1435 1440 10.1016/j.cub.2016.04.047 27212402 · DOI
  33. [39]Tomášek O Opposing effects of oxidative challenge and carotenoids on antioxidant status and condition-dependent sexual signalling Sci. Rep. 2016 6 23546 10.1038/srep23546 27000655 PMC4802301 · DOI
  34. [40]Brockmann H Völker O Der gelbe Federfarbstoff des Kanarienvogels [Serinus canaria canaria (L.)] und das Vorkommen von Carotinoiden bei Vögeln Hoppe-Seylers Z. Für Physiol. Chem. 1934 224 193 215 10.1515/bchm2.1934.224.5-6.193 · DOI
  35. [41]Li W Beta T An evaluation of carotenoid levels and composition of glabrous canaryseed Food Chem. 2012 133 782 786 10.1016/j.foodchem.2012.01.092 · DOI
  36. [42]McGraw KJ Nolan PM Crino OL Carotenoid accumulation strategies for becoming a colourful House Finch: analyses of plasma and liver pigments in wild moulting birds Funct. Ecol. 2006 20 678 688 10.1111/j.1365-2435.2006.01121.x · DOI
  37. [43]Koch RE Wilson AE Hill GE The importance of carotenoid dose in supplementation studies with songbirds Physiol. Biochem. Zool. 2015 89 61 71 10.1086/684485 27082525 · DOI
  38. [44]Laaksonen T Effects of experimental brood size manipulation and gender on carotenoid levels of Eurasian Kestrels Falco tinnunculus PLoS ONE 2008 3 e2374 10.1371/journal.pone.0002374 18545646 PMC2396282 · DOI
  39. [45]Love OP Salvante KG Dale J Williams TD Sex‐specific variability in the immune system across life‐history stages Am. Nat. 2008 172 E99 E112 10.1086/589521 18665797 · DOI
  40. [46]McGraw KJ Nolan PM Crino OL Carotenoids bolster immunity during moult in a wild songbird with sexually selected plumage coloration Biol. J. Linn. Soc. 2011 102 560 572 10.1111/j.1095-8312.2010.01594.x · DOI
  41. [48]Sild E Sepp T Manniste M Horak P Carotenoid intake does not affect immune-stimulated oxidative burst in greenfinches J. Exp. Biol. 2011 214 3467 3473 10.1242/jeb.062182 21957110 · DOI
  42. [49]Al-Murrani PWK Al-Rawi AJ Al-Hadithi MF Al-Tikriti B Association between heterophil/lymphocyte ratio, a marker of ‘resistance’ to stress, and some production and fitness traits in chickens Br. Poult. Sci. 2006 47 443 448 10.1080/00071660600829118 16905470 · DOI
  43. [50]Davis AK Cook KC Altizer S Leukocyte profiles in wild House Finches with and without mycoplasmal conjunctivitis, a recently emerged bacterial disease EcoHealth 2004 1 362 373 10.1007/s10393-004-0134-2 · DOI
  44. [51]French SS Neuman-Lee LA Improved ex vivo method for microbiocidal activity across vertebrate species Biol. Open 2012 1 482 487 10.1242/bio.2012919 23213440 PMC3507210 · DOI
  45. [52]Luloff TW Wishart AE Addison SM MacDougall‐Shackleton SA Hill KA Radiation exposure differentially affects songbird 8‐hydroxy‐2′‐deoxyguanosine plasma profiles: ionizing radiation damage response in songbirds Environ. Mol. Mutagen. 2011 52 658 663 10.1002/em.20666 21809389 · DOI

Cited by

Sorted by citations

Authors
Koch, R. E., Kavazis, A. N., Hasselquist, D., Hood, W. R., Zhang, Y., Toomey, M. B., & Hill, G. E.
Affiliations
  • Monash University (AU)
  • Auburn University (US)
  • Lund University (SE)
  • Buck Institute for Research on Aging (US)
  • Washington University in St. Louis (US)
Corresponding author
Koch, Rebecca E.
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2018-02-05
Volume
9
Issue
1
Pages
491-491
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/s41467-018-02974-x
PMC
PMC5799171
OpenAlex
W2788593837
Cited by
1,924
References
2
Citations by year
2026: 88 · 2025: 179 · 2024: 215 · 2023: 261 · 2022: 371 · 2021: 384 · 2020: 298 · 2019: 105 · 2018: 22
FWCI
170.86
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Communications (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Digital Commons@Becker (Washington University School of Medicine) (submittedVersion)
  • Monash University Research Portal (Monash University) (submittedVersion, other-oa)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
  • Lund University Publications (Lund University) (submittedVersion)
Funders
  • National Science Foundation (1453784)
  • Auburn University
  • Vetenskapsrådet (621‐2013‐4357, 2016-04391)
Topics
  • Life Sciences › Agricultural and Biological Sciences › Ecology, Evolution, Behavior and Systematics › Animal Behavior and Reproduction
  • Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
  • Life Sciences › Immunology and Microbiology › Parasitology › Bird parasitology and diseases
Keywords
dietary carotenoids, immune function, antioxidant defense, oxidative stress, songbirds, avian physiology
MeSH terms
Animals, Antioxidants, Canaries, Carotenoids, Gene Expression Regulation, Immunity, Innate, Lipopolysaccharides, Mutation, Pigmentation, Pigments, Biological, Tetanus Toxoid, Scavenger Receptors, Class B

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.

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