We thank Elias and Williams for their interest in our review [...

Emma Beckett

Mark Lucock

Martin Veysey

Patrice Jones

Nutrients

English

Multidisciplinary Digital Publishing Institute

Reply: “Comment on: The Vitamin D–Folate Hypothesis as an Evolutionary Model for Skin Pigmentation: An Update and Integration of Current Ideas, Nutrients 2018, 10, 554”

Jones, P.

Lucock, M.

Veysey, M.

Beckett, E.

Repository@Hull - Worktribe

nutrientsReplyReply: “Comment on: The Vitamin D–FolateHypothesis as an Evolutionary Model for SkinPigmentation: An Update and Integration of CurrentIdeas, Nutrients 2018, 10, 554”Patrice Jones 1 , Mark Lucock 1,* , Martin Veysey 2 and Emma Beckett 1,31 School of Environmental & Life Sciences, University of Newcastle, Ourimbah, NSW 2258, Australia;patrice.jones@uon.edu.au (P.J.); emma.beckett@newcastle.edu.au (E.B.)2 Hull-York Medical School, University of York, Heslington, York YO10 5DD, UK; martin.veysey@hyms.ac.uk3 School of Medicine and Public Health, University of Newcastle, Ourimbah, NSW 2258, Australia* Correspondence: mark.lucock@newcastle.edu.au; Tel: +61-2-4348-4109Received: 23 October 2018; Accepted: 9 November 2018; Published: 14 November 2018Keywords: vitamin D; skin pigmentation; folate; vitamin D-folate hypothesisIntroductionWe thank Elias and Williams for their interest in our review [1]. While it appears that theauthors have taken issue with our focus, we assert that our review takes a balanced approach tointegrate current thinking into the prominent evolutionary models for skin pigmentation. In particular,we highlight the fact that this review sought to examine the overlap between these models, rather thanaiming to convince the reader of the merits of any one particular hypothesis.Contrary to what has been suggested by Elias and Williams, we do not “take issue” with thenotion that “pigmentation evolved to optimize permeability and antimicrobial barrier function in thehostile, infectious soup of equatorial Africa”. We remain open-minded about the various hypothesesand present them as such in our manuscript—i.e., as hypotheses, not empirically derived facts.Furthermore, where data is becoming available, it is important to incorporate them into the equation.Elias and Williams’ predilection for discussing congenital abnormalities, while interesting, does notadd to the debate. The role of low folate and/or subsequent elevated homocysteine in a great manycomplications of pregnancy would be more germane to the argument. For example, low folate and/orhigh homocysteine are associated with lower placental and birth weights (and, hence, perinatalmortality) [2]. Similarly, an aberrant effect on the gene methylation profile would also be likely [3].Given the intrinsically high rates of miscarriage during very early pregnancy, potential UV-associatedfolate loss, elevated embryotoxic homocysteine, and specific folate-related gene polymorphisms thatalter DNA methyl group-dependent synthesis (depending on folate status) are a nexus of phenomenathat would likely act to silently influence embryo survival. Therefore, any argument focusing ona single relationship between a specific congenital anomaly and reproductive success neglects toconsider folate (as well as vitamin D) as having extremely complex, polygenic, and pleiotropic actions.Elias and Williams’ statement that “folic acid, its metabolites, and its regulatory genes can bereadily degraded in vitro” is misleading, as the degradation of the genes simply does not occur(notwithstanding thermolability). The authors reference three studies that observe no effects of UVA/Bon serum folate levels; however, one of the references provided does not seem related to the pointsmade [4]. Referenced studies by Gambichler et al. (2001) and Juzeniene et al. (2010) report no influenceof UVA/B on serum folate levels in small cohorts [5,6], but an equal amount of other studies do reportan effect. Notably, Borradale et al. (2014) report that increases in solar UV radiation (UVR) exposureNutrients 2018, 10, 1759; doi:10.3390/nu10111759 www.mdpi.com/journal/nutrientsNutrients 2018, 10, 1759 2 of 3over three weeks reduce the efficacy of folic acid supplements and serum folate levels [7]. Additionally,we have recently shown in a larger population study that surface UV irradiance is associated withlong-term systemic folate levels (red cell and serum folate) and that this is strongly influenced by theC677T-MTHFR gene variant [8]. Differences in results between studies likely reflect differences in theUVR parameters assessed (UVA or UVB, single dose or cumulative exposures) and whether otherparameters of folate are considered in the studies (i.e., red cell folate levels or genetic polymorphism).Further controlled studies are warranted, but a lack of consensus does not represent a lack of evidence.In response to Elias and William’s views on vitamin D, we believe their interpretation overlooksseveral salient points made in our review about the integration of other theories proposed forskin depigmentation and the functions of vitamin D. We mentioned the Metabolic Conservationtheory, which proposes that depigmentation involves resources being drawn away from melaninproduction into other metabolic processes. This theory still supports the likelihood of extremedepigmentation in northern Europeans being a mechanism to facilitate vitamin D production inlow-UVR environments. We broadly discussed that the protection of vitamin D and folate statuslikely acted as a critical selection pressure for skin depigmentation and pigmentation close to the polesand the equator, respectively. These UV-related geophysical factors might drive deficiency in thesenutrients, but the primary “driver” in Central European and Asian populations may have been aneed to restrict melanin production and channel these resources into responding to increased energyneeds associated with colder climates. We make the point that this is not to say that the importance ofthese nutrients in populations in intermediate UVR environments is undermined—highlighting rolesin vasodilation/vasoconstriction and adipocyte biology that would have importance in maintainingenergy and temperature homeostasis in such environments.Unfortunately, much of the content in our review appears to have been overlooked by Elias andWilliams’ in their critique. We present an evidence-based discussion of a likely mutually beneficialrelationship between vitamin D, folate, and skin pigmentation that updates and further extends allcurrent theories for the evolution of skin pigmentation and depigmentation. The purpose of our reviewwas not to renounce any of the prominent theories for skin pigmentation and, hence, “cherry-pick” afavourite, but to discuss similarities between them and, hence, potentially extend these models. Thispurpose appears to have been be missed by Elias and Williams, whose response simply seems to bean argument against the vitamin D–folate hypothesis and a supporting letter for the alternate skinbarrier hypothesis.Funding: This research received no external funding.Conflicts of Interest: The authors declare no conflict of interet.References1. Jones, P.; Lucock, M.; Veysey, M.; Beckett, E. The Vitamin D-Folate Hypothesis as an Evolutionary Modelfor Skin Pigmentation: An Update and Integration of Current Ideas. Nutrients 2018, 10, 554. [CrossRef][PubMed]2. Bergen, N.E.; Jaddoe, V.W.; Timmermans, S.; Hofman, A.; Lindemans, J.; Russcher, H.; Raat, H.;Steegers-Theunissen, R.P.; Steegers, E.A. Homocysteine and folate concentrations in early pregnancy andthe risk of adverse pregnancy outcomes: The Generation R Study. BJOG Int. J. Obstet. Gynaecol. 2012, 119,739–751. [CrossRef] [PubMed]3. Joubert, B.R.; den Dekker, H.T.; Felix, J.F.; Bohlin, J.; Ligthart, S.; Beckett, E.; Tiemeier, H.; van Meurs, J.B.;Uitterlinden, A.G.; Hofman, A.; et al. Maternal plasma folate impacts differential DNA methylation in anepigenome-wide meta-analysis of newborns. Nat. Commun. 2016, 7, 10577. [CrossRef] [PubMed]4. Cicarma, E.; Juzeniene, A.; Porojnicu, A.C.; Bruland, O.S.; Moan, J. Latitude gradient for melanoma incidenceby anatomic site and gender in Norway 1966–2007. J. Photochem. Photobiol. B Biol. 2010, 101, 174–178.[CrossRef] [PubMed]5. Gambichler, T.; Bader, A.; Sauermann, K.; Altmeyer, P.; Hoffmann, K. Serum folate levels after UVA exposure:A two-group parallel randomised controlled trial. BMC Dermatol. 2001, 1. [CrossRef]Nutrients 2018, 10, 1759 3 of 36. Juzeniene, A.; Stokke, K.T.; Thune, P.; Moan, J. Pilot study of folate status in healthy volunteers and inpatients with psoriasis before and after UV exposure. J. Photochem. Photobiol. B Biol. 2010, 101, 111–116.[CrossRef] [PubMed]7. Borradale, D.; Isenring, E.; Hacker, E.; Kimlin, M.G. Exposure to solar ultraviolet radiation is associatedwith a decreased folate status in women of childbearing age. J. Photochem. Photobiol. B Biol. 2014, 131, 90–95.[CrossRef] [PubMed]8. Lucock, M.; Beckett, E.; Martin, C.; Jones, P.; Furst, J.; Yates, Z.; Jablonski, N.G.; Chaplin, G.; Veysey, M.UV-associated decline in systemic folate: Implications for human nutrigenetics, health, and evolutionaryprocesses. Am. J. Hum. Biol. 2017, 29. [CrossRef] [PubMed]© 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open accessarticle distributed under the terms and conditions of the Creative Commons Attribution(CC BY) license (http://creativecommons.org/licenses/by/4.0/).

Reply: “comment on: The vitamin D–folate hypothesis as an evolutionary model for skin pigmentation: An update and integration of current ideas, nutrients 2018, 10, 554”

University of Hull Institutional Repository

Directory of Open Access Journals

Reply: “Comment on: The Vitamin D–Folate Hypothesis as an Evolutionary Model for Skin Pigmentation: An Update and Integration of Current Ideas, Nutrients 2018, 10, 554”

https://hull-repository.worktribe.com/preview/2348245/nutrients-10-01759.pdf

Reply: “comment on: The vitamin D–folate hypothesis as an evolutionary model for skin pigmentation: An update and integration of current ideas, nutrients 2018, 10, 554”

Abstract

Similar works

Full text

Available Versions

Multidisciplinary Digital Publishing Institute

Repository@Hull - Worktribe

University of Hull Institutional Repository

Directory of Open Access Journals