{"paper_id":"ea52da75-bf20-4e9f-b33c-d4f80d5b28d4","body_text":"Mini Review \nClinical Microbiology and Infectious Diseases\nClin Microbiol Infect Dis, 2020         doi: 10.15761/CMID.1000171\nISSN: 2398-8096\n Volume 5: 1-2\nIn Finland, a country where, according to the Finnish Meteorological \nInstitute standards, there are seasons of high (summer (1 June-30 \nAugust) autumn (1 September-31 October)) and low sunlight (winter (1 \nNovember-31 March) and spring (1 April-31 May)), it has been observed \nthat low sunlight exposure period (versus high) is associated positively \nwith 25(OH)D2 and negatively with 25(OH)D3 concentrations [13]. \nThe vitD status of the Finnish adult population has been shown to \nimprove considerably due to food fortification, especially of fluid milk \nproducts, and increased vitD supplement use. Other factors, such as \nthe difference in the ultraviolet radiation index may, to a certain extent, \nexplain the rise in vitD concentration. When consuming vitD sources, \nbased on nutritional recommendations, vitD status appears sufficient \n[S-25(OH)D ≥ 50 nmol/L] and, thus, supplementation is generally not \nneeded [14]. Analytically, the mean increase in S-25(OH)D in daily \nfluid milk consumers among supplement non-users is reported at 20 \nnmol/L, which is 6 nmol/L higher than non-consumers. In total, 91% \nof non-users who consumed fluid milk products, fat spreads and fish, \nbased on Finnish nutrition recommendations, reached S-25(OH)D \nconcentrations >50 nmol/L at the end of a study that took one year to \ncomplete [14]. \nBackground concerning vitamin D and endometriosis\nVitamin D influences the functioning of the female reproductive \nsystem and has been associated with polycystic ovary syndrome (PCOS), \nuterine leiomyomas, endometriosis and outcome of in vitro fertilization \nComparative, literature-based, analysis of the effect of \nvitamin D/sunlight in endometriosis between Greece and \nFinland\nVlachos A1 and Vassiliadis S2*\n1Department of Obstetrics and Gynecology, General Maternal Hospital of Athens, Elena Venizelou, Athens, Greece\n2Association of Greek Immunology Graduates, 33 Voriou Ipirou Street, Maroussi, Athens, Greece\nAbstract\nThis is a literature-based comparative analysis for the delineation of the role of sunshine in vitamin D (vitD) synthesis and its impact on endometriosis, an immune, \ninflammatory disease. The findings, between high (Greece) and low (Finland) sun exposed countries show that the prevalence of endometriosis does not change in \nthe general population and that vitD supplementation through sun and/or vitD food fortification does not lower the disease’s risk, thus pointing to a scientific myth \nthat has to be either re-examined or abandoned after thorough further research.\n*Correspondence to: Vassiliadis S, Association of Greek Immunology \nGraduates, 33 Voriou Ipirou Street, Maroussi, 15125 Athens, Greece, Tel: +30 \n2108055126, E-mail: immunology.graduates@gmail.com \nKey words: vitamin D (vitD), sunlight, endometriosis, vitD deficiency, bioactive \ncompounds, Greece, Finland\nReceived: January 17, 2019; Accepted: January 29, 2020; Published: February \n03, 2020\nIntroduction\nBackground concerning vitamin D in healthy subjects\nVitamin D is produced in the skin between March and October, \nwith the highest quantities being produced in the summer months. \nThe intake of vitD both through the skin and from dietary sources \nis described as the vitD level in the blood, or serum 25 hydroxy vitD \n(25(OH)D) concentration. Vitamin D is classified as a pro-hormone \nwhich exists in circulation in two major forms, 25(OH)D: 25(OH)D2 \n(ergocalciferol) and 25(OH)D3 (also known as cholecalciferol) [1,2]. \nThese precursors bind to a binding protein (VDBP) to transit in the \nblood and reach the liver where they are modified into calcidiol (25-\nOH cholecalciferol) then metabolized a second time by the kidney to \ngenerate calcitriol (or 1,25 dihydroxycholecalciferol), the active form of \nvitD [3]. Vitamin D levels are positively associated with bone mineral \ndensity [4] and several studies have reported a link with muscle mass \nand strength [5]. There exists evidence that vitD insufficiency and/\nor deficiency in elderly people, especially women, leads to secondary \nhyperparathyroidism and, consequently, to increased bone turnover \nand, finally, bone loss [6]. \nGreece is considered a country of high sunlight levels according \nto the Hellenic National Meteorological Service (2,600 to 2,800 hours \nyearly) [7]. Based on the important contribution of sunlight exposure \nto the production and maintenance of serum 25(OH)D levels, one \nmight consider that 25(OH)D deficiency may be a problem limited to \ncountries located at higher latitudes. Nevertheless, numerous studies \nfrom countries with high sunlight levels, Greece included, have shown \nthat vitD deficiency is a common occurrence and a global health problem \n[8-10]. A 2016 state-of-the-art review article by Holick, a pioneer in the \nfield of vit D synthesis, concisely outlines all the biological effects of \nsunlight, ultraviolet radiation, visible light and infrared radiation on \nvitD production and benefits for health [11]. The vitD status within \ndifferent European countries shows a high variation. A serum 25(OH)\nD lower than 25nmol/L has been monitored in 2 to 30% of adults [12].\n\nVlachos A (2020) Comparative, literature-based, analysis of the effect of vitamin D/sunlight in endometriosis between Greece and Finland\n Volume 5: 2-2\nClin Microbiol Infect Dis, 2020         doi: 10.15761/CMID.1000171\n5. Rizzoli R, Stevenson JC, Bauer JM, van Loon LJ, Walrand S, et al. (2014) The role \nof dietary protein and vitamin D in maintaining musculoskeletal health in postmenopausal \nwomen: a consensus statement from the European Society for Clinical and Economic \nAspects of Osteoporosis and Osteoarthritis (ESCEO). Maturitas 79(1): 122-132. [Crossref]\n6. Lips P, Duong T, Oleksik A, Black D, Cummings S, Cox D, Nickelsen T (2001) A \nglobal study of vitamin D status and parathyroid function in postmenopausal women \nwith osteoporosis: baseline data from the multiple outcomes of raloxifene evaluation \nclinical trial. J Clin Endocrinol Metab 86: 1212-1221. [Crossref]\n7. Maeda SS, Kunii IS, Hayashi LF, Lazaretti-Castro M (2010) Increases in summer \nserum 25-hydroxyvitamin D (25OHD) concentrations in elderly subjects in Sao Paulo, \nBrazil vary with age, gender and ethnicity. BMC Endocr Disord 10: 12. [Crossref]\n8. Levis S, Gomez A, Jimenez C, Veras L, Ma F, et al. (2005) Vitamin D deficiency and \nseasonal variation in an adult South Florida population. J Clin Endocrinol Metab 90: \n1557-1562. [Crossref]\n9. Matalliotakis M, Goulielmos GN, Matalliotaki C, Trivli A, Matalliotakis I, et al. (2017) \nEndometriosis in adolescent and young girls: report on a series of 55 cases. J Pediatr \nAdolesc Gynecol 30: 568-570. [Crossref]\n10. Holick MF (2016) Biological effects of sunlight, ultraviolet radiation, visible light, \ninfrared radiation and vitamin D for health. Anticancer Res 36: 1345-1356. [Crossref]\n11. Lips P and the International Osteoporosis Foundation (2009) Vitamin D status in \nEurope. Available at:\n12. https://www.iofbonehealth.org/sites/default/files/PDFs/Vitamin_D_Europe.pdf  \n13. Palaniswamy S, Hyppönen E, Williams DM, Jokelainen J, Lowry E, et al. (2017) \nPotential determinants of vitamin D in Finnish adults: a cross-sectional study from the \nNorthern Finland birth cohort 1966. BMJ Open 7: e013161. [Crossref]\n14. Jääskeläinen T, Itkonen S, Lundqvist A, Erkkola M, Koskela T, et al. (2017) The \npositive impact of general vitamin D food fortification policy on vitamin D status in \na representative adult Finnish population: evidence from an 11-y follow-up based on \nstandardized 25-hydroxyvitamin D data. Am J Clin Nutr 105: 1512-1520. [Crossref]\n15. Skowrońska P, Pastuszek E, Kuczyński W, Jaszczoł M, Kuć P, et al. (2016) The role of \nvitamin D in reproductive dysfunction in women - a systematic review. Ann Agric Env \nMed 23: 671-676. [Crossref]\n16. Voulgaris N, Papanastasiou L, Piaditis G, Angelousi A, Kaltsas G, et al. (2017) Vitamin \nD and aspects of female fertility. Hormones 16: 5-21. [Crossref]\n17. Zhao J, Huang X, Xu B, Yan Y, Zhang Q Li Y (2018) Whether vitamin D was associated \nwith clinical outcome after IVF/ICSI: a systematic review and meta-analysis. Repr Biol \nEndocrinol 16: 13-19. [Crossref] \n18. Almassinokiani F, Khodaverdi S, Solaymani-Dodaran M, Akbari P, Pazouki A (2016) \nEffects of vitamin D on endometriosis-related pain: a double-blind clinical trial. Sci \nMonit 22: 4960-4966. [Crossref]\n19. Harris HR, Chavarro JE, Malspeis S, Willett WC, Missmer SA (2013) Dairy-food, \ncalcium, magnesium, and vitamin D intake and endometriosis: a prospective cohort \nstudy. Am J Epidemiol 177: 420-430. [Crossref] \n20. Kalaitzopoulos DR, Lempesis IG, Athanasaki F, Schizas D, Samartzis EP, et al. (2019) \nAssociation between vitamin D and endometriosis: a systematic review. Hormones \n(Athens). [Crossref]\n21. Somigliana E, Panina-Bordignon P, Murone S, Di Lucia P, et al. (2007) Vitamin D reserve \nis higher in women with endometriosis.  Human Reprod 22: 2273-2278. [Crossref]\n22. Vlachos A, Vassiliadis S (2019) The immunological impact of orthomolecular \nmedicine using bioactive compounds as key factors in endometriosis. Bioactive Comp \nHealth Dis 2: 1-10.\n23. Saavalainen L, Lassus H, But A, Tiitinen A, Härkki P, et al. (2018) Risk of gynecologic \ncancer according to the type of endometriosis. Obstet Gyneco1 31: 1095-1102. [Crossref]\n24. Xyda SE, Kotsa K, Doumas A, Papanastasiou M, Samoutis G, et al. (2018) The \nprevalence of Vitamin D deficiency in a Greek and a Cypriot population sample. \nEndocrine Abstracts 56P212. [Crossref]\n25. Finnish Food Authority. Vitamin D. Available at: https://www.ruokavirasto.fi/en/\nthemes/healthy-diet/nutrients/vitamin-d/ \n(IVF) [15]. However, this does not appear to be the case since, in terms \nof infertility, there are no definitive results despite the fact that a high \nprevalence of vitD deficiency among PCOS women exists [16]. The same \nsketchy results have been obtained in the IVF practice [17]. Similarly, \nwhen it comes to endometriosis per se, dysmenorrhea and/or pelvic \npain reduction, both related to the disease, vitD does not exhibit any \nsignificant effect [18], although Harris et al. [19] claim that the greater \npredicted plasma 25(OH)D levels and higher intake of dairy foods are \nassociated with a decreased risk of endometriosis. This view is being \ncontradicted by a recent 2019 systematic review where the Authors \ncannot reach a positive conclusion [20]. Conflicting results also appear \nin an older publication where it is stated that endometriosis is associated \nwith higher serum levels of vitD [21]. A biological plausibility for a role \nof vitD, as an immunomodulator and anti-inflammatory agent, in the \npathogenesis and treatment of endometriosis has been suggested since \nlong-term vitD deficiencies have been linked to a weakened immune \nsystem and to chronic inflammation [22]. Comparing, however, two \ncountries with high (Greece) and low (Finland) sunshine periods, \nin relation to vitD synthesis, it appears that there is no change in the \nprevalence of the disease, which, and this has to be noted, is similar \nin the two countries (approximately, 1 in 10 females) [10,23]. External \nsupplementation of vitD does not also appear to affect the outcome of \nthe disease as the prevalence of vitD deficiency is extremely high in \nboth population samples and particularly in subjects with chronic \ndiseases [24]. Vitamin D uptake via dairy or fat fish supplementation, \nthrough food fortification programs, is evident in the serum of the \nFinnish patients but this increase does not correlate with a lower \nrisk of endometriosis and, thus, a cause-effect relationship is still \nmissing [14]. \nDiscussion / Conclusions\nAccording to the knowledge acquired thus far, vitD deficiency in \nthe Greek population, under an average sunshine exposure of 2,700 \nhours yearly, constitutes an absolute paradox that matches that of the \nFinnish population, with an average sun exposure time of 1,300 hours \nper year, respectively. \nIn terms of endometriosis, there is no solid evidence that vitD \nlowers the risk of the disease, as anticipated, while increased levels of \nserum vitD through food fortification do not appear to ameliorate the \npatients’ status and/or disease’s prevalence.\nEndometriosis is an immune, inflammatory disease and vitD, as an \nimmunomodulator and anti-inflammatory agent, is expected to have \nan -at least- corrective, if not, restorative action.  The above-described \nliterature-based data, however, point to a null correlation between \nendometriosis and role of vitD or insinuate unknown yet mechanisms \nrequired to trigger the proper biochemical reactions towards a positive \nresult. Therefore, the synergistic actions of other dietary bioactive \ncompounds should be studied in order to elucidate whether vitD can \nbe activated beneficially towards endometriosis or whether this theory \nhas to be abandoned.\nReferences \n1. Hossein-nezhad A, Holick MF (2013) Vitamin D for health: a global perspective. Mayo \nClin Proc 88: 720-755. [Crossref]\n2. Huotari A, Herzig KH (2008) Vitamin D and living in northern latitudes-an endemic \nrisk area for vitamin D deficiency. Int J Circumpolar Health 67: 164-178. [Crossref]\n3. Deeb K, Trump D, Johnson C (2007) Vitamin D signalling pathways in cancer: \npotential for anticancer therapeutics. Nat Rev Cancer 7: 684-700. [Crossref]\n4. Tanzy ME, Camacho PM (2011) Effect of vitamin D therapy on bone turnover markers \nin postmenopausal women with osteoporosis and osteopenia. Endocr Pract 17: 873-\n879. [Crossref]\nCopyright: ©2020 Vlachos A. This is an open-access article distributed \nunder the terms of the Creative Commons Attribution License, which permits \nunrestricted use, distribution, and reproduction in any medium, provided the \noriginal author and source are credited.","source_license":"CC0","license_restricted":false}