Journal of Literature Pharmacy Sciences

The Story of Vitamin C and its Versions in Sepsis and COVID-19: Traditional Review
C Vitamininin Hikâyesi ve Sepsis ve COVID-19'daki Versiyonları: Geleneksel Derleme
Omnia Abdo Mahmoud HEMDANa , Sonia SANAJOUa,b, Terken BAYDARa
aHacettepe University Faculty of Pharmacy, Department of Pharmaceutical Toxicology, Ankara, Türkiye
bİstanbul Aydın University Faculty of Pharmacy, Department of Pharmaceutical Toxicology, İstanbul, Türkiye
J Lit Pharm Sci. 2024;13(2):108-16
doi: 10.5336/pharmsci.2024-101309
Article Language: EN
Full Text
ABSTRACT
 The multifaceted role of vitamin C, also known as ascorbic acid, in cellular homeostasis has been underscored, with particular emphasis on its involvement as a co-factor in crucial hydroxylation reactions, facilitation of collagen formation, and participation in enzymatic reactions crucial for maintaining cellular and tissue functions. Moreover, its attributed capacity to neutralize free radicals, protect cells against oxidative stress, and mitigate inflammatory responses accentuates its potential therapeutic significance. This review aims to comprehensively explore the contemporary understanding of vitamin C's therapeutic implications in sepsis and coronavirus disease-2019 (COVID-19) based on the relevant publications from the past years. While previous investigations have encompassed a range of study designs, including epidemiological research, this presented paper deliberately narrows its focus to recent randomized clinical trials (RCTs) and the latest systematic meta-analysis involving only RCTs, providing a higher level of evidence than observational studies. An exception is made for a meta-analysis examining vitamin C's role in COVID-19 patients, including previous RCTs and retrospective studies. The question in the present paper is whether vitamin C is efficacious in preventing and treating critical illnesses, particularly sepsis and COVID-19. The current evidence is still insufficient based on available publications from the last years and recent metaanalyses on this topic. Accordingly, larger high-quality randomized clinical trial studies are needed to provide more definitive insights into the efficacy of vitamin C in addressing critical illnesses.

Keywords: Ascorbate; ascorbic acid; COVID-19; intensive care unit; sepsis; vitamin C
ÖZET
 Askorbik asit olarak da bilinen C vitamininin hücresel homeostazdaki çok yönlü rolü, özellikle önemli hidroksilasyon reaksiyonlarında yardımcı bir faktör olarak rol oynaması, kolajen oluşumunu kolaylaştırması ve hücresel ve doku fonksiyonlarını sürdürmek için çok önemli enzimatik reaksiyonlara katılımı ile vurgulanmaktadır. Ayrıca potansiyel terapötik önemi serbest radikalleri nötralize etme, hücreleri oksidatif strese karşı koruma ve inflamatuar yanıtları azaltma kapasitesine dayandırılmaktadır. Bu derlemede, geçmiş yıllardaki ilgili yayınlar temel alınarak C vitamininin sepsis ve koronavirüs hastalığı2019'daki (COVID-19) terapötik etkilerinin kapsamlı ve güncel bir şekilde araştırmayı amaçlamaktadır. Önceki araştırmalar, epidemiyolojik araştırmalar da dâhil olmak üzere bir dizi çalışma tasarımını kapsarken, sunulan bu makale bilinçli olarak randomize klinik çalışmalara ve yalnızca gözlemsel çalışmalara kıyasla daha yüksek düzeyde kanıt sağlayan randomize klinik çalışmaları içeren en son sistematik metaanalizlere odaklanmaktadır. COVID-19 hastalarında C vitamininin rolünü inceleyen hem önceki randomize klinik çalışmaları hem de retrospektif çalışmaları içeren bir metaanaliz için bir istisna yapılmıştır. Sunulan bu makaledeki soru, başta sepsis ve COVID-19 olmak üzere kritik hastalıkların önlenmesinde ve tedavisinde C vitamininin etkili olup olmadığıdır. Son yıllardaki mevcut yayınlara ve bu konudaki son metaanalizlere dayalı mevcut kanıtlar hâlen yetersizdir. Buna göre C vitamininin kritik hastalıklarda etkinliği hakkında daha kesin bilgiler sağlamak için daha büyük yüksek kaliteli randomize klinik çalışmalara gereksinim vardır.

Anahtar Kelimeler: Askorbat; askorbik asit; COVID-19; yoğun bakım ünitesi; sepsis; vitamin C
REFERENCES:
  1. Chambial S, Dwivedi S, Shukla KK, John PJ, Sharma P. Vitamin C in disease prevention and cure: an overview. Indian J Clin Biochem. 2013;28(4):314-28. [Crossref]  [PubMed]  [PMC] 
  2. Iqbal K, Khan A, Khattak MMAK. Biological significance of ascorbic acid (Vitamin C) in human health -A review. Pakistan Journal of Nutrition. 2004;3(1):5-13. [Crossref] 
  3. German Nutrition Society (DGE). New Reference Values for Vitamin C Intake. Ann Nutr Metab. 2015;67(1):13-20. [Crossref]  [PubMed] 
  4. Agostoni C, Berni Canani R, Fairweather-Tait S, Heinonen M, Korhonen H, La Vieille S, et al. Scientific opinion on dietary reference values for vitamin C. EFSA Journal. 2013;11(11):3418. [Crossref] 
  5. Carr AC, Lykkesfeldt J. Discrepancies in global vitamin C recommendations: a review of RDA criteria and underlying health perspectives. Crit Rev Food Sci Nutr. 2021;61(5):742-55. Epub 2020 Mar 30. [Crossref]  [PubMed] 
  6. Levine M, Conry-Cantilena C, Wang Y, Welch RW, Washko PW, Dhariwal KR, et al. Vitamin C pharmacokinetics in healthy volunteers: evidence for a recommended dietary allowance. Proc Natl Acad Sci U S A. 1996;93(8):3704-9. [Crossref]  [PubMed]  [PMC] 
  7. Padayatty SJ, Sun AY, Chen Q, Espey MG, Drisko J, Levine M. Vitamin C: intravenous use by complementary and alternative medicine practitioners and adverse effects. PLoS One. 2010;5(7):e11414. [Crossref]  [PubMed]  [PMC] 
  8. Braakhuis AJ. Effect of vitamin C supplements on physical performance. Curr Sports Med Rep. 2012;11(4):180-4. [Crossref]  [PubMed] 
  9. Jiang K, Tang K, Liu H, Xu H, Ye Z, Chen Z. Ascorbic Acid Supplements and Kidney Stones Incidence Among Men and Women: A systematic review and meta-analysis. Urol J. 2019;16(2):115-20. [PubMed] 
  10. Mieszczakowska-Frąc M, Celejewska K, Płocharski W. Impact of innovative technologies on the content of vitamin C and its bioavailability from processed fruit and vegetable products. Antioxidants (Basel). 2021;10(1):54. [Crossref]  [PubMed]  [PMC] 
  11. Wróblewski K. Czy stosowanie duzych dawek witaminy C moze być szkodliwe? [Can the administration of large doses of vitamin C have a harmful effect?]. Pol Merkur Lekarski. 2005;19(112):600-3. Polish. [PubMed] 
  12. Oyetade OA, Oyeleke GO, Adegoke BM, Akintunde AO. Stability studies on ascorbic acid (Vitamin C) from different sources. IOSR Journal of Applied Chemistry (IOSR-JAC. 2012;2(4):20-4 [Crossref] 
  13. Santos PHS, Silva MA. Retention of vitamin C in drying processes of fruits and vegetables-A Review. Drying Technology. 2008;26(12):1421-37. [Crossref] 
  14. Lindblad M, Tveden-Nyborg P, Lykkesfeldt J. Regulation of vitamin C homeostasis during deficiency. Nutrients. 2013;5(8):2860-79. [Crossref]  [PubMed]  [PMC] 
  15. Lykkesfeldt J, Tveden-Nyborg P. The pharmacokinetics of vitamin C. Nutrients. 2019;11(10):2412. [Crossref]  [PubMed]  [PMC] 
  16. Levine M, Padayatty SJ, Espey MG. Vitamin C: a concentration-function approach yields pharmacology and therapeutic discoveries. Adv Nutr. 2011;2(2):78-88. [Crossref]  [PubMed]  [PMC] 
  17. Padayatty SJ, Sun H, Wang Y, Riordan HD, Hewitt SM, Katz A, et al. Vitamin C pharmacokinetics: implications for oral and intravenous use. Ann Intern Med. 2004;140(7):533-7. [Crossref]  [PubMed] 
  18. Liang WJ, Johnson D, Jarvis SM. Vitamin C transport systems of mammalian cells. Mol Membr Biol. 2001;18(1):87-95. [Crossref]  [PubMed] 
  19. Vera JC, Rivas CI, Velásquez FV, Zhang RH, Concha II, Golde DW. Resolution of the facilitated transport of dehydroascorbic acid from its intracellular accumulation as ascorbic acid. J Biol Chem. 1995;270(40):23706-12. [Crossref]  [PubMed] 
  20. Savini I, Rossi A, Pierro C, Avigliano L, Catani MV. SVCT1 and SVCT2: key proteins for vitamin C uptake. Amino Acids. 2008;34(3):347-55. [Crossref]  [PubMed] 
  21. Rumsey SC, Levine M. Absorption, transport, and disposition of ascorbic acid in humans. The Journal of Nutritional Biochemistry. 1998;9(3):116-30. [Crossref] 
  22. Linster CL, Van Schaftingen E. Vitamin C. Biosynthesis, recycling and degradation in mammals. FEBS J. 2007;274(1):1-22. [Crossref]  [PubMed] 
  23. Harrison FE, May JM. Vitamin C function in the brain: vital role of the ascorbate transporter SVCT2. Free Radic Biol Med. 2009;46(6):719-30. [Crossref]  [PubMed]  [PMC] 
  24. May JM, Qu ZC, Whitesell RR, Cobb CE. Ascorbate recycling in human erythrocytes: role of GSH in reducing dehydroascorbate. Free Radic Biol Med. 1996;20(4):543-51. [Crossref]  [PubMed] 
  25. Du J, Cullen JJ, Buettner GR. Ascorbic acid: chemistry, biology and the treatment of cancer. Biochim Biophys Acta. 2012;1826(2):443-57. [Crossref]  [PubMed]  [PMC] 
  26. Asada K. The water-water cycle in chloroplasts: scavenging of active oxygens and dissipation of excess photons. Annu Rev Plant Physiol Plant Mol Biol. 1999;50:601-39. [Crossref]  [PubMed] 
  27. Smirnoff N. Ascorbic acid: metabolism and functions of a multi-facetted molecule. Curr Opin Plant Biol. 2000;3(3):229-35. [Crossref]  [PubMed] 
  28. Davey MW, Van Montagu M, Inzé D, Sanmartin M, Kanellis A, Smirnoff N, et al. Plant L-ascorbic acid: chemistry, function, metabolism, bioavailability and effects of processing. Journal of the Science of Food and Agriculture. 2000;80:825-60. [Link] 
  29. Bánhegyi G, Braun L, Csala M, Puskás F, Mandl J. Ascorbate metabolism and its regulation in animals. Free Radic Biol Med. 1997;23(5):793-803. [Crossref]  [PubMed] 
  30. Kojo S. Vitamin C: basic metabolism and its function as an index of oxidative stress. Curr Med Chem. 2004;11(8):1041-64. [Crossref]  [PubMed] 
  31. Knight J, Madduma-Liyanage K, Mobley JA, Assimos DG, Holmes RP. Ascorbic acid intake and oxalate synthesis. Urolithiasis. 2016;44(4):289-97. [Crossref]  [PubMed]  [PMC] 
  32. Doseděl M, Jirkovský E, Macáková K, Krčmová LK, Javorská L, Pourová J, et al, On Behalf Of The Oemonom. Vitamin C-Sources, Physiological Role, Kinetics, Deficiency, Use, Toxicity, and Determination. Nutrients. 2021;13(2):615. [Crossref]  [PubMed]  [PMC] 
  33. Taylor EN, Curhan GC. Determinants of 24-hour urinary oxalate excretion. Clin J Am Soc Nephrol. 2008;3(5):1453-60. [Crossref]  [PubMed]  [PMC] 
  34. Grosso G, Bei R, Mistretta A, Marventano S, Calabrese G, Masuelli L, et al. Effects of vitamin C on health: a review of evidence. Front Biosci (Landmark Ed). 2013;18(3):1017-29. [Crossref]  [PubMed] 
  35. Levine M. New concepts in the biology and biochemistry of ascorbic acid. N Engl J Med. 1986;314(14):892-902. [Crossref]  [PubMed] 
  36. Li W, Khor TO, Xu C, Shen G, Jeong WS, Yu S, et al. Activation of Nrf2-antioxidant signaling attenuates NFkappaB-inflammatory response and elicits apoptosis. Biochem Pharmacol. 2008;76(11):1485-9. [Crossref]  [PubMed]  [PMC] 
  37. Manning J, Mitchell B, Appadurai DA, Shakya A, Pierce LJ, Wang H, et al. Vitamin C promotes maturation of T-cells. Antioxid Redox Signal. 2013;19(17):2054-67. [Crossref]  [PubMed]  [PMC] 
  38. Webb AL, Villamor E. Update: effects of antioxidant and non-antioxidant vitamin supplementation on immune function. Nutr Rev. 2007;65(5):181-217. [Crossref]  [PubMed] 
  39. Dombrovskiy VY, Martin AA, Sunderram J, Paz HL. Rapid increase in hospitalization and mortality rates for severe sepsis in the United States: a trend analysis from 1993 to 2003. Crit Care Med. 2007;35(5):1244-50. [Crossref]  [PubMed] 
  40. Carr AC, Shaw GM, Fowler AA, Natarajan R. Ascorbate-dependent vasopressor synthesis: a rationale for vitamin C administration in severe sepsis and septic shock? Crit Care. 2015;19:418. [Crossref]  [PubMed]  [PMC] 
  41. Wilson JX. Mechanism of action of vitamin C in sepsis: ascorbate modulates redox signaling in endothelium. Biofactors. 2009;35(1):5-13. [Crossref]  [PubMed]  [PMC] 
  42. May JM, Harrison FE. Role of vitamin C in the function of the vascular endothelium. Antioxid Redox Signal. 2013;19(17):2068-83. [Crossref]  [PubMed]  [PMC] 
  43. Chang P, Liao Y, Guan J, Guo Y, Zhao M, Hu J, et al. Combined treatment with hydrocortisone, vitamin C, and thiamine for sepsis and septic shock: a randomized controlled trial. Chest. 2020;158(1):174-82. [Crossref]  [PubMed] 
  44. Aisa-Alvarez A, Soto ME, Guarner-Lans V, Camarena-Alejo G, Franco-Granillo J, Martínez-Rodríguez EA, et al. Usefulness of antioxidants as adjuvant therapy for septic shock: a randomized clinical trial. Medicina (Kaunas). 2020;56(11):619. [Crossref]  [PubMed]  [PMC] 
  45. Hussein AA, Sabry NA, Abdalla MS, Farid SF. A prospective, randomised clinical study comparing triple therapy regimen to hydrocortisone monotherapy in reducing mortality in septic shock patients. Int J Clin Pract. 2021;75(9):e14376. [Crossref]  [PubMed] 
  46. Rosengrave P, Spencer E, Williman J, Mehrtens J, Morgan S, Doyle T, et al. Intravenous vitamin C administration to patients with septic shock: a pilot randomised controlled trial. Crit Care. 2022;26(1):26. [Crossref]  [PubMed]  [PMC] 
  47. Wacker DA, Burton SL, Berger JP, Hegg AJ, Heisdorffer J, Wang Q, et al. Evaluating Vitamin C in Septic Shock: A Randomized Controlled Trial of Vitamin C Monotherapy. Crit Care Med. 2022;50(5):e458-e67. [Crossref]  [PubMed]  [PMC] 
  48. Fowler AA 3rd, Truwit JD, Hite RD, Morris PE, DeWilde C, Priday A, et al. Effect of vitamin C infusion on organ failure and biomarkers of inflammation and vascular injury in patients with sepsis and severe acute respiratory failure: The CITRIS-ALI randomized clinical trial. JAMA. 2019;322(13):1261-70. Erratum in: JAMA. 2020;323(4):379. [Crossref]  [PubMed]  [PMC] 
  49. Hemilä H, Chalker E. Abrupt termination of vitamin C from ICU patients may increase mortality: secondary analysis of the LOVIT trial. Eur J Clin Nutr. 2023;77(4):490-4. [Crossref]  [PubMed]  [PMC] 
  50. Zeng Y, Liu Z, Xu F, Tang Z. Intravenous high-dose vitamin C monotherapy for sepsis and septic shock: A meta-analysis of randomized controlled trials. Medicine (Baltimore). 2023;102(42):e35648. [Crossref]  [PubMed]  [PMC] 
  51. Angriman F, Muttalib F, Lamontagne F, Adhikari NKJ; LOVIT Investigators. IV Vitamin C in Adults With Sepsis: A Bayesian Reanalysis of a Randomized Controlled Trial. Crit Care Med. 2023;51(8):e152-e6. [Crossref]  [PubMed] 
  52. Yanase F, Spano S, Maeda A, Chaba A, Naorungroj T, Ow CPC, et al. Mega-dose sodium ascorbate: a pilot, single-dose, physiological effect, double-blind, randomized, controlled trial. Crit Care. 2023;27(1):371. [Crossref]  [PubMed]  [PMC] 
  53. Aisa-Álvarez A, Pérez-Torres I, Guarner-Lans V, Manzano-Pech L, Cruz-Soto R, Márquez-Velasco R, et al. Randomized clinical trial of antioxidant therapy patients with septic shock and organ dysfunction in the ICU: SOFA Score Reduction by Improvement of the Enzymatic and Non-Enzymatic Antioxidant System. Cells. 2023;12(9):1330. [Crossref]  [PubMed]  [PMC] 
  54. Lu D, Mao W. Hydrocortisone combined with vitamin C and thiamine in the treatment of sepsis/septic shock: a systematic review with meta-analysis and trial sequential analysis. Clin Invest Med. 2023;46(1):E36-49. [Crossref]  [PubMed] 
  55. Mohamed A, Abdelaty M, Saad MO, Shible A, Mitwally H, Akkari AR, et al. Evaluation of hydrocortisone, vitamin C, and thiamine for the treatment of septic shock: a randomized controlled trial (the hyvits trial). Shock. 2023;59(5):697-701. [Crossref]  [PubMed]  [PMC] 
  56. Lyu QQ, Zheng RQ, Chen QH, Yu JQ, Shao J, Gu XH. Early administration of hydrocortisone, vitamin C, and thiamine in adult patients with septic shock: a randomized controlled clinical trial. Crit Care. 2022;26(1):295. [Crossref]  [PubMed]  [PMC] 
  57. Williams Roberson S, Nwosu S, Collar EM, Kiehl AL, Harrison FE, Bastarache J, et al; VICTAS Investigators. Association of Vitamin C, Thiamine, and Hydrocortisone Infusion With Long-term Cognitive, Psychological, and Functional Outcomes in Sepsis Survivors: A Secondary Analysis of the Vitamin C, Thiamine, and Steroids in Sepsis Randomized Clinical Trial. JAMA Netw Open. 2023;6(2):e230380. Erratum in: JAMA Netw Open. 2023;6(4):e2312173. [PubMed]  [PMC] 
  58. Bae M, Kim H. Mini-review on the roles of vitamin C, vitamin D, and selenium in the immune system against COVID-19. Molecules. 2020;25(22):5346. [Crossref]  [PubMed]  [PMC] 
  59. Zhang L, Liu Y. Potential interventions for novel coronavirus in China: A systematic review. J Med Virol. 2020;92(5):479-90. [Crossref]  [PubMed]  [PMC] 
  60. Hemilä H. Vitamin C and infections. Nutrients. 2017;9(4):339. [Crossref]  [PubMed]  [PMC] 
  61. Liu F, Zhu Y, Zhang J, Li Y, Peng Z. Intravenous high-dose vitamin C for the treatment of severe COVID-19: study protocol for a multicentre randomised controlled trial. BMJ Open. 2020;10(7):e039519. [Crossref]  [PubMed]  [PMC] 
  62. Alamdari DH, Moghaddam AB, Amini S, Keramati MR, Zarmehri AM, Alamdari AH, et al. Application of methylene blue -vitamin C -N-acetyl cysteine for treatment of critically ill COVID-19 patients, report of a phase-I clinical trial. Eur J Pharmacol. 2020;885:173494. [Crossref]  [PubMed]  [PMC] 
  63. Tehrani S, Yadegarynia D, Abrishami A, Moradi H, Gharaei B, Rauofi M, et al. An investigation into the effects of intravenous vitamin C on pulmonary CT findings and clinical outcomes of patients with COVID 19 pneumonia a randomized clinical trial. Urol J. 2022;19(6):460-5. [PubMed] 
  64. JamaliMoghadamSiahkali S, Zarezade B, Koolaji S, SeyedAlinaghi S, Zendehdel A, Tabarestani M, et al. Safety and effectiveness of high-dose vitamin C in patients with COVID-19: a randomized open-label clinical trial. Eur J Med Res. 2021;26(1):20. [Crossref]  [PubMed]  [PMC] 
  65. Kumari P, Dembra S, Dembra P, Bhawna F, Gul A, Ali B, et al. The role of vitamin C as adjuvant therapy in COVID-19. Cureus. 2020;12(11):e11779. [Crossref]  [PubMed]  [PMC] 
  66. Zhang J, Rao X, Li Y, Zhu Y, Liu F, Guo G, et al. Pilot trial of high-dose vitamin C in critically ill COVID-19 patients. Ann Intensive Care. 2021;11(1):5. [Crossref]  [PubMed]  [PMC] 
  67. Rawat D, Roy A, Maitra S, Gulati A, Khanna P, Baidya DK. Vitamin C and COVID-19 treatment: A systematic review and meta-analysis of randomized controlled trials. Diabetes Metab Syndr. 2021;15(6):102324. [Crossref]  [PubMed]  [PMC] 
  68. Olczak-Pruc M, Swieczkowski D, Ladny JR, Pruc M, Juarez-Vela R, Rafique Z, et al. Vitamin C supplementation for the treatment of COVID-19: a systematic review and meta-analysis. Nutrients. 2022;14(19):4217. [Crossref]  [PubMed]  [PMC] 
  69. Xu C, Yi T, Tan S, Xu H, Hu Y, Ma J, et al. Association of oral or intravenous vitamin C supplementation with mortality: a systematic review and meta-analysis. Nutrients. 2023;15(8):1848. [Crossref]  [PubMed]  [PMC] 
  70. Reintam Blaser A, Alhazzani W, Belley-Cote E, Møller MH, Adhikari NKJ, Burry L, et al. Intravenous vitamin C therapy in adult patients with sepsis: A rapid practice guideline. Acta Anaesthesiol Scand. 2023;67(10):1423-31. [Crossref]  [PubMed] 

.: Up To Date

.: Process List

Login

 Forgot your password?

 New Registration  

Contact

Ortadoğu Reklam Tanıtım Yayıncılık Turizm Eğitim İnşaat Sanayi ve Ticaret A.Ş.

.: Address

Turkocagi Caddesi No:30 06520 Balgat / ANKARA
Phone: +90 312 286 56 56
Fax: +90 312 220 04 70
E-mail: info@turkiyeklinikleri.com

.: Manuscript Editing Department

Phone: +90 312 286 56 56/ 2
E-mail: yaziisleri@turkiyeklinikleri.com

.: English Language Redaction

Phone: +90 312 286 56 56/ 145
E-mail: tkyayindestek@turkiyeklinikleri.com

.: Marketing Sales-Project Department

Phone: +90 312 286 56 56/ 142
E-mail: reklam@turkiyeklinikleri.com

.: Subscription and Public Relations Department

Phone: +90 312 286 56 56/ 118
E-mail: abone@turkiyeklinikleri.com

.: Customer Services

Phone: +90 312 286 56 56/ 118
E-mail: satisdestek@turkiyeklinikleri.com

1. TERMS OF USE

1.1. To use the web pages with http://www.turkiyeklinikleri.com domain name or the websites reached through the sub domain names attached to the domain name (They will be collectively referred as "SITE"), please read the conditions below. If you do not accept these terms, please cease to use the "SITE." "SITE" owner reserves the right to change the information on the website, forms, contents, the "SITE," "SITE" terms of use anytime they want.

1.2. The owner of the "SITE" is Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. (From now on it is going to be referred as "Turkiye Klinikleri", shortly) and it resides at Turkocagi cad. No:30, 06520 Balgat Ankara. The services in the "SITE" are provided by "Turkiye Klinikleri."

1.3. Anyone accessing the "SITE" with or without a fee whether they are a natural person or a legal identity is considered to agree these terms of use. In this contract hereby, "Turkiye Klinikleri" may change the stated terms anytime. These changes will be published in the "SITE" periodically and they will be valid when they are published. Any natural person or legal identity benefiting from and reaching to the "SITE" are considered to be agreed to any change on hereby contract terms done by "Turkiye Klinikleri."

1.4. The "Terms of Use" hereby is published in the website with the last change on March 30th 2014 and the "SITE" is activated by enabling the access to everyone. The "Terms of Use" hereby is also a part of the any "USER Contract" was and/or will be done with the users using "Turkiye Klinikleri" services with or without a fee an inseparable.

2. DEFINITIONS

2.1. "SITE": A website offering different kind of services and context with a certain frame determined by "Turkiye Klinikleri" and it is accessible on-line on http://www.turkiyeklinikleri.com domain name and/or subdomains connected to the domain name.

2.2. USER: A natural person or a legal identity accessing to the "SITE" through online settings.

2.3. LINK: A link enabling to access to another website through the "SITE", the files, the context or through another website to the "SITE", the files and the context.

2.4. CONTEXT: Any visual, literary and auditory images published in the "Turkiye Klinikleri", "SITE" and/or any website or any accessible information, file, picture, number/figures, price, etc.

2.5. "USER CONTRACT": An electronically signed contract between a natural or a legal identity benefiting from special services "Turkiye Klinikleri" will provide and "Turkiye Klinikleri".

3. SCOPE OF THE SERVICES

3.1. "Turkiye Klinikleri" is completely free to determine the scope and quality of the services via the "SITE".

3.2. To benefit the services of "Turkiye Klinikleri" "SITE", the "USER" must deliver the features that will be specified by "Turkiye Klinikleri". "Turkiye Klinikleri" may change this necessity any time single-sided.

3.3. Not for a limited number, the services "Turkiye Klinikleri" will provide through the "SITE" for a certain price or for free are;

- Providing scientific articles, books and informative publications for health industry.

- Providing structural, statistical and editorial support to article preparation stage for scientific journals.

4. GENERAL PROVISIONS

4.1. "Turkiye Klinikleri" is completely free to determine which of the services and contents provided in the "SITE" will be charged.

4.2. People benefiting from the services provided by "Turkiye Klinikleri" and using the website can use the "SITE" only according to the law and only for personal reasons. Users have the criminal and civil liability for every process and action they take in the "SITE". Every USER agrees, declares and undertakes that they will not proceed by any function or action infringement of rights of "Turkiye Klinikleri"s and/or other third parties', they are the exclusive right holder on usage, processing, storage, made public and revealing any written, visual or auditory information reported to Turkiye Klinikleri" and/or "SITE" to the third parties. "USER" agrees and undertakes that s/he will not duplicate, copy, distribute, process, the pictures, text, visual and auditory images, video clips, files, databases, catalogs and lists within the "SITE", s/he will not be using these actions or with other ways to compete with "Turkiye Klinikleri", directly or indirectly.

4.3. The services provided and the context published within the "SITE" by third parties is not under the responsibility of "Turkiye Klinikleri", institutions collaborated with "Turkiye Klinikleri", "Turkiye Klinikleri" employee and directors, "Turkiye Klinikleri" authorized salespeople. Commitment to accuracy and legality of the published information, context, visual and auditory images provided by any third party are under the full responsibility of the third party. "Turkiye Klinikleri" does not promise and guarantee the safety, accuracy and legality of the services and context provided by a third party.

4.4. "USER"s cannot act against "Turkiye Klinikleri", other "USER"s and third parties by using the "SITE". "Turkiye Klinikleri" has no direct and/or indirect responsibility for any damage a third party suffered or will suffer regarding "USER"s actions on the "SITE" against the rules of the hereby "Terms of Use" and the law.

4.5. "USER"s accept and undertake that the information and context they provided to the "SITE" are accurate and legal. "Turkiye Klinikleri" is not liable and responsible for promising and guaranteeing the verification of the information and context transmitted to "Turkiye Klinikleri" by the "USER"s, or uploaded, changed and provided through the "SITE" by them and whether these information are safe, accurate and legal.

4.6. "USER"s agree and undertake that they will not perform any action leading to unfair competition, weakening the personal and commercial credit of "Turkiye Klinikleri" and a third party,  encroaching and attacking on personal rights within the "SITE" in accordance with the Turkish Commercial Code Law.

4.7. "Turkiye Klinikleri" reserves the right to change the services and the context within the "SITE"  anytime. "Turkiye Klinikleri" may use this right without any notification and timelessly. "USER"s have to make the changes and/or corrections "Turkiye Klinikleri" required immediately. Any changes and/or corrections that are required by "Turkiye Klinikleri", may be made by "Turkiye Klinikleri" when needed. Any harm, criminal and civil liability resulted or will result from changes and/or corrections required by "Turkiye Klinikleri" and were not made on time by the "USER"s belongs completely to the users.

4.8. "Turkiye Klinikleri" may give links through the "SITE" to other websites and/or "CONTEXT"s and/or folders that are outside of their control and owned and run by third parties. These links are provided for ease of reference only and do not hold qualification for support the respective web SITE or the admin or declaration or guarantee for the information inside. "Turkiye Klinikleri" does not hold any responsibility over the web-sites connected through the links on the "SITE", folders and context, the services or products on the websites provided through these links or their context.

4.9. "Turkiye Klinikleri" may use the information provided to them by the "USERS" through the "SITE" in line with the terms of the "PRIVACY POLICY" and "USER CONTRACT". It may process the information or classify and save them on a database. "Turkiye Klinikleri" may also use the USER's or visitor's identity, address, e-mail address, phone number, IP number, which sections of the "SITE" they visited, domain type, browser type, date and time information to provide statistical evaluation and customized services.

5. PROPRIETARY RIGHTS

5.1. The information accessed through this "SITE" or provided by the users legally and all the elements (including but not limited to design, text, image, html code and other codes) of the "SITE" (all of them will be called as studies tied to "Turkiye Klinikleri"s copyrights) belongs to "Turkiye Klinikleri". Users do not have the right to resell, process, share, distribute, display or give someone permission to access or to use the "Turkiye Klinikleri" services, "Turkiye Klinikleri" information and the products under copyright protection by "Turkiye Klinikleri". Within hereby "Terms of Use" unless explicitly permitted by "Turkiye Klinikleri" nobody can reproduce, process, distribute or produce or prepare any study from those under "Turkiye Klinikleri" copyright protection.

5.2. Within hereby "Terms of Use", "Turkiye Klinikleri" reserves the rights for "Turkiye Klinikleri" services, "Turkiye Klinikleri" information, the products associated with "Turkiye Klinikleri" copyrights, "Turkiye Klinikleri" trademarks, "Turkiye Klinikleri" trade looks or its all rights for other entity and information it has through this website unless it is explicitly authorized by "Turkiye Klinikleri".

6. CHANGES IN THE TERMS OF USE

"Turkiye Klinikleri" in its sole discretion may change the hereby "Terms of Use" anytime announcing within the "SITE". The changed terms of the hereby "Terms of Use" will become valid when they are announced. Hereby "Terms of Use" cannot be changed by unilateral declarations of users.

7. FORCE MAJEURE

"Turkiye Klinikleri" is not responsible for executing late or never of this hereby "Terms of Use", privacy policy and "USER Contract" in any situation legally taken into account as force majeure. Being late or failure of performance or non-defaulting of this and similar cases like this will not be the case from the viewpoint of "Turkiye Klinikleri", and "Turkiye Klinikleri" will not have any damage liability for these situations. "Force majeure" term will be regarded as outside of the concerned party's reasonable control and any situation that "Turkiye Klinikleri" cannot prevent even though it shows due diligence. Also, force majeure situations include but not limited to natural disasters, rebellion, war, strike, communication problems, infrastructure and internet failure, power cut and bad weather conditions.

8. LAW AND AUTHORISATION TO FOLLOW

Turkish Law will be applied in practicing, interpreting the hereby "Terms of Use" and managing the emerging legal relationships within this "Terms of Use" in case of finding element of foreignness, except for the rules of Turkish conflict of laws. Ankara Courts and Enforcement Offices are entitled in any controversy happened or may happen due to hereby contract.

9. CLOSING AND AGREEMENT

Hereby "Terms of Use" come into force when announced in the "SITE" by "Turkiye Klinikleri". The users are regarded to agree to hereby contract terms by using the "SITE". "Turkiye Klinikleri" may change the contract terms and the changes will be come into force by specifying the version number and the date of change on time it is published in the "SITE".

 

30.03.2014

Privacy Policy

We recommend you to read the terms of use below before you visit our website. In case you agree these terms, following our rules will be to your favor. Please read our Terms of Use thoroughly.

www.turkiyeklinikleri.com website belongs to Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. and is designed in order to inform physicians in the field of health

www.turkiyeklinikleri.com cannot reach to user’s identity, address, service providers or other information. The users may send this information to the website through forms if they would like to. However, www.turkiyeklinikleri.com may collect your hardware and software information. The information consists of your IP address, browser type, operating system, domain name, access time, and related websites. www.turkiyeklinikleri.com cannot sell the provided user information (your name, e-mail address, home and work address, phone number) to the third parties, publish it publicly, or keep it in the website. Gathered information has a directing feature to be a source for the website’s visitor profile, reporting and promotion of the services.

www.turkiyeklinikleri.com uses the taken information:

-To enhance, improve and maintain the quality of the website

-To generate visitor’s profile and statistical data

-To determine the tendency of the visitors on using our website

-To send print publications/correspondences

-To send press releases or notifications through e-mail

-To generate a list for an event or competition

By using www.turkiyeklinikleri.com you are considered to agree that;

-Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. cannot be hold responsible for any user’s illegal and immoral behavior,

-Terms of use may change from time to time,

-It is not responsible for other websites’ contents it cannot control or the harms they may cause although it uses the connection they provided.

Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. may block the website to users in the following events:

-Information with wrong, incomplete, deceiving or immoral expressions is recorded to the website,

-Proclamation, advertisement, announcement, libelous expressions are used against natural person or legal identity,

-During various attacks to the website,

-Disruption of the website because of a virus.

Written, visual and audible materials of the website, including the code and the software are under protection by legal legislation.

Without the written consent of Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. the information on the website cannot be downloaded, changed, reproduced, copied, republished, posted or distributed.

All rights of the software and the design of the website belong to Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc.

Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. will be pleased to hear your comments about our terms of use. Please share the subjects you think may enrich our website or if there is any problem regarding our website.

info@turkiyeklinikleri.com