Vitamin C can shorten the length of stay in the ICU: a meta-analysis

Harri Hemilä and Elizabeth Chalker

Nutrients 2019

This is Web page for the references of the paper.

The published paper has DOI-links, but some of the papers have other sources,
that are shown here, but they are not available as links in the paper.

References to which additional links are listed here, are marked with bold.

Harri Hemilä
Department of Public Health
University of Helsinki, Helsinki, Finland
This file:
version 2019-4-25


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186. Finkle, P. Vitamin C saturation levels in the body in normal subjects and in various pathological conditions. J. Clin. Invest. 1937, 16, 587-593.

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188. Abbasy, M.A. Vitamin C and infection: excretion of vitamin C in osteomyelitis. Lancet 1937, 230, 177-180.

189. Evans, W. Vitamin C in heart failure. Lancet 1938, 231, 308-309.

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198. Mochalkin, N.I. Ascorbic acid in the complex therapy of acute pneumonia [in Russian].
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199. Kimbarowski, J.A. Colored precipitation reaction of the urine according to Kimbarowski as an index of the effect of ascorbic acid during treatment of viral influenza [in German]. Dtsch. Gesundheitsw. 1967, 22, 2413–2418.

200. Hemilä, H.; Louhiala, P. Vitamin C for preventing and treating pneumonia. Cochrane Database Syst. Rev. 2007, CD005532.
The above Cochrane review (2007) concluded in the Abstract:
”The prophylactic use of vitamin C to prevent pneumonia should be further investigated in populations who have high incidence of pneumonia, especially if dietary vitamin C intake is low. Similarly, the therapeutic effects of vitamin C should be studied, especially in patients with low plasma vitamin C levels.”

However, the strong evidence indicating that vitamin C influences pneumonia incidence in some contexts was shown one decade even earlier, in 1997, see:

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203. Bates, C.J.; Schorah, C.J.; Hemilä, H. Vitamin C intake and susceptibility to the common cold: invited comments and reply. Br. J. Nutr. 1997, 78, 857–866.

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See comments:

206. Anderson, T.W. The effect on winter illness of large doses of vitamin C. Can. Med. Assoc. J. 1974, 111, 31–36.

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208. Ludvigsson, J. Vitamin C as a preventive medicine against common colds in children. Scand. J. Infect. Dis. 1977, 9, 91-98.

209. Hemilä, H. Vitamin C and sex differences in respiratory tract infections. Respir. Med. 2008, 102, 625–626.

210. Tyrrell, D.A. A trial of ascorbic acid in the treatment of the common cold. Br. J. Prev. Soc. Med. 1977, 31, 189-191.

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213. Panagiotou, O.A. Comparative effect sizes in randomised trials from less developed and more developed countries: meta-epidemiological assessment. BMJ 2013, 346, f707.

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217. Wilson, J.X. Evaluation of vitamin C for adjuvant sepsis therapy. Antioxid. Redox Signal. 2013, 19, 2129-2140.

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219. Berger, M.M. Vitamin C supplementation in the critically ill patient. Curr. Opin. Clin. Nutr. Metab. Care 2015, 18, 193-201.

220. Marik, P.E. Hydrocortisone, ascorbic acid and thiamine (HAT therapy) for the treatment of sepsis: focus on ascorbic acid. Nutrients 2018, 10, 1762.

221. Moskowitz, A. Ascorbic acid, corticosteroids, and thiamine in sepsis: a review of the biologic rationale and the present state of clinical evaluation. Crit. Care. 2018, 22, 283.

222. Amrein, K. Vitamin therapy in critically ill patients: focus on thiamine, vitamin C, and vitamin D. Intensive Care Med. 2018, 44,

223. Spoelstra-de Man, A.M.E. Vitamin C: should we supplement? Curr. Opin. Crit. Care 2018, 24, 248-255.

224. Zhang, M. Vitamin C provision improves mood in acutely hospitalized patients. Nutrition 2011, 27, 530–533.

225. Wang, Y. Effects of vitamin C and vitamin D administration on mood and distress in acutely hospitalized patients. Am. J. Clin. Nutr. 2013, 98, 705–711.

226. Padayatty, S.J. Vitamin C pharmacokinetics: implications for oral and intravenous use. Ann. Intern. Med. 2004, 140, 533–537.

227. Levine, M. Vitamin C: a concentration-function approach yields pharmacology and therapeutic discoveries. Adv. Nutr. 2011, 2, 78-88.

228. Padayatty, S.J. Vitamin C: intravenous use by complementary and alternative medicine practitioners and adverse effects. PLoS One 2010, 5, e11414.

229. Mikirova, N. Effect of high-dose intravenous vitamin C on inflammation in cancer patients. J. Transl. Med. 2012, 10, 189.

230. Schencking, M. Intravenous vitamin C in the treatment of shingles: results of a multicenter prospective cohort study. Med. Sci. Monit. 2012, 18, CR215-CR224.

231. Pourmatroud, E. Intravenous ascorbic acid (vitamin C) administration in myomectomy: a prospective, randomized, clinical trial. Arch. Gynecol. Obstet. 2012, 285, 111-115.

232. Hoffer, L.J. High-dose intravenous vitamin C combined with cytotoxic chemotherapy in patients with advanced cancer: a phase I-II clinical trial. PLoS One 2015, 10, e0120228.

233. Jeon, Y. Effect of intravenous high dose vitamin C on postoperative pain and morphine use after laparoscopic colectomy: a randomized controlled trial. Pain Res. Manag. 2016, 2016, 9147279.

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241. Jahan, K. Effect of ascorbic acid in the treatment of tetanus. Bangladesh Med. Res. Counc. Bull. 1984, 10, 24–28.

242. Du, W.D. Therapeutic efficacy of high-dose vitamin C on acute pancreatitis and its potential mechanisms. World J. Gastroenterol. 2003, 9, 2565-2569.

243. Hemilä, H.; Koivula, T. Vitamin C for preventing and treating tetanus. Cochrane Database Syst. Rev. 2013, CD006665.
See references with links:

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245. Clemetson, C.A.B. Barlow’s disease. Med. Hypotheses 2002, 59, 52-56.

246. Hemilä, H.; Kaprio, J. Modification of the effect of vitamin E supplementation on the mortality of male smokers by age and dietary vitamin C. Am. J. Epidemiol. 2009, 169, 946-953.

247. Sisto, T. Pretreatment with antioxidants and allopurinol diminishes cardiac onset events in coronary artery bypass grafting. Ann. Thorac. Surg. 1995, 59, 1519-1523.

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251. Berger, M.M. Influence of early antioxidant supplements on clinical evolution and organ function in critically ill cardiac surgery, major trauma, and subarachnoid hemorrhage patients. Crit. Care 2008, 12, R101.

252. Barbosa, E. Supplementation of vitamin E, vitamin C, and zinc attenuates oxidative stress in burned children: a randomized, double-blind, placebo-controlled pilot study. J. Burn Care Res. 2009, 30, 859-866.

253. Howe, K.P. Mechanical ventilation antioxidant trial. Am. J. Crit. Care 2015, 24, 440-445.

254. Collier, B.R. Impact of high-dose antioxidants on outcomes in acutely injured patients. JPEN J. Parenter. Enteral Nutr. 2008, 32, 384-388.

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256. Kahn, S.A. Resuscitation after severe burn injury using high-dose ascorbic acid: a retrospective review. J. Burn Care Res. 2011, 32, 110-117.

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258. Marik, P.E. Hydrocortisone, vitamin C, and thiamine for the treatment of severe sepsis and septic shock: a retrospective before-after study. Chest 2017, 151, 1229-1238.

259. Balakrishnan, M. Hydrocortisone, vitamin C and thiamine for the treatment of sepsis and septic shock following cardiac surgery. Indian J. Anaesth. 2018, 62, 934-939.

260. Kim, W.Y. Combined vitamin C, hydrocortisone, and thiamine therapy for patients with severe pneumonia who were admitted to the intensive care unit: propensity score-based analysis of a before-after cohort study. J. Crit. Care 2018, 47, 211-218.

261. Hemilä, H. Spectacular reduction in the mortality of acutely injured patients by the administration of vitamins C and E and selenium [reply in 2009, 33, 449]. JPEN J. Parenter. Enteral Nutr. 2009, 33, 447-448.

262. Cathcart, R.F. Vitamin C, titrating to bowel tolerance, anascorbemia, and acute induced scurvy. Med. Hypotheses 1981, 7, 1359–1376.
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See also:

263. Buehner, M. Oxalate nephropathy after continuous infusion of high-dose vitamin C as an adjunct to burn resuscitation. J. Burn Care Res. 2016, 37, e374-e379.

264. Chalmers, T.C. Effects of ascorbic acid on the common cold: an evaluation of the evidence. Am. J. Med. 1975, 58, 532–536.

The Chalmers review has been extensively cited in journal articles and textbooks, see:

Thomas Chalmers was a very influential physician: David Sackett describes in this paper that Thomas Chalmers' 1955 clinical trial report changed his career and led to the emergence of the EBM movement According to Richard Smith and Drummond Rennie, Thomas Chalmers was one of the "three individuals from an earlier generation [who] were particularly important in inspiring" the EBM movement

265. Hemilä, H. Do vitamins C and E affect respiratory infections?
University of Helsinki: Helsinki, Finland, 2006; pp. 21-45, 59-66.
see also:

266. Council of Scientific Affairs, American Medical Association. Vitamin preparations as dietary supplements and as therapeutic agents. JAMA 1987, 257, 1929–1936.

267. Dykes, M.H.M.; Meier, P. Ascorbic acid and the common cold: evaluation of its efficacy and toxicity. JAMA 1975, 231, 1073–1079.

Paul Meier was a very famous statistician, eg:

268. Pauling, L. Ascorbic acid and the common cold: evaluation of its efficacy and toxicity. Part I. Medical Tribune 1976, 17, 18-19.

269. Pauling, L. Ascorbic acid and the common cold. Part II. Medical Tribune 1976, 17, 37-38.

270. Chalmers, T.C. Dissent to the preceding article by H. Hemilä. J. Clin. Epidemiol. 1996, 49, 1085.

271. Hemilä, H. To the dissent by Thomas Chalmers. J. Clin. Epidemiol. 1996, 49, 1087.

272. Richards, E. The politics of therapeutic evaluation: the vitamin C and cancer controversy. Soc. Stud. Sci. 1988, 18, 653-701.

273. Richards, E. Vitamin C and Cancer: Medicine or Politics?
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274. Segerstråle, U. Beleaguering the cancer establishment. Science 1992, 255, 613–615.

275. Goodwin, J.S. Battling quackery: attitudes about micronutrient supplements in American Academic medicine. Arch. Intern. Med. 1998, 158, 2187–2191.

276. Goodwin, J.S. Failure to recognize efficacious treatments: a history of salicylate therapy in rheumatoid arthritis. Persp. Biol. Med. 1981, 31, 78-92.

277. Goodwin, J.S. The tomato effect: rejection of highly efficacious therapies. JAMA 1984, 251, 2387–2390.

278. Louhiala, P.; Hemilä, H. Can CAM treatments be evidence-based? Focus Altern. Complement. Ther. 2014, 19, 84–89.