Intravenous vitamin C in the treatment of allergies: an interim subgroup analysis of a long-term observational study

Claudia Vollbracht, Martin Raithel, Bianka Krick, Karin Kraft, Alexander F Hagel, Claudia Vollbracht, Martin Raithel, Bianka Krick, Karin Kraft, Alexander F Hagel

Abstract

Objective Oxidative stress appears to be a key factor in the pathogenesis of allergic diseases and a potential therapeutic target in allergy treatment. Allergic diseases are reportedly associated with reduced plasma levels of ascorbate, which is a key physiological antioxidant. Ascorbate prevents excessive inflammation without reducing the defensive capacity of the immune system. Methods An interim analysis of a multicenter, prospective, observational study was conducted to investigate the change in disease-specific and nonspecific symptoms (fatigue, sleep disorders, depression, and lack of mental concentration) during adjuvant treatment with intravenous vitamin C (Pascorbin®; Pascoe, Giessen, Germany) in 71 patients with allergy-related respiratory or cutaneous indications. Results Between the start and end of treatment, the mean sum score of three disease-specific symptoms decreased significantly by 4.71 points and that of four nonspecific symptoms decreased significantly by 4.84 points. More than 50% of patients took no other allergy-related medication besides vitamin C. Conclusions Our observations suggest that treatment with intravenous high-dose vitamin C reduces allergy-related symptoms. Our observations form a basis for planning a randomized controlled clinical trial to obtain more definitive evidence of the clinical relevance of our findings. We also obtained evidence of ascorbate deficiency in allergy-related diseases.

Trial registration: Clinical Trials NCT02422901.

Keywords: Ascorbic acid; allergic asthma; allergic rhinitis; dermatitis; eczema; human; intravenous administration; pruritus.

Figures

Figure 1.
Figure 1.
Flowchart of study patients.
Figure 2.
Figure 2.
Frequencies of the three most frequently recorded disease-specific symptoms. The severity of each symptom was documented on a 4-point Likert scale (0 = absent, 1 = mild, 2 = moderate, 3 = severe) by the treating physician or natural health practitioner at start and end of treatment. Valid data for pruritus, n = 31; for rhinitis, n = 26; and for restlessness, n = 15.
Figure 3.
Figure 3.
Frequency of nonspecific symptoms (tiredness/fatigue, sleep disorders, depression, and lack of mental concentration). The severity of each symptom was documented on a 4-point Likert scale (0 = absent, 1 = mild, 2 = moderate, 3 = severe) by the treating physician or natural health practitioner at start and end of treatment. Valid data for tiredness/fatigue, n = 62; for sleep disorders, n = 53; for depression, n = 44; and for lack of mental concentration, n = 60.

References

    1. Kiewiet MB, Gros M, van Neerven RJ, et al. Immunomodulating properties of protein hydrolysates for application in cow's milk allergy. Pediatr Allergy Immunol 2015; 26: 206–217.
    1. Marlow G, Han DY, Wickens K, et al. Differential effects of two probiotics on the risks of eczema and atopy associated with single nucleotide polymorphisms to Toll-like receptors. Pediatr Allergy Immunol 2015; 26: 262–271.
    1. Asher BF, Seidman MD, Reddy WD, et al. Integrative medical approaches to allergic rhinitis. Curr Opin Otolaryngol Head Neck Surg 2015; 23: 221–225.
    1. Resnick ES, Bielory BP, Bielory L. Complementary therapy in allergic rhinitis. Curr Allergy Asthma Rep 2008; 8: 118–125.
    1. Jiang L, Diaz PT, Best TM, et al. Molecular characterization of redox mechanisms in allergic asthma. Ann Allergy Asthma Immunol 2014; 113: 137–142.
    1. Campbell EL, Colgan SP. Neutrophils and inflammatory metabolism in antimicrobial functions of the mucosa. J Leukoc Biol 2015; 98: 517–522.
    1. Brown DI, Griendling KK. Nox proteins in signal transduction. Free Radic Biol Med 2009; 47: 1239–1253.
    1. Ortiz GG, Pacheco-Moises FP, Bitzer-Quintero OK, et al. Immunology and oxidative stress in multiple sclerosis: clinical and basic approach. Clin Dev Immunol 2013; 2013: 708659.
    1. Boldogh I, Bacsi A, Choudhury BK, et al. ROS generated by pollen NADPH oxidase provide a signal that augments antigen-induced allergic airway inflammation. J Clin Invest 2005; 115: 2169–2179.
    1. Ciz M, Lojek A. Modulation of neutrophil oxidative burst via histamine receptors. Br J Pharmacol 2013; 170: 17–22.
    1. Ohmori H, Komoriya K, Azuma A, et al. Xanthine oxidase-induced histamine release from isolated rat peritoneal mast cells: involvement of hydrogen peroxide. Biochem Pharmacol 1979; 28: 333–334.
    1. Ohmori H, Yamamoto I, Akagi M, et al. Properties of hydrogen peroxide-induced histamine release from rat mast cells. Biochem Pharmacol 1980; 29: 741–745.
    1. Hocker M, Rosenberg I, Xavier R, et al. Oxidative stress activates the human histidine decarboxylase promoter in AGS gastric cancer cells. J Biol Chem 1998; 273: 23046–23054.
    1. Schmidt HH, Stocker R, Vollbracht C, et al. Antioxidants in translational medicine. Antioxid Redox Signal 2015; 23: 1130–1143.
    1. Frei B, Stocker R, Ames BN. Antioxidant defenses and lipid peroxidation in human blood plasma. Proc Natl Acad Sci U S A 1988; 85: 9748–9752.
    1. Frei B, England L, Ames BN. Ascorbate is an outstanding antioxidant in human blood plasma. Proc Natl Acad Sci U S A 1989; 86: 6377–6381.
    1. Frei B. Ascorbic acid protects lipids in human plasma and low-density lipoprotein against oxidative damage. Am J Clin Nutr 1991; 54: 1113S–1118S.
    1. Levine M, Rumsey SC, Daruwala R, et al. Criteria and recommendations for vitamin C intake. JAMA 1999; 281: 1415–1423.
    1. Padayatty SJ, Sun AY, Chen Q, et al. Vitamin C: intravenous use by complementary and alternative medicine practitioners and adverse effects. PLoS One 2010; 5: e11414.
    1. Levine M, Padayatty SJ, Espey MG. Vitamin C: Concentration- function approach yields pharmacology and therapeutic discoveries. Adv Nutr 2011; 2: 78–88.
    1. Schencking M, Vollbracht C, Weiss G, et al. Intravenous Vitamin C in the treatment of shingles: Results of a multicenter prospective cohort study. Med Sci Monit 2012; 18: CR215–CR224.
    1. Srivastava VK, Agrawal S, Kadiyala VN, et al. The efficacy of pregabalin for prevention of catheter-related bladder discomfort: a prospective, randomized, placebo-controlled double-blind study. J Anesth 2015; 29: 212–216.
    1. Li Z, Mu G, Chen W, et al. Comparative evaluation of topical pranoprofen and fluorometholone in cases with chronic allergic conjunctivitis. Cornea 2013; 32: 579–582.
    1. Koenig J, Sevinc S, Frohme C, et al. Does visualisation during urethrocystoscopy provide pain relief? Results of an observational study. BMC Urol 2015; 15: 56.
    1. Johnston CS, Thompson LL. Vitamin C status of an outpatient population. J Am Coll Nutr 1998; 17: 366–370.
    1. Institute of Medicine (US) panel on dietary antioxidants and related compounds. Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids. Washington (DC: ): National Academies Press (US), 2000.
    1. Fogarty A, Lewis SA, Scrivener SL, et al. Corticosteroid sparing effects of vitamin C and magnesium in asthma: a randomised trial. Respir Med 2006; 100: 174–179.
    1. Bateman ED, Esser D, Chirila C, et al. Magnitude of effect of asthma treatments on Asthma Quality of Life Questionnaire and Asthma Control Questionnaire scores: Systematic review and network meta-analysis. J Allergy Clin Immunol 2015; 136: 914–922.
    1. Soler ZM, Eckert MA, Storck K, et al. Cognitive function in chronic rhinosinusitis: a controlled clinical study. Int Forum Allergy Rhinol 2015; 5: 1010–1017.
    1. Silverberg JI, Garg NK, Paller AS, et al. Sleep disturbances in adults with eczema are associated with impaired overall health: a US population-based study. J Invest Dermatol 2015; 135: 56–66.
    1. Gonzalez-Nunez V, Valero AL, Mullol J. Impact of sleep as a specific marker of quality of life in allergic rhinitis. Curr Allergy Asthma Rep 2013; 13: 131–141.
    1. LeBovidge JS, Elverson W, Timmons KG, et al. Multidisciplinary interventions in the management of atopic dermatitis. J Allergy Clin Immunol 2016; 138: 325–334.
    1. Nandi BK, Subramanian N, Majumder AK, et al. Effect of ascorbic acid on detoxification of histamine under stress conditions. Biochem Pharmacol 1974; 23: 643–647.
    1. Subramanian N, Nandi BK, Majumder AK, et al. Effect of ascorbic acid on detoxification of histamine in rats and guinea pigs under drug treated conditions. Biochem Pharmacol 1974; 23: 637–641.
    1. Ridzwan BH, Jais AM, Waton NG. The depletion effects of chlorpromazine, reserpine and ascorbic acid on tissue histamine of guinea-pigs. Gen Pharmacol 1988; 19: 631–636.
    1. Johnston CS, Huang SN. Effect of ascorbic acid nutriture on blood histamine and neutrophil chemotaxis in guinea pigs. J Nutr 1991; 121: 126–130.
    1. Johnston CS, Martin LJ, Cai X. Antihistamine effect of supplemental ascorbic acid and neutrophil chemotaxis. J Am Coll Nutr 1992; 11: 172–176.
    1. Johnston CS, Solomon RE, Corte C. Vitamin C depletion is associated with alterations in blood histamine and plasma free carnitine in adults. J Am Coll Nutr 1996; 15: 586–591.
    1. Johnston CS, Retrum KR, Srilakshmi JC. Antihistamine effects and complications of supplemental vitamin C. J Am Diet Assoc 1992; 92: 988–989.
    1. Clemetson CAB. Histamine and Ascorbic Acid in Human Blood. J Nutr 1980; 110: 662–668.
    1. Hagel AF, Layritz CM, Hagel WH, et al. Intravenous infusion of ascorbic acid decreases serum histamine concentrations in patients with allergic and non-allergic diseases. Naunyn Schmiedebergs Arch Pharmacol 2013; 386: 789–793.
    1. Romero SA, Ely MR, Sieck DC, et al. Effect of antioxidants on histamine receptor activation and sustained postexercise vasodilatation in humans. Exp Physiol 2015; 100: 435–449.
    1. Vashisht A, Chhabra SK, Banerjee BD, et al. Rapidly adapting receptor activity during oxidative stress induced airway hyperresponsiveness. Respir Physiol Neurobiol 2013; 186: 273–284.
    1. Johnston CS. The antihistamine action of ascorbic acid. Subcell Biochem 1996; 25: 189–213.
    1. Hasanzadeh Kiabi F, Soleimani A, Habibi MR, et al. Can Vitamin C be used as an adjuvant for managing postoperative pain? a short literature review. Korean J Pain 2013; 26: 209–210.
    1. Li R, Shen L, Yu X, et al. Vitamin C enhances the analgesic effect of gabapentin on rats with neuropathic pain. Life Sci 2016; 157: 25–31.
    1. Chen S, Roffey DM, Dion CA, et al. Effect of perioperative Vitamin C supplementation on postoperative pain and the incidence of chronic regional pain syndrome: a systematic review and meta-analysis. Clin J Pain 2016; 32: 179–185.
    1. Kapoor S. Vitamin C and its emerging role in pain management: beneficial effects in pain conditions besides post herpetic neuralgia. Korean J Pain 2012; 25: 200–201.
    1. Carr AC, Vissers MC, Cook JS. The effect of intravenous vitamin C on cancer- and chemotherapy-related fatigue and quality of life. Front Oncol 2014; 4: 283.
    1. Shanmugasundaram K, Kumar S, Rajajee S. Excessive free radical generation in the blood of children suffering from asthma. Clinica Chimica Acta 2001; 305: 107–114.
    1. Lunec J, Blake DR. The determination of dehydroascorbic acid and ascorbic acid in the serum and synovial fluid of patients with rheumatoid arthritis (RA). Free Radic Res Commun 1985; 1: 31–39.
    1. Mayland CR, Bennett MI, Allan K. Vitamin C deficiency in cancer patients. Palliat Med 2005; 19: 17–20.
    1. Fowler AA, 3rd, Syed AA, Knowlson S, et al. Phase I safety trial of intravenous ascorbic acid in patients with severe sepsis. J Transl Med 2014; 12: 32.
    1. Rodemeister S, Duquesne M, Adolph M, et al. Massive and long-lasting decrease in vitamin C plasma levels as a consequence of extracorporeal circulation. Nutrition 2014; 30: 673–678.
    1. Larsson N, Rankin GD, Bicer EM, et al. Identification of vitamin C transporters in the human airways: a cross-sectional in vivo study. BMJ open 2015; 5: e006979.
    1. Aderele WI, Ette SI, Oduwole O, et al. Plasma vitamin C (ascorbic acid) levels in asthmatic children. Afr J Med Med Sci 1985; 14: 115–120.
    1. Kalayci O, Besler T, Kilinc K, et al. Serum levels of antioxidant vitamins (alpha tocopherol, beta carotene, and ascorbic acid) in children with bronchial asthma. Turk J Pediatr 2000; 42: 17–21.
    1. Vural H, Uzun K. Serum and red blood cell antioxidant status in patients with bronchial asthma. Can Respir J 2000; 7: 476–80.
    1. Leveque N, Robin S, Muret P, et al. In vivo assessment of iron and ascorbic acid in psoriatic dermis. Acta Derm Venereol 2004; 84: 2–5.
    1. Leveque N, Robin S, Muret P, et al. High iron and low ascorbic acid concentrations in the dermis of atopic dermatitis patients. Dermatology 2003; 207: 261–264.
    1. Hoffer LJ, Levine M, Assouline S, et al. Phase I clinical trial of i.v. ascorbic acid in advanced malignancy. Ann Oncol 2008; 19: 1969–1974.
    1. Nielsen TK, Hojgaard M, Andersen JT, et al. Elimination of ascorbic acid after high-dose infusion in prostate cancer patients: a pharmacokinetic evaluation. Basic Clin Pharmacol Toxicol 2015; 116: 343–348.
    1. Monti DA, Mitchell E, Bazzan AJ, et al. Phase I evaluation of intravenous ascorbic acid in combination with gemcitabine and erlotinib in patients with metastatic pancreatic cancer. PLoS One 2012; 7: e29794.

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