High dose intravenous vitamin C for lyme disease: a safety and tolerability study with an exploratory assessment of treatment efficacy.

Main Article Content

Cory Tichauer Jamie Corroon Rachele Fain Andrew Erlandsen Ryan Bradley


Lyme disease is the most common vector-borne disease in the United States with an estimated 476,000 new cases per year. Delays in diagnosis and treatment are common and there is a lack of consensus on the antibiotic therapy protocols to ensure successful outcomes. Much of this discord is due to the observation that more than 50 percent of people treated with conventional antibiotic protocols, which have changed little in the last 30 years, report persistent and/or recurring symptoms within 6 months of completing treatment. Labeled as chronic Lyme or post-treatment Lyme disease, it is a syndrome that afflicts more than 2 million people in the United States and can have a devastating impact on both quality of life and socioeconomic capacity. Despite these known treatment failures, the research community has lacked the funding necessary to advance our understanding of this syndrome or to explore innovative options to improve success. In this regard, complementary and alternative therapies, which are generally not patentable and have little potential for producing large economic gain, are generally disregarded in favor of new designer drugs or old reworked protocols. Intravenous vitamin C is one such example that has research validated effectiveness for a wide range of clinical conditions ranging from infection to cancer care. Achieving serum levels much higher than could be obtained orally, high dose intravenous vitamin C has the capacity to generate a concentration of intracellular peroxide that exerts both cytotoxic and immune stimulating effects. Unfortunately, these high doses of intravenous vitamin C have never been evaluated to establish safety and tolerability in Lyme positive patients. This study’s primary aim is to examine this question with the unique additions of DMSO and calcium EDTA into the formula to enhance tissue penetration and address biofilm formation respectively, both of which are known barriers to antibiotic success. The secondary aim of the study is to determine whether subjects gain relief from Lyme-associated symptoms by tracking changes in both the PROMIS-29 and the Horowitz-Lyme-MSIDS questionnaires. The exploratory objective is to assess changes in Lyme specific labs including the standard immunoblot and the T-cell based Elispot as well as the CD57+ lymphocyte immune marker. Administered at a 75-gram dose twice weekly over 12 weeks, high dose intravenous vitamin C was shown to be both well tolerated and safe. The secondary and exploratory aims of the study provide insight into the potential efficacy of this protocol, as both subjective measures of symptom severity and objective assessment of Lyme biomarkers showed marked improvement. Ultimately, this study paves the way for future research using high dose intravenous vitamin C in Lyme patents either as a stand-alone treatment or in synergy with other therapies. It is this author’s hope that employing an integrative medical approach such as this will eventually see chronic Lyme disease as a rare rather than common occurrence.

Keywords: lyme disease, High dose intravenous vitamin C, vitamin C, treatment efficacy

Article Details

How to Cite
TICHAUER, Cory et al. High dose intravenous vitamin C for lyme disease: a safety and tolerability study with an exploratory assessment of treatment efficacy.. Medical Research Archives, [S.l.], v. 12, n. 1, jan. 2024. ISSN 2375-1924. Available at: <https://esmed.org/MRA/mra/article/view/4941>. Date accessed: 03 mar. 2024. doi: https://doi.org/10.18103/mra.v12i1.4941.
Research Articles


1. Stanek Gerold, gerold.stanek@ meduniwien.ac.at, Medical University of Vienna Institute for Hygiene and Applied Immunology, Vienna, Austria, et al. Lyme borreliosis. The Lancet. 2012;379(9814):461-473.

2. Bratton Robert, J Whiteside, et al. Diagnosis and Treatment of Lyme Disease. Mayo Clinic Proceedings. 2008;83(5):566-571.

3. Sanchez, Joyce. Clinical Manifestations and Treatment of Lyme Disease. Clinics in Laboratory Medicine. 2015;35(4): 765-778.

4. Wormser Gary P., Dattwyler Raymond J., Shapiro Eugene D., et al. The Clinical Assessment, Treatment, and Prevention of Lyme Disease, Human Granulocytic Anaplasmosis, and Babesiosis: Clinical Practice Guidelines by the Infectious Diseases Society of America. Clinical Infectious Diseases. 2022;43(9):1089-1134.

5. Hu LT. Lyme Disease. Ann Intern Med. 2016;164(9)

6. Kowalski TJ, Tata S, Berth W, et al. Antibiotic treatment duration and long-term outcomes of patients with early Lyme disease from a Lyme disease-hyperendemic area. Clin Infect Dis. 2010;50:512-520.

7. Hirsch, AG, Poulsen, MN, Nordberg, C, Moon, KA, Rebman, AW, Aucott, JN, et al. Risk factors and outcomes of treatment delays in Lyme disease: a population-based retrospective cohort study. Front Med (Lausanne). (2020) 7:560018. doi: 10.3389/fmed.2020.560018

8. Asch, ES, Bujak, DI, Weiss, M, Peterson, MG, and Weinstein, A. Lyme disease: an infectious and postinfectious syndrome. J Rheumatol. (1994) 21:454–61.

9. Shadick, NA, Phillips, CB, Sangha, O, Logigian, EL, Kaplan, RF, Wright, EA, et al. Musculoskeletal and neurologic outcomes in patients with previously treated Lyme disease. Ann Intern Med. (1999) 131:919–26. doi: 10.7326/0003-4819-131-12-199912210-00003

10. DeLong, A, Hsu, M, and Kotsoris, H. Estimation of cumulative number of post-treatment Lyme disease cases in the US, 2016 and 2020. BMC Public Health. (2019) 19:352. doi: 10.1186/s12889-019-6681-9

11. Schmidli, J, Hunziker, T, Moesli, P, and Schaad, UB. Cultivation of Borrelia burgdorferi from joint fluid three months after treatment of facial palsy due to Lyme borreliosis. J Infect Dis. (1988) 158:905–6. doi: 10.1093/infdis/158.4.905

12. Liegner, KB, Shapiro, JR, Ramsay, D, Halperin, AJ, Hogrefe, W, and Kong, L. Recurrent erythema migrans despite extended antibiotic treatment with minocycline in a patient with persisting Borrelia burgdorferi infection. J Am Acad Dermatol. (1993) 28:312–4. doi: 10.1016/01 90-9622(93)70043-s

13. Preac-Mursic, V, Weber, K, Pfister, HW, Wilske, B, Gross, B, Baumann, A, et al. Survival of Borrelia burgdorferi in antibiotically treated patients with Lyme borreliosis. Infection. (1989) 17:355–9. doi: 10.1007/bf01645543

14. Adkison H, Embers ME. Lyme disease and the pursuit of a clinical cure. Front Med (Lausanne). 2023 May 24;10:1183344. doi: 10.3389/fmed.2023.1183344. PMID: 372933 10; PMCID: PMC10244525.

15. Auwaerter, PG. Point: antibiotic therapy is not the answer for patients with persisting symptoms attributable to Lyme disease. Clin Infect Dis. (2007) 45:143–8. doi: 10.1086/518854

16. Stricker, RB. Counterpoint: long-term antibiotic therapy improves persistent symptoms associated with Lyme disease. Clin Infect Dis. (2007) 45:149–57. doi: 10.1086/518853

17. Sjöwall, J, Ledel, A, Ernerudh, J, Ekerfelt, C, and Forsberg, P. Doxycycline-mediated effects on persistent symptoms and systemic cytokine responses post-neuroborreliosis: a randomized, prospective, cross-over study. BMC Infect Dis. (2012) 12:186. doi: 10.1186/ 1471-2334-12-186

18. Delong, AK, Blossom, B, Maloney, EL, and Phillips, SE. Antibiotic retreatment of Lyme disease in patients with persistent symptoms: a biostatistical review of randomized, placebo-controlled, clinical trials. Contemp Clin Trials. (2012) 33:1132–42. doi: 10.1016/j.cct.2012.08.009

19. Klempner, MS, Hu, LT, Evans, J, Schmid, CH, Johnson, GM, Trevino, RP, et al. Two controlled trials of antibiotic treatment in patients with persistent symptoms and a history of Lyme disease. N Engl J Med. (2001) 345:85–92. doi: 10.1056/NEJM200107123450202

20. Ang A, Pullar JM, Currie MJ, Vissers MCM. Vitamin C and immune cell function in inflammation and cancer. Biochem Soc Trans. 2018;46(5):1147-59.

21. Böttger F, Vallés-Martí A, Cahn L, Jimenez CR. High-dose intravenous vitamin C, a promising multi-targeting agent in the treatment of cancer. J Exp Clin Cancer Res. 2021 Oct 30;40(1):343. doi: 10.1186/s13046-021-02134-y. PMID: 34717701; PMCID: PMC8557029.

22. Levine M, Padayatty SJ, Espey MG. Vitamin C: a concentration-function approach yields pharmacology and therapeutic discoveries. Adv Nutr Bethesda Md. 2011;2(2):78-88. doi:10.3945/an.110.000109.

23. Lane D.J.R., Merlot A.M., Huang M.L.H., Bae D.H., Jansson P.J., Sahni S., Kalinowski D.S., Richardson D.R. Cellular iron uptake, trafficking and metabolism: Key molecules and mechanisms and their roles in disease. Biochim. Biophys. Acta. 2015;1853:1130–1144. doi: 10.1016/j.bbamcr.2015.01.021.

24. Winterbourn C.C. Toxicity of iron and hydrogen peroxide: The Fenton reaction. Toxicol. Lett. 1995;82:969–974. doi: 10.1016/0378-4274(95)03532-X.

25. Chen Q, Espey MG, Sun AY, et al. Ascorbate in pharmacologic concentrations selectively generates ascorbate radical and hydrogen peroxide in extracellular fluid in vivo. Proc Natl Acad Sci U S A. 2007;104(21) :8749-8754. doi:10.1073/pnas.0702854104

26. Sae-Khow K, Charoensappakit A, Chiewchengchol D, Leelahavanichkul A. High-Dose Intravenous Ascorbate in Sepsis, a Pro-Oxidant Enhanced Microbicidal Activity and the Effect on Neutrophil Functions. Biomedicines. 2022 Dec 25;11(1):51. doi: 10.3390/biomedicines11010051. PMID: 36672559; PMCID: PMC9855518.

27. Dixon S.J., Lemberg K.M., Lamprecht M.R., Skouta R., Zaitsev E.M., Gleason C.E., Patel D.N., Bauer A.J., Cantley A.M., Yang W.S., et al. Ferroptosis: An iron-dependent form of nonapoptotic cell death. Cell. 2012;149:1060–1072. doi: 10.1016/j.cell. 2012.03.042.

28. Levy R., Shriker O., Porath A., Riesenberg K., Schlaeffer F. Vitamin C for the treatment of recurrent furunculosis in patients with imparied neutrophil functions. J. Infect. Dis. 1996;173:1502–1505. doi: 10.1093/infdis/173 .6.1502.

29. Jeong Y.J., Hong S.W., Kim J.H., Jin D.H., Kang J.S., Lee W.J., Hwang Y.I. Vitamin C-treated murine bone marrow-derived dendritic cells preferentially drive naïve T cells into Th1 cells by increased IL-12 secretions. Cell Immunol. 2011;266:192–199. doi: 10.1016/j.cellimm.2010.10.005.

30. Lusitani D, Malawista SE, Montgomery RR. Borrelia burgdorferi Are Susceptible to Killing by a Variety of Human Polymorphonuclear Leukocyte Components. J Infect Dis. 2002;185(6):797-804. doi:10. 1086/339341.

31. Levine M, Padayatty SJ, Espey MG. Vitamin C: a concentration-function approach yields pharmacology and therapeutic discoveries. Adv Nutr Bethesda Md. 2011;2(2):78-88. doi:10.3945/an.110.000109.

32. Levine M, Conry-Cantilena C, Wang Y, et al. Vitamin C pharmacokinetics in healthy volunteers: evidence for a recommended dietary allowance. Proc Natl Acad Sci U S A. 1996;93(8):3704-3709.

33. Padayatty SJ, Sun H, Wang Y, et al. Vitamin C pharmacokinetics: implications for oral and intravenous use. Ann Intern Med. 2004;140(7):533-537.

34. Stephenson CM, Levin RD, Spector T, Lis CG. Phase I clinical trial to evaluate the safety, tolerability, and pharmacokinetics of high-dose intravenous ascorbic acid in patients with advanced cancer. Cancer Chemother Pharmacol. 2013;72(1):139-146. doi:10.1007/ s00280-013-2179-9.

35. SJ Padayatty, AY Sun, Q Chen, et al. Vitamin C: intravenous use by complementary and alternative medicine practitioners and adverse effects. PloS one. 2010;5(7).

36. Sharma B, Brown AV, Matluck NE, Hu LT, Lewis K. Borrelia burgdorferi, the Causative Agent of Lyme Disease, Forms Drug-Tolerant Persister Cells. Antimicrob Agents Chemother. 2015 Aug;59(8):4616-24. doi: 10.1128/AAC.00864-15. Epub 2015 May 26. PMID: 26014929; PMCID: PMC4505243.

37. Bardutzky J, Meng X, Bouley J, Duong TQ, Ratan R, Fisher M. Effects of intravenous dimethyl sulfoxide on ischemia evolution in a rat permanent occlusion model. J Cereb Blood Flow Metab. 2005 Aug;25(8):968-77. doi: 10.1038/sj.jcbfm.9600095. PMID: 15744247; PMCID: PMC2949963.

38. Hoang BX, Tran DM, Tran HQ, et al. Dimethyl Sulfoxide and Sodium Bicarbonate in the Treatment of Refractory Cancer Pain. J Pain Palliat Care Pharmacother. 2011;25(1) :19-24. doi:10.3109/15360288.2010.536306.

39. Karaça M, Kiliç E, Yazici B, Demir S, Torre J de la. Ischemic stroke in elderly patients treated with a free radical scavenger–glycolytic intermediate solution: A preliminary pilot trial. Neurol Res. 2002;24(1):73-80. doi:10.1179/016164102101199567.

40. Sapi E, et al. Characterization of biofilm formation by Borrelia burgdorferi in vitro. PloS One. 2012 Oct 24;7(10):e48277.

41. Körstgens V, et al. Influence of calcium ions on the mechanical properties of a model biofilm of mucoid Pseudomonas aeruginosa. Water Sci Technol. 2001;43(6):49-57.

42. Cavaliere R, et al. The biofilm matrix destabilizers, EDTA and DNaseI, enhance the susceptibility of nontypeable Hemophilus influenzae biofilms to treatment with ampicillin and ciprofloxacin. Microbiologyopen. 2014 Aug;3(4):557-67.

43. Robertson EJ, Wolf JM, Casadevall A. EDTA Inhibits Biofilm Formation, Extracellular Vesicular Secretion, and Shedding of the Capsular Polysaccharide Glucuronoxylomannan by Cryptococcus neoformans. Appl Environ Microbiol. 2012;78(22):7977-7984. doi:10. 1128 AEM.01953-12.

44. Hays RD, Spritzer KL, Schalet BD, Cella D. PROMIS®-29 v2.0 profile physical and mental health summary scores. Qual Life Res. 2018 Jul;27(7):1885-1891. doi: 10.1007/s11136-018-1842-3. Epub 2018 Mar 22. PMID: 29569016; PMCID: PMC5999556.

45. Citera M, Freeman PR, Horowitz RI. Empirical validation of the Horowitz Multiple Systemic Infectious Disease Syndrome Questionnaire for suspected Lyme disease. Int J Gen Med. 2017 Sep 4;10:249-273. doi: 10.2147/IJGM.S140224. PMID: 28919803; PMCID: PMC5590688.

46. Liu S, Cruz ID, Ramos CC, Taleon P, Ramasamy R, Shah J. Pilot Study of Immunoblots with Recombinant Borrelia burgdorferi Antigens for Laboratory Diagnosis of Lyme Disease. Healthcare (Basel). 2018 Aug 14;6(3):99. doi: 10.3390/healthcare6030 099. PMID: 30110913; PMCID: PMC6163603.

47. Jin C, Roen DR, Lehmann PV, Kellermann GH. An Enhanced ELISPOT Assay for Sensitive Detection of Antigen-Specific T Cell Responses to Borrelia burgdorferi. Cells. 2013 Sep 13;2(3):607-20. doi: 10.3390/cells20306 07. PMID: 24709800; PMCID: PMC3972671.

48. Stricker RB, Winger EE. Decreased CD57 lymphocyte subset in patients with chronic Lyme disease. Immunol Lett. 2001 Feb 1;76(1):43-8. doi: 10.1016/s0165-2478(00)003 16-3. PMID: 11222912.

49. Gossel G, Hogan T, Cownden D, Seddon B, Yates AJ. Memory CD4 T cell subsets are kinetically heterogeneous and replenished from naive T cells at high levels. Elife. 2017 Mar 10;6:e23013. doi: 10.7554/eLife.23013. PMID: 28282024; PMCID: PMC5426903.

50. Nielsen CM, White MJ, Goodier MR, Riley EM. Functional Significance of CD57 Expression on Human NK Cells and Relevance to Disease. Front Immunol. 2013 Dec 9;4:422. doi: 10.3389/fimmu.2013.00422. PMID: 2436 7364; PMCID: PMC3856678.

51. Kugeler KJ, Schwartz AM, Delorey MJ, Mead PS, Hinckley AF. Estimating the Frequency of Lyme Disease Diagnoses, United States, 2010-2018. Emerg Infect Dis. 2021 Feb;27(2):616-619. doi: 10.3201/eid270 2.202731. PMID: 33496229; PMCID: PMC7853543.

52. Young JD. Underreporting of Lyme disease. N Engl J Med. 1998 May 28;338(22):1629. doi: 10.1056/NEJM1998052 83382216. PMID: 9606127.

53. Centers for Disease Control and Prevention, National Center for Emerging and Zoonotic Infectious Diseases (NCEZID), Division of Vector-Borne Diseases (DVBD). 2022 Aug 9.

54. Talbot NC, Spillers NJ, Luther P, Flanagan C, Soileau LG, Ahmadzadeh S, Viswanath O, Varrassi G, Shekoohi S, Cornett EM, Kaye AM, Kaye AD. Lyme Disease and Post-treatment Lyme Disease Syndrome: Current and Developing Treatment Options. Cureus. 2023 Aug 8;15(8):e43112. doi: 10.7759/cureus.43112. PMID: 37692614; PMCID: PMC10483257.

55. Bobe JR, Jutras BL, Horn EJ, Embers ME, Bailey A, Moritz RL, Zhang Y, Soloski MJ, Ostfeld RS, Marconi RT, Aucott J, Ma'ayan A, Keesing F, Lewis K, Ben Mamoun C, Rebman AW, McClune ME, Breitschwerdt EB, Reddy PJ, Maggi R, Yang F, Nemser B, Ozcan A, Garner O, Di Carlo D, Ballard Z, Joung HA, Garcia-Romeu A, Griffiths RR, Baumgarth N, Fallon BA. Recent Progress in Lyme Disease and Remaining Challenges. Front Med (Lausanne). 2021 Aug 18;8:666554. doi: 10.3389/fmed.2021.666554. PMID: 344853 23; PMCID: PMC8416313.

56. Cameron DJ, Johnson LB, Maloney EL. Evidence assessments and guideline recommendations in Lyme disease: the clinical management of known tick bites, erythema migrans rashes and persistent disease. Expert Rev Anti Infect Ther. 2014 Sep;12(9):1103-35. doi: 10.1586/14787210. 2014.940900. Epub 2014 Jul 30. PMID: 25077519; PMCID: PMC4196523.

57. Christine J. Hastey, Kimberly J. Olsen, Rebecca A. Elsner, Sophia Mundigl, Giang Vu Vi Tran, Stephen W. Barthold, Nicole Baumgarth; Borrelia burgdorferi Infection–Induced Persistent IgM Secretion Controls Bacteremia, but Not Bacterial Dissemination or Tissue Burden. J Immunol 15 November 2023; 211 (10): 1540–1549. https://doi.org/10.4049/jimmunol.2300384