Skip to main content

Total lymphocyte count in cancer patients with lymphopenia treated with intravenous vitamin C: Results of an observational study



Lymphopenia commonly occurs in cancer patients and predicts poor prognosis. It is caused by radio- and chemotherapy, with malnutrition and treatment-related oxidative stress playing key roles in its pathogenesis. Tumour-related morbidity is reported to be associated with reduced plasma ascorbate, which is a key physiological antioxidant and essential factor in immune function.


A prospective observational study was conducted on 48 cancer patients with lymphopenia (<1500/μL) to investigate the total lymphocyte count (TLC) during four weeks of elective adjuvant treatment with intravenous (iv) vitamin C 7.5 g (Pascorbin®7.5 g) once a week. TLC values at baseline (just prior to start of treatment) and after 4 weeks treatment were compared using descriptive statistics.


After 4 weeks iv vitamin C 7.5 g, TLC increased by a mean of 211/μL (p = 0.0018). Subgroup analyses showed that, in patients with severe lymphopenia (n = 25) (TLC <1000/μL), the increase in TLC was greater with a mean rise of 368/μL (p = 0.0004), than in patients (n = 23) with an initial TLC of 1000–1500 (mean rise of 40/μL) (p = 0.6105). TLC increased by at least 240/μL in half of the patients with severe lymphopenia and by more than 610/μL in 25% of patients.


Our data indicate that iv high-dose vitamin C treatment increases TLC, which strongly implies improvement of immune function, especially in patients with severe lymphopenia. Appropriately-powered, randomized, placebo-controlled trials of iv high-dose vitamin C are now needed to define more precisely its role in the treatment of cancer-related lymphopenia and how this impacts on the patients’ clinical prognosis.


Severe treatment-related hematological toxicities, such as lymphopenia, occur commonly in many cancers [1]. Drastically reduced TLC increases the risk of various forms of infections [2]. Recent studies reveal an association of post-treatment lymphopenia and decreased survival in patients with solid tumours who underwent chemo- or radiotherapy [1, 35]. Adjuvant treatment options are needed to restore this reversible prognostic factor.

Ascorbate, the absorbed form of dietary vitamin C, is an essential factor for immune cells and enhances the immune system in many ways [6, 7]. It enhances leukocyte function and innate immune responses via modulation of chemokinesis and chemotaxis [8]. Leukocytes actively accumulate ascorbate to achieve intracellular concentrations that exceed plasma concentrations by up to 80-fold [9].

Cancer patients are often reported to be vitamin C deficient [10,11,12,13,14,15,16,17,18]. Particularly serious are the deficiencies in patients with advanced cancer [15, 19, 20], where decreased plasma ascorbate levels are associated with shorter survival and impaired quality of life [21].

Intravenous (iv) instead of oral administration of ascorbate is required in order to achieve the high plasma concentrations [22] that have been shown to have potential therapeutic effects [23, 24]. Ten years ago, high dose vitamin C (as sodium ascorbate) was found to have selective tumour cytotoxic effects [25] and its chemotherapeutic potential is still undergoing investigation [26]. Several phase I/IIa studies examined the chemotherapeutic effects of iv high-dose vitamin C as an adjuvant to standard treatment in patients with advanced tumours [27,28,29]. Another potential benefit of iv vitamin C treatment is the favourable effect on the quality of life of cancer patients [30,31,32]. Although iv high dose vitamin C is a popular complementary treatment in the management of cancer conditions [23, 24, 33], there is, as far as we are aware, no published data on its effects on lymphopenia.

The aim of this observational study was the evaluation of the effects of iv high-dose vitamin C on lymphopenia in cancer patients.


The objective of this prospective observational study was to document the use of Pascorbin® 7.5 g (licensed, proprietary medicinal product containing 7.5 g ascorbate for iv infusion; license owner: Pascoe Pharmazeutische Präparate GmbH, Germany) in patients with advanced cancer and lymphopenia, and to monitor its effect on their TLC. Data were collected from those cancer patients attending the ambulatory service of the Clinical Nutrition Department at SOLCA Cancer Hospital, Guayaquil, Ecuador, from February 2012 to October 2014, and who received elective iv ascorbate treatment as an adjuvant to tumour therapy. It was the physicians’ decision to use the infusion in accordance to the indication as an adjuvant to tumour therapy with the aims of to speed up postoperative recovery, to reduce the side effects of conventional oncological therapy (such as chemotherapy, radiotherapy), to reduce periods of hospitalization, to prolong the tumour- and recurrence-free intervals and to improve quality of life. As lymphopenia is a chemotherapy or radiation related hematological side effect, the treatment with iv vitamin C is covered by the approved indication.

The study included 48 cancer patients (aged ≥18 years) with lymphopenia, defined as a TLC below 1500/μL blood [2, 34]. Diagnosis of cancer was previously confirmed and documented by the attending physician. Malignant neoplasm of cervix uteri (n = 11) was the most common (22.9%) cancer documented in the study group, followed by breast cancer (14.6%), with between 2.1 and 8.3% for other cancer types. The study was a non-interventional study aimed to document the routine clinical use of iv vitamin C. Patients agreed, in a signed statement, to study participation and to release of their data. The criteria for patient selection are listed in Table 1.

Table 1 Patient data eligibility criteria

Once a week, patients received iv vitamin C 7.5 g (Pascorbin®), diluted in a suitable carrier solution, such as 100 mL NaCL 0.9%. Data were collected before the start of vitamin C treatment (visit 1, baseline) and after 4 weeks of treatment.

Total lymphocyte count (TLC)

The main study parameter was the change in TLC from baseline to 4 weeks. A quantitative multi-parameter automated hematology analyser (xn 3000 series, sysmex) was used for all patients to measure TLC in peripheral blood samples obtained by venipuncture. The one-sample t-test (two-sided, with α = 0.05) was used to test for significance of the mean change. Additional, separate analyses were carried out on data from patients with TLC of <1000/μL (severe lymphopenia) and patients with TLCs of 1000–1500 lymphocytes/μL before start of treatment. The statistical analyses were performed by an independent statistician.

Nutritional status

Due to the lack of an universally accepted definition of malnutrition, our classification of the nutrition status (Table 2) is based on a combination of patient’s body mass index (BMI) [35] together with a scored Patient-Generated Subjective Global Assessment (PG-SGA) [36], and the Nutritional Risk Screening (NRS) [37]. The BMI allows us to classify overweight or obese patients. Risk of malnutrion (BMI < 20.5) is defined by NRS and the combination of BMI with the PG-SGA allows us to differentiate further to mild, moderate or severe malnutrition.

Table 2 Baseline demographic and clinical characteristics of patients

The safety of the vitamin C treatment was assessed by the attending physician in terms of adverse events and possible relatedness of such events to vitamin C treatment.


A total of 48 patients (mean ± standard deviation of age, 56.4 ± 15.7 years; 79.2% female) with previously confirmed neoplasms were included in the study and all were included in our analysis. Of note, more than half of the patients (60.4%) displayed moderate or severe malnutrition (Table 2). The mean TLC increased significantly (p = 0.0018) from 902.0/μL (±414/μL) at baseline to 1113/μl (±466/μL) after 4 weeks treatment. This was a mean increase in TLC of 211/μL (±442/μL). In patients with <1000 lymphocytes/μL (severe lymphopenia), the mean increase at 4 weeks was 368/μL (±449/μL) (p = 0.0004) compared to an increase of 40/μL (±372/μL) (p = 0.6105) in patients with an initial TLC of 1000–1500 lymphocytes/μL (n = 23) (Table 3).

Table 3 Total lymphocytes count (TLC) at start and at end of treatment

Patients in our study group who were at risk of malnutrition or mild malnutrition had initial TLC values of >1000/μL (mean TLC 1046.9/μL and 1270.0/μL, respectively), whereas the initial mean TLC in patients with moderate or severe malnutrition was <1000/μL (846.5/μL and 774.2/μL, respectively) (Table 4, Fig. 1). TLC at begin and at end of treatment for each patient are available in Table 5.

Table 4 Mean total lymphocytes counts (TLC) for patients of differing nutritional status
Fig. 1
figure 1

Total lymphocytes count (TLC) before and after 4-week iv high-dose vitamin C treatment. The Box Plot displays the data of the study group with initial TLC < 1000 μL. Vertical bar indicates standard deviation, box indicates 25%, median, 75% percentile

Table 5 TLC at begin and end of treatment for each patient

In the study group, no adverse effects related to iv vitamin C were observed.


Our non-interventianal study provides evidence that iv high-dose vitamin C reverses lymphopenia in cancer patients. We included radiotherapy- or chemotherapy-treated cancer patients with a TLC of <1500/μL, which was our definition of lymphopenia [2]. The data indicated a significant increase in the mean TLC value for the whole group while a subgroup analysis revealed a more significant effect in patients with a TLC of <1000/μL.

Several published reports suggest that lymphopenia is a reversible, predictive factor for earlier tumour progression/relapse and reduced survival, as indicated in several retrospective studies [3,4,5, 38, 39]. Poor prognosis of cancer patients is indicated by a TLC value of <1000/μL [39] [38] and is more evident with TLC values of <500/μL [3, 5]. More than 35% of our patients with an initial mean TLC of 551/μL (±212) had a TLC of >1000/μL after 4 weeks of iv vitamin C treatment. Given the increased risk of progression and mortality in severe lymphopenia, a TLC increase to >1000/μL is a clinically relevant and significant improvement.

The reasons for lymphopenia can be diverse [40]. In our study group, it is presumably lymphocyte depletion primarily due to radiotherapy and chemotherapy [40]. Severe stress, malnutrition and protein-energy under-nutrition can also cause lymphopenia [2]. Moderate-to-severe malnutrition was evident in more than half of the patients (60.4%) in our study group and was probably a contributory factor to the lymphopenia. The small size of our study group may explain the absence of statistical significance of any association between nutritional status and lymphocyte counts at the start of treatment. However, we did observe a correlation between risk of malnutrition and lymphopenia in our study group (Table 4 and Fig. 1).

The beneficial effect of iv vitamin C on TLC values in cancer patients is most likely due to its antioxidant actions counteracting treatment-induced oxidative stress. This was also suggested to explain the positive clinical effects of iv high-dose vitamin C observed in other cancer patients [29, 30, 41]. Oxidative stress is considered to be an underlying cause of lymphopenia of different etiologies [42], such as that caused by intensive exercise [43], end-stage renal disease patients [44] and AZT (3′-azido-2′,3′-dideoxythimidine) (an AIDS treatment). This notion is supported by animal data showing that high-dose antioxidants abrogate experimentally-induced lymphopenia [45].

A contributory factor for the favourable effect of vitamin C could be its function as a cofactor in the synthesis carnitine [46], which supports immune cell function, s predominantly through carnitine-dependent energy metabolism of fatty acids. Carnitine deficiency has been demonstrated in patients with impaired immune responses [47]. The ability of vitamin C to increase endogen carnitine synthesis and thereby improving energy metabolism is supported by animal data [46].

The supportive effect of iv vitamin C on the immune system that we have observed is supported by other published findings (such as, stimulation of natural killer cell activity by high dose vitamin C [48]). Furthermore, our data may relate to the increased quality of life and prolonged survival time observed in in phase I/IIa clinical trials of cancer patients treated with iv vitamin C [28, 29].

Intravenous high-dose vitamin C treatment was well tolerated by our patients, which is consistent with data from other clinical studies and comprehensive clinical surveys indicating the good tolerability of iv high-dose vitamin C up to 0.5 g/kg body weight (in phase-I-trials even up to 1.5 g/kg) when contraindications are complied with [23, 27, 33, 49, 50].

As we are aware, our study provides the first evidence that iv high-dose vitamin C treatment improves the immune status of cancer patients treated in daily clinical practice, and that the treatment is well-tolerated by this patient group. However, the clinical interpretation of our data is limited by the absence of a control group and the small size of our study group.


This study provides “real-life” observational evidence of the use of iv high-dose vitamin C in daily practice in the treatment of cancer patients with lymphopenia. Patients with severe lymphopenia seem to particularly benefit from iv vitamin C with a clinically significant increase in TLC. Appropriately-powered, randomized, placebo-controlled trials of iv high-dose vitamin C are now needed to define more precisely its role in the treatment of cancer-related lymphopenia and how this impacts on the patients’ clinical prognosis.





Non-interventional stud


Total lymphocyte count


  1. Grossman SA, Ellsworth S, Campian J, Wild AT, Herman JM, Laheru D, Brock M, Balmanoukian A, Ye X. Survival in patients with severe lymphopenia following treatment with radiation and chemotherapy for newly diagnosed solid tumors. J Natl Compr Cancer Netw. 2015;13(10):1225–31.

    CAS  Google Scholar 

  2. Merck Manual: Lymphocytopenia - Hematology and Oncology - Merck Manuals Professional Edition. [].

  3. Wild AT, Ye X, Ellsworth SG, Smith JA, Narang AK, Garg T, Campian J, Laheru DA, Zheng L, Wolfgang CL, et al. The association between chemoradiation-related lymphopenia and clinical outcomes in patients with locally advanced pancreatic adenocarcinoma. Am J Clin Oncol. 2015;38(3):259–65.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Wu ES, Oduyebo T, Cobb LP, Cholakian D, Kong X, Fader AN, Levinson KL, Tanner EJ, 3rd, Stone RL, Piotrowski A, et al. Lymphopenia and its association with survival in patients with locally advanced cervical cancer. Gynecol Oncol. 2016;140(1):76–82.

  5. Campian JL, Sarai G, Ye X, Marur S, Grossman SA. Association between severe treatment-related lymphopenia and progression-free survival in patients with newly diagnosed squamous cell head and neck cancer. Head Neck. 2014;36(12):1747–53.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Panush RS, Delafuente JC. Vitamins and immunocompetence. World Rev Nutr Diet. 1985;45:97–132.

    Article  CAS  PubMed  Google Scholar 

  7. Strohle A, Hahn A. Vitamin C and immune function. Med Monatsschr Pharm. 2009;32(2):49–54. quiz 55–46.

    PubMed  Google Scholar 

  8. Schwager J, Bompard A, Weber P, Raederstorff D. Ascorbic acid modulates cell migration in differentiated HL-60 cells and peripheral blood leukocytes. Mol Nutr Food Res. 2015;59(8):1513–23.

    Article  CAS  PubMed  Google Scholar 

  9. Moser U. Uptake of ascorbic acid by leukocytes. Ann N Y Acad Sci. 1987;498:200–15.

    Article  CAS  PubMed  Google Scholar 

  10. Abou-Seif MA, Rabia A, Nasr M. Antioxidant status, erythrocyte membrane lipid peroxidation and osmotic fragility in malignant lymphoma patients. Clin Chem Lab Med. 2000;38(8):737–42.

  11. Neyestani TR, Fereydouni Z, Hejazi S, Salehi-Nasab F, Nateghifard F, Maddah M, Karandish M. Vitamin C status in Iranian children with acute lymphoblastic leukemia: evidence for increased utilization. J Pediatr Gastroenterol Nutr. 2007;45(1):141–4.

    Article  PubMed  Google Scholar 

  12. Chevion S, Or R, Berry EM. The antioxidant status of patients subjected to total body irradiation. Biochem Mol Biol Int. 1999;47(6):1019–27.

    CAS  PubMed  Google Scholar 

  13. Tsai SM, Lin SK, Lee KT, Hsiao JK, Huang JC, Wu SH, Ma H, Wu SH, Tsai LY. Evaluation of redox statuses in patients with hepatitis B virus-associated hepatocellular carcinoma. Ann Clin Biochem. 2009;46(Pt 5):394–400.

    Article  CAS  PubMed  Google Scholar 

  14. Sakhi AK, Russnes KM, Thoresen M, Bastani NE, Karlsen A, Smeland S, Blomhoff R. Pre-radiotherapy plasma carotenoids and markers of oxidative stress are associated with survival in head and neck squamous cell carcinoma patients: a prospective study. BMC Cancer. 2009;9:458.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Mahdavi R, Faramarzi E, Seyedrezazadeh E, Mohammad-Zadeh M, Pourmoghaddam M. Evaluation of oxidative stress, antioxidant status and serum vitamin C levels in cancer patients. Biol Trace Elem Res. 2009;130(1):1–6.

    Article  CAS  PubMed  Google Scholar 

  16. Surapaneni KM, Ramana V. Erythrocyte ascorbic acid and plasma vitamin E status in patients with carcinoma of prostate. Indian J Physiol Pharmacol. 2007;51(2):199–202.

    CAS  PubMed  Google Scholar 

  17. Esme H, Cemek M, Sezer M, Saglam H, Demir A, Melek H, Unlu M. High levels of oxidative stress in patients with advanced lung cancer. Respirology. 2008;13(1):112–6.

    Article  PubMed  Google Scholar 

  18. Al-Gayyar MM, Eissa LA, Rabie AM, El-Gayar AM. Measurements of oxidative stress status and antioxidant activity in chronic leukaemia patients. J Pharm Pharmacol. 2007;59(3):409–17.

    Article  CAS  PubMed  Google Scholar 

  19. Shah FD, Patel JB, Shukla SN, Shah PM, Patel PS. Evaluation of plasma non-enzymatic antioxidants in breast cancer etiology. Asian Pac J Cancer Prev. 2009;10(1):91–6.

    PubMed  Google Scholar 

  20. Marcus SL, Petrylak DP, Dutcher JP, Paietta E, Ciobanu N, Strauman J, Wiernik PH, Hutner SH, Frank O, Baker H. Hypovitaminosis C in patients treated with high-dose interleukin 2 and lymphokine-activated killer cells. Am J Clin Nutr. 1991;54(6 Suppl):1292S–7.

    CAS  PubMed  Google Scholar 

  21. Mayland CR, Bennett MI, Allan K. Vitamin C deficiency in cancer patients. Palliat Med. 2005;19(1):17–20.

    Article  PubMed  Google Scholar 

  22. Levine M, Rumsey SC, Daruwala R, Park JB, Wang Y. Criteria and recommendations for vitamin C intake. JAMA. 1999;281(15):1415–23.

    Article  CAS  PubMed  Google Scholar 

  23. 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.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Levine M, Padayatty SJ, Espey MG. Vitamin C: concentration- function approach yields pharmacology and therapeutic discoveries. Adv Nutr. 2011;2:78–88.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Chen Q, Espey MG, Krishna MC, Mitchell JB, Corpe CP, Buettner GR, Shacter E, Levine M. Pharmacologic ascorbic acid concentrations selectively kill cancer cells: action as a pro-drug to deliver hydrogen peroxide to tissues. Proc Natl Acad Sci. USA 2005;102(38):13604–609.

  26. Yun J, Mullarky E, Lu C, Bosch KN, Kavalier A, Rivera K, Roper J, Chio II, Giannopoulou EG, Rago C, et al. Vitamin C selectively kills KRAS and BRAF mutant colorectal cancer cells by targeting GAPDH. Science. 2015;350(6266):1391–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Monti DA, Mitchell E, Bazzan AJ, Littman S, Zabrecky G, Yeo CJ, Pillai MV, Newberg AB, Deshmukh S, Levine M. Phase I evaluation of intravenous ascorbic acid in combination with gemcitabine and erlotinib in patients with metastatic pancreatic cancer. PLoS One. 2012;7(1):e29794.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Welsh JL, Wagner BA, van’t Erve TJ, Zehr PS, Berg DJ, Halfdanarson TR, Yee NS, Bodeker KL, Du J, Roberts 2nd LJ, et al. Pharmacological ascorbate with gemcitabine for the control of metastatic and node-positive pancreatic cancer (PACMAN): results from a phase I clinical trial. Cancer Chemother Pharmacol. 2013;71(3):765–75.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Ma Y, Chapman J, Levine M, Polireddy K, Drisko J, Chen Q. High-dose parenteral ascorbate enhanced chemosensitivity of ovarian cancer and reduced toxicity of chemotherapy. Sci Transl Med. 2014;6(222):222ra218.

    Article  Google Scholar 

  30. Vollbracht C, Schneider B, Leendert V, Weiss G, Auerbach L, Beuth J. Intravenous vitamin C administration improves quality of life in breast cancer patients during chemo-/radiotherapy and aftercare: results of a retrospective, multicentre, epidemiological cohort study in Germany. In Vivo. 2011;25(6):983–90.

    CAS  PubMed  Google Scholar 

  31. Yeom CH, Jung GC, Song KJ. Changes of terminal cancer Patients’ health-related quality of life after high dose vitamin C administration. J Korean Med Sci. 2007;22(1):7–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Takahashi H, Mizuno H, Yanagisawa A. High-dose intravenous vitamin C improves quality of life in cancer patients. Personal Med Univ. 2012;1:49–53.

    Article  CAS  Google Scholar 

  33. Mikirova N, Casciari J, Riordan N, Hunninghake R. Clinical experience with intravenous administration of ascorbic acid: achievable levels in blood for different states of inflammation and disease in cancer patients. J Transl Med. 2013;11(1):191.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Berezne A, Bono W, Guillevin L, Mouthon L. Diagnosis of lymphocytopenia. Presse Med. 2006;35(5 Pt 2):895–902.

    Article  PubMed  Google Scholar 

  35. BMI classification [].

  36. Bauer J, Capra S, Ferguson M. Use of the scored Patient-Generated Subjective Global Assessment (PG-SGA) as a nutrition assessment tool in patients with cancer. Eur J Clin Nutr. 2002;56(8):779–85.

    Article  CAS  PubMed  Google Scholar 

  37. Kondrup J, Rasmussen HH, Hamberg O, Stanga Z. Nutritional risk screening (NRS 2002): a new method based on an analysis of controlled clinical trials. Clin Nutr (Edinburgh, Scotland). 2002;22(3):321–36.

    Article  Google Scholar 

  38. Wei X, Wei Y, Huang F, Jing H, Xie M, Hao X, Feng R. Lymphopenia predicts preclinical relapse in the routine follow-up of patients with diffuse large B-cell lymphoma. Leuk Lymphoma. 2015;56(5):1261–5.

    Article  CAS  PubMed  Google Scholar 

  39. Feng JF, Liu JS, Huang Y. Lymphopenia predicts poor prognosis in patients with esophageal squamous cell carcinoma. Medicine. 2014;93(27):e257.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Regent A, Kluger N, Berezne A, Lassoued K, Moutho L. Lymphocytopenia: aetiology and diagnosis, when to think about idiopathic CD4(+) lymphocytopenia? Rev Med Interne. 2012;33(11):628–34.

    Article  CAS  PubMed  Google Scholar 

  41. Carr AC, Vissers MC, Cook J. Relief from cancer chemotherapy side effects with pharmacologic vitamin C. N Z Med J. 2014;127(1388):66–70.

    PubMed  Google Scholar 

  42. Tanimura Y, Shimizu K, Tanabe K, Otsuki T, Yamauchi R, Matsubara Y, Iemitsu M, Maeda S, Ajisaka R. Exercise-induced oxidative DNA damage and lymphocytopenia in sedentary young males. Med Sci Sports Exerc. 2008;40(8):1455–62.

    Article  CAS  PubMed  Google Scholar 

  43. Kruger K, Mooren FC. Exercise-induced leukocyte apoptosis. Exerc Immunol Rev. 2014;20:117–34.

    PubMed  Google Scholar 

  44. Pernice F, Floccari F, Nostro L, Caccamo C, Belghity N, Mantuano S, Romeo A, Barilla A, Aloisi C, Ruello A, et al. Oxidative stress, sister chromatid exchanges and apoptosis in the pathogenesis of lymphocytopenia in ESRD patients. J Nephrol. 2006;19(5):613–20.

    CAS  PubMed  Google Scholar 

  45. Garcia-de-la-Asuncion J, Gomez-Cambronero LG, Del Olmo ML, Pallardo FV, Sastre J, Vina J. Vitamins C and E prevent AZT-induced leukopenia and loss of cellularity in bone marrow. Studies in mice. Free Radic Res. 2007;41(3):330–4.

    Article  CAS  PubMed  Google Scholar 

  46. Otsuka M, Matsuzawa M, Ha TY, Arakawa N. Contribution of a high dose of L-ascorbic acid to carnitine synthesis in guinea pigs fed high-fat diets. J Nutr Sci Vitaminol. 1999;45(2):163–71.

    Article  CAS  PubMed  Google Scholar 

  47. Famularo G, De Simone C, Trinchieri V, Mosca L. Carnitines and its congeners: a metabolic pathway to the regulation of immune response and inflammation. Ann N Y Acad Sci. 2004;1033:132–8.

    Article  CAS  PubMed  Google Scholar 

  48. Toliopoulos IK, Simos YV, Daskalou TA, Verginadis II, Evangelou AM, Karkabounas SC. Inhibition of platelet aggregation and immunomodulation of NK lymphocytes by administration of ascorbic acid. Indian J Exp Biol. 2011;49(12):904–8.

    CAS  PubMed  Google Scholar 

  49. Hoffer LJ, Levine M, Assouline S, Melnychuk D, Padayatty SJ, Rosadiuk K, Rousseau C, Robitaille L, Miller Jr WH. Phase I clinical trial of i.v. ascorbic acid in advanced malignancy. Ann Oncol. 2008;19(11):1969–74.

    Article  CAS  PubMed  Google Scholar 

  50. Nielsen TK, Hojgaard M, Andersen JT, Poulsen HE, Lykkesfeldt J, Mikines KJ. Elimination of ascorbic acid after high-dose infusion in prostate cancer patients: a pharmacokinetic evaluation. Basic Clin Pharmacol Toxicol. 2015;116(4):343–8.

    Article  CAS  PubMed  Google Scholar 

Download references


The authors thank Professor Gerard Patrick McGregor PhD (OmniScience SA) for his scientific editing of the manuscript.


Laboratory determination of TLC was part of routine labor. Charges for the independent statistician and the language editing service as well as the article-processing charge for the open-access journal were sponsored by Pascoe Natural Medicine, Germany.

Availability of data and materials

TLC at begin and at end of treatment for each patient are available in Table 5 without patient number, because of data protection purposes.

Authors’ contributions

DRV conceived and initiated the study and carried out data evaluation. GTM, MMV, and SHM participated in study design, coordination and data evaluation. CV drafted the manuscript and participated in data evaluation. All authors read and approved the final manuscript. The statistical analyses were performed by an independent statistician (Gesellschaft für Therapieforschung mbH,, Munich, Germany).

Competing interests

DRV, GTM, MMV, and SHM declare that they have no competing interests and received no funding for this observational study. CV is employed by Pascoe Pharmazeutische Präparate GmbH (Giessen, Germany).

Consent for publication

Not applicable.

Ethics approval and consent to participate

The objective of this prospective observational study was to document the use of an authorized medicinal product. Data were collected from those cancer patients who received elective iv ascorbate treatment as an adjuvant to tumour therapy (non-interventional study; NIS). Because this type of study documents the effects of medical routine without given intervention an ethics committee vote is not necessary. According to the ICMJE definition of a clinical trial purely observational studies (those in which the assignment of the medical intervention is not at the discretion of the investigator) will not require registration.

Patients agreed with the study participation and data processing, which was assured by a signed statement.

Author information

Authors and Affiliations


Corresponding author

Correspondence to Dolores Margarita Rodríguez.

Rights and permissions

Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (, which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Rodríguez, D.M., Guerrero, M.E., Maldonado, B.M. et al. Total lymphocyte count in cancer patients with lymphopenia treated with intravenous vitamin C: Results of an observational study. transl med commun 2, 3 (2017).

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: