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Measurement of vitamin C concentrations in plasma from patients receiving cancer chemotherapy or immunotherapy

A 2018/2019 Summer Studentship research project

Vitamin C plays a fundamental role in many biochemical functions in all cells of the body. Preliminary data has suggested that cancer patients may consume suboptimal amounts of the vitamin and subsequently have suboptimal plasma levels. Data from animal studies has suggested that chemotherapy may reduce vitamin C levels. We hypothesise that patients with cancer which is metastatic or affecting the digestive tract may have lower ascorbate levels than those receiving adjuvant therapy. It has been established that plasma levels above 50 µM are adequate and below are inadequate, with levels below 23 µM described as hypovitaminosis C, and those below 11 µM as scurvy. This feasibility study will determine the prevalence of inadequate plasma vitamin C levels in patients undergoing chemotherapy or immunotherapy for cancer. It lays the groundwork for a larger clinical study, and the results may lead to clinical recommendations specifically for this group of people.

Student: Maria Nonis
Supervisors: Associate Gabi Dachs, Dr Matthew Strother, Dr Andrew Das, Professor Bridget Robinson, Professor Margreet Vissers
Sponsor: Cancer Society of New Zealand Canterbury/West Coast Division

Project brief

We are looking for a bright, enthusiastic medical student (ideally with a science background) to join our multidisciplinary cancer and biochemistry research groups. We have close links with the clinic and the proposed study forms an important part of our ongoing research.

Introduction

The role of vitamin C in cancer remains controversial, following initial conflicting results from clinical trials in the 1970s and 1980s. There are now a number of possible mechanisms by which vitamin C could play a role in cancer, and we have shown an association between low tumour vitamin C levels and a more aggressive tumour phenotype in a number of different cancer types. Tumour levels of vitamin C are largely determined by the levels of the vitamin in circulation. The data on vitamin C status of cancer patients is sparse, and data on treated patients even more so. A previous Summer Studentship (Dachs, Munn et al., NZMJ 2014) has shown that 80% of cancer patients do not consume the recommended daily intake of vitamin C, but plasma levels were not measured. We hypothesis that cancer patients undergoing chemotherapy may be at particular risk of vitamin C depletion.

Aim

The aim of this feasibility study is to measure plasma levels of vitamin C in patients who are undergoing chemotherapy or immunotherapy treatment for cancer.

Method

Patients undergoing chemotherapy or immunotherapy treatment at the Oncology Services, Christchurch Hospital, will be approached by the student and invited to take part in the study. Consented patients will answer a simple health questionnaire (diet, BMI, exercise), have weight, height, cancer diagnosis and stage, and chemotherapy / immunotherapy regimen recorded from their medical records, and provide a small blood sample (5ml). The blood sample will be rapidly processed for batched vitamin C analysis, which is measured using HPLC-EC (high performance liquid chromatography with electrochemical detection). The HPLC method of ascorbate measurement is well established in our group, is highly accurate and represents the international gold standard. We aim to recruit at least 60 patients to this study, which is feasible from our previous summer studentship data. Prevalence of inadequate vitamin C in this patient cohort will be determined and analyzed with respect to patient demographics, clinicopathological and treatment information.

Student researcher’s component of the study

The student will explain the study to potential participants, consent the patients, administer a simple questionnaire, rapidly transfer the blood tubes to the laboratory and process the plasma for analysis. The student will, with laboratory support, analyze the plasma samples for vitamin C content using HPLC-EC. The student will then assist with analysis according to age, gender, cancer diagnosis, stage and therapy. We anticipate there may be up to 10 patients who are on immunotherapy, so this analysis will be exploratory. Any findings would need confirming in a larger study.

This study is related to a second study (determining vitamin C in plasma samples from pre-surgical patients with cancer), and it is envisaged that the two students will work closely together on all aspects of the two studies.