SunGold Kiwifruit Consumption Restores Adequate to Optimal Vitamin C Status in People with a History of Severe Respiratory Infections.

Severe respiratory infections are characterised by depleted vitamin C and elevated inflammation and oxidative stress. The aim of this study was to recruit people with a history of severe respiratory infections to undergo a six-week intervention with SunGold kiwifruit to determine if this could restore adequate vitamin C status. Secondary outcomes included changes in inflammatory and oxidative stress biomarkers, self-reported fatigue and subjective mood, and the incidence, duration and severity of respiratory symptoms. The total cohort comprised 20 adults (65% female, age range 31-84 years). The participants had a low median fruit and vegetable intake of 2.3 servings/day and a correspondingly low vitamin C intake of 46 mg/day. Circulating vitamin C status was a median of 45 µmol/L and was in the hypovitaminosis range in 25% of the cohort. Following intervention with two SunGold kiwifruit/day (equivalent to ~300 mg vitamin C), there was an increase in plasma vitamin C concentrations to >60 µmol/L (p < 0.05). Approximately 20% of the participants were unable to reach adequate vitamin C status (≥50 µmol/L), possibly due to current smoking, which enhances vitamin C turnover, and a strong inverse correlation between body weight and vitamin C status (r = -0.734, p < 0.05). Following the intervention, there were indications towards decreases in the inflammatory biomarkers C-reactive protein and TNFα (p > 0.05), but no changes in oxidative stress biomarkers (F2isoprostanes, protein carbonyls). There were decreases in fatigue and depression (p < 0.05) and a lower number of individual respiratory symptoms reported during the kiwifruit intervention phase (8.5 vs. 10, p = 0.05). Overall, the consumption of two SunGold kiwifruit per day for six weeks was able to restore adequate to saturating vitamin C status in ~80% of the participants. Smokers and people with higher body weight may need larger doses and/or longer duration of supplementation. The contribution of vitamin C to reducing fatigue, depression, and number of respiratory symptoms warrants further investigation.

Factors Affecting the Vitamin C Dose-Concentration Relationship: Implications for Global Vitamin C Dietary Recommendations.

Vitamin C status is known to be associated with several demographic and lifestyle factors. These include gender, age, ethnicity, pregnancy/lactation, body weight, smoking status and dietary habits. In the present study, our aim was to investigate the National Health and Nutrition Examination Survey (NHANES) 2017-2018 datasets to assess the impact of these factors on vitamin C dose-concentration relationships to establish if there are higher requirements for vitamin C in certain subpopulations, and the possible extent of these additional requirements. The final cohort comprised 2828 non-supplementing adult males and females (aged 18-80+ years) with both vitamin C serum concentrations and dietary intake data available. The data were subsequently stratified by gender, age tertiles (≤36, 37-58, ≥59 years), ethnicity (non-Hispanic white, non-Hispanic black, and total Hispanic), socioeconomic tertiles (poverty income ratios: ≤1.35, 1.36-3.0, >3.0), weight tertiles (<72, 72-91, >91 kg), BMI tertiles (<26, 26-32, >32 kg/m2) and smoking status. Sigmoidal (four parameter logistic) curves with asymmetrical 95% confidence intervals were fitted to the dose-concentration data. We found that males required vitamin C intakes ~1.2-fold higher than females to reach 'adequate' serum vitamin C concentrations of 50 µmol/L. Males had both higher body weight and a higher prevalence of smoking than females. Smokers required vitamin C intakes ~2.0-fold higher than non-smokers to reach adequate vitamin C concentrations. Relative to adults in the lighter weight tertile, adults in the heavier weight tertile required ~2.0-fold higher dietary intakes of vitamin C to reach adequate serum concentrations. We did not observe any impact of ethnicity or socioeconomic status on the vitamin C dose-concentration relationship, and although no significant difference between younger and older adults was observed at vitamin C intakes > 75 mg/day, at intakes < 75 mg/day, older adults had an attenuated serum response to vitamin C intake. In conclusion, certain demographic and lifestyle factors, specifically gender, smoking and body weight, have a significant impact on vitamin C requirements. Overall, the data indicate that the general population should consume ~110 mg/day of vitamin C to attain adequate serum concentrations, smokers require ~165 mg/day relative to non-smokers, and heavier people (100+ kg) require ~155 mg/day to reach comparable vitamin C concentrations. These findings have important implications for global vitamin C dietary recommendations.

Inflammation and Vitamin C in Women with Prenatal Depression and Anxiety: Effect of Multinutrient Supplementation.

Elevated inflammation has been associated with adverse mood states, such as depression and anxiety, and antioxidant nutrients, such as vitamin C, have been associated with decreased inflammation and improved mood. In the current study comprising a cohort of pregnant women with depression and anxiety, we hypothesised that elevated inflammation would be associated with adverse mood states and inversely associated with vitamin C status and that multinutrient supplementation would optimise vitamin concentrations and attenuate inflammation. Sixty-one participants from the NUTRIMUM trial had blood samples collected between 12 and 24 weeks gestation (baseline) and following 12 weeks of daily supplementation with a multinutrient formula containing 600 mg of vitamin C or active placebo. The samples were analysed for inflammatory biomarkers (C-reactive protein (CRP) and cytokines) and vitamin C content and were related to scales of depression and anxiety. Positive correlations were observed between interleukin-6 (IL-6) and all of the mood scales administered (p < 0.05), including the Edinburgh Postnatal Depression Scale, the Clinical Global Impressions-Severity Scale, the Montgomery and Åsberg Depression Rating Scale, the Depression Anxiety Stress Scale 21, and the Generalized Anxiety Disorder-7 (GAD-7). CRP correlated weakly with GAD-7 (p = 0.05). There was an inverse correlation between CRP and the vitamin C status of the cohort (p = 0.045), although there was no association of the latter with the mood scales (p > 0.05). Supplementation with the multinutrient formula resulted in a significant increase in the vitamin C status of the cohort (p = 0.007) but did not affect the inflammatory biomarker concentrations (p > 0.05). In conclusion, greater systemic inflammation was associated with worse mood states; however, 12-week multinutrient supplementation did not alter inflammatory biomarker concentrations. Nevertheless, the vitamin C status of the cohort was improved with supplementation, which may aid pregnancy and infant outcomes.

Does Aging Affect Vitamin C Status Relative to Intake? Findings from NHANES 2017-2018.

The aging population is growing and fueling a global increase in chronic diseases and healthcare expenditure. In this study, we examine vitamin C dose-concentration relationships based on data from the National Health and Nutrition Examination Survey (NHANES) 2017-2018 to identify a possible age-dependent change in intake vs. concentration relationship among non-supplemented individuals (n = 2828). The vitamin C intake was similar between the younger (18-36 years), middle (37-58 years) and older (59-80+ years) age groups; however, circulating vitamin C concentrations were significantly lower in the middle and older age groups (p < 0.001). For intakes above 75 mg/day, no significant difference in the intake vs. serum concentration relationship was identified between younger and older individuals. However, for intakes below 75 mg/day, we found significantly lower serum concentrations relative to intake for the older compared to younger individuals, despite smoking being more prevalent in the younger compared to older adults (p < 0.001). This effect persisted among non-smokers and was further exacerbated by smoking in older people. Collectively, the present study suggests that healthy aging in non-institutionalized individuals does not increase requirements for vitamin C. In contrast, the lower serum concentrations relative to intake observed in older individuals at intakes < 75 mg/day may suggest that older individuals are more sensitive to a low vitamin C intake, perhaps due to the increased impact of long-term smoking and increased chronic disease prevalence in older adults. This finding may have implications for future intake guidelines in countries with low RDAs and for WHO/FAO, but requires further investigation.

Vitamin C - a scoping review for Nordic Nutrition Recommendations 2023.

Vitamin C has multiple metabolic functions in the body, but the available information on the exact relationship between these functions and the intake necessary to maintain them is very limited. However, most attempts to objectively measure adequacy of vitamin C status, including, for example, replacement of metabolic turnover, chronic disease prevention, urinary excretion, and saturation of immune cells and body compartment, currently point toward 50 µmol/L as a reasonable target plasma concentration. As a strong correlation between body weight and vitamin C status exists, recommended intakes (RIs) for other age groups may be extrapolated from the adult RI based on weight. However, as body weights above 70 kg are becoming increasingly common - also in the Nordic region - an RI of 140 mg/day for individuals weighing 100 kg or more should be considered to compensate for the larger volume of distribution. Finally, smoking continues to be a common contributor to poor vitamin C status; therefore, it is proposed that people who smoke increase their daily vitamin C intake by 40 mg/day to compensate for the increased metabolic turnover induced by smoking.

Supplementation with Oral Vitamin C Prior to and during Myeloablative Chemotherapy and Autologous Haematopoietic Stem Cell Transplantation: A Pilot Study.

Chemotherapy-related side effects are common in patients undergoing myeloablative chemotherapy and haematopoietic stem cell transplantation. Some, such as oral mucositis, are believed to be due to enhanced oxidative stress and inflammation. Vitamin C, a potent antioxidant with anti-inflammatory properties, becomes severely depleted following myeloablative chemotherapy. The aim of our study was to assess the feasibility and efficacy of oral vitamin C supplementation to restore and maintain adequate vitamin C concentrations in patients undergoing myeloablative chemotherapy and stem cell transplantation. We carried out a pilot randomized controlled trial in 20 patients with myeloma and lymphoma. Placebo or vitamin C tablets (1 g twice daily) were initiated one week prior to transplantation and continued for 4 weeks post-transplantation. Blood samples were collected weekly for analysis of plasma vitamin C concentrations using high-performance liquid chromatography. The patients' symptoms and quality of life parameters were monitored using the World Health Organization oral toxicity scale and the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ). Pre-supplementation with oral vitamin C doubled vitamin C concentrations relative to placebo by day 0 (median 61 vs. 31 µmol/L), with 60% of those in the vitamin C group achieving concentrations ≥ 50 µmol/L, compared with only 10% in the placebo group. Following chemotherapy and transplantation, significance between the vitamin C and placebo groups was lost by day 7, with only 30% of the patients in the vitamin C group having plasma concentrations ≥ 50 µmol/L. This was partly due to intolerance of the oral intervention due to nausea/vomiting and diarrhoea (40% of the participants in each group). Oral mucositis was also observed in 40% of the participants at day 7 or 14. Overall, our study showed that whilst short-term oral vitamin C pre-supplementation was able to restore adequate vitamin C status by day 0, ongoing supplementation could not maintain adequate vitamin C concentrations following chemotherapy and transplantation. Thus, intravenous vitamin C should be trialled as this bypasses the gastrointestinal system, negating intolerance issues and improving bioavailability of the vitamin.

Estimation of Vitamin C Intake Requirements Based on Body Weight: Implications for Obesity.

Higher body weight is known to negatively impact plasma vitamin C status. However, despite this well-documented inverse association, recommendations on daily vitamin C intakes by health authorities worldwide do not include particular reference values for people of higher body weight. This suggests that people of higher body weight and people with obesity may be receiving insufficient vitamin C in spite of ingesting the amounts recommended by their health authorities. The current preliminary investigation sought to estimate how much additional vitamin C people with higher body weights would need to consume in order to attain a comparable vitamin C status to that of a lower weight person consuming an average Western vitamin C intake. Data from two published vitamin C dose-concentration studies were used to generate the relationship: a detailed pharmacokinetic study with seven healthy non-smoking men and a multiple depletion-repletion study with 68 healthy non-smoking men of varying body weights. Our estimates suggest that an additional intake of 10 mg vitamin C/day is required for every 10 kg increase in body weight to attain a comparable plasma concentration to a 60 kg individual with a vitamin C intake of ~110 mg/day, which is the daily intake recommended by the European Food Safety Authority (EFSA). Thus, individuals weighing e.g., 80 and 90 kg will need to consume ~130 and 140 mg vitamin C/day, respectively. People with obesity will likely need even higher vitamin C intakes. As poor vitamin C status is associated with increased risk of several chronic diseases including cardiovascular disease, these findings may have important public health implications. As such, dose-finding studies are required to determine optimal vitamin C intakes for overweight and obese people.

Effect of intravenous vitamin C on arterial blood gas analyser and Accu-Chek point-of-care glucose monitoring in critically ill patients.

Background: Intravenous vitamin C is known to interfere with some point-of-care blood glucose meters. We aimed to determine the concentrations at which ascorbate interferes with glucose concentrations measured using a point-of-care blood glucose meter. We also compared the point-of-care meter and an arterial blood gas (ABG) analyser in the intensive care unit with laboratory glucose monitoring in septic patients receiving intravenous vitamin C infusions. Methods: Blood samples containing normal, depleted and supplemented glucose and increasing concentrations of ascorbate (0.1-1.0 mmol/L) were tested using an Accu-Chek Inform II (Roche Diagnostics, USA) glucometer. For the in vivo study, 41 individual blood samples were drawn daily from septic patients (n = 16) receiving infusions of 25 mg/kg of vitamin C every 6 hours. The glucose values of matched blood samples were assessed using Accu-Chek, ABG and laboratory glucose methods. Results: For every 1 mmol/L of ascorbate added, the glucose concentration measured by the point-of-care monitor increased by 1.4 mmol/L (95% CI, 1.0-1.8; P < 0.001). Analysis of matched blood samples collected following intravenous vitamin C infusion indicated that 98% of the ABG and 83% of the Accu-Chek values met the International Organization for Standardization (ISO) 15197:2013 accuracy criteria. One patient had severe renal impairment, which contributed to elevated plasma vitamin C concentrations (median, 0.95 mmol/L; range, 0.64-1.10 mmol/L), resulting in elevated Accu-Chek readings and presenting a moderate clinical risk for the highest value. Conclusions: Vitamin C concentrations < 0.8 mmol/L do not interfere with point-of-care glucose monitoring. Intravenous vitamin C infusion of 25 mg/kg every 6 hours does not interfere with point-of-care glucose monitoring unless the patient has renal impairment, in which case laboratory glucose tests should be used.

Peroxiredoxin 2 oxidation reveals hydrogen peroxide generation within erythrocytes during high-dose vitamin C administration.

Intravenous infusion of high dose (>10 g) vitamin C (IVC) is a common alternative cancer therapy. IVC results in millimolar levels of circulating ascorbate, which is proposed to generate cytotoxic quantities of H2O2 in the presence of transition metal ions. In this study we report on the in vitro and in vivo effects of millimolar ascorbate on erythrocytes. Addition of ascorbate to whole blood increased erythrocyte intracellular ascorbate approximately 35-fold. Within 10 min of ascorbate addition, we detected increased oxidation of erythrocyte peroxiredoxin 2 (Prx2), a major thiol antioxidant protein and a sensitive marker of H2O2 production. Up to 50% of Prx2 was present in the oxidised form after 60 min. The presence of extracellular catalase, removal of plasma or the addition of a metal chelator did not prevent ascorbate-induced Prx2 oxidation, suggesting that the H2O2 responsible for Prx2 oxidation was generated within the erythrocyte. Ascorbate is known to increase the rate of haemoglobin autoxidation and H2O2 production. Through spectral monitoring of oxidised haemoglobin we estimated a generation rate of 15 µM H2O2/min inside erythrocytes. We also investigated changes in erythrocyte ascorbate concentration and Prx2 oxidation following IVC infusion in a cohort of patients with cancer. Plasma ascorbate levels ranged from 7.8 to 35 mM immediately post infusion, while erythrocyte ascorbate levels reached 1.5-3.4 mM 4 h after beginning infusion. Transient oxidation of erythrocyte Prx2 was observed. We conclude that erythrocytes accumulate ascorbate during IVC infusion, providing a significant reservoir of ascorbate, and this ascorbate increases H2O2 generation within the cells. The consequence of increased erythrocyte Prx2 oxidation warrants further investigation.

Vitamin C: From Bench to Bedside.

Vitamin C (ascorbic acid) is a normal liver metabolite in most animals, with humans being a notable exception due to random genetic mutations that have occurred during our evolution [...].

Discrepancies in global vitamin C recommendations: a review of RDA criteria and underlying health perspectives.

The concept of a 'recommended dietary allowance' (RDA) and similar terms describing the daily intake of essential nutrients recommended for healthy individuals is widely used by various health authorities around the world. For vitamin C, however, there remain significant discrepancies in the criteria used to establish dietary recommendations and consequently, global recommendations for daily vitamin C intake vary by more than five fold. While it appears that the scientific data underlying the recommendations are more or less the same, the interpretation differs considerably. Moreover, although a number of the assumptions used in e.g. the body pool estimates of the 1960s and 1970s have later been proven wrong and give rise to significant underestimations, these data are still used as the main support of several recommendations. Aspects that modify vitamin C requirements, such as gender, age, pregnancy, lactation, and smoking, have been taken into consideration by many but not all regulatory authorities, and are thus subject of debate. In contrast, body weight, a significant predictor of vitamin C status and requirement, has not been taken into consideration with respect to vitamin C recommendations, even in the face of the looming global obesity pandemic. The present review examines the discrepancies in vitamin C dietary recommendations of international authorities and critically discusses representative examples of criteria and the underlying health perspectives used to derive current recommended intakes of vitamin C. New biological signatures of vitamin C nutriture are also explored with regard to their potential use for future updates of dietary recommendations.

Patients Undergoing Myeloablative Chemotherapy and Hematopoietic Stem Cell Transplantation Exhibit Depleted Vitamin C Status in Association with Febrile Neutropenia.

Patients undergoing myeloablative chemotherapy and hematopoietic stem cell transplantation (HSCT) experience profound neutropenia and vulnerability to infection. Previous research has indicated that patients with infections have depleted vitamin C status. In this study, we recruited 38 patients with hematopoietic cancer who were undergoing conditioning chemotherapy and HSCT. Blood samples were collected prior to transplantation, at one week, two weeks and four weeks following transplantation. Vitamin C status and biomarkers of inflammation (C-reactive protein) and oxidative stress (protein carbonyls and thiobarbituric acid reactive substances) were assessed in association with febrile neutropenia. The vitamin C status of the study participants decreased from 44 ± 7 µmol/L to 29 ± 5 µmol/L by week one (p = 0.001) and 19 ± 6 µmol/L by week two (p < 0.001), by which time all of the participants had undergone a febrile episode. By week four, vitamin C status had increased to 37 ± 10 µmol/L (p = 0.1). Pre-transplantation, the cohort comprised 19% with hypovitaminosis C (i.e., <23 µmol/L) and 8% with deficiency (i.e., <11 µmol/L). At week one, those with hypovitaminosis C had increased to 38%, and at week two, 72% had hypovitaminosis C, and 34% had outright deficiency. C-reactive protein concentrations increased from 3.5 ± 1.8 mg/L to 20 ± 11 mg/L at week one (p = 0.002), and 119 ± 25 mg/L at week two (p < 0.001), corresponding to the development of febrile neutropenia in the patients. By week four, these values had dropped to 17 ± 8 mg/L (p < 0.001). There was a significant inverse correlation between C-reactive protein concentrations and vitamin C status (r = -0.424, p < 0.001). Lipid oxidation (thiobarbituric acid reactive substances (TBARS)) increased significantly from 2.0 ± 0.3 µmol/L at baseline to 3.3 ± 0.6 µmol/L by week one (p < 0.001), and remained elevated at week two (p = 0.003), returning to baseline concentrations by week four (p = 0.3). Overall, the lowest mean vitamin C values (recorded at week two) corresponded with the highest mean C-reactive protein values and lowest mean neutrophil counts. Thus, depleted vitamin C status in the HSCT patients coincides with febrile neutropenia and elevated inflammation and oxidative stress.

Factors Affecting Vitamin C Status and Prevalence of Deficiency: A Global Health Perspective.

A recent review of global vitamin C status has indicated a high prevalence of deficiency, particularly in low- and middle-income countries, as well as in specific subgroups within high-income countries. Here, we provide a narrative review of potential factors influencing vitamin C status globally. The in vivo status of vitamin C is primarily affected by dietary intake and supplement use, with those who supplement having a higher mean status and a lower prevalence of deficiency. Dietary intake can be influenced by cultural aspects such as traditional cooking practices and staple foods, with many staple foods, such as grains, contributing negligible vitamin C to the diet. Environmental factors can also affect vitamin C intake and status; these include geographic region, season, and climate, as well as pollution, the latter partly due to enhanced oxidative stress. Demographic factors such as sex, age, and race are known to affect vitamin C status, as do socioeconomic factors such as deprivation, education and social class, and institutionalization. Various health aspects can affect vitamin C status; these include body weight, pregnancy and lactation, genetic variants, smoking, and disease states, including severe infections as well as various noncommunicable diseases such as cardiovascular disease and cancer. Some of these factors have changed over time; therefore, we also explore if vitamin C status has shown temporal changes. Overall, there are numerous factors that can affect vitamin C status to different extents in various regions of the world. Many of these factors are not taken into consideration during the setting of global dietary intake recommendations for vitamin C.

Vitamin C Administration by Intravenous Infusion Increases Tumor Ascorbate Content in Patients With Colon Cancer: A Clinical Intervention Study.

The use of high dose ascorbate infusions in cancer patients is widespread, but without evidence of efficacy. Several mechanisms whereby ascorbate could affect tumor progression have been proposed, including: (i) the localized generation of cytotoxic quantities of H2O2; (ii) ascorbate-dependent activation of the 2-oxoglutarate-dependent dioxygenases that control the hypoxia-inducible factors (HIFs) and that are responsible for the demethylation of DNA and histones; (iii) increased oxidative stress induced by dehydroascorbic acid. We hypothesize that the dysfunctional vasculature of solid tumors results in compromised delivery of ascorbate to poorly perfused regions of the tumor and that this ascorbate deficit acts as an additional driver of the hypoxic response via upregulation of HIFs. Using a randomized "therapeutic window of opportunity" clinical study design we aimed to determine whether ascorbate infusions affected tumor ascorbate content and tumor biology. Patients with colon cancer were randomized to receive infusions of up to 1 g/kg ascorbate for 4 days before surgical resection (n = 9) or to not receive infusions (n = 6). Ascorbate was measured in plasma, erythrocytes, tumor and histologically normal mucosa at diagnostic colonoscopy and at surgery. Protein markers of tumor hypoxia or DNA damage were monitored in resected tissue. Plasma ascorbate reached millimolar levels following infusion and returned to micromolar levels over 24 h. Pre-infusion plasma ascorbate increased from 38 ± 10 µM to 241 ± 33 µM (p < 0.0001) over 4 days and erythrocyte ascorbate from 18 ± 20 µM to 2509 ± 1016 µM (p < 0.005). Tumor ascorbate increased from 15 ± 6 to 28 ± 6 mg/100 g tissue (p < 0.0001) and normal tissue from 14 ± 6 to 21 ± 4 mg/100 g (p < 0.001). A gradient of lower ascorbate was evident towards the tumor centre in both control and infusion samples. Lower expression of hypoxia-associated proteins was seen in post-infusion tumors compared with controls. There were no significant adverse events and quality of life was unaffected by ascorbate infusion. This is the first clinical study to demonstrate that tumor ascorbate levels increase following infusion, even in regions of poor diffusion, and that this could modify tumor biology. CLINICAL TRIAL REGISTRATION: ANZCTR Trial ID ACTRN12615001277538 (https://www.anzctr.org.au/).

The Use of Intravenous Vitamin C as a Supportive Therapy for a Patient with Glioblastoma Multiforme.

Glioblastoma multiforme is a high grade malignant brain tumour with a poor prognosis. Here we report the case of a woman with glioblastoma who lived for over four years from diagnosis (median survival 12 months and 2% survival for three years), experiencing good quality of life for most of that time. She underwent initial debulking craniotomy, radiotherapy and chemotherapy, as well as having intravenous vitamin C infusions 2⁻3 times weekly over the four years from diagnosis. Her progress was monitored by blood tests, regular computerised tomography (CT) and magnetic resonance imaging (MRI) scans, clinical reviews and European Organization for the Research and Treatment of Cancer quality of life questionnaires (EORTC QLQ C30). Our case report highlights the benefits of intravenous vitamin C as a supportive therapy for patients with glioblastoma.

Intravenous Vitamin C for Cancer Therapy - Identifying the Current Gaps in Our Knowledge.

The use of intravenous vitamin C (IVC) for cancer therapy has long been an area of intense controversy. Despite this, high dose IVC has been administered for decades by complementary health care practitioners and physicians, with little evidence base resulting in inconsistent clinical practice. In this review we pose a series of questions of relevance to both researchers and clinicians, and also patients themselves, in order to identify current gaps in our knowledge. These questions include: Do oncology patients have compromised vitamin C status? Is intravenous the optimal route of vitamin C administration? Is IVC safe? Does IVC interfere with chemotherapy or radiotherapy? Does IVC decrease the toxic side effects of chemotherapy and improve quality of life? What are the relevant mechanisms of action of IVC? What are the optimal doses, frequency, and duration of IVC therapy? Researchers have made massive strides over the last 20 years and have addressed many of these important aspects, such as the best route for administration, safety, interactions with chemotherapy, quality of life, and potential mechanisms of action. However, we still do not know the answers to a number of fundamental questions around best clinical practice, such as how much, how often and for how long to administer IVC to oncology patients. These questions point the way forward for both basic research and future clinical trials.

Intravenous Vitamin C Administration Improved Blood Cell Counts and Health-Related Quality of Life of Patient with History of Relapsed Acute Myeloid Leukaemia.

A 52-year-old female presented to Integrated Health Options Clinic in October 2014 with a history of relapsed acute myeloid leukaemia (AML, diagnosed in 2009 and relapsed in 2014). Intravenous(IV) vitamin C therapy was initiated (in 2014) following completion of chemotherapy as an alternative to haematopoietic stem cell transplantation. IV vitamin C was administered twice weekly at a dose of 70 g/infusion. Within 4 weeks of initiation of IV vitamin C therapy, there was a dramatic improvement in the patient's blood indices with platelet cell counts increasing from 25 × 108/L to 196 × 108/L and white blood cell counts increasing from 0.29 × 108/L to 4.0 × 108/L, with further improvements observed over the next 18 months. Furthermore, there was a clear and sustained improvement in the patient's health-related quality of life scores assessed using a validated questionnaire. She has remained healthy and in complete remission until the present day. This case study highlights the benefits of IV vitamin C as a supportive therapy for previously relapsed AML.

SunGold Kiwifruit Supplementation of Individuals with Prediabetes Alters Gut Microbiota and Improves Vitamin C Status, Anthropometric and Clinical Markers.

Kiwifruit are a nutrient dense food and an excellent source of vitamin C. Supplementation of the diet with kiwifruit enhances plasma vitamin C status and epidemiological studies have shown an association between vitamin C status and reduced insulin resistance and improved blood glucose control. In vitro experiments suggest that eating kiwifruit might induce changes to microbiota composition and function; however, human studies to confirm these findings are lacking. The aim of this study was to investigate the effect of consuming two SunGold kiwifruit per day over 12 weeks on vitamin C status, clinical and anthropometric measures and faecal microbiota composition in people with prediabetes. This pilot intervention trial compared baseline measurements with those following the intervention. Participants completed a physical activity questionnaire and a three-day estimated food diary at baseline and on completion of the trial. Venous blood samples were collected at each study visit (baseline, 6, 12 weeks) for determination of glycaemic indices, plasma vitamin C concentrations, hormones, lipid profiles and high-sensitivity C-reactive protein. Participants provided a faecal sample at each study visit. DNA was extracted from the faecal samples and a region of the 16S ribosomal RNA gene was amplified and sequenced to determine faecal microbiota composition. When week 12 measures were compared to baseline, results showed a significant increase in plasma vitamin C (14 µmol/L, p < 0.001). There was a significant reduction in both diastolic (4 mmHg, p = 0.029) and systolic (6 mmHg, p = 0.003) blood pressure and a significant reduction in waist circumference (3.1 cm, p = 0.001) and waist-to-hip ratio (0.01, p = 0.032). Results also showed a decrease in HbA1c (1 mmol/mol, p = 0.005) and an increase in fasting glucose (0.1 mmol/L, p = 0.046), however, these changes were small and were not clinically significant. Analysis of faecal microbiota composition showed an increase in the relative abundance of as yet uncultivated and therefore uncharacterised members of the bacterial family Coriobacteriaceae. Novel bacteriological investigations of Coriobacteriaceae are required to explain their functional relationship to kiwifruit polysaccharides and polyphenols.

Appropriate Handling, Processing and Analysis of Blood Samples Is Essential to Avoid Oxidation of Vitamin C to Dehydroascorbic Acid.

Vitamin C (ascorbate) is the major water-soluble antioxidant in plasma and its oxidation to dehydroascorbic acid (DHA) has been proposed as a marker of oxidative stress in vivo. However, controversy exists in the literature around the amount of DHA detected in blood samples collected from various patient cohorts. In this study, we report on DHA concentrations in a selection of different clinical cohorts (diabetes, pneumonia, cancer, and critically ill). All clinical samples were collected into EDTA anticoagulant tubes and processed at 4 °C prior to storage at -80 °C for subsequent analysis by HPLC with electrochemical detection. We also investigated the effects of different handling and processing conditions on short-term and long-term ascorbate and DHA stability in vitro and in whole blood and plasma samples. These conditions included metal chelation, anticoagulants (EDTA and heparin), and processing temperatures (ice, 4 °C and room temperature). Analysis of our clinical cohorts indicated very low to negligible DHA concentrations. Samples exhibiting haemolysis contained significantly higher concentrations of DHA. Metal chelation inhibited oxidation of vitamin C in vitro, confirming the involvement of contaminating metal ions. Although EDTA is an effective metal chelator, complexes with transition metal ions are still redox active, thus its use as an anticoagulant can facilitate metal ion-dependent oxidation of vitamin C in whole blood and plasma. Handling and processing blood samples on ice (or at 4 °C) delayed oxidation of vitamin C by a number of hours. A review of the literature regarding DHA concentrations in clinical cohorts highlighted the fact that studies using colourimetric or fluorometric assays reported significantly higher concentrations of DHA compared to those using HPLC with electrochemical detection. In conclusion, careful handling and processing of samples, combined with appropriate analysis, is crucial for accurate determination of ascorbate and DHA in clinical samples.

The role of vitamin C in the treatment of pain: new insights.

The vitamin C deficiency disease scurvy is characterised by musculoskeletal pain and recent epidemiological evidence has indicated an association between suboptimal vitamin C status and spinal pain. Furthermore, accumulating evidence indicates that vitamin C administration can exhibit analgesic properties in some clinical conditions. The prevalence of hypovitaminosis C and vitamin C deficiency is high in various patient groups, such as surgical/trauma, infectious diseases and cancer patients. A number of recent clinical studies have shown that vitamin C administration to patients with chronic regional pain syndrome decreases their symptoms. Acute herpetic and post-herpetic neuralgia is also diminished with high dose vitamin C administration. Furthermore, cancer-related pain is decreased with high dose vitamin C, contributing to enhanced patient quality of life. A number of mechanisms have been proposed for vitamin C's analgesic properties. Herein we propose a novel analgesic mechanism for vitamin C; as a cofactor for the biosynthesis of amidated opioid peptides. It is well established that vitamin C participates in the amidation of peptides, through acting as a cofactor for peptidyl-glycine α-amidating monooxygenase, the only enzyme known to amidate the carboxy terminal residue of neuropeptides and peptide hormones. Support for our proposed mechanism comes from studies which show a decreased requirement for opioid analgesics in surgical and cancer patients administered high dose vitamin C. Overall, vitamin C appears to be a safe and effective adjunctive therapy for acute and chronic pain relief in specific patient groups.