Vitamin C Deficiency in Patients on Long-Term Deferasirox without Supplementation.

Abstract Background: Under conditions of iron overload, ascorbic acid is oxidised at an increased rate leading to a risk of vitamin C deficiency. With deferoxamine (DFO) standard therapy, vitamin C is usually given at a dose of 2–3mg/kg on the days of DFO infusion as this increases iron excretion by up to 30%. With deferarisox (DFX) chelation treatment, although supplementation is permitted, there is currently no information about the effects of vitamin C supplementation on iron excretion and it is often left to patients or their clinician’s discretion as to whether supplementation is given. With long-term treatment, in the absence of supplementation there is a potential risk that vitamin C deficiency will develop and this could influence response to treatment. Patients and Methods: We have measured fasting plasma vitamin C in 41 patients who have been on long term deferasirox treatment for transfusional iron overload for between 1.5 and 5 years. 32 of these patients had received no supplementation and 9 patients had received 2–3 mg/kg/ day of supplementation. We have examined whether trends in serum ferritin, myocardial T2* and liver iron, during the final year of observation, relate to plasma levels of vitamin C. Results: Fasting plasma Vitamin C was significantly lower in the 41 patients (mean=30.3μmol/l, SD=20.8) than healthy control patients (mean=60.29μmol/l SD=12.6) (P<0.0001). Fasting vitamin C levels were significantly lower in patients without supplementation (mean=26.1μmol/l, n=32) (p=0.011) than in patients who received regular supplementation (mean=45.5μmol/l, n=9). In the 32 patients without supplementation 23 (72%) had plasma levels less than two standard deviations from the control mean. Fasting vitamin C levels after a minimum of 1 year treatment without vitamin C supplementation negatively correlated with liver iron concentration as estimated by T2* MRI. One patient, who was subsequently found to have the lowest fating vitamin c level (2.9μmol/l) developed clinical signs consistent with scurvy with severe gum disease requiring dental clearance. We found no difference in the change of ferritin trend, LIC decrease or cT2* trend in the patients receiving supplementation from those who did not. We found that the correlation between LIC and serum ferritin was less clear in deficient patients (<36μmol/l or 2SD from the mean, r=0.51, p<0.01) than replete patients (>36μmol/l) (r=0.88, p<0.0001). Conclusions: We conclude that with long-term deferasirox therapy without vitamin C supplementation, there is a significant risk of vitamin C deficiency with a potential for clinical scurvy. The risk of ascorbate deficiency is further increased at higher levels of body iron loading. These findings suggest that vitamin C supplementation (2–3mg/kg/day) should be recommended as standard for patients on long-term chelation therapy with deferasirox. It would also be of value to determine whether long term-response was improved by ascorbate supplementation.

Download Full-text

Oral vitamin C supplementation to patients with myeloid cancer on azacitidine treatment: Normalization of plasma vitamin C induces epigenetic changes

Clinical Epigenetics ◽

10.1186/s13148-019-0739-5 ◽

2019 ◽

Vol 11 (1) ◽

Cited By ~ 7

Author(s):

Linn Gillberg ◽

Andreas D. Ørskov ◽

Ammar Nasif ◽

Hitoshi Ohtani ◽

Zachary Madaj ◽

...

Keyword(s):

Vitamin C ◽

Biological Effects ◽

Pilot Trial ◽

Dna Demethylation ◽

Controlled Clinical Trial ◽

Plasma Vitamin ◽

Oral Vitamin ◽

Oral Supplementation ◽

Vitamin C Deficiency ◽

Vitamin C Supplementation

Abstract Background Patients with haematological malignancies are often vitamin C deficient, and vitamin C is essential for the TET-induced conversion of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), the first step in active DNA demethylation. Here, we investigate whether oral vitamin C supplementation can correct vitamin C deficiency and affect the 5hmC/5mC ratio in patients with myeloid cancers treated with DNA methyltransferase inhibitors (DNMTis). Results We conducted a randomized, double-blinded, placebo-controlled pilot trial (NCT02877277) in Danish patients with myeloid cancers performed during 3 cycles of DNMTi-treatment (5-azacytidine, 100 mg/m2/d for 5 days in 28-day cycles) supplemented by oral dose of 500 mg vitamin C (n = 10) or placebo (n = 10) daily during the last 2 cycles. Fourteen patients (70%) were deficient in plasma vitamin C (< 23 μM) and four of the remaining six patients were taking vitamin supplements at inclusion. Global DNA methylation was significantly higher in patients with severe vitamin C deficiency (< 11.4 μM; 4.997 vs 4.656% 5mC relative to deoxyguanosine, 95% CI [0.126, 0.556], P = 0.004). Oral supplementation restored plasma vitamin C levels to the normal range in all patients in the vitamin C arm (mean increase 34.85 ± 7.94 μM, P = 0.0004). We show for the first time that global 5hmC/5mC levels were significantly increased in mononuclear myeloid cells from patients receiving oral vitamin C compared to placebo (0.037% vs − 0.029%, 95% CI [− 0.129, − 0.003], P = 0.041). Conclusions Normalization of plasma vitamin C by oral supplementation leads to an increase in the 5hmC/5mC ratio compared to placebo-treated patients and may enhance the biological effects of DNMTis. The clinical efficacy of oral vitamin C supplementation to DNMTis should be investigated in a large randomized, placebo-controlled clinical trial. Trial registration ClinicalTrials.gov, NCT02877277. Registered on 9 August 2016, retrospectively registered.

Download Full-text

Dietary Intake Insufficient to Support Nutritional Adequacy in Patients with Thalassemia

Blood ◽

10.1182/blood.v124.21.1361.1361 ◽

2014 ◽

Vol 124 (21) ◽

pp. 1361-1361

Author(s):

Ellen B. Fung ◽

Neogi Sushrita ◽

Drucilla Haines ◽

Connie Schroepfer ◽

Ashutosh Lal

Keyword(s):

Vitamin C ◽

Iron Overload ◽

Dietary Intake ◽

Alpha Tocopherol ◽

Nutritional Adequacy ◽

Liver Iron ◽

Vitamin C Deficiency ◽

The Mean ◽

The Relationship ◽

Circulating Levels

Abstract Many patients with beta-thalassemia major have depressed circulating levels of essential micronutrients. These nutritional deficiencies may be caused by an elevated requirement for these nutrients, increased excretion and/or because of inadequate dietary intake. However, the relationship between dietary intake and circulating levels of key nutrients has not been explored. Therefore, the aim of this prospective, cross-sectional study was to quantitate intake using gold standard dietary assessment techniques, as well as to assess circulating levels of key micronutrients in the fasted state in a contemporary sample of subjects with transfusion-dependent thalassemia (age >5 years). Dietary intake was determined with the Block©2005 3-day semi-quantitative food frequency questionnaire (NutritionQuest, Berkeley, CA) completed within 3 months of a pre-transfusion blood sample. Dietary intake (mg/day) was calculated relative to the Institute of Medicine recommendations for age and gender. Intake was then compared to circulating levels of vitamin C, 25-OH vitamin D, alpha & gamma-tocopherol, zinc, copper and selenium. The usage of nutritional supplements was documented. All results were analyzed using STATA (v 9.3, College Station, TX). Forty-one patients (20 male, mean age 28.3 ± 10.7 years) with an average BMI of 22.1 ± 5.2 kg/cm2 and pre-transfusion hemoglobin of 10.9 ± 1.5 g/dL were enrolled. The mean liver iron concentration (LIC) measured by Ferritometer was 13.5 ± 11.3 mg/g dry liver-weight. As has been observed previously, 14 to 30% of patients had low circulating levels of Zn, Cu, 25-OHD, vitamin C and alpha-tocopherol. No deficiencies were observed for selenium. Patients consumed on average 1555 ± 835 kcal/d (80% of estimated energy requirement) and 1.3 ± 0.9 g/kg protein. Average dietary intake was inadequate (less than estimated average requirement) for Ca, Zn, Cu, and vitamins C, D, and E. Among patients with low circulating micronutrient levels, 86% of those with low serum zinc also had low dietary zinc intake; similarly, 88% of those with low circulating copper also had low copper intake. Significant inverse correlations were observed between LIC and blood concentrations of the antioxidants vitamin C (r = -0.62), alpha-tocopherol (r = -0.37) and zinc (r = -0.35). The relationship between iron overload and vitamin C was further explored in a retrospective sample of 49 patients where simultaneous values of both measures were available (228 samples). Vitamin C level progressively decreased with increasing iron burden. The mean vitamin C level was 0.57 ± 0.47 mg/dL with LIC >15 mg/g compared with 1.06 ± 0.45 mg/dL when LIC was <7 mg/g (P <0.001). Serum ferritin levels were not associated with vitamin C deficiency (plasma concentration <0.4 mg/dL) at mild to moderate degrees of liver iron overload. However, with extreme iron overload (LIC >25 mg/g), ferritin levels were significantly greater in the presence of vitamin C deficiency (6545 ± 2597 ng/mL versus 4720 ± 1915 ng/mL, p=0.045). These data suggest that iron overload negatively influences blood levels of several micronutrients. Moreover, dietary intake is insufficient to support circulating levels of nutrients in optimally transfused thalassemia patients. Nutritional adequacy is essential for optimal health, and vitamin C status can impact chelation efficiency. Future research should consider nutritional supplementation and health outcomes in patients with transfusion-dependent thalassemia. Disclosures No relevant conflicts of interest to declare.

Download Full-text

Serum Ferritin Predicts Liver but Not Cardiac Iron Burden by Noninvasive MRI in Sickle Cell Disease (SCD.

Blood ◽

10.1182/blood.v112.11.1421.1421 ◽

2008 ◽

Vol 112 (11) ◽

pp. 1421-1421 ◽

Cited By ~ 1

Author(s):

Robert I. Liem ◽

Cynthia Rigsby ◽

Richard J. Labotka ◽

Andrew DeFreitas ◽

Alexis A. Thompson

Keyword(s):

Iron Overload ◽

Serum Ferritin ◽

Iron Content ◽

Iron Loading ◽

Cell Disease ◽

Liver Iron ◽

Cardiac Iron ◽

Liver Iron Content ◽

The Mean

Abstract BACKGROUND: Assumptions about iron loading as well as the utility of ferritin to predict transfusional iron overload among individuals with sickle cell disease (SCD) are largely based on extrapolation from data generated in patients with thalassemia major (TM). Yet recent studies suggest the natural history of iron overload in patients with SCD differs significantly from chronically transfused patients with TM. We sought to evaluate the extent of myocardial and hepatic siderosis using noninvasive imaging in chronically transfused patients with SCD and examine its clinical associations, including relationship to long-term trends in serum ferritin, transfusion history, chelation status and markers of hemolysis and inflammation. METHODS: We evaluated 17 subjects (mean age 15±3.6 yrs, range 9 to 20). The mean transfusion duration was 7.3±3.6 yrs (range 2 to 15). Thirteen (76%) patients were on chelation with deferasirox at the time of screening; 4 were not on chelation Rx. MRI T2*/R2* of the heart and liver using a multiple gradient echo sequence was performed on a single 1.5T GE scanner. Hepatic iron concentration (HIC) values were predicted from liver R2* values. RESULTS: Mean HIC in subjects was 9.9±6.7 mg/gm liver dry weight (range 2.5 to 20.8) and was ≥15 mg/gm in 6/17 (35%) subjects. The mean long-term serum ferritin (past 5 yrs, or duration of transfusion if < 5yrs) was 2318±1122 ng/mL (range 541 to 4225). Using Pearson’s correlation coefficient, we observed a significant relationship between HIC and ferritin (r=0.765, p=<0.001). We generated a receiver operator characteristic (ROC) curve to assess the utility of ferritin as a predictor of elevated HIC, using a threshold HIC thought to predict serious iron-related complications. A ferritin cut-off value ≥2164 ng/mL correctly identified 80% of cases of HIC ≥15 mg/gm (AUC 0.96, p=0.003) in our subjects with 83% sensitivity and 73% specificity. Despite markedly elevated HIC and ferritin values in some subjects, none had myocardial siderosis. All 17 subjects had cardiac MRI T2* values in the normal range > 25 ms. Cardiac iron load measured by T2* did not correlate with HIC or serum ferritin. We examined C-reactive protein (CRP) and B-type natriuretic peptide (BNP) as markers for inflammation and myocardial strain, respectively, in our subjects but neither demonstrated a significant relationship to ferritin or MRI findings. BNP, however, did correlate modestly with both age (r=−0.574, p=0.013) and left ventricular ejection fraction on cardiac MRI (r=0.510, p=0.036). A subset of subjects (n=8) had histologic iron measurements by percutaneous liver biopsy (LBx) within 6 months of MRI. While liver iron content by LBx correlated significantly with HIC by MRI (r=0.759, p=0.03), liver iron content by LBx did not correlate with ferritin (r=0.312, p=0.452). CONCLUSION: We found that serum ferritin is a good predictor of liver iron by MRI R2*, and that long term ferritin values ≥2164 ng/mL predict significant hepatic iron overload as assessed by this noninvasive method. We did not observe appreciable cardiac iron loading in our subjects with SCD, which otherwise might have been predicted by elevated HIC alone, as in individuals with TM. These data suggest that reliable, long term surveillance of transfusion-induced iron overload in SCD may be achieved using serum ferritin and HIC by MRI R2* as surrogate markers of hepatic siderosis rather than relying on liver iron content measured invasively by LBx. Also, previously determined thresholds for significant cardiac iron loading in TM, based on degree of hepatic siderosis, may not be applicable in SCD. Further investigation into alternative mechanisms of iron loading or distribution in these related but distinct disorders is warranted.

Download Full-text

Long Term Erythrocytapheresis Is Associated with Reduced Liver Iron Concentration in Sickle Cell Disease

Blood ◽

10.1182/blood.v124.21.4867.4867 ◽

2014 ◽

Vol 124 (21) ◽

pp. 4867-4867

Author(s):

Scott N. Myers ◽

Ryan Eid ◽

John Myers ◽

Salvatore J. Bertolone ◽

Ashok B. Raj

Keyword(s):

Iron Overload ◽

Serum Ferritin ◽

Iron Concentration ◽

Iron Chelation ◽

Cell Disease ◽

Liver Iron ◽

Serial Serum ◽

Low Levels ◽

The Impact

Abstract Background: Observational studies and randomized clinical trials have demonstrated that RBC transfusions can alleviate or prevent many complications of sickle cell disease (SCD). Obligatory iron loading is most problematic for those receiving chronic simple transfusions and is managed with chelation therapy to prevent hepatic, cardiac, and endocrinologic complications. Erythrocytapheresis procedures are increasingly used in SCD as they achieve dilution of hemoglobin S without significantly raising the total hematocrit. Some guidelines for the management of iron overload use serum ferritin levels, but non-invasive measurements of liver iron concentration (LIC) using validated and widely available MRI techniques have been described. There is a paucity of data elucidating the impact of long-term erythrocytapheresis (LTE) on LIC. We evaluated LIC with MRI and serial serum ferritin measurements among a population of SCD patients maintained on LTE at a single institution. Methods: Subjects with SCD maintained on the LTE program included those with elevated TCD, history of stroke, recurrent acute chest syndrome, or frequent pain crises unresponsive to hydroxyurea therapy. Serial serum ferritin measurements were followed and chelation with deferasirox was initiated for consistent ferritin level >1000 ng/mL. MRI of liver and cardiac iron was measured on all LTE subjects with non-contrast MRI techniques. A total of n=31 subjects maintained on LTE were enrolled and stratified into two groups: high LIC, ≥5mg/g of dry tissue (n=4, 12.9%) and low LIC, <5mg/g (n=27, 87.1%). Chi-squared and t-test were used to test for differences between the two groups. Logistic regression was used to test what impacted the odds of having a high LIC, while generalized linear mixed-effects modeling was used to test what impacted LIC. Results: None of the subjects had high cardiac iron concentration. Subjects with high LIC were significantly older (17.8 vs. 13.1, p=0.032) and were more likely to be female (100% vs. 44.4%, p=0.038). The duration of LTE was not associated with high and low levels of LIC (8.25 vs. 6.15, p=0.240, Figure 1), levels of LIC (r=0.247, p=0.188, Figure 2), or serum ferritin (r=0.077, p=0.680). The total number of simple of transfusions was not associated with serum ferritin (r=-0.177, p=0.558) or LIC (r=-0.022, p=0.910). Serum ferritin was not significantly associated with LIC (r=0.296, p=0.112, Figure 3). One of the 4 patients with high LIC required chelation with deferasirox for ferritin >1000 ng/mL. Three of the 31 subjects required iron chelation with deferasirox. Conclusions: There was no significant correlation between duration of LTE and LIC. The impact of cumulative simple transfusions on LIC was obviated by maintenance LTE. These findings are consistent with reports that LTE is associated with reduced transfusional iron overload. The lack of significant association between serum ferritin and LIC suggest that validated MRI measurements of LIC may have greater sensitivity for identifying patients with iron overload and guidelines for iron chelation should consider LIC rather than serum ferritin alone. Figure 1. Duration of LTE (years) was not associated with high and low levels of LIC. Figure 1. Duration of LTE (years) was not associated with high and low levels of LIC. Figure 2. Duration of LTE was not associated with levels of LIC. Figure 2. Duration of LTE was not associated with levels of LIC. Figure 3. Serum ferritin was not significantly associated with LIC. Figure 3. Serum ferritin was not significantly associated with LIC. Disclosures No relevant conflicts of interest to declare.

Download Full-text

SEVERE LIVER IRON CONCENTRATIONS (LIC) IN 24 PATIENTS WITH Β-THALASSEMIA MAJOR: CORRELATIONS WITH SERUM FERRITIN, LIVER ENZYMES AND ENDOCRINE COMPLICATIONS

Mediterranean Journal of Hematology and Infectious Diseases ◽

10.4084/mjhid.2018.062 ◽

2018 ◽

Vol 10 ◽

pp. e2018062 ◽

Cited By ~ 3

Author(s):

Vincenzo De Sanctis

Keyword(s):

Iron Overload ◽

Adrenal Insufficiency ◽

Serum Ferritin ◽

Chelation Therapy ◽

Ferritin Level ◽

Iron Chelation ◽

Dry Weight ◽

Thalassemia Major ◽

Liver Iron

Abstract. Introduction: Chronic blood transfusion is the mainstay of care for individuals with β-thalassemia major (BTM). However, it causes iron-overload that requires monitoring and management by long-term iron chelation therapy in order to prevent endocrinopathies and cardiomyopathies, that can be fatal. Hepatic R2 MRI method (FerriScan®) has been validated as the gold standard for evaluation and monitoring liver iron concentration (LIC) that reflects the total body iron-overload. Although adequate oral iron chelation therapy (OIC) is promising for the treatment of transfusional iron-overload, some patients are less compliant with it and others suffer from long-term effects of iron overload. Objective: The aim of our study was to evaluate the prevalence of endocrinopathies and liver dysfunction, in relation to LIC and serum ferritin level, in a selected group of adolescents and young adult BTM patients with severe hepatic iron overload (LIC from 15 to 43 mg Fe/g dry weight). Patients and Methods: Twenty-four selected BTM patients with severe LIC, due to transfusion-related iron-overload, followed at the Hematology Section, National Center for Cancer Care and Research, Hamad Medical Corporation of Doha (Qatar), from April 2015 to July 2017, were retrospectively evaluated. The prevalence of short stature, hypogonadism, hypothyroidism, hypoparathyroidism, impaired fasting glucose (IFG), diabetes, and adrenal insufficiency was defined and assessed according to the International Network of Clinicians for Endocrinopathies in Thalassemia (ICET) and American Diabetes Association criteria. Results: Patients have been transfused over the past 19.75 ± 8.05 years (ranging from 7 to 33 years). The most common transfusion frequency was every 3 weeks (70.8%). At the time of LIC measurements, the mean age of patients was 21.75 ± 8.05 years, mean LIC was 32.05 ± 10.53 mg Fe/g dry weight (range: 15 to 43 mg Fe/g dry weight). Their mean serum ferritin level was 4,488.6 ± 2,779 µg/L. The overall prevalence of growth failure was 26.1% (6/23), IFG was 16.7% (4/24), sub-clinical hypothyroidism was 14.3% (3/21), hypogonadism was 14.3% (2/14), diabetes mellitus was 12.5% (3/24), and biochemical adrenal insufficiency was 6.7% (1/15). The prevalence of hepatitis C positivity was 20.8% (5/24). No case of clinical hypothyroidism, adrenal insufficiency or hypoparathyroidism was detected in this cohort of patients. The prevalence of IFG impaired fasting glucose was significantly higher in BTM patients with very high LIC (>30 mg Fe/g dry liver) versus those with lower LIC (p = 0.044). LIC was correlated significantly with serum ferritin levels (r = 0.512; p = 0.011), lactate dehydrogenase (r = 0.744; p = 0.022) and total bilirubin (r = 0.432; p = 0.035). Conclusions: A significant number of BTM patients, with high LIC and endocrine disorders, still exist despite the recent developments of new oral iron chelating agents. Therefore, physicians’ strategies shall optimize early identification of those patients in order to optimise their chelation therapy and to avoid iron-induced organ damage. We believe that further studies are needed to evaluate if serial measurements of quantitative LIC may predict the risk for endocrine complications. Until these data are available, we recommend a close monitoring of endocrine and other complications, according to the international guidelines.

Download Full-text

Role of Vitamin C As an Adjuvant Therapy with Different Iron Chelators in Young β-Thalassemia Major Patients: Safety and Efficacy in Relation to Tissue Iron Overload

Blood ◽

10.1182/blood.v124.21.4046.4046 ◽

2014 ◽

Vol 124 (21) ◽

pp. 4046-4046 ◽

Cited By ~ 2

Author(s):

Mohsen Saleh Elalfy ◽

Maha Saber ◽

Amira Adly ◽

Eman Ismail ◽

Mohamed Tarif ◽

...

Keyword(s):

Vitamin C ◽

Iron Overload ◽

Cardiac Mri ◽

Thalassemia Major ◽

Hemoglobin Level ◽

Iron Chelators ◽

Vitamin C Deficiency ◽

Tissue Iron ◽

Vitamin C Supplementation ◽

Laboratory Variables

Abstract Background: Treatment with antioxidants may neutralize the deleterious effects of oxidative damage by reactive oxygen species generated from labile plasma iron. Vitamin C has been known to increase the efficacy of desforaxamine (DFO). Few studies examined the influence of vitamin C supplementation in iron overloaded β-thalassemia major (β-TM) patients with oral chelators. Aim: To determine the beneficial effects of Vitamin C as an adjuvant to iron chelators in children and adolescents with β-TM and its relation to tissue iron overload. Methods: A randomized prospective study registered on ClinicalTrials.gov (NCT02083575) included 100 patients with β-TM recruited from the regular attendees of Thalassemia center. Inclusion criteria were β-TM patients 2-18 years with serum ferritin (SF) >1000-2500 ng/ml on regular transfusion-chelation therapy receiving the standard doses of Desferrioxamine (DFO), deferiprone (DFP), deferasirox (DFX) in a ratio1:1:1. All the enrolled patients had vitamin C deficiency. Exclusion criteria included patients suffered from insulin-dependent diabetes, clinical cardiac and/or advanced liver disease. The thalassemia patients received vitamin C in a dose of 100 mg daily. Patients were followed-up for 6 months with assessment of transfusion frequency and index, complete blood count, vitamin C levels, serum iron, total iron binding capacity (TIBC), SF and transferrin saturation (Tsat), liver iron content (LIC) and cardiac magnetic resonance imaging T2* before and after therapy were assessed. Results: Laboratory variables at baseline were similarly distributed among patients receiving different iron chelating agents. Upon comparing baseline and post-therapy clinical and laboratory variables among the studied β-thalassemia patients; transfusion index was significantly decreased after 6 months of vitamin C therapy (p=0.03) and the number of transfused patients <3 weeks dropped from 66% to 57% although the difference did not reach a significant level. Hemoglobin level improved (p<0.01). SF, Tsat and LIC were significantly lower after treatment than baseline levels (p=0.048, p<0.01 and p=0.035, respectively). Cardiac MRI T2* and vitamin C levels increased 6 months after treatment (p=0.025 and p<0.001, respectively). Vitamin C supplementation to patients receiving DFO had significantly lowest transfusion index (p=0.035) with significant improvement in hemoglobin level and cardiac MRI T2* as well as decreased SF, Tsat and LIC (p<0.01). Patients on DFP or DFX showed non-significant improvement in hematological and radiological variables. Vitamin C level was negatively correlated to transfusion index, SF and LIC (p<0.01). Neither serious adverse reactions related to the chelators nor to Vitamin C administration have been reported. Conclusions: Vitamin C in a dose of 100 mg, as an adjuvant therapeutic agent increased the efficacy of DFO in reducing iron burden in the moderately iron overloaded B-TM with vitamin C deficiency; it showed marginal improvement with DFP and DFX. Higher doses of vitamin C therapy might be tried with evaluation of possible additional adverse events. Disclosures No relevant conflicts of interest to declare.

Download Full-text

Vitamin C Status in Transfusionally Iron-Overloaded Patients On Long-Term Deferasirox and Its Relationship to Myocardial Iron Removal.

Blood ◽

10.1182/blood.v114.22.2005.2005 ◽

2009 ◽

Vol 114 (22) ◽

pp. 2005-2005

Author(s):

Maciej W Garbowski ◽

Margarete Fabre ◽

Patricia Evans ◽

John B Porter

Keyword(s):

Vitamin C ◽

Iron Overload ◽

Research Funding ◽

Iron Loading ◽

Myocardial Iron ◽

Liver Iron ◽

One Year ◽

The Impact

Abstract Abstract 2005 Poster Board I-1027 Background Although the benefits to iron balance of supplementing deferoxamine therapy with ascorbic acid (AA, 2-3mg/kg/day) are well established, the role of this approach with deferasirox (DFX) chelation is unknown. We have previously reported that fasting plasma ascorbate (FPA) was significantly lower in patients on long-term DFX without AA supplementation (30.3 ± 20.8 mM) than in healthy controls (60.3 ± 12.6 mM, P<0.0001), with deficiency (defined as >2 SDs from the adult control mean) present in 72% of patients not receiving AA supplementation (Sarantos et all, Blood 112, Abstract 1858, 2008). It is therefore important to establish prospectively the relevance of ascorbate status to iron balance and also to myocardial iron loading in DFX-treated patients. Here we examine changes in FPA and markers of iron overload in the same patients over at least one year follow-up and examine the impact of AA supplementation in selected patients. Patients and Methods: 21 adult patients with a range of transfusional iron overload conditions excluding Sickle Cell Disease (17 with b-Thalassaemia Major, 2 with Congenital Syderoblastic Anaemia, 1 with Red Cell Aplasia, 1 with Diamond-Blackfan Anaemia) on long-term DFX chelation (duration of treatment 3-6 years, mean dose 27.1mg/kg/day) had measurements of FPA, ferritin, cardiac and hepatic T2* on two occasions, separated by a period of approximately one year (median 419 days). Of these, 10 received AA supplementation (2-3mg/kg/day) and 11 did not. The decision to prescribe AA was based on clinical criteria and patient preference rather than by randomisation. FPA was measured under controlled conditions: a 4 ml fasting heparinised blood sample was taken, placed immediately on ice and centrifuged at 4oC at 2000g for 10 minutes. An equal volume of 10% trichloroacetic acid (TCA) was added, the sample re-spun, and stored at —80oC until measurement of vitamin C fluorimetrically as previously described (Speek et al, 305, J Chromatogr, 1984). Results: In 10 patients who received AA supplementation for 1y (432 ± 96 (SD) days) , the FPA increased significantly from mean baseline of 35.99 ± 21.02 mM to 46.94 ± 14.69 mM at follow up (p=0.03) correcting the deficiency in 3 of the 5 scorbutic patients. FPA increased slightly but not significantly (p=0.3) in 11 patients without supplementation rising from 27.4 ± 15.8 mM to 34.0 ± 12.37 mM where deficiency was corrected in 2 of the 8 scorbutic patients. The increment in FPA levels in un-supplemented patients correlated with decrements in liver iron (LIC, r=-0.64, p=0.04), with mean liver R2* decreasing from 209.24 to 178.07 Hz (i.e. estimated LIC from 7.01 to 6.08 mg Fe/g dry weight (dw)), consistent with previous observations that iron overload accelerates oxidation of AA. Significant improvements in myocardial iron (shown as decreasing myocardial R2*) were seen in ascorbate replete patients at 1y (n=13, mean FPA 48.73 ± 10.61 mM) from a mean myocardial R2* of 61.4 to 52.5Hz p=0.008, i.e. T2* of 16.2ms to 19ms). By contrast, in patients who remained AA deficient (mean FPA 26.28 ± 8.44uM, n=8), the improvement in myocardial R2* was less marked (from 50.41 to 46.65Hz, i.e. T2* 19.8 to 21.4 ms) and did not reach significance. Conclusions: AA deficiency is a significant risk in transfusionally iron loaded patients on long term DFX without AA supplementation, particularly in patients with high levels of body iron loading. Our findings suggest that improvement in myocardial and liver iron with DFX therapy is more likely in AA replete than AA deficient patients. A prospective randomised study of the effects of AA supplementation on iron overload and myocardial iron in DFX treated patients is indicated but until such data are available, we recommend that patients on long term chelation with DFX have FPA levels assessed and consideration is given to supplementing deficient patients. Disclosures: Garbowski: Novartis: Research Funding. Evans:Novartis: Research Funding. Porter:Novartis: Consultancy, Research Funding.

Download Full-text

Effect of Dietary or Supplemental Vitamin C Intake on Vitamin C Levels in Patients with and without Cardiovascular Disease: A Systematic Review

Nutrients ◽

10.3390/nu13072330 ◽

2021 ◽

Vol 13 (7) ◽

pp. 2330

Author(s):

Bianca J. Collins ◽

Mitali S. Mukherjee ◽

Michelle D. Miller ◽

Christopher L. Delaney

Keyword(s):

Systematic Review ◽

Cardiovascular Disease ◽

Vitamin C ◽

Antioxidant Properties ◽

Plasma Vitamin ◽

Healthy Population ◽

Post Intervention ◽

Supplemental Vitamin ◽

Vitamin C Supplementation ◽

Elderly Cohort

Atherosclerosis is a pro-oxidative and pro-inflammatory disease state, which is the underlying cause of most cardiovascular events, estimated to affect 5.2% of the Australian population. Diet, and specifically vitamin C, through its antioxidant properties can play a role in impeding the development and progression of atherosclerosis. This systematic review conducted comprehensive searches in Medline, Emcare, Scopus, PubMed, and Cochrane using key search terms for vitamin C, plasma vitamin C, supplementation, and cardiovascular disease (CVD). The results demonstrated that vitamin C supplementation resulted in a significant increase in vitamin C levels in populations with or without CVD, except for one study on the CVD population. It was also seen that the healthy population baseline and post-intervention vitamin C levels were high compared to the CVD population. However, further research is indicated for CVD population groups with varying baseline vitamin C levels, such as low baseline vitamin C, within a more representative elderly cohort in order to formulate and update vitamin C repletion guidelines.

Download Full-text