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Intravenous vitamin C effects on transferrin saturation (TSAT) changes (gray bars) and serum ferritin changes (white bars) in patients receiving hemodialysis.
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Provision of sufficient available iron is a prerequisite to ensure the bodys optimal response to recombinant human erythropoietin (epoetin). Functional iron deficiency (a state when iron supply is reduced to meet the demands for increased erythropoiesis) is a common cause of poor response to epoetin in dialysis patients who have normal iron status,...
Context in source publication
Context 1
... there is no concrete evidence to support this contention, 10 observations are at least compati- ble with it. [4][5][6][7][8][9][10][11][12][13] Most studies have shown a 6-15% rise in TSAT 4-13 and a 5-31% reduction in serum ferritin concentrations 5,6,10,12,13 following administration of IV vitamin C to hemodialysis patients (Figure 2). Other explanations for the positive effect of vitamin C on epoetin responsiveness include amelioration of oxidative stress and inflammation. ...
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Citations
... intravenous iron injection. It also can mobilize iron from the reticuloendothelial system to transferrin [72,73]. Currently, dopaminergic medications (levodopa, ropinirole, pramipexole and rotigotine) and gabapentinoids (gabapentin and pregabalin) are recommended as the first line of drugs for treatment of essential RLS [74]. ...
Objectives:
The objective of this review is to provide updated information on the epidemiology, correlating factors and treatment of chronic kidney disease associated restless legs syndrome (CKD-A-RLS) in both adult and pediatric population.
Materials and methods:
We have reviewed the Medline search and Google Scholar search up to May 2022, using key words restless legs syndrome, chronic kidney disease and hemodialysis and kidney transplant. The reviewed articles were studied for epidemiology, correlating factors, as well as pharmacologic and non-pharmacologic treatment options.
Results:
Our search revealed 175 articles, 111 were clinical trials or cross- sectional studies and 64 were review articles. All 111 articles were retrieved and studied in detail. Of these, 105 focused on adults and 6 on children. A majority of studies on dialysis patients reported a prevalence between 15-30%, which is notably higher than prevalence of RLS in general population (5-10%). The correlation between presence of CKD-A-RLS with age, gender, abnormalities of hemogram, iron, ferritin, serum lipids, electrolytes and parathyroid hormones were also reviewed. The results were inconsistent and controversial. Limited studies have reported on the treatment of CKD-A-RLS. Non-pharmacological treatment focused on the effect(s) of exercise, acupuncture, massage with different oils and infra-red light whereas, pharmacologic treatment options include the effects of dopaminergic drugs, Alpha2-Delta ligands (gabapentin and pregabalin), vitamins E and C, and intravenous iron infusion.
Conclusion:
This updated review showed that RLS is two to three times more common in patients with CKD compared to the general population. More patients with CKD-A-RLS demonstrated increased mortality, increased incidence of cardiovascular accident, depression, insomnia and impaired quality of life than those with CKD without RLS. Dopaminergic drugs such as levodopa, ropinirole, pramipexole and rotigotine as well as calcium channel blockers (gabapentin and pregabalin) are helpful for treatment of RLS. High quality studies with these agents are currently underway and hopefully confirm the efficacy and practicality of using these drugs in CKD-A-RLS. Some studies have shown that aerobic exercise and massage with lavender oil can improve symptoms of CKD-A- RLS suggesting that these measures can be useful as adjunct therapy.
... 4 Moreover, the use of vitamin C may reduce oxidative stress and inflammation. Most of these micronutrients are eliminated to a various range during hemodialysis and, thus, could exacerbate the anemia and the hyporesponsiveness to ESA. 5 A special interest is given to a trace element, in particular selenium. As a matter of fact, selenium is an essential trace element with antioxidative properties, being a component of selenoproteins, including selenoenzymes such as glutathione peroxidase, selenoprotein-P, and thioredoxin reductase. ...
... Thus, elevated ferritin levels do not rule out the possibility of iron deficiency. Evidence suggests that ascorbic acid, a reducing agent, can improve iron utilization by facilitating the release of iron from ferritin and the mobilization of iron from the reticuloendothelial system to transferrin in patients with iron overload undergoing HD [40,41]. ...
Anemia affects millions of patients with chronic kidney disease (CKD) and prompt iron supplementation can lead to reductions in the required dose of erythropoiesis-stimulating agents, thereby reducing medical costs. Oral and intravenous (IV) traditional iron preparations are considered far from ideal, primarily due to gastrointestinal intolerability and the potential risk of infusion reactions, respectively. Fortunately, the emergence of novel iron replacement therapies has engendered a paradigm shift in the treatment of iron deficiency anemia in patients with CKD. For example, oral ferric citrate is an efficacious and safe phosphate binder that increases iron stores to maintain hemoglobin levels. Additional benefits include reductions in fibroblast growth factor 23 levels and the activation of 1,25 dihydroxyvitamin D. The new-generation IV iron preparations ferumoxytol, iron isomaltoside 1000, and ferric carboxymaltose are characterized by a reduced risk of infusion reactions and are clinically well tolerated as a rapid high-dose infusion. In patients undergoing hemodialysis (HD), ferric pyrophosphate citrate (FPC) administered through dialysate enables the replacement of ongoing uremic and HD-related iron loss. FPC transports iron directly to transferrin, bypassing the reticuloendothelial system and avoiding iron sequestration. Moreover, this paper summarizes recent advancements of hypoxia-inducible factor prolyl hydroxylase inhibitors and future perspectives in renal anemia management.
... A role for vitamin C in erythropoietin-hyporesponsive patients has been suggested, despite the lack of evidence to suggest a mechanism of action [6,7,8,9]. A possible mechanism could be related to the antioxidant properties of vitamin C and to its effects on iron metabolism or endogenous erythropoetin synthesis. ...
Vitamin C has been shown to be useful in the treatment of anemia of chronic diseases, but there is insufficient evidence to recommend it in the management of anemia in patient with chronic illness, with chronic kidney disease. We performed a small control study to probe if high dose intravenous vitamin C will raise the hemoglobin and improve the quality of life of patients with chronic diseases. We screened six patients and the study was performed from September to December of 2015, but one quit prior to begin the study. Their age ranges from 37 to 95 years-old, and three are male and two female. Their mean hemoglobin went up from 8.6 g/dL to 9.7 g/dL after they received vitamin C 10 g IV weekly for 6 weeks. The CRP level had a 41.4% effective reduction and their performance status & quality of life as per the questionnaire improved. We demonstrated a clinical benefit of high dose intravenous vitamin C in anemia of chronic diseases even though a small study. We recommend to perform a randomized controlled study with larger sample in a future.
... In vitamin C deficiency, this process gets hampered, which explains the anemic status of our patient. 12,13 Treatment of scurvy involves ingesting approximately 6.5 mg of vitamin C daily, but a dose that both corrects the deficit and rapidly replenishes the body stores rapidly is 100 mg three times a day. 14 The prognosis of scurvy is excellent with this treatment, and manifestations of scurvy tend to resolve rapidly, disappearing completely within a few weeks. ...
Localized gingival enlargement associated with vitamin C deficiency (scurvy) is rarely encountered in the modern era. The purpose of this paper is to report a case of extensive inflammatory gingival enlargement in the mandibular anterior region associated with vitamin C deficiency in a 10 year-old boy. There was a significant improvement of the gingival enlargement seven days after starting oral vitamin C supplementation. Vitamin C deficiency should be included in the differential diagnosis of any gingival enlargement, especially in children.
... A role for vitamin C in erythropoetin-hyporesponsive patients has been suggested, despite the lack of evidence to suggest a mechanism of action [10][11][12][13] . A possible mechanism could be related to the antioxidant properties of vitamin C and to its effects on iron metabolism or endogenous erythropoietin synthesis. ...
... The vast majority of endurance athletes, including elite athletes, take vitamin supplements such as vitamin C, often in large amounts (Sobal and Marquart, 1994), as an antioxidant and antianemic tool. In fact, it has been shown that dietary vitamin C deprivation leads to anemia (Maeda et al., 2000) and that vitamin C administration improves the response to recombinant human erythropoietin (rHuEpo) (Tarng, 2007). Keven et al., (2003) observed higher hemoglobin responses in normal iron status patients treated with vitamin C and recombinant human erythropoietin (rHuEpo). ...
Abstract Martinez-Bello,Vladimir E., Fabian Sanchis-Gomar, Daniel Martinez-Bello, Gloria Olaso-Gonzalez, Mari Carmen Gomez-Cabrera, and Jose Viña. Vitamin C Supplementation Does Not Improve Hypoxia-Induced Erythropoiesis. High Alt Med Biol 13:269-274, 2012.-Hypoxia induces reactive oxygen species production. Supplements with antioxidant mixtures can compensate for the decline in red cell membrane stability following intermittent hypobaric hypoxia by decreasing protein and lipid oxidation. We aimed to determine whether supplementation with vitamin C is implicated in the regulation of erythropoiesis and in the oxygen-carrying capacity of the blood, and also whether antioxidant supplementation prevents the oxidative stress associated to intermittent hypoxia. Twenty-four male Wistar rats were randomly divided into four experimental groups: normoxia control (n=6), normoxia + vitamin C (n=6), hypoxia control (12 h pO(2) 12%/12 h pO(2) 21%) (n=6), and hypoxia + vitamin C (n=6). Animals were supplemented with vitamin C at a dose of 250 mg·kg(-1)·day(-1) for 21 days. Red blood cell count, hemoglobin, hematocrit, reticulocytes, erythropoietin, and oxidative stress parameters such as malondialdehyde and protein oxidation in plasma were analyzed at two different time points: basal sample (day zero) and final sample (day 21). Similar RBC, Hb, Hct, and Epo increments were observed in both hypoxic groups regardless of the vitamin C supplementation. There was no change on MDA levels after intermittent hypoxic exposure in any experimental group. However, we found an increase in plasma protein oxidation in both hypoxic groups. Vitamin C does not affect erythropoiesis and protein oxidation in rats submitted to intermittent hypoxic exposure.
... The potential role of adjuvant therapies in enhancing the efficacy of rhEPO in patients receiving maintenance dialysis has commanded attention in recent years [7][8][9]. Adjuvant therapies may help to reduce rhEPO requirements or allow dialysis patients to achieve increased hemoglobin (Hgb) concentrations, and derive more cost-effectiveness and greater clinical benefits from rhEPO treatment [8][9][10]. Currently, many studies imply that intravenous ascorbic acid (IVAA) treatment in hemodialysis (HD) patients improved Hgb and iron availability in EPO-hyporesponsive HD patients with iron overload. ...
... The potential role of adjuvant therapies in enhancing the efficacy of rhEPO in patients receiving maintenance dialysis has commanded attention in recent years [7][8][9]. Adjuvant therapies may help to reduce rhEPO requirements or allow dialysis patients to achieve increased hemoglobin (Hgb) concentrations, and derive more cost-effectiveness and greater clinical benefits from rhEPO treatment [8][9][10]. Currently, many studies imply that intravenous ascorbic acid (IVAA) treatment in hemodialysis (HD) patients improved Hgb and iron availability in EPO-hyporesponsive HD patients with iron overload. ...
Hemodialysis (HD) patients with functional iron deficiency often develop resistance to recombinant human erythropoietin (rhEPO). Recent studies have shown that intravenous ascorbic acid (IVAA) administration could override rhEPO resistance in HD patients. This study was undertaken to test the effects of IVAA in HD patients with normoferritinemic functional iron deficiency accompanied by EPO-hyporesponsive anemia.Methods
Fifty-eight HD patients with normoferritinemic anemia (between 100 and 500 μg/L) were included and divided into the control (N=25) and IVAA (N=33) groups. IVAA patients received 500 mg of IVAA with each dialysis session for 3 months and an additional 4-month follow-up after the end of the therapy.ResultsTwenty patients had a response to IVAA with a significant increase in hemoglobin level (Hgb>1.0 g/dL) and reduction of weekly rhEPO dosage compared with the control group after 3 months of treatment (P<0.05). Compared with non-responders, transferrin saturation (TSAT) was significantly decreased in the responders group (26±11 vs. 35±14%, P<0.05) on baseline data. There was a significant increase in serum iron and TSAT (baseline vs. 3 months, serum iron 57±22 vs. 108±22 μg/dL, TSAT 26±11 vs. 52±7%, P<0.05) and a decrease in serum ferritin (377±146 vs. 233±145 ng/mL, P<0.05) in the responders group (N=20), but no significant changes in the control and non-responders groups (N=13) at 3-month treatment.ConclusionIVAA can be a potent and effective adjuvant therapy for HD patients with rhEPO-resistant normoferritinemic anemia. In addition, IVAA can reduce the dosage of rhEPO for anemia correction.
... Furthermore, HD patients have low intracellular levels of vitamin E [5]. These two antioxidants have been proposed as potential treatments for HD complications resulting from high oxidative stress like atherosclerosis and anemia [5,18]. Therefore, the perceived effect of vitamins C and E in the reduction of RLS symptoms in this study may be due to their antioxidant properties. ...
... Iron supplementation has been shown to be effective in the treatment of uremic RLS [23]. Vitamin C as a reducing agent has been shown to increase gastrointestinal absorption of iron, to increase the bioavailability of IV iron after injection, and to release iron from ferritin and mobilize iron from the reticuloendothelial system to transferrin [11,18]. Of note in this regard, vitamin C administration to HD patients has been shown to reduce serum ferritin levels and to increase transferrin saturation [18]. ...
... Vitamin C as a reducing agent has been shown to increase gastrointestinal absorption of iron, to increase the bioavailability of IV iron after injection, and to release iron from ferritin and mobilize iron from the reticuloendothelial system to transferrin [11,18]. Of note in this regard, vitamin C administration to HD patients has been shown to reduce serum ferritin levels and to increase transferrin saturation [18]. Therefore, it may be interesting to compare the efficacy of vitamin C plus iron or iron placebo or, alternatively, iron with vitamin C or vitamin C placebo in the treatment of uremic RLS in future randomized blinded trials. ...
Restless legs syndrome (RLS) is a common disorder in hemodialysis patients that leads to insomnia and impaired quality of life. Because high oxidative stress has been implicated in the pathogenesis of RLS, we sought to evaluate the efficacy of vitamins C and E and their combination in reducing the severity of RLS symptoms in hemodialysis patients in this randomized, double-blind, placebo-controlled, four-arm parallel trial.
Sixty stable hemodialysis patients who had all four diagnostic criteria for RLS developed by the International Restless Legs Syndrome Group with no acute illness or history of renal stone were randomly allocated to four fifteen-patient parallel groups to receive vitamin C (200 mg) and vitamin E (400 mg), vitamin C (200 mg) and placebo, vitamin E (400 mg) and placebo, and double placebo daily for eight weeks. International Restless Legs Scale (IRLS) scores were measured for all patients at baseline and at the end of treatment phase. The primary outcome was absolute change in IRLS sum score from baseline to the end of treatment phase.
Means of IRLS sum score decreased significantly in the vitamins C and E (10.3 ± 5.3, 95% CI: 7.4-13.3), vitamin C and placebo (10 ± 3.5, 95% CI: 8.1-11.9), and vitamin E and placebo groups (10.1 ± 6, 95% CI: 6.8-13.5) compared with the double placebo group (3.1 ± 3, 95% CI: 1.5-4.8), (P<0.001); however, no differences were observed between these treatment groups.
Vitamins C and E and their combination are safe and effective treatments for reducing the severity of RLS in hemodialysis patients over the short-term.
... A su vez, por tratarse de un agente reductor, la vitamina C tiene la capacidad de liberar al Fe de la ferritina (depósito de hierro) y movilizarlo desde el sistema reticuloendotelial a la transferrina (proteína transportadora de Fe). Esta movilización llevaría a un incremento de la utilización del Fe (Tarng, 2007), lo que se pone en evidencia a través del aumento de la síntesis de la PE (Bienfait, 1980). Se ha observado en enfermos rena-les que la administración conjunta de vitamina C y eritropoyetina, hormona que ejerce la regulación primaria sobre la síntesis de los glóbulos rojos, potencia el efecto eritropoyético de la hormona (Sirover, 2008;Tarng, 2007;Sunder-Plasssmann, 2001). ...
... Esta movilización llevaría a un incremento de la utilización del Fe (Tarng, 2007), lo que se pone en evidencia a través del aumento de la síntesis de la PE (Bienfait, 1980). Se ha observado en enfermos rena-les que la administración conjunta de vitamina C y eritropoyetina, hormona que ejerce la regulación primaria sobre la síntesis de los glóbulos rojos, potencia el efecto eritropoyético de la hormona (Sirover, 2008;Tarng, 2007;Sunder-Plasssmann, 2001). Las mujeres en edad fértil han demostrado un alto grado de adaptación a situaciones de deficiencia marginal crónica de Fe, como podría ser el caso de la población control ya que la misma persistió en un estado estacionario respecto del Fe. ...
RESUMEN Introducción: En el mundo, una de las deficiencias nutricionales más comunes es la anemia ferropriva. Se buscó desarrollar un alimento funcional para disminuir la posibilidad de padecer anemia por deficiencia de hierro. Para ello se aprovechó la costumbre de la población de consumir yerba mate (Ilex Paraguariensis Saint Hilaire), en su forma tradicional de mate caliente. Para aumentar la biodisponibilidad del hierro presente en forma natural se adicionó un potenciador de su absorción como la vitamina C. Materiales y métodos: Se trabajó con mujeres voluntarias entre 20 y 36 años, las que fueron divididas aleatoria-mente en los grupos experimental y control. Fueron estudiadas a lo largo de seis meses utilizando como marca-dores del estado nutricional del hierro el hematocrito, hemoglobina y protoporfirina eritrocitaria. Resultados: Los resultados obtenidos se ajustaron a una ecuación lineal de segundo orden para los dos grupos. Al comparar las pendientes obtenidas para los grupos control y experimental no se encontraron diferencias esta-dísticamente significativas. Un análisis de los incrementos de los hematocritos cada 30 días, mostró que los del grupo experimental, aumentaban en forma sigmoidea hasta alcanzar un plató, mientras que los del grupo control oscilaban en torno a cero. Para evidenciar el efecto del producto diseñado sobre las voluntarias potencialmente más sensibles, se realizó una clasificación en los grupos control y experimental entre los valores de hematocritos iniciales menores o igua-les a 38 % y mayores a 38 %. Se observó que los grupos con hematocritos mayores a 38 % no presentaron varia-ciones significativas en el tiempo. Sin embargo, el grupo experimental que comenzó el estudio con valores menores de hematocrito, presentó una pendiente mayor que el grupo control con los mismos valores iniciales, de acuerdo a lo esperado biológicamente. Conclusiones: Si bien las variaciones de las variables observadas a lo largo del estudio no fueron estadísticamen-te significativas, el comportamiento del grupo experimental marca una tendencia de respuesta positiva biológi-camente importante. Palabras claves: yerba mate, anemia, hierro, alimento funcional Development and evaluation of the effectiveness of a functional food for the prevention of iron deficiency SUMMARY Introduction: Iron-deficiency anaemia is one of the mostly spread nutritional deficiencies around the world. A functional food was developed to decrease the possibility of suffering from this type of anaemia, taking advantage of the consumption of yerba mate in the traditional form
