|Year : 2016 | Volume
| Issue : 6 | Page : 1148-1154
|Effect of vitamin C supplementation on lipid profile, serum uric acid, and ascorbic acid in children on hemodialysis
Ghada Mohamed El Mashad1, Hanan M ElSayed1, Nahla A Nosair2
1 Pediatrics Department, Faculty of Medicine, Menoufia University, Shebin El Kom, Egypt
2 Department of Clinical Pathology, Tanta University, Tanta, Egypt
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|Date of Web Publication||28-Nov-2016|
| Abstract|| |
Children with end-stage renal disease (ESRD) suffer from dyslipidemia and hyperuricemia that might play a causal role in the progression of cardiovascular disease (CVD). The aim of the study is to assess the effects of Vitamin C supplementation on uric acid, ascorbic acid, and serum lipid levels among children on hemodialysis (HD). This prospective study was conducted in the pediatric nephrology unit at Menoufia University Hospital. The study included a total of 60 children with ESRD on maintenance HD therapy. They were divided into two groups: Group I (supplemented group, n = 30) received intravenous Vitamin C supplementation and Group II (control, n = 30) received placebo (intravenous saline) for three months. The results are shown as a mean ± standard deviation. Statistical evaluation was performed by SPSS software (version 11.5) using paired t-test. After supplementation with Vitamin C, the serum Vitamin C and high-density lipoprotein levels increased significantly with a significant reduction in the levels of serum uric acid, cholesterol, low-density lipoproteins, and triglyceride at the end of the study period. No significant changes were observed in the control group. Vitamin C can serve as a useful urate lowering medicine in HD patients to avoid complications of hyperuricemia. Furthermore, it had favorable effects on the lipid profile. This improvement can be considered as a preventive strategy in the progression of CVD in HD patients. Vitamin C supplementation improves ascorbic acid deficiency in these patients.
|How to cite this article:|
El Mashad GM, ElSayed HM, Nosair NA. Effect of vitamin C supplementation on lipid profile, serum uric acid, and ascorbic acid in children on hemodialysis. Saudi J Kidney Dis Transpl 2016;27:1148-54
|How to cite this URL:|
El Mashad GM, ElSayed HM, Nosair NA. Effect of vitamin C supplementation on lipid profile, serum uric acid, and ascorbic acid in children on hemodialysis. Saudi J Kidney Dis Transpl [serial online] 2016 [cited 2018 Sep 23];27:1148-54. Available from: http://www.sjkdt.org/text.asp?2016/27/6/1148/194602
| Introduction|| |
Renal failure is a pro-oxidant state, which is characterized by insufficient anti-oxidant protection and elevated levels of reactive oxygen species. Patients with end-stage renal disease (ESRD) suffer from dyslipidemia, hypertension, diabetes mellitus, and malnutrition which are associated with increased risk of cardiovascular disease (CVD). ,,, Some micronutrients are able to scavenge free radicals.  Among them, Vitamin C is a potent anti-oxidant that is known to prevent low-density lipoprotein (LDL) from oxidation. ,
Hyperuricemia in chronic kidney disease (CKD) may be caused by a reduction in glomerular filtration rate (GFR), altered uric acid handling associated with certain medications such as diuretic therapy and hyperparathyroidism. Evidence that hyperuricemia might also play a causal role in vascular disease, hypertension, and progression of CKD is accumulating. ,, Epidemiological studies suggest that increased levels of serum uric acid are a risk factor for CVD where oxidative stress plays an important pathophysiological role. ,
Vitamin C deficiency is a prevalent complication in patients undergoing hemodialysis (HD), and an important risk factor for increased inflammatory status, CVD, and its mortality. , Vitamin C deficiency occurs mainly due to its loss during dialysis sessions, which may remove several hundred milligrams of Vitamin C in a single dialysis session, oxidative stress, restriction of intake of potassiumrich foods, or chronic inflammation. ,,, Since Vitamin C is partly metabolized to oxalate, which can accumulate in renal failure patients, many clinicians recommend a dose of only 60-100 mg/day, which may not be optimal. 
Previous studies that investigated the effect of Vitamin C supplementation in children on HD are lacking.
| Aim|| |
The aim of this study was to assess the effects of supplementation of Vitamin C on uric acid, ascorbic acid, and serum lipid levels in children with chronic renal failure on HD.
| Patients and Methods|| |
The study was approved by the Ethics Committee of Faculty of Medicine, Menoufia University, and all patients gave written informed consent to participate in this study. This prospective study was performed in the Pediatric Nephrology Unit at the Menoufia University Hospital, during the period from January 2014 to August 2014. Sixty children with ESRD on maintenance HD therapy were enrolled in this study. HD was performed for 3-4 h thrice weekly for at least three months before the study.
Patients were randomly divided into two groups: Group I (study group, n = 30) received Vitamin C supplementation and Group II (control, n = 30) received placebo (intravenous saline) twice daily for 12 weeks.
The study group received intravenous 250 mg of Vitamin C immediately at the end of each HD session three times a week for 12 weeks. The diet was not changed from what was previously prescribed for HD patients. They were allowed to take their regular medications without any anti-oxidant effect.
The mean age of Group I (16 females and 14 males) was 8.2 ± 17.3 years, (CHECK) and the mean age of the control group (15 males and 15 females) was 9.5 ± 3.1 years. The mean duration on maintenance HD in both groups was 2.91 ± 1.51 years (range: 6 months-5 years).
All patients were dialyzed on Fresenius 4008B dialysis machine (Germany) using polysulfone hollow fiber dialyzers with suitable surface area for the patients (Fresenius F3= 0.4 m 2 , F4 = 0.7 m 2 , F5 = 1.0 m 2 , and F6 = 1.2 m 2 ). Bicarbonate dialysis solution was used in all dialysis sessions. Kt/V value equal to, or >1.2, was used as an index of treatment adequacy. 
- ESRD with GFR <10 mL/min/1.73 m 2 and age <18 years
- Regular HD, having at least three sessions/ week
- Duration on HD more than three months.
- Primary (non-uremic) CVD
- Taking Vitamin C supplementation three months ago
- Participants in another clinical trial.
All patients were subjected to full history taking, thorough clinical examination and laboratory investigations. Hypertension was defined as the presence of a history of hypertension. Patients whose plasma uric acid levels were >7.5 mg/dL (or >6.5 mg/dL, for children aged <13 years) were considered hyperuricemic.  Vitamin C deficiency in children was defined as serum Vitamin C level below 28.4 μmol/L. 
Laboratory investigations included serum uric acid, plasma ascorbic acid, serum triglyceride, total serum cholesterol, high-density lipoprotein (HDL), and LDL. Fasting blood samples were taken from the arteriovenous fistula immediately before the HD session at the beginning and after three months of the study. Determination of the plasma concentration of ascorbic acid and uric acid was made by reversed-phase high-performance liquid chromatography using an ion-pairing reagent with ultraviolet detection. Coefficients of variation for the concentrations of ascorbic acid and uric acid in plasma were <2.1% and <3.5%, respectively. 
Total cholesterol, triglycerides, and HDL were estimated from the sample by the use of Beckman CX5 Synchron automated machine. LDL was calculated by the use of Friedewald equation: LDL = Total cholesterol − HDL − (triglyceride/5). 
| Statistical Analysis|| |
The results are shown as a mean ± standard deviation. Statistical evaluation was performed by Statistical Package for Social Sciences (SPSS) software version 18.0 (SPSS Inc, Chicago, IL, USA) using independent sample t-test. P <0.05 was considered statistically significant.
| Results|| |
Twenty-nine males (48.33%) and 31 females (51.67%) participated in this study. The causes of renal failure in our patients were obstructive uropathy in 27 (45%) (stones in 5, posterior urethral valve in 11, and vesicoureteric reflux in 11), glomerulonephritis in 12 (20%), cystic kidney diseases in five (8.3%), and cystinosis in two (3.33%). Fourteen patients (23.3%) had unknown causes. Hypertension was found in 14 patients. No significant differences were observed between the two groups (study and control) at the beginning of the study. Serum mean uric acid levels were 8.33 ± 1.61 mg/dL in Group I and 7.79 ± 1.99 mg/dL in Group II, and ascorbic acid levels were 8.97 ± 4.38 μmol/L in Group I and 8.83 ± 3.75 μmol/L in Group II. The LDL levels were 108.15 ± 9.75 and 107.59 ± 8.64 mg/dL, respectively, HDL was 40.12 ± 5.45 and 40.79 ± 5.67 mg/dL, respectively, serum cholesterol was 164.3 ± 9.93 and 164.96 ± 9.01 mg/dL, respectively, triglycerides were 172.9 ± 14.18 and 173.8 ± 14.92 mg/dL, respectively, and LDL/HDL ratio was 2.73 ± 0.37 and 2.67 ± 0.43 in Groups I and II, respectively [Table 1].
|Table 1: Laboratory data before Vitamin C supplementation in the studied groups.|
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At the end of the study period, Vitamin C levels increased significantly and serum uric acid decreased significantly in Group I (P <0.001). Furthermore, Vitamin C supplementation caused a significant reduction in the levels of lipids [Table 2] and [Table 3].
|Table 2: Laboratory data before and after Vitamin C supplementation in the supplemented group (Group I).|
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|Table 3: Laboratory data before and after Vitamin C supplementation in the placebo group (Group II).|
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| Discussion|| |
Hyperuricemia is associated with poor outcomes such as cardiovascular mortality and dialysis inadequacy in patients undergoing HD.  Although some medications are effective in lowering serum uric acid by reducing its synthesis or enhancing its excretion, these drugs are contraindicated in patients with ESRD.  Hence, providing alternative and attractive approaches such as supplementation with Vitamin C can play a critical role in the management of hyperuricemia.  Our study investigated the effect of Vitamin C supplementation on serum uric acid levels in HD patients.
Vitamin C has uricosuric properties and also inhibits uric acid synthesis, thus lowering serum uric acid. Previous studies have also reported an inverse association between plasma ascorbic acid levels or Vitamin C intake, and serum uric acid concentrations. A previous prospective cohort study reported that Vitamin C intake from diet sources was associated with a lower risk of developing gout.  Juraschek et al, studied Vitamin C supplementation by pooling the findings from published randomized controlled trials in children and adults not on HD and found significantly lower serum uric acid levels. 
In our study, we found a significant reduction of serum uric acid after Vitamin C supplementation (P <0.0001), with no significant change in the placebo group (P = 0.824). This result agrees with the study done by Biniaz et al (2014), which was conducted on 172 HD adult patients. They were randomly divided into the intervention group, to receive 250 mg of Vitamin C and control groups 1 and 2, to receive placebo injection (saline) and no intervention, respectively. Nearly, half of the patients (46.7%) had a serum uric acid level of >6 mg/dL. The median baseline serum levels of uric acid were 6.2, 5.9 and 6 mg/dL in the intervention, control 1, and control 2 groups, respectively (P = 0.19). After two months, median levels reduced significantly in the Vitamin C group to 5.8 mg/dL as compared to 6.4 mg/dL and 6.3 mg/dL in the control groups (P = 0.02). The mean serum creatinine level had no significant changes during the study.  Ersoy in 2014, had also supported similar results. 
Vitamin C (ascorbic acid) deficiency is a common finding in patients with ESRD, and higher levels are achieved by ascorbic acid supplementation.  Significant increase in Vitamin C levels in the supplemented group was found (P <0.0001), with no significant change in the placebo group (P = 0.912). These results are in accordance with previous studies. ,,,,,,,
Patients with ESRD suffer from dyslipidemia resulting from modification in the composition and metabolism of serum lipids and lipoproteins, which are associated with high cardiovascular risk. Hence, treatment of dyslipidemia seems necessary in these patients. , Vitamin C, a water-soluble antioxidant, acts as an important factor in lipid regulation, increases HDL levels, and protects against LDL oxidation, thus reduces the risk of CVD. ,
Our findings showed a significant increase of HDL concentration, significant decrease in cholesterol, LDL, and triglyceride levels, and also reduction of LDL/HDL ratio in the supplemented group (P <0.0001), with no significant changes in the control group after 12 weeks of supplementation with Vitamin C.
The results of the present study were in accordance with and supported by earlier studies conducted by Khajehdehi,  AfkhamiArdekani et al,  McRae,  Abdollahzad et al,  and Farzaneh et al. 
| Conclusion|| |
Vitamin C supplementation showed a significant reduction of serum uric acid values in children with ESRD on maintenance HD. Thus, Vitamin C can serve as a useful urate lowering medicine in these patients to avoid complications of hyperuricemia.
Furthermore, short-term Vitamin C supplementation had favorable effects on lipid profile. This improvement can be considered as a preventive strategy in the progression of CVD in HD patients. Vitamin C supplementation improves ascorbic acid deficiency in patients on HD.
Further investigations with larger sample size and longer duration are recommended.
Conflict of interest: None declared.
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Ghada Mohamed El Mashad
Pediatrics Department, Faculty of Medicine, Menoufia University, Menoufia
[Table 1], [Table 2], [Table 3]
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