|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
Click here for correspondence address and email
|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 2019 Dec 12];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.|
Click here to view
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).|
Click here to view
|Table 3: Laboratory data before and after Vitamin C supplementation in the placebo group (Group II).|
Click here to view
| 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.
| References|| |
Dousdampanis P, Trigka K, Musso CG, Fourtounas C. Hyperuricemia and chronic kidney disease: An enigma yet to be solved. Ren Fail 2014;36:1351-9.
Garg JP, Chasan-Taber S, Blair A, et al. Effects of sevelamer and calcium-based phosphate binders on uric acid concentrations in patients undergoing hemodialysis: A randomized clinical trial. Arthritis Rheum 2005; 52:290-5.
Lee SM, Lee AL, Winters TJ, et al. Low serum uric acid level is a risk factor for death in incident hemodialysis patients. Am J Nephrol 2009;29:79-85.
Farzaneh M, Mohammad H, Mansour K, Madhurima D. Effect of antioxidant vitamins on lipid profile and total antioxidant capacity in hemodialysis patients. Rawal Med J 2010;35:1-10.
Ohno I, Yamaguchi Y, Saikawa H, et al. Sevelamer decreases serum uric acid concentration through adsorption of uric acid in maintenance hemodialysis patients. Intern Med 2009;48:415-20.
Nakagawa T, Mazzali M, Kang DH, SánchezLozada LG, Herrera-Acosta J, Johnson RJ. Uric acid - A uremic toxin? Blood Purif 2006;24:67-70.
Abdollahzad H, Eghtesadi S, Nourmohammadi I, Khadem-Ansari M, Nejad-Gashti H, Esmaillzadeh A. Effect of Vitamin C supplementation on oxidative stress and lipid profiles in hemodialysis patients. Int J Vitam Nutr Res 2009;79:281-7.
Nacak H, van Diepen M, de Goeij MC, Rotmans JI, Dekker FW; PREPARE-Study Group. Uric acid: Association with rate of renal function decline and time until start of dialysis in incident pre-dialysis patients. BMC Nephrol 2014;15:91.
Chen YC, Su CT, Wang ST, Lee HD, Lin SY. A preliminary investigation of the association between serum uric acid and impaired renal function. Chang Gung Med J 2009;32:66-71.
Gouri A, Dekaken A, Bentorki AA, Touaref A, Yakhlef A, Kouicem N. Serum uric acid level and cardiovascular risks in hemodialysis patients: An Algerian cohort study. Clin Lab 2014;60:751-8.
Muela HC, De Lima JJ, Gowdak LH, de Paula FJ, Bortolotto LA. Prognostic value of serum uric acid in patients on the waiting list before and after renal transplantation. Int J Nephrol 2015;2015:375606.
Glantzounis GK, Tsimoyiannis EC, Kappas AM, Galaris DA. Uric acid and oxidative stress. Curr Pharm Des 2005;11:4145-51.
Ross MA. Determination of ascorbic acid and uric acid in plasma by high-performance liquid chromatography. J Chromatogr B Biomed Appl 1994;657:197-200.
Zhang K, Dong J, Cheng X, et al. Association between Vitamin C deficiency and dialysis modalities. Nephrology (Carlton) 2012;17: 452-7.
Deicher R, Ziai F, Bieglmayer C, Schillinger M, Hörl WH. Low total Vitamin C plasma level is a risk factor for cardiovascular morbidity and mortality in hemodialysis patients. J Am Soc Nephrol 2005;16:1811-8.
Zhang K, Li Y, Cheng X, et al. Cross-over study of influence of oral Vitamin C supplementation on inflammatory status in maintenance hemodialysis patients. BMC Nephrol 2013;14:252.
Handelman GJ. Vitamin C deficiency in dialysis patients - Are we perceiving the tip of an iceberg? Nephrol Dial Transplant 2007;22: 328-31.
Biniaz V, Sadeghi Shermeh M, Ebadi A, Tayebi A, Einollahi B. Effect of Vitamin C supplementation on C-reactive protein levels in patients undergoing hemodialysis: A randomized, double blind, placebo-controlled study. Nephrourol Mon 2013;6:e13351.
Daurgidas JT, Blake PG, Ing TS. Handbook of Dialysis. 4th ed. Philadelphia: Lippincott; 2007. p. 774.
Bosly A, Sonet A, Pinkerton CR, et al. Rasburicase (recombinant urate oxidase) for the management of hyperuricemia in patients with cancer: Report of an international compassionate use study. Cancer 2003;98:1048-54.
Alqanatish JT, Alqahtani F, Alsewairi WM, Al-kenaizan S. Childhood scurvy: An unusual cause of refusal to walk in a child. Pediatr Rheumatol Online J 2015;13:23.
Scharnagl H, Nauck M, Wieland H, März W. The Friedewald formula underestimates LDL cholesterol at low concentrations. Clin Chem Lab Med 2001;39:426-31.
Latif W, Karaboyas A, Tong L, et al. Uric acid levels and all-cause and cardiovascular mortality in the hemodialysis population. Clin J Am Soc Nephrol 2011;6:2470-7.
Biniaz V, Tayebi A, Ebadi A, Sadeghi Shermeh M, Einollahi B. Effect of Vitamin C supplementation on serum uric acid in patients undergoing hemodialysis: A randomized controlled trial. Iran J Kidney Dis 2014;8:401-7.
Gao X, Curhan G, Forman JP, Ascherio A, Choi HK. Vitamin C intake and serum uric acid concentration in men. J Rheumatol 2008; 35:1853-8.
Juraschek SP, Miller ER 3rd, Gelber AC. Effect of oral Vitamin C supplementation on serum uric acid: A meta-analysis of randomized controlled trials. Arthritis Care Res (Hoboken) 2011;63:1295-306.
Ersoy A. Re: Effect of Vitamin C supplementation on serum uric acid in patients undergoing hemodialysis: A randomized controlled trial. Iran J Kidney Dis 2014;8:492-3.
Sirover WD, Liu Y, Logan A, et al. Plasma ascorbic acid concentrations in prevalent patients with end-stage renal disease on hemodialysis. J Ren Nutr 2015;25:292-300.
Candan F, Gültekin F, Candan F. Effect of Vitamin C and zinc on osmotic fragility and lipid peroxidation in zinc-deficient haemodialysis patients. Cell Biochem Funct 2002;20: 95-8.
Chen WT, Lin YF, Yu FC, Kao WY, Huang WH, Yan HC. Effect of ascorbic acid administration in hemodialysis patients on in vitro oxidative stress parameters: Influence of serum ferritin levels. Am J Kidney Dis 2003; 42:158-66.
Cross JM, Donald AE, Nuttall SL, Deanfield JE, Woolfson RG, Macallister RJ. Vitamin C improves resistance but not conduit artery endothelial function in patients with chronic renal failure. Kidney Int 2003;63:1433-42.
Deicher R, Hörl WH. Vitamin C in chronic kidney disease and hemodialysis patients. Kidney Blood Press Res 2003;26:100-6.
Tarng DC, Liu TY, Huang TP. Protective effect of Vitamin C on 8-hydroxy-2'-deoxyguanosine level in peripheral blood lymphocytes of chronic hemodialysis patients. Kidney Int 2004;66:820-31.
Chan D, Irish A, Croft KD, Dogra G. Effect of ascorbic acid supplementation on plasma isoprostanes in haemodialysis patients. Nephrol Dial Transplant 2006;21:234-5.
Kwan BC, Kronenberg F, Beddhu S, Cheung AK. Lipoprotein metabolism and lipid management in chronic kidney disease. J Am Soc Nephrol 2007;18:1246-61.
Washio K, Inagaki M, Tsuji M, et al. Oral Vitamin C supplementation in hemodialysis patients and its effect on the plasma level of oxidized ascorbic acid and Cu/Zn superoxide dismutase, an oxidative stress marker. Nephron Clin Pract 2008;109:c49-54.
Afkhami-Ardekani M, Shojaoddiny-Ardekani A. Effect of Vitamin C on blood glucose, serum lipids & serum insulin in type 2 diabetes patients. Indian J Med Res 2007;126:471-4.
McRae MP. Vitamin C supplementation lowers serum low-density lipoprotein cholesterol and triglycerides: A meta-analysis of 13 randomized controlled trials. J Chiropr Med 2008;7:48-58.
Khajehdehi P. Effect of vitamins on the lipid profile of patients on regular hemodialysis. Scand J Urol Nephrol 2000;34:62-6.
Ghada Mohamed El Mashad
Pediatrics Department, Faculty of Medicine, Menoufia University, Menoufia
[Table 1], [Table 2], [Table 3]
| Article Access Statistics|
| Viewed||2779 |
| Printed||19 |
| Emailed||0 |
| PDF Downloaded||492 |
| Comments ||[Add] |