INTRODUCTION:

Diabetes mellitus is a chronic illness, and increase burden to the society. In India prevalence increase upto 366 million in2030.Identification of the risk factors are important to assist change while face well being challenges.¹An antioxidant is capable to give an electron to a free radical and stability out the unpaired electron, which neutralize the free radical. Whenever the enough quantity of antioxidants are present for the quantity of free radical produced, there should not be any damage to our body, but the quantity of antioxidants is less than the free radicals formed then oxidative stress occurs.

Vitamin C is one of the water soluble antioxidant to fight against free radicals within the plasma and blood². The structural similarity between glucose and Vitamin is quite interesting in diabetes.³ Review on the effect of vitamin C from various 23 observational studies explained that the people suffering from diabetes have at least 30% deficiency in concentration than the normal healthy adults.⁴ The supplementation of vitamin C was studied in three observational studies in diabetes mellitus which states that an improvement of fasting blood sugar and HbA1c was noted after supplementation with a dose of 200mg daily for a period of 90 days and further no improvement is seen ,then the patients supplemented with 500mg daily for 2 months, nor by short term supplementation for 2 weeks.^5-7

METHODOLOGY:

The research work was designed as Randomized, Parallel design active control study.

Sample Size:

Sample size = 2(SD)²x (Z_α/2+Z_β)²

d²

SD = 7.1 (pooled standard deviation of Δ total cholesterol from literatures)

Z_α/2= 1.96; Z_β = 0.84

d = 5

Sample size = 2(7.1)²x (1.96+0.84)²

5²

= 31.68

= 32 patients in each study arm

Total sample size = 64

After getting approval from institutional ethics committee (Ref no: IEC/PHD/2015/2016/01) and the study registered in Clinical Trial Registry India (CTRI/2017/10/010035), patients were enrolled by using randomization procedure and assigned to control group and intervention group. Patients of both genders of age between 35-65 years, diagnosed with diabetes mellitus for a period of not less than 2 years with co-morbid cardiovascular disease (new onset/ past history), HbA1c level above 8.0, in treatment with the standard treatment regimen for diabetes mellitus as per the recommended guidelines and willing to provide written informed consent are included in the study. Patient with concomitant life threatening illness, including myocardial infarction, ischemic stroke or risk of developing NSTEMI, STEMI, patients developed metabolic acidosis; patients who had a history of renal calculi were excluded from the study.32 Patients in the intervention group received Vitamin C 500mg bid supplementation along with antidiabetic and antihyperlipidemic therapy as per the standard treatment protocol for a period of three months. 32 Patients in the control group prescribed anti diabetic and anti hyperlipidemic drugs without Vitamin C.Both the group of patients was not prescribed with any other vitamins. Demographic data and general health characteristics, including education, occupation, height, social habits and food habits were collected in specially structured data collection form by face to face interview during the baseline visit. Measurements were performed at time points of baseline first month, second month and third month of follow-up. The patients were informed to follow the regular food habits. All the patients in the control and intervention group were analyzed for C Reactive Protein, lipid parameters (Total Cholesterol, TGs, LDL, VLDL, HDL) and HbA1c in first, second and third month of treatment.

Statistical analysis:

The datas recorded were analyzed by using the SPSS software (v 23.0; IBM C orporation, Armonk, NY, USA). After the assumption of normality, the continuous variables were presented as mean± S.D. At base line of randomization the difference between the groups was analyzed by independent t-tests. Paired t-test was used to evaluate the difference in mean within the groups before and after an intervention. The statistical significance of the differences between repeated measures was assessed by one-way ANOVA.

RESULTS:

A total of 64 patients were enlisted to participate in the study at baseline level. The mean age of the patients was 50.04±6.3 in which 48% were male 52% were females. The mean BMI, duration of diabetes, SBP and DBP of subjects were 27±4.71, 9.93±4.71, 137.28±20.06 and 81.78±10.23 respectively. The incidence of elevated CRP was found to be 68%. The baseline demographic, anthropometric and clinical characteristics of the patients in both groups were comparable (Table 1). To determine the balance between the patients in the groups, comparisons of all patients’ characteristics were undertaken. Comparative results found that there is no statistically significant difference for any variable of comparison was detected and no difference appeared between the groups in terms of age, sex and BMI. Further, no significant differences in means of clinical variables in comparing groups. Total cholesterol, triglycerides, HDL, LDL, VLDL, FBS, PPBS, HbA1c and C reactive protein. These results for all variables indicate Significant balance between the baseline groups and indicate similarity, because the differences did not reach the significance level of p-value<0.05. Table 2 represents the changes in lipid profile at each time points, from the baseline (before treatment) to end point (after treatment), within groups. In the vitamin C group, the changes appear in variables after each time points of intervention: Total cholesterol (p=0.004), TGL (p=0.032), LDL (p<0.001), can be seen to have reduced significantly. In the control group, the changes appear significantly in two variables after each time points: Total cholesterol (p=0.046) and CRP (p<0.001). Table no 3 presents the changes in blood sugar profile and CRP. In the vitamin C group, the changes appeared in variables after each time points of intervention FBS (0.038), PPBS (0.047), HbA1c (0.026) and CRP (<0.001) can be seen to have reduced significantly. Whereas in control group only CRP level has been found to have significant difference within the group. The changes within the control group could be attributed to changes in lifestyle factors, such as eating habitor level of physical activities etc.as the study is Open-Labeled study in nature. However statistically significant changes found between the treatment group before and after the treatment period did not mean that the supplement was effective in retarding the risk of high levels of patients clinical characteristics. To determine this comparison of the differences between the groups at each time points (after treatment) was done to assess the clinical significance of vitamin C. The significance was detected for T.Chlol (p=0.004), TGL (p=0.032), LDL (p<0.001), FBS (0.038), PPBS (0.047), HbA1c (p=0.026) and CRP(<0.001). Table no 4 represents comparison of differences in means of clinical variables at the endpoint between groups. The statistically significant differences between groups were observed in TGL (p=0.029), LDL (p=0.019), VLDL (p=0.041) and FBS (p<0.001). This data means the reduction in levels of clinical variables after 3 months of daily use of 1g of Vitamin C (500mg bid) were true and resulted from the effect of the supplement.

Table 1: comparison of differences in means of demographic, anthropometric, and clinical variables at baseline (randomization) of patients in both groups.

Parameters	Total mean	Study groups		P value
Parameters	Total mean	Control Arm	Intervention Arm	P value
Age(Years)	50.04±14.58	48.6±16.48	51.4±13.08	0.085
BMI(kg/m²)	27.94±4.71	27.94±4.71	26.34±4.64	0.176
Duration (Years)	9.93±4.83	10.28±5.79	9.59±4.64	0.571
Tot.chol(mg/dl)	239.84±54.08	240.59±44.07	239.09±91.81	0.821
TGL(mg/dl)	150.89±24.11	149.03±23.41	152.74±25.09	0.567
HDL(mg/dl)	48.55±12.08	49.14±11.04	47.96±14.56	0.407
LDL(mg/dl)	115.65±38.45	115.24±31.04	116.06±46.18	0.291
VLDL(mg/dl)	24.71±9.86	24.29±9.41	25.14±10.11	0.456
FBS(mg/dl)	283.24±118.59	281.08±116.46	285.42±121.03	0.647
PPBS(mg/dl)	333.09±94.85	329.62±81.57	336.56±99.24	0.866
HbA1c(%)	9.78±1.98	9.85±1.42	9.68±2.01	0.742
CRP(mg/l)	12±9.14	11.42±8.1	12.58±9.42	0.341

Table no 2: Comparison of differences in means of lipid profile before and after each time points of an intervention in both groups.

Parameters	Study Group	Baseline	1^st Month	2^nd Month	3^rd Month	p-Value
Tot.Chol	Control	240.59±44.07	236.16±48.18	233.26±51.64	232.33±50.09	0.046*
Tot.Chol	Intervention	239.09±91.81	239.16±89.43	228.45±89.19	226.68±88.48	0.004**
TGL	Control	149.03±23.41	151.32±24.08	156.42±21.14	147.78±24.28	0.144
	Intervention	152.74±25.09	151.07±26.71	143.78±25.92	142.58±24.89	0.035*
HDL	Control	49.14±11.04	48.09±11.89	51.14±12.01	52.01±12.03	0.139
HDL	Intervention	47.96±14.56	50.01±17.94	51.87±16.67	53.04±16.98	0.041*
LDL	Control	115.24±31.04	117.81±34.17	115.89±33.07	116.71±32.01	0.417
LDL	Intervention	116.06±46.18	109.11±51.28	108.81±52.09	106.48±50.81	<0.001**
VLDL	Control	24.29±9.41	24.59±8.49	26.14±10.28	25.09±9.51	0.092
VLDL	Intervention	25.14±10.11	24.48±10.98	24.91±12.16	22.84±14.78	0.051

Table 3: Comparison of differences in means of blood sugar profile and CRP before and after each time points of an intervention in both groups.

Parameters	Study Group	Baseline	1^st Month	2^nd Month	3^rd Month	p-Value
FBS	Control	281.08±117.46	282.18±108.21	279.84±121.38	280.34±129.57	0.244
FBS	Intervention	285.42±109.15	266.83±116.2	261.14±101.93	257.09±119.04	0.038*
PPBS	Control	329.62±81.57	321.71±90.09	316.08±85.14	312.14±86.47	0.198
	Intervention	336.56±116.28	321.61±101.9	321.61±128.85	319.47±117.14	0.047*
HbA1c	Control	9.97±1.48	-	-	9.76±1.43	0.081
	Intervention	10.22±1.29	-	-	9.97±1.48	0.026*
CRP	Control	11.42±8.1	4.98±2.24	1.65±0.49	0.82±0.01	<0.001**
	Intervention	12.58±9.42	3.92±1.78	1.09±0.94	0.925±0.11	<0.001**

DISCUSSION:

Vitamin C is an antioxidant; it prevents free radical damage and protects our body. Vitamin C facilitate the functions of cholesterol converted into bile acids, thereby it cholesterol levels lowered.⁸ In type 2 diabetes mellitus due to hyperglycemia, there will be long term, dysfunction, damage, and failure of different organs like eyes (diabetic retinopathy), kidneys (diabetic nephropathy) and nerves (diabetic neuropathy), blood vessels(atherosclerosis) and heart (myocardial infarction).^9-11 Clinical trials were conducted to show the effect of vitamin C in reducing fasting blood glucose level and also on lipid profile. A clinical study conducted at Diabetes Research Center, ShahidSadoughi University of Medical Sciences, Iran, vitamin C 500mg and 1000mg were administered for a period of 6 weeks to patients with type 2 DM. Vitamin C 1000mg showed statistically significant reduction in fasting blood glucose and improvement in lipid profile but there was no significant fall in the serum triglyceride level.¹² Another study conducted by Dakhale et al, it was a randomized double blind study for a 12 weeks period of treatment with metformin and vitamin C showed a significant reduction in the levels of FBS,PPBS and HbA1c.¹³ Similar study conducted by RekhaNayaka M.R. et al showed that vitamin C 2gms helps in increasing HDL level significantly in patients at the end of 8^th week and significant reduction in TGL,T.Chol, LDL within the groups but no significant reduction between the groups at the end of 8^th week.¹⁴ our study showed that vitamin C 1gm helps in increasing HDL level significantly in patients at the end of 3 months and significant reduction in T. Chol, TGL, LDL within the groups as well as significant reduction in between the groups at the end of 3 months. In Ellulu et al study, the effect of vitamin C on FBG was examined after 8 weeks of daily intake. It was found that FBG reduced significantly in both the experimental and control groups and this shows the efficacy of vitamin C, clinical significance was achieved.¹⁵ whereas in our study, FBS, PPBS and HbA1c were found to have reduced significantly in intervention group after three months. No significant difference found in control group. A study by Kalaivanan et al, studied on diabetes and CAD patients, lipid profile were assessed, there is no significant difference. Reducing LDL, Triglycerides and increasing HDL was necessary to prevent from cardiovascular complications¹⁶

CONCLUSION:

Based on the results of this study, it can be concluded that Vitamin C as an adjuvant therapy produces beneficial effect in type 2 diabetes patients. Vitamin C 1g/day showed improved the lipid profile which helps in cardiovascular risk mitigation and Vitamin C adjuvant therapy helps to improve FBS, PPBS and HbA1c. Treatment with Vitamin C with atorvastatin was well tolerated and devoid of any side effects. Which has an advantage of absence of any substantial side effects, cheaper cost, improvement in lipid profile and the fact plasma ascorbic acid levels are decreased in diabetes mellitus and increased after oral supplementation make it a particularly attractive therapeutic adjuvant in the treatment of type 2 DM.

REFERENCES:

1. Wild S, Roglic G, Green A, Sicree R, King H. Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes Care. 2004 May;27(5):1047-53. doi: 10.2337/diacare.27.5.1047. PMID: 15111519.

2. Diplock AT. Antioxidant nutrients and disease prevention: an overview. Am J Clin Nutr. 1991 Jan;53(1 Suppl):189S-193S. doi: 10.1093/ajcn/53.1.189Sb. PMID: 1985386.

3. Mann GV. Hypothesis: the role of vitamin C in diabetic angiopathy. Perspect Biol Med. 1974;17(2):210–217.

4. Will JC, Byers T. Does diabetes mellitus increase the requirement for vitamin C? Nutr Rev. 1996 Jul;54(7):193-202. doi: 10.1111/j.1753-4887.1996.tb03932.x. PMID: 8918139.

5. Bishop N, Schorah CJ, Wales JK. The effect of vitamin C supplementation on diabetic hyperlipidaemia: a double blind, crossover study. Diabet Med. 1985 Mar;2(2):121-4. doi: 10.1111/j.1464-5491.1985.tb00614.x. PMID: 2952396.

6. Eriksson J, Kohvakka A. Magnesium and ascorbic acid supplementation in diabetes mellitus. Ann Nutr Metab. 1995;39(4):217-23. doi: 10.1159/000177865. PMID: 8546437.

7. Lu Q, Bjorkhem I, Wretlind B, Diczfalusy U, Henriksson P, Freyschuss A. Effect of ascorbic acid on microcirculation in patients with Type II diabetes: a randomized placebo-controlled cross-over study. ClinSci (Lond). 2005; 108(6): 507-513.

8. Dunitz JD. Linus Carl Pauling. 28 Febuary 1901-19 August 1994.biographical Memoirs of Fellows of the Royal Society. 1996; 42:316-8

9. American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetic Care.2010;33: S62.

10. Tesfaye S, Gill G. Chronic diabetic complications in Africa. Afr J Diabetes Med. 2011; 19:4-8.

11. Chintan AP, Nimish LP, Nayana B, Bhavna M, Mahendra G, Hardik T. cardiovascular complication of diabetes mellitus. J Appl Pharm Sci. 2011; 4:1-6

12. Mohammad Afkhami-Ardekani& Ahmad Shojaoddiny-Ardekani. Effect of vitamin C on blood glucose, serum lipids & serum insulin in type 2 diabetes patients. Indian J Med Res. November 2007; 126:471-474.

13. Dakhale GN, Chaudhari HV, Shrivastava M. Supplementation of vitamin C reduces blood glucose and improves glycosylated hemoglobin in type 2 diabetes mellitus: a randomized, double-blind study. Adv Pharmacol Sci. 2011; 2011:195271. doi: 10.1155/2011/195271. Epub 2011 Dec 28. PMID: 22242019; PMCID: PMC3254006.

14. Rekha Nayaka M.R. A comparative trial on the efficacy of vitamin C as add on therapy to the oral hypoglycemic agent on serum lipid level in newly diagnosed type 2 diabetes mellitus. IJPR. 2015;5(4):115-118.

15. Mohammed S Ellulu, Asmah Rahmat, Ismail Patimah, Huzwah Khaza, Yehia Abed. Effect of vitamin C on inflammation and metabolic markers in hypertensive and /or diabetic obese adults: a randomized controlled trail. Drug Design, Development and Therapy. 2015:9;3405-3412.

16. Kalaivanan S, Sarumathy S, Anisha Ebens J, Naresh Kumar K, Roobena Parveen A, Nasreen Ashraf M. Clinical Assessment and Comparison of Lipid Profiles among Coronary Artery Disease and type 2 Diabetes Mellitus Patients receiving Statin Therapy. Research J. Pharm. and Tech. 2017; 10(1): 18-20. doi: 10.5958/0974-360X.2017.00005.1

Received on 18.09.2021 Modified on 08.01.2022

Asian J. Pharm. Tech. 2022; 12(2):125-128.

DOI: 10.52711/2231-5713.2022.00021