Effect of Vitamin C Supplementation on Postprandial Oxidative Stress and Lipid Profile in Type 2 Diabetic Patients
Diabetes mellitus is one of the most wide spread endocrine disorders and an important developing health problem in the world. Cardiovascular disease is a common complication of type 2 diabetes. Several risk factors for coronary heart disease cosegregate in type 2 diabetes, including hyperglycemia, hyperlipaemia, increases production of free radical and decrease in antioxidant defense system. In this study we evaluated the effect of vitamin C supplementation on fasting and postprandial oxidative stress and lipid profile in type 2 diabetic patients. 30 patients with type 2 diabetes from Nader Kazemi Clinic, Shiraz, Iran were randomly divided into 2 groups; vitamin C treatment group (1000 mg d-1) and placebo group from May to September 2010. Fasting and postprandial lipid profile and Malondialdehyde (MDA) level were measured at the beginning of the study and after six weeks of supplementation. Data analysis was carried out using Mann-Whitney U test with p<0.05 being significant by SPSS software version 16.The result of the study showed a significantly decrease in fasting (p = 0.006) and postprandial MDA (p<0.001) in vitamin C group compare to placebo group but not in lipid profile. This study suggests that vitamin C supplementation can decrease fasting and postprandial oxidative stress and may prevent diabetes complication.
to cite this article:
Zohreh Mazloom, Najmeh Hejazi, Mohammad-Hossein Dabbaghmanesh, Hamid-Reza Tabatabaei, Afsane Ahmadi and Hasti Ansar, 2011. Effect of Vitamin C Supplementation on Postprandial Oxidative Stress and Lipid Profile in Type 2 Diabetic Patients. Pakistan Journal of Biological Sciences, 14: 900-904.
Received: August 06, 2011;
Accepted: October 14, 2011;
Published: November 26, 2011
Diabetes is one of the major endocrine disorders worldwide. It is responsible
for a numbers of health problems and impaired quality of life. The major contributor
to the increasing number of diabetic patients will be type 2 diabetes which
is characterized by Excessive hepatic glucose production, decreased insulin
secretion and Increase insulin resistance (Rosen et al.,
2001). There is emerging evidence that oxidative stress make a significant
contribution in the development and progression of diabetes. Mechanisms by which
increased oxidative stress involve in diabetic complication are including, oxidizing
and damaging DNA, protein and lipid as well as ability to function as signaling
molecules to activate the number of cellular damage (Evans
et al., 2002).
Cardiovascular Diseases (CVD) mortality is high among diabetic patients due
to abnormalities of plasma lipid and lipoprotein metabolism (Franz,
2004). Evidence shows that postprandial hyperglycemia and hyperlipeamia
can predict cardiovascular disease risks more strongly than fasting values (Franz,
2004; Evans and Rees, 2001). It has been reported
that postprandial hypertriglyceridaemia can cause endothelial dysfunction which
is recognized as an early process of atherosclerosis (Bae
et al., 2001, 2003). The link between acute
postprandial hyperglycemia and cardiovascular risk factor has been suggested
to be oxidative stress (Fox and Lefebvre, 2007; Baynes
and Thorpe, 1999; Feillet-Coudray et al., 1999).
Oxidative stress results from an imbalance between proxidant load and the antioxidant
defense system. In diabetes, non-enzymatic protein glycation and glucose autoxidation
may generate free radicals which in turn catalyses lipid peroxidation (Feillet-Coudray
et al., 1999).
Postprandial increases of lipid and carbohydrate concentrations causes oxidative
stress, by increasing the production of free radicals through activating several
biochemical pathways (Ceriello et al., 1998)
which has been associated with increases susceptibility of LDL oxidation (Sies
et al., 2005) and a higher risk for cardiovascular disease. Evidence
showed that antioxidant can provide protection from the oxidative effects of
postprandial hyperglycemia and hyperlieapiema (Sies et
al., 2005; Ursini and Sevanian, 2002; Ceriello,
2005; Tessier et al., 2009).
Vitamin C is one of the most readily available dietary antioxidants. Treatment
with vitamin C inactivates the circulating free radicals (Levin
et al., 2006). It has also been suggested that vitamin C exert cardiovascular
and other health benefits in humans in part by acting as an antioxidant (Polidori
et al., 2004). Studies have shown that vitamin C is the only antioxidant
in human plasma that can completely protect endogenous lipids from detectable
oxidative damage induced by aqueous peroxyl radicals and other reactive oxygen
species (Frei et al., 1988, 1989).
The aim of the present study was to determine the effects of vitamin C supplementation on postprandial oxidative stress and lipid profile in diabetic patients in order to decrease or prevent cardiovascular disease in this group of population.
MATERIALS AND METHODS
Subjects: A randomized single blind placebo controlled clinical trial was conducted on 30 type 2 diabetic patients (age range 30-65 years; 8 men and 22 women; having diabetes for at least 1 year). All participants were nonsmoker, receiving standard oral hypoglycemic agents, had no history or clinical evidence of overt vascular disease, acute or chronic inflammatory disease.
None of the Patients were treated with lipid lowering drugs, hormone replacement therapy and or diuretics, β-blockers and aspirin. All subjects were fully informed of the purpose and procedures of the trial and were free to leave the trial at any time. Written informed consent was obtained from all participants. This study took place in Nader Kazemi Clinic, Shiraz, Iran, which is affiliated to Shiraz University of Medical Sciences from May to September 2010. The research protocol was approved by the Ethics Committee on Human Experimentation of Shiraz University of Medical Sciences.
Diabetic patients were randomly divided in two groups (4 men and 11 women in each group). Group 1 vitamin C treatment group (1000 mg day-1). Group 2 placebo (acetate cellulose) group (1000 mg day-1). All subjects received supplements and placebo for six weeks.
The supplement and placebo capsules looked identical and were specially prepared for this study by General Nutrition Center (GNC) in the USA.
We wanted from participants to avoid any changes in their medication whenever possible.
Protocol: Five milliliters of blood were collected after overnight fasting, for the measurement of serum total cholesterol, LDL-cholesterol, HDL-cholesterol, triglyceride and malondialdehyde (MDA) level. Each participant was then given a breakfast that contained 80 g fat (include a piece of cake, a small cheese sandwich and 200 mL high fat milk) and afterwards to take a rest in a chair and watch a television without any food, tea and or coffee. Two hours after finishing the test meal Lipid profile and MDA level were measured repeatedly (postprandial state). At this point patients in group 1 received vitamin C (1000 mg day-1) and group 2 received placebo (acetate cellulose) for six weeks. At the end of six weeks the baseline procedure was repeated and fasting and 2 h post-prandial lipid profile and MDA level measured.
Lipid profiles were measured by biosystem A-25 autoanalyser. Plasma MDA concentration was measured by determines levels of TBARS (Thiobarbituric acid reactive substances) as a measure of lipid peroxidation by using spectophotometric assay.
Data analysis: Data analysis was carried out using Mann-Whitney U test to compare the mean differences between both groups by SPSS software version 16. Basic data expressed as Mean±standard deviation, fasting and postprandial biochemical parameters before and after intervention expressed as median (inter quartile range). It was considered significant if the p value was lower than 0.05.
Table 1 shows the general and demographic characteristics,
biochemical parameters and daily doses of drug intake of the 30 diabetic patients
participated in this study.
|| Patient characteristics and biochemical profiles
|*Data expressed as Mean±SD except N (number of participants)
|| Biochemical parameters in fasting and postprandial states
before and after supplementation
|1The Interquartile Range (IQR) is the distance
between the 75th percentile and the 25th percentile. 2p≤0.05
Considering the parameters reported in Table 1, no significant
differences was observed in general characteristics such as sex, age, duration
of diabetes, Body Mass Index (BMI), daily dose of drugs and biochemical parameters
between the vitamin C and placebo groups at baseline. Three patients were excluded
from statistical analysis because they interrupted trial treatment.
After six weeks of supplementation, level of MDA was significantly lower on both fasting (p = 0.006) and postprandial state (p<0.001) in patients treated with 1000 mg day-1 vitamin C compared to placebo. However, no significant differences were observed in the fasting and postprandial lipid profile of patients after vitamin C supplementation (Table 2).
This study demonstrates that supplementation of 1000 mg Vitamin C for 6 weeks
can significantly decrease MDA concentration in fasting and postprandial state
in diabetic patients. While this study showed the effect of vitamin C supplementation
on MDA concentration of diabetic patients, others evaluate the vitamin C effect
on plasma antioxidant status and resistance to lipid peroxidation of healthy
subjects. Short-term and long-term vitamin C supplementation in humans significantly
increases plasma ascorbate concentrations and dose-dependently improves the
resistance of plasma to lipid peroxidation (Polidori et
al., 2004). The finding of this study is in agreement with other studies
that have shown that vitamin C effectively protecting plasma against oxidative
damage (Tessier et al., 2009; Polidori
et al., 2004; Frei et al., 1988, 1989).
In this study we investigated the effect of vitamin C on fasting and postprandial
oxidative stress and lipid profile. Our findings suggest that supplementation
of 1000 mg Vitamin C at least 6 weeks can significantly decrease MDA concentration
in fasting and postprandial state in diabetic patients that was in agreement
with other studies (Tessier et al., 2009; Polidori
et al., 2004; Frei et al., 1988,
1989). We did not observe any effect of Vitamin C on
fasting and/or postprandial lipid profile.
Previous studies have suggested that Diabetes is a disease in which hyperglycemia
and increased Free Fatty Acids (FFA) result in generation of Reactive Oxygen
Species (ROS) which are involved in the pathogenesis of diabetic complications
through increased oxidative stress (Evans and Rees, 2001;
Brownlee, 2001; Maxwell et al.,
1997; Brownlee, 2005; Evans
et al., 2003). One major consequence of this process is the production
of gene products such as pro-inflammatory cytokines (TNF-α and IL-6), endothelin-1
(ET-1) and adhesion molecules which are associated with endothelial dysfunction
(Park et al., 1999). Furthermore, free radicals
are able to damage lipids thorough lipid peroxidation that is strongly contributed
to the development of atherosclerosis (Rosen et al.,
Recent evidence showed that the postprandial hyperglycemia and hyperlipaemia
is an important contributing factor to the development of atherosclerosis (Bonora
and Muggeo, 2001). In diabetes, the postprandial phase is characterized
by a rapid and large increase in blood glucose and Triglyceride (TG) rich lipoprotein
(Ceriello, 2005; Kusunoki et
al., 2000). It has been suggested that over generation of oxidative
stress due to hyperglycemia and hyperlipidemia in diabetic patients, induce
an endothelial dysfunction (Ceriello et al., 2002).
Our study reaffirms that type 2 diabetics is associated with oxidative stress.
Other studies showed a postprandial increase in a product of oxidative damage
(MDA), closely mirroring the changes in blood glucose in diabetic patients (Temelkova-kurktschiev
et al., 2000).
Thus, postprandial hyperglycemia and hypertriglyceridemia may act as predictors
of CVD in diabetic patients (Teno et al., 2000).
Temelkova-kurktschiev et al. (2000) showed that
diabetes mellitus alters the antioxidant defense system. There is also evidence
that treatment with vitamin C may reduce the oxidative stress production (Evans
et al., 2003) and so improving endothelial function and reduces the
cardiovascular related problems (Evans et al., 2002).
This study support previous observation of beneficial effects of vitamin C on
oxidative Stress (Title et al., 2000; Maharjan
et al., 2008; Neri et al., 2005).
Our data demonstrated reduced oxidative stress production in vitamin C supplemented
group as well.
In conclusion this study shows that a short time supplementation of vitamin C can significantly reduces the MDA, a major product of oxidative damage in both fasting and postprandial states of type 2 diabetic patients.
This research was funded by Shiraz University of Medical Sciences in relation
to master of sciences studens thesis (Najmeh Hejazi).
The authors wish to appreciate the Shiraz University of Medical Sciences for their support. We are indebted to the patients for their cooperation.
1: Bae, J., E. Bassenge, K. Kim, Y. Kim and K.S. Kim et al., 2001. Postprandial hypertriglyceridemia impairs endothelial function by enhanced oxidant stress. Atherosclerosis, 155: 517-523.
Direct Link |
2: Bae, J.H., M. Schwemmer, I.K. Lee, H.J. Lee, K.R. Park, K.Y. Kim and E. Bassenge, 2003. Postprandial hypertriglyceridemia-induced endothelial dysfunction in healthy subjects is independent of lipid oxidation. Int. J. Cardiol., 87: 259-267.
3: Baynes, J.W. and S.R. Thorpe, 1999. Role of oxidative stress in diabetic complications: A new perspective on an old paradigm. Diabetes, 48: 1-9.
CrossRef | Direct Link |
4: Brownlee, M., 2001. Biochemistry and molecular cell biology of diabetic complications. Nature, 414: 813-820.
CrossRef | PubMed | Direct Link |
5: Brownlee, M., 2005. The pathobiology of diabetic complications: A unifying mechanism. Diabetes, 54: 1615-1625.
CrossRef | PubMed | Direct Link |
6: Bonora, E. and M. Muggeo, 2001. Postprandial blood glucose as a risk factor for cardiovascular disease in type II diabetes: The epidemiological evidence. Diabetologia, 44: 2107-2114.
7: Ceriello, A., 2005. Postprandial hyperglycemia and diabetes complications: Is it time to treat?. Diabetes, 54: 1-7.
8: Ceriello, A., N. Bortolotti, E. Motz, A. Crescentini and S. Lizzio et al., 1998. Meal generated oxidative stress in type 2 diabetic patients. Diabetes Care, 21: 1529-1533.
9: Ceriello, A., C. Taboga, L. Tonutti, L. Quagliaro and L. Piconi et al., 2002. Evidence for an independent and cumulative effect of postprandial hypertriglyceridemia and hyperglycemia on endothelial dysfunction and oxidative stress generation: Effects of short-and long-term simvastatin treatment. Circulation, 106: 1211-1218.
Direct Link |
10: Evans, M., R.A. Anderson, J.C. Smith, N. Khan and J.M. Graham et al., 2003. Effects of insulin lispro and chronic vitamin C therapy onpostprandial lipaemia, oxidative stress and endothelial function in patients with type 2 diabetes mellitus. Eur. J. Clin. Invest., 33: 231-238.
11: Evans, J.L., I.D., Goldfine, B.A. Maddux and G.M. Grodsky, 2003. Are oxidative stress-activated signaling pathways mediators of insulin resistance and β-cell dysfunction? Diabetes, 52: 1-8.
CrossRef | PubMed | Direct Link |
12: Evans, L.M. and A. Rees, 2001. Diabetic Dyslipidaemia. In: Lipids and Atherosclerosis Annual, Gaw, A. and J. Shepherd, (Eds.). Martin Dunitz, London, pp: 177-197.
13: Feillet-Coudray, C., E. Rock, C. Coudray, K. Grzelkowska, V. Azais-Braesco, D. Dardevet and A. Mazur, 1999. Lipid peroxidation and antioxidant status in experimental diabetes. Clin. Chim. Acta, 284: 31-34.
14: Fox, K. and P. Lefebvre, 2007. Diabetocardiology: Heart Disease in Diabetes. Medicographia, 29: 203-292.
Direct Link |
15: Franz, M.J., 2004. Medical Nutrition Therapy for Diabetes Mellitus and hypoglycemia of Nondiabetic Origin. In: Krause's Food and Nutrition Therapy, Mahan, L.K. and S. Escott-Stump, (Eds.). 11th Ed., WB Saunders, Philadelphia, pp: 792-837.
16: Frei, B., L. England and B.N. Ames, 1989. Ascorbate is an outstanding antioxidant in human blood plasma. Proc. Natl. Acad. Sci. USA., 86: 6377-6381.
PubMed | Direct Link |
17: Frei, B., R. Stocker and B.N. Ames, 1988. Antioxidant defense and lipid peroxidation in human blood plasma. Proc. Natl. Acad. Sci. USA., 85: 9748-9752.
18: Kusunoki, J., K. Aragane, T. Kitamine, H. Kozono and K. Kano et al., 2000. Postprandial hyperlipidemia in streptozotocin-induced diabetic rats is due to abnormal increase in intestinal acyl coenzyme A: Cholesterol acyltransferase activity. Arterioscler. Thromb. Vasc. Biol., 20: 171-178.
19: Levin, M., A. Katz and S.J. Padayatty, 2006. Vitamin C. In: Modern Nutrition and Diet Therapy, Shils, M.E., M. Shike, A.C. Ross, B. Caballera and R.J. Cousins, (Eds.). 10th Ed., Lippincott Williams and Wilkins, Philadelphia, pp: 507-522.
20: Maharjan, B.R., J.C. Jha, D. Adhikari, P. Vishwanath, J. Baxi, V.M. Alurkar and P.P. Singh, 2008. A study of oxidative stress, antioxidant status and lipid profile in diabetic patient in the western region of Nepal. Kathmandu Univ. Med. J., 6: 16-22.
21: Maxwell, S.R., H. Thomason, D. Sandler, C. Leguen and M.A. Baxter et al., 1997. Antioxidant status in patients with uncomplicated insulin-dependent and non-insulin-dependent diabetes mellitus. Eur. J. Clin. Invest., 27: 484-490.
22: Neri, S., S.S. Signorelli, B. Torrisi, D. Pulvirenti and B. Mauceri et al., 2005. Effects of antioxidant supplementation on postprandial oxidative stress and endothelial dysfunction: A single-blind, 15-day clinical trial in patients with untreated type 2 diabetes, subjects with impaired glucose tolerance and healthy controls. Clin. Ther., 27: 1764-1773.
CrossRef | Direct Link |
23: Park, J.Y., S.W. Ha and G.L. King, 1999. The role of protein kinase C activation in the pathogenesis of diabeteic vascular complications. Perit. Dial. Int., 19: S222-S227.
24: Polidori, M.C., P. Mecocci, M. Levine and B. Frei, 2004. Short-term and long-term vitamin C supplementation in humans dose-dependently increases the resistance of plasma to ex vivo lipid peroxidation. Arch. Biochem. Biophys., 423: 109-115.
25: Rosen, P., P.P. Nawroth, G. King, W. Moller, H.J. Tritschler and L. Packer, 2001. The role of oxidative stress in the onset and progression of diabetes and its complications: A summary of a congress series sponsored by UNESCO-MCBN, the American diabetes association and the German diabetes society. Diabetes/Metab. Res. Rev., 17: 189-212.
CrossRef | PubMed | Direct Link |
26: Sies, H., W. Stahl and A. Sevanian, 2005. Nutritional, dietary and postprandial oxidative stress. J. Nutr., 135: 969-972.
PubMed | Direct Link |
27: Temelkova-kurktschiev, T.S., C. Koehler, E. Henkel, W. Leonhardt, K. Fuecker and M. Hanefeld, 2000. Postchallenge plasma glucose and glycemic spikes are more strongly associated with atherosclerosis than fasting glucose or HbA1c level. Diabetes Care, 23: 1830-1834.
28: Teno, S., Y. Uto, H. Nagashima, Y. Endoh, Y. Lwamoto, Y. Omori and T. Takizawa, 2000. Association of postprandial hypertriglyceridemia and carotid intima-media thickness in patients with type 2 diabetes. Diabetes Care, 23: 1401-1406.
29: Title, L.M., P.M. Cummings, K. Giddens and B.A. Nassar, 2000. Oral glucose loading acutely attenuates endothelium-dependent vasodilatation in healthy adults without diabetes: An effect prevented by vitamin C and E. J. Am. Coll. Cardiol., 36: 2185-2191.
30: Tessier, D.M., A. Khalil, L. Trottier and T. Fulop, 2009. Effects of vitamin C supplementation on antioxidants and lipid peroxidation markers in elderly subjects with type 2 diabetes. Arch. Gerontol. Geriatrics, 48: 67-72.
31: Ursini, F. and A. Sevanian, 2002. Postprandial oxidative stress. Bio. Chem., 383: 599-605.
32: Evans, J.L., I.D. Goldfine, B.A. Maddux and G.M. Grodsky, 2002. Oxidative stress and stress-activated signaling pathways: A unifying hypothesis of type 2 diabetes. Endocr. Rev., 23: 599-622.
CrossRef | Direct Link |