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BIOCHEMISTRY Effect of vitamin C in the prevention of nonalcoh olic fatty liver in rats Tionloc; Tiu; Tolentino; Torga; Tuason, A.; Tuason, J.; Tuble; Ubaldo; Uong; Urbi 1 I. Title Effect of vitamin C in the prevention of nonalcoholic fatty liver in rats II. Review of Related Literature a. In the research article published by Harrison et al in the American Journal of Gastroenterology (2003), the researchers performed a prospective, double-blind, randomized, placebo-controlled trial that had a total enrollment of 49 patients with nonalcoholic fatty liver. The subjects were randomized to receive either Vitamin E and C or placebo for a period of six months. Pre and post treatment liver biopsies were reviewed by a single pathologist who was also blinded as to the patient’s treatment regimen. Biopsies were graded based on the modified scoring system published by Brunt et al (Am J Gastroenterology, 1999). Forty-five patients completed 6 months of therapy without significant side effects. Vitamin treatment resulted in a statistically significant improvement in fibrosis score (p=0.002). No changes were noted in inflammation with treatment. Vitamin E and vitamin C, in the doses used in this study, were well tolerated and were effective in improving fibrosis scores in NASH patients. No improvement in necroinflammatory activity or ALT was seen with this combination of drug therapy. The study recommended a larger, multicenter, longer-term trial with vitamin E and vitamin C. b. In a review article published by the Postgraduate Medical Journal (2006) entitled “Treatment of nonalcoholic fatty liver disease” (Adams, et al), it provided a synthesized study on the different research articles and other similar publications that dealt with the treatment of nonalcoholic fatty liver disease (NAFLD). In one of the sub-sections for the treatment options, it discussed the efficacy of antioxidants (in this case, Vitamin E) in the treatment of NAFLD: i. Subjects with NAFLD exhibit increased levels of oxidative stress and lipid peroxidation that may play a part in disease progression. 69,70  Vitamin E is a potent antioxidant and has been evaluated among paediatric and adult patients with NAFLD (table 4). Two small pilot trials have shown reduction of ALT levels among adult and paediatric patients with NASH. Subsequently, two small randomised controlled trials have failed to show any benefit of vitamin E on ALT levels; one study randomised 16 adult subjects to vitamin E (800 IU/day) or no treatment over three months 71 ; the other trial consisted of 28 obese children taking vitamin E (400 mg/daily for two months, 100 mg/daily for three months) or placebo . 72  In the only randomised study assessing histology, Harrison and colleagues randomised 45 patients to vitamins E (1000 IU/day) and C (1000 mg/day) or placebo for six months. 73  Vitamin treatment significantly improved hepatic inflammation and fibrosis compared with baseline. However, the comparison of changes between placebo and vitamin E/C groups

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BIOCHEMISTRY

Effect of vitamin C in the prevention of nonalcoholic fatty liver in rats

Tionloc; Tiu; Tolentino; Torga; Tuason, A.; Tuason, J.; Tuble; Ubaldo; Uong; Urbi 1 

I.  Title

Effect of vitamin C in the prevention of nonalcoholic fatty liver in rats

II. 

Review of Related Literature

a.  In the research article published by Harrison et al in the American Journal of 

Gastroenterology (2003), the researchers performed a prospective, double-blind,

randomized, placebo-controlled trial that had a total enrollment of 49 patients

with nonalcoholic fatty liver. The subjects were randomized to receive either

Vitamin E and C or placebo for a period of six months. Pre and post treatment

liver biopsies were reviewed by a single pathologist who was also blinded as to

the patient’s treatment regimen. Biopsies were graded based on the modified

scoring system published by Brunt et al (Am J Gastroenterology, 1999). Forty-five

patients completed 6 months of therapy without significant side effects. Vitamin

treatment resulted in a statistically significant improvement in fibrosis score(p=0.002). No changes were noted in inflammation with treatment. Vitamin E

and vitamin C, in the doses used in this study, were well tolerated and were

effective in improving fibrosis scores in NASH patients. No improvement in

necroinflammatory activity or ALT was seen with this combination of drug

therapy. The study recommended a larger, multicenter, longer-term trial with

vitamin E and vitamin C.

b.  In a review article published by the Postgraduate Medical Journal (2006) entitled

“Treatment of nonalcoholic fatty liver disease” (Adams, et al), it provided a

synthesized study on the different research articles and other similar

publications that dealt with the treatment of nonalcoholic fatty liver disease(NAFLD). In one of the sub-sections for the treatment options, it discussed the

efficacy of antioxidants (in this case, Vitamin E) in the treatment of NAFLD:

i.  “Subjects with NAFLD exhibit increased levels of oxidative stress and lipid

peroxidation that may play a part in disease progression.69,70

 Vitamin E is

a potent antioxidant and has been evaluated among paediatric and adult

patients with NAFLD (table 4). Two small pilot trials have shown

reduction of ALT levels among adult and paediatric patients with NASH.

Subsequently, two small randomised controlled trials have failed to show

any benefit of vitamin E on ALT levels; one study randomised 16 adult

subjects to vitamin E (800 IU/day) or no treatment over three months71

the other trial consisted of 28 obese children taking vitamin E (400

mg/daily for two months, 100 mg/daily for three months) or placebo.72

 In

the only randomised study assessing histology, Harrison and colleagues

randomised 45 patients to vitamins E (1000 IU/day) and C (1000 mg/day)

or placebo for six months.73

  Vitamin treatment significantly improved

hepatic inflammation and fibrosis compared with baseline. However, the

comparison of changes between placebo and vitamin E/C groups

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occurring with treatment at the end of the study showed no differences

in ALT, hepatic inflammation or fibrosis. Recent evidence has also

suggested that vitamin E supplementation may not be innocuous but may

be associated with an increased risk of death and heart failure.74

 

Therefore in the absence of convincing evidence of benefit and the

possible spectre of harm, vitamin E cannot be recommended fortreatment of NAFLD outside of clinical trials.” 

III.  Objective of the Study

i.  Determine the role of Vitamin C in the prevention of nonalcoholic fatty

liver in rats

IV.  Research Methodology

a.  Please see attached document.