Zinc Co-Supplementation Attenuates the Laboratory-Based Rise in Alanine Aminotransferase During Rosuvastatin Therapy: A Randomised Open-Label Study

Statin therapy is frequently accompanied by asymptomatic elevation of hepatic transaminases, which is a common reason for treatment interruption even when it carries little clinical risk. Zinc is an essential cofactor for antioxidant defence in hepatocytes, and it has been proposed that zinc co-supplementation might reduce statin-associated biochemical hepatic changes. This has not previously been tested prospectively alongside rosuvastatin. In a randomized, single-centre, open-label, prospective study conducted in a tertiary care hospital in Kanpur, India, 400 adults with dyslipidaemia were allocated to rosuvastatin 10 mg once daily (Group I, n = 200) or rosuvastatin 10 mg plus elemental zinc 25 mg once daily (Group II, n = 200) for 12 weeks. Hepatic and renal laboratory parameters were measured at baseline, 6 weeks and 12 weeks. The primary endpoint was the between-group difference in change in alanine aminotransferase (ALT) at 12 weeks, analysed by analysis of covariance adjusted for baseline value, age, sex and body mass index. All 400 patients completed follow-up. ALT rose in both groups but significantly less in Group II, with an adjusted between-group difference of −4.33 U/L (95% confidence interval −5.90 to −2.75; p < 0.001; Cohen d −0.464). Twenty-eight patients in Group I (14.0%) exceeded the upper reference limit of 40 U/L at 12 weeks compared with none in Group II (absolute risk reduction 14.0%, number needed to treat 7.1; p < 0.001), and an ALT rise exceeding 10 U/L occurred in 41.0% versus 8.0% (relative risk 0.200, 95% confidence interval 0.122 to 0.327). No patient in either group reached three times the upper limit of normal. Aspartate aminotransferase, alkaline phosphatase and serum creatinine showed no adjusted between-group difference, and the small difference in serum albumin was not clinically meaningful. The effect on ALT was consistent across sex, age, body mass index and alcohol-use strata, and was larger in patients with a higher baseline ALT. Zinc 25 mg daily co-administered with rosuvastatin attenuated the rise in ALT over 12 weeks and was associated with the absence of any value above the upper reference limit, without measurable effect on other hepatic or renal parameters. The changes observed were of low severity, so the finding should be interpreted as reduction of biochemical abnormality rather than prevention of hepatotoxicity. These findings are preliminary and require confirmation in a blinded, placebo-controlled trial.