Reviewed: Usharani P, Merugu PL, Nutalapati C. Evaluation of the effects of a standardized aqueous extract of Phyllanthus emblica fruits on endothelial dysfunction, oxidative stress, systemic inflammation and lipid profile in subjects with metabolic syndrome: A randomised, double blind, placebo controlled clinical study. BMC Complement Altern Med. May 2019;19(1):97. doi: 10.1186/s12906-019-2509-5.
The National Cholesterol Education Program’s Adult Treatment Panel III (ATP III) has identified these components of metabolic syndrome (MetS): abdominal obesity, insulin resistance with or without glucose intolerance, dyslipidemia, hypertension, and a prothrombotic state. These metabolic abnormalities can lead to endothelial dysfunction (ED), a predictor of cardiovascular disease, by affecting nitric oxide (NO) synthesis or degradation. Amla (Indian gooseberry; Phyllanthus emblica syn. Emblica officinalis, Phyllanthaceae) fruits, which are rich in polyphenolic compounds, are reported to have hypolipidemic, antidiabetic, anti-inflammatory, and antioxidant properties. The authors conducted a prospective, randomized, double-blind, placebo-controlled clinical study to evaluate the effects of two different doses of a standardized aqueous amla extract versus placebo on ED, oxidative stress, systemic inflammation, and lipid profiles in patients with MetS.
The study was conducted at the Department of Clinical Pharmacology and Therapeutics at Nizam’s Institute of Medical Sciences in Hyderabad, India. Male and female patients aged 30 to 68 years who had ED and MetS were included. Of the 65 patients screened, 59 were selected for the study.
The treatments used were Capros® 250 mg and Capros® 500 mg (Natreon, Inc. USA; New Brunswick, New Jersey). Each Capros capsule contained an aqueous extract of amla fruit standardized to contain not less than 60% of low-molecular-weight hydrolyzable tannins, including emblicanin A, emblicanin B, pedunculagin, and punigluconin. Placebo capsules, also supplied by Natreon, Inc., contained microcrystalline cellulose, lactose, and magnesium stearate.
Study participants were randomly assigned to take one Capros 250 mg (n = 20), Capros 500 mg (n = 21), or placebo (n = 18) capsule twice daily for 12 weeks. A salbutamol challenge test was used to evaluate endothelial function by determining the reflection index (RI) using digital volume plethysmography, a predictor of vascular damage, at each visit. Adverse effects and compliance with the treatment protocol were assessed at each visit. At baseline and after 12 weeks, the patients underwent complete physical and laboratory examinations to determine serum levels of the oxidative stress markers NO, malondialdehyde, and glutathione; the systemic inflammation marker high-sensitivity C-reactive protein; lipids; and hepatic and renal function parameters. The primary efficacy outcome was a change in the RI greater than 6%. Secondary outcomes were improvements in lipid profiles and the markers of oxidative stress and inflammation.
Baseline RI was similar among the three groups. In the two Capros groups, RI was significantly reduced at weeks eight and 12 compared with baseline, indicating improved endothelial function (P < 0.001). The improvement was significantly greater in the Capros 500 mg group compared with the Capros 250 mg group (P < 0.05) and in the two Capros groups compared with the placebo group at weeks eight and 12 (P < 0.05 for each). In both Capros groups, improvements were seen in the oxidative stress and inflammation biomarkers after 12 weeks compared with baseline (P < 0.001 for each), with significantly greater improvements in the Capros 500 mg group compared with the Capros 250 mg group (P < 0.01 to P < 0.001). No significant changes were seen in the placebo group.
Significant improvements in lipid profiles were seen in the two Capros groups compared with baseline (P < 0.001 for both), with greater improvements seen in total cholesterol (P < 0.05), low-density lipoprotein cholesterol (P < 0.001), high-density lipoprotein cholesterol (P < 0.001), and triglyceride (P < 0.01) levels in the Capros 500 mg group compared with the Capros 250 mg group. No significant changes were seen in the placebo group.
No significant changes were observed in heart rate, hematological indices, or renal and hepatic functions in any of the groups. No serious adverse effects were reported. Two patients in the Capros groups experienced dyspepsia, and three patients in the placebo group reported mild diarrhea. Those effects were treated symptomatically.
In this study, the 250 mg and 500 mg amla extracts significantly improved endothelial function, oxidative stress, systemic inflammation, and lipid profile, with greater improvements observed with the 500 mg dosage. The authors conclude that Capros may “be used as an adjunct to conventional therapy (lifestyle modification and pharmacological intervention) in the management of MetS.”