The components of metabolic syndrome (MetS) include abdominal obesity, insulin resistance with or without glucose intolerance, dyslipidemia, and hypertension. Conditions promoting thrombosis and inflammation are also associated with MetS. 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. These 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 the lipid profile in patients with MetS.
The study was conducted in 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 and Capros 500 (Natreon, Inc., USA; New Brunswick, New Jersey). Each Capros capsule contained an aqueous extract of amla fruits 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), a predictor of vascular damage, at each visit. Any 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 the markers of oxidative stress, inflammation, and in the lipid profile.
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 Capro 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). In both Capros groups, improvements were seen in the oxidative stress and inflammation biomarkers after 12 weeks compared with baseline (P<0.001), 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 the lipid profile were seen in the two Capros groups compared with baseline (P<0.001), 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 triglycerides (P<0.01) 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 extract 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.”
Natreon, Inc. provided the study medications and the kits used to assess the biomarkers used as outcome measures. The authors declare no competing interests.
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 randomized, double-blind, placebo-controlled clinical study. BMC Complement Altern Med. May 2019;19(1):97. doi: 10.1186/s12906-019-2509-5.