Piperine Shows Potential Pharmacological Benefit for NAFLD, Early Cirrhosis

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Consuming a 5mg piperine capsule once daily for 12 weeks was linked to several pharmacological improvements in patients with NAFLD.

Piperine consumption may have pharmacological benefits for individuals with nonalcoholic fatty liver disease (NAFLD), with findings from a randomized, double-blind, placebo-controlled study highlighting the potential clinical utility of the bioactive alkaloid found in black pepper in the absence of approved medical intervention.

Results showed consuming a single 5mg capsule of piperine each day for 12 weeks positively impacted several biochemical variables in patients with NAFLD, including reduced hepatic enzymes, insulin resistance, and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) levels as well as ameliorated lipid and glucose metabolisms.1

“Some investigations have evaluated the impact of curcumin and a combination of piperine and curcumin on patients with NAFLD. However, no clinical trial has been conducted on the action of piperine alone in management of patients with NAFLD until now,” wrote Masoud Nouri-Vaskeh, MD, of the Immunology Research Center at Tabriz University of Medical Sciences in Iran, and colleagues.1

A natural ingredient of black pepper and other Piper species, piperine acts as a biologically versatile compound that can interact with a variety of chemically and functionally diverse biomolecular targets, either in combination with other bioactive substances or as an isolated supplement. Its known pharmacologic properties make it a viable option for treating chronic inflammatory diseases. Importantly, its use in NAFLD merits further exploration due to the current lack of an approved medical intervention and the subsequent growing need for therapeutic intervention.2

To assess the impact of piperine consumption on the biomedical parameters of individuals with NAFLD, investigators enrolled patients from a referral hospital in a randomized, double-blind, placebo-controlled study between August 2019 and July 2020. Participants were randomly assigned in a 1:1 ratio to treatment with placebo (n = 34) or 5 mg of piperine (n = 34) for 12 weeks.1

Among the cohort, 52% of patients were female. Investigators noted baseline demographics including age, BMI, waist, and hip circumstance were not significantly different between the case and control groups (P >.05), although there were notable differences in cholesterol (P = .030) and low-density lipoprotein (LDL) (P = .085) with greater quantities of each observed in the placebo group.1

Following 12 weeks of treatment, investigators observed substantial differences across several laboratory values between the piperine and placebo groups. Of note, significant reductions in aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase, cholesterol, LDL, triglycerides (TG), fasting blood sugar (FBS), and HbA1c were observed among participants in the piperine group. Statistically significant increases in bilirubin, high-density lipoprotein (HDL), and gamma-glutamyl transferase (GGT) were also observed in this group.1

Investigators noted the only changes in the piperine group that were statistically significant compared to placebo were AST (P = .002), ALT (P <.001), cholesterol (P <.001), LDL (P = .043), TG (P = .005), FBS (P = .011), and GGT (P = .042). They also emphasized a lack of patient-reported complications across either treatment arm, establishing the safety of piperine and its lack of side effects during the study period.1

However, investigators pointed out the study had multiple limitations related to the sonographic liver assessment only being conducted at baseline. Additionally, this test fails to address inflammation and fibrosis associated with NAFLD. Although steatosis was measured in some capacity, change was not evaluated after treatment with piperine.1

“Due to the lack of an approved pharmacologic agent for management of NAFLD and cirrhosis, further studies about the hepatic effects of piperine should be encouraged,” investigators concluded.1


  1. Nouri-Vaskeh M, Hashemi P, Hataminia N, et al. The impact of piperine on the metabolic conditions of patients with NAFLD and early cirrhosis: a randomized double-blind controlled trial. Sci Rep. doi:10.1038/s41598-024-51726-z
  2. Ziegenhagen R, Heimberg K, Lampen A, Hirsch-Ernst KI. Safety Aspects of the Use of Isolated Piperine Ingested as a Bolus. Foods. 2021;10(9):2121. Published 2021 Sep 8. doi:10.3390/foods10092121