Safety Aspects of the Use of Isolated Piperine Ingested as a Bolus.

2021-09-08
Foods (Basel, Switzerland) 10(9)
- Rainer Ziegenhagen
- Katharina Heimberg
- Alfonso Lampen
- Karen Ildico Hirsch-Ernst

PubMed: 34574230
DOI: 10.3390/foods10092121

Study Design

Type: Review
Population: human and animal studies

Piperine is a natural ingredient of Piper nigrum (black pepper) and some other Piper species. Compared to the use of pepper for food seasoning, piperine is used in food supplements in an isolated, concentrated form and ingested as a bolus. The present review focuses on the assessment of the possible critical health effects regarding the use of isolated piperine as a single ingredient in food supplements. In human and animal studies with single or short-term bolus application of isolated piperine, interactions with several drugs, in most cases resulting in increased drug bioavailability, were observed. Depending on the drug and extent of the interaction, such interactions may carry the risk of unintended deleteriously increased or adverse drug effects. Animal studies with higher daily piperine bolus doses than in human interaction studies provide indications of disturbance of spermatogenesis and of maternal reproductive and embryotoxic effects. Although the available human studies rarely reported effects that were regarded as being adverse, their suitability for detailed risk assessment is limited due to an insufficient focus on safety parameters apart from drug interactions, as well as due to the lack of investigation of the potentially adverse effects observed in animal studies and/or combined administration of piperine with other substances. Taken together, it appears advisable to consider the potential health risks related to intake of isolated piperine in bolus form, e.g., when using certain food supplements.

Research Insights

Black Pepper→Impaired Spermatogenesis
Animal studies with higher daily piperine bolus doses than in human interaction studies provide indications of disturbance of spermatogenesis and of maternal reproductive and embryotoxic effects.
Effect
Harmful
Effect size
Moderate
Dose
higher daily bolus doses (animal studies, not human)
Black Pepper→Increased Drug Bioavailability
In human and animal studies with single or short-term bolus application of isolated piperine, interactions with several drugs, in most cases resulting in increased drug bioavailability, were observed. Depending on the drug and extent of the interaction, such interactions may carry the risk of unintended deleteriously increased or adverse drug effects.
Effect
Harmful
Effect size
Moderate
Dose
isolated piperine in bolus form (dose not explicitly quantified in the abstract for human studies)
Black Pepper→Reduced Reproductive Function
Animal studies with higher daily piperine bolus doses than in human interaction studies provide indications of disturbance of spermatogenesis and of maternal reproductive and embryotoxic effects.
Effect
Harmful
Effect size
Moderate
Dose
higher daily bolus doses (animal studies, not human)

Adverse Events Reported

Black Pepper→disturbance of spermatogenesis
Animal studies with higher daily piperine bolus doses than in human interaction studies provide indications of disturbance of spermatogenesis
Finding
Increased risk
Black Pepper→embryotoxic effects
Animal studies with higher daily piperine bolus doses than in human interaction studies provide indications of disturbance of spermatogenesis and of maternal reproductive and embryotoxic effects.
Finding
Increased risk
Severity
Serious adverse event
Black Pepper→interactions with drugs resulting in increased drug bioavailability
In human and animal studies with single or short-term bolus application of isolated piperine, interactions with several drugs, in most cases resulting in increased drug bioavailability, were observed.
Finding
Increased risk
Black Pepper→maternal reproductive effects
Animal studies with higher daily piperine bolus doses than in human interaction studies provide indications of disturbance of spermatogenesis and of maternal reproductive and embryotoxic effects.
Finding
Increased risk
Black Pepper→risk of unintended deleteriously increased or adverse drug effects
Depending on the drug and extent of the interaction, such interactions may carry the risk of unintended deleteriously increased or adverse drug effects.
Finding
Increased risk
Severity
Serious adverse event
Black Pepper→Overall tolerability
Although the available human studies rarely reported effects that were regarded as being adverse, their suitability for detailed risk assessment is limited due to an insufficient focus on safety parameters apart from drug interactions
Finding
Reported