Modulation of the hypothalamic–pituitary–adrenal (HPA) axis by plants and phytonutrients: a systematic review of human trials

ABSTRACT

Introduction

The hypothalamic–pituitary–adrenal (HPA) axis plays a central role in the stress response. Plants, herbs, spices, and plant-based nutrients may influence HPA-axis activity.

Objective

To evaluate randomised controlled, human trials assessing the effects of single plants or phytonutrients on HPA-axis related hormones.

Methods

A systematic review of PubMed, Cochrane library, and the Cumulative Index to Nursing and Allied Health Literature was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Inclusion criteria comprised of human, randomised controlled studies with a control intervention examining the effects of a single herb, spice, plant, or extract on pre- and post-changes in blood, saliva, urine, or hair concentrations of cortisol, cortisone, corticotrophin-releasing hormone, or adrenocorticotropic hormone. Databases were searched from inception until October 2020.

Results

Fifty-two studies were identified examining the effects of ashwagandha, Korean ginseng, St John's Wort, cannabidiol, Rhodiola rosea, curcumin, cherry juice, asparagus, Jiaogulan, Black cohosh, Siberian ginseng, Bacopa monnieri, blueberries, green tea, Caralluma fimbriata, cashew apple juice, melon, American ginseng, Ginkgo biloba, grape juice, grapefruit juice, rosella, hops, mangosteen, holy basil, and pomegranate juice. Due to significant variability in study designs, the effect of phytonutrients on HPA-axis activity in humans was unclear. The most consistent finding was a morning, cortisol-lowering effect from ashwagandha supplementation.

Conclusion

For most phytonutrients, the effects of supplementation on HPA-axis activity in humans is unclear. Before more definitive conclusions about the effects of phytonutrients on the HPA-axis can be made, further research is required.

KEYWORDS:

• Systematic review
• herbs
• spices
• plants
• phytonutrients
• HPA-axis
• cortisol
• human trials

Disclosure statement

Dr Lopresti is the managing director of Clinical Research Australia, a contract research organisation that has received research funding from nutraceutical companies. Dr Lopresti has also received presentation honoraria from nutraceutical companies. Mr Smith is an employee of Clinical Research Australia and declares no other conflicts of interest. Professor Drummond declares no conflicts of interest.

Additional information

Notes on contributors

Adrian L. Lopresti

Adrian L. Lopresti has a PhD from Murdoch University and is a practising clinical psychologist. He regularly conducts sponsor-funded clinical trials, with a specific interest in the effects of herbal, lifestyle, and dietary interventions on mental and cognitive health.

Stephen J. Smith

Stephen J. Smith is pursuing a PhD at Murdoch University, Australia. He is studying the effects of lifestyle, dietary, and herbal interventions on testosterone concentrations in ageing males.

Peter D. Drummond

Peter D. Drummond is a Professor of psychology at Murdoch University, Australia. His specific areas of interest are the mechanism and treatment of chronic pain, the psychophysiology of emotions and their impact on health, and understanding migraine and other forms of headache.