Withanolides are a group of naturally occurring steroidal lactones, most notably found in the plant Withania somnifera (Ashwagandha). Their use in supporting the sympathetic nervous system is supported by a growing body of scientific research, although more large-scale human studies are needed to fully substantiate these effects. Ashwagandha has traditionally been used in Ayurvedic medicine as an adaptogen, believed to help the body cope with stress and maintain homeostasis, which indirectly involves modulation of the sympathetic nervous system.

Preclinical studies, including animal and in vitro data, suggest that withanolides exhibit anxiolytic and anti-stress properties, potentially by modulating the hypothalamic-pituitary-adrenal (HPA) axis and reducing levels of stress hormones such as cortisol. Some human clinical trials have shown that Ashwagandha supplementation can reduce perceived stress and anxiety, indicating a dampening of overactive sympathetic nervous system responses. For example, randomized controlled trials have found significant reductions in cortisol and improvements in stress-related symptoms in individuals taking standardized Ashwagandha extracts.

However, direct evidence specifically linking withanolides to modulation of the sympathetic nervous system is limited, and most studies focus on stress and anxiety endpoints rather than direct assessment of sympathetic activity (such as heart rate variability or catecholamine levels). As such, the evidence supports a moderate scientific basis (3/5) for the use of withanolides in supporting the sympathetic nervous system, primarily through stress reduction mechanisms.