Phosphatidylserine (PS) is a phospholipid found in high concentrations in the brain and is often marketed as a supplement for cognitive health and stress regulation. There is some scientific evidence suggesting that PS can help modulate the stress response, which involves the hypothalamic-pituitary-adrenal (HPA) axis—a system in which the hypothalamus plays a central role. A few small clinical studies have shown that PS supplementation may blunt the rise in cortisol (a stress hormone) following physical or mental stress, indicating possible support for the HPA axis and, by extension, hypothalamic function. For example, a study published by Monteleone et al. (1992) found that PS supplementation reduced ACTH and cortisol responses to physical stress in healthy men. Another study (Hellhammer et al., 2004) showed a reduction in cortisol response to stress in chronically stressed subjects taking PS.

However, while these findings suggest a potential mechanism by which PS may support the hypothalamus via HPA axis modulation, the evidence base is limited and largely indirect. Most studies are small, short-term, and focus on acute stress rather than long-term hypothalamic health or disease states. There is stronger evidence for PS’s effects on cognitive function and memory in older adults, but its direct impact on the hypothalamus is less well established. Therefore, the scientific validation for PS specifically supporting the hypothalamus is modest, justifying a rating of 2.