Phosphatidylserine (PS) a phospholipid component of neuronal cell membranes is acknowledged to be a beneficial tool in the fight against the multi-headed beast that is chronic stress. Stress and physiological stressors come at us from all sides and can be caused by chronic sleep debt over-exercising financial worries employment relationships and more. In dealing with these stressors our bodies often need extra support which can be found in beneficial nutrients such as phosphatidylserine. As a play on words some healthcare practitioners have taken to calling PS phosphatidyl serene for its ability to help regulate our stress hormones most notably cortisol.

A study in which healthy male subjects being given 400mg PS and 400mg phosphatidic acid (a glycerophospholipid precursor to PS) for 42 days resulted in normalized levels of ACTH and cortisol (the latter measured in both saliva and serum) compared to placebo and also compared to 200mg of PS with 200mg phosphatidic acid. Notably this result was observed in subjects defined as chronically high-stressed but not in those with lower stress levels. It could be that lower-stressed individuals have less exaggerated stress responses to begin with and would therefore benefit less from substances that target a lowering of cortisol. 

These findings confirmed an earlier study from the same authors in which PS was found to favorably affect the stress response in a group of healthy men with high chronic stress compared to those with lower regular stress levels. The PS was delivered along with omega-3 DHA and EPA and the cortisol-lowering effect was most significant in the group of men with higher chronic stress. The group with a much lower endocrine response to stress actually showed a slight elevation in cortisol leading the authors to suggest that rather than solely lowering chronically elevated cortisol PS might be considered a normalizing agent.

Regardless of the precise mechanism of action there seems to be a sweet spot in terms of the most effective PS dosage. In a small study in which healthy subjects were given daily doses of 400mg 600mg or 800mg of a soy lecithin phosphatidic acid and PS complex (PAS) for three weeks significant reductions in serum ACTH and serum and salivary cortisol were seen at the 400mg dose compared to placebo but these effects were actually weakened at the higher doses. The authors did not speculate as to the reasoning behind this but they did note that male subjects experienced greater cortisol-lowering effects from the interventions than female subjects. They hypothesized that this could have been related to body weight/PAS ratio; since the male subjects were heavier compared to the females and the females received higher doses of the intervention relative to their body size. The authors also noted that PAS dampened but did not eliminate the endocrine reaction to stress and that basal cortisol levels were not affected. 

The previous studies noted involved social stress tests designed to reliably increase cortisol and other adrenal stress hormones and neurotransmitters in a laboratory setting. But the benefits of PS supplementation on attenuating the stress response have also been demonstrated in studies involving physical stress such as exercise. Of course appropriate levels of exercise are always encouraged for their health-promoting effects but over-exercising either in frequency intensity or duration without sufficient recovery time and nutrient repletion can lead to both acute and long-term physiological damage. Supplementation with PS may help dedicated athletes and weekend warriors alike to reduce the catabolic (and therefore counterproductive) effects of exercise-induced cortisol elevation.

A small study involving supplementation with 600mg PS for 10 days in healthy males showed that PS lowered cortisol after moderate intensity exercise (in this case cycling). It also resulted in slightly elevated testosterone levels (still within normal range) which supports evidence that high cortisol levels impair testosterone production. By raising testosterone and lowering cortisol PS administration dramatically increased the testosterone/cortisol ratio; whereas a low T/C ratio has been used to indicate the negative state of overtraining compared to a more physiologically suitable amount or intensity of exercise.  Growth hormone and lactate levels showed no significant differences between PS and placebo suggesting that PS exerts its effects after-the-fact rather than affecting the exercise performance itself.

Of course stress isn't just about feeling anxious or irritable or overdoing it at the gym. Considering the role of chronically elevated blood glucose in triggering and exacerbating type-2 diabetes and taking into account the effect of cortisol on raising blood glucose PS may be helpful in mitigating downstream endocrine effects of stress that are much more damaging to health than getting aggravated in traffic or tossing and turning with worries at night.

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