Phosphatidylserine and Sleep

Phosphatidylserine is often added to formulas “for sleep and recovery,” although it is not a sleeping aid. The editorial team examined how stress hormones are linked to sleep quality, what studies of PS show and in which situations it makes sense to consider it at all.

Where the link between PS and sleep comes from

Phosphatidylserine (PS) is not a sleeping aid and does not act on the receptors that regulate falling asleep, unlike melatonin or GABA-agonist drugs. Yet it appears often in descriptions of sleep supplements. The reason is its reputation as a modulator of the stress response.

Sleep and cortisol are closely linked. In a healthy person the cortisol level is lowest in the first half of the night and rises sharply before waking. If in the evening the stress system is active — because of late intense training, work problems or anxious thoughts — falling asleep becomes harder and sleep becomes shallow.

Hence the hypothesis: if PS softens the activation of the hypothalamic–pituitary–adrenal axis, it may indirectly help people whose insomnia is linked to stress fall asleep. This hypothesis is logical but, as the editorial team found, poorly tested.

It is also worth noting the reverse link: sleep deprivation itself raises evening cortisol and worsens metabolic measures, which has been well shown in the work of Van Cauter’s group. That is, stress and poor sleep form a vicious circle.

What is known from studies

There are very few direct randomized studies in which the main outcome was sleep quality with intake of pure PS. Most of the data concern the hormonal response to physical or mental stress during the daytime.

In the study by Hellhammer and colleagues (2004) a complex of phosphatidic acid and PS (the so-called PAS) reduced the hormonal response to standardized mental stress in people with a high level of chronic stress. Sleep was not measured separately, and the effect was not the same across all subgroups.

Studies by Monteleone showed a blunting of ACTH and cortisol after physical exertion, but this concerns daytime stress and a form of PS derived from animal brain, which is hardly used today.

There are small Japanese studies of combinations of PS with other substances in children with attention disorders and in older people with memory complaints, where subjective improvements in well-being were recorded. But because of the combined formulas and a design without objective measures of sleep (polysomnography or actigraphy), it is impossible to draw conclusions about PS as a sleep aid.

So the level of evidence for PS specifically as a sleep supplement is currently low. It is possible that in people with pronounced evening stress an effect exists, but it cannot be called proven.

PS compared with other sleep aids

To get a sense of where PS stands among the popular options, the editorial team compiled a comparison table by mechanism and level of evidence.

The European guidelines on the treatment of insomnia (Riemann et al., 2017) name cognitive behavioral therapy, not supplements, as the first line. This is an important reference point for anyone suffering from chronic sleep problems.

PS makes sense to consider as an adjunct only in a specific scenario: a person falls asleep poorly precisely because of evening “overstimulation,” while basic sleep hygiene is already in place.

If the problem is a disrupted circadian rhythm (time-zone changes, shift work), PS logically will not help here — in such a situation melatonin is more evidence-based.

Timing of intake and paradoxical effects

Interestingly, among the side effects of PS in high doses is insomnia. Some users report a feeling of “clarity” in the head that makes it hard to relax if the supplement is taken in the evening.

Because of this, there is no unambiguous recommendation to “take it before bed.” A practical approach that the editorial team considers reasonable:

1. start with intake in the first half of the day to assess tolerance;
2. if the stress peak falls on evening training — try taking it a few hours before it;
3. keep a sleep diary: time of falling asleep, waking, subjective quality;
4. assess the effect no earlier than after 2–3 weeks and stop if there are no changes.

Studies used doses of 300–800 mg per day; for assessing the effect on sleep there is no reason to go beyond these limits. A larger dose more often causes gastric discomfort and, according to reports, agitation.

The combination of PS with melatonin or magnesium in combined products is common, but such formulas make it harder to understand what exactly is working. To assess your personal reaction it is better to test the components separately.

When you need a doctor, not a supplement

Sleep disturbances are a common complaint behind which serious conditions may lie: obstructive sleep apnea, depression, anxiety disorders, thyroid dysfunction, restless legs syndrome. No supplement treats these causes.

You should see a doctor if insomnia lasts more than three months on several nights a week, if there is snoring with pauses in breathing, pronounced daytime sleepiness or mood changes.

Athletes with a high training load should also remember overtraining syndrome, one of the early manifestations of which is disturbed sleep. Here what is needed is correction of the load, not masking the symptom.

People taking medications, especially anticoagulants and drugs that affect the central nervous system, need to agree the use of PS with a doctor.

Editorial conclusions

Phosphatidylserine is not a sleep aid in the direct sense. Its possible effect is indirect, through softening the stress response, and this effect has been studied mainly in daytime conditions and on small samples.

For people whose insomnia is linked to evening stress, PS can be the subject of a cautious experiment, but not a replacement for sleep hygiene, cognitive behavioral therapy or examination by a doctor.

With a disrupted sleep rhythm there is more reason to consider melatonin, and with chronic insomnia — to turn to a specialist.

The editorial team also recommends our materials “Melatonin and sleep,” “Phosphatidylserine during cutting: does it help” and “How to choose quality phosphatidylserine: what to look for on the label.”

References

1. Monteleone P, Beinat L, Tanzillo C, Maj M, Kemali D. Effects of phosphatidylserine on the neuroendocrine response to physical stress in humans. Neuroendocrinology. 1990;52(3):243–248.
2. Hellhammer J, Fries E, Buss C, et al. Effects of soy lecithin phosphatidic acid and phosphatidylserine complex (PAS) on the endocrine and psychological responses to mental stress. Stress. 2004;7(2):119–126.
3. Spiegel K, Leproult R, Van Cauter E. Impact of sleep debt on metabolic and endocrine function. Lancet. 1999;354(9188):1435–1439.
4. Riemann D, Baglioni C, Bassetti C, et al. European guideline for the diagnosis and treatment of insomnia. J Sleep Res. 2017;26(6):675–700.
5. Glade MJ, Smith K. Phosphatidylserine and the human brain. Nutrition. 2015;31(6):781–786.
6. Walsh NP, Halson SL, Sargent C, et al. Sleep and the athlete: narrative review and 2021 expert consensus recommendations. Br J Sports Med. 2021;55(7):356–368.