Phosphatidylserine (PS) helps reduce stress and improve sleep by lowering cortisol, the body’s main stress hormone. Elevated cortisol, especially at night, disrupts deep sleep and can lead to ongoing fatigue and insomnia. PS works by regulating the hypothalamic-pituitary-adrenal (HPA) axis, which controls cortisol production. Studies show that taking 400–800 mg of PS daily can reduce cortisol levels by up to 39%, improving sleep quality and restoring a healthy sleep cycle.
Here’s what you need to know:
Cortisol and Sleep: High cortisol levels at night disrupt deep sleep and increase nighttime wakefulness.
How PS Works: PS reduces cortisol by calming the HPA axis, helping the body relax and promoting restorative sleep.
Dosage: Effective doses range from 400–800 mg per day, with best results when taken in the evening.
Who Benefits: People with chronic stress, irregular schedules, or insomnia caused by high cortisol levels.
PS is a natural, non-sedative option for managing stress-related sleep issues and is often combined with ingredients like magnesium, L-theanine, or ashwagandha for added benefits.
How Cortisol Affects Sleep and Phosphatidylserine's Role
Cortisol and Sleep Disruption
Cortisol, a stress hormone, has a significant impact on sleep. When cortisol levels stay elevated at night, they stimulate the central nervous system, making it harder for the body to relax. This heightened state prevents the transition into slow-wave sleep, instead promoting lighter sleep stages that are more prone to interruptions. As a result, deep recovery becomes difficult.
For individuals with chronic insomnia, the issue is even more pronounced. These individuals often experience ongoing hyperarousal, where ACTH (adrenocorticotropic hormone) and cortisol levels remain high throughout the day and night, especially during the evening and the first half of the night. This creates a "self-perpetuating cycle": high cortisol disrupts sleep, and poor sleep further raises cortisol levels. Additionally, short sleep durations can worsen cortisol's negative effects.
Middle-aged adults are particularly vulnerable to these disruptions. Compared to younger individuals, they exhibit stronger wakefulness responses to stress hormones and experience greater suppression of deep sleep. This heightened sensitivity to cortisol makes managing its effects even more critical for this age group.
How Phosphatidylserine Regulates Cortisol
Phosphatidylserine (PS) plays a key role in controlling cortisol by calming the HPA (hypothalamic-pituitary-adrenal) axis, which is responsible for the body's stress response. By reducing the production of ACTH and cortisol, PS helps to counteract the stress-induced overactivation of this system.
As a glycerophospholipid found in brain cell membranes, PS supports nerve cell membrane fluidity and is essential for neurotransmitter activity and nerve signal transmission. It achieves its cortisol-regulating effects by modulating CRF (corticotropin-releasing factor) receptor interactions and inhibiting arginine vasopressin (AVP), both of which are involved in cortisol release. This action helps normalize the HPA axis, which can be overactive in chronically stressed individuals or underactive in those with a hypo-responsive state.
By addressing the "wired and tired" state - characterized by high cortisol levels that cause daytime fatigue and disrupt nighttime sleep - PS helps restore a more balanced and restorative sleep cycle. Its ability to mitigate cortisol's effects makes it an effective option for promoting deeper, more rejuvenating sleep.
Clinical studies highlight the effectiveness of different PS dosages in regulating cortisol levels:
PS Dosage | Duration | Primary Effect on HPA Axis |
800 mg/day | 10 days | Reduced ACTH and cortisol response to physical stress |
600 mg/day | 10 days | Lowered peak cortisol by 39% and total cortisol by 35% |
400 mg/day (PS/PA complex) | 42 days | Balanced HPA axis in chronically stressed males |
300 mg/day | 30 days | Enhanced mood and reduced feelings of stress |
Research on Phosphatidylserine and Sleep
Animal Studies on Sleep Patterns
Research on animals has shed light on how phosphatidylserine (PS) influences brain function and sleep regulation. In studies involving aged rats, PS was found to restore compromised cortical acetylcholine release, a neurotransmitter crucial for both cognitive abilities and sleep. Long-term PS supplementation also helped reverse dendritic spine loss in the hippocampus, highlighting its role in preserving neuronal connections that naturally weaken with age.
Additionally, PS activates Protein Kinase C (PKC) in the cerebral cortex of aged rats, an enzyme vital for maintaining neuronal health. Behavioral studies, such as the forced swim test, have shown that PS reduces depressive-like behaviors, suggesting it could help address sleep disturbances linked to depression.
These findings in animal models provide a strong basis for human studies exploring PS's effects on cortisol regulation and sleep improvement.
Human Trials on Cortisol Reduction and Stress
Human trials, including randomized, double-blind studies, have consistently demonstrated that PS (in doses of 600–800 mg/day over 10–42 days) helps regulate the hypothalamic-pituitary-adrenal (HPA) axis by reducing excessive ACTH and cortisol levels. For example, a 2014 study involving 75 healthy male participants found that a daily dose of 400 mg of a PS/Phosphatidic Acid complex significantly reduced ACTH (p=0.010), salivary cortisol (p=0.043), and serum cortisol (p=0.035) compared to a placebo group.
In exercise-related studies, PS supplementation improved the testosterone-to-cortisol ratio by 184% compared to placebo, demonstrating its ability to maintain hormonal balance during physical stress.
"PS supplementation promotes a desired hormonal status for athletes by blunting increases in cortisol levels." - Starks MA, et al.
Studies on Elderly and Depression-Related Sleep Issues
PS has also shown promise in addressing sleep disturbances in older adults, particularly those experiencing depression. Dr. Teruhisa Komori from the Mie University Graduate School of Medicine conducted a study involving 18 elderly participants (average age 68.5 years) with late-life depression unresponsive to standard antidepressants. The participants took a supplement containing 100 mg PS, 119 mg DHA, and 70 mg EPA three times daily for 12 weeks. Among them, 8 participants - classified as "responders" - achieved a 25% or greater reduction in Hamilton Depression Scale scores and experienced normalized cortisol rhythms, with peak cortisol levels occurring at the appropriate time upon waking.
"PS and omega-3 fatty acids... may be effective for late life depression, associated with the correction of basal levels and circadian rhythm of salivary cortisol." - Teruhisa Komori, Department of Adult Health and Psychiatric Nursing, Mie University
This normalization of cortisol rhythms is critical, as disrupted cortisol patterns are closely linked to poor sleep and depression in older adults. The combination of PS with omega-3 fatty acids appears to create a synergistic effect, supporting neuroendocrine health and mood regulation, which ultimately leads to improved sleep quality.
How to Use Phosphatidylserine for Better Sleep
Dosage and Timing
To support cognitive health, a daily intake of 300 mg of phosphatidylserine (split into three 100 mg doses) is recommended. If you're targeting elevated cortisol levels that interfere with sleep, studies suggest a daily dose between 400 mg and 800 mg. Research on mental stress even found that 400 mg of a phosphatidylserine complex reduced ACTH and cortisol levels, with no added benefits at higher doses.
Since phosphatidylserine is fat-soluble, it works best when taken with meals containing healthy fats. For addressing high nighttime cortisol, consider taking it with dinner or before bed. However, if you notice any sleep disturbances, try shifting the dose to earlier in the evening.
To further improve sleep quality, combining phosphatidylserine with other targeted sleep aids can amplify its effects.
Combining Phosphatidylserine with Other Sleep Ingredients
Pairing phosphatidylserine with complementary sleep-promoting ingredients can lead to better results. Some effective combinations include:
Magnesium Glycinate (200–400 mg): Helps relax muscles and encourages deeper sleep.
L-Theanine (100–200 mg): Promotes calming alpha brain waves and may help reduce cortisol spikes caused by stress.
Magnolia Bark Extract (200–400 mg): Works with GABA receptors to ease anxiety and deepen sleep.
Glycine: This amino acid supports relaxation and pairs well with phosphatidylserine.
Ashwagandha (250–600 mg): Known for regulating the HPA axis, it has been clinically shown to lower cortisol levels.
For a more convenient option, RST Sleep offers a natural supplement that blends phosphatidylserine with glycine, magnolia bark, extended-release melatonin, and apigenin. This non-habit-forming formula is crafted for night shift workers and those with irregular sleep patterns. Made in GMP-certified facilities, it targets multiple pathways to promote relaxation, enhance sleep quality, and support a balanced sleep cycle.
Optimize Sleep, Enhance Performance, and More | Dr. Andrew Huberman
Conclusion
Phosphatidylserine (PS) stands out as a natural option for addressing stress-related sleep issues without the risk of dependency. Studies suggest that taking between 400 mg and 800 mg of PS can lower peak cortisol levels by as much as 39%, helping to create the right conditions for restorative sleep.
This compound is especially helpful for those dealing with chronic stress, irregular schedules, or elevated nighttime cortisol levels. Dr. Beth Baldwin from ZRT Laboratory explains:
"PS may help blunt the highest cortisol peaks during prolonged stress and reduce elevated cortisol levels at bedtime to allow restorative sleep".
Unlike traditional sleep aids that induce drowsiness, PS works by supporting natural brain functions. It acts as a structural component in brain cells, aiding acetylcholine levels and improving cellular communication - all without pharmacological sedation. With over two decades of clinical research backing its safety, PS offers a well-documented alternative.
For individuals like night shift workers or anyone struggling with stress-induced insomnia, incorporating PS into an evening routine may help regulate cortisol and improve sleep quality. RST Sleep provides a supplement tailored for irregular sleep patterns, combining PS with other research-supported ingredients to promote healthier sleep cycles. By addressing the root cause of stress-related sleep disruptions, PS offers a science-backed way to achieve more restful nights.
FAQs
How does phosphatidylserine help reduce cortisol levels and improve sleep?
Phosphatidylserine plays a role in reducing cortisol levels by helping to regulate the body’s stress response. It does this by calming the hypothalamic-pituitary-adrenal (HPA) axis, the system responsible for managing cortisol production during stressful situations. By keeping cortisol levels in check, it encourages relaxation and sets the stage for deeper, more restorative sleep.
When cortisol levels are balanced, falling asleep becomes easier, and your sleep cycle stays on track. This means you’re more likely to wake up feeling refreshed and ready to take on the day.
Can phosphatidylserine be taken with other supplements to improve sleep?
Yes, you can combine phosphatidylserine with other supplements to help improve sleep and manage stress. Ingredients like magnolia bark, glycine, L-theanine, and magnesium are commonly used alongside phosphatidylserine because they work well together to encourage relaxation and balance cortisol levels.
Studies indicate that phosphatidylserine may help regulate cortisol, the hormone linked to stress, which can lead to better sleep quality over time. Pairing it with other calming ingredients can be especially useful for those dealing with high stress or inconsistent sleep patterns, as it promotes relaxation and supports deeper, more refreshing sleep.
What is the best dosage and timing for taking phosphatidylserine to support better sleep?
The usual suggested dosage of phosphatidylserine is 300 mg per day, typically split into three smaller doses of 100 mg each. Taking it with meals can aid in better absorption and help you maintain a consistent routine.
If you're aiming to support relaxation or improve sleep, try scheduling your final dose in the evening. This timing might assist in reducing cortisol levels, helping your body get ready for a good night's rest. As always, consult a healthcare professional before beginning any new supplement to ensure it aligns with your specific needs.
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