What is Phosphatidylserine?
Phosphatidylserine (PS) is an endogenously produced lipid. Even though the human body is capable of producing some PS, most of what it needs is obtained through diet.
Supplemental PS helps to prevent against age-related cognitive decline and related neurodegenerative disorders, largely through its ability to improve cellular function.
As a nootropic supplement, it’s primarily used for reducing stress, improving mood, and boosting brain health. Other uses include:
- ADHD and focus
- Weight loss
- Adrenal fatigue/Dysfunction of the HPA-axis
- Insomnia and sleep
- Neurotransmitter function (dopamine, serotonin, and acetylcholine)
Phospholipids make up much of our cell membranes, which are phospholipid bilayers that provide protection and support for our cells. PS is found in high concentrations in our brain, and thusly plays an important role in the health and function of our neurons, or brain cells.
When our brain cell membranes are healthy, we can think much clearer, our memories and ability to learn are optimized, and our mental energy is enhanced.
When our neurons are unhealthy, we can experience memory troubles and cognitive decline. This decline is implicated in neurodegenerative diseases, including Alzheimer’s disease and dementia.
Evidence suggests that stacking this nootropic with omega-3 fatty acids, such as DHA and EPA, is particularly beneficial for mood in elderly patients. It has also been shown to promote a healthier stress response, reducing cortisol levels, our main stress hormone.
In both children and adults, ADHD can make work and life much more difficult. Existing medications come with many unwanted side effects, including excessive stimulation, headaches, and reduced appetite. Studies have found promising results of PS supplementation for children with ADHD, without the unwanted side effects of existing medications.
In one study, 36 children between the ages of 4-14 with ADHD were split into either a PS group or a placebo group for two months. (3) The children in the treatment group experienced significant improvements in their symptoms when compared to the placebo group. This improvement was accompanied by a boost in short-term auditory memory.
Two human studies have found this drug to exhibit antidepressant effects.
In one study on elderly women with depression, Phosphatidylserine led to improvements in depression, memory, and behavior. (1) These women took 300 mg/day for 30 days.
In another study, 18 elderly patients with treatment-resistant depression were treated daily for 12 weeks with three doses of 100 mg PS, 119 mg DHA, and 70 mg EPA. (18) Following treatment, a significant improvement in depression was found.
This decrease in depression was linked to lower cortisol levels, suggesting that PS may lead to improved depression by lowering cortisol levels.
For optimal depression relief, it is best to pair PS with DHA and EPA, two omega-3 fatty acids.
Memory, Learning, and Cognition
Multiple human studies have been conducted on both elderly and healthy adults examining the effects of PS on memory, learning, and cognitive function.
In the one study on healthy adults, physically active young men took 200 mg PS before and after acute exercise. Compared to placebo, this nootropic led to improvements in mathematical speed and accuracy, with errors reduced by 39%. (8) This ability for PS to help cognitive function when fatigued is promising for athletes and overachievers alike.
Memory improvements have also been found in two studies on elderly participants, one with those suffering from cognitive decline, and the other from those suffering from depression. (1,2) In both of these studies, participants took 300 mg/day of PS.
In another study on healthy rats, 27 days of supplementation led to enhanced brightness discrimination, which suggests improvements in memory formation. (11)
Other studies have found benefits for those with dementia and memory complaints. The latter was with PS plus DHA, a fatty acid. Short-term auditory memory was also improved in children with ADHD. (3)
Adrenal Fatigue, Cortisol, and Stress
Whether or not adrenal fatigue is a real condition is hotly debated. What is known is that dysfunction of the HPA-axis (hypothalamus-pituitary-adrenal-axis) can occur when we experience prolonged stress, and that this dysregulation can lead to a multitude of health problems.
The HPA-axis is responsible for our stress response and the secretion of cortisol, our primary stress hormone.
This is what happens when our HPA-axis is functioning properly: our body experiences a stressor, the hypothalamus signals the pituitary, which signals the adrenal glands, which then release cortisol into the blood. Cortisol acts as a messenger to help our bodies respond to, and recover from, stress. Once this chain of events is complete, homeostasis returns, and with it, cortisol levels return to baseline.
Mental, physical, and chemical stressors all create this same cascade of events. When we experience chronic stress in our lives, elevated cortisol levels can lead to inflammation and disease. This includes brain fog, fatigue, depression, obesity, metabolic syndrome, cancer, and cardiovascular disease.
Multiple studies have found Phosphatidylserine to help with exercised-induced physical stress. (4,5,9). In golfers, this drug led to lower levels of perceived stress, although the effects did not reach significance. (5)
In another study, 10 days of 800 mg/day PS counteracted the exercise-induced HPA-axis stress response in healthy men. (9) A further study showed that 400 mg/day Phosphatidylserine complex for three weeks led to reductions in serum cortisol in response to mental and emotional stressors. (10)
These studies suggest that PS exerts novel therapeutic potential for dampening the stress response and reducing damage caused by chronically elevated stress and cortisol levels.
Anxiety and Mood
While there have not been any studies linking PS with anxiety relief directly, the ability of this nootropic to lower cortisol levels is likely to help those with anxiety conditions; many anxiety conditions are linked to chronic stress and the related high levels of circulating plasma cortisol.
This reduction in stress combined with its antidepressant effects may lead to an uplifting effect on overall mood.
Through its effects on cortisol, Phosphatidylserine may help those struggling with weight loss. Elevated cortisol levels have been implicated in weight gain, particularly around the midsection. By lowering cortisol, PS may help to reduce stubborn belly fat.
This compound is important for neuroplasticity, which is your brain’s ability to create and repair brain cells. It may be able to help repair damaged, aging brain cells and those harmed by drug or alcohol abuse.
Neuroplasticity decreases with age, and those with greater damage are more likely to suffer from diseases linked to age-related cognitive decline.
Studies have found benefits in cognitive function from those suffering from memory impairments, dementia, and Alzheimer’s disease, suggesting a neuroprotective role. (1,2)
Neurotransmitters: Dopamine, Serotonin, and Acetylcholine
In one study on patients with Alzheimer’s dementia, intravenous injection of phospholipids led to increased serotonin and dopamine metabolites. (6) This suggests that PS may be able to boost the synthesis of these two neurotransmitters. These transmitters are important for regulating mood and positive feelings associated with reward.
Neuronal release of the learning neurotransmitter, acetylcholine (ACh), were increased in rats following PS supplementation. (7) This benefit occurred only in old rats, not in young, healthy rats.
Researchers concluded that this increase in ACh release may be thanks to increased choline availability, which is used in ACh synthesis. PS may also inhibit the production and release acetylcholinesterase, an enzyme responsible for the breakdown of ACh in the brain.
There has only been one study examining the effect of PS supplementation on testosterone. In this study, supplementation before and following exercise was not found to influence testosterone levels. (8)
Insomnia and Sleep
Insomnia is often accompanied by elevated stress hormones, which can be counteracted by Phosphatidylserine. Limited studies indicate reduced feelings of stress thanks to PS, which can help to calm the mind and slow the mental chatter that keeps you awake.
Side Effects & Interactions
PS is considered safe and non-toxic. Side effects reported by users include:
- Trouble sleeping
- Upset Stomach
- Brain fog
These side effects are most common with high dosages (more than 300 mg/day), supplementation shortly before sleep, or when it is taken for months in a row without any break.
The length of supplementation in human studies has been for six months or less, thus the safety of long-term use is unknown. If you want to take the supplement long-term, you may want to cycle, taking a week or month off here and there.
It can interact with both synthetic and natural blood thinners, including Ginkgo Biloba. For a complete list of known interactions, click here.
Phosphatidylserine is a fat-soluble compound with a short half-life. The typical dosage is 300 mg/day, split into three doses, taken with food. Avoid taking this supplement within four hours of sleep to avoid insomnia.
For depression and mood, stack PS with a quality omega-3 fatty acid supplement.
Thanks to its safety profile, you can stack PS with most nootropics to experience the benefits that both have to offer.
Phosphatidylserine and Piracetam
One common stack is PS with members of the racetam family. Racetams help to boost cognition through their impact on the cholinergic system. This system influences acetylcholine levels in the brain.
Piracetam is the first racetam, and as such, has been well-studied and reviewed. By combining these two nootropics you can experience an even greater boost in memory. They both exert neuroprotective benefits and can help protect against age-related cognitive decline.
- 300 mg/day Phosphatidylserine, split into three doses
- 1,600-4,800 mg/day Piracetam, split into three doses
Choline, Phosphatidylserine, and DHA
If you are looking for a stack to enhance the production of cell membranes and promote a positive mood, Phosphatidylserine, choline, and DHA will do just that.
This stack helps improve overall cognitive function. You are likely to experience benefits in clarity of thought, memory, learning, mood, and focus.
It’s best to use a choline supplement that easily crosses over the blood-brain barrier. Good options include Alpha GPC, CDP-Choline (Citicoline), or Centrophenoxine.
- 300 mg/day Phosphatidylserine, split into three doses
- 300 mg/day Alpha GPC, split into two doses
- 600 mg/day DHA, split into three doses
Comparisons to Other Nootropics
Phosphatidylserine vs Phosphatidylcholine
Both Phosphatidylserine and Phosphatidylcholine (PC) are phospholipids produced endogenously by your body that are available in foods and as supplements. PC contains choline and is used in the production of ACh. In the body, some PC will be used to synthesize PS.
PS is a better choice as a nootropic for memory, mood, and stress benefits. PC is better as a source of choline for the body rather than the brain. Other sources of choline are better for brain health.
Alpha GPC vs Phosphatidylserine
Alpha GPC is a highly bioavailable source of choline for the brain. It can be used in the synthesis of ACh, and thus has nootropic benefits of its own. Research suggests that it helps those suffering from age-related cognitive decline.
For overall memory, learning, and protection against age-related cognitive decline, Alpha GPC is a better option. If you’re looking to reduce your feelings of stress and relieve anxiety, PS is a good choice.
Foods Containing Phosphatidylserine
Only a handful of foods commonly consumed in the West contain high levels of this compound. Here is a list of some foods high in Phosphatidylserine, along with their mg/100 g PS:
- Atlantic mackerel: 480
- Atlantic herrine: 360
- Eel: 335
- Tuna: 194
- Chicken leg: 134
- White beans: 107
- Chicken breast: 85
- Beef: 69
- Pork: 57
- Whole grain barley: 20
- Rice: 3
Vegan or vegetarian diet, stress, and aging can lead to deficiencies in Phosphatidylserine. Even if you are consuming plenty of PS in your diet, many studies and user reports have found that supplemental PS may help to improve health.
The PS in supplements is typically derived from soy lecithin, but you can find soy free options made from sunflowers and cabbage. Previously PS was derived from bovine sources, however this was discontinued thanks to fear of mad cow disease.
User Reviews and Experience
“Phosphatidylserine definitely did something for me…It makes me relaxed and in a good mood. I am not sure if the cognitive effects were imagined due to the positive increase in mood/feeling.” Reddit user review
“I’ve been taking it for several weeks and it’s a pretty good nootropic, really I recommend it, before PS I would almost never dream, now with PS I dream every single night and it hasn’t decreased since then, also my creativity and memory have increased.” LongeCity user review
Where to Buy Phosphatidylserine Supplements
This nootropic is available in capsule and bulk powder form. You can find it in brick-and-mortar stores like GNC and the Vitamin Shoppe, or through online vendors. It’s important to purchase a quality PS supplement; typically the higher the price, the better the quality when it comes to these supplements.
Amazon and iHerb both carry a wide variety of PS supplement options with user reviews to help you choose the best one.
Vayarin is a drug composed of PS with the omega-3 fatty acid EPA. This may be a good option if you would like to combine your omega-3 supplement with PS, which may help to support a positive mood.
While many nootropics are not sold in Australia, the UK, and Canada due to legal restrictions, Phosphatidylserine is widely available in these countries as well as the US.
- Effects of phosphatidylserine therapy in geriatric patients with depressive disorders https://www.ncbi.nlm.nih.gov/pubmed/1693032
- Cognitive decline in the elderly: a double-blind, placebo-controlled multicenter study on efficacy of phosphatidylserine administration https://www.ncbi.nlm.nih.gov/pubmed/8323999
- The effect of PS administration on memory and symptoms of ADHD…. https://onlinelibrary.wiley.com/doi/abs/10.1111/jhn.12090
- Effects of PS on exercise capacity during cycling in active males https://journals.lww.com/acsm-msse/Fulltext/2006/01000/Effects_of_Phosphatidylserine_on_Exercise_Capacity.11.aspx
- The effect of PS on golf performance https://jissn.biomedcentral.com/articles/10.1186/1550-2783-4-23
- Dopamine and serotonin metabolic levels… https://www.ncbi.nlm.nih.gov/pubmed/6157799
- PS reverses age-dependent decrease in cortical ACh release… https://www.ncbi.nlm.nih.gov/pubmed/2060587
- The effects of IQPLUS Focus on cognitive function, mood and endocrine response before and following acute exercise https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3210081/
- Blunding by chronic phosphatidylserine administration of the stress-induced activation of the hypothalamo…. https://www.ncbi.nlm.nih.gov/pubmed/1325348
- Effects of soy lecithin phosphatidic acid and phosphatidylserine complex on the endocrine and psychological responses to mental stress https://www.ncbi.nlm.nih.gov/pubmed/15512856
- Enhanced learning in normal adult rodents by repeated oral administration… https://www.ncbi.nlm.nih.gov/pubmed/16006737
- Neurodegeneration from mitochondrial insufficiency.. https://www.ncbi.nlm.nih.gov/pubmed/16366737
- The effects of PS and Omega-3 fatty acid-containing supplement on late life depression https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4508628/