In the world of today where memory, focus, and cognitive advancement are largely used as parameters to judge one’s intelligence, there is no wonder that everyone wants to win that race. 

While one may argue that mental acuity, intelligence, cognition, and focus are largely the result of genetics and consistent practice, naturally occurring supplements definitely aids in cognitive advancement, as per the research. 

And, for that reason, there is a lot of ongoing research on developing new nootropics that could enhance your neurological/brain health in the best possible ways. 

Perhaps what could be better than a naturally existing compound being used as a cognitive supplement and which is also backed up by strong clinical research. 

Yes, today we are talking about Phosphatidylserine (PS), one of the endogenously produced lipids in the body.

Research backs up the benefits of Phosphatidylserine as a potent nootropic compound, and is known to improve cognition and memory, and also manage as well as treat some neurological disorders, such as ADHD, depression, etc. 

By the end of the article, I assure you that you will be able to decide whether to use PS supplementation for its prospective nootropic benefits or not. 

What is Phosphatidylserine?

Phosphatidylserine (PS) is an endogenously produced lipid, specifically phospholipid. Talking about the structure of the PS, it constitutes 2 fatty acids which are attached to different carbons of the glycerol and the serine is attached via phosphodiester linkage to the 3rd carbon (1). 

Even though the human body is capable of producing PS, most of it needs to be obtained through diet to meet the requirements. 

Phospholipids make up much of our cell membranes, which are phospholipid bilayers that provide protection and support for our cells (2). It is important to know that major portion of this acidic phospholipid, PS, is only found in the inner layer of the bilayer. 

While understanding the biosynthesis of Phosphatidylserine can get a bit complicated, you should know that PS can readily be converted to the other phospholipids, such as Phosphatidylethanolamine and Phosphatidylcholine. 

The compound is found in high concentrations in our brain, and thus plays an important role in the health and function of our neurons, or brain cells (3).

How Does It Work? 

While we will dig into the details of the mechanism of action followed by Phosphatidylserine, it broadly plays a role in cell signaling which triggers the process of apoptosis, or cell death.

To really know the inner workings of Phosphatidylserine, let’s first try to understand what happens in cognitive disorders, such as Alzhemiers. 

The decrease in levels of Acetylcholine weakens the level of neuronal connections, thus less communication exists between the neurons. This eventually leads to memory impairment, learning disabilities, and overall cognitive dysfunction (4). 

What Phosphatidylserine does is it triggers the increased synthesis and release of the acetylcholine. Besides, Phosphatidylserine also stimulates protein kinase C pathway and promotes the uptake of Calcium by pre-synaptic cells (5). 

While all of these are potential activities at cellular level which could affect cognitive health, PS is also known to trigger apoptosis. It does this by expressing itself onto the outer layer of phospholipid bilayer. This acts as initiation of transduction pathway, leading to cell death. 

Benefits of Phosphatidylserine 

It is important to dig into each of the individual effects of Phosphatidylserine because of its diverse nootropic effects. 

Improving Attention-deficit hyperactivity disorder (ADHD)

ADHD can make life a lot difficult for people. Not being able to properly focus and pay attention is not only unproductive but also embarrassing at times. 

While there are a lot of medications usually prescribed for ADHD, 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 with minimal side effects (6). 

In one study, 36 children between the ages of 4 and 14 diagnosed with ADHD were split into either a PS group or a placebo group for two months. 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 as well.

Treating Depression

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. 

In another study, 18 elderly patients with treatment-resistant depression were treated daily for 12 weeks with PS supplementation. 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 (7).

Enhancing 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 (8).

In one study on healthy adults, physically active young men took PS before and after acute exercise. Compared to placebo, this nootropic led to improvements in mathematical speed and accuracy, with errors reduced by 39%. This ability for PS to help cognitive function when fatigued is promising for athletes and overachievers both.

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. In both of these studies, participants took PS supplementation, and both experienced improvement.

In another study on healthy rats, 27 days of supplementation led to enhanced brightness discrimination, which suggests improvements in memory formation.

Other studies have also found benefits for those with dementia and memory complaints.

Treating Adrenal Fatigue by lowering Cortisol levels

Whether or not adrenal fatigue is a real condition is a lot 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, and 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 exercise-induced physical stress. 

In another study, PS counteracted the exercise-induced HPA-axis stress response in healthy men. A further study showed that taking Phosphatidylserine complex for three weeks led to reductions in serum cortisol in response to mental and emotional stressors.

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 (9).

Anxiety-Relief

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.

Weight Loss

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.

Brain Repair

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 for those suffering from memory impairments, dementia, and Alzheimer’s disease, suggesting a neuroprotective role.

Influence on 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. 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), was increased in rats following PS supplementation. This benefit occurred only in old rats, not in young, healthy rats.

Researchers concluded that this increase in ACh release may be associated with increased choline availability, which is used in ACh synthesis. PS may also inhibit the production and release of acetylcholinesterase, an enzyme responsible for the breakdown of ACh in the brain.

Dosage

Phosphatidylserine is a fat-soluble compound with a short half-life. The typical dosage is anywhere between 200 to 400 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.

Side Effects & Interactions

Although PS is considered safe and non-toxic, there is always a risk of side effects in case of overdose. Some of the unwanted effects include: 

• Fatigue
• Trouble sleeping
• Upset Stomach
• Brain fog
• Nausea
• Insomnia 

These side effects are most common with high dosages, or supplementation shortly before sleep, or when it is taken for months continuously 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 might be feasible.

It can interact with both synthetic and natural blood thinners. Thus, you need to make sure about that part. 

Foods Containing Phosphatidylserine

Only a handful of foods commonly consumed in the West contain high levels of this compound. 

Some of them are: 

• Atlantic mackerel
• Atlantic herrine
• Eel
• Tuna
• Chicken leg
• White beans
• Chicken breast
• Beef
• Pork
• Whole grain barley
• Rice

A 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 owing to the growing fear of mad cow disease.

User Reviews and Experience

It is always important to know about the personal experiences of people because the anecdotal evidence not only backs up the existing scientific research but also one can relate and feel extremely satisfactory with the product. 

One of the Reddit users with the username FUUAAARRRRKK said, 

“Pretty effective at lowering cortisol for me, I say that because I always get pretty chilled or tired after taking it. I did 100mg doses. Memory did improve on it.”

Michael_Uchiha6 said, 

“PS is one of my favorite Nootropics. Actually have some coming in this morning, haha. I typically use 300mg daily (in divided doses), but I’ve gone as high as 600mg to great effect.

At the former level, there’s a slight bump in focus and memory, while at the latter level, I’ll generally start falling asleep much easier for some reason (which might be cortisol related, others are saying that since PS can lower the stress hormone at higher doses).”

Punkideas, another Reddit user left a comment, saying, 

“I’ve had good luck with it and have been taking it for a bit over a year. It has helped with my sleep quality and energy. I started out with 100mgx3 a day for about a month, and have maintained the benefits with 100mg in the morning. Based on what I’ve seen, this seems to be a supplement that has a lot of variation in efficacy between people, so YMMV.”

While thats the good part, what I have seen is that people have had mixed experiences with PS supplementation. Now lets look at the other part of the story. 

Screw_hypomania reported one of the adverse effects, and said,

“ditto of my experience. I was too mellowed out with even 100mg doses taken daily. I also started to have mild dizziness on standing up (orthostatic hypotension), which made me think my cortisol might be getting too low. Quit.”

Bomb_Jack said, 

“Two considerations. First, you may want to go down to 400mg/day, the studies always range from to 400 to 600. Second, you could move all of your dose before going yo bed at night. In any case, I am surprised of you symptoms, they don’t really seem the ones of low cortisol and in any case I doubt that PS could lower it that much. That being said, I remember if a study where it was specifically stated that soy derived PS had effect whereas bovine one didn’t. I don’t even remember what the study was proving though… :-/”

Stacks

Because of the enhanced nootropic effects of PS, it is generally considered safe to stack it with other nootropics to enjoy synergistic benefits. 

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 and learning. They both exert neuroprotective benefits and can help protect against age-related cognitive decline.

Choline, Phosphatidylserine, and DHA

If you are looking for a stack to enhance the integrity 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.

Phosphatidylserine and Ginkgo Biloba 

Ginkgo Biloba is a plant extract native to China. Having been used for years now, it has traditionally been prescribed for mental benefits. 

Research suggests that Ginkgo Biloba improves cerebral blood circulation. This antioxidant-rich herb is found to be effective in treating cognitive disorders, dizziness, dementia, etc. 

Not only these, but Ginkgo Biloba is also found to be effective in improving your memory, and for all these reasons, it is generally now stacked with Phosphatidylserine to enjoy the optimal cognitive benefits. 

Where to Buy Phosphatidylserine Supplements? 

Phosphatidylserine is currently available in two forms, which are capsules and softgels. 

It’s important to purchase a quality PS supplement because it concerns your health, especially your brain health. 

While many nootropics are not sold in Australia, the UK, and Canada due to legal restrictions, Phosphatidylserine is widely available in USA.

Considering my understanding of the vendors, I have picked out the three top vendors offering high-quality PS which could make your experience worthwhile. 

Phosphatidylserine vs 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 as well. 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.