What exactly is phosphatidylserine?

Phospholipids are a phospholipid. The group of phospholipids is divided into four subgroups: lecithins, cephalins, phosphatidylinositols and sphingomyelins. Phosphatidylserine belongs to the cephalins. Chemically, it consists of glycerol, phosphate and serine. Part of the phosphatidylserine is decarboxylated to phosphatidylethanolamine and in a further step methylated to phosphatidylcholine [cf. Linnemann and Kühl, 2013].

Phospholipids are building blocks for membranes that surround and protect cells. Together with other membrane phospholipids, phosphatidylserine plays a central role in the communication between cells and for the transmission of biochemical signals into the cell interior [cf. Kay and Grinstein, 2013]. In particular, nerve cells depend on phosphatidylserine - therefore, the highest concentration of phosphatidylserine is found in the peripheral and central nervous tissue.

Phosphatidylserine is biosynthesized in small amounts, ie produced by the body itself. However, if there is a deficiency in one of the building blocks phenylalanine, lysine, tyrosine, methionine or tryptophan and/or in one of the cofactors choline, folic acid and vitamin B 12, the brain is not able to produce sufficient phosphatidylserine and a deficiency occurs.

Numerous clinical studies show a positive effect of phosphatidylserine

• on cognitive functions, such as memory and language performance as well as learning and concentration skills [cf. Glade and Smith, 2015]
• in age-related memory impairment and cognitive decline [cf. Kidd, 1996] by enhancing dopamine and acetylcholine release [cf. Mazzari and Battistella, 1980; Vannucchi and Pepeu, 1987; Casamenti et al., 1979]
• on cortisol levels: Phosphatidylserine modulates the release of cortisol during the stress response [cf. Monteleone et al., 1992]
• for depression, among other things due to the induced cortisol reduction [cf. Maggioni et al., 1990]
• on the blood clotting: If a blood vessel is damaged, the platelets are activated. These also contain phosphatidylserine. Phosphatidylserine then "migrates" from the inner to the outer side of the cell membrane. This helps to trigger blood clotting.

Modulation of the stress hormone cortisol

Cortisol is released in increased amounts in both psychological and physical stress situations. ACTH from the anterior pituitary gland stimulates the production of cortisol. Like other stress hormones, cortisol has an "energy-secreting" effect on the body and thus influences both fat metabolism (inhibiting) and carbohydrate metabolism (promoting). It also promotes protein breakdown (proteolysis), reduces testosterone synthesis and reduces the insulin sensitivity of cells. Ultimately, cortisol promotes calcium excretion, reduces calcium absorption and ensures a redistribution of body fat towards the visceral area, which increases the risk of cardiovascular disease as well as obesity and diabetes. Since it promotes sodium accumulation and potassium excretion, it can also lead to the well-known "bloated" appearance.

The release of stress hormones can be significantly reduced as a result of phosphatidylserine administration.  This effect has been demonstrated in various studies (see below).) can be observed in both older people and healthy young people.

phosphatidylserine content in our food

Phosphatidylserine is mainly found in fish and meat. Dairy products and plant-based foods tend to be low in this substance. Especially in low-fat or low-cholesterol diets (e.g. vegetarian, vegan, low-fat), the necessary amount of 200-300 mg of phosphatidylserine per day is often not guaranteed.

The main food sources of phosphatidylserine (per 100 g) are

herring	360 mg
offal	305 mg
white beans	107 mg
chicken breast (with skin)	85 mg
beef	69 mg

Possible therapeutic use of phosphatidylserine

1. Promotion & Maintenance of Cognitive Abilities

As we age, the mass of our brain decreases by up to 100 grams. We lose nerve cells and the density of synaptic connections in the neuronal network decreases. The amount of cholesterol in the brain increases with age, while the amount of phospholipids decreases. From around the age of 45, the phosphatidylserine content in the nervous system. This is due, among other things, to the fact that the building blocks and cofactors required for biosynthesis How  methionine,  folic acid,  vitamin B12  or essential fatty acids decrease with increasing age.

It is assumed that memory performance is stored as a kind of "biochemical change" in the neuronal circuit system. An RNA-dependent synthesis of protein takes place for a new memory trace. Without enough phosphatidylserine, however, this is disrupted because no proper cell wall structure including the necessary proteins is formed. This affects short-term memory.

The result is that the lack of phosphatidylserine leads to poor signal transmission in the brain. The brain tries to compensate for this by increasing its activity level and has to release more stress hormones to do so.

Most intervention studies were conducted on subjects with age-related brain dysfunction, also known as ARCS (Age Related Cognitive Decline or AAMI (Age Associated Memory Impairment). Studies of this group of people were carried out with 20-400 subjects. They received 100-300 mg/day of phosphatidylserine for 1-3 months. Neuropsychological tests were carried out at the same time as the drug was taken. The results showed an improvement in the parameters of attention, concentration, memory and learning ability.

A large double-blind study involved 425 subjects aged 65-93 years who had moderate to severe impairments in mental performance, particularly memory, thinking, speech and motor skills. They were given 300 mg of phosphatidylserine or a placebo daily for 6 months.At the end of the study, significant improvements in behavior and mood as well as in memory and learning performance, which were determined using word recall tests.

Phosphatidylserine was also able to reduce cognitive impairment in clinical studies involving a total of 577 elderly people at a dosage of 300 mg per day (see Table 1). https://www.ncbi.nlm.nih.gov/pubmed/8323999 and https://www.ncbi.nlm.nih.gov/pubmed/20523044 ).

Another study with older people showed significant Improvements in short-term memory, concentration and attentionIn addition, depressive symptoms, the ability to cope with daily life and apathy behavior improved [cf. Palmieri G et al.: Double-blind controlled trial of phosphatidylserine in subjects with senile mental deterioration. Clin Trials J 24: 73-83 (1987)].  Apathy is usually accompanied by, among other things, apathy, lack of excitability and insensitivity to external stimuli.

In another clinical study with 72 subjects, phosphatidylserine was able to improve not only memory performance but also mood (see: https://www.ncbi.nlm.nih.gov/pubmed/24577097 ).

In combination with omega-3 fatty acids and ginkgo biloba, phosphatidylserine was able to help maintain or improve memory performance in three clinical studies with 158 subjects (see: https://www.ncbi.nlm.nih.gov/pubmed/24577097 and https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2981104/ ).

One possible explanation for the improvements in cognitive functions in older people with phosphatidylserine supplementation is the increased synthesis of the neurotransmitter acetylcholineIncreased PS concentrations can lead to a faster and increased release of acetylcholine into the synaptic cleft – gap between two neurons connected in series – This leads to a increased memory and one increased mental performance [Rehner G, Daniel H: Biochemistry of nutrition. 7-14. Spektrum Akademischer Verlag Heidelberg/Berlin; 2002]. Phosphatidylserine could possibly increase the acetyl concentration at the motor – muscular – Endplate increase during physical strength development [cf. Berg JM, Tymoczko JL, Stryer L: Biochemistry. Spektrum Akademischer Verlag; 2003; 5th edition].

With a longer treatment period, studies with 300 mg/day showed no significant differences compared to 100 mg/day, which is why it can be recommended to reduce the dosage from 300 mg to 100 mg/day after a 12-week initial dose.

Important: Phosphatidylserine does not work if taken once. Significant improvements only occur with regular supplementation. Studies show initial improvements at the end of the first month.

2. Alzheimer

Alzheimer's disease is associated with an accumulation of amyloid beta in the brain. Studies have shown that phosphatidylserine prevents this accumulation, which could prevent or slow the progression of this disease (see: https://www.ncbi.nlm.nih.gov/pubmed/17349923 ).

In a clinical study with 51 Alzheimer patients, phosphatidylserine reduced symptoms and improved cognition, with the best results being observed in patients with milder impairments (see Table 1). https://www.ncbi.nlm.nih.gov/pubmed/1609044 ).

In two other studies involving 104 patients with early-stage Alzheimer's disease, phosphatidylserine was able to alleviate symptoms of dementia. However, there is evidence that these effects may diminish over time (see: https://www.ncbi.nlm.nih.gov/pubmed/8038871 and https://www.ncbi.nlm.nih.gov/pubmed/1633433 ).

In a clinical study with 42 senile patients, 300 mg of phosphatidylserine was also able to reduce dementia symptoms (see: https://www.ncbi.nlm.nih.gov/pubmed/3518329 ).

3. ADHD

A lack of phosphatidylserine reduces brain activity levels; to compensate for this, our body releases more stress hormones. In a study with children with ADD, supplementation with phosphatidylserine showed a success rate of 92% in improving symptoms. This included short-term memory, attention and social behavior. Impulsivity and hyperactivity could also be curbed. Children with ADHD who are particularly impulsive and have severe behavioral problems seem to benefit from phosphatidylserine.

In two clinical studies with 236 children, phosphatidylserine alone or in combination with omega-3 fatty acids was able to reduce ADHD symptoms. According to the authors of one of these studies, it may be particularly effective in hyperactive, impulsive and emotionally and behaviorally dysregulated children (see: https://www.ncbi.nlm.nih.gov/pubmed/21807480 and https://www.ncbi.nlm.nih.gov/pubmed/23495677 ).

Micronutrient physicians recommend 150 to 200 milligrams of phosphatidylserine daily for ADHD.

4. stress

Long-term psychological stress leads to an excessive release of stress hormones (especially cortisol). This can lead to a disruption of the body's own stress system - the so-called hypothalamic-pituitary-adrenal axis (HPA axis). Imbalances in this system lead to depression or anxiety. Tiredness, pain and irritability are also possible.

Phosphatidylserine keeps cortisol away from the cells. In a clinical study with 80 subjects under emotional stress, supplementation with phosphatidylserine reduced the plasma levels of both cortisol and ACTH, which controls cortisol secretion (see. https://www.ncbi.nlm.nih.gov/pubmed/15512856). Hellhammer et al used 400mg PS and found that the results did not improve with higher doses (600 or 800mg).

In a study with 48 male students, the subjects were given either 300mg/day or a placebo for 30 days. Mental stress was induced by a math test that took place after the dose. As a result, the phosphatidylserine group felt significantly clearer and more energetic on the day of the test and ultimately achieved better test results.

In two other clinical studies with a total of 135 male subjects, 400 mg of phosphatidylserine in combination with omega-3 fatty acids was also able to normalise ACTH and cortisol levels, although this effect was only observed in chronically stressed subjects (cf. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4237891/ and https://www.ncbi.nlm.nih.gov/pubmed/22575036). Another study with young volunteers showed that phosphatidylserine in a dosage of 300 mg promoted calmness and improved mood in stressful situations (cf. https://www.ncbi.nlm.nih.gov/pubmed/11842886).

For use in (chronic) stress, micronutrient physicians recommend 200 to 400 milligrams of phosphatidylserine per day.

5. sport

Phosphatidylserine can be used in sports due to its regulating effect on stress hormones: Excessive physical exercise causes cortisol to be released. Excessive cortisol release is associated with a drop in performance, muscle pain and severe fatigue.  This is also associated with overtraining.

The  Influence of phosphatidylserine on cortisol levels  was examined in a double-blind study on people who took part in resistance training for all muscle groups. One group took 800 mg of phosphatidylserine in addition to their normal diet, while the other group received a placebo. Immediately after training, the cortisol and testosterone levels as well as mental performance were recorded. The evaluation showed that phosphatidylserine-supplemented group consistently had significantly lower cortisol levels after each training phase. Due to the lower cortisol secretion, the phosphatidylserine group also showed a increased testosterone levels (increased cortisol levels reduce testosterone synthesis). In addition, a large proportion of the participants supplemented with phosphatidylserine reported a improved mental performance.

According to this result Phosphatidylserine in combination with resistance training prevents protein and thus muscle catabolism by inhibiting cortisol production (Cortisol promotes protein breakdown, which leads to  muscle breakdown) and can ultimately lead to an increase in muscle mass. In addition, phosphatidylserine helps promote regeneration after training [cf. Cenacchi T, Bertoldin T, Farina C, Fiori MG, Crepaldi G: Cognitive decline in the elderly: A double-blind, placebo-controlled multicenter study on efficacy of phosphatidylserine administration. Aging (Milano). 1993 Apr;5(2):123-33 / Fahey TD, Pearl M: Hormonal effects of phosphatidylserine during 2 weeks of intense training. Abstract submitted to national meeting of the American College of Sports. Medicine; June 1998 / Henrichs D: Handbuch Nähr- und Vitalstoffe, Orthomolekulare Ernährung. Constantia-Verlag; 4th revised edition / Monteleone P et al.: Effects of phosphatidylserine on the neuroendocrine response to physical stress in humans. Neuroendocrinology. 1990 Sep;52(3):243-8 / Monteleone P, Maj M, Beinat L, Natale M, Kemali D: Blunting by chronic phosphatidylserine administration of the stress-induced activation of the hypothalamo-pituitary-adrenal axis in healthy men. Eur J Clin Pharmacol. 1992;42(4):385-8].

As part of a study at the University of Mississippi, two groups of subjects performed resistance training eight times a week. One group received 600 mg of phosphatidylserine per day and the other group a placebo. Immediately after the training, cortisol and testosterone levels were determined, and mental performance was assessed. As a result, the phosphatidylserine group had consistently lower ACTH and cortisol levels (up to 30%) and higher testosterone levels. A large proportion of the phosphatidylserine group also reported better mental performance.

Further studies summarized by the University of Wales came to the following conclusions:

• The administration of 100-500 mg of phosphatidylserine after training in young female athletes led to a decrease in cortisol levels.
• A group of eight untrained but healthy men aged 24-42 were given 800 mg of phosphatidylserine 10 minutes before training on a bicycle ergometer, while the other group received a placebo. As a result, cortisol levels were reduced by 30% in the phosphatidylserine group.

phosphatidylserine is therefore able to stop muscle catabolism by influencing cortisol and testosterone levels, promote regeneration after training and reduce overtraining. In the studies examined, dosages go up to 800 mg/day. No further positive effects are to be expected above this. After training and in the evening are probably the preferred times to take it.

Bioavailability & Dosage

The effectiveness of oral intake of phosphatidylserine on neuronal membranes and on neurotransmitters such as acetylcholine, noradrenaline, dopamine and serotonin, scientifically well-documented [cf. Toffano et al., 1976; Casamenti et al., 1979; Argentiero and Tavolato, 1980]. Radioactively labelled phosphatidylserine could be detected in the blood 30 minutes after ingestion and subsequently in the brain after passage through the liver and the blood-brain barrier.

Phosphatidylserine is most likely not absorbed in its entirety in the small intestine, but broken down into its components, which are then synthesized into phosphatidylserine again after absorption. Phosphatidylserine is then transported mainly to the liver and brain and stored there.

According to current knowledge, phosphatidylserine is safe and well tolerated: 300 milligrams per day for almost four months did not cause any significant side effects. In rare cases, stomach upsets can occur. A dosage of over 600 milligrams per day can also cause sleep disorders.

There are no official dosage recommendations for phosphatidylserine, but in clinical studies the dosage used was generally between 200 and 400 mg per day.

Depending on the application, the following dosages can be found in the literature:

• Memory: 100-300 mg
• AD(H)D: 150-200 mg
• Stress: 200-400 mg
• Sport: 400-800 mg

Often, a combination of phosphatidylserine with omega 3 fatty acids (EPA & DHA) is recommended due to its synergistic effect, as the body can incorporate omega-3 fatty acids into phosphatidylserine.

Possible interactions

• Drying medications (anticholinergic agents): Some drying medications are called anticholinergic drugs. Phosphatidylserine could increase the levels of chemicals that could reduce the effects of these drying medications
• Drugs against Alzheimer's (anticholinesterase inhibitors): Phosphatidylserine may increase levels of a chemical called acetylcholine in the body. Drugs for Alzheimer's called anticholinesterase inhibitors also increase acetylcholine levels.Taking phosphatidylserine in combination with medications for Alzheimer's disease could increase the effects and side effects of these medications for Alzheimer's disease.
• Different medications for glaucoma, Alzheimer's, and other diseases (cholinergic medications): Phosphatidylserine may increase the levels of a chemical in the body called acetylcholine. This chemical is similar to some medications used to treat glaucoma, Alzheimer's, and other diseases. Taking phosphatidylserine with these medications may increase the risk of side effects.
• Antiphospholipid syndrome: In antiphospholipid syndrome, the immune system attacks the body's own phospholipids. Those affected often have an increased risk of blood clots, stroke or heart attack. Many sufferers then also have antibodies against phosphatidylserine in their blood. Patients with this disease should not take phosphatidylserine to be on the safe side. Its use has not yet been studied.

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