What exactly is phosphatidylserine?

Phosphatidylserine is a phospholipid. The group of phospholipids is divided into four subgroups: lecithins, cephalins, phosphatidylinosites, and sphingomyelins. Phosphatidylserine belongs to the cephalins. Chemically, it consists of glycerol, phosphate, and serine. A portion of the phosphatidylserine is decarboxylated to phosphatidylethanolamine and subsequently methylated to phosphatidylcholine [cf. Linnemann and Kühl, 2013].

Phospholipids are building blocks for membranes that surround and protect cells. Phosphatidylserine, along with other membrane phospholipids, 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]. Nerve cells, in particular, depend on phosphatidylserine. - therefore, the highest concentration of phosphatidylserine is found in peripheral and central nerve tissue.

Phosphatidylserine is biosynthesized in small amounts, d.hPhosphatidylserine is produced by the body itself. However, if there is a deficiency of one of the building blocks phenylalanine, lysine, tyrosine, methionine, or tryptophan and/or one of the cofactors choline, folic acid, and vitamin B12, the brain is unable to produce sufficient phosphatidylserine, resulting in a deficiency.

Numerous clinical studies show a positive effect of phosphatidylserine

• on cognitive functions, How z.BMemory and language performance as well as learning and concentration skills [cf. Glade and Smith, 2015]
• in age-related memory disorders and cognitive decline [cf. Kidd, 1996] by increasing the release of dopamine and acetylcholine [cf. Mazzari and Battistella, 1980; Vannucchi and Pepeu, 1987; Casamenti et al., 1979]
• on cortisol levelsPhosphatidylserine modulates the release of cortisol during the stress response [cf. Monteleone et al., 1992]
• in cases of depression, u.a. due to the induced cortisol reduction [cf. Maggioni et al., 1990]
• on the Blood clottingWhen a blood vessel is injured, platelets are activated. These also contain phosphatidylserine. Phosphatidylserine then migrates from the inner to the outer side of the cell membrane. This contributes to triggering blood clotting.

Modulation of the stress hormone cortisol

Cortisol is released in increased amounts during both psychological and physical stress. ACTH from the anterior pituitary gland stimulates cortisol production. Like other stress hormones, cortisol has an energy-depleting effect on the body, thus influencing both fat metabolism (inhibiting) and carbohydrate metabolism (promoting). It also promotes protein breakdown (proteolysis), reduces testosterone synthesis, and decreases the insulin sensitivity of cells. Ultimately, cortisol promotes calcium excretion, reduces calcium absorption, and redistributes body fat towards the visceral area, increasing the risk of cardiovascular disease, obesity, and diabetes. Furthermore, because it promotes sodium accumulation and potassium excretion, it can lead to the familiar "bloated" appearance.

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

Phosphatidylserine content in our food

Phosphatidylserine is found primarily in fish and meat. Dairy products and plant-based foods are relatively low in this substance. Especially with 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 met.

The most important 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

Potential therapeutic use of phosphatidylserine

1. Financial support &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 neural network decreases. The cholesterol content of the brain increases with age, while the phospholipid content decreases. From about the age of 45, the Phosphatidylserine -Content in the nervous system. This is due to u.a...the fact that the building blocks and cofactors required for biosynthesis How Methionine Folic acid Vitamin B12 or essential fatty acids decrease with age.

Memory performance is thought to be stored as a kind of "biochemical change" in the neuronal switching system. A new memory pathway requires RNA-dependent protein synthesis. However, without sufficient phosphatidylserine, this process is disrupted because a proper cell wall structure, including the necessary proteins, cannot be formed. This affects short-term memory.

The consequence of this is that, due to the phosphatidylserine deficiency, signal transmission in the brain is impaired. The brain attempts to compensate for this through a higher level of activity and therefore has to release more stress hormones.

Most intervention studies were conducted with participants exhibiting age-related cognitive decline, also known as ARCS (Age-Related Cognitive Decline) or AAMI (Age-Associated Memory Impairment). These studies involved 20-400 participants who received 100-300 mg/day of phosphatidylserine for 1-3 months. Neuropsychological tests were administered concurrently. The results showed improvements in attention, concentration, memory, and learning ability.

A large double-blind study involved 425 participants aged 65-93 years who exhibited moderate to severe cognitive impairment, particularly in memory, reasoning, language, and motor skills. They were administered 300 mg of phosphatidylserine or a placebo daily for six months. At the end of the study, the following results were observed: significant improvements in both 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 with a total of 577 elderly people at a dosage of 300 mg per day (see [reference]). https://www.ncbi.nlm.nih.gov/pubmed/8323999 and https://www.ncbi.nlm.nih.gov/pubmed/20523044 ).

In another study with older people, clear differences were observed. Improvements in short-term memory, concentration, and attentionFurthermore, depressive symptoms, the ability to cope with daily life, and apathy 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, indifference, 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 below). 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 3 clinical studies with 158 subjects (see [reference]). 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 function in older people with phosphatidylserine supplementation is the increased synthesis of the neurotransmitter acetylcholineIncreased concentrations of PS can lead to a faster and greater release of acetylcholine into the synaptic cleft. – Gap space between two neurons connected in series – be guaranteed. This leads to a improved memory and one increased mental performance [Rehner G, Daniel H: Biochemistry of Nutrition. 7-14. Spektrum Akademischer Verlag Heidelberg/Berlin; 2002]. Phosphatidylserine might possibly affect the acetyl concentration at the motor cortex. – muscular – Endplate volume increases during physical strength development [cf. Berg JM, Tymoczko JL, Stryer L: Biochemistry. Spektrum Akademischer Verlag; 2003; 5th edition].

In studies with longer treatment durations, no significant differences were found between 300mg/day and 100mg/day, which is why it is recommended to reduce the dose to 100mg/day after a 12-week initial dose of 300mg.

Important: Phosphatidylserine is not effective after a single dose. Significant improvements only occur with regular supplementation. Studies show initial improvements by 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 the disease (see [reference]). https://www.ncbi.nlm.nih.gov/pubmed/17349923 ).

In a clinical study with 51 Alzheimer's patients, phosphatidylserine reduced symptoms and improved perception, with the best results observed in patients with milder impairments (see [reference]). https://www.ncbi.nlm.nih.gov/pubmed/1609044 ).

In two further studies with 104 Alzheimer's patients in the early stages of the disease, phosphatidylserine was able to alleviate symptoms of dementia. However, there are indications that these effects may diminish over time (see [reference]). 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 [reference]). https://www.ncbi.nlm.nih.gov/pubmed/3518329 ).

3. ADHD

A deficiency in phosphatidylserine lowers brain activity levels; to compensate, our body releases increased amounts of stress hormones. In a study with children with ADHD, phosphatidylserine supplementation showed a 92% success rate in improving symptoms. These included short-term memory, attention, and social behavior. Impulsivity and hyperactivity were also reduced. Children with ADHD who exhibit severe behavioral problems and impulsivity appear to particularly benefit from phosphatidylserine.

In two clinical trials 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 could be particularly effective in hyperactive, impulsive, and emotionally and behaviorally dysregulated children (see [reference]). https://www.ncbi.nlm.nih.gov/pubmed/21807480 and https://www.ncbi.nlm.nih.gov/pubmed/23495677 ).

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

4. stress

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

Phosphatidylserine prevents cortisol from entering cells. Thus, in a clinical study with 80 subjects under emotional stress, phosphatidylserine supplementation reduced plasma levels of both cortisol and ACTH, which controls cortisol release (see [reference]). https://www.ncbi.nlm.nih.gov/pubmed/15512856Hellhammer et.al They used 400mg of PS for this purpose and found that the results did not improve further with higher doses (600 or 800mg).

In a study with 48 male students, participants were given either 300 mg/day or a placebo for 30 days. Mental stress was induced by a math test administered after the medication intake. The results showed that the phosphatidylserine group felt significantly clearer and more energetic on the test day 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 normalize ACTH and cortisol levels, although this effect was only observed in chronically stressed subjects (see [reference]). 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 at a dosage of 300 mg promoted calmness and improved mood in stressful situations (see [reference]). https://www.ncbi.nlm.nih.gov/pubmed/11842886).

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

5. sport

Phosphatidylserine can be used in sports due to its regulatory effect on stress hormones: Excessive physical activity leads to the release of cortisol. An excessive release of cortisol is associated with decreased performance, muscle pain, and severe fatigue. This is also associated with overtraining.

The Influence of phosphatidylserine on cortisol levels The study was conducted in a double-blind trial with participants who underwent 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. Cortisol and testosterone levels, as well as mental performance, were measured immediately after the training. The analysis revealed that... The group supplemented with phosphatidylserine consistently showed significantly lower cortisol levels. after each training phase. As a result of the lower cortisol release, the phosphatidylserine group also showed a increased testosterone levels (Elevated cortisol levels reduce testosterone synthesis). Furthermore, a large proportion of the participants supplemented with phosphatidylserine reported a improved mental performance.

As a result Phosphatidylserine, in combination with resistance training, prevents protein and thus muscle catabolism by inhibiting cortisol production. (Cortisol promotes protein breakdown, leading to a Muscle loss leads to) and can ultimately lead to an increase in muscle massFurthermore, phosphatidylserine contributes to promoting 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: Handbook of Nutrients and Vital Substances, Orthomolecular Nutrition. 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].

In a study conducted at the University of Mississippi, two groups of participants performed resistance training eight times per week. One group received 600 mg of phosphatidylserine per day, while the other group received a placebo. Cortisol and testosterone levels were measured immediately after each training session, and mental performance was assessed. The results showed consistently lower ACTH and cortisol levels (up to 30%) and higher testosterone levels in the phosphatidylserine group. A large proportion of the phosphatidylserine group also reported improved 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 years were given 800 mg of phosphatidylserine 10 minutes before exercising on a bicycle ergometer; the other group received a placebo. The results showed a 30% reduction in cortisol levels in the phosphatidylserine group.

Phosphatidylserine It is therefore able to halt muscle catabolism by influencing cortisol and testosterone levels, promote regeneration after training, and reduce overtraining. Dosages in the studies examined go up to 800 mg/day. No further positive effects are to be expected beyond this dosage. After training and in the evening are likely the preferred times for administration.

Bioavailability && Dosage

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

Phosphatidylserine is very likely not absorbed whole in the small intestine, but rather broken down into its components, which are then re-synthesized into phosphatidylserine after absorption. Subsequently, phosphatidylserine is primarily transported to the liver and brain, where it is stored.

Based on current knowledge, phosphatidylserine is safe and well-tolerated: 300 milligrams per day for almost four months caused no significant side effects. In rare cases, stomach upset may occur. Sleep disturbances may also occur at doses above 600 milligrams daily.

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

Depending on the area of ​​application, the following dosages can be found in the literature.:

• Memory: 100-300 mg
• ADHD: 150-200 mg
• Stress: 200-400 mg
• Sports: 400-800 mg

Often, in addition, a Combination of phosphatidylserine with omega 3 fatty acids (EPA & DHA) is recommended due to the 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 may increase the levels of chemicals that could reduce the effectiveness of these drying medications.
• Medications for Alzheimer's disease (anticholinesterase inhibitors): Phosphatidylserine may increase levels of a chemical called acetylcholine in the body. Alzheimer's medications called anticholinesterase inhibitors also increase acetylcholine levels. Taking phosphatidylserine in combination with Alzheimer's medications could intensify the effects and side effects of these medications.
• Various medications for glaucoma, Alzheimer's, and other conditions (cholinergic drugs): Phosphatidylserine may increase the levels of a chemical called acetylcholine in the body. This chemical is similar to some medications used to treat glaucoma, Alzheimer's, and other diseases. Taking phosphatidylserine with these medications could increase the risk of side effects.
• Antiphospholipid syndrome: In antiphospholipid syndrome, the immune system attacks the body's own phospholipids. Affected individuals often have an increased risk of blood clots, stroke, or heart attack. Many also have antibodies against phosphatidylserine in their blood. As a precaution, patients with this condition should not take phosphatidylserine. Its use has not yet been studied.

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