What exactly is phosphatidylserine?

Phosphatidylserine is 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 [see 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 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 peripheral and central nervous tissue.

Phosphatidylserine is biosynthesized in small amounts, d.h. 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, and a deficiency occurs.

Numerous clinical studies show a positive effect of phosphatidylserine

• on cognitive functions, How z.B. Memory and language performance as well as learning and concentration skills [cf. Glade and Smith, 2015]
• in age-associated memory disorders 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, u.adue to the induced cortisol reduction [cf. Maggioni et al., 1990]
• on the Blood clotting: When a blood vessel is injured, the platelets are activated. These also contain phosphatidylserine. Phosphatidylserine then "migrates" from the inner to the outer side of the cell membrane. This contributes to the initiation of 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 cortisol production. Like other stress hormones, cortisol has an energy-secreting effect on the body, thus influencing both fat metabolism (inhibiting) and carbohydrate metabolism (promoting). It also promotes protein breakdown (proteolysis), reduces testosterone synthesis, and lowers cellular insulin sensitivity. Ultimately, cortisol promotes calcium excretion, reduces calcium absorption, and causes a redistribution of body fat toward the visceral region, which increases the risk of cardiovascular disease, obesity, and diabetes. Because it promotes sodium accumulation and potassium excretion, it can also lead to the familiar "puffy" appearance.

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

Phosphatidylserine content in our food

Phosphatidylserine is mainly found in fish and meat. Dairy products and plant-based foods are relatively low in this substance. Especially in low-fat or low-cholesterol diets (e.g., vegetarian, vegan, low-fat), the required 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, our brain mass decreases by up to 100 grams. We lose nerve cells, and the density of synaptic connections in the neural network decreases. The brain's cholesterol content increases with age, while the amount of phospholipids decreases. From about the age of 45, the Phosphatidylserine -content in the nervous system. This is due 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 increasing age.

Memory is thought to be stored as a kind of "biochemical change" in the neuronal circuitry. RNA-dependent protein synthesis takes place to create a new memory trace. However, without sufficient phosphatidylserine, this synthesis is disrupted, as a proper cell wall structure, including the necessary proteins, cannot be formed. This affects short-term memory.

The result is that the phosphatidylserine deficiency leads to impaired signal transmission in the brain. The brain attempts to compensate by increasing its activity level and must release increased amounts of stress hormones.

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

In a large double-blind study, 425 subjects aged 65-93 years who had moderate to severe impairments in mental performance, particularly in memory, reasoning, speech, and motor skills, participated. 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 [1]. https://www.ncbi.nlm.nih.gov/pubmed/8323999 and https://www.ncbi.nlm.nih.gov/pubmed/20523044 ).

In another study with older people, significant Improvements in short-term memory, concentration and attention. In 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 [1]. 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 [1]. 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 elderly people with phosphatidylserine is the increased synthesis of the neurotransmitter acetylcholineIncreased concentrations of PS can lead to a faster and increased release of acetylcholine into the synaptic cleft – Gap space 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 is not effective with a single dose. 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's patients, phosphatidylserine reduced symptoms and improved cognition, with the best results being observed in patients with milder impairments (see [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 [unclear]). 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 (cf. https://www.ncbi.nlm.nih.gov/pubmed/3518329 ).

3. ADHD

A phosphatidylserine deficiency lowers brain activity levels; to compensate for this, our bodies release increased amounts of stress hormones. Phosphatidylserine supplementation in a study with children with ADHD 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 are impulsive seem to benefit most from phosphatidylserine.

In two clinical trials involving 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 [link missing]. 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 AD(H)D.

4. stress

Long-term 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 lead to depression or anxiety. Fatigue, pain, and irritability are also possible.

Phosphatidylserine keeps cortisol away from cells. In a clinical study involving 80 subjects under emotional stress, phosphatidylserine supplementation reduced plasma levels of both cortisol and ACTH, which controls cortisol secretion (see [1]). 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 involving 48 male students, subjects were given either 300 mg/day or a placebo for 30 days. Mental stress was induced by a math test administered after the dose. As a result, the phosphatidylserine group felt significantly more clear-headed and 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 at a dosage of 300 mg promoted calmness and improved mood in stressful situations (see 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 decreased performance, muscle pain, and severe fatigue. This is also associated with overtraining.

The Influence of phosphatidylserine on cortisol levels was investigated in a double-blind study on individuals who participated 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, cortisol and testosterone levels, as well as mental performance, were recorded. The evaluation showed The group supplemented with phosphatidylserine consistently showed significantly lower cortisol levels after each training phase. As a result of 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 participants supplemented with phosphatidylserine reported a improved mental performance.

As a result of this Phosphatidylserine in combination with resistance training prevents protein and thus muscle catabolism by inhibiting cortisol production (Cortisol promotes protein breakdown, which leads to leads to muscle breakdown) and can ultimately lead to an increase in muscle mass. In addition, 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 at the University of Mississippi, two groups of subjects performed resistance training eight times per week. One group received 600 mg of phosphatidylserine per day, the other a placebo. Immediately following the training, cortisol and testosterone levels were measured, as well as mental performance. The results showed consistently lower ACTH and cortisol levels (up to 30%) and higher testosterone levels in the phosphatidylserine group. A large portion 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 were given 800 mg of phosphatidylserine 10 minutes before exercise on a bicycle ergometer, while the other group received a placebo. As a result, cortisol levels in the phosphatidylserine group were reduced by 30%.

Phosphatidylserine By influencing cortisol and testosterone levels, it is able to inhibit muscle catabolism, promote post-workout recovery, and reduce overtraining. Dosages in the studies examined range up to 800 mg/day. No further positive effects are expected above this. After training and in the evening are probably the preferred times of administration.

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]. Radiolabeled 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 rather broken down into its components, which are then synthesized back into phosphatidylserine after absorption. Phosphatidylserine is then transported primarily to the liver and brain, where it is stored.

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 may occur. Doses above 600 milligrams per day may also cause sleep disturbances.

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
• Sports: 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 may increase levels of chemicals that could reduce the effectiveness of these drying medications.
• Drugs for Alzheimer's (anticholinesterase inhibitors): Phosphatidylserine may increase levels of a chemical called acetylcholine in the body. Anticholinesterase inhibitors, drugs used to treat Alzheimer's disease, also increase acetylcholine levels. Taking phosphatidylserine in combination with anti-Alzheimer's medications could increase the effects and side effects of these medications.
• Various medications for glaucoma, Alzheimer's disease, and other diseases (cholinergic medications): Phosphatidylserine may increase levels of a chemical called acetylcholine in the body. This chemical is similar to some medications used to treat glaucoma, Alzheimer's disease, 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 also have antibodies against phosphatidylserine in their blood. Patients with this condition should not take phosphatidylserine as a precaution. Its use has not yet been studied.

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