Phosphatidylserine (as SerinAid®)

“The Brain Nutrient”

SerinAid® Overview

• SerinAid®, is a patented, IGEN non-GMO certified, soy free version of phosphatidylserine.
• SerinAid® is supported by published research in maintaining and improving cognitive function in various age groups, children to older adults. Studies have shown improvements in learning, recall, attention, focus, recognition, repetitive tasking, mood, stress, and the ability to be more physically active. These studies have been conducted using the most common dose range of 100-300 mg. With majority at 300 mg.
• Country of origin: Brazil
• Proposed shelf life of 2 years
• Old Dietary Ingredient (ODI)/US FDA GRAS Status
• Holds two US FDA Qualified Health Claims – Dementia and Memory loss in elderly men and women *If used, these claims must include an FDA disclaimer.
• SerinAid® is nonGMO, gluten free, free of allergens, and contains no artificial or synthetic ingredients.
• SerinAid® is derived from natural chemical synthesis from soy, an oil seed plant containing a complex mixture of phospholipids, glycolipids, triglycerides, sterols, and small quantities of fatty acids, carbohydrates, and sphingolipids.

(TDS SerinAid Free-from Statement), (TDS SerinAid PS Composition), (TDS Spec Sheet SerinAid 70P), (TDS FALCPA Allergen Exemption), (IGEN NonGMO Report), (TDS Phosphatidylserine Reference List 2022) (GRAS Notice 637: Phosphatidylserine derived from Soy Lecithin),

What is phosphatidylserine (PS) and why is it important to health?

• PS is an essential, naturally occurring phospholipid, which serves as an integral component in the structure of the brain and spinal cord and is active at cell membranes.
• Supplemental PS crosses the blood-brain barrier and supports optimal structure and function of brain cells.
• PS is crucial to the “docking port” for neurotransmitters like acetylcholine, helping to positively benefit neurotransmitter release and neurotransmitter receptor density. Nerve cells, in particular, depend on healthy membrane function for normal neurotransmitter metabolism and nerve signal transmission.
• Maintaining brain PS levels has been associated with normal and efficient signal transduction processes, efficient glucose consumption, and other biological pathways that are crucial to ensure normal and healthy cognitive and mental functions.

(Glade, 2015), (Jorissen, 2001), (Ma, 2022), (Kim, 2014)

Composition & Dosing

SerinAid® 70P – contains NLT 70% Phosphatidylserine (PS)

SerinAid® is a registered Trademark of Chemi Nutra, LLC in the USA and other jurisdictions

Clinical dose: Dose ranges from 100-300 mg per day

(TDS Phosphatidylserine Reference List 2022)

What is special about Chemi Nutra’s SerinAid®?

• According to the supplier, SerinAid® is the “Original PS”, since 1994. It is patent protected, 100% natural, not synthetic, along with a high safety and quality profile. It is produced in Chemi’s own FDA inspected plant.
• Although sourced from soy, SerinAid® is soy-protein free and thus soy-allergen free. Their unique production process is highly refined, and no soy is left in the final product. Thus, SerinAid® (unlike other soy derived PS) is exempt from soy allergen labeling under the Food Allergen Labeling and Consumer Protection Act (FALCPA). Absence of soy allergens has been repeatedly confirmed by third party-analyses. (TDS FALCPA Allergen Exemption) (IGEN NonGMO TEST RESULTS Chemi Nutra SerinAid 70P)
• From the literature, there are zero studies on sunflower-derived PS. For anyone to claim sunflower PS is bioequivalent to soy-PS, research must be conducted to substantiate such claims. Therefore, it is crucial to use the soy derived PS to reap the benefits of supplemental phosphatidylserine. **Side note, the existing research that supported the efficacy of PS was on bovine-derived material. Results from a 1999 animal study, found that “treatment with [soy-PS], but not [egg-PS], had positive cognitive effects similar to those of [bovine cortex-PS] ** (Blokland,1999)

(GRAS Notice 637: Phosphatidylserine derived from Soy Lecithin)

• "Phosphatidylserine (PS) may reduce the risk of cognitive dysfunction in the elderly.” Disclaimer: “Very limited and preliminary scientific research suggests that PS may reduce the risk of cognitive dysfunction in the elderly. FDA concludes that there is very little scientific evidence supporting this claim."
• "Phosphatidylserine (PS) may reduce the risk of dementia in the elderly.” Disclaimer: “Very limited and preliminary scientific research suggests that PS may reduce the risk of dementia in the elderly. FDA concludes that there is little scientific evidence supporting this claim."

Natural Medicines Database Safety, Effectiveness & Interaction Analysis

• POSSIBLY SAFE ...when used orally and appropriately. Phosphatidylserine has been used with apparent safety at dose of up to 300 mg daily for up to 6 months
• CHILDREN: POSSIBLY SAFE ...when used orally and appropriately, short-term. Phosphatidylserine has been used with apparent safety in clinical research in doses of 200-300 mg daily for up to 4 months in children aged 4-18 years
• PREGNANCY AND LACTATION: Insufficient reliable information available; avoid using.
• When used orally, flatulence, gastrointestinal upset, headache, insomnia, and nausea are the most common reported adverse effects
• No major drug interactions; theoretically, PS may decrease or increase the effectiveness of certain drugs this data is loosely based on overlapping mechanisms.
• No nutrient interactions found

Human Safety Study

According to Jorissen, 2002. Safety of Soy-derived phosphatidylserine in elderly people, phosphatidylserine is a safe nutritional supplement for older persons if taken up to a dosage of 200 mg three times daily, short term.

Research summary:

Preclinical research:

7 pre-clinical studies have been provided by the supplier relevant to cognitive health; the studies below have been chosen to be reviewed based on the intended health goals and the specific nootropic mechanisms the formula will market.

• Blokland, 1999 (used the SerinAid® material)
• Suzuki, 2001
• Hashioka, 2007

Additional references: (Casamenti, 1979), (Furushiro, 1997), (Suzuki, 2000), (Alves, 2000), (Zhang, 2015)

Human Studies:

36 studies have been included in a reference list provided by the supplier relevant to cognitive health. (TDS Phosphatidylserine Reference List 2022).

The studies below have been chosen to be reviewed based on the appropriate dosage that is in line with the formula, semi similar delivery format, and intended population (adults/older adults) and health goals.

• Kato-Kataoka, 2010

Additional references: The below studies used 100 mg of phosphatidylserine. In Yong, 2012, the demographic was limited to 17–18-year-old students and the delivery format was by phosphatidylserine fortified milk. In Vakhapova, 2014, the demographic was in the elderly and the delivery format was a capsule but enriched with docosahexaenoic acid (PS-DHA).

• Yong, 2012.
• Vakhapova, 2014.

In summary, phosphatidylserine research using a supplemental dose of 100 mg is limited. Most research is based on 300 mg, with the source of PS coming from bovine or soy. Numerous studies have been conducted in the elderly using 300 mg per day. Also, studies have combined PS with Omega 3 fatty acids.

For the purpose of this review, only 1 soy-derived study @ 100 mg dose has been reviewed. A limitation with Kato-Kataoka, 2010 - the soft gelatin capsules contained amounts of MCT, vitamin E, and other phospholipids. The concern is more around the added phospholipids as vitamin E is used as a stabilizer and MCT was too low to have an effect.

The significant results were only seen with the low-score subgroup, while all neuropsychological test scores had similar increases in all groups including placebo group. In which, the researchers (as I agree) note the positive outcomes could have been contributed to the other phospholipids; the phospholipids were at a relatively high dose so it is difficult to justify using PS alone will provide the same result. There are no studies using the SerinAid® brand @ 100 mg for the intended health outcome or similar delivery format.

Other: Phosphatidylserine (including SerinAid®) has been extensively researched in other areas of health such as exercise, mood and stress at dosages of 300 mg and above.

Totality of the evidence: this search criteria was PubMed, targeted search criteria for all data (note, this type of search does not bring up every branded ingredient study as most are not open access)

• Phosphatidylserine= 19,528 results with no filters or specified search criteria
• Phosphatidylserine + cognitive= 161 results with no filters
• Phosphatidylserine + cognitive = 16 results with an RCT filter

Preclinical research

Blokland, 1999. Cognition-enhancing properties of subchronic phosphatidylserine (PS) treatment in middle-aged rats: Comparison of bovine cortex PS with Egg PS and Soybean PS

Purpose: The aim of the present study was to examine whether E-PS and S-PS had behavioral properties similar to those of BC-PS in the laboratory rat.

Population: 36 twelve-month-old Fischer 344 rats, at the start of the study, the rats were considered middle age (17 months old)

Design: Animal study

Dosage: via injection - 15 mg/kg of PS derived from bovine cortex (BS-PS), soybean (S-PS), egg (E-PS), or vehicle

Measurements & Methods: Three different behavioral tests were used to determine psychomotor, and cognitive performance

• Open field test
• Morris water escape task
• Two-way active avoidance

Results:

• In the open field and Morris water task, no effects of PS treatment were found; therefore, there was no effect on behavioral activity or emotional reactivity in rats.
• In the two-way active avoidance, S-PS had similar effects to BC-PS, therefore showing comparison in cognition – the Egg-PS had no effect.

Potential language: Results from animal research, found that “treatment with [soy-PS], but not [egg-PS], had positive cognitive effects similar to those of [bovine cortex-PS]

Notes: Treatment with PS derived from bovine cortex is not desirable because of the potential transfer of infectious diseases. Another constraint against using BC-PS is that the yield of PS from bovine cortex is rather low

Suzuki, 2001. Oral administration of soybean lecithin transphosphatidylated phosphatidylserine improves memory impairment in aged rats

Purpose: To evaluate the effects of age-related memory impairment in rats given soybean lecithin transphosphatidylated phosphatidylserine (SB-tPS)

Population: Male wistar rats, 24- to 25-month-old (aged) or 8 wk. old (young) and were fed a similar diet

Design: Animal study – aged impaired SB-tPS, aged impaired control, aged non-impaired, aged & young

• These trials were performed continuously for 4 d. Eight of 42 aged rats whose average escape latency (EL) on d 4 was below the upper limit of the 99% confidence level for young rats (dotted line in Fig. 1B) were regarded as nonimpaired and excluded from subsequent experiments.
• After the screening, the impaired aged rats were divided into a control and SB-tPS-administered group with the mean EL of each group almost the same
• Dosage: 60 days of oral administration, SB-tPS prepared from soybean lecithin and L-serine (14) was emulsified in water and administered orally in drinking water. The concentration of SB-tPS was adjusted to ensure an average daily intake of 60 mg/kg throughout the experiment. Tap water was given to the control group. The drinking water was replaced every 2 or 3 d.

Measurements & Methods: In this study, the effect of continuous oral administration of SB-tPS on the spatial memory of aged memory-impaired rats was investigated, and some biochemical variables related to the synaptosomal functions, such as potassium-induced acetylcholine release or Na+, K+-ATPase activities of the synaptosomes, were examined to determine the nootropic mechanism of this phospholipid.

• Water maze test apparatus, screening test, escape test 1, spatial probe test, escape test 2
• After escape test 2, the rats were euthanized and the brains were immediately removed and dissected into 8 parts.
• Brain lipid analysis
• Measurement of acetylcholine synthesis and release
• Measurement of Na+, K+, and ATPase activity

Results:

• Escape latency (EL) of the SB-tPS group was significantly shorter than that of the control group on d 3 and d 4
• The time spent in the third quadrant for the SB-tPS group was significantly longer than that for the control group
• The high K+ depolarization-induced acetylcholine release from the synaptosomes of the aged impaired control rats were approximately ½ of that of young rats; whereas, it was 45% greater in the SB-tPS administered group than in the control group. However, neither the basal acetylcholine release from synaptosomes nor the synthesis of acetylcholine or choline was affected by SB-tPS administration.
• SB-tPS also increased acetylcholine release and the Na+, K+-ATPase activity of the synaptosomes prepared from these aged rats to the level in young rats.
• In the SB-tPS group, the cholesterol/phospholipid molar ratio and phosphatidylcholine content in the thalamus and midbrain were significantly higher, whereas the phosphatidylethanolamine content in this region was significantly lower than those of the control group. The groups did not differ in the other seven regions examined.
• Sixty days of oral administration of SB-tPS restored performances in the escape test and the spatial probe test. Therefore, SB-tPS can improve age-related spatial memory impairment in rats.
• Preclinical research suggests, soy-PS exhibits nootropic actions by an enhancement of acetylcholine release through the restoration of biochemical activities (Na+, K+-ATPase activity) contributing to improvement of learning impairment.

Potential language: Preclinical research suggests, soy-PS exhibits nootropic actions by changes in biochemical activities (acetylcholine, Na+/K+ ATPase)

Notes:

Acetylcholine release: Acetylcholine (ACh) is a neurotransmitter, a chemical that carries messages from your brain to your body through nerve cells

Na+/K+ ATPase activity: the sodium-potassium pump that acts to maintain the membrane potential.

Hashioka, 2007. Phosphatidylserine and phosphatidylcholine -containing liposomes inhibit amyloid beta and interferon gamma induced microglial activation

Purpose: To evaluate the effects of liposomes, which comprise both PS and PC (PS/PC liposomes), on the microglial production of tumor necrosis factor-α (TNF-α), nitric oxide (NO), and superoxide induced by amyloid β (Aβ) and interferon-γ (IFN-γ).

Population: Wister rats

Design: Animal (in vitro), Primary microglial cells were isolated from mixed cell cultures from the cerebral cortex of 3-day-old Wister rats according to the methods described previously

Measurements:

• TNF-alpha
• NO
• iNOS
• TNF-α production by Aβ/IFN-γ-activated microglia

Results:

• Pretreatment of microglia with PS/PC liposomes considerably inhibited the TNF-α, NO and superoxide production induced by Aβ/IFN-γ.
• These results suggest that PS/PC liposomes have both neuroprotective and antioxidative properties through the inhibition of microglial activation, thus supporting the nootropic and antidementia effect of PS.

Potential language: Animal research suggests, the neuroprotective and anti-oxidative properties of PS may be important for its nootropic mechanism.

Notes: There is increasing evidence that microglial activation is one of the major pathogenic factors for Alzheimer's disease (AD) and the inhibition of the inflammatory activation of the microglia thus appears to be neuroprotective and a potentially useful treatment for AD.

Additional reference: Zhang, 2015. PS decreased cholinesterase, improved memory, and improved hippocampal inflammation injury in AD brains of rats by increasing SOD and OH- levels. Preclinical research, further shows that PS may have antioxidative properties that contribute to its nootropic mechanism.

Human studies

Kato-Kataoka, 2010. Soybean-derived phosphatidylserine improves memory function of the elderly Japanese subjects with memory complaints

Purpose: To assess the effects of Soy-PS on the cognitive functions of the elderly Japanese subjects with memory complaints

Population: 73 elderly people with mild cognitive impairment, aged 50-69 years completed the study

• All subjects were similar in average age, sex, education year, neuropsychological test score, geriatric depression scale (GDS) and everyday memory checklist (EMC) score

Treatment: Soy-PS (100 mg or 300 mg/day) or placebo for 6 months, with a 3-month follow-up period to see whether the effects of Soy-PS would be maintained after discontinuing its intake.

• Capsules were taken after each meal

Composition:

• PS300: 9 soft gelatin capsules contained 300 mg PS, 663 mg phospholipids other than PS, 702 mg medium chain triglycerides (MCT), 135 mg vitamin E.
• PS100: 9 soft gelatin capsules contained 100 mg PS, 863 mg phospholipids other than PS, 702 mg MCT, and 125 mg vitamin E.
• Placebo: 9 soft gelatin capsules contained 963 mg phospholipids other than PS, 702 mg MCT, and 135 mg vitamin E.

Design: A double-blind, randomized, placebo-controlled study

Measurements: baseline, 6 months, and 3 months post treatment

• Rivermead behavioral memory test (RBMT), which focuses on evaluating memory functions, especially everyday memory
• HDS-R and Mini Mental State Examination (MMSE) for cognitive function
• GDS for evaluating depressive state

Results: Although, significant results were seen in all groups (including placebo), the memory scores of the PS treated groups with low scores at baseline were significantly increased compared to baseline, while the placebo was unchanged. Long term soy-PS supplementation may improve memory function in the elderly population with memory complaints. However, considering the limitations, I would disclose that only the low-score subgroup was significant and added phospholipids may contribute to the results.

Conclusion: Neuropsychological test scores were similarly increased in all groups including placebo group. However, in the subjects with relatively low score at baseline, the memory scores in PS treated groups were significantly increased against the baseline, while those of placebo group remained unchanged. Long term, Soy-PS supplementation may improve the memory function in the elderly population with memory complaints.

Limitations: treatment and placebo contained other components (MCT, additional phospholipids, vitamin E) that could contribute to the significant memory results. The concern is more around the added phospholipids as vitamin E is used as a stabilizer and MCT was too low of a dose for an effect.

Strengths: sufficient sample size, long duration study (6 mo),

Adverse events: None reported, no difference in blood markers and vital signs during treatment

Safety evaluation: blood/urine markers and vital signs

Potential disclosures:

• Japanese population
• Only the low-score subgroup was significant and added phospholipids may contribute to the results.

Additional references

36 studies have been included in a reference list provided by the supplier relevant to cognitive health. (TDS Phosphatidylserine Reference List 2022) (Yong, 2012) (Vakhapova, 2014)

Claim Substantiation summary

• Phosphatidylserine is a naturally occurring phospholipid, that plays an integral part in the structure of the brain and is an essential component of healthy nerve cell membranes
• Supplemental PS crosses the blood-brain barrier and supports optimal structure and function of brain cells.
• Maintaining brain PS levels has been associated with biological pathways that are crucial to ensure normal and healthy cognitive and mental functions.
• Long term, Soy-PS supplementation may improve the memory function in the elderly population with memory complaints.
• Clinical trials have demonstrated that PS supplementation up to 300 mg can support cognitive performance, as well as memory and attention.
• SerinAid® is a branded phosphatidylserine that is superior to other soy-derived PS. It’s patented manufacturing process allows it to be exempt from soy allergen labeling.

US FDA Qualified Health Claims with disclaimer

(GRAS Notice 637: Phosphatidylserine derived from Soy Lecithin)

• "Phosphatidylserine (PS) may reduce the risk of cognitive dysfunction in the elderly.” Disclaimer: “Very limited and preliminary scientific research suggests that PS may reduce the risk of cognitive dysfunction in the elderly. FDA concludes that there is very little scientific evidence supporting this claim."
• "Phosphatidylserine (PS) may reduce the risk of dementia in the elderly.” Disclaimer: “Very limited and preliminary scientific research suggests that PS may reduce the risk of dementia in the elderly. FDA concludes that there is little scientific evidence supporting this claim."