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Phosphatidylserine (PS)

Specific Recommendations:

• Phosphatidylserine at Amazon.com

News & Research:

• Dietary choline associates with reduced risk of dementia - Science Daily, 8/6/19 - "The new study now shows that the risk of dementia was 28% lower in men with the highest intake of dietary phosphatidylcholine, when compared to men with the lowest intake. Men with the highest intake of dietary phosphatidylcholine also excelled in tests measuring their memory and linguistic abilities" - See phosphatidylcholine at Amazon.com.
• Eight nutrients to protect the aging brain - Science Daily, 4/15/15 - "Two pilot studies showed that a combination of phosphatidylserine and phosphatidic acid can help benefit memory, mood, and cognitive function in the elderly (Lonza, 2014)"
• Common food supplement fights degenerative brain disorders, study suggests - Science Daily, 5/21/13 - "Widely available in pharmacies and health stores, phosphatidylserine is a natural food supplement ... the same supplement improves the functioning of genes involved in degenerative brain disorders, including Parkinson's disease and Familial Dysautonomia (FD) ...Not only did phosphatidylserine impact the gene associated with FD, but it also altered the level of a total of 2400 other genes -- hundreds of which have been connected to Parkinson's disease in previous studies ... The researchers believe that the supplement may have a beneficial impact on a number of degenerative diseases of the brain"
• Novel Strategy to Restore Brain Cell Function - Life Extension Magazine, 5/06 - "Alzheimer’s patients taking 300 mg of phosphatidylserine daily performed significantly better on standardized memory tests at the end of the 12-week trial period than did the study participants who received placebo. Importantly, those patients who were the least afflicted by dementia demonstrated the greatest benefit from phosphatidylserine therapy. These results suggest that beginning supplementation very early on, or perhaps even before the appearance of symptoms, can help prevent age-related loss of memory and other cognitive impairments"
• Cortisol, Stress, and Health - Life Extension Magazine, 12/05 - "Supplements to reduce high cortisol levels secondary to stress ... Vitamin C: 1000-3000 mg/day ... Fish oil (omega-3 fatty acids):1-4 gm/day ... Phosphatidylserine: 300-800 mg/day ... Rhodiola rosea: 100-200 mg/day, standardized extract ... Ginseng: 100-300 mg/day, standardized extract ... Ginkgo biloba: 100-200 mg/day, standardized extract ... DHEA: 25-50 mg/day (any hormone supplementation should be monitored by your physician)"
• Cortisol - Keeping a Dangerous Hormone in Check - Life Extension Magazine, 7/04 - "Phosphatidylserine, DHEA, and ginkgo biloba all have been shown to reduce the amount of cortisol produced during stressful events, and these stress fighters can help retard the negative consequences of this hormone"
• Stress and Cortisol Levels - Vitamin Research News, 2/04 - "I want to reduce cortisol levels in my body ... Phosphatidylserine, 300 mg per day, is a good choice"
• Phospholipids: Versatile Nutraceutical Ingredients For Functional Foods - Functional Foods & Nutraceuticals, 12/02 - "Ryser concluded that PS yielded clinically significant benefit to 25 of the 27 children. PS improved attention, concentration, learning, behaviour and academic performance, seemingly extending their level of benefit once they had "plateaued" on fish oil and other nutritional supplements. Those prescribed methylphenidate (Ritalin) or other pharmaceuticals also seemed to derive additional benefit from PS which also benefited the depression and anxiety commonly seen in these children"
• Using Complementary Treatments - PsychiatricTimes.com, 11/15/02 - "Phosphatidylserine is active at cell membranes, including synaptic membrane zones. Partial improvement of learning and recall capacity was noted in subjects with age-related cognitive decline"
• Stress, Cortisol and Health - Supplement Watch Newsletter, 10/02 - "several lines of evidence have converged to solidify the concept that stress makes us fat (because of cortisol), thins our bones (because of cortisol), shrinks our brains (because of cortisol), suppresses our immune system (because of cortisol), saps our energy levels (because of cortisol), and kills our sex drive (because of cortisol) ... Take a daily multivitamin/multi-mineral supplement - because calcium, magnesium, vitamin C and B-complex vitamins are needed for a proper stress response ... Chief among the supplements with documented cortisol-controlling effects are Phosphatidylserine, Beta-sitosterol, Magnolia bark, Theanine, Epimedium, Ashwagandha and Passionflower"
• Phosphatidylserine (PS) The Essential Brain Nutrient - Life Extension Magazine, 9/02 - "Among its list of functions, phosphatidylserine stimulates the release of dopamine (a mood regulator that also control physical sensations, and movement), increases the production of acetylcholine (necessary for learning and memory), enhances brain glucose metabolism (the fuel used for brain activity), reduces cortisol levels (a stress hormone), and boosts the activity of nerve growth factor (NGF), which oversees the health of cholinergic neurons"
• A Supplement to Prevent Alzheimer’s - Dr. Weil, 8/20/02 - "In theory, PS works by strengthening cell membranes thus protecting them and their contents from damage, particularly from the stress hormone cortisol"
• Choline Precursors Lower Stroke Death and Disability Rates, Meta-analysis Indicates - Doctor's Guide, 2/11/02 - "Choline precursors are a group of molecules that get converted to phospholipids in the brain. Phospholipids perform many functions, including serving as crucial nerve cell membrane components and acting as neurotransmitters. Choline precursors include drugs like lecithin and citicoline ... Death and disability rate was 54.6 (611/1119) percent for patients treated with choline precursors compared to 66.4 (561/844) percent for those on placebo ... choline precursors might improve ischemic brain damage in two ways, by neuroprotection or by enhancement of neurorepair processes"
• Phosphatidylserine Boosts Brain Function - Nutrition Science News, 3/01 - "Recent animal studies have now compared PS taken from different sources (egg, soy and cow brain), and have found injectable soy PS to be on par with cow brain PS"
• The Latest from the American College of Sports Medicine - Nutrition Science News, 9/00 - "It is generally accepted that the enzyme creatine kinase is an indicator of cell membrane damage and necrosis of the muscle fibers," says John Seifert, a principal investigator at St. Cloud. "Our work shows that PS supplementation results in significantly lower amounts of creatine kinase (CK) levels 24 hours after exercise. This implies that PS can help minimize muscle fiber damage caused by muscular stress."
• Enhancing Cognitive Function - Life Extension Magazine, 5/00 - "It has been shown that PS can increase the number of neurotransmitter receptors back to youthful levels."

Abstracts:

• A Magtein®, Magnesium L-Threonate, -Based Formula Improves Brain Cognitive Functions in Healthy Chinese Adults - Nutrients 2022, 14(24), 5235 - "Magnesium is one of the most abundant essential minerals in the body. Magnesium supplements mostly have low bioavailability, except magnesium L-threonate. In 2010, a novel magnesium compound, magnesium L-threonate (Magtein®) was identified and was shown to raise the magnesium levels in the brain and neurons effectively. In this double-blind, placebo-controlled study, Magtein®PS, a magnesium L-threonate (Magtein®)- and phosphatidylserine-based formulation additionally containing vitamins C and D, was tested for its cognitive benefits in 109 healthy Chinese adults aged 18–65 years. Subjects were randomly assigned to receive either Magtein®PS or placebo (starch) capsules, at a dose of 2 g/day. “The Clinical Memory Test”, the standard test commonly used in Chinese hospitals and academic institutes for cognitive evaluation, was administered before and 30 days after subjects received the supplement. Subjects receiving Magtein®PS showed significant improvements over the control group in all five subcategories of “The Clinical Memory Test” as well as the overall memory quotient scores. The older participants showed more improvement than younger participants. Results indicated significant benefits of Magtein®PS in improving memory and cognition in healthy Chinese adults" - See Magtein at Amazon.com and phosphatidylserine at Amazon.com.
• Supplementation with phosphatidylethanolamine confers anti-oxidant and anti-aging effects via hormesis and reduced insulin/IGF-1-like signaling in C. elegans - Mech Ageing Dev 2021 May 8 - "Phosphatidylethanolamine is a major component of phospholipids with both structural and metabolic functions in cells. Previous studies have revealed that phosphatidylethanolamine can modulate autophagy with a protective effect against age-related diseases. We examined the effect of dietary supplementation with phosphatidylethanolamine on stress response and aging in Caenorhabditis elegans ... Both mean and maximum lifespans were significantly increased by phosphatidylethanolamine while fertility was reduced as a trade-off. Age-related decline of muscle function was delayed in animals treated with phosphatidylethanolamine. Supplementation with phosphatidylethanolamine suppressed toxic effect of amyloid β and high-glucose diet. Increased ROS levels and induction of stress-responsive genes after dietary supplementation with phosphatidylethanolamine suggest that anti-oxidative stress and anti-aging effects of phosphatidylethanolamine might be though hormesis. Genetic analysis using long-lived mutants and knockdown by RNAi revealed that the lifespan-extending effect of phosphatidylethanolamine overlapped with that of reduced insulin/IGF-1-like signaling and required DAF-16, a downstream transcription factor known to regulate the expression of many stress-responsive genes. These findings indicate that phosphatidylethanolamine has anti-oxidative stress and anti-aging activities with its underlying mechanisms involving hormesis and reduced insulin/IGF-1-like signaling in C. elegans" - Note:  I couldn't find phosphatidylethanolamine supplements.  Phosphatidylcholine complex may contain it.  See phosphatidylcholine at Amazon.com.
• Effects of phytosomal curcumin on anthropometric parameters, insulin resistance, cortisolemia and non-alcoholic fatty liver disease indices: a double-blind, placebo-controlled clinical trial - Eur J Nutr. 2019 Feb 22 - "Subjects were randomized to be treated with indistinguishable tablets (2 per day, to be taken after dinner) containing 800 mg phytosomal curcumin (Curserin®: 200 mg curcumin, 120 mg phosphatidylserine, 480 mg phosphatidylcholine and 8 mg piperine from Piper nigrum L. dry extract) for 8 weeks ... After 56-day treatment, the curcumin-treated group experienced a significant improvement in fasting plasma insulin (FPI), HOMA index, waist circumference, blood pressure, triglycerides (TG), HDL-C, liver transaminases, gamma-GT, index of liver steatosis and serum cortisol compared to the baseline. FPI, TG, liver transaminases, fatty liver index and serum cortisol level also significantly improved compared with the placebo-treated group. Compared to the baseline, at the end of the study placebo group experienced an improvement only in FPG and TG ... supplementation with a phytosomal preparation of curcumin containing phosphatidylserine and piperine could improve glycemic factors, hepatic function and serum cortisol levels in subjects with overweight and impaired fasting glucose" - [Nutra USA] - See curcumin products at Amazon.com, phosphatidylserine at Amazon.com, phosphatidylcholine at Amazon.com and piperine extract at Amazon.com.
• Enhanced aerobic exercise performance in women by a combination of three mineral Chelates plus two conditionally essential nutrients - J Int Soc Sports Nutr. 2017 Nov 13 - "For 1 mo, aerobically fit, young adult women took either a combination of 3 mineral glycinate complexes (daily dose: 36 mg iron, 15 mg zinc, and 2 mg copper) + 2 CENs (daily dose: 2 g carnitine and 400 mg phosphatidylserine), or the same combination with generic mineral complexes, or placebo (n = 14/group) ... In Trial 1, the mineral glycinates + CENs decreased 3 mile run time (25.6 ± 2.4 vs 26.5 ± 2.3 min, p < 0.05, paired t-test) increased stationary bike distance after 25 min (6.5 ± 0.6 vs 6.0 ± 0.8 miles, p < 0.05, paired t-test), and increased steps in the step test (43.8 ± 4.8 vs 40.3 ± 6.4 steps, p < 0.05, paired t-test). The placebo significantly affected only the biking distance, but it was less than for the glycinates-CENs treatment (0.2 ± 0.4. vs 0.5 ± 0.1 miles, p < 0.05, ANOVA + Tukey). The generic minerals + CENs only significantly affected the step test (44.1 ± 5.2 vs 41.0 ± 5.9 steps, p < 0.05, paired t-test) In Trial 2, 3 mile run time was decreased for the mineral glycinates + CENs (23.9 ± 3.1 vs 24.7 ± 2.5, p < 0.005, paired t-test), but not by the placebo" - [Nutra USA] - See Jarrow Zinc Balance at Amazon.com and Extra Strength Phosphatidyl Serine 300 mg Now Foods 50 Softgel at Amazon.com.
• A soy-based phosphatidylserine/ phosphatidic acid complex (PAS) normalizes the stress reactivity of hypothalamus-pituitary-adrenal-axis in chronically stressed male subjects: a randomized, placebo-controlled study - Lipids Health Dis. 2014 Jul 31;13(1):121 - "randomly allocated to one of three study arms (placebo, PAS 200 and PAS 400 per day, respectively) ... Compared to placebo, a supplementation with a daily dose of PAS 400 was effective in normalizing the ACTH (p = 0.010), salivary (p = 0.043) and serum cortisol responses (p = 0.035) to the TSST in chronically high but not in low stressed subjects (all p > 0.05). Compared to placebo, supplementation with PAS 200 did not result in any significant differences in these variables" - See phosphatidylserine at Amazon.com.
• The effect of phosphatidylserine-containing omega-3 fatty acids on memory abilities in subjects with subjective memory complaints: a pilot study - Clin Interv Aging. 2010 Nov 2;5:313-6 - "PS-omega-3 supplementation resulted in 42% increase in the ability to recall words in the delayed condition" - See phosphatidylserine at Amazon.com and Mega Twin EPA at Amazon.com and Jarrow Max DHA at Amazon.com.
• Phosphatidylserine Containing omega-3 Fatty Acids May Improve Memory Abilities in Non-Demented Elderly with Memory Complaints: A Double-Blind Placebo-Controlled Trial - Dement Geriatr Cogn Disord. 2010 Jun 3;29(5):467-474 - "The results indicate that PS-DHA may improve cognitive performance in non-demented elderly with memory complaints. Post-hoc analysis of subgroups suggests that participants with higher baseline cognitive status were most likely to respond to PS-DHA" - See Jarrow Max DHA at Amazon.comand phosphatidylserine products at iHerb.
• Effects of phosphatidylserine supplementation on exercising humans - Sports Med. 2006;36(8):657-69 - "S-PtdSer 800 mg/day reduced the cortisol response to overtraining during weight training while improving feeling of well-being and decreasing perceived muscle soreness"
• Effects of soy lecithin phosphatidic acid and phosphatidylserine complex (PAS) on the endocrine and psychological responses to mental stress - Stress. 2004 Jun;7(2):119-26 - "These data provide initial evidence for a selective stress dampening effect of PAS on the pituitary-adrenal axis, suggesting the potential of PAS in the treatment of stress related disorders"
• The influence of phosphatidylserine supplementation on mood and heart rate when faced with an acute stressor - Nutr Neurosci. 2001;4(3):169-78 - "In young adults, with neuroticism scores above rather than below the median, the taking of 300mg PS each day for a month was associated with feeling less stressed and having a better mood"
• 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 - "chronic oral administration of phosphatidylserine may counteract stress-induced activation of the hypothalamo-pituitary-adrenal axis in man"
• Effects of phosphatidylserine on the neuroendocrine response to physical stress in humans - Neuroendocrinology. 1990 Sep;52(3):243-8 - "Pretreatment with both 50 and 75 mg BC-PS significantly blunted the ACTH and cortisol responses to physical stress"

800 mg active phosphatidylserine has been show to reduce cortisol by 30%.  That's pretty significant.  I feel that if there were a prescription drug that did that, it would be a first line treatment for Cushing's.  I'm sure the medical establishment will argue that there needs to be more studies.  I agree, but who is going to pay for the studies on something that is not patentable and doctors can't get the big bucks to write a prescription for.  Maybe the AMA will fund the study out of the kindness or their heart.  Yea, right!

Most PS sold is actually only 20% PS.  Leci-PS® by Cargil Bbioactives has 20%, 40% and 90% PS.  I've got no affiliation with them but feel that they have the best product.  To get 800 mg active, it's eight 500 mg capsules of the usual 20% PS products.  With Leci-PS 20 (which is 20% PS), it's about a 2.38 teaspoons.  It is expensive stuff.  Probably your best bet for phosphatidylserine is iHerb.

Cushing's syndrome is caused by prolonged exposure of the body's tissues to high levels of the hormone cortisol. I've talked to doctors who implied that it was black and white, i.e. you have Cushing's or you don't.  My personal opinion, and I'm not a doctor, is that there is a linear gray area in between.