Nad+ And Brain Energy — The Molecule That Declines With Age
Quick Read NAD+ is a molecule your brain needs to produce energy and maintain healthy cells. It declines significantly as
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Phosphatidylserine (PS) is a natural fat that your brain cells use to function properly, particularly for memory and learning. As you age, your brain’s PS levels decline, which may explain why memory gets slower. The FDA approved PS as a cognitive health supplement in 2003 based on clinical research, yet it remains largely unknown to mainstream medicine.
Multiple research trials show PS helps older adults who are beginning to experience memory problems. People taking 100 to 300 mg daily showed improvements in memory recall and mental tasks compared to those taking placebo. Some studies combined PS with omega-3 fatty acids and found even better results. One small trial even found that Alzheimer’s patients taking PS maintained their daily functioning better than those on placebo, though larger studies are needed to confirm this.
PS appears to work by restoring the brain’s production of acetylcholine, a chemical essential for memory and attention. Animal research consistently supports this mechanism. Across all human trials reviewed, PS showed no significant side effects, making it safe to use. The main limitations are that most trials involved small numbers of people and lasted only a few months, and many newer studies mix PS with other ingredients, making it harder to know PS’s exact contribution.
Verdict: PS has solid research backing its usefulness for people over 40 experiencing early memory decline, with an excellent safety record, though it’s best given at least six months to show effects and works better when taken with food and omega-3s.
What if one of the most thoroughly researched brain supplements in history had been approved by the FDA, praised in clinical trials, and then almost entirely forgotten by mainstream medicine? That’s not a conspiracy theory. It’s simply what happened to phosphatidylserine, a molecule your brain makes naturally, that scientists have been studying since the 1980s, and that in 2003 received one of the FDA’s rare qualified health claims for cognitive function. And yet, if you asked your GP about it today, chances are you’d be met with a blank stare.
Here’s what four decades of research has actually taught us, and why it might be time to stop ignoring it.
The story of phosphatidylserine (PS) begins not in a laboratory, but inside every neuron in your head.
PS is a phospholipid, a type of fat, that forms a critical part of the membrane surrounding your brain cells. It sits predominantly on the *inner* surface of that membrane, where it plays a quietly essential role in keeping your neurons functioning properly [3]. Think of your cell membrane less like a passive container and more like a living control panel. PS is one of the switches.
When PS is present in the right concentrations, it helps regulate a cascade of signalling processes inside the cell, including the activity of enzymes involved in memory formation and the release of neurotransmitters like acetylcholine, the chemical your brain uses most heavily for learning and recall [3][7]. It also plays a role in neuroinflammation, synaptic refinement, and something called the cholinergic system, essentially the brain’s primary attention and memory network [5].
Here’s the ageing problem: as you get older, the PS content of your neurons gradually declines [13]. Your brain becomes less efficient at maintaining membrane integrity. Signalling pathways slow down. Acetylcholine release drops. And with it, gradually, almost imperceptibly, so does your ability to recall words quickly, remember where you left things, or hold multiple pieces of information in mind at once.
The question researchers have been asking since the 1980s is simple: can you slow that process by supplementing with PS?
The earliest serious PS research used a form derived from bovine (cow) brain cortex, BC-PS. The results from that era were striking enough that by the early 1990s, multiple European countries had approved PS as a prescription treatment for cognitive decline. Then came the BSE crisis, and with it, legitimate fears about prion contamination from bovine brain material. Almost overnight, BC-PS disappeared from the market.
What followed was a scientific pivot, to plant-derived sources, primarily soy lecithin, and later sunflower and marine-derived PS. This shift in raw material is one of the most important reasons you’ll see conflicting results across studies. The fatty acid profile of soy-derived PS differs from bovine-derived PS, and researchers spent years working out whether the benefits transferred [3][15].
Here’s what four decades of research has actually taught us.
Evidence grade: Promising, multiple RCTs in targeted populations, though sample sizes remain modest
The most consistent signal in the human research points to a specific group: older adults who already notice memory problems but haven’t crossed the threshold into dementia. This isn’t the “worried well”, it’s a clinically meaningful population that researchers call mild cognitive impairment (MCI), and PS seems to work best here.
A 2010 double-blind, randomised controlled trial published in Japanese subjects aged 50–69 with memory complaints gave participants either 100 mg or 300 mg of soy-derived PS daily, or a placebo, for six months [6]. The headline result was nuanced: across the whole group, improvements didn’t reach statistical significance versus placebo. But when researchers looked specifically at participants who had lower memory scores at baseline, PS-supplemented groups showed significant improvements in delayed verbal recall, precisely the type of memory that declines earliest in cognitive ageing, while the placebo group remained unchanged [6].
A 2010 placebo-controlled trial examined a novel preparation combining PS with omega-3 DHA (PS-DHA) in non-demented elderly adults with memory complaints [8]. Results suggested improvements in memory abilities in this population, adding to the picture that PS’s benefits may be amplified when paired with supporting fatty acids.
A 2025 Chinese RCT followed 190 adults with mild cognitive impairment (mean age 68) for 12 months, giving the intervention group capsules containing PS (63 mg/day total), alpha-linolenic acid (ALA), and Ginkgo flavonoids alongside B vitamins [1]. Compared to placebo, the intervention group showed significant improvements in arithmetic, similarity testing, and short-term memory. Crucially, the researchers also measured biological markers, and found significant increases in acetylcholine, GABA, and serotonin in the intervention group [1]. Short-term memory improvement was partly mediated by rising ALA levels, suggesting PS may work synergistically with omega-3s to produce its effects.
Evidence grade: Promising, small-to-moderate RCTs in healthy adults, results encouraging but not definitive
The research hasn’t only focused on people with existing cognitive problems. A 2023 randomised, double-blind, placebo-controlled trial published in *Neurology and Therapy* studied 138 healthy adults aged 40–65 who reported subjective memory problems [2]. Participants took a supplement combining PS with whole coffee cherry extract (Neuriva®) for 42 days.
Compared to placebo, the supplement group showed significant improvements in numeric working memory accuracy (p ≤ 0.024), reaction time (p ≤ 0.031), and picture recognition accuracy (p = 0.035) [2]. These are precisely the types of cognitive tasks that matter in daily life, remembering a phone number long enough to dial it, recognising a face, responding quickly.
The caveat worth flagging here: this was a combination product (PS plus coffee cherry extract), so we can’t fully isolate PS’s contribution from the other ingredient. That’s an honest limitation of some of the newer research. Still, the direction of effect is consistent with the PS literature more broadly.
Evidence grade: Promising, small pilot trials, encouraging signals, larger long-term studies needed
One of the most underreported findings in the PS literature comes from a 2014 paper examining soy lecithin-derived PS combined with phosphatidic acid (PA) in Alzheimer’s disease patients [14].
In a two-month randomised, double-blind, placebo-controlled trial of Alzheimer’s patients, those receiving 300 mg PS + 240 mg PA daily maintained their ability to perform activities of daily living, while the placebo group showed measurable decline, falling from a score of 5.62 to 4.90 on a seven-activity daily functioning scale (p = 0.035) [14]. The PS+PA group showed only 3.8% deterioration versus 17.9% in the placebo group. Nearly half of the PS+PA patients reported an improved general condition, versus 26.3% in the placebo group.
These are small numbers, 53 in the PS+PA group and 39 in placebo, over just two months, and the authors are appropriately cautious about drawing firm conclusions. But slowing the rate of functional decline, even modestly, in Alzheimer’s patients is a meaningful signal that deserves larger, longer investigation.
The same research group also found in elderly subjects without dementia that PS+PA significantly improved memory and, interestingly, prevented “winter blues” compared to placebo over three months [14].
Evidence grade: Early stage for the mechanistic detail, strong animal data, supported by human biomarker findings
What’s happening inside the brain when PS works? The animal research gives us a detailed and consistent picture, and the 2025 human trial provides biological corroboration.
A 2001 study in aged rats found that oral soybean-derived PS (60 mg/kg/day for 60 days) significantly improved performance in the Morris water maze memory test, a gold standard for spatial memory, to levels comparable to young rats [7]. Crucially, it also increased acetylcholine release in the synapses and restored the activity of Na+/K+-ATPase (a key enzyme for neuron energy function) to youthful levels.
A 2012 study using krill-derived PS in rats with chemically-induced memory impairment found that PS treatment improved maze performance and protected acetylcholinergic neurons in the hippocampus and medial septum, the memory-critical regions of the brain most affected in early Alzheimer’s [10]. The same year, a study using squid-derived PS showed that PS treatment increased glucose uptake in the frontal lobe and hippocampus by more than twofold, as measured by PET scanning [11]. More energy reaching the brain’s memory centres.
This mechanistic picture, PS restoring acetylcholine release, protecting hippocampal neurons, and improving brain energy metabolism, is biologically coherent and consistent across multiple research groups and PS sources [7][10][11].
Evidence grade: Strong, consistent across all trials reviewed
One thing the research is unambiguous about: PS is safe. Across every human trial reviewed, from six-month RCTs to two-month pilot studies in Alzheimer’s patients, no significant adverse effects were reported [1][2][6][14]. A 2024 comprehensive review concluded that “clinical studies have shown that PS is safe and well tolerated by patients” [3].
The 2025 children’s trial (100 mg sunflower PS daily for 12 weeks in healthy children aged 8–12) also reported PS was safe and well tolerated in that population [4], and the 2015 human brain review confirmed the consistent safety profile across the literature [13].
This matters. When weighing whether to supplement with something, the risk/benefit calculation is meaningless if you ignore the risk side. For PS, the risk side is consistently reported as minimal.
Honesty matters here, and the PS literature has some genuine gaps worth naming.
The source problem. Most of the dramatic early results came from bovine brain-derived PS, which is no longer commercially available. Modern supplements use soy, sunflower, or marine-derived PS, and while the evidence for plant-derived PS is encouraging, the fatty acid profiles differ from bovine PS, and we don’t yet know whether the magnitude of effects is equivalent [3][15]. This is likely one reason some modern trials show smaller effect sizes than the older European studies.
Isolating PS from combination products. Several of the more recent positive trials used PS alongside other ingredients, ALA, ginkgo, coffee cherry extract, phosphatidic acid [1][2][14]. The effects may be genuinely synergistic, and PS may work better in combination. But it makes it harder to know precisely how much PS alone is doing.
Sample sizes. No individual trial here involved more than 190 participants, and most were considerably smaller. The effects are real and consistent in direction, but we need larger, longer trials to pin down optimal dosing, which populations benefit most, and what duration of supplementation is needed for lasting results [6][8][14].
The children’s data is limited. The 2025 children’s trial found no significant effect in the total group, only in a subgroup of children with below-median baseline scores [4]. This mirrors the adult pattern, PS appears to work best in those who need it most, but it means we shouldn’t overgeneralise PS’s benefits to healthy populations with no cognitive concerns.
Long-term data in dementia is missing. The Alzheimer’s findings are genuinely intriguing, but two months is a short window. Whether PS+PA can meaningfully slow cognitive decline over one to five years in dementia patients remains an open and important question [14].
Here’s what four decades of research, sifted from the Vitacuity database of over 1.77 million research papers, actually tells us about phosphatidylserine.
This is not a hyped supplement with one promising rodent study behind it. PS has been through multiple randomised controlled trials in humans. It has FDA qualified health claim status. Its mechanism inside the brain is biologically coherent and well-documented. And across every trial reviewed, it has an excellent safety record.
The consistent signal in the human research points clearly toward one group who should take particular notice: people over 40 who are noticing the first signs of cognitive slippage, the word that won’t come, the name you should know, the mental fog that wasn’t there five years ago. This is precisely the population where PS has repeatedly shown its strongest effects.
What would a sensible, informed person actually do with this information?
PS is not water-soluble, so it isn’t simply excreted if you take more than you need, but toxicity has not been observed at supplemental doses across any reviewed study. The doses used in successful trials range from 100 mg to 300 mg per day, with 100–200 mg appearing to be the practical sweet spot for daily supplementation [6][14]. You don’t need a blood test first. You don’t need your GP’s permission (though do mention it if you take anticoagulant medication, since PS is involved in blood clotting pathways [3]). The risk of doing nothing, allowing natural PS decline in your neurons to go unaddressed, is, on balance, meaningfully greater than the risk of supplementing at normal doses.
A few practical pointers:
– Take PS with food, it’s fat-soluble and absorbs better alongside dietary fat [14] – Give it time, the most convincing trials ran for six to twelve months [1][6]; don’t judge it at four weeks – Look for consistent sourcing, soy-derived and sunflower-derived PS have the best human trial data among modern plant sources – Consider pairing it with omega-3s, the 2025 trial and the PS-DHA research both suggest a synergistic effect between PS and omega-3 fatty acids [1][8], which is biologically plausible given that PS’s own membrane function is influenced by the fatty acids attached to its backbone
The science here is not perfect. It never is. But the arc of the evidence, from the early European trials, through the FDA recognition, through to the 2025 RCT data, points consistently in the same direction. PS works for memory and cognitive function in people who are beginning to lose ground. It’s safe. It’s well-understood mechanistically. And it has been quietly waiting for you to rediscover it for the better part of thirty years.
That feels like enough.
[1] Effects of a food supplement containing phosphatidylserine on cognitive function in Chinese older adults with mild cognitive impairment: A randomized double-blind, placebo-controlled trial (2025). DOI: 10.1016/j.jad.2024.09.131 | https://pubmed.ncbi.nlm.nih.gov/39317299/
[2] A Randomized, Double-Blind, Placebo-Controlled, Parallel Study Investigating the Efficacy of a Whole Coffee Cherry Extract and Phosphatidylserine Formulation on Cognitive Performance of Healthy Adults with Self-Perceived Memory Problems (2023). DOI: 10.1007/s40120-023-00454-z | https://pubmed.ncbi.nlm.nih.gov/36929344/ | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10195946/
[3] Phosphatidylserine: A comprehensive overview of synthesis, metabolism, and nutrition (2024). DOI: 10.1016/j.chemphyslip.2024.105422 | https://pubmed.ncbi.nlm.nih.gov/39097133/
[4] The cognitive effects of supplementation with sunflower phosphatidyl serine in healthy children aged 8 to 12 years: a randomized controlled trial (2025). DOI: 10.1186/s12937-025-01264-9 | https://pubmed.ncbi.nlm.nih.gov/41318468/ | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12772107/
[5] Role of Enzymes Capable of Transporting Phosphatidylserine in Brain Development and Brain Diseases (2024). DOI: 10.1021/acsomega.4c05036 | https://pubmed.ncbi.nlm.nih.gov/39157110/ | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11325426/
[6] Soybean-derived phosphatidylserine improves memory function of the elderly Japanese subjects with memory complaints (2010). https://pubmed.ncbi.nlm.nih.gov/21103034/
[7] Oral administration of soybean lecithin transphosphatidylated phosphatidylserine improves memory impairment in aged rats (2001). DOI: 10.1093/jn/131.11.2951 | https://pubmed.ncbi.nlm.nih.gov/11694624/
[8] Phosphatidylserine containing omega-3 fatty acids may improve memory abilities in non-demented elderly with memory complaints: a double-blind placebo-controlled trial (2010). https://pubmed.ncbi.nlm.nih.gov/20523044/
[10] Krill-Derived Phosphatidylserine Improves TMT-Induced Memory Impairment in the Rat (2012). https://pubmed.ncbi.nlm.nih.gov/24116297/
[11] Chronic Treatment with Squid Phosphatidylserine Activates Glucose Uptake and Ameliorates TMT-Induced Cognitive Deficit in Rats via Activation of Cholinergic Systems (2012). https://pubmed.ncbi.nlm.nih.gov/22675385/
[13] Phosphatidylserine and the human brain (2015). https://pubmed.ncbi.nlm.nih.gov/25933483/
[14] Positive effects of soy lecithin-derived phosphatidylserine plus phosphatidic acid on memory, cognition, daily functioning, and mood in elderly patients with Alzheimer’s disease and dementia (2014). DOI: 10.1007/s12325-014-0165-1 | https://pubmed.ncbi.nlm.nih.gov/25414047/ | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4271139/
[15] Phosphatidylserine. Monograph (2008). https://pubmed.ncbi.nlm.nih.gov/18950250/
This article is for informational purposes only and does not constitute medical advice. Food supplements should not be used as a substitute for a varied and balanced diet and healthy lifestyle. If you are pregnant, breastfeeding, taking medication or have a medical condition, consult your doctor before taking any supplement. These statements have not been evaluated by the Food and Drug Administration (FDA) or the Medicines and Healthcare products Regulatory Agency (MHRA). This product is not intended to diagnose, treat, cure, or prevent any disease.
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