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Keeping a sharp mind is a priority for many of us. Whether you’re a grad student suffering from the afternoon slump in mental focus or an older adult concerned about a few recent memory slips, you’re not alone if maintaining a healthy brain is on your mind.
Your brain is vital to your well-being—it manages most of your body’s processes and allows you to create thoughts, experience emotions, and establish your identity. So, it’s easy to see why taking supplements to optimize brain health has become popular.
The term “nootropic” refers to any substance that positively affects mental function. Alpha-GPC and phosphatidylserine are two compounds that have gained recognition as nootropics. Both are phospholipids—fatty substances that are essential components of all living cells—and common ingredients in cognitive and memory supplements.
Let’s explore the science behind how these compounds may help improve your brain’s function.
Scientifically termed L-alpha glycerylphosphorylcholine, alpha-GPC is a phospholipid that contains choline. Your body needs choline to produce acetylcholine—a chemical messenger that plays an essential role in brain function. In the brain, acetylcholine is involved in arousal, memory, attention, and motivation.1
Choline is also essential in forming phosphatidylcholine (PC), which is used in constructing cell membranes. When the brain runs low on choline and needs more, it breaks down PC from cell membranes to create alpha-GPC. This highlights the importance of maintaining an adequate level of choline or the brain's storage form of choline (alpha-GPC).
Some research suggests alpha-GPC may help improve memory and learning, slow cognitive decline, and improve stroke recovery.
In one small study, 32 healthy participants took either alpha-GPC or a placebo for ten days. On day 11, participants were injected with scopolamine—a drug that impairs memory and the learning of new information—or a placebo. Those who took alpha-GPC scored better on tests of attention and memory than those who took the placebo.2
Another randomized controlled trial looked at the effect of alpha-GPC on 126 people with probable Alzheimer's-type dementia. Those who received alpha-GPC exhibited significant cognitive improvements on behavioral and psychological tests compared to those who took a placebo.3
In a trial involving 2044 patients, alpha-GPC was given to people who had suffered from a recent stroke or transient ischemic attack (often referred to as a “mini-stroke”). After receiving alpha-GPC for six months, participants’ results on tests of mental status significantly improved. By the end of the trial, 71% of patients had scores corresponding to no “cognitive decline” or “forgetfulness.”4
Your body produces alpha-GPC naturally, so it is generally well-tolerated as a supplement. Side effects tend to be mild and rare. These include fatigue, heartburn, nausea, diarrhea, headaches, nervousness, insomnia, confusion, dizziness, and skin rash or redness. Any such reaction may indicate that choline levels in your body are too high.
A large 2021 cohort study suggested supplementing with alpha-GPC may increase stroke risk. The study included over 12 million people aged 50 years or older. Researchers found that participants who had taken alpha-GPC over the past ten years had a significantly higher risk of stroke than those who had never taken the supplement.5
However, this study had limitations. The alpha-GPC users were older and had more medical conditions than the non-users. So, they may have had some baseline atherosclerosis (fat and cholesterol build-up in the arteries) which would have put them at elevated risk for stroke.
Your brain needs phosphatidylserine (PS) to function optimally. PS is a phospholipid that serves several important functions in the brain, including:
When brain cells are healthy, the cell membranes are fluid and flexible. But your body’s store of phospholipids, including PS, begins to decrease once you age into your 20s. Brain cell membranes start hardening, and mood, memory, attention, and concentration decline.6
Studies suggest phosphatidylserine may benefit memory for learning and improve memory impairment associated with age-related cognitive decline.
In a randomized, placebo-controlled study, 120 students between the ages of 17 and 18 drank milk fortified with either phosphatidylserine or a placebo for 40 days. They were given memory tests before and after the treatment period. Those who drank milk containing PS showed significant memory improvement compared to those who consumed the placebo.7
Another study of 149 individuals looked at the effects of PS on learning and memory tasks of daily life in people with age-associated memory impairment. Those who took phosphatidylserine for 12 weeks performed better on learning and memory tests than those who received a placebo.8
Research suggests PS may help alleviate depression.
In a double-blind study, 72 individuals aged 60 to 80 were given either PS or a placebo. After three months of daily consumption, those who took PS showed notable improvement in mood, while the group who consumed a placebo exhibited no significant mood change.9
In a small clinical trial, ten older women with depressive disorders were given a placebo for 15 days, followed by PS for 30 days. The women completed a depression assessment scale before and after taking the placebo and following 30 days of PS. Each woman’s depressive symptoms improved after taking PS.10
Preliminary studies indicate phosphatidylserine may enhance attention and concentration.
In one randomized, double-blind study of 36 children with attention deficit hyperactivity disorder (ADHD), those who were given PS for two months showed significant improvement in their inattention compared to those who took a placebo.11
Another small double-blind study looked at the cognitive effect of PS on a group of 18 college-aged men. After taking PS for two weeks, participants exhibited improved speed and accuracy in performing calculation tasks compared to placebo. The study authors concluded that PS supplementation could improve attention and concentration.12
Most of the studies on PS conducted in the United States used PS sourced from cow brains. However, bovine-derived PS sales have declined due to the fear of mad cow disease. Currently, most PS supplements are plant-based, produced from soy or cabbage. While the fear persists, no incidents of contracting mad cow disease from bovine-derived PS have been reported in the US.
Like alpha-GPC, your body produces PS naturally. So, PS is also generally well-tolerated. Scientists suggest a dose of 300 to 800 mg of PS per day is safe and absorbed efficiently.13
Possible side effects include insomnia and gastrointestinal issues such as bloating or stomach upset. These side effects most often occur when taking higher-than-recommended doses.
PS may have a blood-thinning effect, so be cautious if you take anti-inflammatory medications or blood thinners such as warfarin. PS may also interact with antihistamines, antidepressants, and medications that treat glaucoma or Alzheimer’s disease.
As with any nootropic, you should consult your health care provider before starting PS supplementation—especially if you’re taking medications or have a medical condition.
References:
By Dr. Venus Ramos, M.D.
