Phosphatidylserine as a therapeutic supplement

DEFINITION: Natural substance of the human body used as a supplement to treat specific health conditions.

PRINCIPAL PROPOSED USES: Age-related memory loss, Alzheimer’s disease

OTHER PROPOSED USES: Depression, enhancing mental function in young people, enhancing sports performance and recovery, stress

Overview

Phosphatidylserine (PS) is a member of a class of chemical compounds known as phospholipids. PS is an essential component in all human cells and a major component of the cell membrane. The cell membrane is a kind of skin that surrounds living cells. Besides keeping cells intact, this membrane performs vital functions, such as moving nutrients into cells and pumping waste products out of them. PS plays an important role in many of these functions.

Good evidence suggests that PS can help declining mental function and depression in older adults, and it is widely used for this purpose in Italy, Scandinavia, and other parts of Europe. PS has also been marketed as a brain booster for people of all ages, said to sharpen memory and increase thinking ability. However, the evidence to support this use is incomplete and inconsistent.

Requirements and Sources

The human body makes all the PS it needs. However, the only way to get a therapeutic dosage of PS is to take a supplement. PS was initially manufactured from cows' brains, but manufacturers later began sourcing PS from soybeans and other plants because animal brain cells can harbor viruses.

There are reasons to expect that plant-source PS should function very similarly to PS made from cows’ brains, and some animal studies suggest it is effective. However, in preliminary trials, soy-based PS and cabbage-based PS failed to prove beneficial. Other natural sources of PS include eggs, chicken, fish, soybeans, and some animal livers.

Therapeutic Dosages

To improve mental function, PS is usually taken in doses of 100 milligrams (mg) two to three times daily. After maximum effect is achieved, the dosage can reportedly be reduced to 100 mg daily without losing any benefit. PS can be taken with or without meals. When taking PS for sports purposes, athletes sometimes take as much as 800 mg daily. Other studies used 200 to 400 milligrams daily for one to two months.

Therapeutic Uses

Meaningful evidence from numerous double-blind studies suggests that animal-source PS is an effective treatment for Alzheimer’s disease and other forms of age-related mental decline. Vegetable-derived PS has little supporting evidence.

PS is widely marketed as a treatment for ordinary age-related memory loss as well. While there is little direct evidence that it works, in studies of severe mental decline, PS appears to have been equally effective, whether the cause was Alzheimer’s disease or something entirely unrelated, such as multiple small strokes. This suggests that PS may have a positive impact on the brain that is not specific to any one condition. From this observation, it is not a great leap to suspect that it might be useful for much less severe problems with memory and mental function, such as those that seem to occur in nearly all people older than forty. Indeed, double-blind studies have found that phosphatidylserine could improve mental function in people with age-related memory loss. However, two studies failed to find plant-source PS effective for this condition.

PS has also been proposed for enhancing mental function in young people, but there is no direct evidence that any form is effective. Animal-source PS has also shown promise for improving depression, mood disorders, and attention deficit hyperactivity disorder, though further research is needed to confirm these findings.

PS also gained popularity among athletes hoping to build muscle more efficiently. This use is based on weak evidence that PS slows the release of cortisol following heavy exercise. Cortisol is a hormone that causes muscle tissue to break down. After heavy exercise, the body increases cortisol production by 30 to 50 percent. Strength athletes believe that this natural cortisol release works against their efforts to rapidly build muscle mass and hope that PS will help them advance more quickly. However, only two double-blind placebo-controlled studies of PS as a sports supplement have been reported, and neither one found effects on cortisol levels. Of all these trials, the possible ergogenic benefit was mixed. In studies using plant-based PS, little evidence supports its use for exercise and sports performance.

Interestingly, PS has also been advocated as an aid to recovery from heavy exercise, according to the theory that the use of PS would help reduce muscle soreness. This would seem to contradict the proposed effects on cortisol, as cortisol has anti-inflammatory properties. Nonetheless, researchers performed a double-blind study to evaluate whether 750 mg daily of soy-source PS would reduce muscle soreness following downhill racing, but no benefits were seen.

One study found preliminary evidence that combining soy-based PS and lecithin may moderate the body’s reaction to mental stress. Another study evaluated the use of phosphatidylserine for reducing stress in golfers, but the benefits seen failed to reach statistical significance. Participants who were given phosphatidylserine did, however, tee off successfully at a greater rate than those given a placebo.

Scientific Evidence

Alzheimer’s disease and other forms of dementia. Overall, the evidence for animal-source PS in dementia is fairly strong. Double-blind studies involving a total of more than one thousand people suggest that phosphatidylserine is an effective treatment for Alzheimer’s disease and other forms of dementia.

The largest of these studies followed 494 older subjects in northeastern Italy over the course of six months. All suffered from moderate to severe mental decline, as measured by standard tests. Treatment consisted of either 300 mg daily of PS or a placebo. The group that took PS did significantly better in both behavior and mental function than the placebo group. Symptoms of depression also improved. These results agree with those of numerous other smaller double-blind studies involving a total of more than five hundred people with Alzheimer’s and other types of age-related dementia. However, all these studies involved cow-brain PS; studies of plant-source PS for dementia have reported marginally positive results.

Ordinary age-related memory loss. There is some evidence that PS can also help people with ordinary age-related memory loss. In one double-blind study that enrolled 149 people with memory loss but not dementia, phosphatidylserine provided significant benefits compared with a placebo. People with the most severe memory loss showed the most improvement. In another study, 131 older individuals with memory problems but no dementia were randomized to receive a combination of PS and omega-3 fatty acids or placebo. Those in the treatment group had improvements in their cognitive abilities compared with those in the placebo group. It is unclear which of the components, if not both, produced the beneficial effect.

However, a double-blind trial of 120 older people with memory complaints but not dementia failed to find benefits. This discrepancy may have to do with the type of phosphatidylserine used; this trial used the more modern soy-derived form of the supplement. A cabbage-based source of PS has also failed to prove effective for relatively mild memory loss.

Athletic performance. Weak evidence suggests that PS might decrease the release of the hormone cortisol after intense exercise. Among its many effects, cortisol acts to break down muscle tissue–exactly the opposite of the effect desired by a strength athlete or bodybuilder. This double-blind, placebo-controlled study on eleven intensely trained athletes found that 800 mg of PS taken daily reduced the cortisol rise by 20 percent compared with placebo. Another small study on nine nonathletic males found that daily doses of 400 and 800 mg of PS reduced cortisol levels after exercise by 16 and 30 percent, respectively. Another study found that phosphatidylserine could relieve some overtraining symptoms, including muscle soreness, possibly because of its effects on cortisol.

Based on these preliminary trials, PS has been proposed as a sports supplement. However, there is no direct evidence to support the claims that PS helps athletes build muscles more quickly and with less training effort. Furthermore, some of the best-designed studies using vegetable-source PS failed to find any effect on cortisol release, muscle soreness, or markers of muscle damage.

Safety Issues

Phosphatidylserine is generally regarded as safe when used at recommended dosages. Side effects are rare, and when they do occur, they usually consist of nothing much worse than mild gastrointestinal distress. One study found that the use of phosphatidylserine did not alter results on standard medical screening tests. However, the maximum safe dosages for young children, pregnant or nursing women, and those with severe liver or kidney disease have not been established.

PS is sometimes taken with ginkgo because they both appear to enhance mental function. However, some caution might be in order. Ginkgo is a blood thinner, and PS might be one as well. PS is known to enhance the effect of heparin, a very strong prescription blood thinner. The combined use of PS and any drug or supplement that thins the blood may interfere enough with normal blood clotting to cause problems. Some medications and supplements to consider include warfarin (Coumadin), aspirin, pentoxifylline (Trental), clopidogrel (Plavix), ticlopidine (Ticlid), garlic, ginkgo, and vitamin E.

Notably, Alzheimer’s disease and other types of severe age-related neurodegenerative and neurodevelopmental diseases are too serious for self-treatment with PS or any other supplement. In some cases, the symptoms of these diseases may be confused with symptoms of other serious conditions. Persons who believe they or a loved one has a severe age-related condition should consult a doctor for diagnosis and treatment.

Important Interactions

Those persons taking prescription blood thinners, such as warfarin (Coumadin), heparin, aspirin, pentoxifylline (Trental), clopidogrel (Plavix), or ticlopidine (Ticlid) should not use phosphatidylserine except on a physician’s advice. Taking phosphatidylserine along with ginkgo, garlic, or vitamin E might conceivably thin the blood too much.

Phosphatidylserine increases the body’s acetylcholine levels, so taking other medications that also increase acetylcholine, like cholinergic drugs that treat Alzheimer’s disease and glaucoma, may cause side effects. Additionally, anticholinergic drugs block the impact of acetylcholine and make them less effective. Anticholinergics should be avoided, including the antihistamine diphenhydramine, the Parkinson’s disease medication trihexyphenidyl, and the muscle relaxer solifenacin.

Bibliography

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Kingsley, M. I., et al. “Phosphatidylserine Supplementation and Recovery Following Downhill Running.” Medicine and Science in Sports and Exercise, vol. 38, 2006, pp. 1617-25.

Kingsley, M. I., et al. “Effects of Phosphatidylserine on Oxidative Stress Following Intermittent Running.” Medicine and Science in Sports and Exercise, vol. 37, 2005, pp. 1300-06.

Ma, Xiaohua, et al. “Phosphatidylserine, Inflammation, and Central Nervous System Diseases.” Frontiers in Aging Neuroscience, vol. 14, Aug. 2022, doi:10.3389/fnagi.2022.975176.

Vakhapova, V., et al. “Phosphatidylserine Containing Omega-3 Fatty Acids May Improve Memory Abilities in Nondemented Elderly Individuals with Memory Complaints: Results From an Open-label Extension Study.” Dementia and Geriatric Cognitive Disorders, vol. 38, no. 1-2, 2010, pp. 39-45. doi:10.1159/000357793.

Wong, Cathy. "The Mental Health Benefits of Phosphatidylserine." Verywell Mind, 28 Apr. 2024, www.verywellmind.com/the-benefits-of-phosphatidylserine-89496. Accessed 20 Sept. 2024.