Phosphatidylserine: Cell Membrane Nutrient for Stress Resiliency

Phosphatidylserine (PS) and other phospholipid compounds constitute the fundamental structural matrix of all cell membranes. The PS molecular structure consists of a phosphoserine head group, a glycerol backbone, and two fatty acid tails (see image).1

PS is an active and integral component of the cell membrane and is necessary for proper cell-to-cell recognition and communication. PS is known to enhance cellular metabolism and transfer of biochemical messages by regulating the function of membrane proteins and by influencing the fluidity of the membrane. PS regulates cell receptors, enzymes, ion channels, and signaling molecules, and via these functions, PS directly affects both endocrine and cognitive function.1

PS is likewise active within the cell, in membranes of secretory vesicles and the mitochondrial membrane system. PS is most concentrated in the cells of organs carrying a high metabolic demand, i.e., brain, heart, lungs, liver, and skeletal muscle.1,2

PS is also a nutrient found in high concentrations in fish,meat, egg yolk, and organ meats, with smaller amounts present in many other common foods. Supplemental PS is commonly derived from soybeans, although it may be sourced from sunflower seeds. The average daily PS intake from a Western diet is estimated to be ~130 mg. A diet high in animal protein provides ~180 mg, while a vegetarian diet supplies ~50 mg.2 The body can synthesize PS only through a complex series of reactions requiring substantial energy, therefore it is considered a semi-essential nutrient.1

Results of numerous clinical trials indicate that supplemental PS provides metabolic support for cognitive functions that tend to decline with age, including memory, learning, language skills, concentration, reasoning, and decision making.3 Indeed, PS is the only dietary supplement that holds FDA qualified health claims for reducing the risk of cognitive dysfunction and dementia.3 Supplemental PS also has been shown to enhance mood, immunity, and the capacity to cope with stress.1,2

One of the primary indications for use of supplemental PS is to modulate aspects of the stress response and to improve stress adaptation. Early research in elderly patients using bovine cortex-derived PS showed benefits for conserving hypothalamic function and normalizing the hypothalamic-pituitary-adrenal (HPA) axis response.4 Likewise, a recent study determined that soybean-derived PS (supplemented with essential fatty acids and antioxidant nutrients) is effective at improving mood, moderating high cortisol levels, and normalizing diurnal cortisol rhythms in a subset of elderly patients with major depression.5

Additional clinical studies in middle-aged and younger adults note similar benefits of supplemental PS in attenuating perceived stress and modulating the cortisol response relating to demanding mental tasks. In healthy young adults faced with a mental and emotional stressor, a soy-derived PS-containing supplement was able to blunt acute adrenocorticotropic hormone (ACTH) and cortisol responses while decreasing perceived mental and emotional distress. These effects were more pronounced in men than in women.6 A more recent study confirmed that a soy-derived PS-containing supplement can reduce levels of perceived stress and normalize acute ACTH and cortisol responses in chronically stressed, but otherwise healthy, young men.7 Another similar study of an omega-3 rich PS supplement reported a normalization (modest increase) of the cortisol response to acute stress in chronically stressed young men with depressed cortisol levels at baseline.8

Although not all studies document a normalization of cortisol levels in individuals under mental stress, the benefit of PS on the subjective perception of stress is reported more consistently.9 Notably, PS may support chronically stressed students by improving the perception of stress load and enhancing mood.10

Several additional clinical trials note related benefits of supplemental PS for modulating the stress response due to strenuous exercise training. In an early study, bovine-derived PS effectively blunted the rise of cortisol and the ACTH response to strenuous exercise in healthy young men.11 Likewise, a soy-derived PS supplement decreased the cortisol response to intensive resistance training by 20 percent, reduced muscle soreness, and improved perception of well-being in young male athletes participating in intensive exercise training.12 A more recent study confirmed and elaborated on these results, finding that soy-derived PS lowers resting cortisol levels before exercise, reduces overall cortisol output during exercise, and increases the testosterone to cortisol ratio after exercise.13

Not all studies document these improvements in cortisol response to exercise. However, the reviewed clinical trials all note benefits of PS on modulating related aspects of exercise induced stress.2 In particular, supplementation with PS may improve exercise capacity and antioxidant protection,14,15 as well as cognitive and overall performance related to training.16,17 Dosages of PS in these studies ranged from 200-800 mg/day, and duration of supplementation ranged from 10 days to 12 weeks.

In summary, PS has been found to improve HPA axis integration by normalizing ACTH and cortisol responses to stress. As a result, PS effectively improves adaptability to stress, moderates perception of stress load, and enhances actual performance and recovery in a variety of stressful situations, including intensive exercise training and demanding mental and emotional tasks. As mentioned above, numerous clinical studies also document the benefits of PS supplementation on the enhancement of mood, immunity, and overall cognitive function.

Supplemental PS may be most beneficial for chronically stressed individuals who exhibit elevated cortisol on testing and who also suffer from anxiety, depression, or cognitive decline. PS may also help normalize cortisol output in chronically stressed patients who have low cortisol levels on testing. Additionally, PS is particularly indicated for athletes who aim to optimize performance and speed recovery after intensive training. Overall, supplemental PS can be a valuable tool for regulating the stress response in patients of all ages and fitness levels.



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