The global obesity crisis is escalating, with over 650 million adults worldwide living with obesity, a condition strongly linked to cardiovascular disease, diabetes, and metabolic disorders. Traditional weight loss interventions often fail to address a critical underlying factor: chronic stress and its hormonal impact on fat metabolism. Phosphatidylserine (PS) emerges as a promising solution, targeting multiple pathways simultaneously. This article explores the connection between phosphatidylserine, cortisol, weight loss, and cognitive function.
Understanding Phosphatidylserine
Phosphatidylserine (PS) (CAS No. 51446-62-9) is a phospholipid with the molecular formula C₄₂H₈₂NO₁₀P, naturally abundant in neural and mitochondrial membranes. While historically recognized for cognitive support, its emerging role in weight loss stems from unique structural properties that influence metabolic signaling. Modern supplementation uses soy or sunflower-derived PS (typically 100-300mg), avoiding earlier bovine sources due to prion concerns.
The Link Between Chronic Stress, Cortisol, and Weight Gain
Chronic stress and weight gain correlate with cortisol, the body’s primary stress hormone. Produced by the adrenal glands in response to physical or psychological stressors, cortisol triggers a cascade of metabolic changes designed to provide emergency energy. Chronic elevated cortisol triggers fat accumulation, interferes with insulin sensitivity, and increases cravings for high-calorie foods. This biochemical sabotage makes phosphatidylserine and weight loss strategies particularly valuable.
Phosphatidylserine and Cortisol Regulation
The phosphatidylserine and weight loss connection lies in its cortisol-regulating capabilities. Research shows that by reducing cortisol levels by 22-27% at clinically studied doses (200mg/day), phosphatidylserine helps restore metabolic balance. PS competitively binds to glucocorticoid receptors as a structural component of neuronal membranes, blunting excessive cortisol signaling that triggers fat storage (particularly visceral adiposity). The phosphatidylserine fat loss advantage lies in breaking this vicious cycle at its source-by competitively binding to cortisol receptors, PS helps restore metabolic equilibrium.
How Phosphatidylserine Promotes Fat Loss
The phosphatidylserine weight loss effect begins with its ability to regulate cortisol, the primary stress hormone that directly influences fat storage and metabolism. When cortisol binds to receptors in fat cells-particularly in the abdominal region-it activates lipoprotein lipase (LPL). This enzyme promotes fat storage while inhibiting hormone-sensitive lipase (HSL), which breaks down stored fat. Additionally, chronic cortisol elevation disrupts insulin sensitivity, leading to higher blood sugar levels, increasing fat disposition. Phosphatidylserine helps restore metabolic balance by improving GLUT4 translocation, allowing muscle cells to take up glucose more efficiently rather than storing it as fat.
Read also: Manage Cortisol for Weight Loss
Phosphatidylserine Dosage and Timing for Weight Loss
Moderate Stress Levels: For individuals experiencing moderate stress levels that may contribute to weight retention, a daily dose of 100-200mg of phosphatidylserine has shown clinically significant benefits. This dosage range has been demonstrated to reduce cortisol levels by approximately 20% in working professionals, according to a 2021 Journal of the International Society of Sports Nutrition study.
Athletes: The phosphatidylserine weight loss advantage for athletes comes from strategic 200-300mg dosing around workouts. This timing blunts post-exercise cortisol spikes by 22-30% while enhancing recovery - a dual benefit confirmed in multiple sports nutrition studies. Research shows this strategy prevents workout-induced catabolism and creates optimal hormonal conditions for fat utilization.
Chronic Stress Sufferers: Clinical research demonstrates higher doses (300-400mg daily) provide robust support for chronic stress sufferers. This intensive protocol delivers sustained cortisol modulation across daily stress cycles, with studies showing 27% reductions in stress-eating episodes. The benefits are particularly noticeable when splitting doses (morning/evening), with the evening administration crucial for those battling sleep-related metabolic disruptions.
Nighttime Dosing: Nighttime phosphatidylserine weight loss dosing (100-150mg) targets the critical cortisol-sleep-metabolism axis. This strategy normalizes nocturnal hormone patterns, with clinical data showing a 31% improvement in sleep quality in stressed adults. The benefits extend to next-day appetite regulation and energy levels.
Phosphatidylserine for Athletes: Reducing Exercise-Induced Stress
Phosphatidylserine supplementation can be used to reduce exercise-induced stress caused by cortisol. Supplementation with 600 mg of S-PS per day for 10 days blunted cortisol response before and during exercise-induced stress. In addition, PS significantly increases the testosterone to cortisol ratio. These findings suggest that PS is an effective supplement for combating exercise-induced stress.
Read also: Is the Cortisol Cocktail Effective?
Phosphatidylserine and Cognitive Function
In addition to its effects on cortisol, PS is also one of the most well-researched ingredients for cognitive support and has been shown to support attention, memory, learning and mental flexibility. Since 2003, PS has been granted a qualified health claim by the FDA, related to cognitive dysfunction and dementia in the elderly. This status allows labels to state "consumption of phosphatidylserine may reduce the risk of dementia and cognitive dysfunction in the elderly," but it must appear along with the disclaimer "very limited and preliminary scientific research suggests that phosphatidylserine may reduce the risk of cognitive dysfunction in the elderly.
Phosphatidylserine and PMS
The cortisol-lowering effect of PS was also observed in a recent study of 40 women aged 18-45 years with a diagnosis of PMS. After a baseline cycle, they were assigned to take either PAS (containing 400 mg PS and 400 mg PA per day) or a placebo over the course of 3 menstrual cycles. PMS symptoms as assessed by the DRSP total score showed significantly better improvement with PAS intake as compared to placebo. In addition, the salivary cortisol percentage increase of the CAR was significantly less pronounced in the follicular phase of cycle 4 than in that of cycle 1 for subjects taking PAS. Serum cortisol levels of PAS-treated females slightly decreased between visit 1 and visit 5, while cortisol levels in the placebo group increased.
Formulations and Combinations
Standalone PS Capsules: Deliver pure phosphatidylserine weight loss benefits (100-200mg/capsule) for customized supplementation.
Stress & Metabolism Complexes: Combine phosphatidylserine cortisol weight loss benefits (150mg) with adaptogens like ashwagandha and Rhodiola.
Pre-Workout/Recovery Blends: Feature phosphatidylserine weight loss doses (200mg) with performance nutrients.
Read also: Cortisol's Role in Sleep Apnea
Sleep Support Formulas: Pair nighttime phosphatidylserine cortisol weight loss doses (100mg) with melatonin and GABA.
Manufacturers developing weight management supplements often combine phosphatidylserine fat loss support with other well-researched ingredients to enhance efficacy.
This combination leverages phosphatidylserine fat loss mechanisms by modulating cortisol, while caffeine and green tea extract work synergistically to boost thermogenesis and fat oxidation.
In this blend, phosphatidylserine fat loss benefits are complemented by L-carnitine’s role in fatty acid metabolism and chromium picolinate’s ability to support insulin sensitivity and carbohydrate metabolism.
These formulations highlight how phosphatidylserine can be strategically paired with other evidence-based ingredients to create targeted weight management solutions.
Examples of other ingredients that can be combined with phosphatidylserine include:
Green Tea Extract (Camellia sinensis): Green tea extract, with the primary active constituent EGCG (CAS Number: 989-51-5), has a molecular formula of C₂₂H₁₈O₁₁ and a molecular weight of 458.37 g/mol.
Garcinia Cambogia (Hydroxycitric Acid, HCA): Hydroxycitric acid (CAS Number: 27750-10-3) is the active component of Garcinia cambogia, with a molecular formula of C₆H₈O₈ and a molecular weight of 208.12 g/mol. Derived or extracted from the fruit rind of Garcinia cambogia, HCA functions as a competitive inhibitor of ATP-citrate lyase, reducing the conversion of carbohydrates into stored fat.
Caffeine (Anhydrous): Caffeine (CAS Number: 58-08-2) has a molecular formula of C₈H₁₀N₄O₂ and a molecular weight of 194.19 g/mol. Found naturally in coffee beans, tea leaves, and guarana, caffeine stimulates the central nervous system, increasing lipolysis and energy expenditure via beta-adrenergic receptor activation.
L-Carnitine: L-Carnitine (CAS Number: 541-15-1) is a quaternary ammonium compound with a molecular formula of C₇H₁₅NO₃ and a 161.20 g/mol molecular weight.
Lifestyle Factors Influencing Hormones and Weight Control
Obesity is a multifaceted problem with many contributing factors including but not limited to genetics, hormone levels, overconsumption of food, and sedentary lifestyle. Dietary adherence has been shown to be negatively associated with the degree of caloric restriction. Development of strategies to promote weight loss in the absence of purposeful caloric restriction could be advantageous in the battle against obesity.
Several different lifestyle factors that may be modified in order to contribute to weight reduction in the absence of caloric restriction. These lifestyle factors are macronutrient composition of meals, meal frequency, exercise, sleep, and psychological stress. In particular, this paper focuses on how the manipulation of these lifestyle factors may positively or negatively influence ghrelin, glucocorticoids (in particular, cortisol), insulin, and leptin to promote weight loss.
Macronutrient Composition of Meals
The macronutrient composition of meals is one variable that may contribute to excessive caloric intake under ad libitum conditions resulting in unwanted weight gain and the onset of obesity. The postprandial endocrine response associated with meals of varying macronutrient proportions may give some insight as to why certain food combinations lead to greater satiety resulting in less caloric ingestion than others. Identifying and exploiting the macronutrient proportions that are associated with satiety and favorable postprandial endocrine responses may be a useful strategy for initiating weight loss through appetite regulation in the absence of purposeful calorie restriction.
Generally, obese individuals exhibit lower fasting ghrelin levels than their normal-weight counterparts which suggests that it may not be the initial amount of plasma ghrelin that regulates appetite but the magnitude and duration of postprandial ghrelin suppression and its ensuing rise to fasting levels.
The fat, protein, and carbohydrate compositions of meals have differing effects on ghrelin suppression as well as appetite regulation and satiety. Isocalorically increasing the proportion of fat calories in relation to calories from carbohydrates and proteins is not a viable strategy to decrease appetite and ad libitum calorie ingestion.
Numerous studies provide evidence that supports the use of a high-protein diet to induce appetite suppression and decreased ad libitum energy intake. Weigle et al. [20] reported that an increase of protein from 15% to 30% of dietary intake resulted in a decrease of ad libitum caloric intake and weight loss. These effects were evident in the absence of ghrelin suppression. Beasley et al. [8] also reported that a meal with 25% protein suppressed appetite (compared to a 15% protein, high-fat group and a 15% protein, high-carbohydrate group). Similar to the results presented by Weigle et al. [20], reduction of appetite could not be explained by a suppression of postprandial ghrelin [8]. The likely mechanism of action of high-protein diets on appetite suppression and decreased caloric intake may be outside of the control of ghrelin.
In addition to a relatively high protein intake (~30% of total calorie intake), moderate carbohydrate intake may also be important in regulating sensations of hunger and calorie ingestion. Endogenous insulin secretion may result in the suppression of ghrelin. In a recent study of healthy Pima Indians, higher plasma insulin responses were associated with a decrease in subsequent carbohydrate consumption and less weight gain. These results further point to insulin as a regulator of calorie consumption.
In conclusion, evidence tends to suggest that for the regulation of ad libitum caloric ingestion, a high-protein diet (~30% of total calories) may be beneficial whereas high-fat diets should most likely be avoided. It would appear to be most beneficial if the additional protein is ingested from solid food sources as food form also appears to play a role in feelings of satiety.
Meal Frequency
Another factor associated with weight control that may not necessarily have a concomitant decrease in caloric intake is meal frequency. Caloric intake can be affected by caloric density in food, total energy consumption as well as meal frequency, but Solomon et al. [32] suggests that feeding frequency has received the least amount of empirical research. Additionally Stote et al. [33] most recently reported that nutrient-dense and low-calorie diets have received significant attention with regards to weight control and health outcomes, but the influence of meal frequency is yet to be firmly established.
To date evidence suggests that less frequent meal consumption with a large bolus of calories at each meal can lead to increases in adipose tissue. Conversely consuming the same amount of calories with more frequent and smaller meals does not seem to impact the deposition of fat. Additionally Solomon et al. [32] report an increase in snacking has positive associations with BMI, but also with caloric intake, suggesting the need for studies involving meal frequency and weight control.
Much of the research regarding weight control and hormones has focused principally on ghrelin, a hormone produced primarily in the gastrointestinal tract with larger amounts in the stomach [35]. Recent findings have suggested that ghrelin may play a role in the control of food intake and meal frequency as well as energy intake [36].
Safety and Side Effects
Phosphatidylserine is well tolerated with few side effects typically. Possible side effects may include:
- Upset stomach
- Gas
- Insomnia
- Headache
- Skin rash
- Mood changes
- Low blood sugar
Taking higher than recommended doses of this supplement can lead to side effects. If you have a shellfish allergy, look for phosphatidylserine made from sunflower or other non-shellfish sources.
Precautions
Always talk to a healthcare provider before taking any supplements. They’ll let you know if the supplement is safe and if it will interact with any other medications you currently take.
Research is ongoing to learn more about whether or not phosphatidylserine is safe to take if you’re pregnant or thinking about becoming pregnant or breastfeeding. Many manufacturers don’t recommend taking this medication if you’re pregnant or planning on becoming pregnant or breastfeeding.
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