Can phosphatidylserine (PS) interfere with low cortisol levels?

Phosphatidylserine and Low Cortisol Levels: Potential Interference

Phosphatidylserine (PS) supplementation should be avoided in patients with low cortisol levels as it may further reduce cortisol production and potentially worsen adrenal insufficiency symptoms.

Mechanism of Action and Concerns

Phosphatidylserine has been demonstrated to blunt cortisol responses, which is beneficial in states of excess cortisol but potentially harmful in states of cortisol deficiency:

• Research shows that PS supplementation can reduce cortisol concentrations by 39% and area under the curve by 35% compared to placebo during exercise-induced stress 1
• PS appears to normalize hypothalamic-pituitary-adrenal axis (HPAA) function by reducing hyperresponsiveness in chronically stressed individuals 2
• This cortisol-lowering effect could be detrimental in patients with already low cortisol levels

Clinical Implications for Adrenal Insufficiency

Adrenal insufficiency is characterized by inadequate cortisol production and requires careful management:

• Primary adrenal insufficiency presents with low cortisol and high ACTH levels 3, 4
• Secondary adrenal insufficiency presents with low cortisol and low/inappropriately normal ACTH levels 4
• Both conditions require cortisol replacement therapy, typically with hydrocortisone 15-25 mg daily in split doses 3

Taking PS while having adrenal insufficiency could:

• Further suppress already inadequate cortisol production
• Potentially precipitate or worsen an adrenal crisis
• Interfere with the accurate assessment of cortisol levels during diagnostic testing

Management Considerations

For patients with known or suspected low cortisol:

1. Diagnostic accuracy: PS supplementation may interfere with cortisol testing, leading to falsely low results during diagnostic workup

2. Treatment interference: For patients on cortisol replacement therapy, PS might counteract the therapeutic effects of prescribed glucocorticoids

3. Adrenal crisis risk: In patients with marginal cortisol production, PS could potentially trigger an adrenal crisis, which is a life-threatening emergency requiring immediate treatment with IV hydrocortisone and fluid resuscitation 3, 4

Special Populations and Considerations

• Patients recovering from exogenous steroid use: These individuals often have suppressed adrenal function and should avoid PS until normal adrenal function is restored

• Patients with subclinical adrenal insufficiency: Even mild cortisol deficiency could be exacerbated by PS supplementation

• Patients undergoing stress: During periods of physical stress (illness, surgery), cortisol requirements increase, making PS supplementation particularly risky 3, 4

Conclusion

While PS supplementation may have benefits for certain conditions, including its potential to reduce excessive cortisol in chronically stressed individuals 2, 5 or improve exercise capacity 6, it should be avoided in patients with low cortisol levels due to the risk of further suppressing cortisol production and potentially precipitating an adrenal crisis.

Patients with suspected or confirmed adrenal insufficiency should focus on appropriate medical management with glucocorticoid replacement rather than supplements that could interfere with cortisol levels.