Supplements to Reduce Cortisol

Among supplements used to reduce cortisol, ashwagandha has one trial involving 64 participants that found lower resting serum cortisol.¹ Phosphatidylserine and omega-3 reduced cortisol responses during acute laboratory or physical stressors, but this does not establish that they lower day-to-day cortisol.^2-4 The cited review on magnesium includes no cortisol outcome.⁵ None has been proven to be the best cortisol supplement, and proprietary blends with undisclosed amounts cannot be evaluated. Repeated high results require correctly timed testing and clinical interpretation before supplementation.

Cortisol and the Stress Response

Cortisol is a steroid hormone produced by the adrenal glands. It helps regulate the stress response, metabolism, inflammation, blood pressure, and the sleep-wake cycle.⁶

Cortisol also follows a daily rhythm. Collection timing can change the result, which limits the value of interpreting one reading without context.⁶

Trials of cortisol supplements usually measure one of two outcomes. Some measure resting cortisol. Others measure the cortisol response during controlled exercise or a laboratory stress test. Those outcomes answer different questions.

A smaller cortisol response during a controlled stressor does not prove that baseline cortisol will fall during ordinary life. The evidence table keeps that distinction intact.

Evidence Grades for Cortisol Supplements

Human trials provide limited and narrowly defined support for several cortisol supplements. The confidence grade applies to the cortisol claim alone. It does not rate the supplement’s effects on other health outcomes.

Supplement	What the best evidence is	What it showed	Confidence
Ashwagandha	One randomized, double-blind, placebo-controlled trial involving 64 adults reported a resting serum cortisol result.1 A separate crossover trial in aging, overweight men found no statistically significant between-group difference in cortisol.7	The 64-participant trial found lower resting serum cortisol with ashwagandha. This is the only cited ashwagandha trial showing lower resting cortisol.1	Low. One small positive trial and one null trial do not establish a consistent effect across populations.
Phosphatidylserine	Two studies from 1990 and 1992 examined eight and nine healthy men, respectively.2,3 The first used 50 or 75 mg of intravenous, brain-cortex-derived phosphatidylserine. The second used oral bovine brain-cortex-derived phosphatidylserine at 800 mg per day.2,3	Both studies reported a smaller cortisol response to acute physical stress or exercise. The 1992 trial reported a cortisol result of P = 0.03.2,3 Neither study established lower resting cortisol.	Very low for current consumer products. The studies were tiny, decades old, and used source materials that differ from current soy- or sunflower-derived capsules. One used intravenous administration.
Omega-3	A randomized controlled trial substudy measured salivary cortisol around a Trier Social Stress Test in 138 midlife adults.4	The group studied at 2.5 g per day had 19% lower overall cortisol than placebo during the laboratory stressor. The overall cortisol result was P = 0.03.4	Low for acute stress reactivity. This was one controlled stress-test study. It does not establish lower resting cortisol or a day-to-day effect.
Magnesium	A review examined the two-way relationship between magnesium status and stress.5 It was not a cortisol-lowering trial.	The review described how stress can affect magnesium status and how magnesium status may relate to stress. It reported no trial outcome showing that magnesium supplementation lowered cortisol.5	Insufficient. The cited evidence does not contain a cortisol outcome.

Ashwagandha and Resting Cortisol

Ashwagandha has the most direct resting-cortisol result among these four ingredients, but the evidence rests on one 64-participant trial.¹ A separate study in aging, overweight men found no statistically significant cortisol difference between ashwagandha and placebo.⁷

A meta-analysis of randomized trials reported improvements in stress and anxiety scores. The authors rated the certainty of evidence as low, and cortisol was not an outcome in that analysis.⁸ Stress scores cannot substitute for a hormone measurement.

Ashwagandha therefore earns a low confidence grade. The available research supports further study. It does not establish ashwagandha as a proven treatment for persistently high cortisol.

Phosphatidylserine and Acute Physical Stress

Phosphatidylserine reduced cortisol responses during acute physical stress in two very small studies.^2,3 Both trials also measured adrenocorticotropic hormone, which is part of the hormonal pathway that stimulates cortisol release.

The study details limit how far those findings can travel. The 1990 study involved eight men and delivered brain-cortex-derived phosphatidylserine intravenously.² The 1992 study involved nine men and used an oral product derived from bovine brain cortex.³

Current consumer phosphatidylserine is generally derived from soy or sunflower. A result from intravenous or bovine brain-derived material cannot be assumed to apply to a current capsule. Neither study demonstrated lower resting cortisol in an ordinary stressed adult.

Omega-3 and Laboratory Stress

Omega-3 has one controlled result showing a smaller cortisol response during a laboratory stress test.⁴ Omega-3 is commonly marketed in products claiming to reduce cortisol and inflammation, but those are separate outcomes.

The trial measured salivary cortisol around a Trier Social Stress Test. Participants in the group studied at 2.5 g per day had 19% lower overall cortisol than the placebo group, with a P value of 0.03.⁴

This finding applies to cortisol during a controlled stressor. The study does not establish that omega-3 lowers resting cortisol or treats a persistent cortisol abnormality.

Magnesium Status and Cortisol Claims

Magnesium has no direct cortisol result in the cited evidence. The review describes a two-way relationship in which stress may affect magnesium status while magnesium status may also affect the response to stress.⁵

That relationship does not prove that magnesium supplementation lowers cortisol. Magnesium may have a separate rationale when a clinician identifies an intake problem or deficiency, but a cortisol claim requires its own evidence.

Unsupported Cortisol Supplement Claims

Rhodiola, holy basil, L-theanine, vitamin C, and proprietary blends do not have supporting cortisol trials within this evidence set. That does not prove that every ingredient is ineffective. It means a cortisol-lowering claim has not been established by the sources assessed here.

Proprietary blends present another problem. If the label does not disclose the amount of each ingredient, the formula cannot be compared with any trial. A blend may also contain several ingredients, making it impossible to identify which one caused a benefit or adverse reaction.

Terms such as adrenal support and cortisol balance do not define a measurable outcome. A useful claim identifies whether the product affected resting cortisol, a timed daily measurement, or the response to an acute stressor.

Ingredient identity, disclosed amounts, medication interactions, and the reason for supplementation all matter when evaluating a product. The Opt Health guide to supplements for men provides a broader framework for supplement selection.

Cortisol Testing and Clinical Evaluation

A single elevated cortisol reading is not a diagnosis. Cortisol changes across the day, so a result needs the collection time, testing method, medication context, and reason for testing.⁶

A repeated high value collected under comparable, clinician-selected conditions carries more information. A repeated abnormal pattern accompanied by relevant symptoms or changes in related markers warrants clinical investigation before supplementation. The clinician can then decide whether another test or a broader hormone evaluation is appropriate.

Sleep, alcohol use, and training load can move cortisol more than any supplement discussed here; the Opt Health cortisol guide covers those levers and the signs associated with high cortisol.

Collection timing also matters in testosterone blood testing, although testosterone and cortisol tests answer different clinical questions. Hormone results become more useful when a physician interprets the collection conditions, symptoms, medications, and related biomarkers together.

At Opt Health, physicians review hormone results as part of a broader biomarker pattern. Treatment decisions follow that interpretation rather than an isolated cortisol value.

Safety and Interaction Concerns

Natural supplements to reduce cortisol can cause adverse effects and medication interactions. Ashwagandha has the clearest safety concern among the ingredients reviewed here.

LiverTox assigns ashwagandha a likelihood score of B, meaning it is considered a likely cause of clinically apparent liver injury.⁹ Reported injury usually begins 2 to 12 weeks after starting ashwagandha. The typical presentation includes jaundice and pruritus, which means yellowing of the skin or eyes and itching.⁹

Rare cases have ended in death or required emergent liver transplantation.⁹ People with cirrhosis or advanced chronic liver disease should avoid ashwagandha. Anyone who develops jaundice or persistent itching after starting it should stop the product and seek medical care.

Several other situations require clinician review before using ashwagandha:

• Pregnancy. Anyone who is pregnant should avoid starting ashwagandha without first speaking with a prenatal clinician.
• Thyroid medication. Ashwagandha may affect thyroid function, which can complicate thyroid laboratory results and medication management.
• Immunosuppressants. Possible immune effects may interfere with the purpose of immunosuppressive treatment.
• Sedatives. Additional sedation may increase drowsiness or impairment when ashwagandha is combined with a sedating medication.

A prescriber or pharmacist should review the full ingredient label because combination products can introduce additional interactions. This review is especially important when a blend does not disclose the amount of each ingredient.

Frequently asked questions

This content is for informational purposes and does not replace evaluation or treatment by a qualified medical professional.