Is phosphatidylserine safe to take daily?

Phosphatidylserine is generally considered safe for daily use at doses of 400 to 800 mg per day, with few reported adverse effects in clinical trials. It's most effective when timed around predictable stressors like exercise or high-pressure work events. Long-term safety data beyond 6 months are limited, so periodic breaks or cycling may be prudent if using it chronically.

Supplements That Lower Cortisol: What Actually Works

Creator: Superpower
Published: 2026-03-07

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What supplements actually do to cortisol levels

Ashwagandha has the strongest evidence for lowering baseline cortisol, at 300 to 600 mg a day of a standardized extract. Phosphatidylserine, at 600 to 800 mg a day, blunts the cortisol spikes exercise triggers.

Cortisol is your body's primary stress hormone, released by the adrenal glands in response to physical or psychological stress. It's regulated by the hypothalamic-pituitary-adrenal (HPA) axis, a feedback loop that adjusts cortisol output based on what your body needs. When cortisol stays elevated for too long due to chronic stress, sleep deprivation, or metabolic dysfunction, it can drive weight gain, blood sugar dysregulation, immune suppression, and mood changes.

Supplements that lower cortisol work through different mechanisms. Some modulate the HPA axis directly, reducing the signal to produce cortisol. Others buffer the physiological stress response by supporting neurotransmitter balance or cellular energy production. A few work by blunting cortisol spikes triggered by acute stressors like exercise or mental tasks. The key distinction is whether a supplement lowers baseline cortisol, reduces stress-induced spikes, or both.

The evidence varies widely by compound, dose, and study design. Most clinical trials use specific doses and durations, and deviating from these can reduce effectiveness or increase the risk of side effects.

Supplement	Cortisol evidence	Dose studied	Baseline vs acute spike	Timing
Ashwagandha	Strongest; 27.9% drop from baseline in 1 RCT, confirmed by a 2024 meta-analysis	300-600 mg/day of standardized extract (5% withanolides) for 8-12 weeks	Lowers baseline cortisol	Split into 2 doses or once in the evening, with a meal containing fat
Phosphatidylserine	Blunts exercise-induced spikes; 35% lower cortisol area under the curve at 600 mg/day	600-800 mg/day	Acute spikes, not baseline	30-60 minutes before a known stressor, with food
Rhodiola rosea	Mixed; eases stress and fatigue, but cortisol often unchanged	200-600 mg/day of standardized extract (3% rosavins, 1% salidroside)	Neither shown consistently	Morning or early afternoon
Magnesium	Indirect; trials have not consistently shown a cortisol drop	Not established for cortisol	Neither shown consistently	No cortisol-specific timing
L-theanine	Minimal direct effect on cortisol	Not established for cortisol	Neither shown consistently	No cortisol-specific timing
Omega-3 (fish oil)	Mixed; 19% lower cortisol during a lab stressor in 1 RCT, no change in another	2.5 g/day for 4 months	Stress-induced cortisol; baseline not shown	No cortisol-specific timing

Ashwagandha (Withania somnifera)

Ashwagandha is an adaptogenic herb that modulates the HPA axis by reducing the overactivation of stress pathways. It contains bioactive compounds called withanolides, which appear to influence cortisol secretion at the level of the adrenal glands and the brain. Multiple randomized controlled trials and a 2024 systematic review and meta-analysis confirm that ashwagandha supplementation significantly reduces serum cortisol, stress, and anxiety compared to placebo. One RCT found a 27.9 percent reduction from baseline at 600 mg per day over 60 days.

A separate crossover trial in aging overweight men found an 18 percent greater increase in DHEA-S compared to placebo, though that same study found no significant between-group differences in cortisol. Adverse effects in clinical trials were generally mild, including occasional digestive upset, though rare but serious cases of liver injury have been reported in post-marketing surveillance.

Ashwagandha is fat-soluble, so taking it with a meal that contains fat improves absorption. Most trials show effects after 8 to 12 weeks of consistent use, though some people notice changes in stress and sleep within 2 to 4 weeks. Taking it in the evening may support better sleep by reducing nighttime cortisol, which should naturally be low.

Phosphatidylserine

Phosphatidylserine is a phospholipid found in cell membranes, particularly concentrated in brain tissue. It appears to dampen cortisol release in response to acute stress by modulating the HPA axis at the pituitary level. A study in healthy men found that 600 mg per day reduced exercise-induced cortisol area under the curve by 35 percent compared to placebo. An earlier trial found that 800 mg per day for 10 days significantly blunted both ACTH and cortisol responses to exercise. Another trial showed improved mood and reduced perceived stress during mental tasks.

Because phosphatidylserine blunts acute cortisol spikes, it's most useful when timed around predictable stress. Taking it chronically at baseline may not provide the same benefit as strategic use before stress exposure. It's also fat-soluble, so absorption improves when taken with food.

Rhodiola rosea

Rhodiola is another adaptogen with a long history in traditional medicine for stress resilience. It contains rosavins and salidroside, compounds thought to influence serotonin and dopamine pathways, which indirectly affect cortisol regulation. A 2022 systematic review found that rhodiola improved symptoms of stress, fatigue, and burnout in several trials, but direct cortisol measurements were often not included or showed no significant change. One trial on burnout patients found improved attention and reduced fatigue, but cortisol levels were not significantly different from placebo. Rhodiola may work more through neurotransmitter modulation than direct HPA axis suppression.

Rhodiola has mild stimulant properties, so taking it late in the day may interfere with sleep in some people. Effects on fatigue and mental clarity may appear within 1 to 2 weeks, but stress-related benefits take longer.

Magnesium and L-theanine

Magnesium and L-theanine are often marketed for stress reduction, but their effects on cortisol are indirect. Magnesium supports the nervous system and may reduce stress-related symptoms. Tea's calming effect comes from L-theanine, an amino acid that promotes relaxation by increasing GABA and serotonin, but its impact on cortisol is minimal. These supplements may improve how you feel under stress without necessarily changing cortisol levels.

To lower cortisol quickly, phosphatidylserine is the supplement shown to blunt an acute spike when taken before a known stressor; for non-supplement options, see how to lower cortisol naturally.

Omega-3 fatty acids

Omega-3s from fish oil may soften the cortisol response to stress, though the evidence is thin. In one four-month trial of sedentary, overweight, middle-aged adults, 2.5 g a day of omega-3 produced 19 percent lower cortisol than placebo during a stressful speech task. A shorter trial in healthy young adults found that 2.8 g a day of fish oil for 35 days did not change the cortisol response to stress. With two small trials pointing in different directions, a cortisol benefit from omega-3 is possible but unproven.

How cortisol-lowering supplements affect the HPA axis and stress response

The HPA axis is a tightly regulated feedback system. When your brain perceives stress, the hypothalamus releases corticotropin-releasing hormone (CRH), which signals the pituitary gland to release adrenocorticotropic hormone (ACTH). ACTH then tells the adrenal glands to produce cortisol. Once cortisol levels rise, they feed back to the hypothalamus and pituitary to shut down further release. This is called negative feedback.

Supplements like ashwagandha appear to enhance this negative feedback loop, making the system more sensitive to cortisol's signal to stop producing more. This prevents the chronic overactivation seen in prolonged stress. Phosphatidylserine works slightly differently by blunting the pituitary's release of ACTH in response to acute stressors, which means less cortisol gets produced in the first place during short-term stress events.

Effects on neurotransmitters and mood

Cortisol doesn't act in isolation. Chronic elevation disrupts neurotransmitter balance, particularly serotonin, dopamine, and GABA, which regulate mood, motivation, and anxiety. Preclinical studies show ashwagandha acts as a potent agonist at GABA receptors in the brain, which produces a calming effect and may partly explain why it reduces anxiety alongside cortisol in human trials. Rhodiola influences serotonin and dopamine pathways, which can improve mood and mental clarity even when cortisol changes are modest.

Effects on metabolic and immune function

Elevated cortisol promotes insulin resistance, increases blood sugar, and shifts the body toward fat storage, particularly around the abdomen. It also suppresses immune function by reducing the activity of white blood cells. Supplements that lower cortisol can improve insulin sensitivity and support immune resilience, but these effects are secondary to cortisol reduction. If your cortisol is already in a healthy range, further lowering it won't necessarily improve metabolism or immunity and may even impair the stress response you need for exercise recovery or acute illness.

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Who should use caution with cortisol-lowering supplements

Not everyone responds the same way to cortisol-lowering supplements, and some people should avoid them entirely. Individual variation depends on baseline cortisol levels, the type of stress you're experiencing, existing health conditions, and medications.

People with low baseline cortisol

If your cortisol is already low due to adrenal insufficiency, chronic illness, or HPA axis dysregulation, further suppression can worsen fatigue, low blood pressure, and immune vulnerability. A 2026 case report described a 55-year-old woman who developed Cushingoid features and confirmed adrenal insufficiency after taking approximately 950 mg of ashwagandha daily for one year, with HPA axis suppression persisting six months after discontinuation. Testing baseline cortisol before starting a supplement helps avoid this.

Liver health

Multiple case reports and case series have documented ashwagandha-induced liver injury. Symptoms typically include jaundice, nausea, and abdominal discomfort appearing 2 to 12 weeks after starting supplementation. While rare, liver injury can be serious, particularly in people with pre-existing liver disease. If you develop signs of liver problems such as yellowing of the skin, dark urine, or persistent abdominal pain while taking ashwagandha, discontinue use and consult a physician.

Drug interactions

Ashwagandha may interact with thyroid medications, sedatives, and immunosuppressants. Clinical trials and case reports confirm it has thyroid-stimulating effects that can be problematic for people with hyperthyroidism or those taking thyroid hormone replacement, with documented cases of thyrotoxicosis in susceptible individuals. It also enhances the effects of sedatives and anxiolytics, increasing the risk of excessive drowsiness. Phosphatidylserine may interact with blood thinners and anticholinergic medications.

Pregnancy and breastfeeding

Safety data for ashwagandha, phosphatidylserine, and rhodiola during pregnancy and breastfeeding are limited. Ashwagandha has traditionally been avoided during pregnancy due to concerns about uterine stimulation. Until more research is available, these supplements should be used only under medical supervision during pregnancy or lactation.

Autoimmune conditions

Ashwagandha may stimulate immune activity, which could theoretically worsen autoimmune conditions like rheumatoid arthritis, lupus, or multiple sclerosis. Clinical evidence is limited, but caution is warranted if you have an autoimmune disorder.

Contaminated "adrenal support" supplements

Many over-the-counter "adrenal support" supplements contain glandular extracts from animal adrenal tissue. These products are not well regulated and have been found to contain undeclared thyroid hormones, corticosteroids, and other contaminants. A 2018 study in Mayo Clinic Proceedings analyzed 12 adrenal supplements and found that all contained detectable triiodothyronine (T3), with daily exposure up to 1,322 nanograms based on recommended doses, and most also contained steroid hormones, none of which were declared on the label. The FDA has issued warnings about infections and serious adverse effects from adrenal extract injections. If you're considering an adrenal supplement, choose products that have been third-party tested and avoid glandular extracts unless prescribed by a physician.

From data to action: Using biomarkers to guide supplement decisions

Feeling less stressed doesn't always mean cortisol has changed, so test before you start and track over time. Superpower's 100+ biomarker panel includes morning cortisol, DHEA-S, hs-CRP, fasting glucose, and TSH. Markers to track:

Morning cortisol: Reflects baseline HPA axis activity and should be highest in the morning.
DHEA-S: Balances cortisol's effects; low DHEA-S relative to cortisol suggests chronic stress.
High-sensitivity C-reactive protein (hs-CRP): Elevated cortisol often drives inflammation; tracking hs-CRP shows whether cortisol reduction improves inflammatory status.
Fasting glucose and insulin: Chronic cortisol elevation impairs glucose metabolism; improvements in these markers suggest metabolic benefit from cortisol reduction.
Thyroid-stimulating hormone (TSH) and free T3: Ashwagandha can influence thyroid function; monitoring TSH and T3 ensures you're not over-stimulating the thyroid.

Directionality matters more than any single value: a drop from 18 to 12 mcg/dL over 8 weeks of ashwagandha use, with you feeling better, is meaningful. A drop to 4 mcg/dL with fatigue and low blood pressure has gone too far.

Frequently Asked Questions

Ashwagandha has the strongest clinical evidence for lowering cortisol. One RCT found a 27.9 percent reduction from baseline at 600 mg per day, and a 2024 meta-analysis confirmed significant reductions across seven trials. Phosphatidylserine is effective for reducing cortisol spikes during acute stress, particularly exercise-induced cortisol, with studies showing reductions of 20 to 35 percent at doses of 600 to 800 mg. Rhodiola may improve stress symptoms but has less consistent effects on cortisol levels.

Ashwagandha is generally well tolerated, with occasional mild digestive upset or drowsiness. Rare cases of liver injury have been reported with high doses or prolonged use. Phosphatidylserine has few reported side effects. Adrenal glandular supplements, which contain animal adrenal tissue, carry significant risks including contamination with thyroid hormones, corticosteroids, and infectious agents. The FDA has warned against their use due to serious infections and hormonal imbalances.

Chronic use of high-dose cortisol-lowering supplements, particularly ashwagandha, may suppress the HPA axis if cortisol is driven too low for too long. A 2026 case report described a patient who developed confirmed adrenal insufficiency after taking high-dose ashwagandha chronically, with HPA axis suppression persisting six months after stopping. This risk is higher in people with already low cortisol or those using multiple HPA-suppressing interventions. Testing baseline cortisol before starting and monitoring during use reduces this risk.

Most clinical trials show measurable reductions in cortisol after 8 to 12 weeks of consistent use at 300 to 600 mg per day. Some people notice subjective improvements in stress and sleep within 2 to 4 weeks, but objective cortisol changes take longer. Taking ashwagandha with food improves absorption, and splitting the dose or taking it in the evening may enhance effects on sleep and nighttime cortisol.

Magnesium and L-theanine support the nervous system and may reduce stress-related symptoms, but they don't consistently lower cortisol in clinical trials. Magnesium deficiency can worsen stress reactivity, so correcting low magnesium may indirectly improve cortisol regulation. L-theanine promotes relaxation through GABA and serotonin pathways but has minimal direct effect on cortisol. They're better suited for managing how you feel under stress than for lowering cortisol levels.

There's no evidence that combining ashwagandha and phosphatidylserine is unsafe, but there's also no clinical research on their combined effects. Ashwagandha lowers baseline cortisol over time, while phosphatidylserine blunts acute cortisol spikes. Using both may provide complementary benefits, but it also increases the risk of over-suppressing cortisol. If you combine them, start with lower doses of each and monitor how you feel and, ideally, test cortisol levels to ensure you're not driving it too low.

Adrenal glandular supplements, which contain animal adrenal tissue, are not well regulated and carry significant safety risks. Studies have found contamination with thyroid hormones, corticosteroids, and infectious agents. The FDA has issued warnings about serious infections and hormonal imbalances from adrenal extracts. If you're considering adrenal support, choose evidence-based supplements like ashwagandha or phosphatidylserine instead of glandular products.