Best Evidenced Supplements for Stress: Ashwagandha, Rhodiola, and Magnesium

Ashwagandha, rhodiola, and magnesium are three of the most searched supplements for stress support, but the quality of evidence behind each one varies considerably. This guide summarizes what the NIH Office of Dietary Supplements (ODS) and the National Center for Complementary and Integrative Health (NCCIH) currently report, so you can have a more informed conversation with your clinician.

Supplements are not intended to diagnose, treat, cure, or prevent any disease, and these statements have not been evaluated by the FDA.

Ashwagandha

What it is

Ashwagandha is a plant used in Ayurvedic tradition and is commonly marketed as an adaptogen, a term describing something said to help the body resist and adapt to physical, chemical, and biological stress. The NIH ODS notes that this is a traditional-use concept and not an established nutrient function. The plant is rich in phytochemicals called withanolides, a group of steroidal lactones, along with alkaloids, which are thought to drive many of its proposed effects.

What the research shows

No adult daily target or upper intake limit has been established for ashwagandha by nutrition authorities. Research to date has focused on perceived stress, anxiety, and serum cortisol levels. According to the NIH ODS, the evidence grades are as follows:

• Perceived stress, anxiety, and serum cortisol: Ashwagandha extracts may reduce perceived stress and anxiety and lower serum cortisol. Evidence grade: Limited.
• Sleep quality: Ashwagandha extracts may improve sleep quality, efficiency, total sleep time, and sleep latency, especially in people with insomnia. Evidence grade: Limited.
• Adaptogen claim: The idea that ashwagandha helps the body resist stress in the adaptogen sense is not supported by sufficient evidence. Evidence grade: Insufficient.
• Cognitive function: Claims that ashwagandha improves cognitive function are also not yet supported. Evidence grade: Insufficient.

Safety and interactions

Ashwagandha appears well tolerated for up to about three months, but its long-term safety is not known. Common side effects include loose stools, nausea, drowsiness, and stomach upset. There are also a small number of reports of more serious effects, including adverse effects on liver function and on thyroid function. Some experts advise against use during pregnancy.

Key drug interactions to discuss with a clinician or pharmacist include:

• Thyroid medications: Ashwagandha may affect thyroid hormone levels, and cases of thyrotoxicosis have been reported, so it may interact with thyroid medications.
• Antidiabetes medications: A potential interaction exists because ashwagandha may affect blood glucose.
• Antihypertensive medications: A potential interaction exists because ashwagandha may affect blood pressure.
• Immunosuppressants: Ashwagandha may stimulate immune activity, which could interfere with immunosuppressant drugs.

Rhodiola Rosea

What it is

Rhodiola rosea is a flowering plant with a long history of traditional use for fatigue, endurance, and physical stamina. It is also promoted as an adaptogen for stress. No adult daily target or upper intake limit has been established by nutrition authorities.

What the research shows

The NCCIH describes the research on rhodiola as low to moderate in quality overall. Evidence grades for the most common claims are:

• Athletic or physical performance: Insufficient evidence to confirm a benefit.
• Stress reduction or adaptogen effects: Insufficient evidence to confirm a benefit.
• Fatigue relief or increased energy: Insufficient evidence to confirm a benefit.
• Mood or depression: Insufficient evidence to confirm a benefit.
• Cognitive function: Insufficient evidence to confirm a benefit.

The NCCIH states plainly that the evidence is not sufficient to confirm any of these uses at this time.

Safety and interactions

The NCCIH describes rhodiola as possibly safe when taken by mouth for up to 12 weeks. Safety beyond that period has not been established. Reported side effects include dizziness, headache, insomnia, and either dry mouth or excessive saliva production. Rhodiola should be avoided during pregnancy and breastfeeding unless a clinician specifically advises otherwise, because very little is known about its safety in those situations.

The NCCIH reports that interactions between rhodiola and losartan, a medication used for high blood pressure, have been documented. Because herbs and medications can interact in harmful ways, the NCCIH advises speaking with a health care provider before using rhodiola alongside any prescription medication.

Magnesium

What it is

Unlike the two botanicals above, magnesium is an essential mineral with well-established physiological roles. According to the NIH ODS, it serves as a cofactor in more than 300 enzyme systems that regulate diverse biochemical reactions, including protein synthesis. It also supports normal muscle and nerve function and contributes to blood glucose control and blood pressure regulation.

What the research shows

Evidence grades for magnesium are generally stronger than for the botanicals in this guide:

• Core physiological functions (cofactor activity, muscle and nerve function, energy production, DNA and RNA synthesis, bone structure): Strong evidence.
• Migraine prevention: Magnesium may help prevent migraine headaches. Evidence grade: Moderate.
• Blood pressure, bone health, type 2 diabetes risk, and cardiovascular health: Associations exist between higher magnesium intake and lower risk in these areas. Evidence grade: Limited for each.

Reference values and safety

The NIH ODS reports the following reference values for adults. Men aged 19 to 50 need 400 to 420 mg per day; women aged 19 to 50 need 310 to 320 mg per day. The Tolerable Upper Intake Level for supplemental magnesium is 350 mg per day for anyone aged 9 and older. This limit applies only to magnesium from dietary supplements and medications, not to magnesium naturally present in food and beverages. Exceeding the supplemental limit is associated with diarrhea and gastrointestinal effects. Doses used in some research, such as for migraine prevention, exceed the upper limit and should only be taken under the direction of a clinician.

Drug interactions

• Bisphosphonates (such as alendronate): Separate dosing by at least two hours to avoid reduced absorption.
• Tetracycline and quinolone antibiotics (such as doxycycline and ciprofloxacin): Take these antibiotics at least two hours before or four to six hours after a magnesium supplement.
• Loop and thiazide diuretics (such as furosemide and hydrochlorothiazide): Chronic use can increase urinary magnesium loss and lead to depletion.
• Potassium-sparing diuretics (such as amiloride and spironolactone): These reduce magnesium excretion and may raise magnesium levels.

Bottom Line

Of the three supplements covered here, magnesium has the strongest evidence base because it is an essential mineral with confirmed physiological roles. Ashwagandha has limited evidence suggesting it may reduce perceived stress and support sleep, while rhodiola currently has insufficient evidence to support any of its commonly promoted uses. All population reference values in this guide come from the NIH Office of Dietary Supplements. Please consult a clinician or pharmacist for personal dosing guidance and before combining any of these supplements with prescription or over-the-counter medications.