Ashwagandha and GLP-1: Cortisol, Stress Eating, and Combined Use Evidence

Five things to know before combining ashwagandha with a GLP-1

1. No pharmacokinetic drug interaction, but that is not the whole story. The FDA Section 7 Drug Interactions sections of Wegovy, Ozempic, Zepbound, and Mounjaro do not list ashwagandha or any adaptogenic herb as a contraindicated or cautioned combination. There is no documented pharmacokinetic interaction.
2. Hepatotoxicity is real and documented — including fatal cases. The NIH LiverTox database assigns ashwagandha a Likelihood Score of B (“likely cause of clinically apparent liver injury”). Case series from multiple countries document cholestatic hepatitis, prolonged jaundice, and acute liver failure — including fatal outcomes in patients with pre-existing liver disease.^[8][12]
3. Ashwagandha raises thyroid hormones — relevant if you are also on levothyroxine. Sharma et al. 2018 (PMID 28829155) found significant TSH reduction and T3/T4 increase with 600 mg/day in subclinical hypothyroid patients. The Wegovy FDA label also documents a 33% increase in levothyroxine exposure via delayed gastric emptying. GLP-1 + levothyroxine + ashwagandha is a three-way thyroid monitoring scenario.^[7]
4. The cortisol/stress-eating mechanism is plausible but modest. Three RCTs confirm ashwagandha reduces serum cortisol and perceived stress scores versus placebo.^[3][4][5]GLP-1s suppress appetite through central pathways. These are complementary mechanisms, not competing ones — but the cortisol effect is small and not clinically equivalent to GLP-1-class weight loss.
5. Ashwagandha is contraindicated in pregnancy. So are GLP-1 receptor agonists. Patients of childbearing potential taking both must use reliable contraception and contact their prescriber immediately if pregnancy occurs.

Are there drug-drug interactions between ashwagandha and GLP-1 medications? What the FDA labels actually say.

The short answer is no specific interaction is listed — but the absence of a labeled interaction does not mean the combination is clinically uncomplicated. Here are the verbatim FDA Section 7 Drug Interactions passages for each approved GLP-1 receptor agonist, followed by the clinical considerations that apply.

Wegovy (semaglutide) — DailyMed SetID ee06186f

Verbatim — Section 7.2 Oral Medications, Wegovy prescribing information (DailyMed SetID ee06186f, Novo Nordisk):

“WEGOVY causes a delay of gastric emptying and thereby has the potential to impact the absorption of concomitantly administered oral medications. In clinical pharmacology trials with semaglutide 1 mg once weekly injection, semaglutide did not affect the absorption of orally administered medications [see Clinical Pharmacology (12.3)]. In a drug interaction study with the semaglutide tablet, levothyroxine exposure was increased 33% (90% CI: 1.25–1.42). Monitor the effects of oral medications concomitantly administered with WEGOVY.”

Ozempic (semaglutide) — DailyMed SetID adec4fd2

Verbatim — Section 7.2 Oral Medications, Ozempic prescribing information (DailyMed SetID adec4fd2, Novo Nordisk):

“OZEMPIC causes a delay of gastric emptying, and thereby has the potential to impact the absorption of concomitantly administered oral medications. In clinical pharmacology trials, semaglutide did not affect the absorption of orally administered medications to any clinically relevant degree [see Clinical Pharmacology (12.3)]. Nonetheless, caution should be exercised when oral medications are concomitantly administered with OZEMPIC.”

Zepbound (tirzepatide) — DailyMed SetID 487cd7e7

Verbatim — Section 7.2 Oral Medications, Zepbound prescribing information (DailyMed SetID 487cd7e7, Eli Lilly):

“ZEPBOUND delays gastric emptying and thereby has the potential to impact the absorption of concomitantly administered oral medications. Caution should be exercised when oral medications are concomitantly administered with ZEPBOUND. Monitor patients on oral medications dependent on threshold concentrations for efficacy and those with a narrow therapeutic index (e.g., warfarin) when concomitantly administered with ZEPBOUND.”

Mounjaro (tirzepatide) — DailyMed SetID d2d7da5d

Verbatim — Section 7.2 Oral Medications, Mounjaro prescribing information (DailyMed SetID d2d7da5d, Eli Lilly):

“MOUNJARO delays gastric emptying and thereby has the potential to impact the absorption of concomitantly administered oral medications. Caution should be exercised when oral medications are concomitantly administered with MOUNJARO. Monitor patients on oral medications dependent on threshold concentrations for efficacy and those with a narrow therapeutic index (e.g., warfarin) when concomitantly administered with MOUNJARO.”

What this means for ashwagandha

None of the four FDA labels lists ashwagandha specifically, which reflects the reality that no formal pharmacokinetic interaction study between ashwagandha and any GLP-1 has been conducted. Ashwagandha is not an oral medication with a narrow therapeutic index (like warfarin) — it is an herbal supplement. The gastric-emptying delay warning in all four labels is directed at drugs whose absorption is critical — not at dietary supplements.

The clinically relevant interactions are not pharmacokinetic. They are:

• Thyroid hormone elevation (see the thyroid section below) — relevant if you are also on levothyroxine, which both the Wegovy label and the Ozempic label flag separately.
• Additive sedation — ashwagandha has mild sedative properties; GLP-1-related fatigue can be significant during titration.
• Hepatotoxicity risk — completely independent of any GLP-1 interaction, but relevant to patient monitoring.
• Compounding GI symptoms — ashwagandha's known side effects include loose stools and nausea, which overlap with the most common GLP-1 titration complaints.

The bottom line: the FDA labels do not prohibit the combination. A prescriber who is aware you are taking ashwagandha can monitor appropriately — liver function if there is any hepatic concern, thyroid function if you are on levothyroxine, and GI symptoms during titration.

The cortisol and stress-eating mechanism: does it apply during GLP-1 weight loss?

Stress eating and cortisol-driven fat deposition are well-documented physiological phenomena — and they operate through a pathway that GLP-1 medications do not directly address.

How chronic cortisol elevation drives weight gain

Elevated cortisol has several weight-relevant effects. Glucocorticoid receptor activation in visceral adipocytes promotes fat deposition in abdominal depots. Cortisol increases appetite through upregulation of neuropeptide Y and stimulation of ghrelin. The resulting food cravings are preferentially directed at calorie-dense, palatable foods — the classic “stress eating” behavior that is often rewarding in the short term and metabolically harmful chronically. Cortisol also blunts insulin sensitivity, promoting the same glucolipotoxic cycle that makes GLP-1s effective in type 2 diabetes and metabolic obesity.

What GLP-1s do — and don't — target

GLP-1 receptor agonists suppress appetite primarily through central nervous system pathways: GLP-1 receptors in the hypothalamus (arcuate nucleus, ventromedial nucleus) and brainstem (area postrema, nucleus tractus solitarius) reduce hunger signaling and food intake. STEP-1 (PMID 33567185) documented −14.9% mean body weight reduction at Week 68 with semaglutide versus −2.4% with placebo.^[1] SURMOUNT-1 (PMID 35658024) documented −20.9% with tirzepatide 15 mg at Week 72.^[2]

GLP-1s also reduce “food noise” — the intrusive preoccupation with food between meals that many patients report resolves dramatically after starting treatment. This is consistent with GLP-1 receptor signaling in the mesolimbic dopamine system (reward circuitry).

What GLP-1s do not specifically address is the HPA-axis cortisol response to chronic psychological stress. If your appetite suppression on a GLP-1 partially reasserts itself under stress — if the food noise comes back when work pressure peaks or sleep is poor — that may reflect an active HPA-axis signal that is upstream of the GLP-1 receptor.

What the ashwagandha cortisol RCTs actually show

Three randomized, double-blind, placebo-controlled trials provide primary-source evidence for ashwagandha's cortisol-reducing effects. All three were verified by direct PubMed E-utilities fetch before inclusion here.

Chandrasekhar et al. 2012 (PMID 23439798).^[3] 64 chronically stressed adults randomized to 300 mg twice daily of full-spectrum ashwagandha root extract (KSM-66) versus placebo for 60 days. The ashwagandha group showed significant reductions in serum cortisol and in Perceived Stress Scale, anxiety (Hamilton Anxiety Scale), and General Health Questionnaire scores. This is the most cited primary cortisol RCT for ashwagandha.

Lopresti et al. 2019 (PMID 31517876).^[5] 60 stressed healthy adults randomized to 240 mg/day of a standardized ashwagandha extract (Shoden) versus placebo for 60 days. The ashwagandha group showed significant reductions in Hamilton Anxiety Rating Scale scores, serum cortisol, and DHEA-S compared with placebo. This trial used a lower dose (240 mg/day) than Chandrasekhar and still showed cortisol reduction.

Salve et al. 2019 (PMID 32021735).^[4] 60 adults with high self-reported stress randomized to 250 mg/day, 500 mg/day, or placebo for 8 weeks. Both active doses produced statistically significant reductions in serum cortisol, Perceived Stress Scale, and food craving scores compared with placebo. The food craving reduction is the specific mechanism most relevant to stress-eating during GLP-1 therapy.

Clinical plausibility with conservative framing

The biological logic of combining an HPA-axis adaptogen with a central appetite suppressant is coherent: they theoretically address different upstream contributors to food intake. The problem is that no published trial has tested this combination directly. The cortisol effect of ashwagandha, while statistically significant in these small RCTs (n = 60–64), is a secondary endpoint in studies powered for anxiety and stress, not for weight loss. Effect sizes on serum cortisol are modest. And the populations studied are stressed but otherwise healthy adults — not patients on GLP-1 therapy with metabolic obesity.

The reasonable patient-facing statement is: if you experience cortisol-driven stress eating that seems to blunt GLP-1 efficacy (episodes of appetite returning during high-stress periods), the plausibility of ashwagandha as an adjunct is real — but so are the safety considerations below. The efficacy evidence does not justify the risk for patients with hepatic history, thyroid disease, or pregnancy.

Warning: Ashwagandha hepatotoxicity — case reports, LiverTox classification, and what to watch for

NIH LiverTox classification — verbatim

The NIH National Library of Medicine's LiverTox database (https://www.ncbi.nlm.nih.gov/books/NBK548536/) is the authoritative U.S. government resource for drug-induced liver injury data. The ashwagandha entry, references updated December 2024, states:

Verbatim — NIH LiverTox database, ashwagandha entry, https://www.ncbi.nlm.nih.gov/books/NBK548536/:

“Despite widescale use, ashwagandha is considered generally safe and without major adverse effects. In clinical trials, there have been no reports of serum enzyme elevations occurring during therapy and no mention of serious adverse events or hepatotoxicity. Recently, however, cases of clinically apparent liver injury have been reported in patients taking commercial herbal products that are labelled as containing ashwagandha. Typically, the liver injury presented 2 to 12 weeks after starting ashwagandha usually with a cholestatic or mixed pattern of injury, jaundice, and pruritus. Immunoallergic and autoimmune features were not prominent. Occasional cases were hepatocellular initially, but in general the ensuing jaundice was protracted although it ultimately resolved completely. Rare instances of fatal liver injury or need for emergent liver transplantation have been reported particularly in patients with preexisting liver disease and cirrhosis.”

“Thus, clinically apparent liver injury attributable to ashwagandha occurs although rarely, and its use should be avoided in patients with cirrhosis or advanced chronic liver disease.”

“Likelihood score: B (likely cause of clinically apparent liver injury).”

“Most cases of ashwagandha associated liver injury have been mild-to-moderate in severity and self-limited in course, but fatal cases due to acute liver failure or acute-on-chronic liver failure have been described. Protracted jaundice is not uncommon, but chronic liver injury and vanishing bile duct syndrome have not been described. In most instances, the liver injury subsides within 1 to 4 months of discontinuing the herbal product. Rechallenge with the same product should be avoided.”

Philips et al. 2023 case series — the largest Indian series

The most comprehensive published series of single-ingredient ashwagandha hepatotoxicity is Philips CA et al. 2023 (PMID 37756041), published in Hepatology Communications.^[8] Researchers retrospectively analyzed records from multiple centers in India from January 2019 through December 2022.

• 23 patients had liver injury attributed to ashwagandha products during this period.
• 8 patients met criteria for single-ingredient ashwagandha HILI (herb-induced liver injury) with no other hepatotoxic agents.
• 5 of the 8 had underlying chronic liver disease.
• 3 presented with acute-on-chronic liver failure — all 3 died on follow-up.
• Cholestatic hepatitis was the most common presentation.
• Liver biopsy revealed cholestatic features with hepatocellular necrosis and lymphocyte/eosinophil portal-based inflammation.
• Chemical analysis of the implicated products confirmed only natural phytochemicals — no adulteration or contamination — meaning ashwagandha's own components were responsible.

A 2025 Spanish case report (Casiano-Manzano et al., PMID 37982556, published in Revista Española de Enfermedades Digestivas) describes life-threatening acute-on-chronic liver failure in a patient with pre-existing liver disease — consistent with the Philips series pattern.^[9] The authors note that “the lack of solid clinical evidence supporting Ashwagandha's health claims emphasizes the need for an evidence-based approach.”

Mechanism of ashwagandha liver injury

Per LiverTox: “The cause of hepatotoxicity from products containing ashwagandha is unclear. Among the many ingredients the withanolides have been most suspect.” The withanolides are steroidal lactones — the same bioactive compounds credited with the adaptogenic (cortisol- reducing) effects. In other words, the ingredients responsible for the marketed benefit may also be responsible for the hepatotoxic risk. Adulteration of commercial supplements with unlabeled hepatotoxic herbs is also possible and cannot be excluded with off-the-shelf products lacking third-party testing.

Who is at highest risk

The LiverTox note that risk is highest in patients with pre-existing liver disease or cirrhosis is clinically important for the GLP-1 patient population: metabolic-dysfunction-associated steatotic liver disease (MASLD, formerly NAFLD) is highly prevalent in adults with obesity. Before adding ashwagandha, the practical question is whether any liver disease is present — a question that requires at minimum a review of recent liver function tests (ALT, AST, ALP, bilirubin) with your prescriber.

Warning signs to watch for

The LiverTox timeline for ashwagandha hepatotoxicity onset is 2–12 weeks after starting use. Patients should watch for:

• Yellowing of the skin or whites of the eyes (jaundice)
• Dark-colored urine (tea- or cola-colored)
• Light-colored or clay-colored stools
• Right-upper-quadrant or abdominal pain or tenderness
• Itching without a skin rash (pruritus from bile salt accumulation)
• Severe unexplained fatigue or nausea

Stop ashwagandha immediately if any of these develop and seek medical attention. Do not restart the same product. Rechallenge is explicitly warned against in the LiverTox record.

Thyroid hormone effects: relevant for Hashimoto's patients and anyone on levothyroxine

Ashwagandha has a documented effect on thyroid hormone levels — a finding that creates a specific clinical concern for patients on a GLP-1 who are also on thyroid medication.

Sharma et al. 2018 — subclinical hypothyroidism RCT

Sharma AK, Basu I, Singh S. (PMID 28829155) conducted a prospective, randomized, double-blind, placebo-controlled trial in 50 subjects with elevated TSH (4.5–10 µIU/L, i.e., subclinical hypothyroidism) at a single center in Varanasi, India.^[7] Subjects received 600 mg/day of ashwagandha root extract or starch placebo for 8 weeks.

• TSH decreased significantly in the ashwagandha group (p < 0.001)
• T3 (triiodothyronine) increased significantly (p = 0.0031)
• T4 (thyroxine) increased significantly (p = 0.0096)
• Time-effect analyses were significant for all three markers
• The authors conclude that “treatment with ashwagandha may be beneficial for normalizing thyroid indices” in subclinical hypothyroidism

The NIH ODS fact sheet confirms this finding: “In one study, three adult men who took 500 mg/day of a standardized ashwagandha root and leaf extract for 8 weeks had small increases in blood thyroxine (T4) levels. A small clinical trial with 50 participants with subclinical hypothyroidism found that ashwagandha root extract, at a dose of 300 mg twice daily for 8 weeks, lowered serum thyroid-stimulating hormone (TSH) and increased triiodothyronine (T3) and T4 levels compared with placebo.”^[13]

The NIH ODS also notes: “Three case reports have also described thyrotoxicosis in women who were taking ashwagandha extract (age range 32–73 years). Discontinuing ashwagandha resolved the symptoms of thyrotoxicosis in all three cases.”^[13]

The three-way thyroid monitoring concern: GLP-1 + levothyroxine + ashwagandha

Patients with hypothyroidism (including Hashimoto's thyroiditis) taking levothyroxine who then start a GLP-1 already face a monitoring consideration: the Wegovy DailyMed label (SetID ee06186f) documents that levothyroxine exposure was increased 33% in a drug interaction study with semaglutide tablet. This is not the injected pen — it is a gastric-emptying effect with the oral semaglutide formulation — but the Ozempic and Wegovy injection labels both instruct monitoring for all oral medications.

Adding ashwagandha to this combination means a third factor is pushing thyroid hormone levels: ashwagandha raises T3 and T4, while levothyroxine provides exogenous T4, and GLP-1 may affect the bioavailability of any other orally administered drugs. Thyroid hormone levels above the therapeutic range can cause:

• Heart palpitations and atrial fibrillation risk
• Anxiety and insomnia (paradoxical, since ashwagandha is being used for stress)
• Heat intolerance and excess sweating
• Bone density reduction with chronic overtreatment

If you are on levothyroxine and considering ashwagandha while on a GLP-1, the appropriate step is a conversation with your prescriber and a TSH/free T4 check before starting. This is not a contraindication in patients with normal thyroid function and no thyroid medication — but in patients on levothyroxine, monitoring is appropriate.

Does ashwagandha cause weight loss on its own? What the trials actually show.

Marketing for ashwagandha sometimes implies it is a weight-loss supplement. The trial evidence does not support this characterization.

Choudhary et al. 2017 (PMID 27055824) — stress-mediated weight effects

Choudhary D, Bhattacharyya S, and Joshi K conducted a double-blind, randomized, placebo-controlled trial with 52 chronically stressed adults who received 300 mg of standardized ashwagandha root extract twice daily (or placebo) for 8 weeks.^[6] Secondary efficacy measures included Oxford Happiness Questionnaire, Three-Factor Eating Questionnaire, serum cortisol, body weight, and BMI.

The ashwagandha group showed statistically significant improvements in body weight and BMI versus placebo. However:

• The population was specifically chronically stressed — a group where cortisol-driven hyperphagia is the proposed mechanism.
• The absolute weight change was modest.
• The food craving questionnaire also improved — suggesting the weight effect was mediated by reduced stress-driven eating, not a direct metabolic action.
• n = 52 is a small study.

A 2023 trial showing a null primary outcome

Smith SJ, Lopresti AL, and Fairchild TJ (PMID 37740662, published in Journal of Psychopharmacology) conducted a 12-week RCT in overweight or mildly obese adults (n = 67 completers) with self-reported stress.^[11] Participants received 200 mg of ashwagandha root extract (Witholytin) twice daily.

The key finding: supplementation with ashwagandha was associated with a significant reduction in stress based on the Perceived Stress Scale — but the improvements were not significantly different from placebo (p = 0.867) on the primary outcome. There was a significant fatigue reduction vs placebo on the Chalder Fatigue Scale. This trial illustrates the heterogeneity of the ashwagandha evidence base — positive results are not universal.

Magnitude comparison with GLP-1s

To provide context: STEP-1 (PMID 33567185) found −14.9% mean body weight reduction with semaglutide at Week 68.^[1] SURMOUNT-1 (PMID 35658024) found −20.9% with tirzepatide 15 mg at Week 72.^[2] The stress-mediated weight effect of ashwagandha in the Choudhary 2017 trial was a modest secondary outcome in a small stressed population. These are not comparable interventions. Ashwagandha is not an anti-obesity agent.

The correct framing for a GLP-1 patient considering ashwagandha: it is a cortisol/stress-management tool with some evidence behind it, not an additive weight-loss agent. If it reduces cortisol-driven stress eating on top of GLP-1 appetite suppression, that is a plausible mechanism — but do not expect it to amplify the GLP-1 weight-loss curve meaningfully. The safety profile (hepatotoxicity, thyroid effects) should drive the decision, not weight-loss expectations.

Sedation: ashwagandha's sleep-inducing properties and compounding GLP-1 fatigue

The species name somnifera is Latin for “sleep-inducing.” This is not coincidental — ashwagandha has genuine sedative-adjacent properties documented in RCTs.

Langade D, Kanchi S, Salve J, Debnath K, and Ambegaokar D (PMID 31728244) randomized 60 patients with insomnia and anxiety to 300 mg of ashwagandha root extract twice daily (600 mg/day total) or placebo for 10 weeks.^[10] Sleep actigraphy showed significant improvements in sleep onset latency, total sleep time, sleep efficiency, and wake-after-sleep-onset in the ashwagandha group. This is a beneficial effect for patients with chronic stress-related insomnia — but it also means daytime drowsiness is a real possibility if ashwagandha is taken during the day.

For GLP-1 users managing fatigue, the interaction is worth planning around:

• Take ashwagandha at bedtime rather than morning or midday to redirect the sedative effect toward sleep quality rather than daytime drowsiness.
• GLP-1 fatigue is most prominent during the titration phase and in the first weeks after a dose escalation. If you are actively managing fatigue on a GLP-1, consider delaying ashwagandha until the titration period stabilizes.
• The NIH ODS notes that drowsiness is among the common side effects of ashwagandha: “Common side effects are mild and include stomach upset, loose stools, nausea, and drowsiness.”^[13]
• Loose stools from ashwagandha compound the GI side effects that Wegovy, Ozempic, Zepbound, and Mounjaro all produce during titration (nausea, diarrhea). Time ashwagandha introduction after the GLP-1 dose has been tolerated for at least 4 weeks.

If drowsiness is unacceptable on a full 600 mg/day dose, some patients tolerate 300 mg/day at bedtime with a meaningful reduction in daytime sedation while retaining some stress and sleep benefit. Evidence for lower-dose efficacy exists (the Lopresti 2019 trial used 240 mg/day with positive cortisol outcomes).

What NIH says about ashwagandha: the Office of Dietary Supplements fact sheet

The NIH Office of Dietary Supplements maintains a health professional fact sheet on ashwagandha at ods.od.nih.gov/factsheets/Ashwagandha-HealthProfessional/. The following passages are verbatim from this NIH publication, which is regularly reviewed and represents the U.S. government's summary of the evidence base.^[13]

Verbatim — NIH ODS Ashwagandha Fact Sheet for Health Professionals:

On efficacy for stress and anxiety: “Research suggests that ashwagandha extracts may lower stress, anxiety, and cortisol levels. [A 2021 systematic review of 7 studies in 491 adults] found that ashwagandha significantly reduced stress and anxiety levels (subjectively measured by validated rating scales), reduced sleeplessness and fatigue, and reduced serum cortisol levels (a stress hormone) when compared with placebo. In several studies, the benefits appeared to be greater with doses of 500 to 600 mg/day than with lower doses.”

On common side effects: “Common side effects are mild and include stomach upset, loose stools, nausea, and drowsiness. Increased heart rate variability has also been reported. Evidence on the safety of using ashwagandha over many months or years is lacking.”

On liver injury: “There are a few reports of more serious side effects associated with ashwagandha use, including adverse effects on liver function. [Five cases] experienced signs of liver injury, such as jaundice, pruritus, nausea, lethargy, abdominal discomfort, and hyperbilirubinemia. In these cases and others, the conditions of the individuals improved over time after they stopped taking the supplement.”

On thyroid effects: “Some research suggests that ashwagandha might affect thyroid function. [A trial in 50 subclinical hypothyroid patients] found that ashwagandha root extract, at a dose of 300 mg twice daily for 8 weeks, lowered serum thyroid-stimulating hormone (TSH) and increased triiodothyronine (T3) and T4 levels compared with placebo. Three case reports have also described thyrotoxicosis in women who were taking ashwagandha extract. Discontinuing ashwagandha resolved the symptoms of thyrotoxicosis in all three cases. These findings suggest that ashwagandha might interact with thyroid hormone medications.”

On pregnancy: “Some experts advise against the use of ashwagandha by women who are pregnant and by men with hormone-sensitive prostate cancer.”

The NIH ODS also notes: “Evidence on the safety of using ashwagandha over many months or years is lacking.” This absence-of-long-term-data point is relevant for GLP-1 users who may be on their medication for years. Short-term cortisol trials (6–12 weeks) do not speak to safety over a 2-year GLP-1 treatment course.

Dose, form, and brand quality: what to look for

KSM-66 vs Sensoril — the two most-studied extracts

Most ashwagandha RCTs use one of two standardized root extracts:

• KSM-66 (by Ixoreal Biomed) — full-spectrum root-only extract, standardized to a minimum 5% withanolides. Used in Chandrasekhar 2012 and Choudhary 2017. The most studied extract in cortisol and stress trials.
• Sensoril (by Natreon) — root and leaf extract, standardized to 10% withanolides + 32% oligosaccharides. Used in Lopresti 2019 (Shoden, a related Arjuna Natural extract) and other trials. Slightly higher withanolide content per gram.

The evidence does not conclusively favor one extract over the other for cortisol reduction. Both have credible RCT data. Generic bulk ashwagandha powders sold as “1000mg Organic Ashwagandha” with no standardized extract disclosure have no comparable trial evidence and no guarantee of withanolide content.

Evidence-based dose range

The dose range with consistent positive cortisol-reduction data is 300–600 mg/day of standardized extract (KSM-66 or equivalent), divided into one or two doses. Higher doses (1000+ mg/day) have not been shown to outperform the 500–600 mg range for stress outcomes and have been associated with more GI side effects.

Third-party testing matters for YMYL supplement safety

The FDA does not pre-approve dietary supplements for safety or efficacy. A key finding from the Philips 2023 case series (PMID 37756041) was that chemical analysis of some implicated products confirmed natural phytochemicals without adulteration — meaning verified ashwagandha products caused the liver injury. For non-verified products, the contamination risk is additional and on top of the inherent risk.

Look for independent certification on the supplement label:

• NSF International Certified for Sport — tests for label accuracy, contaminants, and banned substances.
• USP Verified — confirms identity, potency, and purity testing.
• Informed Sport / Informed Choice — batch-testing standard.

Absent one of these marks, the product's withanolide content, identity, and freedom from contamination cannot be assumed. This is not a minor caveat for a supplement with a LiverTox Likelihood Score B.

What to tell your prescriber

GLP-1 prescribers are increasingly familiar with patients who take adaptogenic supplements. Here is how to structure the conversation:

• “I'm considering adding ashwagandha for stress and cortisol management. I'm aware there are documented liver injury case reports — can you check my recent ALT/AST and confirm it's safe given my liver history?”
• If you are on levothyroxine: “I've read that ashwagandha can raise T3 and T4. Can we check a TSH before I start and plan a recheck at 8 weeks?”
• If you have any liver disease, hepatic steatosis (fatty liver), elevated liver enzymes, or a history of alcohol use: “I know the NIH LiverTox database says ashwagandha should be avoided in advanced liver disease — given my history, is this supplement appropriate for me?”
• “I plan to start at 300 mg/day at bedtime to limit daytime sedation while I'm on [Wegovy / Zepbound / Ozempic / Mounjaro] and managing GI side effects from titration.”
• “I will stop immediately and call if I develop jaundice, dark urine, or significant fatigue — and I won't restart it.”

There is no FDA-labeled contraindication to ashwagandha supplementation in any GLP-1 prescribing information — but the LiverTox B classification and the thyroid-elevation data are clinically meaningful, and your prescriber needs the full picture.

Related research

• Creatine on GLP-1: lean mass preservation, hydration, and combined use evidence — companion article in the supplement-on-GLP-1 vertical. Covers creatine pharmacokinetics (no interaction per FDA Section 7), SURMOUNT-1 DXA body composition data, kidney safety considerations, and loading vs maintenance dosing during GLP-1 titration. Read alongside this article for a complete picture of the supplement landscape.
• GLP-1 fatigue: mechanisms and management — covers the five mechanisms behind GLP-1-related fatigue including caloric restriction energy gaps, lean-mass loss, and dehydration. Relevant because ashwagandha's sedative properties can compound GLP-1 fatigue during titration — includes a cross-reference to timing considerations.
• Stress, cortisol, and food noise: the HPA-axis and GLP-1 evidence — covers the broader cortisol and stress-eating mechanism with verified PMIDs on the Epel 2000 visceral fat data, Björntorp 2001 HPA-axis review, Spiegel 2004 sleep/leptin/ghrelin trial, and the documented food noise reduction with semaglutide.
• GLP-1 side effects: questions answered — Q&A hub covering nausea, fatigue, hair loss, and supplement compatibility questions on GLP-1 therapy.