Cortisol Support

Best-in-class: Phytisone

Thorne Phytisone. Per two-capsule serving: vitamin C 250 mg, KSM-66 ashwagandha extract 150 mg, pantothenic acid 100 mg, Asian ginseng root extract 75 mg at 8% ginsenosides, eleuthero extract 75 mg, ginger extract 50 mg, licorice 25 mg at 12% glycyrrhizic acid, thiamine 24 mg, astragalus root extract 14 mg, pyridoxal 5-phosphate 6.8 mg and zinc picolinate 2 mg, taken one to two times daily. It contains no adrenal glandular of any kind.

How Cortisol Support actually works

An adaptogen-and-cofactor formula aimed at the axis and at the acute stress response rather than at the gland, which is the more defensible target since the problem is usually rhythm rather than output. KSM-66 ashwagandha at 150 mg is the component with the cortisol trial behind it; Asian ginseng, eleuthero, astragalus and licorice sit beside it, and the pantothenic acid, thiamine, B6, vitamin C and zinc are there as cofactors of steroidogenesis rather than as actives in their own right.

Where to get Cortisol Support

The evidence for Cortisol Support

Graded by what exists behind each claim.

✅ Clinically validated

• Adaptogenic components have RCT support for stress/cortisol modulation; blend-level trials limited.
• Provides adrenal cofactors (vitamin C, B5) used heavily under stress.

📊 Correlative data

• Chronic stress and HPA dysregulation track with fatigue and poor recovery.

🧪 Theoretical / extrapolated benefits

• The 'adrenal fatigue' model is debated — treat benefits as supportive, not a diagnosis fix.

How to read these tiers: they say how much human evidence exists, not how well something works — and ✗ flags harm, never a disappointing trial. How the evidence tiers work →

What Cortisol Support actually does

First, what is actually in it — because the card on this site describes a different product. The most recent Phytisone label filed with the NIH Dietary Supplement Label Database lists, per two-capsule serving: vitamin C 250 mg, thiamine 24 mg, pyridoxal 5-phosphate 6.8 mg, pantothenic acid 100 mg, zinc picolinate 2 mg, KSM-66 ashwagandha extract 150 mg, Asian ginseng root extract 75 mg standardized to 8% ginsenosides, eleuthero extract 75 mg at 0.5% eleutherosides, ginger extract 50 mg at 5% gingerols, astragalus root extract 14 mg, and licorice 25 mg standardized to 12% glycyrrhizic acid, taken two capsules one to two times daily NIH 2023. There is no adrenal glandular in it, and no phosphatidylserine, holy basil or rhodiola. Everything below is written against that list.

The axis, at the steps that have names. Corticotropin-releasing hormone from the hypothalamic paraventricular nucleus drives ACTH from pituitary corticotrophs; ACTH binds MC2R on the adrenal zona fasciculata; StAR ferries cholesterol into the mitochondrion; CYP11A1 cleaves its side chain; and CYP17A1, 3-beta-HSD, CYP21A2 and CYP11B1 finish the job as cortisol. Cortisol then shuts the loop off through the glucocorticoid receptor at pituitary and hypothalamus. There are therefore three completely different places a supplement could act — make less, clear it faster, or feel it less — and a product called Cortisol Support does not say which it claims.

Ashwagandha is the only ingredient here with placebo-controlled human cortisol data, and it acts on the top of the axis. Withanolides are proposed to damp the central drive rather than the gland, and the measured endpoint in the trial that made this ingredient's name was serum cortisol: 64 adults with chronic stress, 300 mg of a high-concentration full-spectrum root extract twice daily for 60 days, serum cortisol substantially reduced at P = 0.0006 and every stress scale improved at P < 0.0001 Chandrasekhar 2012. That is a genuine result at the endpoint the product is named after.

Licorice acts at the opposite end, and it does the opposite thing. Glycyrrhetinic acid inhibits 11-beta-hydroxysteroid dehydrogenase type 2, the enzyme that converts cortisol into inactive cortisone inside mineralocorticoid target tissue. In seven normal subjects given liquorice, sodium retention was accompanied by a significant change in cortisol metabolism indicating 11-beta-HSD inhibition — a failure of renal cortisol-to-cortisone conversion leaving high intrarenal cortisol to act on type 1 mineralocorticoid receptors Stewart 1987. Congenital deficiency of the same enzyme produces the syndrome of apparent mineralocorticoid excess, and the pharmacology of licorice is now written up as a spectrum from pseudohyperaldosteronism to therapeutic use Sabbadin 2019. Read that carefully: licorice does not lower cortisol. It protects cortisol from being switched off in tissue. An ingredient that prolongs cortisol's local action sits in a product sold to reduce it.

Vitamin C and pantothenic acid are substrate arguments, and they should be labeled as such. Pantothenic acid is the precursor of coenzyme A, and every acyl transfer in steroidogenesis — including the cholesterol supply that feeds it — runs through CoA; the adrenal cortex also holds one of the highest ascorbate concentrations of any tissue, and ascorbate is co-secreted with cortisol on ACTH stimulation and is a cofactor for dopamine beta-hydroxylase in the medulla. Both are real biochemistry. Neither is a demonstration that adding 100 mg or 250 mg NIH 2023 changes cortisol output in somebody who is not deficient, and no trial in this file tested it.

And the model the category is named for has been systematically reviewed. Searching for adrenal fatigue, adrenal burnout, hypoadrenia and cortisol-plus-exhaustion returned 3,470 articles, of which 58 met criteria — 33 in healthy individuals and 25 in symptomatic patients — and the finding was almost systematically conflicting results, with poor-quality fatigue assessment and cortisol methodology not endorsed by endocrinologists. The conclusion was that adrenal fatigue is not a substantiated medical condition Cadegiani 2016. That does not mean stress does not wreck people. It means the mechanism this product's category invokes has been looked for at scale and not found.

Cell, rodent, human — and where it stops

There is no blend-level trial. Not one. Everything below belongs to a single ingredient at a dose that is usually not the dose in the capsule, and the arithmetic is the point of this section.

Ashwagandha, dose against dose. The cortisol trial used 300 mg twice daily — 600 mg/day — for 60 days Chandrasekhar 2012. The insomnia and anxiety trial used the same regimen for 10 weeks and reported sleep onset latency of 29.00 ± 7.14 minutes against 33.94 ± 7.65 on placebo (p = 0.019) and sleep efficiency rising from 75.63 to 83.48 against 75.14 to 79.68 Langade 2019. Phytisone carries 150 mg per serving, at one to two servings a day NIH 2023: 150 to 300 mg/day, a quarter to a half of the trial dose. Nobody has tested 150 mg against placebo for cortisol. Taking the label's maximum gets you to half.

And the two ashwagandha trials that measured cortisol disagree. A 16-week randomized crossover in overweight men aged 40 to 70, using a different standardized extract delivering 21 mg of withanolide glycosides a day, found DHEA-S 18% higher (p = .005) and testosterone 14.7% higher (p = .010) than placebo — and no significant between-group difference in cortisol, nor in estradiol, fatigue or vigor Lopresti 2019. So one trial finds serum cortisol falling at 600 mg/day of one extract Chandrasekhar 2012 and another finds salivary cortisol unmoved at a much smaller withanolide dose of a different extract, while the androgens move instead. Different extracts, different doses, different sampling media, different answers. That is the actual state of the evidence for the flagship ingredient.

Licorice, dose against threshold, and this one is reassuring. Twenty-five milligrams standardized to 12% glycyrrhizic acid is 3 mg of glycyrrhizic acid per serving — at most 6 mg a day at the label's maximum NIH 2023. The intake at which regulators set a guidance ceiling for glycyrrhizic acid is around 100 mg a day Sabbadin 2019, so this product delivers somewhere between a sixteenth and a thirty-third of it. The 11-beta-HSD2 mechanism is real Stewart 1987; at this dose it is not the thing to worry about, and saying so with the arithmetic is more useful than the reflex licorice warning.

The rest of the botanicals are at doses no trial has used. Asian ginseng 75 mg at 8% ginsenosides is 6 mg of ginsenosides; eleuthero 75 mg at 0.5% eleutherosides is 0.375 mg; ginger 50 mg at 5% gingerols is 2.5 mg; astragalus is 14 mg NIH 2023. Ginseng and eleuthero trials are conventionally run at several hundred milligrams of extract, and astragalus work is done in grams. These are not small doses of studied interventions; they are quantities chosen so the ingredient can appear on a label.

So the specific obstacle here is arithmetic rather than biology. On every other page in this cohort the failure is a gut wall or a missing trial. Here the mechanism is real, the trial exists, and the bottle contains a fraction of what the trial used, spread across nine other things at fractions of their own. A blend cannot inherit an ingredient's evidence at a quarter of its dose, and this one is asked to do that ten times over.

Cortisol Support — which form, and does it matter

The extract name is the only ashwagandha specification worth reading, and this label does give it. KSM-66 NIH 2023 is a root-only, water-based extract standardized to withanolides. That matters because the human trials in this file used three different preparations: a high-concentration full-spectrum root extract at 600 mg/day for cortisol Chandrasekhar 2012, the same regimen for sleep Langade 2019, and a different standardized extract dosed by withanolide glycoside content — 21 mg a day — for the hormone study Lopresti 2019. Two of those describe the dose in milligrams of extract and one in milligrams of active. They cannot be converted into each other, which is why ‘600 mg of ashwagandha’ is not a specification.

Root versus whole plant is the one substitution that changes the molecule. Ashwagandha leaf is richer in withaferin A, a highly cytotoxic withanolide, and the traditional and trialed material is root. A label that says only ‘Withania somnifera extract’ without naming the plant part has not told you which chemistry you are buying, and the safety file below McIntyre 2026 is a reason to care.

The vitamin forms here are the good kind and worth crediting. B6 is supplied as pyridoxal 5-phosphate rather than pyridoxine hydrochloride, which skips the hepatic phosphorylation step; zinc is picolinate; pantothenic acid is calcium pantothenate NIH 2023. None of that makes the product work, but it is the difference between a formulator who thought about absorption and one who bought the cheapest powder.

Two label facts to weigh before buying. The zinc is 2 mg per serving NIH 2023 — a fifth of a typical daily intake and nothing like a corrective dose, so if zinc status is the reason you are here, this is not the product. And the serving is two capsules, one to two times daily, meaning the label's own range spans a two-fold difference in every ingredient. Which end of that range you take determines whether you are at a quarter or a half of the ashwagandha trial dose Chandrasekhar 2012, and nobody tells you to take the top of it.

What would have to be true, and how you would know it was not

1. cortisol, drawn properly, and the honest expectation is nothing. Morning serum cortisol between 8 and 9 a.m., same hour both times, before and at eight weeks on the label's maximum dose. Predict no change. The trial that moved cortisol used 600 mg/day Chandrasekhar 2012; the label maximum is 300 mg/day NIH 2023; and a second ashwagandha trial with a cortisol endpoint found no between-group difference at all Lopresti 2019. Single morning cortisol also swings by tens of percent day to day, which is why the review of this whole field found conflicting results across 58 studies Cadegiani 2016.

2. The prediction that is more likely to come true than the one on the label. Predict dhea-s and total-testosterone rise before cortisol falls. In the one trial that measured all four, DHEA-S rose 18% and testosterone 14.7% while cortisol and estradiol did not move Lopresti 2019. If that is what ashwagandha does, then the marker that reports whether this product is working is an androgen, not a glucocorticoid — which is the opposite of what the box says and is testable on the same blood draw.

3. tsh and free-t4, and this is the prediction that matters most for safety. Ashwagandha root extract at 600 mg/day for eight weeks significantly improved TSH (p < 0.001), T3 (p = 0.0031) and T4 (p = 0.0096) in 50 people with subclinical hypothyroidism Sharma 2018 — that is a real thyroid effect, in the direction of more thyroid hormone. Predict TSH drifts down. In somebody hypothyroid and untreated that might be welcome; on levothyroxine it is a reason the dose may need revisiting, and in hyperthyroidism it is the wrong direction entirely. Draw TSH at baseline and twelve weeks.

4. Potassium and blood pressure, predicted flat, with the arithmetic that says why. Six milligrams of glycyrrhizic acid a day at the label maximum NIH 2023 against a roughly 100 mg/day guidance ceiling Sabbadin 2019 predicts no change in serum potassium and no change in blood pressure. The falsifier is stacking: add licorice tea, a second adrenal blend and a liquorice confection and the total can reach the range where 11-beta-HSD2 inhibition shows up as a low potassium and a raised blood pressure Stewart 1987. If potassium falls, look at everything you are taking rather than at this bottle alone.

5. alt and ast, drawn because of a live signal. Predict unchanged. Ashwagandha-associated liver injury has now been reviewed as a clinical entity McIntyre 2026, so a baseline and a twelve-week repeat is proportionate rather than paranoid — and it converts a scary headline into a number you can act on.

6. And the read-out that is not a blood test. The sleep trial's endpoints were sleep onset latency and sleep efficiency by actigraphy, and it moved them at 600 mg/day: 29.0 minutes to sleep against 33.9 on placebo Langade 2019. If you are going to score anything on this product, score time-to-sleep from a wearable across a fortnight before and a fortnight at week eight. It is more sensitive than a morning cortisol and it is free.

What nobody has tested yet

Nobody has tested this product. There is no trial of Phytisone, or of any blend with this composition NIH 2023. Eleven ingredients, one of which has real cortisol evidence at twice the dose supplied, and no study of the combination at any dose. That is not unusual for a blend; it is worth stating because the card, the reviews and the price all imply otherwise.

Nobody has tested 150 mg of ashwagandha for cortisol. The trials are at 600 mg/day Chandrasekhar 2012 Langade 2019 Sharma 2018. A dose-ranging study — 150, 300 and 600 mg against placebo with serum cortisol and a stress scale — would tell every buyer of every ashwagandha blend whether the smaller doses do anything, and it has never been published.

Nobody has reconciled the two cortisol results. One extract at 600 mg/day lowered serum cortisol Chandrasekhar 2012; another at 21 mg of withanolide glycosides did not move salivary cortisol but raised DHEA-S and testosterone Lopresti 2019. Extract, dose, matrix and population all differ, so any of them could explain it. A head-to-head with both extracts, both sampling media and one population is the obvious study and nobody has funded it.

Nobody knows whether the cofactors do anything. Whether 100 mg of pantothenic acid or 250 mg of vitamin C NIH 2023 alters cortisol output, the cortisol awakening response or the diurnal slope in a replete adult has not been tested. Both are cheap, both are safe, and the experiment is a fortnight of salivary sampling — the measure the field's own review found most used Cadegiani 2016 — in thirty people.

Cortisol Support — its own safety story, not its category's

The one to take seriously is the liver, and it is specific to the lead ingredient. Ashwagandha-associated liver injury has been characterized well enough to warrant a scoping review of its clinical features and safety implications McIntyre 2026. It is uncommon, it is idiosyncratic, and the pattern reported is typically cholestatic with jaundice appearing after weeks to months rather than days. Dark urine, pale stools, itching or yellow eyes on an ashwagandha-containing product are a same-week medical problem and a reason to stop, not to reduce the dose.

The thyroid interaction is the one this blend owns and nobody prints. Ashwagandha at 600 mg/day significantly moved TSH, T3 and T4 in subclinical hypothyroidism Sharma 2018. A supplement that can shift thyroid indices is a supplement that interacts with levothyroxine, carbimazole and methimazole — and with the monitoring, since a TSH drawn during an unannounced course of ashwagandha will be interpreted as a dose problem. Tell whoever manages your thyroid that you are taking it.

The licorice risk is real and this dose is not it — but stacking is. 11-beta-HSD2 inhibition causes sodium retention, potassium loss and hypertension Stewart 1987 Sabbadin 2019, and 6 mg/day of glycyrrhizic acid NIH 2023 is far below where that happens. Anyone already taking a second adrenal or digestive blend containing licorice, drinking licorice tea, or on a potassium-wasting diuretic should add the sources up rather than assume each is negligible, because the mechanism does not care which bottle the glycyrrhizin came from.

The diagnostic risk is the biggest one on the page. Genuine cortisol excess and genuine cortisol deficiency both present as fatigue and both are missed for years. Cushing's syndrome brings central weight gain, purple striae, proximal muscle weakness, new diabetes and new hypertension; Addison's brings weight loss, salt craving, hyperpigmentation, low sodium and a collapse under physical stress that can kill. The systematic review of this space found the cortisol methodology most used in the ‘adrenal fatigue’ literature is not the methodology endocrinologists endorse Cadegiani 2016, which is precisely how a real diagnosis gets managed for two years with a blend.

Who should leave this one alone. Anyone pregnant or breastfeeding — none of the eleven ingredients NIH 2023 has pregnancy safety data worth the name. Anyone on levothyroxine or antithyroid medication without telling their prescriber Sharma 2018. Anyone with existing liver disease McIntyre 2026. And anyone whose cortisol has actually been measured as abnormal in either direction, for whom this is not a treatment and is a delay.

Sources read for this page

• NIH DSLD. Phytisone (Thorne) — Supplement Facts, DSLD label ID 284254. NIH Dietary Supplement Label Database, label recorded 2023
• Chandrasekhar K, et al. A prospective, randomized double-blind, placebo-controlled study of safety and efficacy of a high-concentration full-spectrum extract of ashwagandha root in reducing stress and anxiety in adults. Indian Journal of Psychological Medicine, 2012 · PMID 23439798
• Lopresti AL, et al. A Randomized, Double-Blind, Placebo-Controlled, Crossover Study Examining the Hormonal and Vitality Effects of Ashwagandha (Withania somnifera) in Aging, Overweight Males. American Journal of Men's Health, 2019 · PMID 30854916
• Langade D, et al. Efficacy and Safety of Ashwagandha (Withania somnifera) Root Extract in Insomnia and Anxiety: A Double-blind, Randomized, Placebo-controlled Study. Cureus, 2019 · PMID 31728244
• Sharma AK, et al. Efficacy and Safety of Ashwagandha Root Extract in Subclinical Hypothyroid Patients: A Double-Blind, Randomized Placebo-Controlled Trial. The Journal of Alternative and Complementary Medicine, 2018 · PMID 28829155
• McIntyre D, et al. Ashwagandha (Withania somnifera)-Associated Liver Injury: A Scoping Review of Clinical Characteristics and Safety Considerations. Cureus, 2026 · PMID 42367407
• Stewart PM, et al. Mineralocorticoid activity of liquorice: 11-beta-hydroxysteroid dehydrogenase deficiency comes of age. Lancet 1987 · PMID 2889032
• Sabbadin C, Bordin L, Dona G, et al. Licorice: From Pseudohyperaldosteronism to Therapeutic Uses. Frontiers in Endocrinology 2019 · PMID 31379750
• Cadegiani FA, et al. Adrenal fatigue does not exist: a systematic review. BMC Endocrine Disorders 2016 · PMID 27557747

How you would know if it worked

Cortisol Support — safety & side effects

Bloodwork to run alongside Cortisol Support

Baseline first, then again at 8–12 weeks.

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Cortisol Support — frequently asked questions

What Cortisol Support is used for

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