Deglycyrrhizinated Licorice
Deglycyrrhizinated Liquorice
Deglycyrrhized Liquorice
DGL Licorice

---
canonical_name: DGL
alternate_names: Deglycyrrhizinated Licorice, Deglycyrrhizinated Liquorice, Deglycyrrhized Liquorice, DGL Licorice
canonical_topic: DGL for Health & Longevity
short_topic_lc: dgl
creation_date: 2026-0622-0107
creator_ai_fullname: Opus 4.8
ep_keywords:
---

# DGL for Health & Longevity

Evidence Review created on 06/22/2026 using [AI4L](https://github.com/forever-healthy/AI4L) / Opus 4.8

**Also known as:** Deglycyrrhizinated Licorice, Deglycyrrhizinated Liquorice, Deglycyrrhized Liquorice, DGL Licorice

## Motivation

DGL is a processed form of licorice root in which most of a compound called glycyrrhizin has been removed. Whole licorice has been used for thousands of years to soothe the stomach, but glycyrrhizin can raise blood pressure and disturb the body's salt and water balance when taken regularly. Removing it leaves behind the plant's soothing and protective parts while stripping away the main safety concern. The result is a chewable or powdered supplement taken mainly to calm the digestive tract.

For most of the twentieth century, before modern acid-blocking drugs existed, DGL was studied as a treatment for stomach and small-intestine ulcers, and it remains a popular self-care option for heartburn, indigestion, and recurring mouth ulcers. It is thought to work by helping the lining of the gut produce more of its own protective mucus rather than by blocking acid.

This review examines what the evidence says about DGL's benefits and risks, the quality of that evidence, how it is typically used, and where the most meaningful uncertainties remain.

**[Benefits](#expected-benefits) - [Risks](#potential-risks--side-effects) - [Protocol](#therapeutic-protocol) - [Conclusion](#conclusion)**

## Recommended Reading

This section lists high-quality, high-level overviews of DGL and licorice in digestive health, drawn from recognized experts and clinical literature.

* [Get Rid of Heartburn and GERD Forever in Three Simple Steps](https://chriskresser.com/get-rid-of-heartburn-and-gerd-forever-in-three-simple-steps/) - Chris Kresser

This functional-medicine overview situates DGL within a broader gut-restoration approach for reflux, explaining its proposed role in supporting the mucosal lining rather than suppressing acid. It is a useful practitioner perspective on how DGL is positioned in integrative protocols.

* [Healthy Ways To Stop Acid Reflux](https://www.lifeextension.com/Magazine/2017/2/Heartburn-Relief-Without-Drugs/Page-01) - Michael Downey

This article reviews non-drug options for reflux and indigestion, including DGL, and describes the proposed mucosal-protective mechanism in accessible terms. It gives a consumer-facing summary of why the deglycyrrhizinated form is preferred over whole licorice.

* [Deglycyrrhizinized liquorice in duodenal ulcer](https://pubmed.ncbi.nlm.nih.gov/5096890/) - Whiting & Thomson, 1971

This early controlled report documented endoscopic healing of chronic duodenal ulceration with DGL tablets, one of the foundational primary studies that established DGL's reputation in ulcer care. It is valuable for understanding the historical evidence base on its own terms.

* [Clinical trial of deglycyrrhizinized liquorice in gastric ulcer](https://pubmed.ncbi.nlm.nih.gov/4889526/) - Turpie et al., 1969

This early controlled trial assessed DGL in gastric ulcer and reported on both efficacy signals and tolerability, including the absence of the salt-retention effects seen with whole licorice. It anchors the original clinical case for the deglycyrrhizinated form.

* [A Review of the Pharmacological Efficacy and Safety of Licorice Root from Corroborative Clinical Trial Findings](https://pubmed.ncbi.nlm.nih.gov/31874059/) - Kwon et al., 2020

This narrative review summarizes licorice's pharmacology and clinical effects across digestive, oral, and other systems, and clearly explains how glycyrrhizin drives the mineralocorticoid-like risks that deglycyrrhization is intended to avoid. It provides essential context for interpreting DGL safety.

*Note: No dedicated DGL content from Rhonda Patrick, Peter Attia, or Andrew Huberman could be located; their platforms return only passing or absent mentions, so the remaining slots were filled with qualifying primary research and a narrative review.*

## Grokipedia

* [Deglycyrrhizinated licorice](https://grokipedia.com/page/Deglycyrrhizinated_licorice)

This Grokipedia entry provides a general-reference overview of DGL, covering its preparation, proposed digestive uses, and the rationale for removing glycyrrhizin. It is a convenient starting orientation but is not a substitute for the clinical sources cited elsewhere in this review.

## Examine

* [Licorice](https://examine.com/supplements/licorice/)

This Examine page compiles the human evidence on licorice and its forms, including deglycyrrhizinated licorice, with attention to dosing, effectiveness, and safety. It is a rigorously sourced reference for cross-checking specific claims about DGL.

## ConsumerLab

* [Licorice and DGL Supplements, Candies, and Tea Review](https://www.consumerlab.com/reviews/dgl-licorice-root-supplement-tea-candy/licorice/)

This ConsumerLab review independently tests licorice and DGL supplements, candies, and teas, reporting measured glycyrrhizin content alongside quality and cost comparisons. It is directly useful for confirming that a product labeled deglycyrrhizinated actually has low glycyrrhizin, the central sourcing concern for DGL.

## Systematic Reviews

This section summarizes systematic reviews and meta-analyses relevant to DGL and licorice in the digestive and oral-mucosal contexts where DGL is primarily used.

* [Non-Chinese herbal medicines for functional dyspepsia](https://pubmed.ncbi.nlm.nih.gov/37323050/) - Báez et al., 2023

This Cochrane review of 41 trials assessed 27 herbal medicines for functional dyspepsia and found that *Glycyrrhiza glabra* (licorice) produced a large improvement in symptoms in a single 50-participant trial (moderate-certainty evidence). It is the most authoritative pooled appraisal touching on licorice for upper-gut symptoms.

* [Effect of polyphenol compounds on Helicobacter pylori eradication: a systematic review with meta-analysis](https://pubmed.ncbi.nlm.nih.gov/36604137/) - Wang et al., 2023

This meta-analysis of 12 randomized trials found that polyphenol compounds, including licorice, improved *Helicobacter pylori* (a stomach bacterium linked to ulcers) eradication rates when added to standard triple therapy, without increasing side effects. It is relevant because anti-H. pylori activity is one proposed contributor to licorice's ulcer benefits.

* [Topical Licorice for Aphthous: A Systematic Review of Clinical Trials](https://pubmed.ncbi.nlm.nih.gov/37786470/) - Dorsareh et al., 2023

This systematic review of six trials in 314 subjects found that topical licorice significantly reduced pain, ulcer size, and healing time in recurrent aphthous stomatitis (recurring mouth ulcers) without adverse effects. It supports the oral-mucosal use for which DGL is commonly taken as a chewable.

* [Comparative Efficacy of Therapeutic Interventions for the Management of Recurrent Aphthous Ulcers: A Systematic Review and Network Meta-Analysis](https://pubmed.ncbi.nlm.nih.gov/38035895/) - Cheng et al., 2023

This network meta-analysis of 38 trials in 2,773 patients ranked treatments for recurrent mouth ulcers and identified a licorice-containing formulation among the more effective options for reducing ulcer diameter. It places licorice's oral-ulcer effect in the context of competing therapies.

## Mechanism of Action

* **Mucosal protection over acid suppression:** DGL's proposed central action is enhancing the stomach and intestinal lining's own defenses rather than reducing acid. It is thought to increase the secretion and quality of protective mucus, prolong the lifespan of surface mucosal cells, and stimulate new cell growth in the gut wall, thereby strengthening the barrier that normally shields tissue from acid and pepsin (a digestive enzyme).

* **Prostaglandin-related pathway:** Several lines of evidence attribute DGL's protective effect to local increases in prostaglandins (hormone-like lipids that promote mucus and bicarbonate secretion and support mucosal blood flow). This contrasts with NSAIDs (non-steroidal anti-inflammatory drugs such as aspirin), which damage the gut by suppressing the same prostaglandins.

* **Anti-Helicobacter and anti-inflammatory activity:** Licorice flavonoids show activity against *Helicobacter pylori*, the bacterium responsible for most peptic ulcers, and exert anti-inflammatory and antioxidant effects on inflamed mucosa. These may contribute to ulcer healing and symptom relief, though their relative importance in DGL specifically is uncertain.

* **Why glycyrrhizin is removed:** Whole licorice's glycyrrhizin is metabolized to glycyrrhetic acid, a potent inhibitor of 11β-HSD2 (11-beta-hydroxysteroid dehydrogenase type 2, an enzyme that protects the mineralocorticoid receptor from cortisol). Inhibiting it produces a state resembling excess aldosterone (the salt-retaining hormone), causing high blood pressure, low potassium, and fluid retention. Deglycyrrhization removes this compound, separating the mucosal benefits from the salt-retention risk.

* **Competing mechanistic views:** Some pharmacological studies (e.g., on rat gastric mucosa) found that DGL had little or no effect on prostaglandin synthesis, challenging the prostaglandin hypothesis and suggesting that direct cytoprotection or other flavonoid actions may dominate. The exact mechanism therefore remains incompletely resolved.

* **Pharmacological properties:** DGL is a multi-component botanical extract rather than a single defined drug, so it has no single half-life, selectivity profile, or clearance pathway; with glycyrrhizin removed, the systemically active glycyrrhetic acid that drives whole-licorice pharmacokinetics is largely absent, and its actions are believed to be predominantly local within the gut lumen and mucosa.

## Historical Context & Evolution

* **Original use:** Licorice root has been used for millennia in traditional Chinese, Ayurvedic, Greek, and European medicine as a remedy for cough, sore throat, and digestive complaints, and as a flavoring and sweetening agent. Its use as an antacid and soother for "gastric discomfort and peptic ulcers" predates modern pharmacology.

* **Path to deglycyrrhization:** In the mid-twentieth century, whole licorice and the semi-synthetic derivative carbenoxolone were used for peptic ulcers but caused frequent salt retention, high blood pressure, and low potassium due to glycyrrhizin. Researchers developed deglycyrrhizinated licorice to retain the ulcer-healing effect while eliminating these adverse effects, and standardized preparations on experimental gastric ulcers in animals.

* **What the early research found:** Controlled clinical studies from 1969 to 1982 reported endoscopic healing of gastric and duodenal ulcers with DGL tablets, in some series with healing rates and mucosal normalization comparable to mucosal-protective drugs of the era. Pharmacological work in rats showed DGL protected against aspirin-induced mucosal damage and accelerated renewal of stomach epithelium, and that DGL combined with cimetidine (an early acid-reducing drug) gave greater protection than low doses of either alone.

* **Evolution of standing:** With the arrival of H2 blockers (histamine-blocking acid-reducing drugs), proton pump inhibitors, and H. pylori eradication therapy from the 1980s onward, interest in DGL as a primary ulcer treatment faded, and the older trials are widely viewed as methodologically limited by modern standards. Rather than being formally disproven, DGL was largely displaced by more potent, better-studied drugs; it has persisted in integrative and self-care use for reflux, indigestion, and mouth ulcers, and renewed interest in non-drug mucosal support and in licorice flavonoids keeps the question open as to what role, if any, it holds today.

## Expected Benefits

A dedicated search of clinical trials, systematic reviews, and expert sources was performed to compile the benefit profile below before writing this section.

### Medium 🟩 🟩

#### Recurrent Aphthous (Canker) Sore Relief

Licorice applied to or dissolved in the mouth appears to reduce the pain, size, and healing time of recurrent mouth ulcers. A 2023 systematic review of six randomized trials (314 subjects) reported significant benefits with no adverse effects, and a 2023 network meta-analysis of 38 trials ranked a licorice-containing formulation among the more effective options for reducing ulcer diameter. DGL chewable tablets and patches are a common practical vehicle, though most trials tested licorice extracts generally rather than DGL by name, which limits how precisely the effect can be attributed to DGL.

**Magnitude:** Faster healing (typically within 4–8 days versus longer untreated) with meaningful reductions in pain and ulcer size across trials.

#### Functional Dyspepsia Symptom Relief

DGL and licorice are taken for indigestion-type symptoms such as upper-abdominal discomfort, fullness, and early satiety. The 2023 Cochrane review of herbal medicines for functional dyspepsia found that *Glycyrrhiza glabra* produced a large symptom improvement in one 50-participant trial graded as moderate-certainty, placing it among the better-performing single herbs reviewed. The evidence is limited to small numbers of participants and short durations, and trials used various licorice preparations rather than standardized DGL.

**Magnitude:** Standardized mean difference of about −1.86 (a large effect) in the single trial of *Glycyrrhiza glabra* in the Cochrane review.

### Low 🟩

#### Peptic Ulcer (Gastric and Duodenal) Healing

The historical clinical case for DGL rests on gastric- and duodenal-ulcer healing. Controlled studies from 1969–1982 reported endoscopic healing of chronic ulcers, and animal work showed protection against aspirin-induced mucosal damage via enhanced mucus, cell turnover, and barrier function. The grade is Low because these trials are old, small, and methodologically weak by modern standards, and DGL has not been re-evaluated against contemporary acid-suppressing and H. pylori-eradication therapy, which is now the standard of care.

**Magnitude:** Older series reported ulcer healing in a majority of treated patients over several weeks; no reliable modern effect estimate exists.

#### Protection Against NSAID-Related Gastric Irritation

By strengthening mucosal defenses rather than blocking acid, DGL is proposed to blunt the gastric damage caused by aspirin and similar NSAIDs. This rests mainly on animal experiments showing DGL reduced aspirin-induced mucosal damage and on the prostaglandin-related mechanism, with limited direct human confirmation. It is presented for the proactive, risk-aware reader who may use NSAIDs and is interested in gut-lining support, not as an established preventive.

**Magnitude:** Not quantified in available studies.

### Speculative 🟨

#### Helicobacter pylori Support Alongside Standard Therapy

Licorice flavonoids show activity against *Helicobacter pylori*, and a 2023 meta-analysis found polyphenol compounds (including licorice) improved eradication rates when added to standard triple therapy. Whether DGL specifically contributes meaningfully as an add-on, and at what dose, has not been established in dedicated DGL trials; the basis is mechanistic plus indirect pooled data on licorice.

#### Soothing of Reflux and Heartburn Symptoms

DGL is widely used for reflux and heartburn on the rationale that it supports the esophageal and gastric lining rather than suppressing acid. This use is supported chiefly by mechanistic reasoning and practitioner experience; controlled trials of DGL specifically for gastroesophageal reflux are lacking, so the benefit remains anecdotal and mechanistic.

## Benefit-Modifying Factors

* **Genetic polymorphisms:** No genetic variants are established to predict who benefits more from DGL; as a multi-component botanical acting locally in the gut, its efficacy is not known to depend on drug-metabolizing or transporter polymorphisms (e.g., CYP (cytochrome P450, the liver's main drug-metabolizing enzymes) or ABCB1 (a gene encoding a drug-efflux transporter) variants), so no pharmacogenetic factor reliably modifies the benefit.

* **Helicobacter pylori status:** Whether a person's ulcer or dyspepsia is driven by *Helicobacter pylori* infection likely influences response; benefit may be greater when antibacterial flavonoid activity is relevant, and DGL is not a substitute for guideline eradication therapy when infection is present.

* **Baseline symptom severity and cause:** Those with mild, lining-related upper-gut symptoms may notice more benefit than those whose symptoms stem from causes DGL does not address (e.g., motility disorders or non-acid reflux). Baseline ulcer presence (confirmed by endoscopy) was the population in which the historical healing signal was seen.

* **Concurrent NSAID or irritant exposure:** People regularly exposed to aspirin, other NSAIDs, or alcohol may derive more relative benefit from a mucosal-protective agent, since DGL's proposed action targets exactly this type of injury.

* **Sex-based differences:** No reliable sex-specific efficacy differences for DGL have been established; the historical trials enrolled both sexes without reporting consistent sex effects, so any difference remains unquantified.

* **Age-related considerations:** Older adults, who have higher background rates of ulcers, reflux, and NSAID use, are a plausible group to benefit, but they are also more likely to be on interacting medications and to have conditions requiring formal evaluation rather than self-treatment; benefit should be weighed against the need to rule out serious causes of upper-gut symptoms.

## Potential Risks & Side Effects

A dedicated search of drug-reference and clinical sources was performed to compile the side-effect profile below before writing this section.

### Low 🟥

#### Residual Glycyrrhizin and Pseudohyperaldosteronism

Although deglycyrrhization removes most glycyrrhizin, products vary and trace amounts can remain; very high or prolonged intake could still, in principle, contribute to pseudohyperaldosteronism (a salt-retention state that mimics excess of the salt-holding hormone aldosterone) seen with whole licorice. A documented case described a person who developed high blood pressure, low potassium, fainting, and dangerous heart-rhythm disturbances after ingesting large amounts of a product labeled deglycyrrhizinated licorice for years. This underscores that "deglycyrrhizinated" does not guarantee zero glycyrrhizin and that quality and dose matter.

**Magnitude:** Rare at typical doses; risk rises with large, chronic intake or poorly deglycyrrhized products. True licorice raises systolic blood pressure measurably, whereas properly deglycyrrhized DGL is expected to have a markedly smaller effect.

#### Mild Gastrointestinal Effects

As an orally taken botanical, DGL can cause minor digestive complaints such as nausea, stomach upset, or changes in bowel habits in some users. These are generally mild and self-limiting. The chewable forms also contain sweeteners and flavorings that some people tolerate poorly.

**Magnitude:** Not quantified in available studies.

### Speculative 🟨

#### Drug and Hormone Interactions via Licorice Constituents

Licorice constituents can affect potassium balance and may interact with drugs sensitive to potassium levels or with hormone-related pathways; some licorice components show mild estrogen-like activity in laboratory and animal models. With glycyrrhizin largely removed, these concerns are attenuated for DGL, but residual constituents and product variability mean interaction potential cannot be fully dismissed. The basis is mechanistic and from whole-licorice data rather than DGL-specific human trials.

#### Pregnancy and Sensitive Populations

High licorice intake in pregnancy has been linked in observational research to adverse outcomes, attributed chiefly to glycyrrhizin. Whether well-deglycyrrhized DGL carries any comparable risk is unstudied, so its safety in pregnancy, breastfeeding, and other sensitive states is unknown and rests on extrapolation from whole-licorice data.

## Risk-Modifying Factors

* **Genetic and individual sensitivity:** Some individuals are inherently more sensitive to the mineralocorticoid-like effects of licorice constituents, so even small residual glycyrrhizin may matter more for them; people with known sensitivity should be especially cautious about product quality and dose.

* **Baseline biomarkers:** Pre-existing low potassium or borderline high blood pressure raises the consequence of any residual glycyrrhizin effect; baseline blood pressure and potassium help gauge risk.

* **Sex-based differences:** No consistent sex-based difference in DGL adverse effects has been established; the estrogen-like activity of certain licorice components is a theoretical consideration more relevant to whole licorice than to DGL.

* **Pre-existing conditions:** People with high blood pressure, heart failure, kidney disease, low potassium, or heart-rhythm disorders are most vulnerable to any salt-retention effect and should regard chronic or high-dose use with particular caution.

* **Age-related considerations:** Older adults more often have hypertension, take diuretics or other potassium-affecting drugs, and have reduced physiological reserve, which amplifies the consequences of any residual glycyrrhizin effect and warrants closer attention at the older end of the target range.

## Key Interactions & Contraindications

* **Antihypertensive drugs:** Any residual glycyrrhizin can oppose blood-pressure-lowering medicines (e.g., ACE inhibitors (angiotensin-converting-enzyme inhibitors, which relax blood vessels) such as lisinopril, ARBs (angiotensin-receptor blockers, which also relax blood vessels) such as losartan, calcium channel blockers such as amlodipine). Severity: caution. Consequence: reduced blood-pressure control. Mitigation: use well-deglycyrrhized products at standard doses and monitor blood pressure.

* **Diuretics and potassium-depleting drugs:** Loop and thiazide diuretics (e.g., furosemide, hydrochlorothiazide) and stimulant laxatives can lower potassium; combined with any residual glycyrrhizin this raises the risk of dangerously low potassium. Severity: caution to avoid with high-dose use. Consequence: hypokalemia (low blood potassium causing weakness and arrhythmia). Mitigation: avoid high-dose or prolonged use; monitor potassium.

* **Digoxin:** Low potassium increases the toxicity of digoxin (a heart medication). Severity: caution. Consequence: digoxin toxicity (nausea, visual changes, dangerous arrhythmias). Mitigation: avoid potassium-lowering combinations; monitor potassium and digoxin levels.

* **Corticosteroids:** Licorice constituents can prolong and intensify corticosteroid (anti-inflammatory steroid) effects by slowing their breakdown. Severity: caution. Consequence: enhanced steroid effect and side effects. Mitigation: separate use and monitor for steroid excess; prefer well-deglycyrrhized products.

* **Over-the-counter NSAIDs and antacids:** DGL is often used alongside NSAIDs (e.g., ibuprofen, aspirin) for gut protection and alongside antacids; no harmful interaction is established, and timing DGL before meals is the usual practical approach. Severity: monitor. Consequence: none well documented.

* **Supplement interactions and additive effects:** Other potassium-affecting or blood-pressure-affecting supplements (e.g., whole licorice extract, high-dose stimulant herbs) can add to any residual glycyrrhizin effect; combining DGL with whole-licorice products is the clearest additive concern. Other mucosal-soothing supplements (e.g., slippery elm, marshmallow root, zinc-carnosine) are commonly combined without documented harm. Severity: caution for whole-licorice stacking. Consequence: additive salt retention.

* **Populations who should avoid or use only under supervision:** Those with uncontrolled hypertension, heart failure (e.g., NYHA (New York Heart Association) Class III–IV, severe symptomatic heart failure), significant kidney disease, low potassium, serious heart-rhythm disorders, and those who are pregnant or breastfeeding should avoid chronic or high-dose use given the residual glycyrrhizin uncertainty.

## Risk Mitigation Strategies

* **Choose genuinely deglycyrrhized products:** To mitigate residual-glycyrrhizin pseudohyperaldosteronism, select products specifying low glycyrrhizin content (commonly stated as under 3% or "glycyrrhizin-free"); this directly limits the salt-retention risk that whole licorice carries.

* **Keep doses standard and time-limited:** To mitigate cumulative glycyrrhizin exposure, use typical chewable doses (often 380–400 mg, one to two tablets up to three times daily before meals) and reassess after a few weeks rather than using high doses indefinitely; chronic high intake is the main driver of documented harm.

* **Monitor blood pressure and potassium with prolonged use:** To mitigate high blood pressure and low potassium, those using DGL regularly, especially older adults or those on diuretics, can check blood pressure periodically and have potassium measured if symptoms (weakness, palpitations) arise.

* **Avoid stacking with whole licorice:** To prevent additive salt retention, do not combine DGL with whole-licorice teas, candies, or extracts that retain glycyrrhizin.

* **Rule out serious causes first:** To mitigate the risk of masking a treatable or dangerous condition, persistent or alarm-feature symptoms (unintended weight loss, difficulty swallowing, vomiting blood, black stools, anemia) warrant medical evaluation rather than self-treatment with DGL.

## Therapeutic Protocol

* **Standard chewable regimen:** Leading integrative practitioners typically describe DGL as a chewable tablet of roughly 380–400 mg taken before meals, often one to two tablets two to three times daily, on the rationale that mixing with saliva activates its mucosal-soothing action. This reflects the most common practitioner-described approach rather than a regimen validated by modern trials.

* **Competing approaches:** Two main approaches exist without one being the default. The conventional path treats reflux and ulcers with acid suppression (proton pump inhibitors, H2 blockers) and H. pylori eradication; the integrative path uses DGL as a mucosal-support adjunct or alternative for milder symptoms. Each addresses a different target (acid versus mucosal defense), and the choice depends on symptom cause and severity.

* **Who popularized it:** DGL's use in integrative gut protocols has been promoted by naturopathic and functional-medicine practitioners and by consumer-health publications; the historical clinical groundwork came from mid-twentieth-century British and European ulcer researchers.

* **Best time of day:** DGL is generally taken before meals (commonly 15–20 minutes prior) and is sometimes added at bedtime for nighttime symptoms, aligning dosing with periods of symptom provocation.

* **Half-life:** As a multi-component botanical acting largely within the gut, DGL has no single defined half-life; with glycyrrhizin removed, the long-acting systemic constituent of whole licorice is largely absent, and effects are believed to be local and relatively short-lived, supporting repeated dosing around meals.

* **Single versus split dosing:** Split dosing before each main meal (and optionally at bedtime) is the typical pattern rather than a single daily dose, matching the local, meal-related rationale for its action.

* **Genetic considerations:** No pharmacogenetic markers reliably guide DGL dosing; individual sensitivity to residual licorice constituents (mineralocorticoid-like effects) is the main person-level variable and is not predicted by a defined gene test.

* **Sex-based differences:** No established sex-based differences in DGL dosing or response exist; trials have not reported consistent differences.

* **Age-related considerations:** Older adults may warrant more conservative dosing and closer blood-pressure and potassium attention, given more frequent comorbidities and interacting medications.

* **Baseline biomarkers:** Baseline blood pressure and potassium are reasonable to note before regular use, since they frame the residual-glycyrrhizin risk; no efficacy biomarker guides DGL dosing.

* **Pre-existing conditions:** Those with hypertension, heart failure, kidney disease, or low potassium should use the lowest effective dose for the shortest period, or avoid chronic use, given the salt-retention uncertainty.

## Discontinuation & Cycling

* **Lifelong versus short-term:** DGL is generally used short-term and symptomatically (for an ulcer-healing course or for episodic reflux, indigestion, or mouth ulcers) rather than as a lifelong daily supplement, in keeping with its symptom-targeted rationale and the lack of long-term safety data.

* **Withdrawal effects:** No specific withdrawal syndrome is described for DGL; stopping it is expected mainly to allow symptoms to return if the underlying cause persists.

* **Tapering:** No tapering protocol is required for DGL; it can generally be stopped directly. Whole licorice, by contrast, may warrant more caution after heavy chronic use because of its glycyrrhizin effects.

* **Cycling:** Cycling is not established as necessary for maintaining efficacy; the practical pattern is use-as-needed during symptomatic periods with breaks when symptoms resolve, which also limits cumulative residual-glycyrrhizin exposure.

## Sourcing and Quality

* **Confirm deglycyrrhization:** Look for products that state a low glycyrrhizin content (commonly under 3%) or label themselves glycyrrhizin-free, since "DGL" labeling alone does not guarantee how thoroughly glycyrrhizin was removed and residual amounts drive the main safety concern.

* **Third-party testing:** Prefer products carrying independent quality verification (e.g., NSF, USP, or equivalent third-party testing) to confirm identity, label accuracy, and absence of contaminants, as supplement quality varies widely and some marketed licorice health foods have shown inconsistent component levels.

* **Form and excipients:** Chewable tablets are the most studied practical form for upper-gut and oral use; check the sweeteners, flavorings, and fillers, which differ between brands and can affect tolerability.

* **Reputable suppliers:** Established supplement brands and reputable pharmacies that publish certificates of analysis are preferable; the historical clinical preparations were standardized extracts, and standardization remains a useful marker of quality.

## Practical Considerations

* **Time to effect:** Symptomatic soothing of reflux, indigestion, or mouth-ulcer pain may be noticed within days; the historical ulcer-healing data involved several weeks of use, so structural healing, if it occurs, is not immediate.

* **Common pitfalls:** Frequent mistakes include confusing DGL with whole licorice or licorice candy (which retain glycyrrhizin and can raise blood pressure), swallowing rather than chewing chewable forms, using high doses indefinitely, and relying on DGL for alarm-feature symptoms that need medical evaluation.

* **Regulatory status:** In the United States, DGL is sold as a dietary supplement, not an approved drug; it is not FDA-approved for treating ulcers or reflux, and licorice is recognized as a food additive in limited concentrations with warnings about excess intake.

* **Cost and accessibility:** DGL is inexpensive, widely available over the counter, and easy to access; cost is not a meaningful barrier.

## Interaction with Foundational Habits

* **Sleep:** Indirect interaction. By easing nighttime reflux and indigestion for some users, DGL taken before bed may improve sleep continuity; there is no evidence it directly alters sleep architecture, and any benefit is secondary to symptom relief.

* **Nutrition:** Direct, meal-linked interaction. DGL is taken before meals so it can coat and soothe the gut lining as food and acid arrive; it pairs naturally with reflux-friendly eating patterns (smaller meals, limiting alcohol and trigger foods). It should not be combined with whole-licorice foods or teas, which reintroduce glycyrrhizin.

* **Exercise:** No meaningful direct interaction. DGL is not known to blunt or enhance training adaptations; for the proactive reader who uses NSAIDs around heavy training, its proposed gut-lining support is the only plausible, and unproven, point of contact.

* **Stress management:** Indirect interaction. Because stress aggravates reflux and dyspepsia and may affect ulcer healing, stress-reduction practices can complement DGL's mucosal-support role; DGL itself is not established to affect cortisol or the stress response once glycyrrhizin is removed.

## Monitoring Protocol & Defining Success

Baseline assessment is worthwhile mainly to frame the residual-glycyrrhizin safety question and to characterize the symptoms being treated before starting regular DGL use.

Ongoing monitoring is light for short-term use; for prolonged or higher-dose use, blood pressure and potassium can be checked periodically (for example, at baseline, then every 3–6 months, or sooner if symptoms of salt retention appear).

| Biomarker | Optimal Functional Range | Why Measure It? | Context/Notes |
|-----------|--------------------------|-----------------|---------------|
| Blood pressure | ~110–125 / 70–80 mmHg | Detects salt-retention effect from any residual glycyrrhizin | Check at baseline and periodically with regular use; more important in older adults and those on diuretics |
| Serum potassium | 4.0–4.5 mmol/L | Low potassium (hypokalemia) is the hallmark of glycyrrhizin excess | Conventional reference range (3.5–5.0 mmol/L) is wider; functional target favors the mid-upper range; check if symptoms arise |
| Helicobacter pylori status | Negative | Identifies infection that needs guideline eradication, not self-treatment | Stool antigen or breath test; best done off acid suppressants per testing guidance |
| Symptom score (reflux/dyspepsia) | Marked reduction from baseline | Defines whether DGL is actually helping | Track via a simple symptom diary; reassess after a few weeks |

Qualitative markers help define success beyond labs:

* Reduction in heartburn, regurgitation, or upper-abdominal discomfort frequency and intensity
* Faster healing and less pain from recurrent mouth ulcers
* Improved comfort after meals and fewer nighttime symptoms
* Absence of new symptoms suggesting salt retention (unusual weakness, swelling, palpitations)

## Emerging Research

* **Fermented DGL for diabetic nerve damage:** A completed phase 2 randomized, double-blind, placebo-controlled trial [NCT07148804](https://clinicaltrials.gov/study/NCT07148804) (83 participants) tested a fermented deglycyrrhizinated licorice extract providing an amylase enzyme for early diabetic polyneuropathy (nerve damage from diabetes), reporting improved nerve conduction; this extends DGL research beyond the gut, though it uses a specialized fermented preparation. Results were published as [Massoud et al., 2026](https://pubmed.ncbi.nlm.nih.gov/41627541/).

* **Licorice plus low-dose amoxicillin for H. pylori:** A planned trial [NCT06881524](https://clinicaltrials.gov/study/NCT06881524) (374 participants) will test licorice and lotus root powder combined with low-dose amoxicillin against high-dose amoxicillin for *Helicobacter pylori* eradication; if positive, it would strengthen the case that licorice constituents meaningfully support ulcer-related infection treatment.

* **Licorice mucoadhesive films for oral lesions:** A completed phase 1/2 trial [NCT02075749](https://clinicaltrials.gov/study/NCT02075749) (60 participants) compared licorice mucoadhesive films with a topical steroid for mouth lesions, addressing pain outcomes relevant to DGL's oral-ulcer use and to delivery-format innovation.

* **Future direction — modern reflux and ulcer trials:** The clearest gap is the absence of contemporary, well-powered randomized trials of standardized DGL for reflux and peptic ulcer using endoscopic and validated symptom endpoints; such studies could either confirm or weaken the historical signal summarized in [Báez et al., 2023](https://pubmed.ncbi.nlm.nih.gov/37323050/).

* **Future direction — flavonoid mechanism and H. pylori:** Research clarifying which licorice flavonoids drive mucosal protection and anti-*Helicobacter pylori* activity, building on the pooled signal in [Wang et al., 2023](https://pubmed.ncbi.nlm.nih.gov/36604137/), could redefine DGL's role as either a useful adjunct or an inferior option versus standard care.

## Conclusion

DGL is a processed licorice extract, taken mostly as a chewable, in which the blood-pressure-raising compound glycyrrhizin has been largely removed, leaving the soothing parts of the root. It is used chiefly to calm the digestive tract, with the best current support for easing recurring mouth ulcers and indigestion-type symptoms, weaker and largely historical support for healing stomach and small-intestine ulcers, and mostly mechanism-based reasoning behind its popular use for heartburn. Its proposed action is to strengthen the gut's own protective lining rather than to block acid.

The evidence base is uneven. The clinical trials behind its reputation are old and small, and most pooled analyses studied licorice in general rather than DGL by name. Safety is its relative strength: removing glycyrrhizin removes the main risk of whole licorice, though poorly processed products or very high, long-term intake can still cause salt retention, low potassium, and raised blood pressure. Overall, DGL emerges as a low-cost, generally well-tolerated option with reasonable support for easing mouth ulcers and mild indigestion, while its value for healing stomach ulcers and relieving heartburn rests largely on older or mechanism-based evidence.

**[Top](#top) - [Benefits](#expected-benefits) - [Risks](#potential-risks--side-effects) - [Protocol](#therapeutic-protocol)**


---
canonical_name: DHEA
alternate_names: Dehydroepiandrosterone, Prasterone, Androstenolone
canonical_topic: DHEA for Health & Longevity
short_topic_lc: dhea
creation_date: 2026-0718-0041
creator_ai_fullname: Opus 4.8
---

# DHEA for Health & Longevity

Evidence Review created on 07/18/2026 using [AI4L](https://github.com/forever-healthy/AI4L) / Opus 4.8

**Also known as:** Dehydroepiandrosterone, Prasterone, Androstenolone

## Motivation

DHEA (dehydroepiandrosterone) is a hormone made mainly by the adrenal glands, the small glands that sit above the kidneys. The body uses it as a raw material to build the sex hormones testosterone and estrogen. It draws attention in the health and longevity world because blood levels of DHEA peak in a person's twenties and then fall steadily, so that by the seventies they sit at roughly ten to twenty percent of their youthful high. This steep, age-linked decline has led many to ask whether topping the hormone back up could slow some features of aging.

Interest grew because people with naturally higher DHEA levels tend, on average, to be healthier in later life, and because the hormone touches so many systems at once, including bone, mood, and the immune response. It is sold widely as an inexpensive over-the-counter supplement in some countries and treated as a regulated hormone in others.

This review examines what the evidence shows about taking DHEA to support health and longevity, weighing the measured benefits against the hormonal risks, the quality of the underlying studies, and the practical details of how it is used.

**[Benefits](#expected-benefits) - [Risks](#potential-risks--side-effects) - [Protocol](#therapeutic-protocol) - [Conclusion](#conclusion)**

## Recommended Reading

This section collects high-level, directly relevant expert commentary and lay-accessible overviews that introduce DHEA and frame its role in healthy aging.

* [Risks and Benefits of DHEA Supplementation](https://www.youtube.com/watch?v=McgzzI1DEPE) - Peter Attia

  A focused video discussion in which Peter Attia and guest Derek (More Plates More Dates) weigh the practical case for and against DHEA supplementation, including how baseline hormone status shapes who might benefit and who is unlikely to.

* [The Science of How to Optimize Testosterone & Estrogen](https://www.hubermanlab.com/episode/the-science-of-how-to-optimize-testosterone-and-estrogen) - Andrew Huberman

  A mechanistic lecture that situates DHEA within the wider network of sex-hormone regulation, explaining why the same dose can push toward testosterone in one person and toward estrogen in another depending on body fat and the aromatase enzyme.

* [What Is DHEA?](https://www.lifeextension.com/magazine/2021/12/what-is-dhea) - Chancellor Faloon

  A plain-language overview aimed at a longevity audience that summarizes the age-related decline of DHEA and the observational and trial evidence for restoring it, including effects on bone, immune function, and cardiovascular risk.

* [Q&A #9 with Dr. Rhonda Patrick](https://www.foundmyfitness.com/episodes/qa-9-dr-rhonda-patrick) - Rhonda Patrick

  A question-and-answer episode with a dedicated segment on epigenetic aging and DHEA, addressing whether supplementing the hormone meaningfully changes aging biomarkers and how it interacts with testosterone, especially in women.

* [Andropause (A.K.A. "Manopause", Male Menopause)](https://chriskresser.com/episode-14-andropause-a-k-a-manopause-male-menopause/) - Chris Kresser

  A functional-medicine discussion of age-related male hormone decline that covers DHEA among the adrenal and sex-hormone markers to assess, and takes a cautious, testing-first stance on hormone restoration.

## Grokipedia

* [Dehydroepiandrosterone](https://grokipedia.com/page/Dehydroepiandrosterone) - Grokipedia

  The Grokipedia entry provides a broad reference overview of DHEA's biochemistry, physiological roles, age-related decline, and supplement uses, useful as an orienting summary before consulting the primary clinical literature.

## Examine

* [DHEA](https://examine.com/supplements/dhea/) - Examine

  Examine's DHEA page is an independent, citation-dense synthesis of the human trial evidence, grading outcomes such as bone density, body composition, mood, and sexual function and flagging where results are weak or inconsistent.

## ConsumerLab

* [DHEA Supplement Reviews & Top Picks](https://www.consumerlab.com/reviews/dhea-supplements/dhea/) - ConsumerLab

  ConsumerLab independently tests DHEA products for label accuracy, disintegration, and contaminants, reporting large price differences for the same dose and identifying products that pass or fail quality checks.

## Systematic Reviews

The following systematic reviews and meta-analyses represent the higher tiers of evidence on DHEA, selected for relevance to healthy-aging outcomes, recency, and study size.

* [A systematic review and meta-analysis of randomized placebo-controlled trials of DHEA supplementation of bone mineral density in healthy adults.](https://pubmed.ncbi.nlm.nih.gov/31237150/) - Lin et al., 2019

  This pooled analysis of placebo-controlled trials found that DHEA produced a small but statistically significant improvement in hip and trochanter bone mineral density in older women, with little effect in men, framing DHEA as a modest skeletal support rather than a primary osteoporosis therapy.

* [A dose-response and meta-analysis of dehydroepiandrosterone (DHEA) supplementation on testosterone levels: perinatal prediction of randomized clinical trials.](https://pubmed.ncbi.nlm.nih.gov/33045358/) - Li et al., 2020

  A dose-response meta-analysis quantifying how oral DHEA raises circulating testosterone, confirming a clear dose-dependent rise that is far larger in women than in men and underpinning both the hormonal benefits and the androgenic risks discussed later.

* [Dehydroepiandrosterone for depressive symptoms: A systematic review and meta-analysis of randomized controlled trials.](https://pubmed.ncbi.nlm.nih.gov/32930419/) - Peixoto et al., 2020

  Pooling randomized trials, this review reports that DHEA moderately reduced depressive symptoms compared with placebo, while cautioning that most trials were small and heterogeneous in dose and population.

* [Dehydroepiandrosterone and Dehydroepiandrosterone Sulfate in Alzheimer's Disease: A Systematic Review and Meta-Analysis.](https://pubmed.ncbi.nlm.nih.gov/30983988/) - Pan et al., 2019

  This meta-analysis found lower circulating DHEA-S (dehydroepiandrosterone sulfate, the stable, longer-lasting circulating form of DHEA), but not DHEA itself, in people with Alzheimer's disease relative to controls, an association that motivates interest in cognitive protection but does not by itself establish that supplementation helps.

* [Association of endogenous DHEA/DHEAS with coronary heart disease: A systematic review and meta-analysis.](https://pubmed.ncbi.nlm.nih.gov/31347187/) - Wu et al., 2019

  A synthesis of observational cohorts showing that lower natural DHEA and DHEA-S levels track with higher coronary heart disease risk, supporting a biomarker relationship while leaving open whether restoring the hormone changes cardiovascular outcomes.

## Mechanism of Action

DHEA and its sulfated storage form, DHEA-S (dehydroepiandrosterone sulfate, the longer-lasting circulating reservoir of the hormone), are the most abundant steroid hormones in the human bloodstream. They are produced largely in the adrenal cortex under the control of ACTH (adrenocorticotropic hormone, the pituitary signal that drives adrenal hormone output).

The primary mechanism is that DHEA acts as a prohormone: a precursor that peripheral tissues convert into androgens (male-type hormones such as testosterone) and estrogens (female-type hormones such as estradiol) through an intracrine process, meaning the conversion happens locally inside target tissues rather than being released back into the blood. This lets tissues such as skin, bone, brain, and the vaginal lining generate the sex hormones they need locally. The balance of the output depends on the local activity of enzymes, particularly aromatase (which converts androgens to estrogens); in people with more body fat and higher aromatase activity, more of a DHEA dose is steered toward estrogen.

Beyond acting as a precursor, DHEA has proposed direct signaling effects that are less firmly established. It appears to act as a mild antagonist at glucocorticoid receptors (partly opposing the effects of the stress hormone cortisol), to modulate GABA-A and NMDA receptors in the brain (channels involved in calming and in learning signals, respectively), and to influence IGF-1 (insulin-like growth factor 1, a growth-signaling hormone) and immune-cell activity. These non-precursor actions are frequently cited to explain effects on mood and immunity but rest more on mechanistic and animal data than on human outcome trials.

Competing mechanistic interpretations exist. Proponents argue the intracrine conversion restores a youthful hormonal environment tissue-by-tissue with self-limiting local control. Skeptics counter that in men, whose testosterone comes overwhelmingly from the testes, supplemental DHEA adds little usable androgen, which would explain why many male trials are null; the same skeptics note that measurable clinical benefit is concentrated in states of genuine deficiency (aging women, adrenal insufficiency) rather than in hormonally replete adults.

As an endogenous steroid, DHEA has a short circulating half-life of roughly 15–30 minutes for the free form, though the sulfated DHEA-S reservoir persists for hours; oral DHEA is extensively metabolized on first pass through the liver, and downstream sex-steroid metabolism proceeds through the standard steroidogenic and cytochrome P450 enzymes.

## Historical Context & Evolution

DHEA was first isolated from urine in 1934, and its sulfate was identified as the most plentiful steroid in human blood over the following decades. Its original scientific interest was purely physiological: understanding adrenal steroid production. It had no initial therapeutic "intended use" in the way a designed drug does; instead, it became a therapy candidate because researchers noticed its dramatic, reproducible decline with age.

The reasons it came to be considered for health optimization trace to two observations from the 1980s and 1990s. First, epidemiological work reported that higher endogenous DHEA-S was associated with lower cardiovascular mortality in men. Second, small human trials by researchers such as Samuel Yen at UC San Diego reported that restoring DHEA to youthful levels improved well-being and body composition markers. These findings, described directly, were genuinely encouraging on their own terms: modest changes in perceived well-being and in some metabolic markers.

When the larger and longer trials arrived in the 2000s, the picture became more mixed rather than simply "debunked." The two-year Mayo Clinic trial in older adults found little benefit for body composition, physical performance, or quality of life, while other trials continued to show effects on bone, skin, and, via the intravaginal route, genitourinary tissue. The honest reading is that early enthusiasm was partly tempered by rigorous trials, but the evidence did not collapse; it segregated by outcome and population.

The evolution of opinion is therefore best described not as a settled verdict but as a narrowing of claims: broad "anti-aging" marketing gave way to specific, better-supported uses (notably FDA approval of intravaginal prasterone for painful intercourse in 2016), while systemic longevity benefits remain contested, with new evidence still emerging on both sides.

## Expected Benefits

Benefits below are framed for risk-aware adults actively pursuing healthy aging, and are grouped by the strength of the underlying human evidence.

### High 🟩 🟩 🟩

#### Genitourinary & Vaginal Health

For postmenopausal women, locally applied (intravaginal) DHEA restores the sex-hormone supply to vaginal and vulvar tissue through local conversion, thickening the tissue and improving lubrication. This is the single best-supported DHEA benefit: multiple randomized controlled trials (RCTs, studies that randomly assign participants to treatment or placebo) led to regulatory approval of intravaginal prasterone for moderate-to-severe painful intercourse. Because conversion occurs locally, blood hormone levels rise minimally. The relevance to a longevity audience is direct, since genitourinary decline is a common, quality-of-life-limiting feature of aging.

**Magnitude:** In pivotal RCTs, 6.5 mg intravaginal DHEA reduced pain-severity scores for intercourse by roughly 1.3–1.5 points from baseline on a 0–3 scale over 12 weeks — about 0.3–0.5 points more than placebo.

### Medium 🟩 🟩

#### Mood & Depressive Symptoms

DHEA has a modest antidepressant signal, attributed both to its conversion to sex steroids and to direct effects on brain receptors and on the cortisol-buffering system. Pooled RCT evidence (Peixoto et al., 2020) shows a small-to-moderate reduction in depressive symptoms versus placebo, including in midlife and in people with sub-syndromal low mood. The effect is real but the trials are small and heterogeneous, so it is best viewed as supportive rather than a stand-alone treatment.

**Magnitude:** Meta-analysis reports a small-to-moderate pooled reduction in standardized depression rating scores (standardized mean difference roughly −0.3, with wide confidence intervals).

#### Bone Mineral Density

By supplying androgens and estrogens to bone tissue, DHEA modestly supports bone mineral density (BMD, a measure of bone strength), most consistently at the hip and trochanter in older women. Meta-analysis of placebo-controlled trials in healthy adults (Lin et al., 2019) confirms a small but significant gain in women and little effect in men, consistent with the sex difference in how much usable hormone DHEA yields.

**Magnitude:** Roughly a 1–2% increase in hip and trochanter BMD in older women over 12 months of supplementation; negligible change in men.

#### Sexual Function & Libido

Beyond the local vaginal effect, systemic DHEA can improve sexual desire, arousal, and satisfaction, chiefly in women with low baseline androgen levels and in those with adrenal insufficiency. The proposed mechanism is restoration of circulating and locally produced testosterone. Evidence is moderate and strongest where baseline levels are genuinely low; trials in hormonally replete individuals are frequently null.

**Magnitude:** Roughly a 0.3–0.6 standardized mean difference improvement in validated sexual-function questionnaire scores in women with low baseline androgens; inconsistent and generally null effects in men.

### Low 🟩

#### Skin Health & Aging

DHEA supplied to skin is converted locally to sex steroids that stimulate sebum production, hydration, and collagen support, and small trials in older adults report increased epidermal thickness and improved hydration. The evidence base is limited to small, short studies, so the effect is plausible but not well quantified.

**Magnitude:** Not quantified in available studies.

#### Body Composition ⚠ Conflicted

Some trials report small reductions in fat mass (especially visceral fat) and minor gains in lean mass, while the largest and longest trials found no meaningful change. The mechanism would be androgen-mediated shifts in fat and muscle. The evidence is directly conflicted: positive short trials sit against the null two-year Mayo Clinic trial, likely reflecting differences in dose, sex, age, and baseline hormone status.

**Magnitude:** Where positive, reductions of roughly 1–2 kg fat mass; multiple well-controlled trials show no significant change.

#### Metabolic & Insulin Sensitivity ⚠ Conflicted

A subset of trials reports reduced visceral fat and improved insulin sensitivity (the body's responsiveness to its blood-sugar hormone), with anti-inflammatory changes; others find no effect on glucose handling. The conflict tracks with population and adiposity, being more apparent in older adults with higher visceral fat.

**Magnitude:** Where positive, modest improvements in insulin-sensitivity indices and small drops in visceral fat; several trials show no change.

### Speculative 🟨

#### Immune Modulation

Mechanistic and small human data suggest DHEA can enhance certain immune responses and partially offset the immune-suppressing effect of cortisol, but controlled outcome trials in healthy adults are lacking, so this remains hypothesis-generating.

#### Cognitive Protection

Lower DHEA-S is associated with Alzheimer's disease (Pan et al., 2019), yet the few supplementation trials have not shown clear cognitive benefit, leaving any protective effect speculative and based on association plus mechanism.

#### Cardiovascular & Longevity Signaling

Observational cohorts link higher endogenous DHEA-S to lower coronary heart disease and all-cause mortality, but these associations may reflect general health rather than causation, and no supplementation trial has demonstrated a mortality or cardiovascular-event benefit.

## Benefit-Modifying Factors

* **Sex:** The strongest modifier. Women, who produce little androgen from the ovaries after menopause, derive far larger hormonal gains from DHEA than men, whose testicular testosterone dominates and dwarfs any DHEA-derived contribution.

* **Baseline DHEA-S level:** Benefit concentrates in those with genuinely low starting levels (older adults, adrenal insufficiency). Individuals with youthful, replete levels have little to gain and are the group in which trials most often show null results.

* **Age:** Because DHEA falls steeply with age, older adults have more headroom for restoration; those at the older end of the target range typically show the clearest bone, skin, and sexual-function responses.

* **Body composition and aromatase activity:** Higher body fat increases aromatase activity, steering more of a dose toward estrogen. This can enhance bone and vaginal benefits but blunt androgen-dependent effects and shift the risk profile.

* **Genetic polymorphisms:** Variants in steroid-metabolizing enzymes such as CYP19A1 (aromatase, which converts androgens to estrogens) and SULT2A1 (which sulfates DHEA into its DHEA-S reservoir) plausibly alter how much active hormone a given dose yields, though pharmacogenetic guidance is not yet established.

* **Pre-existing conditions:** Adrenal insufficiency represents true deficiency and predicts response; conditions marked by androgen excess (such as some presentations of polycystic ovary syndrome) predict little benefit and greater risk.

## Potential Risks & Side Effects

Risks are framed for the target audience of proactive adults and grouped by strength of evidence.

### High 🟥 🟥 🟥

#### Androgenic Side Effects

Because DHEA converts to testosterone, the most common and best-documented adverse effects are androgenic: acne, oily skin, and unwanted facial or body hair, and, with prolonged higher doses, scalp hair thinning and voice changes in women. These are dose-dependent and largely reversible on stopping. Women are far more susceptible than men because the same dose raises their testosterone proportionally much more.

**Magnitude:** Acne and oily skin are the most frequently reported effects, occurring in a substantial minority of users at 50 mg/day, rising with dose; unwanted hair growth is less common but well documented.

#### Elevation of Sex-Steroid Levels

DHEA reliably raises circulating testosterone and, via aromatase, estradiol. In women a common 50 mg/day dose can push testosterone to or above the upper physiologic range, and estradiol also rises. This is the intended mechanism but is also a risk when it produces supraphysiologic hormone exposure, particularly unmonitored.

**Magnitude:** Oral DHEA raises testosterone in a clear dose-dependent manner (Li et al., 2020), with proportionally much larger increases in women than men; 25–50 mg/day frequently normalizes or overshoots youthful levels in women.

### Medium 🟥 🟥

#### Hormone-Sensitive Cancer Concern ⚠ Conflicted

Because DHEA feeds estrogen and androgen pathways, there is a theoretical concern about stimulating hormone-sensitive cancers (breast, endometrial, prostate, ovarian). Evidence is directly conflicted: some observational data link higher endogenous androgens to breast cancer risk, while intervention trials have not demonstrated increased cancer incidence, and follow-up is generally too short to be reassuring. The prudent reading is caution rather than established harm.

**Magnitude:** No trial has demonstrated an increase in cancer incidence, but trials are short and underpowered for cancer endpoints; the concern is mechanistic and precautionary.

#### Unfavorable Lipid Changes in Women

DHEA can lower HDL cholesterol (high-density lipoprotein, the "protective" cholesterol fraction) in women, an androgen-mediated effect that could theoretically offset cardiovascular benefit. The change is usually small but consistent enough across trials to warrant monitoring.

**Magnitude:** Small reductions in HDL cholesterol in women at 50 mg/day; generally modest and reversible.

### Low 🟥

#### Neuropsychiatric & Sleep Effects

A minority of users report irritability, agitation, anxiety, insomnia, or, conversely, mania-like activation, plausibly reflecting the hormone's central receptor effects and shifts in sex-steroid balance. Reports are inconsistent and usually mild, but they matter for people with mood disorders.

**Magnitude:** Infrequent, generally mild reports of insomnia, irritability, or agitation; rare activation in people with bipolar-spectrum conditions.

#### Palpitations & Blood-Pressure Effects

Isolated reports describe palpitations or minor blood-pressure changes, likely secondary to androgenic and sympathetic effects. These are uncommon and poorly quantified but occasionally prompt discontinuation.

**Magnitude:** Uncommon; isolated reports of palpitations, not consistently reproduced in controlled trials.

### Speculative 🟨

#### Cardiac Arrhythmia at High Doses

Whether supraphysiologic DHEA exposure meaningfully raises arrhythmia risk is unresolved; the concern rests on hormonal plausibility and scattered reports rather than controlled data.

#### Long-Term Effects of Chronic Supraphysiologic Dosing

The consequences of years of high-dose, unmonitored DHEA on hormone-sensitive tissues are essentially unstudied, so long-term safety at above-replacement doses is unknown and can only be inferred.

## Risk-Modifying Factors

* **Sex:** Women face substantially higher risk of androgenic effects and lipid changes at any given dose; men are relatively insensitive to both benefit and androgenic harm from DHEA specifically.

* **Baseline hormone levels:** People who already have adequate or high androgens (for example, some polycystic ovary syndrome presentations) are more likely to reach harmful supraphysiologic levels and see androgenic side effects.

* **Dose and formulation:** Risk scales with dose. High over-the-counter doses (50–100 mg/day) taken without testing carry the most risk; low physiologic doses and the localized intravaginal route minimize systemic exposure.

* **Age and hormone-sensitive tissue status:** Older adults with undiagnosed early prostate or breast lesions could theoretically have hormone-sensitive tissue stimulated; this shifts the risk calculus toward baseline screening.

* **Pre-existing conditions:** A personal or strong family history of hormone-sensitive cancer, liver disease (relevant to first-pass metabolism), or mood disorders raises the risk profile.

* **Genetic polymorphisms:** High aromatase (CYP19A1) activity increases estrogen conversion and estrogen-related risks, while variation in androgen receptor sensitivity may modify androgenic side-effect susceptibility.

## Key Interactions & Contraindications

* **Prescription drugs:** Aromatase inhibitors (anastrozole, letrozole) used in breast cancer may be counteracted by added hormone precursor — an absolute concern in that population. Estrogen or testosterone therapy is additive and can produce supraphysiologic levels. DHEA may alter the effect of insulin and oral antidiabetic drugs (metformin, sulfonylureas) by shifting insulin sensitivity, warranting glucose monitoring. Anticoagulants such as warfarin have a theoretical interaction. Inducers of CYP3A4 (a liver enzyme that metabolizes steroids and many drugs), such as carbamazepine and rifampin, can accelerate steroid metabolism and alter exposure.

* **Over-the-counter medications:** No major clinically established OTC drug interactions exist; theoretical additive effects with high-dose OTC hormonal or "testosterone-support" products should be considered.

* **Supplement interactions:** Pregnenolone and 7-keto-DHEA (a DHEA metabolite) overlap in pathway and can be additive. Androgen-supporting botanicals and phytoestrogen-rich products (soy isoflavones) may shift the estrogen/androgen balance unpredictably.

* **Additive-effect supplements:** Other sex-steroid precursors and hormone-modulating supplements (pregnenolone, boron marketed for testosterone, high-dose licorice affecting adrenal steroids) can add to DHEA's hormonal load and should be counted toward total exposure.

* **Other interventions:** Concurrent hormone replacement therapy or fertility hormone protocols interact directly and should be coordinated with a clinician.

* **Populations who should avoid DHEA:** Anyone with active or prior hormone-sensitive cancer (breast, ovarian, endometrial, prostate); pregnant or breastfeeding women; women with untreated androgen excess or significant hirsutism (excess unwanted facial or body hair); and men with elevated PSA (prostate-specific antigen, a prostate screening marker) above the screening threshold (e.g., PSA > 4 ng/mL) or known prostate cancer.

* **Severity and consequence:** Use with aromatase inhibitors is an absolute contraindication (undermines therapy); use in active hormone-sensitive cancer is an absolute contraindication (potential tumor stimulation); combination with other hormones warrants caution and monitoring (supraphysiologic hormone exposure); diabetic co-management warrants monitoring (altered glycemic control).

* **Mitigating actions:** Where any interaction applies, the mitigations are dose reduction to the lowest physiologic level, monitoring of the relevant hormone or lab, and separation from or avoidance of the interacting therapy under clinical supervision.

## Risk Mitigation Strategies

* **Baseline testing before starting:** Baseline testing of DHEA-S, testosterone, estradiol, and — in men over 40 — PSA before use confirms a genuine deficiency and avoids dosing people who are already hormonally replete, which prevents unnecessary androgenic and estrogenic overexposure.

* **Low starting dose with the lowest effective target:** Protocols typically begin at 10–25 mg/day (women often 5–10 mg) rather than the common 50 mg over-the-counter dose, escalating only if labs and symptoms justify it, keeping hormone levels within youthful physiologic ranges and limiting acne, hair changes, and HDL reduction.

* **Prefer the localized route where the goal is genitourinary:** For vaginal and sexual-comfort goals, intravaginal DHEA (about 6.5 mg) achieves tissue benefit with minimal systemic hormone rise, mitigating systemic androgenic and cancer-related concerns.

* **Periodic hormone monitoring:** Periodic rechecks of testosterone and estradiol at roughly 3 months and then every 6–12 months, targeting mid-youthful ranges, catch and correct the supraphysiologic drift that drives most side effects.

* **Lipid and prostate surveillance:** Annual monitoring of HDL cholesterol in women and PSA in men detects the specific medium-evidence risks (HDL reduction, prostate stimulation) early enough to adjust or stop.

* **Avoid stacking hormone precursors:** Combining DHEA with pregnenolone, 7-keto-DHEA, or exogenous hormones without supervision is avoided, since it adds to the supraphysiologic hormonal load.

## Therapeutic Protocol

* **Standard restorative protocol:** Leading longevity and functional-medicine practitioners typically use low, replacement-level oral dosing — commonly 25–50 mg/day for men and 5–25 mg/day for women — titrated to restore DHEA-S and downstream hormones to the mid-range of youthful values rather than to a fixed dose.

* **Competing approaches presented without default:** A conventional-medicine stance restricts DHEA largely to documented adrenal insufficiency and to intravaginal prasterone for genitourinary symptoms, using the lowest effective dose under monitoring. An integrative/longevity stance uses broader low-dose restoration in aging adults with low measured levels. A third, localized approach favors intravaginal DHEA for genitourinary goals to minimize systemic exposure. Each is a legitimate strategy for a different goal.

* **Who popularized each approach:** Early systemic restoration protocols trace to researchers such as Samuel Yen (UC San Diego) and were popularized for longevity by organizations such as Life Extension; the intravaginal prasterone approach was developed and championed by Fernand Labrie and colleagues, leading to regulatory approval.

* **Best time of day:** DHEA is typically taken in the morning to mirror the body's natural adrenal rhythm, which peaks early in the day, and to reduce the chance of sleep disruption.

* **Half-life considerations:** Free DHEA has a short half-life (roughly 15–30 minutes), but the sulfated DHEA-S reservoir persists for hours, which is why once-daily dosing is generally sufficient to sustain levels.

* **Single versus split dosing:** Most protocols use a single morning dose; splitting into morning and midday is occasionally used at higher doses to smooth levels, though evidence for any advantage is limited.

* **Genetic considerations:** Where known, high aromatase (CYP19A1) activity argues for lower doses to limit estrogen conversion; androgen-receptor sensitivity may influence individual response, though routine pharmacogenetic testing is not established.

* **Sex-based differences:** Women require substantially lower doses than men for the same hormonal effect and need closer androgenic monitoring; men often show minimal benefit, informing whether to use DHEA at all.

* **Age-related considerations:** Older adults with the lowest baseline levels are the most appropriate candidates and the most responsive; dosing still starts low and is titrated to labs.

* **Baseline biomarkers guiding dose:** Starting DHEA-S, testosterone, and estradiol determine both candidacy and initial dose, with the aim of correcting a measured deficiency rather than treating age alone.

* **Pre-existing conditions:** In polycystic ovary syndrome or other androgen-excess states, systemic DHEA is generally avoided; in adrenal insufficiency it is used as genuine replacement.

## Discontinuation & Cycling

* **Lifelong versus short-term:** DHEA restoration is generally framed as an open-ended, long-term measure tied to maintaining youthful hormone levels, but it is entirely reversible and can be stopped at any time; there is no established need for indefinite use in the absence of a deficiency.

* **Withdrawal effects:** No physiological withdrawal syndrome is described. On stopping, hormone levels simply return to the untreated baseline, and any androgenic side effects gradually resolve.

* **Tapering:** Because there is no dependence or withdrawal, abrupt discontinuation is acceptable; no formal taper is required, though some clinicians step the dose down while rechecking labs.

* **Cycling:** There is no strong evidence that cycling maintains efficacy or is necessary; some practitioners nonetheless use periodic breaks with lab reassessment to confirm ongoing need and to re-evaluate hormone levels.

* **Practical discontinuation trigger:** Persistent androgenic side effects, supraphysiologic hormone levels on testing, a rising PSA, or a new hormone-sensitive diagnosis are all reasons to stop, with levels expected to normalize within weeks.

## Sourcing and Quality

* **Regulatory and purity variability:** In the United States DHEA is sold as a dietary supplement, so product quality varies; independent testing has found large differences in actual dose and, occasionally, failed disintegration, meaning some products may not release their contents.

* **What to look for:** Quality products carry third-party testing or verification (for example, USP, NSF, or ConsumerLab-passed products); a labeled milligram dose that matches clinical ranges and a micronized form support more reliable absorption.

* **Reputable options:** Independent testing has identified quality-passing products from established supplement makers (for example, Life Extension, Pure Encapsulations, and Douglas Laboratories among those tested), and compounded prasterone or intravaginal prasterone is available by prescription where a pharmaceutical-grade product is preferred.

* **Cost caveat:** Because the same 25 mg dose has been found to range roughly ten-fold in price between products, third-party quality — not price — should drive selection.

* **Form-specific note:** For genitourinary goals, prescription intravaginal prasterone offers pharmaceutical-grade dosing and is preferable to improvised use of oral products.

## Practical Considerations

* **Time to effect:** Hormonal levels change within days, but clinical effects unfold over weeks to months — sexual-function and mood changes over roughly 4–8 weeks, skin and bone effects over 3–12 months.

* **Common pitfalls:** The most frequent mistakes are dosing by the common 50 mg capsule rather than by lab-guided need, failing to test hormones before and during use, women using male-typical doses, and stacking DHEA with other hormone precursors.

* **Regulatory status:** DHEA is an over-the-counter dietary supplement in the United States but is banned in competitive sport by the World Anti-Doping Agency, is prescription-only in several countries (including much of the EU, Canada, and Australia), and the intravaginal prasterone form is an approved prescription drug for painful intercourse.

* **Cost and accessibility:** Oral DHEA is inexpensive and widely accessible where sold as a supplement; the prescription intravaginal form is costlier and requires a prescription, and access is restricted in countries treating DHEA as a regulated hormone.

## Interaction with Foundational Habits

* **Sleep:** The interaction is direct and bidirectional. Taken late in the day, DHEA can disrupt sleep in sensitive users via activating hormonal effects, so morning dosing is preferred; conversely, poor sleep raises cortisol, which DHEA partly opposes, so aligning dosing with the natural morning adrenal peak is the practical rule.

* **Nutrition:** The interaction is mainly indirect. Body fat drives aromatase activity, so a nutrition pattern that reduces excess adiposity shifts DHEA's output away from estrogen toward androgens; taking DHEA with a meal containing some fat may modestly aid absorption of this fat-soluble steroid.

* **Exercise:** The interaction is potentiating and indirect. Resistance and endurance exercise independently raise endogenous DHEA and improve the hormonal milieu, and exercise-driven fat loss favors androgen conversion; there is no good evidence that DHEA blunts training adaptations, and any additive effect on lean mass is small.

* **Stress management:** The interaction is direct at the level of the adrenal axis. Chronic stress raises cortisol and can lower DHEA, worsening the cortisol-to-DHEA balance; practices that lower cortisol (sleep, meditation, reduced overtraining) complement DHEA's proposed cortisol-buffering role and may reduce the dose needed.

## Monitoring Protocol & Defining Success

Baseline testing should be completed before starting DHEA to confirm a genuine deficiency, establish candidacy, and set the target for titration; it is not merely implied by the table below but is a required first step, especially DHEA-S, sex hormones, and (for men over 40) prostate screening.

Ongoing monitoring follows a defined cadence: recheck hormones at approximately 6–12 weeks after starting or after any dose change, then every 6–12 months once stable, with annual lipid and prostate surveillance in the relevant groups.

| Biomarker | Optimal Functional Range | Why Measure It? | Context/Notes |
| --------- | ------------------------ | --------------- | ------------- |
| DHEA-S (serum) | Mid-to-upper range for a healthy 30-year-old, sex-specific | Confirms deficiency and tracks restoration | DHEA-S (dehydroepiandrosterone sulfate) is the stable circulating form; draw in the morning; the primary dosing guide |
| Total & Free Testosterone | Mid-youthful physiologic range, sex-specific | Detects androgenic overshoot, the main side-effect driver | Free testosterone is the active fraction; morning draw; especially important in women |
| Estradiol | Age- and sex-appropriate physiologic range | Detects excess estrogen conversion via aromatase | Higher body fat raises conversion; relevant to hormone-sensitive risk |
| SHBG | Within reference range | Interprets true free-hormone exposure | SHBG (sex hormone-binding globulin) binds sex hormones; needed to interpret total testosterone |
| PSA (men ≥40) | < 4 ng/mL and stable year-over-year | Prostate safety surveillance | PSA (prostate-specific antigen) is a prostate screening marker; a rising trend prompts stopping |
| HDL Cholesterol | > 50 mg/dL (women), > 40 mg/dL (men) | Detects the androgen-mediated HDL drop, mainly in women | HDL (high-density lipoprotein) is the protective cholesterol fraction; part of a fasting lipid panel |
| Fasting Insulin & Glucose (or HbA1c) | Fasting insulin < 8 µIU/mL; HbA1c < 5.4% | Tracks the metabolic/insulin-sensitivity effect | HbA1c (a 3-month average blood-sugar marker); fasting draw; these functional targets are stricter than conventional ranges (conventional fasting insulin reference extends to ~25 µIU/mL, HbA1c normal < 5.7%); relevant given conflicting metabolic data |
| IGF-1 | Age-appropriate mid-range | Contextualizes growth-signaling effects | IGF-1 (insulin-like growth factor 1) is a growth-signaling hormone; optional, interpreted alongside overall goals |

Qualitative markers of success complement the labs and are worth tracking:

* Energy and daytime vitality
* Mood stability and sense of well-being
* Libido and sexual function
* Sleep quality
* Skin condition (hydration, texture)
* Absence of androgenic side effects (acne, unwanted hair)

## Emerging Research

Research framed for proactive, health-optimizing adults is moving from broad "anti-aging" claims toward specific, testable questions about who benefits and at what dose.

* **DHEA in a multi-component longevity protocol:** The [Thymus Regeneration, Immunorestoration, and Insulin Mitigation Extension Trial (TRIIM-X)](https://clinicaltrials.gov/study/NCT04375657) ([NCT04375657](https://clinicaltrials.gov/study/NCT04375657)), a Phase 2 study of roughly 85 participants, combines DHEA with recombinant growth hormone and metformin and uses epigenetic age and thymus regeneration as primary endpoints, directly testing whether a DHEA-containing regimen can move aging biomarkers.

* **Localized DHEA versus estrogen for genitourinary aging:** The [VEDA Study (DHEA vs Estradiol)](https://clinicaltrials.gov/study/NCT07574216) ([NCT07574216](https://clinicaltrials.gov/study/NCT07574216)), enrolling around 324 women, compares intravaginal DHEA against estradiol for genitourinary symptoms, addressing whether the locally converted precursor matches estrogen for a common quality-of-life problem of aging.

* **Bone as a future-defining question:** Whether DHEA meaningfully protects against fracture — not just bone density — remains open; the existing density signal in women ([Lin et al., 2019](https://pubmed.ncbi.nlm.nih.gov/31237150/)) motivates longer, fracture-endpoint trials that could strengthen or weaken the skeletal case.

* **Cognition, both directions:** The association between low DHEA-S and Alzheimer's disease ([Pan et al., 2019](https://pubmed.ncbi.nlm.nih.gov/30983988/)) invites intervention trials that could either support a protective role or, as prior small trials suggest, show no cognitive benefit and weaken the hypothesis.

* **Cardiovascular causation:** Observational links between higher endogenous DHEA-S and lower coronary heart disease ([Wu et al., 2019](https://pubmed.ncbi.nlm.nih.gov/31347187/)) will only be resolved by trials with hard cardiovascular endpoints, which could confirm benefit or reveal the association to be non-causal.

## Conclusion

DHEA is a natural adrenal hormone that the body turns into testosterone and estrogen, and whose steep fall with age has made it a long-standing candidate for supporting healthy aging. The clearest benefit is for older women: locally applied DHEA reliably improves vaginal comfort and sexual health, and taken by mouth it modestly supports bone strength, mood, and desire where hormone levels are genuinely low. Effects on body fat, blood sugar, immunity, memory, and heart health remain mixed or unproven, and men generally gain little because their own testosterone overshadows what DHEA can add.

The main trade-offs are hormonal. Because it raises testosterone and estrogen, DHEA can cause acne, unwanted hair, and small drops in protective cholesterol, mostly in women, and it carries a precautionary concern around hormone-sensitive cancers that current studies are too short to fully settle. The evidence base is uneven: strong for the vaginal use, moderate for a few outcomes, and thin or conflicting for the broad longevity claims, with much of the enthusiasm resting on associations rather than proof.

Taken together, the picture is of a low-cost hormone with a few well-supported, mostly deficiency-related uses and many still-open questions, best understood through measured hormone levels rather than age alone.

**[Top](#top) - [Benefits](#expected-benefits) - [Risks](#potential-risks--side-effects) - [Protocol](#therapeutic-protocol)**