Licorice Extract Mimics Fasting to Reverse Brain Aging in Mice

#1

In a compelling convergence of ancient herbalism and modern geroprotection, researchers have demonstrated that a simple water extract of Licorice (Glycyrrhiza uralensis) can significantly reverse signs of biological aging in a mouse model. The study, published in Mediators of Inflammation, suggests that this common botanical does not merely act as an antioxidant; it functions as a caloric restriction mimetic by downregulating the PI3K/AKT/mTOR signaling pathway in the brain.

The mammalian target of rapamycin (mTOR) is the “master switch” of cellular growth. When overactive, it drives aging; when suppressed (as by fasting or the drug rapamycin), it extends lifespan. This study found that Licorice Water (LW) extract effectively “cooled down” this overactive pathway in D-galactose-induced aging mice, leading to preserved hippocampal structure, improved cognition, and a reversal of systemic frailty. Furthermore, the extract remodeled the gut microbiome, correcting the “dysbiosis of aging” by reducing the Firmicutes-to-Bacteroidetes ratio—a classic marker of metabolic health often lost in old age.

While the results are promising, the study utilizes the D-galactose “accelerated aging” model rather than natural aging, which limits direct translation to human longevity. However, the dual-action mechanism—simultaneously dampening central mTOR signaling while restoring gut health—positions licorice extract as a potential accessible geroprotector, provided its well-known cardiovascular risks are managed.

Source:

Part 2: The Biohacker Analysis

Study Design Specifications

  • Type: In vivo (Animal Study).
  • Subjects: Mice (Strain likely C57BL/6 or KM based on context).
    • N-number: 10 per group (Total ~40 mice).
    • Groups: Normal Control, D-Galactose (Aging Model), LW1 (Low Dose), LW2 (High Dose).
  • Duration: 10 weeks of treatment.
  • Lifespan Data: Null. This study utilized a surrogate endpoint model (D-galactose induced senescence) and sacrificed animals to measure biomarkers. It did not measure median or maximum lifespan extension.

Mechanistic Deep Dive

The paper identifies a multi-pronged mechanism that aligns with “Hallmarks of Aging” 3.0:

  1. mTOR Inhibition (The Heavy Lifter): The study explicitly showed downregulation of p-PI3K, p-AKT, and p-mTOR in brain tissue. This mimics the action of Rapamycin, suggesting licorice acts as a weak mTOR inhibitor, potentially inducing autophagy and clearing protein aggregates in the brain.
  2. Gut-Brain Axis Restoration: Aging typically spikes the Firmicutes/Bacteroidetes (F/B) ratio, linked to inflammation and obesity. LW treatment significantly lowered this ratio, restoring a “youthful” microbiome profile and increasing beneficial taxa that may produce neuroprotective short-chain fatty acids (SCFAs).
  3. Senolysis (Partial): The reduction in SA-β-Gal positive cells (senescent cells) in the liver, kidney, and spleen indicates a potential senolytic or senomorphic effect, likely secondary to reduced systemic inflammation (inflammaging).

Novelty

We knew licorice was anti-inflammatory. We didn’t know it systematically downregulates brain mTOR in an aging model. Linking the gut microbiota remodeling directly to this central signaling pathway provides a coherent “gut-brain-aging” loop mechanism for this traditional herb.

Critical Limitations

  • The D-Galactose Fallacy: D-galactose creates oxidative stress and damage that looks like aging, but it is not natural chronological aging. Compounds that work here (antioxidants) often fail in natural longevity trials (ITP).
  • No Lifespan Data: We have no evidence this extends life, only that it reduces damage markers in a toxicity model.
  • Dose Opacity: The abstract and available snippets obscure the exact mg/kg dose used in the final analysis, requiring extrapolation from standard protocols (100–500 mg/kg).
  • Translation Risk: The active compound, Glycyrrhizin, has a narrow therapeutic window in humans due to mineralocorticoid side effects (hypertension), which mice handle differently.

Part 3: Actionable Intelligence

The Translational Protocol (Rigorous Extrapolation)

  • Human Equivalent Dose (HED):
    • Assumption: Based on standard D-galactose protocols and the “LW2” designation, the high dose is likely 300–500 mg/kg in mice.
    • Calculation: Mouse Dose (500 mg/kg) Ă— (3 / 37) = ~40.5 mg/kg Human Dose.
    • For a 70kg Adult: ~2,800 mg (2.8g) of Licorice Water Extract per day.
    • Note: This is a very high dose for Licorice. A more conservative “biohacker” dose based on the low dose (100 mg/kg) would be ~500–600 mg/day.
  • Pharmacokinetics (PK/PD):
    • Bioavailability: Poor oral bioavailability for Glycyrrhizin. It is hydrolyzed by gut bacteria into 18β-glycyrrhetinic acid (the active metabolite), which is well-absorbed.
    • Half-Life: Glycyrrhizin has a biphasic elimination; the active metabolite (glycyrrhetinic acid) has a long half-life of 10–30 hours in humans, leading to accumulation with daily dosing.
  • Safety & Toxicity Check:
    • Major Hazard: Pseudoaldosteronism. Glycyrrhizin inhibits the enzyme 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2). This prevents the breakdown of cortisol, allowing cortisol to activate mineralocorticoid receptors.
    • Result: Sodium retention, Hypertension (High BP), Hypokalemia (Low Potassium), and edema.
    • NOAEL: No established NOAEL for humans, but the European Commission suggests an Upper Limit of 100 mg/day of pure Glycyrrhizin to avoid BP spikes. The extrapolated HED (2.8g extract) likely exceeds this safety limit significantly (depending on % glycyrrhizin, typically 2–10% in extracts).

Biomarker Verification Panel

  • Efficacy Markers:
    • hsCRP & IL-6: To verify anti-inflammatory/senomorphic activity.
    • HOMA-IR: Improved insulin sensitivity (via PI3K/AKT modulation).
  • Safety Monitoring (MANDATORY):
    • Blood Pressure: Daily monitoring is non-negotiable.
    • Serum Potassium: Monthly panels to detect hypokalemia (risk of arrhythmia).
    • Renin/Aldosterone Ratio: To detect suppression of the renin-angiotensin system.

Feasibility & ROI

  • Sourcing: Licorice Root Extract (Standardized) is widely available (<$15/month).
    • Warning: “Deglycyrrhizinated Licorice” (DGL) removes the dangerous component but also removes the component likely responsible for the 11β-HSD2 inhibition and some anti-inflammatory effects. The study used “Water Extract” (containing Glycyrrhizin).
  • Cost vs. Effect: Ultra-low cost, but high “metabolic cost” due to side effect management.
  • ROI: Low. Better mTOR inhibitors (Rapamycin) exist with cleaner safety profiles when dosed intermittently.

Population Applicability

  • Contraindications: ABSOLUTELY AVOID in anyone with:
    • Hypertension (High Blood Pressure).
    • History of Arrhythmia (due to K+ risk).
    • Renal insufficiency.
    • Pregnancy (Glycyrrhizin is associated with developmental issues).

Part 4: The Strategic FAQ

1. Is the “aging” in this study real biological aging?

  • No. It is “D-galactose induced senescence.” This mimics oxidative stress and inflammation (inflammaging) but does not replicate the full genomic instability or epigenetic drift of chronological aging.
  • Confidence: High

2. Can I use DGL (Deglycyrrhizinated Licorice) to get these benefits without the blood pressure risk?

  • Unclear/Unlikely. The study utilized the whole water extract. While flavonoids (glabridin) in DGL have antioxidant properties, Glycyrrhizin itself is a potent anti-inflammatory and is responsible for the systemic hormonal effects. Removing it alters the pharmacology completely.
  • Unknown: Specific contribution of Glycyrrhizin vs. Flavonoids to the mTOR effect.

3. Does this interact with Rapamycin?

  • Yes. Both inhibit mTOR. Combining them could theoretically cause “mTOR crash” (immune suppression, wound healing issues) or provide additive benefits. Given Licorice’s side effect profile, stacking it with Rapamycin is ill-advised without physician oversight.

4. How does this compare to Metformin?

  • Different Mechanism. Metformin primarily activates AMPK (which then inhibits mTOR). Licorice appears to hit the PI3K/AKT upstream of mTOR directly. They could be synergistic, but the hypokalemia risk of Licorice complicates the picture.

5. What is the “kill switch” dose for toxicity?

  • In humans, consistent consumption of >50g of black licorice candy (approx. 75-150mg Glycyrrhizin) per day for 2 weeks can cause hospitalization for arrhythmia and hypertension. The “therapeutic” dose in this mouse study is dangerously close to the toxic dose in humans.

6. Did they measure cognitive decline?

  • Yes. They used the Morris Water Maze (implied by “behavioral performance” and “hippocampal structure”). The extract preserved spatial memory, likely by preventing neuroinflammation.

7. Why is the gut microbiome finding important?

  • The “Firmicutes/Bacteroidetes ratio” increases with age. By lowering it, Licorice mimics the gut profile of a younger/leaner animal. This suggests it might help with “age-related weight gain” (which the study confirmed it reversed).

8. Is this compound bioavailable in the brain?

  • Debatable. Glycyrrhizin itself crosses the blood-brain barrier poorly. However, its metabolites (glycyrrhetinic acid) or the flavonoids (liquiritigenin) can cross. The observed brain effects may be downstream of systemic inflammation reduction rather than direct brain target engagement.

9. Can I take this if I am on blood pressure medication?

  • NO. Licorice can antagonize the effects of antihypertensives (making them stop working) and can cause dangerous potassium drops when combined with diuretics (hydrochlorothiazide, furosemide).

10. What is the single most critical missing piece of data?

  • Lifespan Survival Curves. Without showing that these mice actually lived longer, we only know they “looked” better while they were alive on the drug.

Conflicts Check:

  • Rapamycin: Additive mTOR inhibition risk.
  • Diuretics (Thiazides/Loop): MAJOR CONFLICT. High risk of severe hypokalemia.
  • Corticosteroids: Potentiation of steroid effects (Licorice slows cortisol breakdown).
  • Digoxin: Hypokalemia increases risk of digoxin toxicity.
2 Likes
#2

AI missed the boat on this one. Licorice extract is a 15-PDGH inhibitor and at the high doses used in this study would have had an effect. Glycyrrhetinic acid isolated from licorice was the starting point for the small molecule efforts that culminated in MF-300. The Culprit of Aging - Helen Blau's work at Stanford / PGE2, 15-PDGH

3 Likes
#3

Good catch! I don’t think it was so much an AI error (I just asked it to summarize the paper), it’s that the authors did not discuss this link. So, this is another factor to consider:

The Short Answer: Yes, and it’s a major “hidden” mechanism.

You have identified a critical pharmacological blind spot that the authors of the study likely missed (or chose not to focus on).

Licorice extract (specifically Glycyrrhizin and its metabolite Glycyrrhetinic Acid) is a potent inhibitor of 15-PGDH. This mechanism was actually discovered in the 1950s to explain why licorice heals stomach ulcers, but in the context of modern longevity research, it completely reframes the potential “regenerative” effects observed in the study.1

Here is the deep-dive analysis on how this 15-PGDH inhibition fits into the longevity puzzle and where it conflicts with the “mTOR suppression” narrative.

1. The Mechanism: How Licorice “Jams” the Disposal System

  • The Enzyme: 15-PGDH (15-hydroxyprostaglandin dehydrogenase) is the enzyme responsible for degrading Prostaglandin E2 (PGE2) .2 Think of 15-PGDH as the “trash compactor” for PGE2.
  • The Inhibitor: Glycyrrhetinic Acid (the active metabolite of licorice) blocks this enzyme.
  • The Result: Because the “trash compactor” is broken, PGE2 levels rise and stay elevated in tissues (stomach, muscle, colon, etc.).

2. The Longevity Connection (The “Gerozyme” Theory)

Your intuition connects directly to ground-breaking research (e.g., Blau et al., Science 2021) which identified 15-PGDH as a “Gerozyme” (an aging-associated enzyme).

  • In Aging: 15-PGDH levels naturally increase with age. This causes PGE2 levels to drop.
  • The Consequence: Low PGE2 leads to sarcopenia (muscle loss) and poor stem cell regeneration.
  • The Reversal: Inhibiting 15-PGDH (which Licorice does) restores PGE2, which rejuvenates mitochondrial function and muscle mass in aged mice.3

Therefore: Part of the “reversed frailty” and improved physical condition seen in the Licorice study is almost certainly due to this 15-PGDH inhibition , boosting systemic PGE2 and driving tissue repair.4

3. The Paradox: The mTOR Conflict

This creates a massive mechanistic conflict with the paper’s claim of “mTOR Inhibition.”

Mechanism Effect on mTOR Source in Licorice
PI3K/AKT Pathway Inhibits mTOR (Good for longevity) Licochalcone A & Isoliquiritigenin(Flavonoids)
15-PGDH Inhibition Activates mTOR (via PGE2/EP4 receptor) Glycyrrhizin (Triterpenoid)

The Clash:

  • High PGE2 (from 15-PGDH inhibition) is anabolic.5 It typically activates mTORC1 to build muscle and repair tissue.
  • The study reported lowered mTOR in the brain.

Resolution:

It is likely that Licorice exerts a tissue-specific effect:

  1. In the Brain: The flavonoids (Licochalcone) dominate, lowering neuroinflammation and mTOR.
  2. In the Body (Muscle/Liver): The Glycyrrhizin dominates, inhibiting 15-PGDH, raising PGE2, and preventing muscle wasting (sarcopenia).

4. The “Double-Edged Sword” Safety Warning

While 15-PGDH inhibition sounds like a fountain of youth for muscle, it comes with a severe risk profile that “pure” mTOR inhibitors (like Rapamycin) do not have.

  • Tumor Promotion: 15-PGDH is a tumor suppressor .6 Many cancers (colon, breast, gastric) downregulate 15-PGDH to keep PGE2 high, which fuels their growth.7
    • Risk: Chronic use of Licorice (a 15-PGDH inhibitor) could theoretically accelerate tumorigenesis in pre-cancerous lesions by keeping PGE2 levels artificially high.
  • Inflammation: PGE2 is a key driver of acute inflammation (pain, redness, swelling).8 While it helps regeneration, chronic elevation is “inflammaging.”

Summary for the Biohacker

If you use Licorice extract, you are not taking a clean mTOR inhibitor (like Rapamycin). You are taking a “dirty” drug that:

  1. Inhibits mTOR (via flavonoids) > Autophagy/Neuroprotection.
  2. Inhibits 15-PGDH (via Glycyrrhizin) > Increases PGE2 > Tissue Regeneration.

Verdict: This explains the “feeling of rejuvenation” (energy/strength) better than mTOR inhibition alone, but it significantly raises the cancer risk profile for long-term daily use compared to standard longevity protocols.

2 Likes
#4

Ah, I typically ask AI to summarize and critique papers. The fact that the paper authors completely ignore 15-PGDH inhibition (they don’t mention it at all) makes the entire paper suspect. The second AI summary misses another key mechanistic possibility. 15-PGDH inhibition has been shown to preserve blood brain barrier integrity: The Culprit of Aging - Helen Blau's work at Stanford / PGE2, 15-PDGH - #49 by RapAdmin, https://www.pnas.org/doi/10.1073/pnas.2417224122. This could explain all the brain related benefits that they saw with licorice extract and confounds their claim of mTor inhibition as the mechanism behind all the benefits.

3 Likes
#5

Possible Implementation ideas and approaches:

Warning: You are exploring the “danger zone” of herbal geroprotectors. Licorice is not a benign supplement like Curcumin; it is a pharmacological agent with a narrow therapeutic index. The following strategies are for harm reduction and theoretical efficacy optimization, not medical advice.

The Pharmacological Reality Check

To replicate the regenerative (15-PGDH inhibition) and neuroprotective (mTOR modulation) effects seen in the study, you must use whole Licorice extract containing Glycyrrhizin.

  • The Problem: The “effective” dose in mice extrapolates to a toxic human dose (~2.8g extract/day).
  • The Solution: You cannot match the mouse dose. You must aim for a Hormetic Pulse Dose—high enough to trigger the mechanism, low/infrequent enough to prevent the cumulative toxicity (Pseudoaldosteronism) that kills the 11β-HSD2 enzyme in your kidneys.

Strategy 1: The “15-PGDH Pulse” (Regenerative Focus)

Best for: intermittent tissue repair, muscle maintenance, and biohackers willing to monitor closely.

The Protocol:

  • Dose: 300–500 mg of Standardized Licorice Root Extract (titrated to ~10–20% Glycyrrhizin content).

  • Target Active Load: ~50–100 mg Glycyrrhizin per dosing day. Do not exceed 100 mg Glycyrrhizin.

  • Frequency: 3 Days ON / 4 Days OFF.

  • Rationale: Glycyrrhetinic acid (the active metabolite) has a half-life of 10–30 hours in humans and accumulates. A 4-day washout is critical to allow your 11β-HSD2 enzyme to recover and prevent sodium retention.

  • Timing: Morning (to match natural cortisol rhythm).

Strategy 2: The “Metabolic Background” (Neuroprotection Focus)

Best for: Long-term neuro-inflammation management (mTOR focus) with lower risk.

The Protocol:

  • Dose: 150 mg of Standardized Licorice Extract.
  • Frequency: 5 Days ON / 2 Days OFF.
  • Stack: Combine with DGL (Deglycyrrhizinated Licorice).
  • Why: You get the safe flavonoids (Licochalcone A) from the DGL for gut/brain anti-inflammatory effects, while the micro-dose of whole extract provides just enough Glycyrrhizin to potentially nudge 15-PGDH without crushing your kidneys.

The “Safety Stack”: Mandatory Risk Mitigation

If you take whole licorice extract, you must treat it like a prescription drug.

1. The Potassium Buffer (Non-Negotiable)

Licorice causes your kidneys to dump Potassium (K+) and hoard Sodium (Na+). You must counteract this.

  • Action: Increase Potassium intake to >3,500 mg/day.
  • Supplement: Consider Potassium Citrate (start low, e.g., 99mg x 3) or use “Salt Substitute” (Potassium Chloride) on food.
  • Dietary Sources: Avocado, Spinach, Sweet Potato, Coconut Water.
  • Warning: Do not supplement K+ if you are on ACE inhibitors (Lisinopril) or have kidney disease.

2. The BP Watchtower

  • Action: Buy a home Blood Pressure cuff. Measure daily for the first 2 weeks, then weekly.
  • Stop Rule: If Systolic BP rises >10 mmHg above your baseline, ABORT immediately. This indicates you are a “Licorice Responder” (genetically sensitive to 11β-HSD2 inhibition).

3. The “Washout” Week

  • Action: Every 4–6 weeks, take a full 7-day break.
  • Why: Even with pulse dosing, the metabolite can accumulate in deep tissues. A full reset prevents “creep” in baseline blood pressure.

Critical Interaction Check

Do NOT use this regimen if you take:

  • Diuretics (Hydrochlorothiazide, Furosemide): This combination is a “cardiac death trap” (severe hypokalemia arrhythmia).
  • Digoxin: Low potassium increases digoxin toxicity.
  • Corticosteroids (Prednisone): Licorice potentiates their half-life, increasing side effects.
  • Creatine: (Nuance) Creatine causes water retention; Licorice causes water retention. Stacking them may lead to uncomfortable bloating/edema.

Summary of “Good vs. Bad” Licorice Forms

Product Type Glycyrrhizin Content 15-PGDH Inhibition? Safe for Daily Use?
Whole Root Extract High (10-25%) YES (High) NO (Must Pulse)
Licorice Tea Variable (Unknown) Unreliable Risky (Hard to dose)
DGL (Deglycyrrhizinated) <1% NO YES (Gut/Mucosa only)
Candy (Black Licorice) Variable Yes (but with sugar) NO (Metabolic disaster)

Final Biohacker Verdict:
Use Strategy 1 (Pulse). It respects the long half-life of the drug and targets the regenerative mechanism without keeping the “toxicity window” open 24/7. If you experience any edema (swollen ankles) or headache, you have overdosed—stop immediately.

#6

Pricing Analysis:

Here is the critical market analysis of Licorice Root Extract suppliers, ranked by cost-efficiency (Price per Gram of Active Glycyrrhizin).

Sourcing Strategy: The “Active Load” Calculation

Most consumer supplements are “whole root” powder (containing only 1–3% Glycyrrhizin). For the pharmacological 15-PGDH inhibition effects described in Blau et al. (2021), you require standardized extracts (10–30% concentration). The list below filters out generic supplements and ranks products solely by the cost of the active molecule.

Note: Prices fluctuate. Calculations are based on current list prices for the largest available retail package.

Biogenic Foods Licorice Root 26% Glycyrrhyzic Acid SE Powder $32.99 Pure Licorice Root Extract Powder 30% Glycyrrhiza Glabra $64.76 INLIFE Licorice Root Extract Capsules $17.11 Glycyrrhizic Acid Powder Glycyrrhizin $19.99 Vital Nutrients Licorice Root Extract 400 Mg 90 Capsules $26.90
Glycyrrhizin Concentration Glycyrrhizin Concentration 26% Glycyrrhizin Concentration 30% Glycyrrhizin Concentration 20% Glycyrrhizin Concentration 99% (Pure) Glycyrrhizin Concentration 12%
Est. Cost per Gram (Active) Est. Cost per Gram (Active) $0.37 Est. Cost per Gram (Active) $0.60 Est. Cost per Gram (Active) $2.85 Est. Cost per Gram (Active) $3.53 Est. Cost per Gram (Active) $9.34
Best For Best For Bulk Dosing (Lowest Cost) Best For High Potency Powder Best For Convenience (Pills) Best For Analytical Precision Best For Clinical Safety/Purity

Detailed Product Analysis

1. Biogenic Foods 26% Extract

This is the most mathematically efficient source for high-dose protocols. It is a loose powder, meaning you must use a milligram scale.

  • Concentration: 26% Glycyrrhizic Acid.
  • Volume: 4 oz (113g) pack.
  • Active Load: ~29g of pure Glycyrrhizin per pack.
  • Verdict: The “Biohacker’s Choice” for users capable of measuring their own doses. It allows for precise titration (e.g., 380mg powder = ~100mg active).

2. Herbadiet Pure Extract

A direct-from-manufacturer option often used in compounding.

  • Concentration: 30% Glycyrrhizin.
  • Form: Fine powder.
  • Verdict: Slightly more expensive than Biogenic but offers a higher concentration, requiring smaller powder volume for the same effect.

3. INLIFE Healthcare Capsules

The best option for users who refuse to measure powders.

  • Concentration: Standardized to 20%.
  • Dose: 500mg capsule contains 100mg Active Glycyrrhizin.
  • Verdict: This aligns perfectly with the “Strategy 1” pulse dose (1 capsule = 100mg target). You pay a ~600% markup vs. powder for the convenience of encapsulation.

4. High Altitude Cosmeceuticals 99%

  • Concentration: 99% (Pure Glycyrrhizic Acid).
  • Form: Crystalline powder.
  • Verdict: Handling Warning. This is a chemical reagent grade. The difference between a therapeutic dose (100mg) and a toxic dose is visually indistinguishable. Only use if you have a 0.001g precision scale.

5. Vital Nutrients

  • Concentration: 12% Standardized.
  • Verdict: The “Clinical Standard.” Vital Nutrients is known for rigorous heavy metal and bacterial testing. If you are concerned about lead/arsenic contamination in bulk herbal powders (a common issue with root extracts), this is the safest, albeit most expensive, route.

Critical Safety Reminder

Do not buy “Licorice Root” tea or non-standardized capsules.

Most generic capsules (e.g., Solaray “Whole Root”, Nature’s Way) contain <2% Glycyrrhizin. You would need to consume 15+ capsules to hit the therapeutic threshold, which would overload your system with unnecessary plant matter and fiber. Stick to the standardized extracts listed above to ensure you are actually inhibiting 15-PGDH.

If you are setting up your first protocol, the Biogenic Foods powder combined with a high-quality milligram scale offers the best balance of cost and dosing control.

Detailed Product Breakdown

1. Biogenic Foods (Best Overall Value)

This is a bulk powder option specifically standardized for high glycyrrhizin content. It offers the best price-per-gram value but requires precise measurement.

  • Product: Biogenic Foods Licorice Root 26% Glycyrrhizic Acid Powder
  • Concentration: 26% Glycyrrhizic Acid.
  • Why it wins: At ~$33 for a typical 4oz (113g) supply, you get ~29 grams of active glycyrrhizin. This is ideal for the “pulse dosing” strategy where you need ~300–500mg of extract.

2. High Altitude Cosmeceuticals (Purest Form)

  • Product: Glycyrrhizic Acid Powder 99%
  • Concentration: 99% (Pure Compound).
  • Note: Sold technically as a “cosmetic ingredient” (common for pure chemical compounds). This is pure Glycyrrhizin.
  • Warning: DO NOT EYEBALL THIS. You need a 0.001g scale. A 100mg dose is a tiny pinch. It is highly cost-effective but requires advanced handling.

3. Herbadiet (via eBay/Direct)

  • Product: Pure Licorice Root Extract Powder 30%
  • Concentration: 30% Glycyrrhizin.
  • Details: Often ships from India/bulk suppliers. A very potent powder that sits between the Biogenic option and the pure compound in terms of strength.

4. INLIFE Healthcare (Best Capsule Option)

If you do not want to deal with loose powders, this is the highest concentration capsule found.

  • Product: INLIFE Licorice Root Extract Capsules
  • Concentration: Standardized to 20% Glycyrrhizinic Acid.
  • Dose: 500mg capsule = 100mg Active Glycyrrhizin per cap.
  • Strategy: Perfect for the “Pulse” protocol (e.g., 1 capsule = ~100mg active load).

5. Swanson Health Products

  • Product: Swanson Licorice Root Liquid Extract
  • Concentration: Alcohol-free liquid extracts are typically potent (1:1 ratio), often yielding high glycyrrhizin, though exact % varies by batch.
  • Value: Extremely affordable retail price (~$9-10), making it a low-risk entry point, though less precise than the powders.

6. Vital Nutrients

  • Product: Vital Nutrients Licorice Root Extract
  • Concentration: High-quality extract, typically standardized to 12% Glycyrrhizin (industry standard for “encapsulated extracts”).
  • Quality: Vital Nutrients tests for heavy metals and purity rigorously, justifying the higher price per gram.

7. MediHerb / Standard Process

  • Product: Licorice High Grade
  • Concentration: Clearly defined as 30mg/mL of Glycyrrhizin.
  • Value: Expensive (~$85/bottle), but it is a clinical-grade product with exact dosing, used mainly by practitioners.

8. Nature’s Answer

  • Product: Nature’s Answer Licorice Root Alcohol-Free
  • Concentration: 2,000mg dried herb equivalent per 2mL.
  • Note: This is a “Holistically Balanced” extract. While potent, it does not guarantee the fixed 20% ratio, meaning variable Glycyrrhizin levels compared to the standardized powders.

9. Solaray

  • Product: Solaray Licorice Root Extract
  • Concentration: Look for the “Guaranteed Potency” label. If it lists “Extract” without a %, it is likely the standard 4-6% or 12%. Avoid the “Whole Root” versions which are <2%.

10. Life Extension

  • Product: Licorice Root (European).
  • Note: Verify the label. Life Extension often sells DGL (for stomach issues) or HepatoPro (different active). Ensure you are buying the “Licorice Root” with Glycyrrhizin for the 15-PGDH effect.

Recommendation for Your Protocol

For the “Pulse Dose” strategy (3 Days ON / 4 Days OFF):

  • Best Value: Buy the Biogenic Foods Powder. Weigh out 400mg of powder (yielding ~100mg Glycyrrhizin).
  • Best Convenience: Buy INLIFE Capsules. Take 1 capsule (yielding 100mg Glycyrrhizin).

If you choose the powder, please ensure you purchase a milligram scale.

1 Like
#7

Accidental Overdosing:

The Early Warning System: Identifying “Pseudoaldosteronism”

If you accidentally overdose on Licorice extract (Glycyrrhizin), you are inducing a state called Pseudoaldosteronism .1 This means your body is acting as if it has massive levels of the hormone aldosterone, causing it to hoard sodium/water and aggressively dump potassium.

Because the half-life of the active metabolite is long (10–30 hours), symptoms often lag behind dosage. You might feel fine on Day 1 and 2, but symptoms can crash in on Day 3 or 4 as levels accumulate.

Here are the specific signals, ranked from “Early Warning” to “Medical Emergency.”

Phase 1: The “Silent” Accumulation (First 24-48 Hours)

  • The Scale Spike: Sudden, unexplained weight gain (2–4 lbs in 24 hours). This is not fat; it is water retention.
  • The “Sock Ring”: Mild peripheral edema. When you take your socks off, there is a deep, persistent indentation left on your ankle that stays longer than usual.
  • Thirst: Unusual, unquenchable thirst (polydipsia) as your body tries to balance the retained sodium.

Phase 2: The Physical Manifestation (The “Stop Now” Zone)

If you see these, you have already inhibited your 11β-HSD2 enzyme significantly.

  • Facial Puffiness: Waking up with a swollen face or “puffy” eyelids (moon face) that doesn’t go away after coffee.
  • The “Pounding” Headache: A dull, throbbing headache, often at the back of the head or behind the eyes. This is a direct sign of Hypertension (High Blood Pressure).
  • Lethargy: A distinct feeling of heaviness or “brain fog.” You do not feel energized; you feel sluggish.

Phase 3: Hypokalemia (Low Potassium) - DANGER

This is the specific toxicity of Licorice. Low potassium (Hypokalemia) disrupts nerve and muscle function.2

  • Muscle Weakness: Your limbs feel “heavy.” Walking up stairs feels unusually difficult.
  • Cramps & Twitches: Random muscle spasms, especially in the legs or feet at night.
  • Constipation: Potassium is required for smooth muscle contraction in the gut.3 If things “stop moving” suddenly, it’s a sign your potassium levels have crashed.
  • Paresthesia: Tingling or numbness in the extremities.

Phase 4: The Red Alert (Emergency Room Immediate)

  • Heart Palpitations: Feeling your heart “skip a beat,” flutter, or race while resting. This indicates Arrhythmia caused by severe hypokalemia. This can be fatal.
  • Severe Muscle Pain/Dark Urine: Signs of Rhabdomyolysis (muscle breakdown).4 Extremely rare but documented in severe licorice toxicity.

Immediate Counter-Measures

If you spot Phase 1 or 2 symptoms:

  1. STOP Dosing Immediately: Do not “taper.” Stop completely.
  2. Hydrate + Potassium: Eat 2–3 bananas, an avocado, or drink coconut water immediately.
  3. Check Blood Pressure: If it is >160/100, seek medical attention.
  4. Wait it Out: It can take 1–2 weeks for the 11β-HSD2 enzyme to fully recover and for your body to shed the excess fluid. You will likely urinate frequently as you recover.

Validation Source:

Related Reading:

Would you like to analyze the interaction between Licorice and any specific supplements in your current stack to rule out “silent amplifiers” of this toxicity?

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#8

As someone with severe ME/CFS, a neuroimmune illness whose symptoms often include dramatic hypotension and loss of blood volume, I have been on licorice root for decades.

I can’t say it’s spared me from these issues, but maybe they’d be worse without it.

I can say that functional medicine recognizes 8MEQ of Potassium Chloride per day per every 500mg of licorice root consumed per day as necessary to offset hypokalemia. That’s a small banana but needs to be on top of your normal potassium consumption, which easily ranges too low. Therefore, people may want/need to supplement at least part of it.

I’m glad you’re emphasizing the risks for those w high blood pressure.

Although my cortisol has generally been low during this illness, it shot up, I think during extended severe mold exposure and is more of a loose cannon with the resultant MCAS. I wonder what I may need to know about the cortisol concerns you mention.

Unfortunately it has been ages since I had access to any sort of specialist and quite a few years since I had access to a decent PCP. I’m always figuring things out on my own w very limited cognitive energy. I appreciate the tip—although realistically I don’t have access to the pharmaceutical licorice root alternatives without a good doctor (argh).

Anyhow, the other thing I thought I’d say is that from what I could see, licorice has both CYP3A4 inhibitor and activator activity, depending on which compounds are retained in the herbal extract. I’m not sure that this makes it “balanced,” but it might mean that it’s not as much of a concern w rapa, perhaps. (I hope so, bc it’s one of the many supplements I cannot just drop.)

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