2S-Hesperidin
Hesperidin 2S
Standardized Citrus Hesperidin Extract
Citrus sinensis Hesperidin Extract

---
canonical_name: Cordiart
alternate_names: 2S-Hesperidin, Hesperidin 2S, Standardized Citrus Hesperidin Extract, Citrus sinensis Hesperidin Extract
canonical_topic: Cordiart for Health & Longevity
short_topic_lc: cordiart
creation_date: 2026-0628-0221
creator_ai_fullname: Opus 4.8
---

# Cordiart for Health & Longevity

Evidence Review created on 06/28/2026 using [AI4L](https://github.com/forever-healthy/AI4L) / Opus 4.8

**Also known as:** 2S-Hesperidin, Hesperidin 2S, Standardized Citrus Hesperidin Extract, Citrus sinensis Hesperidin Extract

## Motivation

Cordiart is a branded citrus extract whose active ingredient is hesperidin, a natural plant compound found in the peel and pulp of oranges. What sets Cordiart apart from ordinary hesperidin is that it is standardized to a specific, more absorbable form of the molecule, marketed to support the health of blood vessels and the heart. It is taken as an oral supplement, usually at 500 mg per day.

Hesperidin has long been studied as part of the broader interest in why diets rich in citrus and other plant foods are linked to better heart health. The molecule appears to help the thin inner lining of blood vessels relax and widen, and it dampens some markers of low-grade inflammation. A widely cited study reported that a daily dose improved blood vessel function in people with several heart-disease risk factors, which helped spark commercial interest in concentrated, better-absorbed citrus extracts such as Cordiart.

This review examines what is known about Cordiart and its active compound: how it may work in the body, the benefits and risks suggested by human studies, how it is typically used, and where the evidence is strong, weak, or still unsettled.

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

## Recommended Reading

This section lists high-level, accessible resources that discuss hesperidin, the active compound in Cordiart, and its role in vascular and metabolic health.

* [Activate Your Fat Burning Enzyme!](https://www.lifeextension.com/magazine/2023/6/activate-your-fat-burning-enzyme) - Downey

  This consumer-facing article explains how hesperidin activates AMP-activated protein kinase (AMPK, a cellular energy sensor that promotes fat and glucose metabolism) and connects this mechanism to vascular and metabolic benefits, giving a plain-language overview relevant to Cordiart's active compound.

* [Citrus polyphenol hesperidin stimulates production of nitric oxide in endothelial cells while improving endothelial function and reducing inflammatory markers in patients with metabolic syndrome](https://pubmed.ncbi.nlm.nih.gov/21346065/) - Rizza et al., 2011

  This foundational human study showed that 500 mg of hesperidin daily improved blood vessel widening and lowered inflammation markers, and it explains the nitric-oxide mechanism that underpins most claims made for Cordiart.

* [Hesperidin Bioavailability Is Increased by the Presence of 2S-Diastereoisomer and Micronization—A Randomized, Crossover and Double-Blind Clinical Trial](https://pubmed.ncbi.nlm.nih.gov/35745211/) - Crescenti et al., 2022

  This trial directly addresses why Cordiart uses the 2S form of hesperidin, demonstrating that the 2S-diastereoisomer plus micronization markedly raises how much of the compound the body absorbs.

* [Randomized clinical trial on the efficacy of hesperidin 2S on validated cardiovascular biomarkers in healthy overweight individuals](https://pubmed.ncbi.nlm.nih.gov/27797708/) - Salden et al., 2016

  This is the pivotal human trial of the specific 2S-hesperidin ingredient behind Cordiart, reporting effects on adhesion molecules and blood pressure and the limits of its effect on vessel function in a general overweight population. Note a financial conflict of interest: this trial was conducted with the ingredient developer BioActor (a co-author's affiliation), the commercial maker of the 2S-hesperidin product, which has a direct interest in favorable results.

* [Hesperidin: The Citrus Bioflavonoid that Supports the Brain & Heart](https://draxe.com/nutrition/hesperidin/) - Jillian Levy

  This accessible expert overview situates hesperidin among the bioactive compounds in citrus and describes its anti-inflammatory, vascular, and blood-pressure roles, providing plain-language context on the active compound that Cordiart standardizes and delivers.

_Note: No dedicated, substantial standalone content on Cordiart or hesperidin was found from Rhonda Patrick, Peter Attia, Andrew Huberman, or Chris Kresser; only passing references within broader material exist, which do not meet the relevance bar. Life Extension Magazine has substantial coverage and is represented above._

## Grokipedia

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

This Grokipedia entry covers hesperidin, the active compound in Cordiart, summarizing its chemistry, citrus food sources, proposed mechanisms, and the state of clinical evidence, which is the most directly relevant primary page for this intervention.

## Examine

[Hesperidin](https://examine.com/supplements/hesperidin/)

This Examine page provides an independent, evidence-graded summary of hesperidin's benefits, dosage, and side effects, serving as a neutral reference for the compound that Cordiart standardizes and delivers.

## ConsumerLab

[What is hesperidin, what is it used for and is it safe?](https://www.consumerlab.com/answers/what-is-hesperidin/hesperidin-supplement/)

This ConsumerLab answer reviews the evidence on standalone hesperidin—including the Cordiart 2S form by name—summarizing its modest, mixed effects on blood pressure and lack of clear benefit on cholesterol, triglycerides, and blood sugar, and noting its short-term safety, serving as an independent reference for the compound Cordiart delivers.

## Systematic Reviews

This section summarizes systematic reviews and meta-analyses of hesperidin, the active compound in Cordiart, focusing on cardiometabolic outcomes.

* [Effects of Hesperidin Supplementation on Cardiometabolic Markers: A Systematic Review and Meta-analysis of Randomized Controlled Trials](https://pubmed.ncbi.nlm.nih.gov/39038797/) - Heidari et al., 2025

  This meta-analysis of randomized controlled trials (RCTs — studies that randomly assign participants to treatment or placebo) found that hesperidin significantly reduced fasting blood sugar, triglycerides, total and LDL ("bad" low-density lipoprotein) cholesterol, systolic blood pressure, and the inflammation marker TNF-α (tumor necrosis factor-alpha, a pro-inflammatory signaling protein), with stronger effects at doses above 500 mg/day and durations beyond 12 weeks. It used formal certainty-of-evidence grading, making it the most rigorous current synthesis.

* [The effects of hesperidin supplementation on cardiovascular risk factors in adults: a systematic review and dose-response meta-analysis](https://pubmed.ncbi.nlm.nih.gov/37502716/) - Khorasanian et al., 2023

  This dose-response meta-analysis reported significant reductions in triglycerides, total and LDL cholesterol, TNF-α, and systolic blood pressure, but noted a small increase in body weight and no effect on several glycemic markers, suggesting an effective dose near 1,000 mg/day for some endpoints.

* [Effect of hesperidin on blood pressure and lipid profile: A systematic review and meta-analysis of randomized controlled trials](https://pubmed.ncbi.nlm.nih.gov/38462779/) - Shylaja et al., 2024

  Pooling nine RCTs with 2,414 participants, this review found significant reductions in LDL cholesterol, total cholesterol, and triglycerides but no significant change in blood pressure, and it explicitly concluded that further high-quality studies are needed to firmly establish clinical efficacy.

* [Efficacy and safety of dietary polyphenol supplementation in the treatment of non-alcoholic fatty liver disease: A systematic review and meta-analysis](https://pubmed.ncbi.nlm.nih.gov/36159792/) - Yang et al., 2022

  This review of dietary polyphenols in fatty liver disease found that hesperidin may lower body mass index, liver enzymes, blood lipids, and insulin resistance, while cautioning that the hesperidin evidence base is small and that more RCTs are required.

## Mechanism of Action

The biological effects attributed to Cordiart are those of hesperidin and its main active breakdown product, hesperetin.

* **Nitric oxide and endothelial function:** Hesperetin activates a signaling cascade (Src → Akt → AMPK → endothelial nitric oxide synthase, the enzyme eNOS that makes the vessel-relaxing gas nitric oxide) in the cells lining blood vessels. This increases nitric oxide production, which relaxes and widens arteries (vasodilation) and supports healthy blood flow. This pathway was demonstrated directly in human vascular cells.

* **Anti-inflammatory and anti-adhesion effects:** Hesperetin reduces the expression of vascular cell adhesion molecule-1 (VCAM-1, a "sticky" protein that lets immune cells attach to vessel walls) and lowers circulating markers such as high-sensitivity C-reactive protein (hs-CRP, a general inflammation marker). By limiting immune-cell adhesion to the vessel wall, it may slow the earliest steps of plaque formation.

* **Antioxidant and AMPK activity:** Hesperidin scavenges reactive oxygen molecules and activates AMP-activated protein kinase (AMPK, a cellular energy sensor that promotes fat and glucose breakdown). AMPK activation is the proposed link to the observed effects on blood lipids and glucose.

* **Competing mechanistic interpretation:** A nuance in the human data is that the nitric-oxide signaling pathway requires a small, transient burst of hydrogen peroxide to work. Some researchers therefore argue that hesperetin's benefit reflects a mild beneficial-stress (hormetic) signal rather than simple antioxidant activity, and that high co-administration of strong antioxidants could theoretically blunt the effect. This remains a hypothesis rather than a settled point.

* **Pharmacological properties:** Hesperidin itself is poorly absorbed intact; it is hydrolyzed by gut bacteria to hesperetin, which is then absorbed and circulated mainly as glucuronide and sulfate conjugates. The plasma half-life of these metabolites is roughly 5–7 hours, supporting once- or twice-daily dosing. Bioavailability is highly variable between individuals and depends heavily on gut microbiome composition; the 2S-diastereoisomer used in Cordiart is absorbed substantially better than the standard mixture. Metabolism occurs via gut microbial enzymes and hepatic phase-II conjugation rather than through the cytochrome P450 (CYP) drug-metabolizing enzymes that dominate most pharmaceutical interactions.

## Historical Context & Evolution

* **Original use:** Hesperidin was first isolated from orange peel in the 19th century and was historically grouped with "vitamin P" (a now-abandoned term for citrus bioflavonoids). Its earliest medical uses were for capillary fragility and venous conditions such as varicose veins and hemorrhoids, where hesperidin combined with diosmin remains a registered phlebotonic (vein-toning) treatment in parts of Europe.

* **Shift toward cardiometabolic health:** Interest broadened as population studies linked higher citrus and flavonoid intake to lower cardiovascular risk. Mechanistic and clinical work in the 2000s and 2010s—most notably the demonstration that oral hesperidin improved blood vessel function and lowered inflammation markers in people with metabolic syndrome—reframed hesperidin from a vein remedy into a candidate for general vascular and metabolic support.

* **Findings, not just reception:** The pivotal metabolic-syndrome trial reported an absolute improvement in flow-mediated dilation (the ultrasound measure of how well an artery widens) and reductions in hs-CRP and other inflammatory proteins. A later trial of the specific 2S form in a healthier overweight population did not reproduce the vessel-widening effect in the whole group, finding benefit only in a subgroup with healthier baseline vessel function. These differing results are best read as evidence that the effect depends on the starting vascular state, not as one study debunking the other.

* **Emergence of Cordiart:** Recognizing that ordinary hesperidin is erratically absorbed, ingredient developers created standardized, better-absorbed forms. Cordiart is a commercial extract built around the 2S-diastereoisomer to maximize bioavailability, and it has more recently received FDA generally-recognized-as-safe (GRAS) status as a food ingredient. A relevant conflict of interest should be kept in view here: much of the human evidence specific to the 2S form (including the bioavailability and pivotal cardiovascular trials) was produced by or with the ingredient developer BioActor/Eurecat, which has a direct financial stake in the product's adoption.

* **Evolution of opinion:** The scientific picture is still moving. Meta-analyses now fairly consistently show small improvements in blood lipids, while effects on blood pressure and blood sugar remain inconsistent across reviews. The current state is one of promising but not definitive evidence, with the direction of future trials likely to refine rather than close the question.

## Expected Benefits

A dedicated search of clinical trials, meta-analyses, and expert sources was performed to compile the benefit profile of hesperidin, the active compound in Cordiart. Benefits are framed for risk-aware adults seeking to optimize vascular and metabolic health, who may act on modest, biomarker-level signals.

### Medium 🟩 🟩

#### Improved Blood Lipid Profile

Hesperidin supplementation modestly lowers total cholesterol, LDL ("bad") cholesterol, and triglycerides. The proposed mechanism is AMPK activation influencing fat metabolism plus reduced vascular inflammation. Multiple independent meta-analyses of randomized controlled trials converge on a significant lipid-lowering effect, which is the most reproducible finding across the hesperidin literature. The magnitude is small and would be most meaningful as one component of a broader strategy rather than as a standalone lipid therapy.

**Magnitude:** Meta-analyses report reductions of roughly 0.3–0.6 mmol/L for LDL and total cholesterol and about 0.2 mmol/L for triglycerides versus placebo.

#### Reduced Vascular Inflammation Markers

Hesperidin lowers circulating inflammation and endothelial-activation markers, including high-sensitivity C-reactive protein (hs-CRP), TNF-α, and cell-adhesion molecules that let immune cells stick to vessel walls. The mechanism is reduced expression of adhesion molecules and dampened inflammatory signaling in the vessel lining. Human trials in metabolic syndrome and overweight populations show consistent directional reductions, though absolute changes are modest and not uniform across all markers.

**Magnitude:** In a controlled trial, hs-CRP fell by roughly a third versus baseline; meta-analysis confirms a significant TNF-α reduction.

### Low 🟩

#### Improved Endothelial Function ⚠ Conflicted

Hesperidin can improve flow-mediated dilation—the ability of an artery to widen in response to increased blood flow—via increased nitric oxide production, with benefit clearest in people who already have impaired vessel function or metabolic syndrome and absent in healthier groups, which keeps this benefit at the Low grade despite a plausible mechanism. The evidence is directly conflicted: the Rizza et al. metabolic-syndrome trial (500 mg/day) found a clear improvement in flow-mediated dilation, whereas the Salden 2016 trial of the 2S form (450 mg/day) in healthier overweight adults found no improvement in the overall group and benefit only in a subgroup with relatively healthy baseline vessel function. The discrepancy is most plausibly explained by differences in baseline vascular health and population, illustrating that any vessel benefit appears state-dependent rather than universal.

**Magnitude:** One trial reported flow-mediated dilation of 10.3% on hesperidin versus 7.8% on placebo (≈2.5 percentage-point gain) in impaired-vessel populations; another found no whole-group effect in healthier adults.

#### Lower Systolic Blood Pressure

Some meta-analyses report a small reduction in systolic (top number) blood pressure with hesperidin, attributed to nitric-oxide-mediated vessel relaxation. The signal is inconsistent—at least one large pooled analysis found no significant blood-pressure effect—so it is graded Low and would be most relevant to those with elevated baseline readings.

**Magnitude:** Where significant, systolic reductions are on the order of 2–4 mmHg; several analyses report no significant change.

#### Modest Glycemic and Metabolic Improvements

Hesperidin may slightly lower fasting blood sugar and improve some markers in people with metabolic syndrome or fatty liver disease, plausibly through AMPK activation and reduced inflammation. Findings are inconsistent across reviews, with effects on insulin and insulin-resistance indices generally not significant, supporting a Low grade.

**Magnitude:** Fasting glucose reductions are small and variable; effects on insulin resistance are generally not statistically significant.

### Speculative 🟨

#### Support for Healthy Aging via Reduced Vascular Inflammation

Because chronic low-grade inflammation and declining vessel function are central features of biological aging, the anti-inflammatory and nitric-oxide effects of hesperidin have been proposed to support long-term vascular health and longevity. This is mechanistically reasonable but rests on surrogate biomarkers and short trials; no controlled study has measured hard outcomes such as cardiovascular events, mortality, or lifespan, so the longevity framing remains hypothesis-generating only.

#### Cognitive and Cerebral Blood Flow Benefits

Hesperidin's nitric-oxide and blood-flow effects have prompted interest in possible cognitive benefits, and an ongoing trial of a related glucosyl-hesperidin is examining cerebral blood flow and cognition. Current human evidence specific to cognition is preliminary and largely indirect, so any cognitive benefit is anecdotal or mechanistic at this stage.

## Benefit-Modifying Factors

* **Genetic polymorphisms:** No specific human gene variant (e.g., in drug-metabolizing or transporter genes) has been established as modifying hesperidin's benefits. The dominant biological determinant of response is not a germline polymorphism but the gut-microbiome's capacity to convert hesperidin to absorbable hesperetin, which varies widely between individuals.

* **Gut microbiome composition:** Because hesperidin must be converted to hesperetin by gut bacteria before absorption, individuals classified as "high producers" of hesperidin metabolites are likely to derive more benefit than "low producers." This is the single largest source of variability in response and is partly addressed by the better-absorbed 2S form in Cordiart.

* **Baseline vascular health:** The clearest vessel-function benefits appear in people with metabolic syndrome or impaired baseline endothelial function; those with already-healthy arteries may see little measurable change.

* **Baseline biomarker levels:** Those with elevated baseline LDL cholesterol, triglycerides, hs-CRP, or blood pressure have more room to improve and tend to show larger absolute changes than people already in optimal ranges.

* **Pre-existing conditions:** People with metabolic syndrome, type 2 diabetes, or non-alcoholic fatty liver disease are the populations in which benefits have most often been detected.

* **Sex-based differences:** Trials have generally enrolled both sexes without reporting consistent sex-specific differences in response; dedicated analyses are lacking, so sex-based effects are currently undefined rather than established.

* **Age:** Endothelial function and nitric-oxide availability decline with age, so older adults within the target range may have more to gain from a nitric-oxide-supporting compound, though this has not been directly tested across age strata.

## Potential Risks & Side Effects

A dedicated search of trial safety data, drug-reference sources, and pharmacovigilance information was performed to compile the risk profile of hesperidin, the active compound in Cordiart. Hesperidin has a long history of food and supplement use and a favorable safety record; identified risks are predominantly mild.

### Low 🟥

#### Gastrointestinal Discomfort

The most commonly reported adverse effects are mild digestive complaints—abdominal pain, diarrhea, or nausea—likely related to gut fermentation of the compound. These are infrequent, generally self-limiting, and comparable to placebo in most trials. They are more likely at higher doses and tend to resolve with continued use or dose reduction.

**Magnitude:** Reported in a small minority of participants across trials, with rates generally similar to placebo.

#### Modest Weight Increase

At least one dose-response meta-analysis observed a small but statistically significant increase in body weight with hesperidin supplementation, the mechanism of which is unclear and possibly a chance or confounded finding. This is the only consistently flagged unexpected signal in the otherwise benign profile and warrants noting for an audience tracking body composition.

**Magnitude:** A small average increase in body weight reached statistical significance in one pooled analysis; not confirmed elsewhere.

### Speculative 🟨

#### Bleeding Risk with Anticoagulants

Like several flavonoids, hesperidin may have mild antiplatelet effects and could theoretically add to the action of blood-thinning medications, increasing bleeding risk. No clinical bleeding events have been attributed to hesperidin in trials, so this risk is mechanistic and precautionary rather than demonstrated.

#### Drug-Metabolizing Enzyme and Transporter Effects

In laboratory studies hesperidin can influence certain drug-handling proteins (such as P-glycoprotein and some metabolizing enzymes), raising a theoretical possibility of altered levels of co-administered medications. These effects have not been shown to be clinically meaningful at supplement doses in humans, keeping this in the speculative range.

#### Pregnancy and Lactation Safety

There is insufficient controlled human data on concentrated hesperidin supplementation during pregnancy or breastfeeding to establish safety. The risk is one of unknown rather than demonstrated harm, and dietary citrus intake is not implicated.

## Risk-Modifying Factors

* **Genetic polymorphisms:** No specific human gene variant has been shown to modify hesperidin's risk or side-effect profile. Because hesperidin is cleared mainly through gut-microbial and hepatic phase-II conjugation rather than the polymorphic cytochrome P450 enzymes that drive many drug-level interactions, common pharmacogenetic variants are not expected to meaningfully alter its safety.

* **Concurrent anticoagulant or antiplatelet use:** People taking blood thinners or antiplatelet drugs may be more susceptible to any additive bleeding effect and represent the group warranting most caution.

* **Baseline biomarker levels:** Those already on lipid- or glucose-lowering therapy could in principle experience additive effects; monitoring relevant biomarkers helps detect over-correction, though clinically significant additive effects have not been reported.

* **Pre-existing conditions:** Individuals with bleeding disorders, or those scheduled for surgery, fall into a higher-caution category for the theoretical antiplatelet effect.

* **Pregnancy and lactation:** Pregnant or breastfeeding individuals constitute a population for whom concentrated supplementation lacks safety data, modifying the risk-benefit balance toward caution.

* **Sex-based differences:** No sex-specific differences in adverse-effect rates have been established in the available trials.

* **Age:** No age-specific safety concerns have been identified within the adult range; the safety profile appears consistent across the age groups studied.

## Key Interactions & Contraindications

* **Anticoagulant and antiplatelet drugs:** Warfarin, direct oral anticoagulants (apixaban, rivaroxaban), and antiplatelet agents (aspirin, clopidogrel) — caution, theoretical additive bleeding risk. Clinical consequence: potential for increased bleeding. Mitigation: monitor for bruising or bleeding and discuss with a clinician before combining.

* **Antihypertensive drugs:** Blood-pressure-lowering medications (ACE inhibitors [angiotensin-converting enzyme inhibitors, which relax blood vessels] such as lisinopril, calcium channel blockers such as amlodipine) — caution, possible additive lowering of blood pressure. Clinical consequence: low blood pressure or dizziness in susceptible individuals. Mitigation: monitor blood pressure, especially when starting.

* **Lipid-lowering and glucose-lowering drugs:** Statins and oral glucose-lowering agents (metformin) — monitor; any additive effect on lipids or glucose is likely small. Mitigation: track relevant labs.

* **Over-the-counter medications:** Over-the-counter antiplatelet agents (aspirin) and NSAIDs (non-steroidal anti-inflammatory drugs, common pain and anti-inflammatory medicines such as ibuprofen and naproxen) — caution for additive bleeding tendency.

* **Supplement interactions:** Other blood-pressure-lowering or blood-thinning supplements (e.g., omega-3 fish oil, garlic, *Ginkgo biloba*, nattokinase) may have additive vascular or antiplatelet effects. Other nitric-oxide-supporting supplements (L-citrulline, beetroot/nitrate) could be additive for vasodilation.

* **Substrates of drug transporters/enzymes:** Medications handled by P-glycoprotein or affected phase-II enzymes — theoretical interaction only; no specific clinical guidance established.

* **Populations who should avoid or use caution:** Pregnant or breastfeeding individuals (insufficient safety data); people with bleeding disorders or scheduled for surgery within roughly 2 weeks; individuals on multiple blood-pressure or blood-thinning agents without clinician oversight.

## Risk Mitigation Strategies

* **Conservative dosing aligned with studied range:** Use the clinically studied 500 mg/day rather than higher experimental doses to mitigate the gastrointestinal discomfort and the unexplained weight-increase signal seen at higher intakes; there is no clear benefit to exceeding the studied dose for vascular endpoints.

* **Pre-surgical washout:** To mitigate the theoretical additive bleeding risk, discontinue at least 1–2 weeks before scheduled surgery or invasive procedures, consistent with general guidance for antiplatelet-acting supplements.

* **Blood-pressure monitoring when combining vasoactive agents:** To mitigate the risk of excessive blood-pressure lowering, monitor blood pressure when taking Cordiart alongside antihypertensive drugs or other blood-pressure-lowering supplements, particularly in the first few weeks.

* **Bleeding awareness with anticoagulants:** To mitigate additive bleeding risk, those on anticoagulant or antiplatelet therapy should watch for unusual bruising or bleeding and obtain clinician sign-off before starting.

* **Gradual introduction with food:** To mitigate gastrointestinal discomfort, take the dose with a meal and, if sensitive, begin with a lower amount before reaching the full 500 mg/day.

* **Avoidance in unstudied populations:** To avoid exposure where safety is undefined, pregnant and breastfeeding individuals should refrain from concentrated supplementation pending adequate data.

## Therapeutic Protocol

* **Standard dose:** Most human trials of hesperidin for cardiometabolic endpoints, and the marketing of Cordiart, center on 500 mg once daily of the standardized extract. This is the dose with the most supporting human data for vascular and inflammation markers.

* **Higher-dose approach:** Some dose-response analyses suggest certain endpoints (fasting glucose, lipids) may respond more at doses near 1,000 mg/day of conventional hesperidin. With the better-absorbed 2S form in Cordiart, the lower 500 mg dose is intended to achieve comparable exposure, so escalation is generally unnecessary. These competing approaches—higher dose of standard hesperidin versus standard dose of a high-bioavailability form—are presented without one being framed as definitive.

* **Form selection (popularized approach):** The 2S-diastereoisomer plus micronization approach was developed and characterized by the BioActor/Eurecat group and underlies Cordiart; it aims to overcome the erratic absorption of ordinary hesperidin.

* **Best time of day:** No strong chronobiological data exist. Taking it with a meal supports absorption and may reduce digestive complaints; consistency of timing matters more than the specific hour.

* **Half-life and dose splitting:** Circulating hesperetin metabolites have a half-life of roughly 5–7 hours. A single daily dose is the studied and common approach; splitting into two doses is a reasonable option to maintain steadier metabolite levels but has no demonstrated outcome advantage.

* **Genetic and microbiome considerations:** No specific human gene variants (e.g., APOE4, a variant affecting fat metabolism and cardiovascular risk; MTHFR, a gene controlling folate processing; COMT, an enzyme that breaks down stress-related neurotransmitters) are established as dose-modifiers. The most relevant biological variable is gut-microbiome conversion capacity; "low-producer" individuals may benefit from the higher-bioavailability 2S form rather than dose escalation.

* **Sex-based differences:** No validated sex-specific dosing differences have been established.

* **Age considerations:** No age-specific dose adjustment is defined; older adults within the target range may be a priority group given age-related decline in vessel function, but dosing is the same.

* **Baseline biomarkers:** Those with elevated LDL, triglycerides, hs-CRP, or blood pressure are the individuals most likely to register measurable change and may use these markers to gauge response.

* **Pre-existing conditions:** People with metabolic syndrome or fatty liver disease are the populations in which benefits have most often been observed and a reasonable focus for a trial of the intervention.

## Discontinuation & Cycling

* **Lifelong versus short-term use:** Hesperidin's benefits on biomarkers appear to persist only while it is taken; there is no evidence of durable change after stopping, so it is best viewed as an ongoing supplement rather than a time-limited course.

* **Withdrawal effects:** No withdrawal syndrome or rebound effect has been reported on discontinuation; any biomarker improvements would be expected to gradually revert toward baseline.

* **Tapering:** No tapering is required; the compound can be stopped abruptly without known adverse consequence.

* **Cycling:** There is no evidence that the body develops tolerance to hesperidin or that cycling improves or maintains efficacy; continuous daily use is the studied pattern, and cycling is neither supported nor needed.

## Sourcing and Quality

* **Standardization to the active form:** The key quality marker for a Cordiart-type product is standardization to a high hesperidin content in the 2S-diastereoisomer form, which drives the improved absorption that distinguishes it from generic hesperidin.

* **Third-party testing:** Look for products with third-party testing or certification for identity, potency, and contaminants (heavy metals, microbial limits), since botanical extracts can vary in quality between manufacturers.

* **Source material and traceability:** Reputable extracts specify the citrus source (typically *Citrus sinensis*, sweet orange) and provide a clear standardization percentage; the branded Cordiart ingredient is supplied by Solabia Nutrition/BioActor and carries FDA generally-recognized-as-safe (GRAS) status, which supports its identity and food-grade quality.

* **Distinguishing forms:** Be aware that "hesperidin," "2S-hesperidin," and "glucosyl-hesperidin" (an enzymatically modified, water-soluble form sold under other brand names) are not identical; the evidence summarized here applies most directly to standardized 2S-hesperidin as in Cordiart.

* **Reputable suppliers:** Finished products built on recognized standardized ingredients (such as the Cordiart branded ingredient itself) are preferable to generic, unstandardized citrus bioflavonoid powders when the goal is the vascular effects described in trials.

## Practical Considerations

* **Time to effect:** Biomarker changes in trials typically emerged over 3–12 weeks; vascular and inflammation markers shifted within about 3 weeks in the metabolic-syndrome study, while lipid changes were clearer at 12 weeks or longer. Benefits are gradual, not acute.

* **Common pitfalls:** Using generic, poorly absorbed hesperidin and expecting the results seen with standardized 2S forms; expecting symptomatic effects when the changes are biomarker-level; and combining with multiple blood-pressure or blood-thinning agents without monitoring.

* **Regulatory status:** In the United States hesperidin is sold as a dietary supplement and the Cordiart ingredient holds FDA generally-recognized-as-safe (GRAS) status as a food ingredient; it is not an approved drug for any cardiovascular indication. In parts of Europe, hesperidin-diosmin combinations are registered for venous conditions, a separate regulatory context.

* **Cost and accessibility:** Cordiart and standardized 2S-hesperidin products are widely available and modestly priced relative to many specialty supplements; cost is not a major barrier.

## Interaction with Foundational Habits

* **Sleep:** Interaction is indirect and minimal. Hesperidin is not a stimulant and has no established effect on sleep architecture; some preliminary work suggests citrus flavonoids may be neutral-to-mildly-favorable for sleep, but there is no reliable signal and no specific timing precaution.

* **Nutrition:** Interaction is direct and potentiating in the sense that taking the dose with a meal—particularly one that supports gut fermentation and contains some fat—aids absorption of the metabolite. A diet already rich in citrus and other flavonoids provides background intake; the supplement adds a standardized, better-absorbed dose on top of that dietary base.

* **Exercise:** Interaction is potentially potentiating and indirect. Both exercise and hesperidin support nitric-oxide-mediated vessel function and blood flow, so effects may be complementary; an ongoing trial is examining a related glucosyl-hesperidin for exercise performance and recovery. There is no evidence it blunts training adaptations, and no specific timing around workouts is established.

* **Stress management:** Interaction is indirect. By lowering inflammatory markers, hesperidin may modestly counter some downstream effects of chronic stress on the vasculature, but it has no demonstrated direct effect on cortisol or the stress response, and it is not a substitute for stress-management practices.

## Monitoring Protocol & Defining Success

Baseline testing before starting Cordiart helps identify whether an individual is likely to register measurable benefit and provides a reference point. Because the intervention acts on cardiometabolic biomarkers, a baseline lipid panel, fasting glucose, hs-CRP, and blood pressure are the most informative starting measures.

Ongoing monitoring can be done at baseline, then at roughly 12 weeks, then every 6–12 months, reflecting the time course over which lipid and inflammation changes emerge.

| Biomarker | Optimal Functional Range | Why Measure It? | Context/Notes |
|-----------|--------------------------|-----------------|---------------|
| LDL cholesterol | < 100 mg/dL (often < 70 mg/dL for high-risk) | Primary lipid target hesperidin may lower | Fasting preferred; part of a standard lipid panel |
| Triglycerides | < 100 mg/dL | Responsive lipid marker | Requires 9–12 h fast; affected by recent alcohol and refined carbohydrate |
| Total cholesterol | < 180 mg/dL | Broad lipid overview | Interpret alongside LDL, HDL ("good" high-density lipoprotein cholesterol), and triglycerides |
| High-sensitivity C-reactive protein (hs-CRP) | < 1.0 mg/L | Tracks vascular inflammation, a key proposed effect | Avoid measuring during acute illness or injury, which falsely elevates it |
| Fasting blood glucose | 70–85 mg/dL | Detects modest glycemic effect | Requires fasting; pair with HbA1c (glycated hemoglobin, a 3-month average of blood sugar) for trend |
| Systolic/diastolic blood pressure | < 120/80 mmHg | Captures any vascular-relaxation effect | Measure seated, rested; average multiple readings; conventional "normal" is < 130/80 |

Qualitative markers complement lab data and reflect how an individual feels over time.

* Energy levels and general sense of vitality
* Exercise tolerance and perceived circulation (e.g., cold hands and feet)
* Absence of digestive discomfort indicating good tolerability

## Emerging Research

Research framed for risk-aware adults seeking vascular and metabolic optimization continues across both supportive and skeptical directions.

* **Glucosyl-hesperidin for blood flow, exercise, and cognition:** A randomized trial is evaluating a related, highly water-soluble form (glucosyl-hesperidin, "CitraPeak") on brachial artery blood flow, exercise performance, recovery, and cognition. [NCT06672952](https://clinicaltrials.gov/study/NCT06672952) is a dose-response study enrolling about 60 participants, with primary endpoints including peak oxygen uptake and post-ingestion blood flow.

* **Bioflavonoids and vascular wall remodeling:** A trial examining hesperidin-containing bioflavonoids on vascular wall remodeling in varicose veins, [NCT06367166](https://clinicaltrials.gov/study/NCT06367166), enrolls about 100 participants with biomarkers of venous wall remodeling as primary endpoints, extending the historical venous-health use into mechanistic territory.

* **Bioavailability optimization:** Work characterizing the 2S-diastereoisomer and micronization, such as Crescenti et al. ([PMID 35745211](https://pubmed.ncbi.nlm.nih.gov/35745211/)), continues to refine how to deliver more active compound, which could change effective dosing for future products.

* **Direction that could strengthen the case:** Adequately powered trials in metabolic-syndrome and impaired-endothelium populations, where benefits have been clearest, could firm up the vascular-function and inflammation findings reported by Rizza et al. ([PMID 21346065](https://pubmed.ncbi.nlm.nih.gov/21346065/)).

* **Direction that could weaken the case:** The neutral whole-group result in healthier overweight adults from Salden et al. ([PMID 27797708](https://pubmed.ncbi.nlm.nih.gov/27797708/)) and the inconsistent blood-pressure findings across meta-analyses suggest that larger, more rigorous trials could attenuate some currently reported benefits, particularly for blood pressure and endothelial function in lower-risk groups.

* **Future research areas:** Long-term studies measuring hard cardiovascular outcomes rather than biomarkers, and analyses stratifying by gut-microbiome conversion capacity, are the most likely to change current understanding.

## Conclusion

Cordiart is a standardized, better-absorbed citrus extract whose active ingredient is hesperidin, a flavonoid from oranges. Its appeal rests on the idea that it supports the inner lining of blood vessels by raising production of the vessel-relaxing molecule nitric oxide and by calming low-grade inflammation. For adults focused on optimizing heart and metabolic health, the most dependable signal is a small lowering of blood fats and inflammation markers, seen consistently across pooled analyses of human trials. Effects on blood vessel widening, blood pressure, and blood sugar are real in some studies but absent in others, and appear to depend on a person's starting health—benefits are clearest in those with existing risk factors and least apparent in already-healthy people. The compound has a long history of food and supplement use and a reassuring safety profile, with only mild digestive complaints commonly reported and a few theoretical cautions around blood-thinning medicines and pregnancy. Importantly, the evidence to date rests on short trials and blood-test markers rather than long-term outcomes such as heart events or lifespan. A further caveat is that much of the evidence specific to the branded, better-absorbed form comes from the ingredient's commercial developer, a conflict of interest worth weighing. Overall, the case for Cordiart is promising but unsettled, and how much absorbed compound an individual's gut produces may shape whether it helps at all.

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


Cordyceps sinensis
Ophiocordyceps sinensis
Cordyceps militaris
Dong Chong Xia Cao
Chinese caterpillar fungus

Cordyceps is a traditional caterpillar fungus, now mostly grown in laboratories as Cordyceps militaris or fermented mycelium, valued for centuries as an energy and stamina tonic. The best-supported benefit for active, health-focused adults is a modest improvement in aerobic endurance and tolerance to hard exercise, seen mainly after several weeks of consistent higher-dose use. There is also reasonable evidence that it nudges immune-cell activity upward and lowers some inflammation markers, though whether this means fewer illnesses in healthy people is unproven. Its clearer medical uses — supporting kidney and lung function — come from add-on therapy in patients and rest on low-quality studies. Longevity claims are still speculative, based on cell and animal work rather than human outcomes.

The main practical concerns are not the fungus itself but product quality: wild material and cheap powders can carry arsenic and other contaminants or be watered down with starch, so verified, tested, cultivated products matter. Side effects are generally mild, though it may add to blood-thinning and blood-sugar-lowering medicines and is best avoided in autoimmune or transplant situations. The overall evidence base is uneven — promising for stamina, plausible for immunity, and thin for healthy aging — much of it from small or lower-quality trials, leaving real uncertainty about how much a proactive, health-focused user can expect from a well-chosen product.

---
canonical_name: Cordyceps
alternate_names: Cordyceps sinensis, Ophiocordyceps sinensis, Cordyceps militaris, Dong Chong Xia Cao, Chinese caterpillar fungus
canonical_topic: Cordyceps for Health & Longevity
short_topic_lc: cordyceps
creation_date: 2026-0617-0005
creator_ai_fullname: Opus 4.8
ep_keywords: Medicinal Mushrooms, Mushrooms, Fungi
---

# Cordyceps for Health & Longevity

Evidence Review created on 06/17/2026 using [AI4L](https://github.com/forever-healthy/AI4L) / Opus 4.8

**Also known as:** Cordyceps sinensis, Ophiocordyceps sinensis, Cordyceps militaris, Dong Chong Xia Cao, Chinese caterpillar fungus

## Motivation

Cordyceps is a group of parasitic fungi traditionally harvested from the Tibetan plateau, where one species grows out of the bodies of caterpillar larvae. For centuries it has been brewed into tonics meant to restore energy, stamina, and resilience. Today most products use a laboratory-grown relative, *Cordyceps militaris*, or fermented mycelium rather than the rare and costly wild fungus. Its best-known active compound, cordycepin, is chemically close to a building block the body uses to make cellular energy, which is why it draws interest from people focused on stamina and healthy aging.

The fungus became prominent outside Asia in the 1990s after Chinese runners credited it for record-breaking performances, sparking interest in whether it could genuinely improve oxygen use and endurance. Beyond athletics, it is studied for immune signaling, kidney support, and the fatigue that often accompanies aging.

This review examines what the human and laboratory evidence shows about Cordyceps for stamina, immune function, and broader health and longevity goals, where the data are strong, where they are thin, and where commercial quality concerns complicate the picture.

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

## Recommended Reading

This section lists high-level overviews and expert commentary that introduce Cordyceps and its primary uses for a general health- and longevity-oriented audience.

* [Q&A #52: supplemental tyrosine, lion's mane, cordyceps, aging tests, and sunscreen](https://www.foundmyfitness.com/episodes/qa-52-dr-rhonda-patrick) - Rhonda Patrick

  Patrick addresses listener questions on functional mushrooms including Cordyceps, discussing the limited human evidence behind popular energy and cognition claims and the gap between marketing and data — a useful skeptical primer for this audience.

* [Beat Fatigue and Boost ATP Production with a Powerful Herbal Duo](https://www.lifeextension.com/magazine/2014/2/beat-fatigue-and-boost-atp-production-with-powerful-herbal-duo) - Aram Stepovich

  A consumer-facing overview of how Cordyceps is proposed to raise cellular energy (ATP — adenosine triphosphate, the body's main energy currency) production and reduce fatigue, summarizing the mechanistic rationale that drives most longevity-oriented interest in the fungus.

* [Ergogenic Aid by Cordyceps: Does It Work??](https://doi.org/10.1007/s13668-025-00690-9) - Dewi & Khemtong, 2025

  A recent narrative review in Current Nutrition Reports that weighs the human exercise-performance evidence for Cordyceps, including its limitations, providing a balanced expert appraisal of the most-marketed benefit.

* [Current Evidence of Ergogenic and Post-Exercise Recovery Effects of Dietary Supplementation with Cordyceps militaris in Humans](https://pubmed.ncbi.nlm.nih.gov/41829950/) - Jędrejko et al., 2026

  A narrative review focused specifically on *Cordyceps militaris* — the species in most modern supplements — summarizing what controlled human trials show about endurance, recovery, and dosing.

* [Edible mushrooms: an ancient remedy rediscovered by modern science](https://chriskresser.com/edible-mushrooms-an-ancient-remedy-rediscovered-by-modern-science/) - Chris Kresser

  A practitioner overview of medicinal mushrooms with a dedicated *Cordyceps militaris* section covering its traditional tonic use, exercise-performance and anti-fatigue evidence, immune effects, and how the cultivated species differs from wild *Ophiocordyceps sinensis* — an accessible expert primer for this audience.

*Note: No dedicated, in-depth standalone Cordyceps content was found from Peter Attia or Andrew Huberman; one qualifying academic source was added in their place to reach five high-quality items.*

## Grokipedia

* [Cordyceps](https://grokipedia.com/page/Cordyceps)

  The Grokipedia entry compiles the taxonomy, traditional use, bioactive compounds, and modern research directions for Cordyceps, providing a broad single-page reference that situates the supplement within both its biological and therapeutic context.

## Examine

* [Cordyceps](https://examine.com/supplements/cordyceps/)

  Examine's evidence-graded page reviews the human research on Cordyceps for outcomes such as exercise performance, immune markers, and fatigue, making it a rigorous, citation-backed counterweight to promotional sources.

## ConsumerLab

No dedicated ConsumerLab article on Cordyceps was found.

## Systematic Reviews

This section summarizes the most relevant systematic reviews and meta-analyses of Cordyceps identified through a real-time PubMed search.

* [Effects of fungal supplementation on endurance, immune function, and hematological profiles in adult athletes: a systematic review and meta-analysis](https://pubmed.ncbi.nlm.nih.gov/41280379/) - Shu et al., 2025

  Pooling 14 randomized controlled trials (RCTs — studies that randomly assign participants to treatment or placebo) in 528 athletes, this meta-analysis found *Cordyceps sinensis* significantly improved endurance performance, ventilatory threshold, and peak oxygen uptake (VO₂peak) with low heterogeneity, the strongest synthesis to date for the performance claim.

* [Adjuvant treatment with Cordyceps sinensis for lung cancer: A systematic review and meta-analysis of randomized controlled trials](https://pubmed.ncbi.nlm.nih.gov/38484953/) - Wang et al., 2024

  Across 12 RCTs and 928 patients, *Cordyceps sinensis* added to conventional lung-cancer therapy improved tumor response, immune markers, and quality of life while reducing chemotherapy-related blood toxicity; trials were largely conducted in China and add-on to standard care, limiting generalizability.

* [Efficacy of traditional Chinese medicine Cordyceps sinensis as an adjunctive treatment in patients with renal dysfunction: a systematic-review and meta-analysis](https://pubmed.ncbi.nlm.nih.gov/39839641/) - Wu et al., 2024

  This meta-analysis reports that Cordyceps preparations added to standard kidney care improved markers of renal function; as with most Cordyceps trials, methodological quality of the included studies was modest.

* [Cordyceps sinensis (a traditional Chinese medicine) for treating chronic kidney disease](https://pubmed.ncbi.nlm.nih.gov/25519252/) - Zhang et al., 2014

  A Cochrane review of 22 trials (1,746 participants) found Cordyceps as add-on therapy may lower serum creatinine and proteinuria, but rated the evidence low-quality due to high or unclear risk of bias across nearly all studies — a recurring theme for this fungus.

* [Effectiveness and Safety of Oral Cordyceps sinensis on Stable COPD of GOLD Stages 2-3: Systematic Review and Meta-Analysis](https://pubmed.ncbi.nlm.nih.gov/31073318/) - Yu et al., 2019

  Fifteen RCTs (1,238 participants) suggested Cordyceps may improve lung function, exercise endurance, and quality of life in chronic obstructive pulmonary disease (COPD — a progressive lung disease), but the authors note no trial was placebo-controlled or of high methodological quality.

## Mechanism of Action

Cordyceps acts through several compound classes rather than a single drug-like molecule, which makes its pharmacology diffuse and product-dependent.

* **Cordycepin (3′-deoxyadenosine):** The signature constituent is structurally almost identical to adenosine, a building block of the cellular energy molecule ATP. This similarity lets cordycepin interact with nucleotide-handling enzymes and RNA synthesis, and is the basis for proposed effects on energy metabolism and cell signaling. Cordycepin is rapidly broken down by the enzyme adenosine deaminase, so much of its activity in the body may come from downstream metabolites.

* **Polysaccharides and β-glucans:** Cordyceps cell walls are rich in complex sugars that engage pattern-recognition receptors on immune cells, notably Dectin-1, triggering natural killer (NK) cell and macrophage activation. This is the leading mechanistic explanation for the immune-signaling effects seen in trials.

* **Adenosine and nucleosides:** Beyond cordycepin, the fungus supplies adenosine and related nucleosides that may support vasodilation (widening of blood vessels) and oxygen delivery — the proposed route for endurance benefits.

Where mechanisms compete: proponents argue cordycepin raises ATP availability and oxygen efficiency in working muscle, supported by animal swim-time and human VO₂max (maximal oxygen uptake, the peak rate of oxygen the body can use during exercise) data. Skeptics counter that cordycepin's very short half-life and extensive first-pass metabolism mean little intact compound reaches tissues after oral dosing, so observed benefits may instead reflect polysaccharide-driven anti-inflammatory or immune effects, or be inconsistent across products with widely varying cordycepin content. Both views remain unresolved because few trials measure blood levels of active compounds.

As a multi-compound botanical rather than a single pharmacological agent, Cordyceps has no defined systemic half-life, selectivity, tissue distribution, or single metabolic pathway; cordycepin specifically is metabolized primarily by adenosine deaminase to 3′-deoxyinosine.

## Historical Context & Evolution

* **Original use:** Wild *Ophiocordyceps sinensis* — a fungus that infects and grows out of caterpillar larvae on the Tibetan plateau — has been used in traditional Tibetan and Chinese medicine for centuries as a tonic (Dong Chong Xia Cao) for fatigue, kidney and lung complaints, low libido, and convalescence. Its rarity made it one of the most expensive natural products in the world, historically reserved for nobility.

* **Why it came to health optimization:** Western interest surged in 1993 when Chinese distance runners set multiple world records and their coach attributed performance partly to a Cordyceps-based tonic. This drew researchers to test whether the fungus genuinely improved oxygen uptake and endurance, shifting it from a traditional tonic toward a studied ergogenic (performance-enhancing) and longevity supplement.

* **What the early research actually found:** Initial Western exercise trials in the late 1990s and 2000s using wild-type or early cultivated extracts were largely null or weak for VO₂max, which tempered enthusiasm. The actual findings were modest, not dramatic — a contrast to the marketing that grew around the 1993 running story.

* **Standing of that research today:** Rather than being simply dismissed, the early null trials are now read alongside later studies using *Cordyceps militaris* and standardized cultivated products, some of which (e.g., the 2016 high-intensity exercise trial and a 2025 meta-analysis) report measurable endurance gains. The picture that emerged is that species, dose, cultivation method, and exercise intensity all matter — earlier negative results may reflect lower-potency preparations rather than a true absence of effect. The current evidence base remains evolving rather than settled, with quality of trials the main limiting factor on either side.

## Expected Benefits

A dedicated search of clinical trial databases, meta-analyses, and expert sources was performed to compile the complete benefit profile below. Benefits are framed for risk-aware adults considering Cordyceps as a self-directed health and longevity supplement.

### High 🟩 🟩 🟩

No benefit currently meets the threshold of consistent, high-quality, placebo-controlled human evidence in healthy adults. The strongest signals are graded Medium below.

### Medium 🟩 🟩

#### Aerobic Endurance & Exercise Capacity

Cordyceps may modestly improve aerobic capacity and tolerance to high-intensity exercise, the most consistently studied benefit and the one most relevant to active longevity-focused adults. The proposed mechanism is improved oxygen utilization and ATP availability in working muscle. The evidence basis is a 2025 meta-analysis of 14 RCTs in athletes showing significant gains in endurance, ventilatory threshold, and VO₂peak with low heterogeneity, plus a double-blind RCT showing VO₂max rose by roughly 4.8 ml·kg⁻¹·min⁻¹ after three weeks of a *Cordyceps militaris* blend. Nuance: benefits appear with chronic dosing (≥3 weeks) and higher doses (around 4 g/day), are absent acutely, and several earlier trials with wild-type extracts were null.

**Magnitude:** VO₂max increase of approximately +4.8 ml·kg⁻¹·min⁻¹ and time-to-exhaustion gains of +28 to +70 seconds after 1–3 weeks at 4 g/day in one RCT; meta-analytic improvements in VO₂peak and ventilatory threshold across 14 trials.

#### Immune Signaling (NK Cell Activity)

Cordyceps appears to increase natural killer (NK) cell activity and modulate immune signaling, of interest to adults focused on immune resilience with age. The mechanism is engagement of immune receptors (notably Dectin-1) by fungal β-glucans and polysaccharides. The evidence basis includes a 2024 placebo-controlled RCT in healthy adults where a fermented *Cordyceps militaris* beverage significantly raised NK cell activity and lowered inflammatory cytokines (interleukins IL-1β and IL-6), alongside adjuvant cancer trials reporting raised immune markers. Nuance: changes are in laboratory immune markers, not demonstrated reductions in infections or clinical disease in healthy people.

**Magnitude:** Significant within- and between-group increases in NK cell activity over 4–8 weeks; reductions in IL-1β and IL-6 from baseline. Clinical endpoints (illness frequency) not quantified.

### Low 🟩

#### Kidney Function Support (Adjunctive)

In people with chronic kidney disease, Cordyceps added to standard care may lower serum creatinine and protein in the urine. The mechanism is proposed to involve anti-inflammatory and anti-fibrotic effects on kidney tissue. The evidence basis is a Cochrane review of 22 trials and several later meta-analyses, all rating included studies as low quality with high or unclear bias; this is a therapeutic-population benefit rather than a longevity benefit for healthy adults.

**Magnitude:** Mean serum creatinine reduction of about 60 μmol/L and 24-hour proteinuria reduction of about 0.15 g in pooled analyses, with low confidence.

#### Anti-Fatigue & Subjective Energy

Cordyceps is traditionally used and widely marketed to reduce fatigue and improve subjective energy. The mechanism is the proposed ATP and oxygen-utilization effects. The evidence basis is largely animal swim-time studies (20–94% increases) and small or open-label human reports; rigorous placebo-controlled trials in healthy, non-fatigued adults are sparse. Anti-fatigue claims should be read as plausible but weakly substantiated in humans.

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

#### Lung Function in COPD (Adjunctive)

In chronic obstructive pulmonary disease, Cordyceps preparations added to standard therapy may improve lung function and exercise endurance. The mechanism overlaps with its oxygen-utilization and anti-inflammatory effects. The evidence basis is a meta-analysis of 15 RCTs, none placebo-controlled or high quality; this is a clinical-population benefit, not a general longevity claim.

**Magnitude:** Improvements in measures such as the six-minute walk distance and FEV1 (forced expiratory volume in one second, a standard lung-function measure) reported across trials, with low methodological confidence.

### Speculative 🟨

#### Healthy-Aging & Longevity Signaling

Direct human evidence that Cordyceps extends healthspan or lifespan does not exist; the longevity rationale is extrapolated from mechanistic and animal work. Cordycepin influences energy-sensing and inflammatory pathways (including signaling related to mTOR and AMPK, cellular nutrient- and energy-sensing systems), and rodent studies report antioxidant and metabolic effects. The basis here is mechanistic and preclinical only, with no controlled human longevity outcomes.

#### Libido, Sexual & Reproductive Function

Traditional use emphasizes restoration of vitality and libido, and some animal studies report improved sperm parameters and testosterone signaling. Human controlled trials are minimal, so any sexual-function benefit rests on traditional use, mechanistic plausibility, and isolated reports rather than robust clinical data.

## Benefit-Modifying Factors

* **Genetic factors:** No validated genetic polymorphisms are known to modify Cordyceps benefits. Individual variation in adenosine-handling enzymes (such as adenosine deaminase, which breaks down cordycepin) could plausibly influence response to the cordycepin-driven effects, but this is mechanistic speculation and not clinically established or actionable.

* **Cordycepin content of the product:** Benefits track active-compound dose, and commercial products vary enormously — from negligible cordycepin in mislabeled or mycelium-on-grain products to several milligrams per serving in standardized *Cordyceps militaris* extracts. A product with little cordycepin or β-glucan is unlikely to reproduce trial results regardless of the user.

* **Baseline fitness and training status:** Endurance gains appear most measurable in already-active or athletic individuals tested at high exercise intensity; sedentary users may notice less, and ceiling effects may limit gains in highly trained athletes.

* **Baseline immune and inflammatory status:** Immune-marker changes (NK activity, cytokine reduction) may be more apparent in those with elevated baseline inflammation than in robustly healthy individuals already at optimal markers.

* **Pre-existing kidney or lung disease:** The clearest clinical benefits are seen in people with chronic kidney disease or COPD as add-on therapy; these do not necessarily transfer to healthy adults using Cordyceps for prevention.

* **Sex-based differences:** A 2024 RCT found the timing and magnitude of NK-activity increases differed between men and women (men responding by 4 weeks, women by 8 weeks), suggesting sex may modify immune response, though data are too limited to be definitive.

* **Age:** Older adults with age-related decline in mitochondrial efficiency or immune function are the implied target for longevity use, but no trials have specifically demonstrated greater benefit at the older end of the adult range; this remains an assumption rather than a finding.

## Potential Risks & Side Effects

A dedicated search of drug-reference and safety sources was performed to compile the complete risk profile below. Cordyceps is generally well tolerated in trials, and most concerns relate to product quality and specific populations rather than intrinsic toxicity.

### High 🟥 🟥 🟥

No severe, frequent, well-documented adverse effect of standardized Cordyceps in healthy adults rises to the High evidence level. The most substantiated concerns are graded Medium and Low below.

### Medium 🟥 🟥

#### Heavy Metal & Adulterant Contamination

The most consistently documented real-world risk is not the fungus itself but contamination and adulteration of products. The mechanism is environmental uptake of toxic elements and deliberate substitution. The evidence basis includes published analyses finding arsenic, lead, cadmium, and mercury in wild *Cordyceps sinensis* — with arsenic sometimes exceeding national limits — and repeated reports of cheaper products adulterated with non-Cordyceps material, starch, or undeclared fillers. For chronic longevity-oriented use, cumulative exposure to inorganic arsenic is the principal concern.

**Magnitude:** Arsenic content in wild material can exceed regulatory limits; inorganic (toxic) arsenic reported around 8–9% of total arsenic in some samples, with potential accumulation over prolonged intake.

#### Mild Gastrointestinal Effects

The most common direct side effect is mild gastrointestinal upset — nausea, dry mouth, diarrhea, or stomach discomfort. The mechanism is nonspecific tolerability of a high-dose fungal powder. The evidence basis is adverse-event reporting in clinical trials, where such effects are infrequent, mild, and self-limiting; serious adverse events are rarely reported.

**Magnitude:** Generally affects a small minority of users; transient and dose-related.

### Low 🟥

#### Bleeding Risk / Antiplatelet Effect

Cordyceps may have mild blood-thinning (antiplatelet) activity. The mechanism is proposed adenosine-related inhibition of platelet aggregation. The evidence basis is mechanistic and isolated case-level concern rather than trial-documented bleeding; relevant mainly when combined with anticoagulant or antiplatelet drugs or before surgery.

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

#### Immune Stimulation in Autoimmune Conditions

By increasing immune cell activity, Cordyceps could theoretically worsen autoimmune disease or interfere with immunosuppressive therapy. The mechanism is β-glucan-driven immune activation. The evidence basis is mechanistic extrapolation from its documented NK-cell and cytokine effects, not direct reports of autoimmune flares; caution is precautionary.

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

#### Hypoglycemia (Additive)

Cordyceps may modestly lower blood glucose. The mechanism is improved insulin sensitivity reported in animal and some human data. The evidence basis is preclinical and limited clinical signal; the practical risk is additive lowering when combined with diabetes medication.

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

### Speculative 🟨

#### Allergic / Hypersensitivity Reactions

As a fungal product, Cordyceps could provoke allergic reactions in mold- or fungus-sensitive individuals. Reports are rare and isolated, so the basis is anecdotal rather than from controlled data.

#### Drug-Metabolism Interactions

Cordyceps constituents could theoretically alter activity of drug-metabolizing liver enzymes, affecting other medications. Human data are minimal, making this a mechanistic possibility rather than a documented effect.

## Risk-Modifying Factors

* **Genetic factors:** No validated genetic polymorphisms are known to modify Cordyceps-related risks. Variation in adenosine-handling enzymes (such as adenosine deaminase, which breaks down cordycepin) could in principle influence the adenosine-mediated antiplatelet effect, and variants affecting drug-metabolizing enzymes could theoretically alter interaction risk, but neither is clinically established or actionable for this fungus.

* **Product source and testing:** The single largest risk modifier is whether the product is third-party tested for heavy metals and verified for species identity. Cultivated *Cordyceps militaris* from tested suppliers carries far lower contamination risk than wild *sinensis* of uncertain origin.

* **Concurrent anticoagulant or antiplatelet use:** Genetic and clinical factors affecting bleeding risk (e.g., individuals on warfarin, direct oral anticoagulants, or aspirin) amplify the theoretical antiplatelet concern.

* **Baseline glucose and diabetes treatment:** People on insulin or sulfonylureas may be more susceptible to additive blood-sugar lowering.

* **Autoimmune disease or immunosuppression:** Individuals with autoimmune conditions or organ transplants on immunosuppressants are the population in whom the immune-activation risk is most relevant.

* **Sex-based differences:** No clinically meaningful sex-based differences in adverse effects have been established in the available trials.

* **Age and organ function:** Older adults and those with reduced kidney or liver function may clear contaminants such as arsenic less efficiently, making cumulative-exposure concerns more pertinent at the older end of the target range.

## Key Interactions & Contraindications

* **Anticoagulant and antiplatelet drugs:** Combining Cordyceps with prescription blood thinners (warfarin, apixaban, rivaroxaban) or antiplatelet agents (clopidogrel, aspirin) may additively increase bleeding risk. Severity: caution. Consequence: increased bleeding. Mitigation: avoid the combination around surgery; separate use and monitor for bruising or bleeding.

* **Antidiabetic medications:** Cordyceps may add to the glucose-lowering effect of insulin, sulfonylureas (glipizide, glyburide), and metformin. Severity: caution/monitor. Consequence: hypoglycemia. Mitigation: monitor blood glucose, especially when starting.

* **Immunosuppressants:** Because Cordyceps activates immune cells, it may oppose drugs such as cyclosporine, tacrolimus, and corticosteroids used after transplant or for autoimmune disease. Severity: caution to avoid. Consequence: reduced drug efficacy or graft risk. Mitigation: avoid in transplant recipients unless supervised.

* **Over-the-counter NSAIDs and aspirin:** Over-the-counter blood-thinning pain relievers (ibuprofen, naproxen, aspirin) compound the theoretical antiplatelet effect. Severity: caution. Consequence: additive bleeding tendency. Mitigation: timing separation and monitoring.

* **Supplement interactions:** Additive effects are plausible with other supplements that thin the blood or lower glucose. Supplements with additive antiplatelet effects include fish oil (EPA & DHA), ginkgo (*Ginkgo biloba*), garlic, and high-dose vitamin E; supplements with additive glucose-lowering effects include berberine, chromium, and alpha-lipoic acid. Severity: caution. Mitigation: avoid stacking multiple agents with the same direction of effect without monitoring.

* **Other interventions:** Cordyceps is often sold in mushroom blends (with reishi/*Ganoderma lucidum*, lion's mane/*Hericium erinaceus*); blends complicate attribution of both benefit and risk and may carry additive immune effects.

* **Populations who should avoid it:** People with autoimmune disease, organ-transplant recipients on immunosuppression, those with bleeding disorders or scheduled for surgery (discontinue ≥2 weeks prior), pregnant or breastfeeding individuals (insufficient safety data), and those with poorly controlled diabetes on medication without monitoring.

## Risk Mitigation Strategies

* **Choose third-party tested, cultivated products:** To address the heavy-metal and adulteration risk, select cultivated *Cordyceps militaris* or fermented mycelium products with a certificate of analysis showing testing for arsenic, lead, cadmium, and mercury, and verified species identity — avoiding untested wild *sinensis*.

* **Verify active-compound standardization:** To address the risk of an ineffective or mislabeled product, look for products that disclose cordycepin and/or β-glucan content (e.g., a stated percentage), which also reduces reliance on starch-heavy mycelium-on-grain fillers.

* **Stop before surgery:** To mitigate the bleeding/antiplatelet risk, discontinue Cordyceps at least 2 weeks before any scheduled surgery or invasive procedure.

* **Monitor glucose if diabetic:** To mitigate additive hypoglycemia, individuals on diabetes medication should check blood glucose more frequently for the first few weeks and adjust under medical guidance.

* **Start at a low dose:** To reduce gastrointestinal upset and detect intolerance, begin at the low end (around 1 g/day) and titrate up to the studied 3–4 g/day range over 1–2 weeks.

* **Avoid in immune-sensitive conditions:** To mitigate immune-activation risk, those with autoimmune disease or on immunosuppressants should avoid use unless supervised by a clinician.

## Therapeutic Protocol

* **Standard protocol:** Most performance and immune trials use 1–4 g/day of *Cordyceps militaris* extract or fermented mycelium, taken daily for at least 3–6 weeks before judging effect; the 2016 exercise RCT that found VO₂max gains used 4 g/day for 3 weeks. Practitioners oriented toward energy and immunity typically suggest 1–3 g/day of a standardized extract.

* **Competing approaches:** Two main approaches coexist without one being clearly superior. One favors cultivated *Cordyceps militaris* for its higher and more controllable cordycepin content; the other favors fermented *Ophiocordyceps sinensis* mycelium products (such as Cs-4/Paecilomyces hepiali strains) used in most kidney and lung trials. Whole-fruiting-body extracts and standardized hot-water/dual extracts are promoted by the supplement-quality community over mycelium-on-grain powders.

* **Who popularized each:** The fermented Cs-4 mycelium approach derives largely from Chinese pharmaceutical research and the renal/pulmonary trial literature; the standardized *militaris* extract approach is favored by Western supplement-quality advocates and sports-nutrition researchers (e.g., the University of North Carolina exercise group behind the 2016 trial).

* **Best time of day:** Daily timing is not well established; for exercise benefit, dosing earlier in the day or before training is common, and some users avoid late-evening dosing in case of a mild stimulating effect, though no strong data dictate timing.

* **Half-life:** Cordyceps has no single defined half-life as a multi-compound botanical; cordycepin itself is cleared rapidly by adenosine deaminase, which is why sustained daily dosing rather than single doses is used.

* **Single vs. split dosing:** Because higher daily totals (3–4 g) are used and cordycepin clears quickly, splitting into two doses is reasonable, though most trials administered the daily amount without strict split-dose protocols.

* **Genetic factors:** No validated pharmacogenetic markers guide Cordyceps dosing; individual variation in adenosine-handling enzymes is plausible but not clinically actionable.

* **Sex-based differences:** A 2024 RCT suggested immune responses may emerge later in women than men, hinting that women may need longer dosing periods before immune-marker changes appear; this is preliminary.

* **Age-related considerations:** Older adults are the implied longevity audience; no age-specific dose adjustment is established, though starting low is prudent given reduced organ reserve at the older end of the range.

* **Baseline biomarkers:** Baseline kidney function, glucose, and inflammatory markers can contextualize who is most likely to respond and should be monitored where relevant.

* **Pre-existing conditions:** Those with kidney or lung disease using Cordyceps adjunctively should do so under medical supervision, consistent with the trial settings in which benefit was observed.

## Discontinuation & Cycling

* **Lifelong vs. short-term:** Cordyceps is used both as short courses (3–6 weeks for a performance block) and as ongoing daily supplementation for general energy and immune goals; no evidence mandates indefinite use, and there is no established maintenance requirement.

* **Withdrawal effects:** No withdrawal syndrome or dependence has been documented; benefits such as endurance gains would be expected to fade gradually once supplementation stops, as they appear to depend on continued dosing.

* **Tapering:** No tapering protocol is necessary; the supplement can be stopped abruptly without known rebound effects.

* **Cycling:** Some users cycle Cordyceps (e.g., several weeks on, then a break) on the theory of preserving responsiveness, but there is no controlled evidence that cycling maintains efficacy or that continuous use causes tolerance. Cycling also serves to limit cumulative heavy-metal exposure from lower-quality products.

## Sourcing and Quality

* **Species and form matter most:** Look for clearly labeled cultivated *Cordyceps militaris* or fermented *Ophiocordyceps sinensis* mycelium (e.g., Cs-4); avoid vague "Cordyceps" labels and unverified "wild" *sinensis*, which is expensive, frequently adulterated, and more prone to heavy-metal contamination.

* **Standardization:** Prefer extracts that disclose cordycepin and/or β-glucan percentages and specify an extraction method (hot-water or dual extraction) rather than raw mycelium-on-grain powders, which are often high in starch and low in active compounds.

* **Third-party testing:** Choose products with a published certificate of analysis covering heavy metals (arsenic, lead, cadmium, mercury), microbial limits, and identity verification — directly addressing the contamination and adulteration risks.

* **Reputable suppliers:** Brands oriented toward verified mushroom extracts (for example, suppliers that publish full certificates of analysis and beta-glucan content, such as Real Mushrooms and Nammex-sourced products) are commonly cited by quality-focused reviewers; this is not an endorsement but reflects transparency practices to look for.

* **Avoid proprietary blends without disclosure:** Many products bundle Cordyceps into proprietary mushroom blends without stating the Cordyceps dose, making it impossible to match the amounts used in trials.

## Practical Considerations

* **Time to effect:** Exercise and immune benefits in trials appeared after roughly 3 weeks or more of consistent daily dosing, not acutely; users should expect to dose for several weeks before judging effect.

* **Common pitfalls:** The most common mistakes are buying underdosed mycelium-on-grain products, using proprietary blends that hide the Cordyceps amount, expecting acute stimulant-like effects, and dosing below the 3–4 g/day range used in positive trials.

* **Regulatory status:** Cordyceps is sold as a dietary supplement in the United States and most Western markets, not an approved drug; it is not FDA-evaluated for efficacy, and quality is the manufacturer's responsibility. In parts of Asia, Cordyceps preparations are used as registered traditional medicines.

* **Cost and accessibility:** Cultivated *militaris* and fermented mycelium products are widely available and affordable; genuine wild *Ophiocordyceps sinensis* is among the most expensive natural products in the world and is largely impractical (and ecologically strained) as a supplement source.

## Interaction with Foundational Habits

* **Sleep:** The interaction is likely indirect and minimal. Some users report a mild energizing effect, so a small number may prefer to avoid late-evening dosing; there is no strong evidence Cordyceps disrupts or improves sleep architecture. Practical consideration: if mild stimulation is noticed, dose earlier in the day.

* **Nutrition:** The interaction is indirect. Cordyceps is a whole-fungus product with no established food-timing requirement; taking it with food may reduce the mild gastrointestinal upset some users experience. No nutrient depletion is documented. Practical consideration: take with a meal if stomach upset occurs.

* **Exercise:** The interaction is direct and potentiating for the primary studied benefit — endurance and high-intensity exercise tolerance improved in trials when Cordyceps was combined with training. A 2024 mechanistic RCT also suggested it accelerates muscle stem-cell recruitment and recovery after intense exercise. Practical consideration: pair chronic dosing (≥3 weeks) with an endurance or interval training program to align with the evidence.

* **Stress management:** The interaction is indirect and not well characterized. Cordyceps is traditionally framed as an adaptogen (a substance claimed to help the body resist stress), and animal data suggest effects on stress and fatigue resilience, but controlled human cortisol or stress-response data are lacking. Practical consideration: treat stress-resilience claims as unproven and rely on established stress-management practices.

## Monitoring Protocol & Defining Success

Before starting Cordyceps, establishing a few baseline measures helps gauge whether the supplement is delivering its intended benefit and remaining safe over time, particularly for those using it long-term or with relevant conditions.

Baseline testing should be performed before the first dose; for healthy users a minimal panel suffices, while those with kidney disease, diabetes, or on interacting medications warrant the fuller panel below. Ongoing monitoring is reasonable at roughly 3 months after starting and then every 6–12 months for long-term users, with more frequent glucose checks in the first few weeks for those on diabetes medication.

| Biomarker | Optimal Functional Range | Why Measure It? | Context/Notes |
| --------- | ------------------------ | --------------- | ------------- |
| Fasting glucose | 75–86 mg/dL | Detects additive glucose-lowering, especially if on diabetes medication | Fasting required; pair with HbA1c |
| HbA1c | < 5.4% | Tracks longer-term glucose effect | Glycated hemoglobin, a 3-month blood-sugar average; no fasting needed; reflects ~3 months |
| eGFR | > 90 mL/min/1.73m² | Relevant for those using Cordyceps for kidney support or with chronic kidney disease (CKD) | Estimated glomerular filtration rate, a kidney-function measure; paired with serum creatinine; conventional cutoff for normal is ≥60 |
| Serum creatinine | 0.6–1.0 mg/dL | Primary kidney marker improved in CKD trials | Hydration and muscle mass affect values |
| hs-CRP | < 1.0 mg/L | Captures the anti-inflammatory/immune signal | High-sensitivity C-reactive protein, an inflammation marker; avoid testing during acute illness; conventional "normal" extends to 3.0 mg/L |
| CBC with platelets | Within standard lab range | Screens immune/blood effects and bleeding risk | CBC = complete blood count; best paired with review of any anticoagulant use |
| Heavy metals (blood/urine arsenic) | Below detectable/regulatory limits | Surveillance for contamination with long-term use | Consider only with prolonged use or unverified products |

Qualitative markers are often the most practical gauge of benefit for this audience:

* Perceived endurance and exercise tolerance (e.g., ability to sustain a given pace or intensity)
* Energy levels and resistance to fatigue across the day
* Recovery quality after intense exercise
* Frequency and duration of minor illnesses (a rough proxy for immune effect)
* Subjective stamina and sense of vitality

## Emerging Research

Research framed for proactive adults is shifting from traditional kidney/lung uses toward exercise performance, immune signaling, and standardized *Cordyceps militaris* products, with several registered trials underway.

* **Sport and exercise applications of standardized *C. militaris*:** A completed 2025 trial ([NCT07310108](https://clinicaltrials.gov/study/NCT07310108), Lindenwood University, n=32) evaluated a specific *Cordyceps militaris* strain for exercise-nutrition applications in healthy active adults, with primary endpoints including time to exhaustion and VO₂max — directly testing the endurance claim in a Western setting.

* **Immune-response confirmation:** A completed RCT ([NCT06138444](https://clinicaltrials.gov/study/NCT06138444), University of Phayao, n=40) tested a *Cordyceps militaris* beverage on NK cells, immunoglobulins, and inflammatory cytokines in healthy adults — the trial underlying the 2024 immune-signaling findings, strengthening the case for the immune benefit.

* **Aging and inflammation biomarkers:** A completed botanical-formulation trial ([NCT06065241](https://clinicaltrials.gov/study/NCT06065241), LL Prosper Inc., n=32) measured proteomic inflammatory and cardiovascular biomarkers in healthy older individuals using a Cordyceps-containing formulation, probing the longevity-relevant inflammation angle (though Cordyceps is one of several ingredients).

* **Long COVID fatigue:** An ongoing trial ([NCT05684952](https://clinicaltrials.gov/study/NCT05684952), Hong Kong Baptist University, Phase 2, n=152) tests a Cordyceps-containing Chinese herbal medicine for post-viral fatigue, an outcome relevant to the anti-fatigue claim that could strengthen or weaken it depending on results.

* **Respiratory infection prevention:** A recruiting Phase 4 trial ([NCT07174076](https://clinicaltrials.gov/study/NCT07174076), n=300) examines *Cordyceps sinensis* for preventing recurrence of *Mycobacterium avium* complex pulmonary disease, extending the lung-immune evidence into infection prevention.

* **Future directions that could change understanding:** Key open questions include whether standardized cordycepin dosing produces dose-dependent endurance effects, whether immune-marker changes translate into fewer real-world infections, and whether any longevity-relevant outcomes (inflammation, metabolic markers) hold in adequately powered, placebo-controlled human trials. A 2024 mechanistic RCT on muscle stem-cell recruitment after exercise (Dewi et al., [10.1039/d3fo03770c](https://doi.org/10.1039/d3fo03770c)) points toward recovery as an emerging research direction. Studies that could weaken the case include rigorous placebo-controlled trials in untrained adults, where earlier wild-type extracts repeatedly failed to show benefit.

## Conclusion

Cordyceps is a traditional caterpillar fungus, now mostly grown in laboratories as *Cordyceps militaris* or fermented mycelium, valued for centuries as an energy and stamina tonic. The best-supported benefit for active, health-focused adults is a modest improvement in aerobic endurance and tolerance to hard exercise, seen mainly after several weeks of consistent higher-dose use. There is also reasonable evidence that it nudges immune-cell activity upward and lowers some inflammation markers, though whether this means fewer illnesses in healthy people is unproven. Its clearer medical uses — supporting kidney and lung function — come from add-on therapy in patients and rest on low-quality studies. Longevity claims are still speculative, based on cell and animal work rather than human outcomes.

The main practical concerns are not the fungus itself but product quality: wild material and cheap powders can carry arsenic and other contaminants or be watered down with starch, so verified, tested, cultivated products matter. Side effects are generally mild, though it may add to blood-thinning and blood-sugar-lowering medicines and is best avoided in autoimmune or transplant situations. The overall evidence base is uneven — promising for stamina, plausible for immunity, and thin for healthy aging — much of it from small or lower-quality trials, leaving real uncertainty about how much a proactive, health-focused user can expect from a well-chosen product.

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