What is Epimedium?

In May 2025, Endurance Boost with Horny Goat Weed, sold on Amazon, was recalled nationwide because it contained sildenafil and propoxyphenylsildenafil that were not on the label. The company's recall notice, posted by FDA on May 6, 2025, covered one lot (250214PRO, expiration 02/14/2027) and warned that the hidden drugs can interact with nitrates such as nitroglycerin and cause a drop in blood pressure that may be life threatening. A horny goat weed product that behaves like Viagra within the hour is more plausibly carrying a PDE5 drug than delivering enough icariin to matter, and the arithmetic is in the next section.

Epimedium is a genus of about 62 species of low woodland perennials in the barberry family (Berberidaceae), 52 of them in China, according to the 2022 taxonomic review by Zhang, Li, Wang and Liang in Chinese Herbal Medicines. The medicinal material is the dried leaf, yin yang huo (Epimedii Folium), roughly "lustful goat herb," after a legend of a shepherd who noticed rams mating more often after grazing on it.

The current Chinese standard accepts the leaves of four species as Epimedii Folium: Epimedium brevicornu Maxim., E. sagittatum (Sieb. et Zucc.) Maxim., E. pubescens Maxim. and E. koreanum Nakai. In practice, Guo and colleagues estimated in 2003 that more than 20 species may be sold as yin yang huo. American shelves carry it as a dietary supplement, usually an extract labeled by icariin content, and as a staple of "male enhancement" blends: in a 2019 analysis of the six top-ranked erectile dysfunction supplements on Amazon (Balasubramanian and colleagues, Journal of Sexual Medicine), horny goat weed was among the four most popular ingredients.

Common Names

Horny goat weed, yin yang huo, yinyanghuo, Epimedii Folium, Herba Epimedii, Epimedium leaf, xian ling pi, barrenwort, faeries spleen, copper wire grass, "Epimedium extract," "icariin extract." Labels also use species names outside the Chinese standard, notably Epimedium grandiflorum, and the catch-all "Epimedium spp."

Primary Active Compounds

Prenylated flavonol glycosides, which carry a five-carbon prenyl group at carbon 8 of the flavonoid ring: icariin (the marker almost every label names), epimedin A, epimedin B and epimedin C (often more abundant than icariin in the raw leaf), baohuoside I (the same molecule as icariside II), icariside I, and sagittatosides A and B. Gut bacteria strip the sugars to give icariside II and the aglycones icaritin and desmethylicaritin, and those metabolites, not icariin, are what human blood contains after a dose.

Key Note

The risk that can kill a buyer of this herb is not the herb. It is a sexual enhancement product carrying an undeclared PDE5 drug, taken by a man who also uses a nitrate for angina (Sections 7 and 17).

What follows: what icariin does to PDE5 and how little reaches the blood, the one long human bone trial and what it tested, the estrogen-like metabolites, and the products caught with prescription drugs inside.

Primary Functions & Benefits

PDE5 inhibition in a test tube: three labs, one direction

Three independent groups have measured icariin against the human enzyme, and all three found real but weak inhibition.

• Dell'Agli and colleagues (Milan, 2008) screened Tribulus terrestris, Ferula hermonis, Cinnamomum cassia and Epimedium brevicornum extracts against recombinant human PDE5A1. Only the Epimedium extract was active (80% inhibition at 50 micrograms per milliliter), and icariin was its active principle. The same paper made a semisynthetic derivative, 3,7-bis(2-hydroxyethyl)icaritin, in which both sugars are replaced by hydroxyethyl groups. It inhibited PDE5A1 at 75 nanomolar, essentially equal to sildenafil's 74, 80 times more potent than icariin, with better selectivity than sildenafil against PDE6, the retinal enzyme behind blue-tinged vision. It is a laboratory molecule, not in the plant and not in any supplement.

• Ning and colleagues (University of California San Francisco, Urology, 2006) tested icariin isolated from Epimedii herba against three PDE5 isoforms and found half-maximal inhibition at 1.0, 0.75 and 1.1 micromolar for PDE5A1, A2 and A3, about three times weaker than the older research inhibitor zaprinast (0.33, 0.23 and 0.32 micromolar).

• Li and colleagues (Chinese Medicine, 2022) isolated six flavonoids from processed E. sagittatum leaf and measured half-maximal inhibition of 8.275 micromolar for icariin, 3.233 for 2"-O-rhamnosylicariside II and 5.473 for baohuoside I (icariside II).

Across labs icariin's figure runs from about 0.75 to 8.3 micromolar, and icariside II, the metabolite that actually circulates, sits in the same range. Every one of those figures is far above the concentrations measured in animal or human blood after oral dosing (Section 15).

Erectile function in animals

In spontaneously hypertensive rats given icariin by gavage at 10 mg per kilogram per day for 4 weeks (Liu and colleagues, Andrology, 2020; 5 per group), the ratio of peak penile pressure to arterial pressure under nerve stimulation was roughly double that of untreated hypertensive rats (0.40 versus 0.21 at the highest values reported). In rats with surgically narrowed pudendal arteries, 5 and 10 mg per kilogram per day for 30 days raised intracavernous pressure and restored endothelial nitric oxide synthase expression (Tian and colleagues, 2004). In rats with crushed cavernous nerves, a model of nerve damage after prostate surgery, icariin at 1.5 mg per kilogram alone was not enough; only icariin plus daily sildenafil preserved erectile pressure and penile tissue (Xu and colleagues, Andrology, 2017). Several of these papers attribute the effect less to acute PDE5 blockade than to slower changes in nitric oxide synthase, oxidative stress and tissue structure over weeks. These are animal results, the doses are per kilogram of rat, and none of them is a dose for a man.

Erectile function in humans

In PubMed searches run for this issue in October 2026, I found no randomized controlled trial of Epimedium or icariin alone for erectile dysfunction published in English. Chinese-language databases were not searched, so that statement is bounded to the English literature. A 2026 review by Meng and Jiang in Sexual Medicine Reviews concluded that icariin's clinical efficacy "still requires further confirmation in high-quality randomized controlled trials." The two controlled human trials that include Epimedium tested multi-herb products:

• Cappra, a Thai traditional formula containing Epimedium together with Cistanche, Cynomorium and safflower (Carthamus), in a double-blind crossover trial in 63 men with mild or mild to moderate erectile dysfunction, two weeks per period (Punyawudho and colleagues, 2012). Sixty-one completed. The erectile function score rose 4.87 points on Cappra and 3.44 on placebo (p = 0.032).

• LEOPIN ROYAL, a Japanese nonprescription product with six ingredients (aged garlic extract, ginseng, oriental bezoar, velvet antler, cuscuta seed and epimedium herb), in an open-label randomized comparison with Kampo medicine in 49 men with symptoms of aging over 6 months (Nishimatsu and colleagues, The Aging Male, 2014). The IIEF-5 score improved more on LEOPIN ROYAL (p = 0.02 for the group by month interaction), with no placebo and no blinding.

Neither trial can attribute anything to Epimedium.

Libido

I found no human trial measuring sexual desire in men or women given Epimedium alone. The "libido" claim on labels rests on the traditional record and the animal erectile studies above.

Postmenopausal bone density

This is the one indication with a long, placebo-controlled human trial. Zhang, Qin and Shi at the Chinese University of Hong Kong (Journal of Bone and Mineral Research, 2007) randomized 100 healthy women 10 to 18 years past menopause, with lumbar spine T-scores between minus 2 and minus 2.5, to Epimedium-derived phytoestrogen flavonoids or placebo for 24 months. The daily treatment was 60 mg icariin, 15 mg daidzein and 3 mg genistein; everyone also took 300 mg of elemental calcium. Eighty-five completed. Placebo lost bone: lumbar spine minus 1.7% at 12 months (p = 0.019) and minus 2.4% at 24 months (p = 0.002), femoral neck minus 1.8% at 24 months (p = 0.048). The treated group held steady, with small nonsignificant gains. The between-group difference was significant at the lumbar spine at 12 months (p = 0.044) and 24 months (p = 0.006), and at the femoral neck at 24 months (p = 0.008), marginal at 12 (p = 0.061). Urinary deoxypyridinoline, a bone resorption marker, fell 43% at 12 months and 39% at 24 months on treatment; osteocalcin did not change significantly. Serum estradiol and endometrial thickness did not change in either group. Fracture was not among the outcomes the trial reports. Two limits: the preparation contained daidzein and genistein, the isoflavones best known from soy, so icariin's own contribution cannot be separated, and the result is in 85 completers, not 100.

A shorter trial measured markers rather than density. Yong and colleagues (Phytomedicine, 2021) gave 58 postmenopausal women a purified Epimedium prenylflavonoid extract at 740 mg daily or placebo for 6 weeks. Bone-specific alkaline phosphatase, a bone formation marker, was higher on treatment (p less than 0.05) and TRAF6 protein in blood monocytes trended lower (p = 0.068), with no change in liver, kidney or blood counts.

Two meta-analyses pool randomized trials of Epimedium preparations, including decoctions, used instead of or alongside standard osteoporosis drugs: Shi and colleagues (Frontiers in Pharmacology, 2022) included 12 trials and 1,017 patients, and Zhang and colleagues (Frontiers in Medicine, 2025) included 10 trials and 890 patients. Both reported better bone density and "effective rates" with Epimedium and both called for more rigorous trials.

Forms & Standardization

Raw and cut leaf (Epimedii Folium)

The dried leaf of the four standard species. The Chinese Pharmacopoeia 2020 monograph, unchanged on these points from its August 30, 2019 public-comment draft, requires total flavonoids, measured by ultraviolet absorbance at 270 nm and expressed as icariin, of not less than 5.0%, and a combined content of epimedin A, B and C plus icariin of not less than 1.5% for E. brevicornu, E. sagittatum and E. pubescens, and not less than 0.50% for E. koreanum. These are minimums. The 2015 edition had used icariin alone, at not less than 0.5%, and a 2021 survey of Epimedii Folium from East Asian producing regions (Li and colleagues, Frontiers in Pharmacology) noted reports of icariin being undetectable in some commercial batches and found some of its own samples below the 2020 standard.

Fat-processed leaf (zhi yin yang huo)

The same standard specifies 20 kg of rendered mutton fat per 100 kg of leaf, stir-fried until glossy. In rats and in Caco-2 gut-cell layers, adding suet oil to baohuoside I improved its uptake into bile-salt micelles and its oral bioavailability (Gu and colleagues, 2019). For processed leaf the standard requires baohuoside I of not less than 0.030% and epimedins A, B and C plus icariin of not less than 1.2% (0.40% for E. koreanum). I did not find a US supplement label that states fat processing.

Extracts labeled by icariin percentage

US products state icariin content in at least three different ways, and the difference changes the dose by a factor of three or more.

• "Minimum 3% icariin," with no test method stated. NOW Foods Horny Goat Weed Extract (product 4758): one 750 mg tablet of aerial-part (leaf) extract, species not named, plus 150 mg maca root (covered in its own issue). The label gives no milligrams of icariin; 3% of 750 mg is about 22.5 mg.

• "10% flavonoids, calculated as icariin." Nature's Way Horny Goat Weed: one 500 mg capsule of aerial-part extract from "Epimedium spp.," with the label stating 50 mg of flavonoids as icariin. It is not 50 mg of icariin. Planetary Herbals Full Spectrum Horny Goat Weed uses the same convention for the 1 g of extract in its 1,200 mg tablet.

• "10% icariin." Some products state a straight icariin percentage by HPLC, for example a 500 mg capsule of E. brevicornum aerial parts sold by Nootropics Depot with a minimum of 10% icariin by HPLC (about 50 mg).

Purified metabolites

Icaritin, the aglycone, is approved by China's National Medical Products Administration as a prescription drug for hepatocellular carcinoma.

Multi-ingredient "male enhancement" blends

These pair horny goat weed with maca, Tribulus, tongkat ali, yohimbe, ginseng, L-arginine and zinc, usually in a proprietary blend that discloses no per-ingredient amount. This is also the category in which FDA finds hidden drugs (Section 18).

Which form the human trials used

The 24-month bone trial used a defined flavonoid preparation of 60 mg icariin plus 15 mg daidzein and 3 mg genistein daily. The Singapore pharmacokinetic and bone-marker trials used a purified prenylflavonoid extract at 370 to 1,110 mg single doses and 740 mg daily. No published human trial that I found used a US retail horny goat weed capsule.

Food Sources

Epimedium is not a food, and icariin and the epimedins are not present in any common food in amounts that matter. Dietary intake is effectively zero. Exposure comes by four routes.

• Chinese prescriptions. The Chinese Pharmacopoeia 2020 monograph lists 6 to 10 g of leaf per day in decoction. That is a practitioner's prescription quantity for a crude herb that a practitioner also combines with other herbs, not a supplement dose.

• Chinese patent medicines, notably Xianling Gubao, a nonprescription osteoporosis capsule that is 70% Epimedii Folium by weight, with Dipsacus root 10% and Psoralea fruit, danshen root, Rehmannia root and Anemarrhena rhizome at 5% each (Piao and colleagues, BMC Complementary Medicine and Therapies, 2022). Its liver record is in Section 14.

• US dietary supplements: single-ingredient extracts and, far more often, multi-ingredient sexual enhancement blends.

• Tainted sexual enhancement products, which are a route of exposure to prescription PDE5 drugs rather than to the herb (Section 18).

Who Should Take Epimedium

No group has been shown in a randomized trial to benefit from a US retail horny goat weed product for erections or for sexual desire. A man buying it for erectile dysfunction is choosing an unproven extract over approved PDE5 drugs that have large placebo-controlled trials, known doses and known interaction lists, in a product category whose leading safety problem is undeclared prescription drug. Erectile dysfunction that is new, worsening or persistent deserves a medical evaluation in its own right.

The one group with a long human trial behind it is late postmenopausal women with low bone density, where the Hong Kong preparation held density steady while placebo lost about 2% over two years. Three caveats belong with that result: the preparation also contained soy-type isoflavones, it was compared with placebo rather than with an osteoporosis drug that has fracture data, and the preparation is not on a US shelf as far as I could find. A woman in that situation who wants to try an Epimedium product is making a reasonable bet only if she has no history of estrogen-sensitive cancer, tells her clinician, and keeps getting bone density scans.

Anyone who uses it anyway should buy a single-ingredient product and skip "male enhancement" blends (Section 18).

Who Should AVOID or Use Caution

Contraindications

• Anyone using a nitrate in any form: nitroglycerin tablets, spray, ointment or patch, isosorbide mononitrate, isosorbide dinitrate, or nitrite "poppers." The Viagra label contraindicates sildenafil in patients using "organic nitrates or organic nitrites in any form, either regularly and/or intermittently." A product sold as horny goat weed may contain sildenafil, tadalafil or an analog of either (Section 18), and the buyer cannot know which.

• Anyone taking riociguat (Adempas), a guanylate cyclase stimulator for pulmonary hypertension, which the Viagra label also contraindicates with PDE5 inhibitors, for the same reason.

• Pregnancy and breastfeeding. The circulating metabolites icaritin and desmethylicaritin act on the estrogen receptor (Section 15), and I found no human pregnancy or lactation data. The NOW Foods label itself says not recommended for pregnant or nursing women.

• A history of estrogen-receptor-positive breast cancer, or endometrial cancer. Icaritin and desmethylicaritin stimulated estrogen-receptor-positive MCF-7 breast cancer cells at 1 nanomolar to 10 micromolar, an effect the antiestrogen fulvestrant (ICI 182,780) blocked (Wang and Lou, European Journal of Pharmacology, 2004), and 740 mg a day of extract produced a median peak desmethylicaritin level of 60.9 nanomolar in postmenopausal women, inside that range. A mouse study found an E. brevicornum extract did not promote MCF-7 tumors (Indran and colleagues, Planta Medica, 2013), so the evidence points both ways; with no human data, a cancer survivor should not be the one to find out.

• Bipolar disorder. Partin and Pushkin (Psychosomatics, 2004) reported tachyarrhythmia and new-onset hypomania in a 66-year-old man with congestive heart failure, hospitalized with chest pain and shortness of breath after two weeks of daily horny goat weed taken as a sexual enhancer. The product was not tested, and the authors raised the possibility of other unidentified herbs or drugs in it. A 2025 report of psychosis in a man with Parkinson's disease (below) is a second psychiatric signal.

• Children.

Use Caution

• Men with heart disease. The Viagra label opens its warnings by noting "a potential for cardiac risk of sexual activity in patients with preexisting cardiovascular disease." A man who has been told not to take a PDE5 drug should not take a product that may contain one. The Partin and Pushkin patient (above) had heart failure and was hospitalized with a new symptomatic arrhythmia.

• Parkinson's disease, especially on ropinirole. Deliz and colleagues (Movement Disorders Clinical Practice, 2025) reported paranoid psychosis, delirium and new atrial fibrillation in a 59-year-old man with Parkinson's disease after a month of daily horny goat weed; he was hospitalized for 3 weeks. The authors raised CYP1A2 inhibition, which would raise ropinirole levels, and noted that the product's contents were unknown.

• Men on alpha blockers (doxazosin, tamsulosin and others) or strong CYP3A4 inhibitors such as ritonavir. Both multiply the effect of a hidden PDE5 drug; the specifics are in Section 17.

• Liver disease. The published record includes a US case of jaundice after more than a year of daily horny goat weed, and a Chinese formula that is 70% Epimedium leaf carries a liver injury notice (Section 14).

• Women on tamoxifen, letrozole, anastrozole or exemestane, or with endometriosis, fibroids or other estrogen-sensitive conditions. The metabolites' estrogen-receptor activity runs against these drugs and toward these conditions. This is theoretical, with no clinical report; the 24-month trial found no endometrial thickening at its dose, which is reassuring for that dose and population only.

• People on narrow-margin drugs handled by CYP1A2, CYP2B6, CYP2C9 or UGT1A1 and UGT1A9, where laboratory data show inhibition by Epimedium extract or icaritin (Section 17).

Critical Safety Point

The established hazard is the product category, not the plant. From 2007 through 2016, FDA warned about 776 adulterated dietary supplements, of which 353 (45.5%) were marketed for sexual enhancement, and sildenafil was the most common hidden drug in that group, found in 166 of the 353 (Tucker and colleagues, JAMA Network Open, 2018). Of 28 products named in repeat warnings, 19 had a new hidden ingredient the second time. The May 2025 Endurance Boost recall shows that "horny goat weed" on the front of the box is no protection. If you use any nitrate, do not take any sexual enhancement supplement, whatever its label says. If you reach an emergency department with chest pain after taking one, tell the staff what you took and when, because nitroglycerin is a first-line chest pain treatment.

Recommended Dosages

Epimedium has no clinically established dose for erections or libido; no human trial of the herb alone that I found measured either outcome. What follows describes what the products contain and the one human dose with a long-term result. Rat doses and the Chinese practitioner quantity live under Special Considerations instead, where they cannot be mistaken for a serving size.

Extracts stating an icariin percentage

NOW Foods directs one 750 mg tablet daily (about 22.5 mg icariin); a 500 mg capsule at 10% icariin by HPLC holds about 50 mg. Section 15 explains why even the higher figure falls far short of the enzyme data.

Extracts stating flavonoids "as icariin"

Nature's Way directs one 500 mg capsule twice daily, 100 mg a day of total flavonoids expressed in icariin units; actual icariin is not stated and is lower.

For postmenopausal bone

The only human dose with a two-year result is the Hong Kong trial's: 60 mg icariin, 15 mg daidzein and 3 mg genistein daily, with 300 mg elemental calcium, for 24 months. I found no US product that reproduces that combination. The Singapore extract at 740 mg daily was studied for 6 weeks, for safety, blood levels and bone markers, not for density.

Purified icariin (98%)

I found no human study of purified icariin for any sexual outcome, so there is no number to give.

Multi-ingredient blends

Proprietary blends do not disclose the horny goat weed amount, so no dose can be calculated. Avoid them for the reasons in Section 18.

Duration

Human safety data run to 24 months for the Hong Kong preparation and 6 weeks for the Singapore extract. I found no long-term human safety data for US retail extracts, and the one published US liver injury case followed more than a year of daily use.

Timing & Administration

No human study tests timing for any outcome. The pharmacokinetics argue against the "take before sex" pattern many blends suggest, because gut bacteria must strip the sugars before the absorbable forms appear (Section 10). Single-ingredient labels direct daily use, NOW "preferably with a meal."

Timeline of Effects

Onset in the blood

In a placebo-controlled single-dose trial in 30 healthy men, icariside II peaked 4.1 to 4.3 hours after the dose and desmethylicaritin 24.1 to 24.4 hours after, and icariin itself never appeared (Teo and colleagues, 2018). In the 6-week Singapore trial in women, the dominant circulating metabolite was desmethylicaritin.

The one-hour test

Sildenafil's label puts its peak plasma level 30 to 120 minutes after an oral dose (a prescription drug's figure, given here only as a red-flag test). Nothing in Epimedium's human pharmacokinetics supports a noticeable effect within that window. A product sold as horny goat weed that reliably produces a strong erection within an hour, or causes flushing, headache, nasal congestion or blue-tinged vision, is behaving like a PDE5 drug. Stop it and report it to FDA MedWatch.

Bone

In the Singapore trial, bone-specific alkaline phosphatase was higher on treatment within an 8-week window (6 weeks of dosing and 2 weeks of follow-up). In the Hong Kong trial, the spine density difference between groups was significant at 12 months and larger at 24 months. A fair test of anything claimed for bone therefore means a density scan after at least a year, not a feeling after a month.

Erections and desire

No human trial of Epimedium alone supplies a timeline. There is no trial-derived point at which to judge it working, and erectile dysfunction that persists is a reason for a medical evaluation rather than a longer course.

Benefits of Taking Epimedium

For bone, one placebo-controlled human trial of a defined Epimedium flavonoid preparation found that postmenopausal women with low bone density held their spine and hip density steady over 24 months while the placebo group lost about 2%. Trials of decoctions and formulas, pooled in two meta-analyses of 1,017 and 890 patients, point the same way at lower methodological quality. None of the trials described here reported fracture outcomes.

For erections and desire, no benefit of Epimedium alone has been demonstrated in humans, because the trials have not been done. That case rests on rat studies and on tradition.

Potential Negatives & Side Effects

In the controlled trials

The Singapore extract produced no significant adverse symptoms and no change in liver, kidney or blood tests over 6 weeks, and no adverse effects in the single-dose trial in men. In the Thai multi-herb crossover trial, dizziness was reported by 13.3% on the product and 9.6% on placebo, and facial numbness and tachycardia by 1.6% each on the product; those figures belong to a four-herb formula.

Case reports

• Tachyarrhythmia and new-onset hypomania in a 66-year-old man with heart failure after two weeks of daily use as a sexual enhancer (Partin and Pushkin, Psychosomatics, 2004).

• A painful vasculitic rash, with a 3-day hospital stay and normal liver tests, in a 77-year-old man taking Ginkgo biloba and horny goat weed together (Metz and colleagues, BMJ Case Reports, 2009).

• New-onset psychosis, delirium and new atrial fibrillation in a 59-year-old man with Parkinson's disease on ropinirole after a month of daily use (Deliz and colleagues, Movement Disorders Clinical Practice, 2025; Section 7).

• Severe muscle spasms with raised creatine kinase and creatinine, requiring admission, in a 33-year-old man one month after starting an internet-bought horny goat weed supplement (Ledo and colleagues, Cureus, 2025).

• Increased opioid cravings in a patient on buprenorphine after starting Herba Epimedii, which the authors attributed to a CYP3A4 interaction (Burke and colleagues, Cureus, 2024).

• Acute liver injury in a 53-year-old man after more than a year of daily use (2025, detailed in Section 14).

What military product-safety reviewers list

The Department of Defense's Operation Supplement Safety page (October 2024) lists stomach upset, nausea, vomiting, diarrhea, shortness of breath, chest pain, rapid or irregular heartbeat, irritability, aggression, inappropriate verbal or sexual behavior, dizziness, dry mouth, fever, headache, muscle spasm, nosebleeds and painful rash as reported with horny goat weed supplements. It does not say which products were involved, and several of those symptoms fit an undeclared PDE5 drug or a stimulant co-ingredient as well as the herb.

Estrogenic effects

The metabolites are estrogen-receptor agonists in cell assays (Section 15). I found no human study that looked for estrogenic effects in men taking Epimedium, such as breast tenderness or shifts in testosterone and estradiol, so the absence of reports reflects an absence of looking.

Deficiency Symptoms

What Epimedium addresses

No deficiency state exists. Prenylated flavonol glycosides are not required by any human tissue, and someone who has never eaten Epimedium is missing nothing. Erectile dysfunction is a vascular, neurological, hormonal or psychological condition, and postmenopausal bone loss follows the fall in the body's own estrogen; neither is a shortage of icariin.

Bottom line

There is no blood test for "Epimedium status" and no level to restore. Compare vitamin D, where a 25-hydroxyvitamin D measurement can identify a real shortfall; no equivalent marker exists for Epimedium.

Toxicity Symptoms

At high intake

The human liver record comes mostly through a multi-herb product. Xianling Gubao, 70% Epimedii Folium by weight, drew 2,665 reports to China's national adverse drug reaction database between January 1, 2004 and July 21, 2016, of which 81 (3.1%) were classed as severe, mainly raised liver enzymes and bilirubin. The China Food and Drug Administration issued a notice on its liver injury risk on December 8, 2016 (both as reported by Piao and colleagues, 2022). A 2024 case analysis (Li and colleagues, Chinese Herbal Medicines) scored one patient's acute severe hepatocellular injury on Xianling Gubao tablets as "highly probable" (updated RUCAM score 9), with no adulterant, pesticide or heavy metal excess in the product.

Which ingredient is responsible is disputed. Piao and colleagues found that of the six herbs only Psoralea fruit impaired mitochondrial respiration in human liver cells, through five of its compounds led by psoralidin, while Epimedii Folium extract, icariin and epimedin A did not, although in their earlier cell viability work Epimedii Folium was the most cytotoxic of the six after Psoralea. A 2023 rat study tied the more hepatotoxic of two Xianling Gubao extraction processes to 29.8 times more bakuchiol, a Psoralea compound. Against that, a Beijing group at the PLA Fifth Medical Centre reports that Epimedii Folium itself causes idiosyncratic, immune-mediated liver injury: icariside II and icariside I each amplified NLRP3 inflammasome activation in macrophages and, combined with a non-toxic dose of bacterial lipopolysaccharide, injured mouse livers in a way blocked by an NLRP3 inhibitor (Wang and colleagues, Acta Pharmaceutica Sinica B, 2020; Gao and colleagues, Cell Communication and Signaling, 2021). Icariside II is the main metabolite humans actually absorb.

For horny goat weed in the US, the published liver record I found is one case: a 53-year-old man with more than a year of daily use who presented with nausea, vomiting, dark urine and jaundice, total bilirubin 4.94 and ALT 516, and improved after stopping the herb and atorvastatin; he denied recent acetaminophen use (Shueb and colleagues, Spartan Medical Research Journal, September 2025). The product was not analyzed, no brand or dose was reported, and the statin is a competing cause. LiverTox, last updated August 2022, rates horny goat weed E, an unlikely cause of clinically apparent liver injury, and notes rare reports in multi-ingredient products where attribution "has not always been very clear."

Signs to reduce or stop

Stop at once and get liver tests (ALT, AST, alkaline phosphatase, bilirubin) for fatigue, nausea, loss of appetite, dark urine, pale or clay-colored stools, itchy skin or yellowing of the eyes. Stop and seek care for a racing or irregular pulse, chest pain, fainting, severe muscle spasms, or a sudden loss of vision or hearing. Stop for decreased need for sleep, racing thoughts, paranoia, confusion or uncharacteristic irritability. Stop and report the product to FDA MedWatch if it acts like a PDE5 drug (Section 10).

General note

There is no established toxic dose of Epimedium in humans. The more realistic acute danger from a "horny goat weed" bottle is a pharmaceutical dose of a PDE5 drug, or of an unapproved analog with no safety data at all, such as the propoxyphenylsildenafil in the 2025 recall, in a man who also uses nitrates or alpha blockers.

How Epimedium Works

From glycoside to metabolite

Icariin is icaritin carrying a rhamnose at carbon 3 and a glucose at carbon 7. Gut bacteria remove the glucose to make icariside II; losing the rhamnose gives icaritin, which can be demethylated to desmethylicaritin, and the liver adds glucuronide and sulfate groups. In rats given 30 mg per kilogram of pure icariin by mouth (Cheng and colleagues, 2015), icariside II appeared in plasma within 5 minutes and its total exposure was 13 times that of icariin itself; by the authors' calculation 91.2% of the oral icariin was converted. The molecule on the label is not the molecule in the body.

The PDE5 pathway, and why nitrates are the danger

Sexual stimulation releases nitric oxide in the penis; nitric oxide switches on guanylate cyclase, which makes cyclic GMP, which relaxes smooth muscle so blood flows in. PDE5 breaks cyclic GMP down, so an inhibitor amplifies the signal rather than starting it. A nitrate drug donates nitric oxide to the same pathway in blood vessels throughout the body, and with a working PDE5 inhibitor on board the two drive cyclic GMP up together, which is the mechanism behind the dangerous blood pressure falls on every PDE5 drug label. Riociguat stimulates the same guanylate cyclase.

The concentration gap, worked through

These comparisons use total plasma concentrations and ignore protein binding, for both drugs.

• Sildenafil: its label gives a reference peak of about 440 ng/mL after a 100 mg dose, which is about 930 nanomolar, roughly 12 times the 74 nanomolar figure for sildenafil in the Milan assay.

• Icariside II in rats: after 30 mg per kilogram of oral icariin, peak plasma icariside II was 29.6 ng/mL, about 57 nanomolar, roughly 95 times below the 5.47 micromolar figure for baohuoside I in the 2022 Chinese study.

• Icariside II in humans: after the highest single extract dose in the 2018 Singapore trial (1,110 mg), total icariside II exposure across the whole curve was 23.0 nanogram-hours per milliliter, about a fifth of the roughly 107 nanogram-hours per milliliter the rats reached after 30 mg per kilogram of pure icariin.

• Scale: FDA's 2005 guidance on starting doses converts a rat dose to a human equivalent by body surface area, dividing by about 6.2, so 30 mg per kilogram in a rat corresponds to about 4.8 mg per kilogram in a person, roughly 290 to 340 mg of pure icariin for a 60 to 70 kg adult. That is 13 to 15 times the 22.5 mg in a NOW tablet, and in rats it still left blood levels far below the enzyme's half-blocking range. This conversion is offered to show the size of the gap, not as a dose; no human has been studied on purified icariin for erections.

Estrogen-receptor activity

Icariin itself does not behave like an estrogen in breast cancer cell assays. Its aglycones do. In MCF-7 cells, 1 micromolar icaritin and desmethylicaritin produced 90% and 94% of the growth stimulation of estradiol, raised the estrogen-responsive progesterone receptor message, and were fully blocked by the antiestrogen ICI 182,780 (Ye and Lou, Phytomedicine, 2005; Wang and Lou, 2004). In mice, an E. brevicornum extract behaved like a selective estrogen receptor modulator, raising uterine weight only at the lowest dose and, at the highest, shrinking implanted MCF-7 tumors (Indran and colleagues, 2013). This is the most plausible route for the bone effect, alongside effects on osteoclast signaling through TRAF6, and the reason for the cancer and hormone-therapy cautions in Section 7.

Synergistic Supplements

Calcium (and the isoflavones that came with the trial preparation)

The 24-month bone result sat on top of 300 mg of elemental calcium a day in both groups, and the active preparation carried daidzein and genistein with the icariin. Any synergy is built into the product tested and cannot be separated out.

Prescription PDE5 drugs: not a stack to build yourself

There is no human study of the combination. The practical problem is that a horny goat weed product may already contain sildenafil or tadalafil, so adding a prescription tablet can mean taking two doses of the same drug class without knowing it.

What not to stack

Other sexual enhancement blends, which multiply the hidden-drug risk; stimulant co-ingredients such as yohimbe (covered in its own issue); concentrated phytoestrogen products such as red clover or soy isoflavone extracts in anyone with a hormone-sensitive cancer history; and Psoralea fruit (bu gu zhi) or bakuchiol products, given the liver signal in Section 14.

Interactions & What NOT to Take

Nitrates and nitrites

Nitroglycerin (sublingual, spray, ointment, patch), isosorbide mononitrate, isosorbide dinitrate, and amyl or other alkyl nitrite "poppers." Contraindicated with every PDE5 drug, and therefore with any sexual enhancement product that might hide one. For tadalafil, the manufacturer advises that at least 48 hours should pass after the last dose before a nitrate is considered, and then only under close medical supervision with blood pressure monitoring; for sildenafil, its label says it is unknown when nitrates can be given safely.

Guanylate cyclase stimulators

Riociguat (Adempas). Contraindicated with PDE5 inhibitors on the sildenafil label.

Alpha blockers and other blood pressure drugs

Doxazosin, terazosin, prazosin, tamsulosin, alfuzosin and silodosin, plus multiple antihypertensives together. Additive hypotension if the product contains a PDE5 drug.

Drugs that raise PDE5 drug levels

Ritonavir, ketoconazole, itraconazole, erythromycin and cimetidine raise sildenafil exposure; the label limits sildenafil to 25 mg in 48 hours with ritonavir. A hidden dose plus one of these is an unmeasured overdose.

Drug-metabolizing enzymes: the herb's own data

There is no human interaction study. Two case reports point at enzymes: increased opioid cravings on buprenorphine, attributed to CYP3A4 (Burke and colleagues, Cureus, 2024), and psychosis on ropinirole, where the authors raised CYP1A2 (Deliz and colleagues, 2025). The rest is laboratory or animal data:

• Icaritin inactivated CYP2C9 in a time-dependent, irreversible way in vitro (Chen and colleagues, Drug Metabolism and Disposition, 2023). CYP2C9 clears warfarin (the anticoagulant story belongs to another issue), phenytoin, glipizide and celecoxib. Icariin has also inhibited platelet activation in laboratory work (reviewed by Fang and Zhang, Frontiers in Pharmacology, 2017); I found no human bleeding report.

• Icaritin inhibited the glucuronidating enzymes UGT1A1 and UGT1A9 in human liver microsomes with inhibition constants of 2.694 and 1.431 micromolar (Rong and colleagues, Biopharmaceutics and Drug Disposition, 2024). UGT1A1 handles the active metabolite of irinotecan; UGT1A9 handles propofol and mycophenolic acid.

• An ethanol extract of E. koreanum inhibited CYP1A2 (half-maximal at 121.8 micrograms per milliliter, with time-dependent inhibition) and CYP2B6 (59.5 micrograms per milliliter) in human liver microsomes (Zhong and colleagues, Journal of Pharmacy and Pharmacology, 2017). CYP1A2 clears theophylline, tizanidine, clozapine and ropinirole; CYP2B6 clears bupropion and efavirenz. Repeated icaritin dosing reduced CYP1A2, CYP2C9 and CYP3A4 activity in rats (Liang and Zheng, Pharmazie, 2014).

Hormone-active drugs

Tamoxifen, raloxifene, aromatase inhibitors (letrozole, anastrozole, exemestane), estrogen-containing hormone therapy and contraceptives. Theoretical, through the estrogen-receptor activity of icaritin and desmethylicaritin.

Liver-loading drugs

Regular high-dose acetaminophen, methotrexate, isoniazid, valproate and other hepatotoxic drugs. The liver signal in Section 14 is modest and disputed, but there is no reason to add an unmeasured one.

Quality, Testing & Adulteration

Hidden prescription drugs

This is the defining quality failure of the category. The May 2025 Endurance Boost with Horny Goat Weed recall involved sildenafil plus propoxyphenylsildenafil, an unapproved analog for which I could find no published human safety data; the recall notice states plainly that "products containing sildenafil cannot be marketed as dietary supplements." Of the adulterated supplements FDA flagged in 2014 to 2016, 38.6% were found through online purchases and 34.3% through international mail shipments (Tucker and colleagues, 2018).

Species substitution

US labels often say only "Epimedium spp." or name E. grandiflorum, a species outside the Chinese standard. DNA barcoding does not fully solve this: in a study of 37 Chinese species (Guo and colleagues, Genes, 2018), the best single barcode region distinguished nine species and the best multi-region combinations 17, of which 12 are used medicinally. Chemical fingerprinting of the epimedin A, B, C and icariin pattern is the more practical identity test, and commercial leaf has been reported with no detectable icariin at all (cited by Li and colleagues, 2021).

Assay scope

"Icariin" and "flavonoids as icariin" are different measurements (Section 4). A product can meet its label claim on total flavonoids by ultraviolet absorbance while containing a small fraction of that as icariin by HPLC.

Third-party programs

ConsumerLab has tested sexual enhancement supplements since at least 2002 (9 of 22 passed that year; 3 of 10 in 2011), with current Epimedium-specific results behind its paywall. I did not find a USP or NSF certification program or a USP dietary supplement monograph specific to Epimedium. Horny goat weed is not on the Department of Defense prohibited ingredients list, though the department warns that products may be contaminated with prescription drugs.

What a certificate of analysis should carry, and what a shopper can confirm unaided

Ask the seller for the batch document before buying. It should name the species and plant part, the extraction solvent and ratio, icariin by HPLC in milligrams per serving (ideally epimedins A, B and C too), lead, cadmium, arsenic and mercury, microbial counts, and a mass spectrometry screen for PDE5 drugs and their analogs, with the laboratory named. Without a lab, a buyer can still choose a single-ingredient product over a blend, reject any "proprietary blend" or promise of results within minutes or hours, check that the panel distinguishes icariin from "flavonoids," and search the product name in FDA's tainted products database and recall list before the first dose.

Special Considerations

Rat doses and practitioner quantities, with their caveats

Rat studies used icariin by gavage at 1.5 to 10 mg per kilogram per day for 4 to 5 weeks or 30 days, and 30 mg per kilogram in the single-dose pharmacokinetic work. These are rat doses chosen to answer laboratory questions. The Chinese practitioner quantity is 6 to 10 g of crude leaf per day in decoction, and the Xianling Gubao clinical dose is 3 g per day of a six-herb formula, both prescribed in a system that also selects the species, the processing and the companion herbs. Icaritin is a purified prescription cancer drug in China. None of these is a supplement dose.

Women

Labels marketing horny goat weed to women for desire have no trial behind them.

Research Status & Evidence Quality

Tier 1: moderate human evidence, bone

One 24-month randomized, double-blind, placebo-controlled trial (n = 100 randomized, 85 completed) of a defined Epimedium flavonoid preparation containing icariin plus soy-type isoflavones, showing preserved spine and hip density in late postmenopausal women with low bone density. Supported by a 6-week marker trial and by two meta-analyses of lower-quality trials. Not replicated with the same preparation; no fracture outcome.

Tier 2: human pharmacokinetics

Two placebo-controlled studies from Singapore (30 men, single doses; 58 women, 6 weeks) establish that icariin itself is not detectable in human serum after oral extract and that icariside II, icaritin and desmethylicaritin are the circulating forms. Solid for what it measures.

Tier 3: in vitro and animal pharmacology, erections

PDE5 inhibition replicated across three laboratories at 0.75 to 8.3 micromolar for icariin; consistent improvements in erectile pressure in several rat models, mostly from a small number of Chinese groups with 5 to 12 animals per arm.

Tier 4: human evidence for erections or desire

No randomized trial of Epimedium alone found in the English literature. Two trials of multi-herb products, one small placebo-controlled crossover over two weeks and one open-label comparison with no placebo.

Research Limitations

The marker compound (icariin) is not the circulating compound, so standardizing products to icariin measures the wrong thing for systemic effects. The PDE5 potency data come from purified enzymes and isolated tissue at concentrations no oral dose has been shown to reach. The liver signal comes mostly through a six-herb Chinese formula, with laboratory evidence pointing at both Psoralea fruit and Epimedium's own metabolites. I found no human data on pregnancy, lactation, children or men's hormones on long-term use, and no human interaction studies.

Summary & Key Takeaways

Bottom Line

Epimedium is a real medicinal plant with a real, weak effect on the PDE5 enzyme in a test tube and a real, modest effect on postmenopausal bone loss in one two-year trial. For erections, the gap between the enzyme data and what reaches blood is about two orders of magnitude, I found no English-language trial of the herb alone, and a fast, drug-like effect is the signature of the sildenafil and tadalafil FDA keeps finding in this category. Its circulating metabolites act on the estrogen receptor, which helps explain the bone result and creates its own cautions.

Key Safety Points

• Never combine any sexual enhancement supplement, including one labeled only horny goat weed, with nitroglycerin, isosorbide, nitrite poppers or riociguat.

• A product that gives a drug-like erection within an hour, or flushing, headache and blue-tinged vision, is behaving like a PDE5 drug; stop it and report it.

• Avoid in pregnancy, breastfeeding, estrogen-receptor-positive breast cancer or endometrial cancer history, and bipolar disorder; use caution with Parkinson's disease on ropinirole.

• Stop and get liver tests for fatigue, nausea, dark urine, itching or jaundice.

• Men on alpha blockers or strong CYP3A4 inhibitors, and anyone told to avoid PDE5 drugs, should treat these products as if they contain one.

Special Note

The species name on the bottle, the icariin percentage and the word "natural" do not tell you whether a sexual enhancement capsule contains a prescription drug. Only an analysis does, and FDA's recall of Endurance Boost with Horny Goat Weed in May 2025 is a recent public example of what that analysis can find.

Researched and drafted with AI assistance. Every claim verified against primary sources and human-reviewed before publication. Last reviewed: October 19, 2026. Corrections: reply to any issue.

This issue is educational and is not medical advice. If you take any medication, especially a nitrate, an alpha blocker or a hormone therapy, have a diagnosed condition, or are pregnant or breastfeeding, talk to a clinician before changing anything.