Icariin is the main active compound of the Epimedium plant species, commonly known as horny goat weed. These plants are traditionally used in China as aphrodisiacs and to enhance erectile function. Limited research suggests icariin may help repair bone fractures, reduce stress, and improve mood. Read below to learn more about the potential health benefits of this plant flavonoid.
What Is Icariin?
Horny Goat Weed’s Active Compound
Icariin is an active flavonoid component of the Epimedium plant species commonly known as Horny Goat Weed. Extracts from these plants have long been used in Traditional Chinese Medicine for enhancing libido and male sexual function [1].
Due to its widespread distribution and movement in the body including the brain, icariin exhibits several potential biological activities such as antioxidant and anti-inflammatory effects, neuroprotection, anti-tumor activity, as well as promoting overall health in the heart, bones, and a variety of other organs [2, 3].
Health Benefits of Icariin
Insufficient Evidence for:
1) Bone Growth and Repair
Icariin increased hip and lower spine bone density in a clinical trial on 100 postmenopausal women by inhibiting a bone breakdown-marker (deoxypyridinoline) and maintaining a bone-formation one (osteocalcin) [4].
Similarly, icariin improved bone mineral density and strength in female rats with removed ovaries [5, 6, 7].
Icariin may also promote the production and activity of bone cells (osteoblast) based on the results of cell-based studies [8, 9, 10].
Icariin stimulated the generation of cultured human bone (osteoblast) cells by increasing bone morphogenetic protein (BMP-2) production, a key protein involved in bone and cartilage formation [11].
It also enhanced the production of primary osteoblasts (by increasing bone formation markers ALP, osteocalcin, COL-1 and OPG and decreasing RANKL, a protein involved in osteoclast formation) [12].
Icariin inhibited the formation and bone-resorbing action of osteoclasts by increasing OPG/RANKL ratios in bone cells [13].
Osteoprotegerin (OPG) is known to inhibit RANKL activity, which plays a role in osteoclast formation and bone destruction [14].
In addition, icariin may suppress osteoclast formation by decreasing superoxides, reactive oxygen species that are required for osteoclast survival and activity [12].
Icariin may also inhibit cartilage and bone breakdown in arthritic mice (by inhibiting cathepsin K, an enzyme that breaks down cartilage and bone) [15].
Although promising, the evidence to back the use of icariin supplementation to promote bone repair is based on a single clinical trial and a few animal and cell-based studies. Larger, more robust clinical trials are required.
2) Lowering Stress & Improving Mood
In a small trial on 10 people with bipolar disorders and alcohol abuse, icariin (up to 300 mg/day) reduced depressive symptoms and alcohol consumption [16].
The HPA (hypothalamic-pituitary-adrenal) axis plays a role in mitigating physiological responses to stress, with hyperactivity implicated in depressive and anxiety disorders [17].
Icariin normalizesd HPA axis activity (by reducing CRF and cytokines IL-6 and TNF-alpha) in CMS (chronic mild stress) rat models [18, 19].
Cytokines IL-6 and TNF-alpha activate CRF, which increases HPA axis activity characterized by high levels of cortisol, a stress hormone [18].
Thus, icariin may act as an antidepressant by decreasing HPA axis hyperactivity through inhibition of CRF and cytokine levels in depressive patients [17].
A small clinical trial and a few animal and cell studies cannot be considered sufficient evidence that icariin lowers stress and improves mood. Further clinical research is needed.
3) Premature Ejaculation
In a clinical trial on 80 men with a lifelong history of premature ejaculation, PDE5 inhibitors delayed ejaculation from vibratory stimulation. This preliminary finding should be confirmed in additional clinical studies on larger populations [20].
Animal and Cell Research (Lack of Evidence)
No clinical evidence supports the use of icariin for any of the conditions listed in this section. Below is a summary of the existing animal and cell-based research, which should guide further investigational efforts. However, the studies listed should not be interpreted as supportive of any health benefits.
Erectile Dysfunction & Sex Drive
Icariin inhibits phosphodiesterase type 5 (PDE5), an enzyme that breaks down cyclic guanosine monophosphate (cGMP) [21].
PDE5 inhibition stimulates the NO/cGMP pathway and improves reproductive function in animal models.
This is due to increased cGMP and nitric oxide levels which lead to smooth muscle relaxation, widening of blood vessels and increased blood flow to the penis, facilitating erection [1].
Chronic treatment of icariin suppressed penile smooth muscle cell death in multiple animal studies [22].
Additionally, icariin significantly increased pelvic nerve length when cultured with nerve fragments, indicating that it may enhance penile rehabilitation [1].
Icariin also increased free testosterone levels in rats [23].
Research indicates that high levels of testosterone are correlated with increased sexual desire in aging males and females, suggesting that icariin may act as a natural aphrodisiac in individuals with diminished libido [24, 25].
Cognitive Function
Icariin exhibited anti-amyloid activity in many animal studies [26, 27, 28].
Beta-amyloid peptides (Aβ) are proteins that cause plaque formation and cell damage in Alzheimer’s disease [29].
Icariin was shown to markedly decrease β-amyloid-induced toxicity in rat adrenal embryonic cells (by inhibiting tau protein hyperphosphorylation, a key biological marker of Alzheimer’s disease) [30].
This is likely due to activation of the PI3K/Akt pathway, which plays a critical role in cell survival [31].
Icariin also exhibited protective effects against learning and memory deficiencies in animal models [32, 33, 34].
Icariin improved dementia in aluminum-intoxicated rats by reducing oxidative damage and β-amyloid deposits in the hippocampus. This is in part due to increased superoxide dismutase (SOD), an enzyme that reduces oxidative damage [32].
In rats with brain inflammation, short-term icariin treatment improved spatial learning and memory abilities. This effect is thought to be due to the lowering of pro-inflammatory cytokines (TNF-alpha and IL-B), as well as COX-2, an enzyme responsible for fever, inflammation, and pain [33].
Icariin may also suppress neuroinflammation by inhibiting the activation of microglia, macrophage-like cells in the brain nervous system that play a pivotal role in initiating the neuroinflammatory response [35].
The anti-inflammatory effect of icariin may be attributed to its inhibition of the NF-κB and p38 MAPK pathways, which are involved in microglia and proinflammatory marker activation [35].
Another animal study showed that icariin lessened cognitive decline by increasing BDNF and its receptor tyrosine kinase TrkB [34].
BDNF is a neurotrophic factor involved in cognition, synaptic plasticity, and neuronal survival [36, 37].
In rats recovering from a stroke, icariin protected against cognitive deficits by increasing acetylcholine metabolism in the hippocampus, a key neurotransmitter involved in learning and memory [38].
In addition, icariin may enhance cognitive function via stimulation of the NO/cGMP pathway. Elevated levels of cGMP and nitric oxide (via icariin inhibition of PDE5) improved brain blood flow, synaptic plasticity, neurovascular dysfunction, and β-amyloid elimination from the hippocampus (memory center) and cortex [39, 40].
Due to its potent anti-inflammatory, antioxidative and anti-amyloid activity in the brain, icariin may serve as a promising therapeutic option for cognitive disorders such as Alzheimer’s disease and other forms of dementia [41, 42].
Protecting the Brain
Icariin inhibited neurotoxicity induced by corticosterone, aluminum, hydrogen peroxide, and other toxins and promotes neuronal survival in numerous animal models [43, 32, 44].
Icariin suppressed neurotoxicity by maintaining intracellular calcium homeostasis in rat hippocampal neurons [45].
Icariin also inhibited β-amyloid-induced neurotoxicity (by increasing CART (cocaine and amphetamine-regulated transcript) in cortical neuron cells. Found widely in the brain, CART functions in preventing energy loss and preserving mitochondrial function [46, 47].
Mitochondria are known to play a key role in increasing energy production for brain cell survival during a stroke [48].
Icariin also promoted brain cell survival during a stroke by increasing Sirtuin 1 (SIRT1), an enzyme that promotes cellular stress resistance, in animal studies [48, 49].
SIRT1 activates the PGC-1alpha pathway, which is known to promote mitochondrial biogenesis and energy metabolism [48].
Also, SIRT1 can reduce oxidative stress, a key factor involved in protein and DNA damage in the cell [44].
Icariin stimulated neurogenesis by activating dormant neural stem cells in animal studies [50, 51].
Heart Health
Icariin exhibited heart protective effects in many animal studies [52, 53, 54].
It improved heart function and reduced tissue death in rats with an acute heart attack by activating the PI3K-Akt pathway, which plays a critical role in cell survival [52].
Icariin also prevented heart muscle cell death during reoxygenation following an acute heart attack by increasing Bc1-2 (an anti-cell death factor) and decreasing Bax ( a pro-cell death factor). These effects are in part due to activation of the PI3K/Akt pathway, which increases Bc1-2 in heart muscle cells [55].
In another study, icariin inhibited heart muscle cell death by suppressing matrix metalloproteinase (MMP) activity in rats with heart failure. MMPs are enzymes involved in heart remodeling after injury [53].
Icariin also improved heart function by reducing oxidative damage in the mitochondria of diabetic rat hearts. Icariin may improve blood flow to the heart by widening heart vessels via inhibition of Ca2+ channels, which helps reduce the risk of heart stroke and tissue death [54, 56].
Artery hardening (atherosclerosis) is a common cause of stroke and heart attack. Icariin may reduce the risk of hardening of the arteries by lowering cholesterol levels in the blood, as seen in a study in rabbits [57].
Multiple studies show that icariin can promote new heart muscle cell formation by inducing cell death, increasing reactive oxygen species generation, and activating the P38 MAPK and NF-kappaB pathways in mouse embryonic stem cells. This suggests that icariin may have a potential application in heart tissue engineering [58, 59, 60].
Inflammation & Immunity
Icariin reduced intestinal inflammation and improved disease symptoms in mice with irritable bowel syndrome (by inhibition of STAT1 and STAT3 phosphorylation which is responsible for activating and increasing Th1 and Th17 T-cells and pro-inflammatory cytokines) [61].
Furthermore, it improved airway inflammation in asthmatic rats (by adjusting the Th1/Th2 cytokine imbalance in the lung tissue). Icariin also inhibited the activation of the NF-κB pathway in lung tissue, which is involved in inflammation [62].
Another study showed that icariin decreased lung inflammation (by inhibiting pro-inflammatory markers TNF-α, IL-6, COX-2 and iNOS in the lung via activation of the PI3K/Akt pathway and inhibition of NF-κB) [63].
Multiple sclerosis (MS) is an autoimmune disease in which T-cells attack them in the brain nervous system (CNS), causing axon damage and disability. Icariin improved disease symptoms in mice with induced MS (by suppressing the production of T cells and Th1 and Th17 cells) [64].
Icariin increased the production of toll-like receptor 9 (TLR9) in mouse macrophages. TLR9 is a protein that functions in pathogen recognition and activation of the innate immune response [65].
Fatigue
Icariin reduced physical fatigue and increased endurance in mice during a weight loaded swimming test. In this study, icariin increased blood glucose, hemoglobin and glycogen levels, all of which are known to improve speed, endurance, and exercise ability.
Icariin also decreased blood lactic acid (BLA) and blood urea nitrogen (BUN) levels, indicating that this compound might reduce protein breakdown to produce energy and delay the buildup of lactic acid, both factors known to prevent fatigue [2].
Regrowing Blood Vessels
New blood vessel formation improves stroke-related tissue injuries and wound healing by increasing oxygen and nutrients to the affected area [56].
Icariin stimulated blood vessel growth (by activating the MEK/ERK and PI3K/Akt/eNOS pathways) in human blood vessel cells. These pathways are associated with the generation, movement and structural shaping of blood vessel cells during blood vessel growth [66].
Jetlag
PDE5 inhibitors enhanced circadian responses to light and decreased the amount of time necessary for re-entrainment in mice [67].
This helps when you fly eastward. Imagine you fly east 3 time zones from California to New York. If you normally go to sleep at 11 PM California time, then you will be going to sleep at 2 AM New York time. If you want to go to sleep earlier, you need to wake up earlier and ‘advance’ your cycle so that you go to sleep earlier and you wake up earlier.
Icariin and PDE5 inhibitors may help you advance your rhythm. See my interview with the author of this study.
DNA Damage & Aging
Icariin protected DNA from radical-induced damage by reducing oxidative damage (through increasing SIRT1 and antioxidant enzymes CAT and Prx1) [68, 44].
Icariin also delayed aging in mice by increasing SIRT6. This enzyme promotes DNA repair and energy metabolism and inhibits the NF-kB pathway, which is involved in cellular aging, death, and inflammation [69].
Icariin also delayed aging in worms by promoting stress resistance, muscle function and movement, and preventing protein buildup toxicity [70].
Acne
In one study, icariin inhibited biofilm formation by Propionibacterium acnes in part by killing the bacterial cells. Propionibacterium acnes is a bacterium linked to the skin condition of acne, indicating that icariin may be used as a natural anti-acne drug [71].
Note, however, that this result hasn’t been validated in humans or even in animals. Clinical research is needed to confirm this preliminary finding.
Cancer
Icariin inhibited tumor formation in various types of cancer cells, including breast cancer, leukemia, Burkitt lymphoma, and liver cancer [72, 73, 74].
In stomach cancer cells, icariin suppressed tumor cell movement and invasion by inhibiting the Rac1-dependent VASP pathway, which is involved in cellular motility [75].
In another study, icariin suppressed the attachment and movement of stomach cancer cells by inactivation of protein kinase A (PKA), an enzyme known to promote cell production and survival [76].
Icariin inhibited gallbladder cancer cell production and induced cell death by suppressing NF-κB activity. The NF-kB pathway plays a key role in cancer cell survival by increasing anti-cell death factors survivin and Bc1 [72].
Icariin also triggered liver cancer cell death by activating the ROS/JNK-dependent mitochondrial pathway which plays a key role in initiating cell death [77].
Note, however, that many substances have anti-cancer effects in cells, including downright toxic chemicals like bleach. This doesn’t mean that they have any medical value. On the contrary, most substances (natural or synthetic) that are researched in cancer cells fail to pass further animal studies or clinical trials due to a lack of safety or efficacy.
Mechanisms
- Inhibited PDE5 [1]
- Increased cGMP [1]
- Increased neuronal nitric oxide synthase (nNOS), inducible nitric oxide synthase (iNOS), endothelial nitric oxide synthase (eNOS) and nitric oxide [78]
- Increased free form testosterone in the blood [79]
- Inhibited tau protein [30]
- Decreased superoxide [12], increased SOD activity and decreased malondialdehyde (MDA) and β-amyloid in the hippocampus (memory center) [32]
- Inhibited NF-kB [35], IL-6, TNF-a, IL-1b, and COX-2 in the hippocampus (memory center) [33, 18]
- Elevated BDNF in the hippocampus (memory center) [34]
- Increased acetylcholine in the hippocampus (memory center) [38]
- Increased CART [46]
- Increased SIRT1 and PGC-1a, catalase [48, 44]
- Decreased CRF, cortisol [18]
- Increased bone morphogenetic protein (BMP) [10], ALP, osteocalcin, COL-1, and OPG, decreased RANKL [12]
- Activated Wnt/β-catenin pathway [80]
- Inhibited MMP activity [53]
- Decreased creatine kinase (CK), ischemia-modified albumin (IMA), and lactate dehydrogenase (LDH) [55]
- Reduced levels of total cholesterol and LDL Cholesterol in the blood [57].
- Inhibited STAT1 and STAT3 [61].
- Increased blood glucose, hemoglobin and glycogen levels, decreased blood lactic acid (BLA) and blood urea nitrogen (BUN) levels [2].
- Inhibited insulin/ IGF-1 [70]
Icariin Supplements
Tips
Keep in mind that icariin is a relatively unresearched substance and its purported benefits are supported by either limited, low-quality clinical studies or only animal and cell-based studies. Remember to speak with a doctor before taking icariin supplements. Icariin should never be used as a replacement for approved medical therapies.
Many icariin supplements are available. Be sure to buy from a reputable manufacturer that states the icariin content on the label.
Some brands combine horny goat weed with other libido enhancers, such as
If that’s what you’re looking for, check out our post about Surprising Natural Aphrodisiacs to Increase Libido.
Other brands sell icariin with Yohimbine for fat reduction.
