Currently, there are four orally active drugs are available to treat ED. These include: sildenafil citrate (Viagra [Pfizer, USA]), vardenafil hydrochloride (Levitra [Bayer, Germany]), tadalafil (Cialis [Eli Lilly, USA]) and avanafil (Stendra, Spedra [Vivus Inc, USA]). These drugs inhibit the enzyme phosphodiesterase type 5 (PDE-5), which is responsible for the hydrolysis of cGMP. PDE-5 inhibitors and cGMP act as effectors of dilation of smooth muscle of cavernosal bodies. PDE-5 inhibitors are contraindicated in patients taking any kind of nitrate therapy for angina, and may not be appropriate for men with certain health conditions, such as severe heart disease, heart failure, history of stroke or heart attack, uncontrolled high blood pressure or diabetes, and patients with pigmental retinopathy. PDE-5 inhibitors are less effective in men with diabetes and men who have been treated for prostate cancer. PDE-5 inhibitors are also not effective in men with retinitis pigmentosa, a genetic disease involving PDE-5 deficiency. The common side effects of PDE-5 inhibitors include gastrointestinal upset, headache, nasal congestion, back pain and dizziness. The PDE-5 inhibitors may interact with other medications including antihypertension drugs. Nonetheless, the PDE-5 inhibitors are generally safe and effective for most men. The primary mechanism of action of these drugs is through the mediation of NO. NO is one of the key molecules involved in ED. It is a short-lived, highly permeable, pleiotropic, gaseous molecule, secreted from the postganglionic cavernosal parasympathetic nerves, endothelium of the cavernosal blood vessels, platelets in the cavernosal sinuses and phagocytic cells (monocytes, macrophages and neutrophils). NO acts on platelets to inhibit platelets adhesion and aggregation. NO causes relaxation of the smooth muscle of the cavernosal blood vessels of the penis, leading to vasodilation, tumescence and stimulation. Release of NO in the corpus cavernosum of the penis during stimulation activates the enzyme guanylate cyclase, which results in increased levels of cGMP, producing smooth muscle relaxation in the corpus cavernosum and resulting in increased blood flow (5). NO is mainly produced from cavernosal nerves, which are nonadrenergic, noncholinergic nerves within the penis, and acting via its second messenger cGMP. It has been suggested that maintaining normal body weight and mild exercise, as well as dietary supplementation of folic acid, zinc, calcium, vitamin C, vitamin E and L-arginine, a precursor of NO, can support the biochemical pathway leading to NO release [6]. NO is an effector molecule that is involved in a number of intracellular functions such as vasorelaxation, endothelial regeneration, inhibition of leukocyte chemotaxis and platelet adhesion [7]. A small proportion of autonomic nerves do not release either Ach or norepinephrine [8]. For example, the cavernous nerves predominantly release NO in the penis. The exact mechanism is not known, but it is believed to be through increased intracellular calcium. Another gaseous molecule produced in the corpora cavernosa is hydrogen sulphide (H2S), which is also known to be involved in erectile function [9]. H2S activates ATP-sensitive potassium channels in smooth muscle cells. Some reports indicate that NO acts in large vessels and H2S in small vessels. A high level of tumour necrosis factor-alpha has been shown in ED patients [10]. Although current ED therapies using PDE-5 inhibitors are safe and effective, approximately 40% of ED patients do not respond to currently available treatment [11,12]. For these patients, herbal therapy may be useful.

This herb has been used by men for many years and has been referred to as Asian Viagra because it’s made from the roots of a tree that grows in Malaysia, Thailand and Indonesia. Tongkat Ali is used to treat erectile dysfunction, and to increase sexual desire, libido and sexual performance. It is thought to work by increasing levels of testosterone, the dominant male hormone.
If you’re stressed about not being able to maintain an erection, there are more reliable and scientifically tested methods out there. Drinking less alcohol, eating healthier foods, staying away from sugar, and doing pelvic exercises have all been proven to partially help with ED. The best part to these alternatives to the “alternative”?  They are inexpensive and don’t require a shaman.
Many stores sell herbal supplements and health foods that claim to have sexual potency and fewer side effects. They’re also often cheaper than prescribed medications. But these options have little scientific research to back up the claims, and there’s no uniform method on testing their effectiveness. Most results from human trials rely on self-evaluation, which can be subjective and difficult to interpret.
Epimedium extract (Horny Goat Weed) (11), (Figure 9): the Chinese refer to this herb as ‘yin yang huo’, which has been loosely translated as ‘licentious goat plant’; hence, its common name is well known as ‘horny goat weed’ by many Western cultures. Scientifically, studies have shown that Epimedium may restore low levels of both testosterone and thyroid hormone, bringing low levels back to their normal levels (5), which may account for some of its benefits in improving sexual libido. Other benefits to Epimedium involve increased muscle mass. Used for fatigue and aging, And vasodilatation effect; thus, most frequently used in treatment of sexual dysfunction in Traditional Chinese Medicine (12). The active substance from horny goat weed was reported by Xin Zhong Cheng at Beijing Medical University as Icarin—acts by increasing sexual activities and ICP levels in castrated rats after long term oral administration. It has no effects on serum testosterone level in castrated rats after long term oral administration. Instead Icariin increases nNOS and iNOS mRNA and protein expression in the corpus cavernosum after long term oral administration and hence may have long term efficacy on erectile dysfunction after oral administration.
Maca root (Lepedium meyenii W): this native Peruvian root has been cultivated for thousands of years. Considered an integral part of the diet, the Incans found maca root so potent (14), it was restricted to royal use only. Known for its energy enhancing abilities, maca root enjoys a special place amongst herbalists and health seekers. Like ginseng, this plant is employed to increase strength, libido and sexual function (14). Clinically its effects have been proved with experimental animals (5,15).

Historically, it has been shown that herbal medicines may cure or prevent certain ailments. However, there are very little recorded data available to support the dose, efficacy, side effects and interactions. Because the safety and efficacy of herbal remedies have not been assessed, unlike synthetic drugs, well-controlled and randomized studies are warranted to establish the therapeutic efficy and safety of such products. Determination of side effects and interactions with prescription medicines are also needed. The amount of active ingredients in herbals may vary among preparations; thus, standardization of herbal medicines is required.
"Ikawe has really boosted my sex drive as you said it would! My wife used to complain that I was never interested. She said her friends always complained that their husbands wanted too much sex but she hardly got any. Seriously - it was affecting my marriage. After taking Ikawe for 10 days I could already feel the difference. I also have much more energy." - Derrick S., USA
ED can also occur as a side effect of some medications, for example some high blood pressure medications such as certain diuretics and beta blockers. If you think that a medication you are taking has a negative effect on your sex life, you should discuss this with your prescribing doctor. Your doctor may be able to recommend an alternative treatment.
Red Ginseng — One small randomized trial found evidence that red ginseng may offer modest improvements in ED symptoms (as compared with placebo). A meta-anaylsis published in the British Journal of Clinical Pharmacology states, “Traditionally red ginseng has been used to restore and enhance normal well-being, and is often referred to as an adaptogenic….Possible mechanisms of action of red ginseng include hormonal effects similar to those of testosterone. Others have postulated that red ginseng might induce relaxation of the smooth muscles.”  (5)

The basis of ED herbal therapies is that they are anti-inflammatory, antioxidant and immunomodulatory, and can stimulate testosterone production. On the other hand, the synthetic drugs act via NO. The principal mediator of the relaxation of corporal smooth muscle of the penis has been shown to be NO, which is released mainly from parasympathetic nerves and endothelium [13]. NO is believed to relax the corporal smooth muscle by activating soluble guanylate cyclase to increase cGMP content [14,15]. Penile rigidity depends on maximizing inflow of blood while minimizing outflow [6]. The increased blood flow in the cavernous sinuses puts pressure on the walls of the surrounding veins, causing the lumen of the veins narrow, temporarily interfering with the flow of blood but causing tumescence. Normally, the parasympathetic nerve produces Ach. Ach acts on muscarinic receptors and nicotinic cholinergic receptors. When the parasympathetic nerve is stimulated, preganglionic neurons release Ach at the ganglion, which acts on nicotinic receptors on postganglionic receptors. Postganglionic neurons then release Ach to stimulate muscarinic receptors of the target organs. The muscarinic receptor M3, present in the endothelial cells and smooth muscle, is activated, and the M2 receptor in the heart may also be activated. This may result in the production of Ach, which can cause endothelial cells to produce NO. Ach released from postganglionic parasympathetic nerves acting through G-protein-mediated muscarinic receptors and nicotinic cholinergic receptors helps to release NO. Normally, M1, M2 and M3 receptors are found in secretory glands, heart, smooth muscle and endothelial cells, respectively. M1, M2 and M3 receptors cause activation of phospholipase C and generate inositol trisphosphate and diacylglycerol, which increase calcium. Activation of M4 may inhibit adenylate cyclase, decreasing the messenger cyclic AMP. This mechanism may be involved in the relaxation and contraction of cavernosal smooth muscle cells.

A study published in May 2014 in The Journal of Sexual Medicine found that some men can reverse erectile dysfunction with healthy lifestyle changes, such as exercise, weight loss, a varied diet, and good sleep. The Australian researchers also showed that even if erectile dysfunction medication is required, it's likely to be more effective if you implement these healthy lifestyle changes.

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