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Phosphodiesterase 5 (PDE5) inhibitors are a type of drug that can affect blood flow and how cells communicate in the body. PDE5 inhibitors can also appear in some foods and supplements.

An image of Kaempferia parviflora (KP) rootstalk, known as black ginger, which is on a list of pde5 inhibitors.Share on Pinterest
Kaempferia parviflora is a plant that naturally contains PDE5 inhibitors.

People may take PDE5 inhibitors to manage conditions such as erectile dysfunction (ED) or pulmonary hypertension.

In this article, we explain how PDE5 inhibitors work and the potential risks and side effects of taking them. We also provide a list of drugs and substances that contain them.

Please note that the writer of this article has not tried these products. All information presented is purely research-based and correct at the time of publication.

Medical News Today follows a strict product selection and vetting process. Learn more here.

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PDE5 is an enzyme in the walls of blood vessels. It affects blood flow and how cells signal within the body.

PDE5 inhibitors block the PDE5 enzyme to prevent it from working. This inhibition relaxes the blood vessels and increases blood flow.

People may take PDE5 inhibitors to treat ED or pulmonary hypertension.

In people with ED, PDE5 inhibitors increase blood flow to the penis, improving erectile function.

In people with pulmonary hypertension, PDE5 inhibitors can help by:

  • controlling blood flow to the arteries in the lungs
  • increasing blood flow to the lungs
  • lowering blood pressure

Research also suggests that PDE5 inhibitors may help treat heart disease, diabetes, and cancer.

Current research looks into whether PDE5 inhibitors are also effective in treating cognitive disorders like dementia.

Read more about the best pills for ED here.

Various PDE5 inhibitor drugs are available, and people usually take them in tablet form.

In the United States, the following prescription PDE5 inhibitors are available:

Avanafil (Stendra)

Avanafil, brand name Stendra, is a relatively new ED medication. An older study reports that this drug takes effect quicker than other ED treatments, taking effect around 15 minutes after ingestion, and does not last as long, with a maximum duration of 6 hours.

Additionally, a 2016 study states that avanafil has fewer side effects than some other ED medications, and the shorter onset time allows people to have more spontaneous sex.

Vardenafil (Levitra)

Vardenafil, brand name Levitra, achieves maximum effect around 60 minutes after ingesting. It lasts for a maximum of 12 hours inside the body.

Learn more about vardenafil here.

Tadalafil (Cialis, Adcirca)

Tadalafil, which has the brand names Cialis and Adcirca, has the slowest onset of ED medications, achieving maximal effect around 120 minutes after ingesting. However, it lasts for a maximum of 36 hours in the body.

Learn more about tadalafil here.

Sildenafil (Viagra)

Sildenafil, brand name Viagra, takes effect around 60 minutes after ingestion. It lasts for around 12 hours in the body.

Learn more about sildenafil here.

People can only receive ED medication through prescription. A healthcare professional must write a valid prescription that a pharmacy must fill.

However, several telemedicine companies offer prescription ED medications. Some companies also offer online doctor appointments to receive prescriptions if a person does not already have one.

Options include:


Hims is a telehealth company specializing in male health conditions, including erectile dysfunction.

This company offers sildenafil (Viagra), tadalafil (Cialis), and avanafil (Stendra). It also offers online appointments with healthcare professionals.

Learn more about Hims here.

Price: The cost of ED medication starts from $3 per dose.


Roman is a telehealth company also specializing in male health conditions, including treatment for ED.

It offers sildenafil (Viagra) and tadalafil (Cialis). Similar to Hims, Roman also offers online appointments with healthcare professionals.

Learn more about Roman here.

Price: The cost of ED medication starts from $2 per dose.

There are also several other substances and supplements that are PDE5 inhibitors. However, a person should not take any supplements that claim to treat ED without first seeking the advice of a healthcare professional.

The FDA warns that many ED supplements contain undeclared prescription medication that can cause harm.

Phentolamine (Regitine)

Phentolamine (Regitine) is a prescription medication for hypertension.

However, healthcare professionals may inject this medication if a person does not respond to any prescription PDE5 inhibitors.

Individuals should contact a doctor and discuss whether phentolamine is the right medication for their circumstances.


L-arginine is a type of amino acid available in many foods.

A 2020 study suggests that combining L-arginine with tadalafil may increase the effectiveness of the ED medication. The researchers also found that L-arginine had a smaller beneficial effect on ED when the participants only took this supplement.

Yohimbine (Yocon)

Yohimbine is a compound in a tree native to central and western Africa. Traditional medicine uses the bark to increase sexual arousal and performance.

The National Center for Complementary and Integrative Health states that there is not enough evidence to say that yohimbine is effective for erectile dysfunction. Additionally, yohimbine has an association with heart attacks and seizures and interacts negatively with antidepressants.

Due to safety concerns, several countries have banned yohimbine.

Black ginger

Black ginger, or kaempferia parviflora, may have a slight PDE5 inhibiting effect.

A small 2018 study of 14 participants found that ethanol extract from this plant may improve erection function. However, more research on larger sample sizes is necessary to determine the safety and effectiveness of this plant.

Tongkat ali

Eurycoma Longifolia, or tongkat ali, is a plant native to Indonesia and Malaysia.

There is some evidence that Tongkat ali may increase testosterone levels and arousal, which may help improve ED.

Tribulus terrestris

According to a 2013 study on rodents, this substance has a relaxing effect on arterial pressure, which may help improve ED.

There is slight evidence that this plant may help improve a person’s libido, however, there needs to be more research on this tribulus terrestris’ effect on humans.

Horny goat weed

Horny goat weed contains icariin, an extract from the Epimedium plant.

An older study on rats found that horny goat weed extract may benefit ED. However, there have been no clinical trials on humans.

The following table compares the PDE5 inhibitors in this article.

FDA approval for EDFDA regulationPrescription or over the counter
L-argininenonoover the counter
Yohimbinenonoover the counter, banned in some countries
Black gingernonoover the counter
Tongkat alinonoover the counter
Tribulus terrestrisnonoover the counter
Horny goat weednonoover the counter

People who are taking nitrate medication should avoid taking PDE5 inhibitors. The combination of both medications can cause a severe decrease in blood pressure, which can potentially be fatal.

People may be taking nitrate medications for chest or heart issues. These drugs include:

  • nitroglycerin (Nitrostat)
  • isosorbide dinitrate (Dilatrate-SR, Isordil) or isosorbide mononitrate (Imdur, Monoket)
  • amyl nitrate, or “poppers”

PDE5 inhibitors can also potentially be harmful to people with certain conditions. Before taking these medications, a person should make their doctor aware if they:

Common, and usually mild, side effects of PDE5 inhibitors can include:

  • headaches
  • flushing
  • symptoms resembling those of the common cold
  • stomach upset
  • muscle and back pain

Rare side effects may include:

  • changes in vision, or sudden loss of vision, for which people with heart disease or diabetes are more at risk
  • sudden loss of hearing
  • prolonged or painful erections that will require treatment to prevent lasting damage

PPDE5 inhibitors may interact negatively with grapefruit juice and alcohol. They can potentially also interact with other medications, so people should make their doctor aware if they are taking other drugs or supplements.

Some herbs contain PDE5 inhibitors, so people may find them in certain supplements or herbal remedies.

However, herbs and supplements may contain additional unlisted ingredients, cause adverse side effects, or interact with other drugs.

The FDA warns that herbal or natural remedies for conditions such as ED may contain active ingredients that are also present in prescription drugs.

It is advisable to speak to a doctor before taking substances and supplements that contain PDE5 inhibitors or promise results equivalent to those of PDE5 inhibitor prescription drugs.

A person may wish to contact a doctor if they are finding it difficult to have and maintain an erection.

Doctors may ask questions about a person’s sexual history, such as:

  • the frequency and length they have erections for
  • whether any factors make it harder to have an erection, such as stress
  • how often the person has sex
  • whether the person is already trying treatments
  • if the person has a partner, whether they would be willing to be involved with treatment

Healthcare professionals may also ask questions about certain risk factors, such as whether a person has type 2 diabetes or high blood pressure. They may also ask if the person smokes, drinks, uses drugs, or does regular activities.

These questions help doctors determine the best treatment option for each person. They may recommend prescription medication, such as sildenafil, to help people maintain their erection for longer.

Here we answer some common questions.

Can you mix caffeine and Viagra?

Currently, there are no known interactions between caffeine and Viagra or sildenafil.

However, people may wish to contact their doctor or another healthcare professional for advice if they intend to have beverages with high caffeine content alongside PDE5 inhibitors.

What everyday foods contain PDE5 inhibitors?

There are several supplements containing ingredients that may act as PDE5 inhibitors. These include horny goat weed and black ginger.

Scientists have not conducted clinical trials investigating the effects of horny goat weed on humans.

A small 2018 study of 13 participants found that black ginger may be effective in improving erectile function and males ages 50-70 without erectile dysfunction. However, more research is necessary with larger sample sizes to investigate the efficacy and safety of this plant.

However, the FDA warns people against taking supplements that companies market as natural remedies for erectile dysfunction. These supplements may contain undeclared prescription medication that can cause harm.

PDE5 inhibitors block PDE5, an enzyme in the walls of blood vessels. Blocking PDE5 causes blood vessels to relax, increasing blood flow to certain areas of the body.

This effect means that they can help manage conditions such as ED and pulmonary hypertension.

People taking nitrate medication should not take PDE5 inhibitors because the combination of drugs can cause a dangerous drop in blood pressure, which can be life-threatening.

Other drugs, foods, supplements, or herbal remedies may contain PDE5 inhibitors. These may not have FDA regulations and could contain unlisted ingredients or contaminants, or interact with other medications.

People should discuss any potential side effects or drug interactions of PDE5 inhibitors with their doctor before taking these medications.