Men often think of erectile dysfunction treatment as a choice between a prescription medication or a supplement.

The biology is more complicated.

Prescription PDE5 inhibitors such as sildenafil work with a signaling system that already depends heavily on nitric oxide (NO). That means understanding nitric oxide may help explain why blood flow matters so much to erectile function, why ED medications work the way they do, and why researchers are now studying whether nitric oxide support can complement medications such as sildenafil.

Recent published research involving AFFIRM® provides new objective data on that relationship.

Here is what men should understand about nitric oxide, sildenafil, blood flow and erectile health.

What Is Nitric Oxide?

Nitric oxide is a signaling molecule produced naturally throughout the body.

One of its most important jobs is helping blood vessels relax and widen, a process known as vasodilation.

When blood vessels relax, blood can flow more easily.

That function matters throughout the body, including the cardiovascular system and the blood vessels involved in an erection.

In erectile tissue, nitric oxide helps trigger production of another signaling molecule called cyclic guanosine monophosphate, or cGMP.

cGMP causes smooth muscle surrounding penile blood vessels to relax, increasing blood flow into erectile tissue.

In simple terms:

Nitric oxide helps tell blood vessels to open.

That makes nitric oxide an important part of normal erectile physiology.

Why Nitric Oxide Matters for Erections

An erection is largely a vascular event.

Sexual stimulation triggers nerve and chemical signals that cause blood vessels supplying the penis to expand.

More blood enters the erectile tissue. At the same time, the mechanisms that normally drain blood from the penis become restricted, helping maintain firmness.

Nitric oxide is involved near the beginning of this process.

Without adequate vascular signaling, increasing and maintaining penile blood flow becomes more difficult.

This is why erectile health and vascular health are so closely connected.

Board-certified urologist and men's health researcher Judson Brandeis, MD has spent years studying this relationship between nitric oxide, circulation and male sexual performance.

Dr. Brandeis: "Nitric oxide is one of the key signals that allows blood vessels to relax. When we're talking about erections, we're fundamentally talking about blood flow."

Suggested quote for Dr. Brandeis to review and approve before publication.

Where Does Sildenafil Fit Into the Nitric Oxide Pathway?

Sildenafil, the active ingredient in Viagra®, is a PDE5 inhibitor.

It works downstream from nitric oxide.

Nitric oxide helps stimulate production of cGMP.

An enzyme called phosphodiesterase type 5, or PDE5, normally breaks cGMP down.

Sildenafil inhibits this enzyme.

That means sildenafil helps the cGMP signal remain active longer, supporting the blood-vessel relaxation necessary for an erection when sexual stimulation occurs.

A useful way to think about the process is:

Nitric oxide helps create the signal. Sildenafil helps preserve the signal.

This relationship is one reason researchers became interested in studying nitric oxide support and sildenafil together.

Can Nitric Oxide Support Complement Sildenafil?

That question was recently evaluated in clinical research led by Dr. Judson Brandeis.

The study, "Combining a Nitric Oxide Boosting Dietary Supplement With Sildenafil Improves Nighttime Erections More Than Sildenafil Alone," was published in The Journal of Sexual Medicine.

Researchers compared nighttime erectile activity when men took:

Sildenafil 40 mg alone

versus

Sildenafil 40 mg combined with a nitric oxide-boosting dietary supplement

The supplement used in the research is commercially available as AFFIRM.

Rather than relying only on questionnaires, researchers objectively measured nighttime erectile activity using the FirmTech TechRing™.

What Did the Research Find?

Twenty-two men completed the study.

Their average age was 55.

When participants took sildenafil 40 mg alone, average nighttime erectile activity measured as AUC per hour of sleep was:

87

When participants took sildenafil 40 mg plus the nitric oxide-supporting supplement, that measurement increased to:

117

That represents a 34% increase in the study's primary nighttime erectile measurement.

Participants also averaged:

3.25 erections per night with sildenafil alone

compared with

3.87 erections per night with sildenafil plus the supplement.

No side effects were self-reported during the study from either the supplement or the sildenafil/supplement combination.

You can read the published scientific abstract in The Journal of Sexual Medicine here.

For a detailed breakdown of the research protocol and results, also see:

New Study: Nitric Oxide Supplement Boosts Sildenafil's Effect on Nighttime Erections by 34%

Why Is This Different From Simply Taking More Sildenafil?

This is an important distinction.

Increasing a medication dose and supporting another part of the erectile pathway are not the same thing.

Sildenafil works by reducing the breakdown of cGMP.

Nitric oxide support focuses farther upstream in the same general pathway by supporting the body's ability to produce the nitric oxide signal involved in cGMP production.

This is why the researchers describe the two mechanisms as potentially synergistic.

They affect related but different steps in erectile physiology.

The study does not establish that men should lower, raise or otherwise change their prescription sildenafil dose.

Medication decisions should always be made with the prescribing healthcare professional.

What the research does provide is objective evidence supporting further investigation of the relationship between nitric oxide support and PDE5 inhibitors.

Why Was AFFIRM Developed?

AFFIRM was formulated by Dr. Judson Brandeis around ingredients selected for their roles in nitric oxide production, circulation and male sexual health.

Each tablet contains:

• 750 mg L-Citrulline
• 65 mg Muira Puama Extract 4:1
• 45 mg Red Beet Root Extract 4:1
• 35 mg Panax Ginseng Root Extract 4:1

The formulation approaches nitric oxide support through several ingredients rather than relying on a single ingredient.

L-Citrulline and Nitric Oxide

L-citrulline is an amino acid.

The kidneys convert L-citrulline into L-arginine.

L-arginine can then be used by the body in the production of nitric oxide.

This is one of the primary reasons L-citrulline appears in supplements designed to support nitric oxide production and circulation.

AFFIRM contains 750 mg of L-citrulline per tablet.

Beet Root and the Nitrate Pathway

Beets offer another route to nitric oxide.

Red beet root contains naturally occurring nitrates.

The body can convert dietary nitrate into nitrite and ultimately nitric oxide.

That pathway is different from the L-citrulline/L-arginine pathway, which is why beet root and L-citrulline are often discussed together in the context of nitric oxide support.

Panax Ginseng and Men's Sexual Health

Panax ginseng has been studied extensively as a botanical ingredient and has a long history of use in men's health.

AFFIRM combines Panax ginseng with L-citrulline, red beet root and Muira puama rather than positioning any one ingredient as a complete solution by itself.

Muira Puama

Muira puama is a botanical traditionally associated with sexual wellness.

It is included as one component of AFFIRM's four-ingredient formulation.

The important point when looking at the recent sildenafil research is that researchers evaluated the complete formulation, not isolated individual ingredients.

Not All Nitric Oxide Supplements Are the Same

Typing "nitric oxide supplement" into a search engine produces hundreds of products.

That does not mean those products are interchangeable.

Different supplements may use:

• Different ingredients
• Different ingredient quantities
• Different extracts
• Different combinations
• Different manufacturing standards

Most importantly, the fact that one formulation has been studied does not automatically mean every product containing one of the same ingredients will produce the same result.

The nitric oxide-boosting formulation in the recent sildenafil study was specifically identified in the published research as AFFIRM.

View the AFFIRM formulation and product details here.

Why Researchers Measured Nighttime Erections

One of the most interesting features of this research is how erectile function was measured.

Sexual performance while awake can be affected by many variables:

• Stress
• Anxiety
• Relationships
• Alcohol
• Fatigue
• Expectations
• Sexual stimulation
• Environment

Men also have to remember and subjectively rate their erectile performance when completing traditional questionnaires.

Nighttime erections provide another way to evaluate erectile physiology.

Men normally experience involuntary erections during REM sleep.

Because they occur independently of intentional sexual activity, researchers can use nighttime erectile activity as an objective indicator of erectile function.

The FirmTech TechRing: Measuring Instead of Guessing

Researchers used the FirmTech TechRing™ Smart Performance Men's Health Tracker during the study.

Participants wore the TechRing while sleeping.

The device uses sensors and a connected interface to measure the firmness and duration of nighttime erections.

This allowed researchers to compare actual measurements from nights using sildenafil alone with nights using sildenafil plus the nitric oxide-supporting supplement.

That objective measurement is particularly important because it reduces dependence on self-reported impressions.

Men interested in how the technology works can read:

What Is the FirmTech TechRing? How At-Home Erection Tracking Works

Can You Measure Your Own Nighttime Erections?

Yes.

The FirmTech TechRing used in the published study is also available as a consumer device.

This gives men a way to objectively track changes in nighttime erectile activity over time.

Instead of relying only on questions such as:

"Do my erections feel stronger?"

or

"Do I think something is working?"

tracking can provide measurable data.

That can be particularly useful when evaluating changes involving sleep, exercise, nutrition, medication or other aspects of sexual and vascular health.

Nitric Oxide Is About More Than Sexual Performance

Nitric oxide is not an "erection chemical."

It is a signaling molecule used throughout the vascular system.

Because its primary role involves blood-vessel relaxation and circulation, nitric oxide research extends well beyond men's sexual health.

That also helps explain why erectile health can sometimes reflect broader vascular health.

For a deeper introduction to nitric oxide, read:

The Health Benefits of Nitric Oxide

AFFIRM Science also has a detailed overview of the research behind individual ingredients:

Scientific Data on AFFIRM Ingredients

What If Sildenafil Isn't Working as Well as Expected?

If you're experiencing erectile dysfunction despite using sildenafil, don't assume that simply taking more medication is the answer.

Many factors can influence erectile function and medication response, including:

• Cardiovascular health
• Penile blood flow
• Medication timing
• Food intake
• Alcohol
• Other medications
• Hormones
• Nerve function
• Sleep
• Stress
• The underlying cause of erectile dysfunction

Men with persistent erectile dysfunction should discuss their symptoms with a qualified physician or urologist.

Dr. Judson Brandeis treats men with erectile and sexual-health concerns through Brandeis MD Male Rejuvenation Center in San Ramon, California.

You can also read his physician-focused explanation of the nitric oxide and sildenafil research:

Nitric Oxide and Sildenafil for Erectile Dysfunction: Dr. Brandeis Explains the Research

Can You Take AFFIRM With Sildenafil?

AFFIRM was combined with sildenafil 40 mg in the published clinical study, and no side effects were self-reported by participants during that protocol.

However, that does not mean every supplement and medication combination is appropriate for every person.

Talk with your physician before combining dietary supplements with prescription medication, particularly if you:

• Take cardiovascular medications
• Have low blood pressure
• Have heart disease
• Take multiple prescription medications
• Have significant underlying medical conditions

It is particularly important to understand that nitric oxide-supporting dietary supplements are not the same thing as prescription nitrate medications.

Sildenafil should not be taken with prescription nitrates because the combination may cause a dangerous decrease in blood pressure.

Is AFFIRM an Erectile Dysfunction Medication?

No.

AFFIRM is a dietary supplement, not an FDA-approved medication for erectile dysfunction.

It was formulated to support nitric oxide production, circulation and male sexual wellness.

Prescription medications such as sildenafil and tadalafil have a different mechanism of action and regulatory status.

This distinction matters.

The recent clinical research is interesting precisely because it studied what happened when a nitric oxide-supporting dietary supplement and a PDE5 inhibitor were used together under a controlled protocol.

What Makes AFFIRM Different?

AFFIRM was developed by a urologist with a specific focus on the physiology of blood flow and male sexual health.

Its four-ingredient formulation includes:

L-Citrulline + Red Beet Root Extract + Panax Ginseng + Muira Puama

The same formulation was subsequently evaluated in published clinical research using objective nighttime erectile measurements.

For men researching nitric oxide supplements, that creates an important distinction between:

a product marketed around nitric oxide

and

the specific formulation that was actually used in the published study.

Explore AFFIRM

Learn more about AFFIRM and view the 150-tablet formula.

Frequently Asked Questions

Does nitric oxide help with erections?

Nitric oxide plays a central role in the biological pathway responsible for relaxing penile blood vessels and increasing blood flow during an erection.

It stimulates production of cGMP, which helps smooth muscle relax and blood vessels dilate.

Does sildenafil increase nitric oxide?

Sildenafil does not work primarily by producing nitric oxide.

Instead, it inhibits PDE5, the enzyme that breaks down cGMP. Nitric oxide helps stimulate cGMP production, while sildenafil helps preserve cGMP.

Can a nitric oxide supplement make sildenafil work better?

A published study involving 22 men found that adding the nitric oxide-supporting formulation commercially available as AFFIRM to sildenafil 40 mg increased the study's nighttime erectile AUC/hr measurement by 34% compared with sildenafil 40 mg alone.

That is evidence involving this particular formulation and study protocol, not proof that all nitric oxide supplements improve sildenafil.

Read the published research here.

What nitric oxide supplement was used in the sildenafil study?

The published study identifies the supplement as AFFIRM.

The formulation contains L-citrulline, red beet root extract, Panax ginseng root extract and Muira puama extract.

View AFFIRM here.

How were erections measured?

Participants wore the FirmTech TechRing while sleeping.

Researchers used TechRing data to evaluate nighttime erectile activity, including firmness and duration.

Why are nighttime erections important?

Nighttime erections happen involuntarily during sleep and can provide useful information about erectile physiology without some of the psychological and situational factors associated with sexual activity while awake.

Is AFFIRM a replacement for Viagra or sildenafil?

No.

AFFIRM is a dietary supplement and sildenafil is a prescription PDE5 inhibitor.

They have different mechanisms and are not interchangeable.

The published study investigated whether their different effects on the nitric oxide-cGMP pathway could complement one another.

The Bottom Line

Nitric oxide and sildenafil are connected through the same biological pathway, but they act at different points.

Nitric oxide helps initiate the cGMP signal responsible for relaxing blood vessels. Sildenafil helps keep that cGMP signal from being broken down too quickly.

That biological relationship is why researchers investigated the two together.

In published research involving 22 men, adding the nitric oxide-supporting formulation commercially available as AFFIRM to sildenafil 40 mg increased objectively measured nighttime erectile activity compared with sildenafil alone.

The primary AUC/hr measurement increased 34%, from 87 to 117.

The study used the FirmTech TechRing to objectively measure nighttime erections rather than relying solely on questionnaires.

The research is relatively small and additional studies are warranted, but it provides new clinical data about nitric oxide support, sildenafil and erectile physiology.

Explore the Research and Products

Shop AFFIRM Nitric Oxide Support

Read the Clinical Study in The Journal of Sexual Medicine

Learn About the FirmTech TechRing Used in the Study

Read the AFFIRM Study Breakdown

Learn More From Urologist Judson Brandeis, MD

About Dr. Judson Brandeis

Judson Brandeis, MD is a board-certified urologist, men's health specialist, clinical researcher and founder of AFFIRM Science.

His work focuses on erectile health, male sexual wellness, vascular function and evidence-based approaches to improving men's health.

Dr. Brandeis was an author of the study "Combining a Nitric Oxide Boosting Dietary Supplement With Sildenafil Improves Nighttime Erections More Than Sildenafil Alone," published in The Journal of Sexual Medicine.

Disclosure

Authors of the published study disclosed industry relationships with AFFIRM Science and FirmTech. The study used objective TechRing measurements to evaluate nighttime erectile activity. Readers should consider this relationship when interpreting the findings and review the original published research for complete study details.

Medical Disclaimer

This content is for educational purposes only and is not intended to diagnose, treat, cure or prevent any disease. AFFIRM is a dietary supplement and is not an FDA-approved treatment for erectile dysfunction. Sildenafil is a prescription medication. Consult a qualified healthcare professional before starting a supplement or changing prescription medication.