Medically reviewed by Judson Brandeis, MD, Board-Certified Urologist and Men’s Health Specialist
Men searching for better treatments for erectile dysfunction often come across two very different options: prescription medications such as sildenafil and supplements marketed as nitric oxide boosters.
But can the two approaches work together?
Research led by urologist and men’s health specialist Judson Brandeis, MD, examined whether combining a nitric oxide-boosting dietary supplement with sildenafil could improve nighttime erections more than sildenafil alone.
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, Volume 22, Supplement 4.
The findings provide an interesting look at how nitric oxide, blood flow and PDE5 inhibitor medications such as sildenafil may work through complementary parts of the same biological pathway.
Dr. Brandeis: “Nitric oxide helps create the signal that opens blood vessels. Sildenafil helps that signal last longer. Our research looked at what happens when we support both sides of that pathway.”
Suggested expert quote for Dr. Brandeis to review and approve before publication.
What Does Nitric Oxide Have to Do With Erections?
Nitric oxide plays an important role in erectile function.
When a man becomes sexually stimulated, nitric oxide participates in a series of signals that increase levels of a molecule called cyclic guanosine monophosphate, or cGMP.
cGMP helps smooth muscle in penile blood vessels relax, allowing more blood to flow into the penis and helping produce an erection.
This is one reason healthy blood vessels and good cardiovascular health are closely connected with sexual function.
According to Dr. Brandeis, supporting nitric oxide production may therefore be one way to support the blood-flow mechanisms involved in erections.
How Does Sildenafil Work for Erectile Dysfunction?
Sildenafil, commonly known by the brand name Viagra, belongs to a group of medications called PDE5 inhibitors.
Other PDE5 inhibitors include tadalafil, commonly known as Cialis.
Sildenafil helps preserve the cGMP signal involved in increasing penile blood flow.
An enzyme called PDE5 normally breaks down cGMP. Sildenafil inhibits PDE5, allowing cGMP to remain active longer.
The relationship can be explained simply:
Nitric oxide helps produce the cGMP signal involved in an erection. Sildenafil helps prevent that signal from being broken down too quickly.
That led Dr. Brandeis to investigate an important question:
Could supporting nitric oxide while simultaneously slowing the breakdown of cGMP improve erectile function more than sildenafil alone?
That question became the basis of his research.
The Study: Nitric Oxide Supplement Plus Sildenafil vs. Sildenafil Alone
Dr. Brandeis and his research team investigated whether adding a nitric oxide-boosting dietary supplement to 40 mg of sildenafil could improve nighttime erectile function compared with taking sildenafil alone.
The supplement studied was AFFIRM®, a nitric oxide-supporting dietary supplement developed by Dr. Brandeis.
Its formulation contains:
- L-citrulline
- Red beet root extract
- Panax ginseng
- Muira puama
Rather than relying only on questionnaires or subjective reports, researchers objectively tracked nighttime erectile activity using the FirmTech TechRing™ Smart Performance Men’s Health Tracker.
The wearable device is designed to monitor erectile activity during sleep, allowing the study to compare changes in the duration and intensity of nighttime erections under different conditions.
What Did the Study Find?
The published study in The Journal of Sexual Medicine included 22 men with an average age of 55.
Researchers measured erectile activity using area under the curve per hour of sleep, or AUC/hr.
With sildenafil 40 mg alone:
Average AUC/hr: 87
With sildenafil 40 mg plus the nitric oxide-boosting supplement:
Average AUC/hr: 117
That was a 34% increase in the study’s primary nighttime erectile measurement.
The average number of nighttime erections also increased from 3.25 to 3.87 erections per night.
The researchers concluded that combining sildenafil with the studied nitric oxide-boosting supplement increased the measured duration and intensity of nighttime erections compared with sildenafil alone.
Dr. Brandeis: “What makes these results interesting is that we weren’t simply asking men whether they thought their erections were better. We objectively measured erectile activity while they slept.”
Suggested expert quote for Dr. Brandeis to review and approve before publication.
The study was relatively small, so the findings should be viewed as promising clinical evidence rather than proof that every man with erectile dysfunction will experience the same result.
Read the full published scientific abstract here.
Why Measure Nighttime Erections?
Healthy men normally experience multiple erections during REM sleep.
Measuring nighttime erections can provide information about erectile physiology without many of the variables that affect sexual activity while awake.
Sexual performance can be influenced by:
- Anxiety
- Relationship issues
- Alcohol
- Stress
- Fatigue
- Sexual stimulation
- Expectations
- Sleep quality
For this study, Dr. Brandeis’s team used the FirmTech TechRing™ to objectively monitor erectile activity during sleep.
This made it possible to evaluate changes in erectile performance using measurable nighttime data rather than depending entirely on how participants remembered or rated their sexual performance.
Dr. Brandeis: “Nighttime erections give us a window into erectile health without many of the psychological and situational factors that can affect sexual performance while a man is awake.”
Suggested expert quote for Dr. Brandeis to review and approve before publication.
How Was Erectile Performance Measured?
One of the most important parts of the study was the use of an objective measurement tool.
The FirmTech TechRing™ Smart Performance Men’s Health Tracker was worn during sleep to track nighttime erectile activity.
This allowed researchers to measure changes in factors such as:
- Duration of nighttime erections
- Intensity of erectile activity
- Number of erections during sleep
- Erectile activity standardized to hours of sleep
Using a wearable measurement device is important because erectile function can otherwise be difficult to evaluate objectively.
Questionnaires remain useful, but answers can be influenced by memory, stress, relationship factors, confidence and expectations.
The FirmTech measurements gave the researchers another way to quantify whether the intervention was actually associated with changes in nighttime erectile physiology.
Why Did the Study Use 40 mg of Sildenafil?
Dr. Brandeis intentionally studied 40 mg of sildenafil rather than the maximum 100 mg dose.
The reason was methodological.
If researchers started with a dose already producing close to a participant’s maximum response, it could become difficult to measure whether adding nitric oxide support produced an additional improvement.
Using a lower sildenafil dose provided more room to identify a potential additional effect.
This leads to a clinically interesting question:
Could supporting nitric oxide improve the response to a lower dose of sildenafil in some men?
The study provides early evidence worth investigating further, but men should not change their sildenafil dosage or combine medications and supplements without discussing it with their physician.
Can Nitric Oxide Boosters Help Erectile Dysfunction?
There is growing interest in the connection between nitric oxide and erectile dysfunction because nitric oxide plays a fundamental role in blood-vessel relaxation and penile blood flow.
One commonly studied ingredient is L-citrulline.
The body converts L-citrulline into L-arginine, which participates in nitric oxide production.
Beets and leafy green vegetables provide another nitric oxide pathway because they contain dietary nitrates.
However, this does not mean every product marketed as a “nitric oxide booster” has been clinically evaluated for erectile function.
Supplements can contain dramatically different ingredients, doses and combinations.
The Brandeis study specifically evaluated AFFIRM, rather than nitric oxide supplements as a general category.
What Is AFFIRM?
AFFIRM Science was founded around formulations developed by Dr. Judson Brandeis, a board-certified urologist and sexual medicine specialist.
The AFFIRM formulation evaluated in the study includes:
L-Citrulline
L-citrulline is an amino acid the body can convert to L-arginine, which participates in nitric oxide production.
Red Beet Root Extract
Beets contain nitrates that can be converted through a separate biological pathway into nitric oxide.
Panax Ginseng
Panax ginseng has been investigated in men’s health research, including research related to sexual function.
Muira Puama
Muira puama is a botanical traditionally associated with sexual wellness and is included as part of the complete AFFIRM formulation.
The key distinction is that the research evaluated the specific AFFIRM combination, not each ingredient independently and not every supplement marketed as a nitric oxide booster.
Learn more about AFFIRM Science.
Is a Nitric Oxide Supplement a Replacement for Sildenafil?
Not necessarily.
Nitric oxide-supporting supplements and PDE5 inhibitor medications affect different parts of the same general erectile pathway.
The purpose of Dr. Brandeis’s research was not simply to determine whether a supplement could replace prescription ED medication.
Instead, the study asked whether supporting nitric oxide production could complement sildenafil’s effect on the nitric oxide-cGMP pathway.
Some men respond very well to sildenafil or tadalafil alone. Other men experience incomplete results, side effects or additional medical issues contributing to their erectile dysfunction.
There is no single erectile dysfunction treatment that is right for every man.
Sildenafil vs. Tadalafil for Erectile Dysfunction
Sildenafil and tadalafil are both PDE5 inhibitors, but they have different durations of action.
Sildenafil generally has a shorter active period, while tadalafil remains active considerably longer.
The right medication may depend on:
- How frequently a man has sex
- Desired spontaneity
- Previous response to ED medications
- Side effects
- Other medications
- Cardiovascular health
- Overall medical history
A men’s health urologist can help determine the most appropriate treatment rather than simply increasing medication without investigating why erectile dysfunction is occurring.
Are Erectile Dysfunction Supplements Safe to Take With Sildenafil?
Men should speak with a qualified physician before combining supplements with sildenafil, tadalafil or other prescription medications.
“Natural” does not automatically mean safe or appropriate for every individual.
There is also an important distinction between supplements intended to support natural nitric oxide pathways and prescription nitrate medications.
Sildenafil should not be taken with nitrate medications or nitric oxide donor drugs because the combination can cause a dangerous drop in blood pressure.
Men taking medications for cardiovascular disease should speak with their physician before using sildenafil or adding supplements.
Erectile Dysfunction Can Be a Health Signal, Not Just a Sexual Problem
An erection requires interaction among:
- Blood vessels
- Nerves
- Hormones
- Brain signaling
- Penile tissue
- Cardiovascular function
Because penile arteries are small blood vessels, changes in erectile function can sometimes provide useful information about a man’s overall vascular health.
Dr. Brandeis: “Erectile dysfunction isn’t always just a bedroom problem. Erections depend heavily on vascular health, which is why changes in erectile function deserve to be taken seriously.”
Suggested expert quote for Dr. Brandeis to review and approve before publication.
When Should You See a Urologist for Erectile Dysfunction?
Consider seeing a urologist or men’s sexual health specialist if you are experiencing:
- Difficulty getting an erection
- Difficulty maintaining an erection
- Weaker erections
- Fewer nighttime or morning erections
- Sildenafil or tadalafil that no longer works as well
- Side effects from ED medications
- Changes in sexual performance
- Concerns about testosterone or other aspects of men’s sexual health
You don’t have to wait until erectile dysfunction becomes severe.
Identifying why erectile function has changed can help determine the most appropriate treatment.
Men’s Sexual Health and Erectile Dysfunction Treatment in San Ramon, California
Judson Brandeis, MD is a board-certified urologist and men’s health specialist at Brandeis MD Male Rejuvenation Center in San Ramon, California.
Dr. Brandeis’s work focuses on men’s sexual health, erectile function and innovative approaches to improving men’s health and quality of life.
His background includes undergraduate education at Brown University, Vanderbilt University School of Medicine, research at Harvard Medical School and general surgery and urology training at UCLA.
In addition to treating patients, Dr. Brandeis conducts research and creates educational resources designed to help men understand the science behind their health and treatment options.
Looking for an Erectile Dysfunction Doctor or Men’s Health Urologist?
If you’re searching for an erectile dysfunction specialist, men’s health urologist or sexual health doctor in the San Francisco Bay Area, Brandeis MD Male Rejuvenation Center evaluates men experiencing changes in sexual function.
Brandeis MD Male Rejuvenation Center
Judson Brandeis, MD
100 Park Pl, Suite 140
San Ramon, CA 94583
Phone: (925) 255-7867
Frequently Asked Questions
Does nitric oxide help erections?
Nitric oxide plays an important role in the biological signaling process that allows penile blood vessels to relax and blood flow to increase during an erection.
Do nitric oxide supplements help erectile dysfunction?
Some ingredients that support nitric oxide pathways have been studied in relation to erectile function. However, evidence varies considerably between products and formulations.
Dr. Brandeis’s research specifically studied AFFIRM in combination with sildenafil rather than making conclusions about all nitric oxide supplements.
What is the best nitric oxide booster for erectile dysfunction?
There is no single nitric oxide supplement proven to be best for every man.
Rather than relying on marketing claims, men should consider whether a particular formulation has actually been evaluated in clinical research.
AFFIRM was the specific nitric oxide-supporting formulation evaluated in Dr. Brandeis’s published study.
How were nighttime erections measured in the study?
Researchers used the FirmTech TechRing™ Smart Performance Men’s Health Tracker to objectively track nighttime erectile activity during sleep.
This allowed the research team to measure changes in erection duration, intensity and frequency rather than relying solely on subjective questionnaires.
Can sildenafil and nitric oxide work together?
They affect related portions of the same erectile signaling pathway.
Nitric oxide contributes to cGMP production, while sildenafil inhibits the PDE5 enzyme that breaks down cGMP.
In Dr. Brandeis’s study, nighttime erectile measurements were greater when sildenafil was combined with the studied nitric oxide-supporting formulation than with sildenafil alone.
The Bottom Line
Nitric oxide helps initiate one of the important biological signals involved in penile blood flow, while sildenafil helps preserve that signal by reducing the breakdown of cGMP.
In research published in The Journal of Sexual Medicine, Judson Brandeis, MD and colleagues found that combining sildenafil 40 mg with the studied nitric oxide-boosting supplement produced a 34% greater nighttime erectile AUC/hr measurement than sildenafil 40 mg alone.
Those nighttime measurements were captured using the FirmTech TechRing™, giving researchers an objective way to compare erectile activity during sleep.
The findings are promising but come from a relatively small study of 22 participants, and additional research is needed.
For men experiencing erectile dysfunction, weaker erections or declining sexual performance, the goal shouldn’t only be finding a stronger pill.
It should also be understanding why erectile function is changing.
A men’s health urologist can help identify possible causes and discuss appropriate treatment options based on each man’s individual health.
Schedule or learn more at BrandeisMD.com.
About Judson Brandeis, MD
Judson Brandeis, MD is a board-certified urologist, clinical researcher and founder of BrandeisMD in San Ramon, California.
He is the author of The 21st Century Man: Advice from 50 Top Doctors and Men’s Health Experts So You Can Feel Great, Look Good and Have Better Sex and conducts research and education focused on men’s sexual health and healthy aging.
Additional educational resources are available through Global Men’s Wellness.
Research
Brandeis J, Tu A, Justin E.
“Combining a Nitric Oxide Boosting Dietary Supplement With Sildenafil Improves Nighttime Erections More Than Sildenafil Alone.”
The Journal of Sexual Medicine. Volume 22, Supplement 4.
Relevant Resources
- Brandeis MD Male Rejuvenation Center
- AFFIRM Science
- FirmTech TechRing™ Smart Performance Men’s Health Tracker
- Published Clinical Study in The Journal of Sexual Medicine
- Global Men’s Wellness
Medical Disclaimer
This article is intended for educational purposes and is not a substitute for individualized medical advice, diagnosis or treatment. Sildenafil is a prescription medication and may not be appropriate for everyone. Always discuss medications and supplements with a qualified healthcare professional before changing treatment.
