Tadalafil, Nitric Oxide and Longevity: A Biomarker Case Study Review

"Why I've Become More Bullish on Tadalafil"

Over the last few years, tadalafil has become one of the most discussed compounds within the longevity and biohacking community. While most people know it as a treatment for erectile dysfunction, emerging research suggests its benefits may extend far beyond sexual health.

At Epic Genetics, we have become increasingly interested in tadalafil because of its potential effects on endothelial function, blood pressure regulation, vascular ageing, and nitric oxide signalling.

This article reviews both the published literature and real-world biomarker trends observed by Epic Genetics founder Tony Pemberton and a small group of clients who have incorporated tadalafil into their broader health optimisation protocols.

The Research: More Than an Erectile Dysfunction Drug

A 2024 meta-analysis including 16 cohort studies and more than 1.2 million participants reported that PDE5 inhibitor users demonstrated:

• 22% lower major adverse cardiovascular events

• 30% lower all-cause mortality

While observational data cannot prove causation, the magnitude of these associations is difficult to ignore.

More recently, a systematic review and meta-analysis of 63 randomized controlled trials found that PDE5 inhibitors were associated with:

• Lower systolic blood pressure

• Lower diastolic blood pressure

• Improved flow-mediated dilation

• Reduced arterial stiffness markers

These findings are particularly interesting because vascular ageing is increasingly recognised as one of the central drivers of biological ageing.

Why Nitric Oxide Matters

Nitric oxide is often referred to as one of the body's most important signalling molecules.

When nitric oxide is released by the endothelium, it stimulates production of cyclic guanosine monophosphate (cGMP), which signals smooth muscle cells surrounding blood vessels to relax.

This results in:

• Improved circulation

• Better endothelial function

• Increased nutrient delivery

• Improved vascular flexibility

Tadalafil works by inhibiting PDE5, the enzyme responsible for breaking down cGMP.

Put simply:

Nitric oxide creates the signal.

cGMP carries the signal.

PDE5 destroys the signal.

Tadalafil helps preserve the signal.

For longevity-focused individuals, the implications extend well beyond sexual function.

Founder Case Study: Tony Pemberton

Over the past year, Tony has gradually increased his tadalafil usage from intermittent use to a more consistent protocol.

During this period, several vascular-related biomarkers showed meaningful improvements.

Vanillactic Acid (VAA)

Vanillactic Acid is a metabolite associated with phenylalanine metabolism.

Higher levels have been associated with:

• Cardiovascular disease risk

• Hypertension

• Vascular inflammation

• Oxidative stress

Tony's VAA marker improved from approximately the 85th percentile to the 47th percentile.

This represents a substantial reduction in a biomarker associated with cardiovascular risk pathways.

ADMA / SDMA Marker

ADMA (Asymmetric Dimethylarginine) is particularly interesting because it directly interferes with nitric oxide production.

Higher ADMA levels are associated with:

• Reduced nitric oxide bioavailability

• Endothelial dysfunction

• Higher cardiovascular risk

• Reduced kidney function

The aggregate ADMA / SDMA biomarker improved from approximately the 93rd percentile to the 21st percentile.

This is directionally consistent with improved nitric oxide signalling and vascular function.

Importantly, the TruHealth report itself notes that PDE5 inhibitors may influence this pathway, making the observation biologically plausible.

Additional Client Observations

While individual case studies should never be interpreted as proof of efficacy, Epic Genetics has observed similar trends in several clients using tadalafil as part of a broader optimisation strategy.

Across three additional case studies:

Vanillactic Acid (VAA)

Average improvement:

15 percentile points

This suggests a consistent trend toward improved phenylalanine metabolism and reduced cardiovascular risk signalling.

ADMA / SDMA Marker

Average improvement:

22 percentile points

Given the close relationship between ADMA and nitric oxide production, this is perhaps the most interesting finding observed across the group.

These changes occurred alongside various combinations of:

• Exercise

• Nutritional interventions

• Blood pressure optimisation

• Nitric oxide support strategies

• General health improvements

Therefore, tadalafil should not be viewed as the sole cause of these changes.

However, the consistency of the direction of change makes the observations noteworthy.

Blood Pressure, Biological Ageing and Real-World Monitoring

One of the reasons Tony has become increasingly interested in tadalafil is its potential impact on blood pressure and vascular health.

Blood pressure is one of the most important predictors of long-term cardiovascular risk and is closely linked to biological ageing. Several biological ageing algorithms, including components incorporated within DunedinPACE and other longevity-focused models, utilise cardiovascular and metabolic health markers due to their strong association with future disease risk.

Beyond traditional blood pressure measurements, biomarkers such as ADMA, SDMA and Vanillactic Acid provide additional insight into nitric oxide signalling, endothelial function, vascular inflammation and cardiovascular health.

Over recent months, Tony observed an average reduction of approximately 5 mmHg in systolic blood pressure while increasing tadalafil use and paying closer attention to vascular health markers.

Importantly, blood pressure readings should always be interpreted within context.

A blood pressure reading taken:

• Immediately after exercise

• Following a large meal

• During work-related stress

• After caffeine consumption

may be significantly different from a reading taken while fully relaxed.

Tony typically measures blood pressure during the evening while resting and semi-reclined in bed. Under these conditions, his personal target is approximately:

• 105 mmHg systolic

• 65 mmHg diastolic

While individual targets will vary, maintaining healthy blood pressure remains one of the most important longevity interventions available.

Across the additional client case studies reviewed, all participants utilised tadalafil at approximately 5 mg daily alongside broader health optimisation strategies.

These individuals demonstrated average improvements of:

• 15 percentile points in Vanillactic Acid (VAA)

• 22 percentile points in the ADMA / SDMA marker

While these observations cannot establish causality, they are consistent with the growing body of evidence supporting improved endothelial function and nitric oxide signalling.

Future Experiments

Going forward, Tony plans to continue monitoring these biomarkers through TruDiagnostic TruHealth and TruAge testing.

In addition to his current protocol of taking tadalafil before morning training sessions, he is considering experimenting with evening administration to evaluate whether maintaining more consistent 24-hour PDE5 inhibition may provide additional benefits for:

• Blood pressure control

• Recovery

• Vascular function

• Nitric oxide signalling

• Overnight circulation

Future testing will focus on whether these adjustments continue to improve cardiovascular biomarkers and biological ageing metrics over time.

The Bigger Picture

Tadalafil should not be viewed as a replacement for:

• Exercise

• Sleep

• Nutrition

• Blood pressure management

• Metabolic health

However, growing evidence suggests it may be a useful adjunct for supporting endothelial function and cardiovascular health.

Combined with emerging human data and encouraging biomarker trends, tadalafil has become one of the more interesting compounds currently being explored within the longevity community.

Interested in Your Own Biomarkers or Tadalafil Prescription?

If you'd like help interpreting your TruHealth, TruAge, cardiovascular, nitric oxide, kidney health or biological-age biomarkers, contact admin@epicgenetics.co.uk.

Where appropriate, we can help connect clients with our clinical partners to discuss therapies such as tadalafil and determine whether they may be suitable candidates for prescription treatment.