Beyond ED | The Blue Pill for Longevity

Happy Friday!

I just released a brand-new long-form video on Spotify that I have been meaning to record for months.

It’s about Viagra for longevity.

If you have followed my work for a while, you already know I have been a big supporter of low-dose Cialis for healthspan and performance.

That conversation has slowly started to gain traction.

What almost nobody is talking about, though, is Viagra (sildenafil) itself and the depth of data behind it for cardiovascular health, brain aging, pulmonary function, metabolic health, and overall mortality.

In this new episode, I walk through the research, the mechanisms, and my own experience rotating Viagra and Cialis in a way that keeps lasting benefits.

This email is the written companion to that episode.

Here is why the “little blue pill” deserves to be taken seriously in the longevity conversation.

Viagra Is a Longevity Drug

Viagra was originally developed in the 1990s for angina and hypertension.

Erectile dysfunction was an unexpected side effect that changed how the drug was marketed, but its original purpose matters. Sildenafil was designed to work on blood vessels.

At the core, Viagra is a PDE5 inhibitor. It blocks the enzyme that breaks down cyclic GMP, which amplifies nitric oxide signaling throughout the body.

Nitric oxide is one of the most important molecules we have for vascular health. It relaxes smooth muscle, improves blood flow, lowers vascular resistance, and supports endothelial function.

This pathway is active throughout the cardiovascular system, the lungs, the brain, skeletal muscle, and even platelets. When nitric oxide signaling improves, blood reaches organs more efficiently, platelet aggregation decreases, and the endothelium becomes healthier.

Endothelial health is one of the strongest predictors of cardiovascular aging.

Even if sildenafil improved endothelial function alone, it would already qualify as a longevity tool.

What makes it more interesting is that it goes far beyond that.

More Than Blood Flow

When sildenafil increases cGMP, it activates protein kinase G, which triggers downstream effects that overlap heavily with pathways targeted in longevity medicine.

We see ischemic preconditioning effects, meaning cells become more resilient to stress.

We see activation of PGC-1 alpha, one of the master regulators of mitochondrial biogenesis.

Sildenafil also activates AMPK, a pathway most people associate with metformin.

At the same time, it suppresses inflammatory signaling through NF-kappa B and increases antioxidant enzyme activity that helps neutralize reactive oxygen species.

The combined effect is reduced inflammation, improved mitochondrial efficiency, and enhanced cellular energy metabolism.

The brain, lungs, heart, and metabolic tissues all benefit from improved blood flow and intracellular signaling.

PDE5 is highly expressed in vascular tissue and lung vasculature, which explains why sildenafil later gained FDA approval for pulmonary arterial hypertension.

Human Data

We now have decades of real-world data from millions of men using PDE5 inhibitors.

A 2024 study of more than 500,000 middle-aged men with erectile dysfunction found a 17% lower risk of heart attack, a 22% lower risk of stroke, and a 24% reduction in all-cause mortality among PDE5 inhibitor users.

Those are large effects.

Other studies show sildenafil increases coronary artery diameter, improves endothelial responsiveness, and reduces platelet activation. In many men, low-dose Viagra or Cialis alone meaningfully lowers blood pressure.

The brain data is even more compelling.

Large observational datasets show substantially lower rates of Alzheimer’s disease and dementia in sildenafil users.

One analysis reported a 69% reduction in Alzheimer’s risk over a 6-year follow-up.

Mechanistically, this aligns with sildenafil's mechanism of action.

It improves cerebral blood flow, crosses the blood-brain barrier, enhances synaptic plasticity through cGMP signaling in the hippocampus, reduces tau phosphorylation, lowers beta-amyloid production, and supports mitochondrial function in neurons.

System-Wide Benefits

Sildenafil’s pulmonary benefits are well established.

It is FDA approved for pulmonary arterial hypertension at 20 mg three times daily, where it improves exercise capacity by dilating pulmonary blood vessels.

The same mechanism may support people with secondary pulmonary hypertension related to COPD, pulmonary fibrosis, sleep apnea, and even high-altitude exposure.

As people age, pulmonary circulation stiffens, and oxygen delivery declines.

Maintaining the lung vasculature's responsiveness is a major factor in long-term exercise tolerance and cardiovascular health.

Metabolically, a randomized trial in people with prediabetes showed that 3 months of sildenafil improved insulin sensitivity, reduced markers of vascular inflammation, and improved kidney microvascular health.

Some benefits persisted months after stopping the drug, suggesting structural improvements rather than temporary effects.

There are also emerging signals regarding fat metabolism, bone health, and adjunctive cancer therapy, driven by improved blood flow and cellular signaling.

Essentially, sildenafil improves the biological environment in which cells live.

How I Use It

For erectile dysfunction, sildenafil is typically used at 50 to 100 mg as needed. I approach it differently for longevity.

For pulmonary hypertension, sildenafil is dosed at 20 mg three times daily, suggesting it can be used at lower doses.

For longevity purposes, I generally see 20 to 40 mg per day as a reasonable range for most men, taken once daily or split.

Personally, I often use 20 mg pre-workout three to four times per week to take advantage of blood flow and performance benefits.

What has worked best for me long-term is rotating.

I will use low-dose Cialis for several weeks, then switch to low-dose Viagra.

Cialis works extremely well, but I notice a gradual loss of subjective effects over time.

Rotating keeps sensitivity high while maintaining endothelial and performance benefits.

If you are healthy and already have lower blood pressure, start conservatively and pay attention to how you feel.

Avoid nitrates and be cautious if you are using other blood pressure medications. This approach works best when used intelligently rather than aggressively.

Final Thoughts

This strategy makes sense for men who care about cardiovascular health, brain aging, exercise performance, and metabolic resilience.

It may be especially useful for people with family histories of heart disease or dementia who want to support vascular health early.

Women can also use sildenafil at much lower doses. It improves blood flow and has been studied for the treatment of menstrual cramps, Raynaud’s phenomenon, and microvascular angina. For women, I would start very low (around 5mg) and increase slowly.

Supporting endothelial health and mitochondrial signaling matters in your twenties just as much as it does later in life.

The key is restraint. Higher daily doses reduce sensitivity over time, which is why I prefer lower, consistently used doses and cycling when needed.

Viagra is one of the most studied vascular drugs available. There is no reason to feel awkward about using a tool that supports blood flow, organ health, and long-term resilience.

If you want the full breakdown, the episode is live now on Spotify.

Thank you for being here and for supporting this work. Have a fantastic weekend!

Best

Hunter Williams

Further Reading