This episode explores tadalafil (Cialis) as a potential longevity drug, though no randomized human trials prove it extends lifespan. Cialis works by blocking PDE5, enhancing nitric oxide signaling, and improving blood flow through vasodilation. Originally approved for pulmonary hypertension, it's also used for erectile dysfunction and BPH. Its 36-hour half-life makes it superior to Viagra for continuous longevity effects. The host frames vascular aging and endothelial dysfunction as key drivers of age-related diseases (heart disease, stroke, dementia, kidney disease). Observational data shows Cialis users have 44% lower mortality, fewer cardiovascular events, reduced dementia risk, and lower mortality in diabetics. Additional benefits include improved cardiac function, reduced infarct size, arrhythmia suppression, and regression of left ventricular hypertrophy. A 2024 meta-analysis found it lowers hemoglobin A1C, possibly via improved microvascular perfusion, insulin sensitivity, and mitochondrial function. Cialis crosses the blood-brain barrier and may improve neurovascular coupling and hippocampal plasticity, potentially benefiting those with or at risk of dementia. Safety is generally good with long-term daily use (2.5–5 mg), though cautions include avoiding use with nitrates, low blood pressure, or certain retinal disorders. Common side effects are headache, nasal congestion, and acid reflux. The host recommends consulting a doctor and references potential synergy with telmisartan. Tadalafil (Cialis) — MedlinePlus drug info: [https://medlineplus.gov/druginfo/meds/a604008.html](https://medlineplus.gov/druginfo/meds/a604008.html) Sildenafil (Viagra) — MedlinePlus drug info: [https://medlineplus.gov/druginfo/meds/a699015.html](https://medlineplus.gov/druginfo/meds/a699015.html) Key mechanisms mentioned Nitric Oxide (NO) — NCBI Bookshelf: [https://www.ncbi.nlm.nih.gov/books/NBK554485/](https://www.ncbi.nlm.nih.gov/books/NBK554485/) Cyclic GMP (cGMP) — NCBI Bookshelf: [https://www.ncbi.nlm.nih.gov/books/NBK542234/](https://www.ncbi.nlm.nih.gov/books/NBK542234/) Conditions mentioned in the episode Benign Prostatic Hyperplasia (BPH) — MedlinePlus: [https://medlineplus.gov/benignprostatichyperplasia.html](https://medlineplus.gov/benignprostatichyperplasia.html) Pulmonary Arterial Hypertension (PAH) — MedlinePlus: [https://medlineplus.gov/pulmonaryhypertension.html](https://medlineplus.gov/pulmonaryhypertension.html) Blood pressure drug mentioned Telmisartan — MedlinePlus drug info: [https://medlineplus.gov/druginfo/meds/a601249.html](https://medlineplus.gov/druginfo/meds/a601249.html) Other longevity / comparison drugs mentioned Metformin — MedlinePlus drug info: [https://medlineplus.gov/druginfo/meds/a696005.html](https://medlineplus.gov/druginfo/meds/a696005.html) Sirolimus (Rapamycin) — MedlinePlus drug info: [https://medlineplus.gov/druginfo/meds/a602026.html](https://medlineplus.gov/druginfo/meds/a602026.html) Side-effect helper mentioned Ibuprofen (Advil) — MedlinePlus drug info: [https://medlineplus.gov/druginfo/meds/a682159.html](https://medlineplus.gov/druginfo/meds/a682159.html) Dementia meds mentioned Donepezil (Aricept) — MedlinePlus drug info: [https://medlineplus.gov/druginfo/meds/a697032.html](https://medlineplus.gov/druginfo/meds/a697032.html) Amantadine — MedlinePlus drug info: [https://medlineplus.gov/druginfo/meds/a682064.html](https://medlineplus.gov/druginfo/meds/a682064.html) Lab markers mentioned Hemoglobin A1C (HbA1c) test — MedlinePlus lab test: [https://medlineplus.gov/lab-tests/hemoglobin-a1c-hba1c-test/](https://medlineplus.gov/lab-tests/hemoglobin-a1c-hba1c-test/) Insulin in blood test — MedlinePlus lab test: [https://medlineplus.gov/lab-tests/insulin-in-blood/](https://medlineplus.gov/lab-tests/insulin-in-blood/) People referenced (where the claims were mentioned) Huberman Lab (Dr. Andrew Huberman) — site: [https://www.hubermanlab.com/](https://www.hubermanlab.com/) Clip about low-dose tadalafil (2.5–5mg) — X post: [https://x.com/tbpn/status/2022350426394534334](https://x.com/tbpn/status/2022350426394534334) Bryan Johnson (Blueprint) — site: [https://blueprint.bryanjohnson.com/](https://blueprint.bryanjohnson.com/) Dr. David Sinclair (Harvard profile) — site: [https://sinclair.hms.harvard.edu/people/david-sinclair](https://sinclair.hms.harvard.edu/people/david-sinclair) Show Notes 00:00 Welcome to the Hart2Heart Podcast. 01:56 What Cialis Is: PDE5 Inhibition, cGMP & Nitric Oxide Explained 03:43 Approved Uses & Origin Story: Pulmonary Hypertension, ED, and BPH 05:33 Why Cialis Over Viagra: 36-Hour Half-Life & 24/7 Vascular Benefits 06:52 Vascular Aging 101: Endothelium, Perfusion, and Why It Drives Disease 11:14 What the Human Data Shows: Observational Evidence for Mortality, CVD & Dementia 13:04 Mechanisms Deep Dive: Heart Protection, Heart Failure, and Anti-Atherosclerosis 15:02 Cialis for Diabetics: Lowering A1C and Improving Insulin Sensitivity 16:21 Brain Effects: Blood–Brain Barrier, Neurovascular Coupling & Dementia Potential 18:21 Safety, Who Should Avoid It, and Daily Longevity Dosing (2.5–5 mg) + Wrap-Up The Hart2Heart podcast is hosted by family physician Dr. Michael Hart, who is dedicated to cutting through the noise and uncovering the most effective strategies for optimizing health, longevity, and peak performance. This podcast dives deep into evidence-based approaches to hormone balance, peptides, sleep optimization, nutrition, psychedelics, supplements, exercise protocols, leveraging sunlight, and de-prescribing pharmaceuticals — using medications only when absolutely necessary. Beyond health science, we explore the intersection of public health and politics, exposing how policy decisions shape our health landscape and what actionable steps people can take to reclaim control over their well-being. Guests range from out-of-the-box thinking physicians such as Dr. Casey Means (author of "Good Energy") and Dr. Roger Sehult (Medcram lectures) to public health experts such as Dr. Jay Bhattacharya (Director of the National Institutes of Health (NIH) and Dr. Marty Mckary (Commissioner of the Food and Drug Administration (FDA) and high-profile names such as Zuby and Mark Sisson (Primal Blueprint and Primal Kitchen). If you're ready to take control of your health and performance, this podcast is for you.We cut through the jargon and deliver practical, no-BS advice that you can implement in your daily life, empowering you to make positive changes for your well-being. Connect with Dr. Mike Hart Instagram: @drmikehart Twitter: @drmikehart Facebook: @drmikehart