Hart2Heart with Dr. Mike Hart

#202 Better Alternatives To Metformin

Hart2Heart with Dr. Mike Hart

Show Notes

In this solo episode, the host discusses the effects of metformin, berberine, and dihydroberberine on exercise adaptation and longevity. While metformin is known for its longevity benefits and is popular in the biohacking community, it has been shown to significantly reduce exercise adaptations and VO2 max gains. Berberine, a supplement with similar effects to metformin, is easier to obtain but still has some negative effects on exercise and significant GI side effects. The episode introduces dihydroberberine (DHB), a compound with fewer GI issues and less impact on exercise adaptation, making it more suitable for athletes. The host explains the mechanisms behind these compounds, including their effects on AMPK and mTOR pathways, and offers practical advice on when to take DHB in relation to different types of exercise to maximize benefits and minimize drawbacks.

Links: Harvard longevity researcher known for NAD+ & aging research. Diabetes drug often discussed for longevity. Energy-sensing enzyme that promotes catabolic (fat-burning) pathways.

Show Notes: 00:00 Welcome back to the Hart2Heart Podcast with Dr. Mike Hart 00:14 "Metformin may blunt up to 50% of your VO₂ max gains — that's a massive hit for any athlete." 00:30 Metformin: the popular longevity drug 01:00 Berberine: the over-the-counter alternative 02:30 Understanding AMPK and mTOR 04:30 Metformin's mechanism and drawbacks 06:00 Berberine's mechanism and side effects 07:30 Dihydro berberine: the superior choice 10:30 DHB and exercise: timing and benefits 18:00 Comparing Metformin, berberine, and DHB

— 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 light, and de-prescribing pharmaceuticals—using medications only when absolutely necessary.

Beyond health science, we tackle 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 is the podcast 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 on social with Dr. Mike Hart: Instagram: @drmikehart

Twitter: @drmikehart

Facebook: @drmikehart

More from Hart2Heart with Dr. Mike Hart

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In this solo Hart2Heart Podcast episode (focused on male androgenetic alopecia), Dr. Mike Hart reviews hair-loss treatments, emphasizing that regrowth is harder if follicles are gone after 12–18 months. He highlights minoxidil (topical or oral), noting similar efficacy between 2.5 mg and 5 mg oral dosing, comparable results between oral 5 mg and topical 5% twice daily, and that adding 0.01% tretinoin may allow once-daily topical use; combining oral and topical is unstudied but not necessarily dangerous. He advises avoiding systemic DHT blockers due to side effects, favoring 0.05% topical dutasteride for minimal blood DHT reduction, and recommends weekly microneedling (~0.75 mm) without applying products immediately after. As growth-factor adjuncts, he prioritizes PRP or placental exosomes, discusses limited evidence for ketoconazole shampoo and copper peptides, warns DHT-derived anabolic steroids won't be helped by dutasteride, and reviews emerging anti-androgen options and their systemic-risk concerns.

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Dr. Mike Hart and Dr. Ira Price explore how medicine is adapting as patients gain greater access to emerging treatments, health information, and tools once limited to physicians. They discuss unapproved peptides and GLP-1 drugs, the growing shift toward personalized and patient-centered care, and the challenges doctors face when evidence and regulation lag behind real-world use. The conversation expands into Canada's opioid crisis, drug decriminalization, fentanyl and medetomidine contamination, emergency-room strain, physician burnout, and broader problems within the Canadian healthcare system. They also examine medical cannabis, CBD and lesser-known cannabinoids, psychedelic medicine, sleep, longevity, and the importance of balancing individual choice with evidence, clinical judgment, and responsible medical guidance. Dr. Ira Price is an emergency physician, sports medicine specialist, and longtime cannabinoid-medicine practitioner whose work sits at the intersection of acute care, emerging therapeutics, and patient-centered medicine. Over nearly two decades working with cannabinoids and years on the front lines of emergency care, he has developed a strong focus on helping patients navigate treatments that often move faster than traditional medical guidelines. His approach emphasizes collaboration rather than gatekeeping, encouraging physicians to remain lifelong learners while helping patients critically evaluate evidence, understand risks and benefits, and make more informed decisions about their health. He brings a practical perspective shaped by emergency medicine, sports medicine, cannabinoid research and clinical practice, and firsthand experience with the evolving challenges facing modern healthcare.

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Dr. Mike Hart sits down with lipidologist Dr. Spencer Nadolsky for a practical discussion on cardiovascular prevention, cholesterol management, and metabolic health. They break down how to interpret ApoB, LDL, HDL, triglycerides, and Lp(a), when cholesterol-lowering medications may make sense, and why long-term exposure matters when thinking about heart disease risk. The conversation also explores statins, PCSK9 inhibitors, plaque progression, supplements, insulin resistance, and the evolving role of GLP-1 medications in obesity treatment and long-term cardiometabolic health. Dr. Spencer Nadolsky is a physician specializing in obesity medicine, lipidology, and cardiometabolic health, with a strong focus on preventing chronic disease before it develops. His approach combines evidence-based medicine with individualized risk assessment, helping patients make sense of cholesterol, metabolic health, body weight, medications, and lifestyle without relying on one-size-fits-all recommendations. Known for translating complex medical research into practical guidance, he emphasizes sustainable health decisions, meaningful clinical outcomes, and finding the balance between being proactive about longevity and becoming overly consumed by it.

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Dr. Mike Hart discusses how oral peptides can still have biological effects despite limited or no systemic absorption, using examples including KPV, BPC-157, linaclotide (Constella), oral semaglutide, and cyclosporine. He explains protein digestion into dipeptides/tripeptides and the PEPT1 transporter that moves some small peptides into enterocytes for local cellular effects, noting that KPV can act in intestinal cells without entering circulation and that carnosine is another PEPT1-absorbed example. He outlines multiple local mechanisms (acting in the gut lumen, on the enterocyte surface, inside enterocytes, and in nearby gut tissue) and contrasts these with systemic absorption examples like semaglutide formulated with SNAC (only 0.4–1% reaches blood yet remains effective) and cyclosporine's unusual properties. He notes exceptions like glutathione and discusses theories for BPC-157's oral effects, emphasizing regulated products and upcoming discussion on GLP-1s and obesity with Dr. Spencer Nadolsky.

See all episodes →