Podcast Summary:

The Human Upgrade with Dave Asprey
Episode #1302: Why Big Pharma Hates Nitric Oxide (And How to Use It Anyway)
Guest: Dr. Nathan Bryan
Date: July 17, 2025

Overview

This episode features Dr. Nathan Bryan, a globally recognized expert on nitric oxide (NO), who discusses its pivotal role in human health, metabolism, cognitive function, and performance. Host Dave Asprey and Dr. Bryan explore why NO is fundamental, how modern lifestyle and pharmaceutical practices undermine its benefits, and how to optimize your NO levels for longevity and vitality—often contrary to “Big Pharma” interests.

Key Discussion Points & Insights

1. Nitric Oxide: The Master Switch for Human Performance

• [00:07-01:20]
  • NO is foundational, not a cure-all, but vital in:
    • Regulating blood flow and circulation
    • Enhancing libido, mitochondrial function, cognition, and glucose uptake
    • Preventing telomere shortening, mobilizing stem cells, and modulating insulin resistance
  • “If you want to heal and regenerate and optimize your human performance, nitric oxide’s really at the top of the list.” — Dr. Bryan [00:09]

2. Production and Loss of Nitric Oxide

• [02:38-05:01]
  • Two main NO production pathways:
    1. Enzyme-dependent (nitric oxide synthase—found in blood vessels, brain, immune cells, even red blood cells)
       • Over time, Western lifestyle (sugar, processed foods, sedentary habits, toxins) impairs this pathway.
    2. Dietary pathway (oral microbiome + stomach acid + nitrates in food)
       • Redundant but vital, as enzyme function declines with age/lifestyle.
  • “You can’t even think about developing rational therapies or improving someone’s nitric oxide if at first you don’t understand how the human body makes it naturally.” — Dr. Bryan [03:31]

3. Diet, Lifestyle & Nitric Oxide

• [05:21-08:37]
  • Sugar is the worst food for NO: spikes blood sugar, damages enzymes, alters microbiome
    • “Anything that leads to an increase in blood sugar... completely shuts down nitric oxide production.” — Dr. Bryan [05:26]
  • Best foods: Balance of good protein, fats, antioxidants, and moderate carbs—tailored to the individual.
  • Leafy greens and beets: Have nitrate but need proper oral bacteria; mouthwash, fluoride, and antacids can block conversion.
    • “If you have fluoride in your toothpaste or are using antiseptic mouthwash, you get no nitric oxide benefit from that.” — Dr. Bryan [08:55]

4. Oral Microbiome and Oral Care

• [09:23-11:57 & 30:38-34:56]
  • Healthy oral bacteria crucial for NO synthesis from food
    • Commercial prebiotics/probiotics mostly ineffective in restoring needed bacteria
    • Some specialized NO lozenges (like N101) act as both direct NO sources and prebiotics
  • Mouthwash & Fluoride: Destroy oral microbiome, raise blood pressure, and ruin NO production
    • “Would you throw an atomic bomb in your mouth two to three times a day?” — Dr. Bryan [31:24]
    • “If you have fresh breath because of mouthwash use, you’re not going to be able to get an erection because you don’t have any nitric oxide.” — Dr. Bryan [31:49]
  • Alternative: Hydroxyapatite-based, fluoride-free toothpaste designed to restore oral health and NO production

5. Supplements, Beets, and Nitric Oxide Myths

• [11:05-17:41; 16:32-19:13]
  • Most commercial beet products are “dead beets”—no nitrate content, ineffective
    • Labs have used commercial beet powders as placebos
    • Excessive oxalates in beets can cause kidney stones and other issues
      • “All they do is turn your pee and poop red and cause a lot of anxiety. There’s no nitrate in them.” — Dr. Bryan [17:33]
  • Arginine/citrulline supplements ineffective for most—body usually has enough; enzyme dysfunction is often the issue
    • “It doesn’t make sense to supplement what’s not missing.” — Dr. Bryan [12:32]
  • Proper NO supplements fix underlying enzyme function rather than dumping more substrate

6. Blood Sugar, Insulin Resistance, and NO

• [19:25-22:16; 25:22-26:52]
  • NO is needed for insulin signaling and glucose uptake
    • Insulin binds cells, triggers NO production, which then activates GLUT4 transporter for glucose entry
    • “Insulin resistance and type 2 diabetes is a symptom of nitric oxide deficiency.” — Dr. Bryan [19:37]
  • Strategy: NO supplementation can help process carbs more efficiently

7. Medications that Impair NO, and Systemic Problems

• [22:28-26:21]
  • Proton Pump Inhibitors (PPIs): Shut down NO; up to 40% higher rates of heart attack, stroke, Alzheimer’s if used long-term
    • “It’s never a good idea to shut down stomach acid production.” — Dr. Bryan [22:56]
  • Statins (cholesterol-lowering drugs): Also impair NO and associated health markers
  • Advice: Focus on supporting natural stomach acid and salt intake; avoid unnecessary suppression

8. COVID-19, Brain Fog, and Immune Response

• [37:00-42:06]
  • NO showed promise as early COVID treatment—helped keep patients out of hospital and reduce severe outcomes
  • Bureaucracy/government focus on vaccines over “early therapeutics” stonewalled wider adoption
  • Brain fog: Often due to decreased blood flow/hypoxia in brain (NO deficiency)
    • Increasing NO enhances brain perfusion and cognitive clarity

9. Carnivore, Keto, and Standard American Diets

• [48:38-50:40]
  • Carnivore/keto (with limited carbs) are generally favorable for NO, mostly by eliminating sugar and processed foods
  • Standard American Diet (SAD) destroys NO production—supplementation is crucial for SAD lifestyle

10. NO, Nitrates, and Nitrates in Food

• [44:39-47:46]
  • Distinctions: Nitric oxide (NO) ≠ Nitrous oxide (“laughing gas”) ≠ Nitrate/nitrite
  • Nitrate/nitrite in veggies and cured meats isn’t dangerous as popularly believed, especially when vitamin C is present to block nitrosamine formation
    • “85% of our nitrate and nitrite burden comes from vegetables… You can’t blame the bacon for that anymore.” — Dr. Bryan & Dave Asprey [45:43-45:55]

11. Why Big Pharma Hates Nitric Oxide

• [11:05-13:59; 28:16-30:31; 36:29-37:00]
  • Proper NO therapy could vastly reduce the need for chronic medications (blood pressure, diabetes, ED drugs)
  • Pharmaceutical industry profits from symptom management, not root cause correction
    • “Pfizer and the companies selling PDE5 inhibitors (Viagra) should be sending us royalties, because now those 50% that didn’t respond are going to respond.” — Dr. Bryan [36:38]

Notable Quotes & Memorable Moments

• “Nitric oxide is what we call foundational. It’s not a panacea… But it regulates blood flow, activates your mitochondria, controls cognition, improves glucose uptake, prevents telomeres from shortening, and mobilizes stem cells.” — Dr. Bryan [01:20]
• “Anything that leads to an increase in blood sugar... completely shuts down nitric oxide production.” — Dr. Bryan [05:26]
• “If you eat a straight vegetarian diet, but you use fluoride toothpaste or antiseptic mouthwash, you get no nitric oxide benefit from that.” — Dr. Bryan [08:55]
• “Would you throw an atomic bomb in your mouth two to three times a day?” (re: mouthwash) — Dr. Bryan [31:24]
• “If you have fresh breath... because of mouthwash use, you’re not going to be able to get an erection because you don’t have any nitric oxide.” — Dr. Bryan [31:49]
• “Insulin resistance and type 2 diabetes is a symptom of nitric oxide deficiency.” — Dr. Bryan [19:37]
• “PPIs completely shut down systemic nitric oxide production. People on these for 3 years have up to 40% higher risk of heart attack, stroke, and Alzheimer’s.” — Dr. Bryan [22:32]
• “If we target the microbiome, we enhance nitric oxide production. And now, for the first time in the history of western medicine, you have a conversation about how to get people off of drugs.” — Dr. Bryan [34:35]
• “Nitrite/nitrate phobia is based on a 1950s myth—vegetarians would have more cancer if it were true, but the opposite is shown.” — Dr. Bryan [45:39]
• On Big Pharma’s conflict: “It’s the best financial model in the world, man.” — Dr. Bryan [26:48]

Practical Biohacker Takeaways

• Prioritize foods and oral care that preserve the oral microbiome; avoid antimicrobials, fluoride, and excessive sugar.
• NO supplementation (e.g., N101 lozenges) is especially important for those with impaired enzyme pathways or on NO-suppressing meds (PPIs, statins).
• NO supports cardiovascular, metabolic, cognitive, and sexual health—often outperforming standard drugs, especially when combined with lifestyle changes.
• NO lozenges can, in some cases, reverse complex chronic conditions (personalized protocols may vary).
• Testing: Use blood pressure, subjective “morning kickstand,” or advanced blood markers as indicators for NO efficacy.

Timestamps for Major Segments

• [00:07] — What NO does in the body
• [02:38] — How long NO lasts; synthesis pathways
• [03:19] — Dr. Bryan’s origin story & foundational research
• [05:26] — Sugar as a NO killer
• [08:55] — Why leafy greens or beets may not work due to oral bacteria
• [09:23] — Prebiotics/probiotics and NO production
• [11:57] — Supplementation vs. restoring enzyme function
• [16:32] — Mythbusting: Beets and beet products
• [19:25] — NO’s role in fasting glucose and insulin
• [22:28] — Medications (PPIs/statins) that destroy NO
• [26:48] — Big Pharma incentives and “best financial model”
• [30:38] — Mouthwash disaster and proper oral care
• [34:35] — Toothpaste reformulation for NO and real health outcomes
• [41:00] — NO’s role in COVID, brain fog, and circulation
• [44:39] — NO vs. Nitrous vs. dietary nitrate/nitrite
• [48:38] — Carnivore/keto/SAD impact on NO
• [50:40] — NO supplementation, especially for those on medications
• [53:05] — Where NO fits into a foundational supplement stack

Bottom Line

Nitric oxide is a critical “upstream” molecule for virtually every dimension of health (energy, mood, metabolism, immunity, sexual function, and brain power). Modern diets, oral hygiene practices, and many medications are silently sabotaging our ability to make NO. Restoring and optimizing NO—by diet, microbiome support, and direct supplementation—holds the potential to upend chronic disease, outperform legacy drugs, and dramatically upgrade human performance.

Recommended Protocol (per Dr. Bryan):

• One N101 NO lozenge twice daily (adjust as needed)
• Use hydroxyapatite-based, fluoride-free toothpaste
• Avoid mouthwash/antiseptics except in rare, acute circumstances
• Minimize sugar, processed foods, Western diet patterns
• Exercise regularly and eat for your metabolic type

“If you want to deliver nutrients and vitamins to every cell in the body, but those cells aren’t getting adequate blood supply because you have microvascular dysfunction… It’s like I-35 [with] a traffic jam. Take the N101, open up the microcirculation, and you’re better delivering that cargo.” — Dr. Bryan [53:05]

For more, listen to the full episode or visit Dr. Nathan Bryan’s and Dave Asprey's resources for supporting research and recommended products.