Melatonin might be one of the most misunderstood supplements in the wellness space.
Professor Dom D’Agostino has been taking it since 1993—over three decades—and his research reveals why the common fears about this molecule might be overblown.
From neuroprotection to muscle preservation during fasting, D’Agostino unpacks controversial topics that challenge mainstream narratives.
In a recent conversation, the metabolic researcher shared insights on everything from melatonin’s brain benefits to an unconventional fasting protocol involving sardines.
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The Melatonin Myth That Won’t Die
Many people avoid melatonin because they’ve heard it suppresses natural hormone production. D’Agostino studied this extensively and found no human evidence supporting these claims.
I’ve been taking melatonin since 1993, since I was a senior in high school. It’s when I started taking creatine, too, when it first came out.
His research in graduate school demonstrated melatonin’s neuroprotective effects and ability to reduce oxidative stress in brain tissue. The molecule crosses the blood-brain barrier easily, acting as a powerful antioxidant in neurons.
If you want something simple that actually works, this is one of the most effective tools I’ve used to build strength, conditioning, and endurance without needing a full gym setup.
- Full-body training with one weight using swings, squats, and presses
- Solid cast iron build that feels stable and lasts for years
- Comfortable grip that makes high-rep workouts easier to handle
Contrary to popular belief, melatonin doesn’t suppress your body’s natural production. D’Agostino even tested this on himself and found no reduction in endogenous melatonin levels.
Melatonin does not suppress hormones. So, there’s no feedback mechanism that would suppress, for example, luteinizing hormone, follicle-stimulating hormone, or testosterone.
The confusion likely stems from animal studies in hibernating species, where hormonal suppression does occur. But in humans? The literature is silent.
D’Agostino’s Melatonin Protocol
His approach is surprisingly simple: 2.5mg sublingual melatonin before bed. He typically buys 10mg tablets, cuts them into quarters, and holds the piece under his tongue for faster absorption.
The sublingual route allows melatonin to enter the bloodstream directly and reach the brain more efficiently. But sleep isn’t his primary motivation.
I’ve been in situations where I forget the melatonin and I fall asleep equally fast and have a great night’s sleep. So, I’m not physically or even psychologically dependent on it.
The real reason? Neuroprotection. D’Agostino’s research showed melatonin reduces superoxide production and protects against mitochondrial dysfunction in brain cells.
Creatine for Brain Health: Beyond Muscle
While creatine’s muscle benefits are well-established, emerging research suggests higher doses may benefit cognitive function. The mechanism is fascinating.
If you want something simple that actually works, this is one of the most effective tools I’ve used to build strength, conditioning, and endurance without needing a full gym setup.
- Full-body training with one weight using swings, squats, and presses
- Solid cast iron build that feels stable and lasts for years
- Comfortable grip that makes high-rep workouts easier to handle
At typical 5g doses, the liver and muscles absorb most of the creatine. But at 10-20g daily, enough spills into circulation to cross the blood-brain barrier and increase brain stores.
Studies indicate this could mitigate sleep deprivation and support brain energy metabolism during periods of cognitive stress. There are now hundreds of clinical trials on creatine—making it perhaps the most studied nutritional supplement available.
Managing GI Upset from Higher Doses
Many people struggle with gastrointestinal discomfort at higher creatine doses. D’Agostino’s strategy involves three key adjustments:
- Take it with food rather than on an empty stomach
- Split doses across meals instead of taking it all at once
- Use Creapure creatine, a micronized German source that’s often better tolerated
Interestingly, vegetarians and vegans often experience dramatic responses to creatine supplementation since their diets contain virtually none.
I have so much energy now and so much stronger. I had a response to creatine in 1993.
One caveat: emerging evidence suggests avoiding creatine in coffee, as caffeine may interfere with its absorption and signaling.
Lessons from a 117-Year-Old Woman
A recent paper examined Maria Branyas Morera, who died at 117 years and 168 days—the oldest verified woman at the time. Her metabolic profile revealed surprising insights.
If you want something simple that actually works, this is one of the most effective tools I’ve used to build strength, conditioning, and endurance without needing a full gym setup.
- Full-body training with one weight using swings, squats, and presses
- Solid cast iron build that feels stable and lasts for years
- Comfortable grip that makes high-rep workouts easier to handle
Despite her extraordinary longevity, she had short telomeres—comparable to average population levels for her age rather than the extended telomeres you’d expect.
What did stand out? Youthful mitochondrial function, a healthy microbiome, and remarkably low inflammatory markers. Her hsCRP was exceptionally low, which may carry more significance than LDL levels for longevity.
D’Agostino emphasized factors beyond biochemistry:
Her curiosity, her gratitude, her being socially connected, but also like light exercise. She wasn’t a marathon runner. She wasn’t like, you know, pounding heavy weights or anything.
She consumed yogurt three times daily containing Streptococcus thermophilus and Bifidobacterium delbrueckii subspecies bulgaricus—probiotics commonly found in quality yogurts.
The Gardening Connection
Maria was passionate about gardening, spending significant time outdoors. This resonated with D’Agostino’s observations of farmers he worked with who lived 10 years beyond average male lifespan—despite significant chemical exposure.
All these farmers lived 10 years beyond the normal male lifespan. They had a sense of purpose. They were outside every day. They were out in the sun sunlight.
Purpose, social connection, and time in nature may mitigate other risk factors that receive disproportionate attention in medical literature.
If you want something simple that actually works, this is one of the most effective tools I’ve used to build strength, conditioning, and endurance without needing a full gym setup.
- Full-body training with one weight using swings, squats, and presses
- Solid cast iron build that feels stable and lasts for years
- Comfortable grip that makes high-rep workouts easier to handle
Sardine Fasting: Elite Biohacker Protocol
Perhaps the most unconventional strategy D’Agostino discussed was sardine fasting—a modified fasting approach that preserves muscle while promoting fat loss.
Traditional extended fasts often result in lean mass loss and hunger. Sardines provide a unique solution.
If there is a perfect food, I think sardines, if we could just live off if one food was nutritionally complete, it’d probably be sardines.
Sardines deliver maximum nutrition in minimal calories. They’re rich in protein, omega-3 fatty acids, calcium (from bones), and have remarkably low heavy metal contamination compared to larger fish.
Why Sardines Preserve Muscle During Fasting
Multiple mechanisms make sardine fasting muscle-protective:
- Protein provision without excessive calories
- Ketosis induction from low overall calorie intake
- FGF21 elevation from protein restriction, which spares muscle and may increase fat burning
- Omega-3s with anti-catabolic and anti-inflammatory effects
Sardines also increase satiety hormones including GLP-1, CCK, and PYY, making the fast more tolerable.
How to Implement Sardine Fasting
D’Agostino recommends one can per 50 pounds of body weight daily. For a 200-pound person, that’s four cans—approximately 600 calories, similar to fasting-mimicking diets.
If you want something simple that actually works, this is one of the most effective tools I’ve used to build strength, conditioning, and endurance without needing a full gym setup.
- Full-body training with one weight using swings, squats, and presses
- Solid cast iron build that feels stable and lasts for years
- Comfortable grip that makes high-rep workouts easier to handle
Key specifications:
- Choose sardines with bones and skin for calcium and complete nutrition
- Select ones packed in extra virgin olive oil
- Preferred brands include Wild Planet, King Oscar, and Seasons
- Divide intake into two meals for easier digestion
One can typically contains 140-155 calories and roughly 8 grams of protein. The low protein intake maintains ketosis while still supporting muscle tissue.
The Broader Picture: What Actually Matters
Throughout the conversation, a pattern emerged: the metrics receiving obsessive attention in clinical medicine aren’t always the most important.
LDL cholesterol gets intense focus not necessarily because it’s most predictive, but because it’s easily measurable and pharmaceutically targetable. Meanwhile, factors like social connection, purpose, and mindset—consistently present in supercentenarians—remain understudied.
Mindset really does change your metabolism.
Research is beginning to uncover mechanisms, like how stress directly impacts liver metabolism via brain-to-liver signaling, causing increased glucose output. But translating subjective experiences like purpose into precise biological mechanisms remains challenging.
D’Agostino’s three-decade journey with supplements like melatonin and creatine, combined with his research into unconventional protocols like sardine fasting, offers a roadmap for evidence-based experimentation. His approach balances rigorous science with practical implementation and n-of-1 testing.
If you want something simple that actually works, this is one of the most effective tools I’ve used to build strength, conditioning, and endurance without needing a full gym setup.
- Full-body training with one weight using swings, squats, and presses
- Solid cast iron build that feels stable and lasts for years
- Comfortable grip that makes high-rep workouts easier to handle
The takeaway isn’t to abandon biomarker optimization, but to recognize that longevity likely depends more on modifiable factors like mitochondrial function, microbiome health, social connection, and maintaining purpose than any single blood value.
