In this episode of The Human Upgrade, Host Dave Asprey sits down with naturopathic physician Greg Kelly for a deep, practical masterclass on creatine and human energy. They break down how creatine supports mitochondria, buffers ATP, and fuels both the brain and muscles during high demand, reframing weight loss, cravings, focus, and emotional regulation as energy problems rather than willpower failures. Dave and Greg explore creatine’s role in cognition, sleep debt recovery, metabolism, and longevity, including why women often need more than men, how creatine supports the brain during stress and fatigue, and why quality, dosing, timing, magnesium, and methylation all matter. The conversation cuts through myths around kidneys, bloating, and caffeine, explains why red meat is the primary dietary source, and shows how creatine fits into a Smarter Not Harder approach to biohacking, supplements, and sustainable human performance.
Creatine is a hot subject right now, but I’m guessing you might not know as much about it as you could. Well step into a new creatine masterclass with our friends from Qualia. This episode shows you why it is not just for muscle, but one of the most powerful and well studied upgrades for brain energy, metabolism, sleep resilience, and long term human performance. You will learn how creatine supports mitochondria, buffers ATP, reduces cravings, and helps you think, train, and recover with more energy instead of relying on willpower.
Host Dave Asprey sits down with Greg Kelly for a deep, practical masterclass on creatine and energy biology. Greg Kelly is a naturopathic physician, functional medicine expert, and longtime researcher in supplements and nootropics. He has spent decades studying creatine, mitochondrial function, cognition, and performance, and has contributed to peer reviewed research while working directly with athletes, clinicians, and high performers.
Together, Dave and Greg break down how creatine works at the cellular level, why it matters for cognition, emotional regulation, and metabolism, and how it supports the brain and body during stress, sleep deprivation, dieting, and recovery. They explore neuroplasticity, ATP production, magnesium, methylation, and why energy availability drives discipline, focus, and resilience more effectively than willpower alone. They also explain why creatine matters for women, aging adults, and people dealing with fatigue or obesity, and how creatine supports brain function even when muscle mass is low.
This conversation connects bodybuilding research with modern longevity science, nootropics, functional medicine, and sleep optimization. Dave and Greg also expose why creatine quality matters, how contaminants can impair mitochondrial function, why some products fail label claims, and how to choose forms that absorb better and cause less bloating. Practical strategies like dosing, timing, stacking with magnesium, and using creatine with hot coffee are all covered, including why Dave uses it with Danger Coffee as part of his Smarter Not Harder approach.
You’ll Learn:
Dave Asprey is a four time New York Times bestselling author, founder of Bulletproof Coffee, and the father of biohacking. With over 1,000 interviews and 1 million monthly listeners, The Human Upgrade is the top podcast for people who want to take control of their biology, extend their longevity, and optimize every system in the body and mind. Each episode features cutting edge insights in health, performance, neuroscience, supplements, nutrition, hacking, emotional intelligence, and conscious living.
Episodes are released every Tuesday and Thursday, where Dave asks the questions no one else dares, and brings you real tools to become more resilient, aware, and high performing.
Keywords: creatine brain energy, creatine ATP buffering, creatine mitochondria, creatine cognitive performance, creatine supplementation science, creatine dosing cognition, creatine sleep deprivation, creatine emotional regulation, creatine cravings metabolism, creatine fatigue brain, creatine women dosing, creatine longevity science, creatine nootropics, creatine brain optimization, ATP brain energy, mitochondrial energy production, magnesium creatine ATP, creatine methylation TMG, creatine bioavailability, danger coffee creatine, dave asprey creatine, greg kelly creatine, smarter not harder energy
Resources:
00:00 – Trailer
A fast paced preview highlighting why creatine matters for brain energy, metabolism, sleep resilience, and human performance.
01:25 – Introduction
Host Dave Asprey introduces Greg Kelly and frames the episode around energy, mitochondria, and why creatine goes far beyond bodybuilding.
04:57 – History of Creatine
Creatine’s discovery in 1832, early research, and its breakthrough moment at the 1992 Olympics with British athletes.
07:47 – How Creatine Works
Creatine buffers ATP by cycling between creatine and phosphocreatine to power muscles and the brain during high demand.
12:00 – Dietary Sources
Red meat is the primary source, providing about 2 grams per pound, with minimal amounts in other foods.
13:30 – Dosing Guidelines
Body weight and activity level determine needs, with 2 to 5 grams daily for maintenance and higher doses for performance.
18:08 – Cognitive Benefits
The thalamus shows the highest creatine uptake, improving focus, decision making, and executive function.
19:36 – Bodybuilding vs Biohacking Doses
Traditional bodybuilding uses 2 to 3 grams daily, while biohackers often take 10 to 20 grams for cognitive enhancement.
22:08 – Kidney Function and Safety
Creatine is extremely safe with over 700 studies; elevated creatinine is a measurement artifact, not kidney damage.
24:42 – Sleep and Recovery
Creatine helps with sleep debt recovery and may reduce sleep needs while improving cognitive performance when sleep deprived.
26:08 – Bloating and Absorption
Ultra fine, highly soluble forms reduce bloating by improving upper GI absorption and limiting gut fermentation.
30:53 – Timing and Caffeine
Hot coffee increases creatine solubility and absorption; caffeine and creatine work synergistically despite old myths.
34:07 – Forms of Creatine
Creatine monohydrate has the most research, while newer forms like magnesium creatine chelate offer better solubility.
43:06 – Weight Loss and Obesity
Creatine helps obese individuals by increasing brain ATP, reducing fatigue and cravings, and improving willpower.
45:50 – Testosterone and Hormones
Studies show creatine increases testosterone in men and supports reproductive health in both sexes through mitochondrial function.
47:47 – Women and the Menstrual Cycle
Women need more creatine than men and benefit from daily supplementation to stabilize energy and mood across their cycle.
50:12 – Pregnancy and Fertility
Animal studies show safety and benefits; 1 to 5 grams daily may support mitochondrial demands during pregnancy and conception.
53:44 – Magnesium Connection
Magnesium is essential for converting creatine to phosphocreatine and for ATP function, making it a critical cofactor.
56:17 – Methylation and TMG
Creatine synthesis requires methyl groups; TMG (betaine) supports methylation and ATP production through separate pathways.
01:01:18 – Quality and Contaminants
Cheap creatine may contain dicyandiamide, which converts to cyanide, creatinine, and other contaminants that harm mitochondria.
01:09:17 – Practical Tips
Mix creatine into hot beverages for better absorption and build it into your daily routine for consistency.
01:15:46 – Kids and Teenagers
Creatine is safe for teens at adult doses; children may benefit from 0.5 to 1 gram daily with medical guidance.
“Follow” or “subscribe” to The Human Upgrade™ with Dave Asprey on your favorite podcast platform.
Go to Apple Podcasts at daveasprey.com/apple and leave a (hopefully) 5-star rating and a creative review.
Got a comment, idea or question for the podcast? Submit via this form!
Follow @thehumanupgradepodcast on Instagram and Facebook.
Learn directly from Dave Asprey alongside others in a membership group: ourupgradecollective.com.

Smarter Not Harder: The Biohacker’s Guide to Getting the Body and Mind You Want is about helping you to become the best version of yourself by embracing laziness while increasing your energy and optimizing your biology.
Subscribe to become an “Insider”, and receive weekly biohacking tips and tech directly from Dave to start hacking your way to stronger mental performance and physical results.
Receive weekly biohacking tips and tech by becoming a Dave Asprey insider.