The Optimal Creatine Protocol For Strength, Brain, And Longevity

Creatine isn’t just for athletes. A growing body of scientific evidence now shows creatine supplementation helps preserve muscle mass during aging, prevent bone resorption, improve memory and cognition (especially during stress), and speed muscle recovery after intense exercise. The Optimal Creatine Protocol For Strength, Brain, And Longevity

To explore the mechanisms, optimal dosing strategies, and practical considerations of creatine supplementation, I invited Dr. Darren Candow, a leading creatine researcher with more than 140 scientific publications, onto the podcast.

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The Rep-Extending Benefits of Creatine:

* Creatine increases intramuscular phosphocreatine by ~20–30%, enhancing ATP regeneration for high-intensity exercise.

* Supplementation improves performance across multiple sets by delaying fatigue and supporting repeated efforts.

* When combined with resistance training, creatine leads to greater lean mass gains—especially in type II muscle fibers.

* It accelerates recovery between sets and post-workout by boosting energy availability and reducing muscle breakdown markers.

Creatine is one of the most well-researched supplements for enhancing muscle performance and strength, especially during high-intensity and repetitive efforts. It works by increasing intramuscular phosphocreatine (PCr) stores, which accelerates the regeneration of ATP—the main fuel for muscular contractions.

With supplementation, total muscle creatine levels can rise by 20–30%, which helps delay fatigue and boost performance during exercises like sprinting, lifting, and intervals. Creatine is especially effective during the second, third, and fourth sets of repeated efforts, when the body’s energy reserves are most taxed.

Creatine also improves recovery in two key ways: first, between sets or efforts, by speeding up PCr resynthesis by up to 40%, which helps sustain training intensity; and second, after hard workouts by reducing muscle breakdown and inflammatory markers like TNF-α and IL-1β.

This anti-catabolic effect can be particularly helpful after endurance events or high-volume training.

It’s not a standalone muscle builder—but when combined with resistance training, creatine can significantly increase lean mass, particularly in fast-twitch muscle fibers. In older adults, studies have shown it can double muscle gain compared to placebo during resistance training interventions.

Brain And Cognitive Performance

* Creatine supports ATP regeneration in neurons under metabolic stress.

* High doses (up to 0.35 g/kg or 20–25 grams or more) may be used acutely during sleep deprivation or metabolic stress.

* Daily supplementation (~5–10g) can improve resilience, processing speed, and reduce mental fatigue.

While most people associate creatine with physical performance, its benefits for the brain are equally compelling. The brain uses about 20% of the body’s energy, and creatine plays a key role in maintaining that energy balance, especially under stress.

Supplementation increases brain creatine stores by 5–10% and has been shown to improve memory, attention, and reaction time—particularly in situations of cognitive fatigue or sleep deprivation.

This makes creatine especially valuable for shift workers, students, or anyone experiencing chronic stress or mental overload.

Creatine may also protect the brain in more serious scenarios. Early research suggests potential benefits in traumatic brain injury, concussion recovery, and even neurodegenerative diseases like Parkinson’s and Huntington’s.

There’s also growing evidence that creatine may enhance the effectiveness of antidepressants, with one study showing faster recovery in women taking creatine alongside SSRIs.

How Creatine Prevents Bone Breakdown

* Creatine may indirectly enhance bone strength by improving muscle mass and force production, increasing stress on bones and stimulating adaptation.

* Higher doses (8–10 g/day) may be more effective for bone outcomes than standard 3–5 g/day protocols.

* Creatine is best viewed as a complementary strategy for skeletal health—not a replacement for exercise or other medical treatments.

While creatine alone has limited direct effects on bone mineral density (BMD), it appears to help prevent bone loss by supporting osteoblast (bone-building cell) activity and reducing osteoclast (bone breakdown cell) activity.

Creatine may even enhance the energy status of bone cells, although much of this evidence comes from in vitro or animal studies.

In humans, the clearest benefits are seen when creatine is paired with mechanical loading—such as resistance training or impact-based activity.

Studies show modest increases in bone cross-sectional area and preservation of density at weight-bearing sites like the tibia, especially in postmenopausal women.

Amplify Creatine’s Muscle- And Brain-Boosting Benefits With Science-Backed Training Strategies—Download Your Free Guide.

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About Dr. Rhonda Patrick

Perciavalle Patrick has a Ph.D. in biomedical science from the University of Tennessee Health Science Center, Memphis TN and St. Jude Children’s Research Hospital, Memphis TN. She also has a Bachelor’s of Science degree in biochemistry/chemistry from the University of California, San Diego. She has done extensive research on aging, cancer, and nutrition. She did her graduate research at St. Jude Children’s Research Hospital where she investigated the link between mitochondrial metabolism, apoptosis, and cancer. Her groundbreaking work discovered that a protein that is critical for cell survival has two distinct mitochondrial localizations with disparate functions, linking its anti-apoptotic role to a previously unrecognized role in mitochondrial respiration and maintenance of mitochondrial structure. Her dissertation findings were published in the 2012 issue of Nature Cell Biology.

Dr. Patrick trained as a postdoctoral fellow at Children’s Hospital Oakland Research Institute with Dr. Bruce Ames. She investigated the effects of micronutrient (vitamins and minerals) inadequacies on metabolism, inflammation, DNA damage, and aging and whether supplementation can reverse the damage. In addition, she also investigated the role of vitamin D in brain function, behavior, and other physiological functions and has published papers in FASEB on how vitamin D regulates serotonin synthesis and how this relates to autism and other neuropsychiatric disorders.

Dr. Patrick has also done research on aging at the Salk Institute for Biological Sciences. At the Salk, she investigated what role insulin signaling played in protein misfolding, which is commonly found in neurodegenerative diseases such as Alzheimer’s disease.

She frequently engages the public on topics including the role micronutrient deficiencies play in diseases of aging, the role of genetics in determining the effects of nutrients on a person’s health status, benefits of exposing the body to hormetic stressors, such as through exercise, fasting, sauna use or heat stress, or various forms of cold exposure, and the importance of mindfulness, stress reduction, and sleep. It is Dr. Patrick’s goal to challenge the status quo and encourage the wider public to think about health and longevity using a proactive, preventative approach.

Publications:

* Vitamin D and the Omega-3 Fatty Acids Control Serotonin Synthesis and Action, Part 2: Relevance for ADHD, Bipolar, Schizophrenia, and Impulsive Behavior FASEB Journal
* Vitamin D Hormone Regulates Serotonin Synthesis. Part 1: Relevance for Autism FASEB Journal
* Requirement for Anti-Apoptotic MCL-1 in the Survival of BCR-ABL B-Lineage Acute Lymphoblastic Leukemia Blood
* Delving Deeper: MCL-1′s Contribution to Normal and Cancer Biology Trends in Cell Biology
* Anti-Apoptotic MCL-1 Localizes to the Mitochondrial Matrix and Couples Mitochondrial Fusion to Respiration Nature Cell Biology
* Ubiquitin-Independent Degradation of Anti-Apoptotic MCL-1 Molecular and Cellular Biology
* Opposing Activities Protect Against Age-Onset Proteotoxicity Science

Updated: 4-18-2025

Americans Are Obsessed With Protein And It’s Driving Nutrition Experts Nuts

Food companies pack the nutrient into candy, coffee and even water; ‘How about a chicken breast, people?’

Morgan Gates starts off his day eating six eggs. Later he will down a smoothie made with Greek yogurt, protein powder and berries. For dinner, it’s a pound of red meat.

The 28-year-old sales representative is big on protein. “I found that if I prioritized protein and half-assed the rest of everything else, it gave me the body I wanted,” he said.

Gates’s two dogs follow a similar diet. The $367 billion U.S. food industry is on board, too, pushing protein beyond cereals and snack bars and into new realms like coffee, sweets and water.

Snack maker Wilde created a protein chip from chicken breasts, egg whites and bone broth. Protein Pints made its national debut this spring, offering cookie dough and mint chip-flavored ice cream tubs with 30 grams of protein each.

Ontario-based Protein Candy rolled out brightly colored confections promising 14 grams of protein a bag—the equivalent of eating a half cup of cottage cheese—calling it for a while “candy that works as hard as you do.”

To wash it down, there are protein-infused beverages made from whey or peas and collagen—a staple ingredient in wrinkle creams and lip injections sourced from animal bones, skin or cartilage.

Feisty soda boasts 10 grams a can, making it more protein-dense than an egg, according to the brand. U.K.-based Vieve, a purveyor of fruit-flavored protein water, says it took the company two years to figure out how to slip 20 grams of protein into the drink.

Founder Rafael Rozenson said the idea was born from an intense dislike of other options on the market, especially for gym-goers.

“Some people don’t need our product,” Rozenson said. “If you’re sitting on the sofa it might not be interesting for you.”

Other food executives have taken note of Americans’ mission to jam more of the star nutrient into their diets. Food makers in 2024 introduced 97 new products with “protein” in the brand name, more than double the year prior, according to market-research firm Mintel.

In the year to Feb. 22, the fastest-growing grocery items were those with the most protein per serving—25 grams or more, according to NielsenIQ data.

People like Daniel Imberman, a software engineer in California, are eating it up. The self-professed protein connoisseur says his focus is discovering “protein crap,” healthy options that taste like junk food.

A fan of protein chips and protein ice cream, he’s also partial to Barebells—2-ounce protein bars that come in flavors like marshmallow peanut road, birthday cake and salty peanut. “They’re my guilty pleasure,” he said.

Imberman wolfs one down five times a week. “People love to get the blessing to do the thing they know they’re not supposed to do,” he said.

But the processed protein buffet is driving many nutrition experts and personal trainers nuts.

Constance Contursi, a personal trainer in suburban Chicago, says many of her clients mistake junk food as healthy because it contains added protein. “How about a chicken breast, people?” she said. “How about an egg?”

America’s long-running love affair with protein has intensified as weight-loss drugs like Ozempic have taken off, with many users trying to boost protein intake to offset lost muscle mass while they shed pounds.

Meanwhile, a social-media-fueled focus on health and fitness is crowding more protein powders into kitchen cupboards, moving the chalky substances from a gym-rat mainstay to the mainstream.

Tricked out algorithms on TikTok are pushing everything from the carnivore diet to protein Diet Coke, a dubious combination of soda and a protein shake.

Protein shakes themselves recently starred in the third season of HBO’s hit show, “The White Lotus,” when Patrick Schwarzenegger’s addiction to the drinks became a pivotal plot point.

Most Americans aren’t hurting for protein. U.S. nutrition recommendations call for healthy adults to consume 0.8 grams per kilogram of body weight a day. For a 150-pound person, that works out to about 54 grams—found in a half-pound chicken breast, or two eggs with a cup of plain, nonfat Greek yogurt plus a cup of nuts.

Even with protein, you can have too much of a good thing, said Bettina Mittendorfer, professor of medicine, nutrition and exercise physiology at the University of Missouri School of Medicine.

Mittendorfer led a study that found that overload of certain amino acids, found in protein, can lead to cardiovascular disease.

For the study, her team shoehorned extra protein into the pasta and sauces they cooked for participants. “It’s like eating sand on the beach,” she said.

Mittendorfer said stuffing protein into waffles and soup has more to do with marketing than anything else. The nutrient Americans do need more of is fiber, she said. But that’s a harder sell. “Would you rather have muscle strength and vitality, or prunes and Metamucil?”

Ballerina Farm, the ranch and viral social-media account run by Hannah Neeleman and her husband, Daniel Neeleman, recently launched a protein powder made with bovine colostrum, the milk-like fluid a mother cow produces in the first few days after giving birth.

Ms. Neeleman is a Juilliard-trained ballerina who has captured online fame with photos and videos depicting her lifestyle in rural Utah as a mother of eight.

Mr. Neeleman is a weightlifter and bona fide protein devotee, starting his day with bone broth and later consuming protein powder, creatine and amino acids.

But the protein powder’s real star is Dandy, a beloved family milk cow.

Ms. Neeleman said the couple began drinking Dandy’s leftover colostrum—plain and in smoothies—each time she gave birth to a calf.

“You have this concentrated dose of God-given elixir,” said Mr. Neeleman. Soon, the idea for Farmer Protein was born.

Bovine colostrum as a wellness trend has its detractors, including animal rights groups that argue it, like milk, is for mother cows to feed their babies.

The Neelemans said they source colostrum from farms that make sure to give calves the colostrum they need, and only use the excess for protein powder.

It’s now their bestselling product, surpassing wooden measuring spoons, beef jerky and sourdough starter (pairs well with the farm’s high-protein flour).

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