High Protein Intake Supports Autophagy and Satiety in Calorie Restriction - Episode Hero Image

High Protein Intake Supports Autophagy and Satiety in Calorie Restriction

Dr. Jockers Functional Nutrition · · Listen to Original Episode →
Original Title:

TL;DR

  • New human research indicates high protein intake does not inhibit autophagy when calories are restricted, challenging prior beliefs about protein timing and cellular repair.
  • Prioritizing protein intake naturally reduces cravings and stabilizes blood sugar through the protein leverage effect, making eating more satisfying and effortless.
  • High-protein fasting mimicking diets significantly reduce visceral fat and offer stronger metabolic benefits, including improved triglycerides and gut microbiome diversity, compared to low-protein versions.
  • Protein intake is the primary driver of satiety, and insufficient protein consumption is a key reason for overeating and persistent cravings, not a lack of willpower.
  • The "anabolic window" for protein consumption is less critical than total daily protein intake, reducing stress for individuals who cannot adhere to strict meal timing.
  • Protein sparing modified fasting (PSMF) offers a viable strategy for fat loss while preserving muscle mass, with potential benefits for hormonal balance and metabolic health.
  • Autophagy can be upregulated even with higher protein intake during calorie restriction, suggesting that caloric deficit, not just protein suppression, is key for cellular cleanup.

Deep Dive

The discussion begins by referencing an Amazon advertisement for holiday deals, highlighting that Amazon was named the lowest-priced online retailer in the U.S. for the ninth consecutive year by Profitero, with prices being 14% lower on average and up to 5% lower in electronics and toys. The advertisement suggests that these savings are significant for holiday budgets and that Amazon offers a wide selection from major brands to small businesses.

The conversation then shifts to a new human research study published in the Journal of Clinical Nutrition in August 2025, conducted at the University of Nottingham in the UK. This study, titled "The Effects of Fasting Mimicking Diets with Low and High Protein Content on Cardiometabolic Health and Autophagy," was a seven-day randomized parallel group study. It challenged the long-held belief that high protein levels block autophagy, even in a calorie-restricted state. The study found that individuals on a high-protein, calorie-restricted diet exhibited the same level of autophagy as those on a protein-restricted diet.

The podcast then introduces guest Vanessa Spina, an expert in nutrition and protein, a sports nutrition specialist, best-selling author of "Keto Essentials," and creator of the Tone device, a ketone breath analyzer. Her work focuses on high-protein, low-carb nutrition, metabolic health, and body recomposition for women, emphasizing an evidence-based approach.

A brief segment discusses hydration and electrolytes, noting that while water is crucial, cells require electrolytes for proper absorption. Paleovalley Essential Electrolytes are promoted as a sugar-free, artificial-ingredient-free option made with unprocessed sea salt to improve hydration, energy, focus, and skin health.

The discussion revisits the protein absorption study, referencing a study by Dr. Luc van Loon and Dr. Jorn Plummelen. This study, involving isotopically labeled amino acids and muscle biopsies over 12 hours, tested the effects of consuming 100 grams of protein in a single meal. Contrary to previous beliefs that only 30 grams of protein are absorbed per meal, this research indicated that amino acids remained circulating for 12 hours and a significant portion reached contractile muscle tissue. While debated by some scientists regarding its hyperbolic title and participant demographics (trained males), the study's main implication, according to the discussion, is that daily protein intake quantity is more critical than precise timing, alleviating stress about eating within an "anabolic window" after workouts for the average person.

Vanessa Spina shares her personal experience with intermittent fasting and a high-protein diet to manage irritable bowel syndrome and regain lost muscle mass, contrasting it with the conventional advice she received about protein intake limitations. She emphasizes that her positive results, despite consuming large amounts of protein in a restricted eating window, suggested the prevailing scientific understanding was incomplete.

The conversation returns to the protein timing study, with Spina highlighting that it allows individuals to relax about protein scheduling. While athletes may benefit from precise timing for a competitive edge, the average person can focus on meeting their daily protein target alongside resistance training for body composition optimization.

Key nutrition principles are summarized: reducing processed foods, prioritizing protein (a minimum of 30 grams per meal, potentially up to 50-60 grams or more), incorporating healthy fats (excluding seed oils), and consuming colorful fruits and vegetables to tolerance. The concept of "protein leverage" is explained, suggesting that individuals will continue to seek food until their protein needs are met. Prioritizing protein is presented as a transformative strategy that naturally leads to satiety, displacing excess carbohydrates and fats, and making it easier to achieve and maintain a lean physique.

The discussion delves into the benefits of ketones, including satiety, reduced inflammation in the brain for improved clarity and mood, balanced neurotransmitters, and reduced risk of all-cause morbidity and neurodegenerative conditions. The traditional ketogenic diet's emphasis on lower or moderate protein intake is contrasted with newer findings, with Spina explaining her personal shift to a high-protein ketogenic diet which she found optimized her testosterone levels and overall well-being, despite slightly lower ketone levels.

The conversation then focuses on the "Effects of Fasting Mimicking Diets with Low and High Protein Content on Cardiometabolic Health and Autophagy" study. Spina emphasizes the importance of human trials over animal studies, noting that many autophagy findings are based on cell cultures or animal models that do not translate directly to humans. The study compared a low-protein (10% of calories) fasting-mimicking diet with a high-protein (30% of calories) version, both at approximately 850 calories per day, over seven days.

The results indicated that both groups experienced reduced body weight, fat mass, fasting glucose, and IGF-1. Crucially, autophagy gene expression was upregulated in both the low-protein and high-protein groups, challenging the notion that high protein blocks autophagy when calories are restricted. The high-protein group showed additional benefits, including significant visceral fat reduction, stronger metabolic benefits such as decreased triglycerides and improved heart rate variability, and a better gut microbiome diversity, with upregulation of the autophagy initiation gene ULK1. The low-protein group, however, had higher ketones and more classic fasting signaling (FOXO1 and SIRT1).

Spina shares her experience with a protein-sparing modified fast (PSMF), where she lost 14 pounds of fat while preserving muscle mass. She describes her PSMF meals as high in protein and low in fat, often featuring lean proteins like shrimp, turkey, and chicken tenderloin, along with non-starchy vegetables and sometimes cauliflower rice. She notes the importance of strategic protein sources to maintain leanness and the potential for fat refeeds to support hormone health.

The discussion highlights that PSMF, typically involving 800-1000 calories daily with high protein (around 1-2.4 grams per kilogram of body weight) and around 30 grams of fat, can be an effective strategy for rapid fat loss. Spina advocates for incorporating one day a week of PSMF for its longevity benefits, including autophagy upregulation, as an alternative to water fasting, which she found more challenging. She contrasts this with alternate-day fasting, suggesting that its calorie restriction might not provide sufficient protein.

Spina describes her typical PSMF meals, including combinations like roasted turkey with butternut squash and cauliflower rice, or tenderloin steak with broccolini and zucchini, emphasizing micronutrient density. She finds PSMF more appealing and sustainable than water fasting due to the inclusion of satisfying, high-protein meals.

The podcast concludes by recommending that listeners try both PSMF and water fasting for a few months to assess their individual responses. Spina mentions her Tone device as a tool for tracking ketones and fat burning, and reiterates her availability on the Optimal Protein podcast and ketogenicgirl.com. Dr. Jockers offers a final reminder to leave reviews and share the episode.

Action Items

  • Create meal plan: Prioritize protein intake (0.7-1g/lb bodyweight) to enhance satiety and reduce cravings, displacing excess carbs and fats.
  • Implement one-day fasting protocol: Conduct a weekly protein-sparing modified fast (800-1000 calories, high protein, low fat) to promote autophagy and visceral fat reduction.
  • Track metabolic markers: Measure fasting glucose, triglycerides, and heart rate variability weekly to assess the impact of dietary changes on cardiometabolic health.
  • Evaluate body composition: Monitor fat mass and visceral fat reduction monthly to confirm effectiveness of protein-focused strategies and fasting protocols.

Related Episodes

Key Quotes

"Most people don't overeat because they lack willpower -- they lack protein."

The author argues that a common misconception is that overeating stems from a lack of self-control. This quote suggests that the underlying issue is actually insufficient protein intake. This perspective reframes the problem of overeating from a psychological deficit to a nutritional one.

"we've been told that high protein levels stop autophagy and in this study individuals that were on a high protein diet but they were also calorie restricted and that's really important we're going to dive into that in detail but they actually showed that they actually had the same level of autophagy as people that were protein restricted and so if you've been listening to me for any period of time you know i'm a huge advocate of protein but this was really it was eye opening because again the the idea in the functional nutrition world is that high protein even in a calorie restricted state would stop autophagy and deep cellular healing and this study showed that that's not true"

The speaker highlights a new study that challenges a long-held belief in functional nutrition. This research indicates that high protein intake, when combined with calorie restriction, does not inhibit autophagy, a crucial cellular repair process. The speaker expresses surprise and validation, as this finding supports their advocacy for protein consumption.

"The main thing that it sort of overturned was our thinking about protein distribution because so many people i think in the health space they don't necessarily eat three to six protein meals a day and so what it really showed is that the number one thing is not when you eat your protein or how often it's do you get the protein you need in the day and that's in a 24 hour period and it also shows that you don't have to eat it within 45 minutes of a workout which some people you know like to say you don't have to eat it you don't have to be walking out of the gym and you know slamming a protein shake if all that matters is you have it at some point 24 hours after you do your exercise and all that matters really is that you hit that target of protein"

The speaker explains how a particular study has shifted the understanding of protein intake timing. The research suggests that the total daily protein consumption is more critical than the frequency or specific timing of meals, such as within a post-workout window. This finding alleviates the pressure many individuals feel to adhere to strict meal schedules for protein consumption.

"I have come to rely way more on human trials than on animal trials and our things like mitochondrial biogenesis being activated from fasted exercise that was something that a lot of us believed and it was actually from rodent studies and it turns out that a lot of things that we have extrapolated to humans from animals they just don't translate"

The speaker emphasizes a shift in their research evaluation, prioritizing human trials over animal studies. They note that findings from rodent research, such as the activation of mitochondrial biogenesis from fasted exercise, do not always translate to humans. This highlights the importance of human-specific data for accurate health and nutrition recommendations.

"So the results both groups had reduced body weight compared to the control considerable amount of reduced body weight and fat mass and their fasting glucose dropped in both groups and igf 1 decreased by about 35 in both groups Now when it came to autophagy autophagy gene expression was upregulated in both groups in both the low protein and the high protein groups and I think this was you know pretty shocking"

The speaker details the findings of a study comparing low-protein and high-protein fasting-mimicking diets. Both dietary groups experienced significant reductions in body weight, fat mass, fasting glucose, and IGF-1. The speaker expresses surprise that autophagy gene expression was upregulated in both the low-protein and high-protein groups, challenging previous assumptions.

"but what what are you optimizing for if you're optimizing for the highest amount of ketones then you might want to suppress protein closer to 10 but if you're optimizing for reducing your fat mass and your visceral fats then definitely the high protein is the way to go and there were also stronger metabolic benefits in the high protein group so they had more decreased triglycerides better hrv improvement better gut microbiome diversity which is really cool because this could all be sort of connected you know with the autophagy and and then upregulation of ulk1 which did not happen in the low protein group"

The speaker contrasts the outcomes of low-protein versus high-protein diets in a study, focusing on different optimization goals. While the low-protein group showed higher ketone levels, the high-protein group demonstrated greater reductions in visceral fat and stronger metabolic benefits, including improved triglycerides, HRV, and gut microbiome diversity. The speaker suggests that the high-protein approach is superior for fat loss and overall metabolic health.

Resources

External Resources

Books

  • "Keto Essentials" by Vanessa Spina - Mentioned as a best-selling book authored by the guest.

Research & Studies

  • "The Science of Protein Cycling, Autophagy and Fat Loss" - Mentioned as a new human research study discussed in the episode.
  • "Effects of fasting-mimicking diets with low and high protein content on cardiometabolic health and autophagy" (Journal of Clinical Nutrition, August 2025) - Mentioned as a randomized parallel group study from the University of Nottingham, UK, that challenges previous notions about protein intake and autophagy.
  • Study on high protein fasting mimicking diet - Mentioned as a study that showed autophagy gene expression was upregulated in both low and high protein groups.
  • Study on protein absorption - Mentioned in relation to debunking protein myths.
  • Tormellin et al. paper - Mentioned as a study from the previous year that suggested no upper limit on muscle protein synthesis.
  • Isotopically labeled protein studies - Mentioned as expensive and demanding studies used to trace amino acid pathways.
  • Research on fasting and mitochondrial biogenesis - Mentioned as an example of rodent study findings that did not translate to humans.
  • Research on autophagy from cell culture - Mentioned as a source of headlines that may not be directly applicable to humans.
  • Clinical research on protein sparing modified fasting - Mentioned as recommending 1.5 grams of protein per kilogram of body weight.
  • Revised research by Dr. Eric Helms and Dr. Martin Ruscello - Mentioned as suggesting protein intake closer to 2 to 2.4 grams per kilogram of body weight for protein sparing modified fasting.

Tools & Software

  • Tone device - Mentioned as a ketone breath analyzer created by Vanessa Spina.

People

  • Vanessa Spina - Guest, author of "Keto Essentials," creator of the Tone device, and host of the Optimal Protein Podcast.
  • Dr. Jockers - Host of the podcast "Dr. Jockers Functional Nutrition" and co-host of the episode.
  • Dr. Luke Van Loon - Mentioned as leading a study on protein intake.
  • Dr. Jørn Plummelen - Mentioned as having the idea for a study on protein intake.
  • Dr. Josh Axe - Host of "The Dr. Josh Axe Show" podcast.
  • Dr. Valter Longo - Mentioned as having a product for fasting mimicking diets.
  • Dr. Christie Stroestruck - Mentioned for conducting a human study on fasting and mitochondrial biogenesis.
  • Dr. Stu Phillips - Mentioned for stating that only 10-15% of rodent research may apply to humans.
  • Maria Emrick - Mentioned for her approach to protein sparing modified fasting and a related book.
  • Dr. Eric Helms - Mentioned for revised research on protein sparing modified fasting.
  • Dr. Martin Ruscello - Mentioned for revised research on protein sparing modified fasting.

Organizations & Institutions

  • University of Nottingham - Location of the study "Effects of fasting-mimicking diets with low and high protein content on cardiometabolic health and autophagy."
  • School of Life Sciences at the University of Nottingham - Mentioned as the location where a study was conducted.
  • Profitero - A third-party analytics and research firm that named Amazon the lowest-priced online retailer.

Websites & Online Resources

  • ketogenicgirl.com - Vanessa Spina's website.
  • drjockers.com - Dr. Jockers' website, mentioned for health coaching and resources.
  • paleovalley.com/jockers - Website for Paleovalley Essential Electrolytes, with a discount code.
  • researchgate.net - URL provided for the study "Effects of fasting-mimicking diets with low and high protein content on cardiometabolic health and autophagy."

Podcasts & Audio

  • Dr. Jockers Functional Nutrition - The podcast where this episode was featured.
  • The Dr. Josh Axe Show - Mentioned as a podcast hosted by Dr. Josh Axe.
  • Optimal Protein Podcast - Vanessa Spina's podcast, mentioned for discussions on nutrition research.

Other Resources

  • Protein Leverage Effect - A concept explaining that individuals seek food until their protein needs are met.
  • Autophagy - A cellular cleanup process discussed extensively in the episode.
  • Ketones - Mentioned for their role in satiety and metabolic benefits.
  • Protein Sparing Modified Fasting (PSMF) - A dietary approach discussed for fat loss while preserving muscle.
  • Intermittent Fasting - A dietary pattern discussed in relation to personal experiences and benefits.
  • Gluconeogenesis - A metabolic process discussed in relation to protein intake and ketosis.
  • Mtor and Ampk pathways - Cellular pathways discussed in relation to autophagy.
  • IGF-1 - A marker that decreased in both low and high protein fasting mimicking diet groups.
  • Visceral fat reduction - A benefit observed specifically in the high protein fasting mimicking diet group.
  • Gut microbiome diversity - Improved in the high protein fasting mimicking diet group.
  • Ulk1 - An autophagy initiation gene upregulated in the high protein group but not the low protein group.
  • Foxo1 and Sirt1 signaling - Classic fasting signatures observed in the low protein group.
  • Growth hormone - Discussed in relation to its interaction with cortisol and its benefits.
  • Cortisol - A stress hormone discussed in relation to its effects and buffering by growth hormone.
  • Glp1 - A hormone stimulated by protein, discussed for its benefits.
  • Anabolic window - A concept related to post-workout protein intake that was challenged.
  • Ketogenesis - The process of ketone production.
  • Nutritional ketosis - A metabolic state achieved through diet.
  • Metabolic flexibility - Discussed in relation to protein's impact.
  • Cellular rejuvenation - A benefit of autophagy.
  • Hormone health - Discussed in relation to fat intake and protein sparing modified fasting.
  • Body composition - A key outcome discussed in relation to protein intake and fasting.
  • Cardiometabolic health - A measure that improved in both low and high protein fasting mimicking diet groups.
  • Hrv (Heart Rate Variability) - Improved more significantly in the high protein group.
  • Real food diet - A general dietary principle emphasized.
  • Processed foods - Advised to be reduced.
  • Seed oils - Advised to be avoided.
  • Healthy fats - Recommended sources include avocados, olive oil, and grass-fed butter.
  • MCT oil and coconut oil - Mentioned as sources of healthy fats.
  • Colorful fruits and vegetables - Recommended to be consumed to tolerance.
  • Protein-sparing modified fasting (PSMF) days - Described as low-fat, high-protein days.
  • Fat refeeds - Periods of higher fat intake used in conjunction with PSMF.
  • Carb refeeds - Periods of higher carbohydrate intake used in conjunction with PSMF.
  • White rice, bananas, oatmeal - Examples of foods used in carb refeeds.
  • Shrimp taco bowls with lettuce, cauliflower rice, tomatoes, cilantro, and hot sauce - Example meal for PSMF.
  • Shrimp fried rice with cauliflower rice - Example meal for PSMF.
  • High protein crepes - Example breakfast for PSMF.
  • High protein French toast - Example breakfast for PSMF.
  • Maria Emrick's protein bread - Used for sandwiches on PSMF days.
  • High protein cream cheese - Mentioned as a low-fat option.
  • Cold cuts and low-fat cheese - Used with protein bread on PSMF days.
  • 90/10 ground beef rinsed in a colander - Method to reduce fat content for PSMF.
  • Fatty coffees - Advised against on PSMF days, but acceptable on maintenance or refeed days.
  • Egg whites and turkey - Low-fat protein sources for PSMF.
  • Roasted turkey, roasted butternut squash, and cauliflower rice - Example meal for PSMF.
  • Tenderloin steak with broccolini and roasted zucchini - Example meal for PSMF.
  • Water fasting - An alternative fasting method discussed.
  • Alternate day fasting (ADF) - A popular intermittent fasting approach discussed.
  • Ozempic and semaglutide - Medications mentioned as alternatives for appetite suppression with potential side effects.

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