Optimal Protein Podcast with Vanessa Spina

What is T2, and why have researchers been investigating its effects on metabolism?
In this episode of the Optimal Protein Podcast, I'm welcoming back Dr. Amie Hornaman to explore 3,5-diiodothyronine, commonly called T2—a lesser-known thyroid hormone derivative studied for its effects on energy expenditure, fatty acid oxidation, and mitochondrial function.
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We walk through research on liver cells, skeletal muscle, and brown fat, unpacking the machinery that helps fatty acids enter the mitochondria and a process called mitochondrial uncoupling, in which energy is released as heat.
We also explore possible connections with ketogenic diets and the question that matters so much to us here: what could these findings mean for losing body fat while preserving muscle?
Much of the research discussed comes from animal studies. We examine a small human report involving just two participants, and Amie shares observations from an uncontrolled group of 14 women who used her T2-containing product. These findings raise interesting questions, but they do not establish that supplemental T2 is a safe or effective approach to fat loss.
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For a limited time, save 40% sitewide at ⁠ketogenicgirl.com with code BACKTOSCHOOL40, including the Protein-Sparing Modified Fasting Library, ToneLUX Red Light Therapy Collection, and Tone Breath Ketone Analyzer.
In this episode, we discuss:
What T2 is and how it relates to the better-known thyroid hormones T3 and T4.
The 2005 rat study reporting less fat accumulation and greater liver fatty acid oxidation.
How the carnitine shuttle helps transport long-chain fatty acids into the mitochondria.
AMPK, ACC, and malonyl-CoA—and their roles in regulating fat oxidation.
Mitochondrial uncoupling, ATP production, and thermogenesis.
Research on T2 and brown fat in animals with low thyroid function.
Potential overlaps with ketogenic metabolism.
The limited human evidence and the need for larger, controlled studies.
Why increased fat burning, lower body weight, and muscle preservation are different outcomes.
Protein, resistance training, and body composition during weight loss.
Important context for interpreting the research
The approximately 50% lower fat mass reported in the 2005 rat study was a comparison with the untreated high-fat-diet group. It does not mean the animals lost half of their starting body fat.
The 2011 human report described approximately 4% lower body weight, not proof that all weight lost was fat. Neither that report nor the uncontrolled 14-woman project establishes long-term safety or that T2 caused the reported changes.
Changes in muscle-cell fuel use do not establish muscle preservation during weight loss. Shared metabolic pathways also do not establish that combining keto and T2 provides additional benefits.
Studies discussed
Lanni and colleagues, 2005: T2, fat accumulation, and liver fatty acid oxidation in rats receiving a high-fat diet.
⁠Read the study
Lombardi and colleagues, 2009: T2, skeletal muscle fatty acid oxidation, AMPK signaling, and thermogenesis in rats.
⁠Read the study
Antonelli and colleagues, 2011: Preliminary human report on T2, resting metabolic rate, and body weight in two participants.
⁠Read the study
Cavallo and colleagues, 2013: Rapid effects of T2 on fatty acid oxidation and mitochondrial function in liver cells from hypothyroid rats.
⁠Read the study
Lombardi and colleagues, 2015: T2 and brown adipose tissue thermogenesis in hypothyroid rats.
⁠Read the study
Additional safety references
Padron and colleagues, 2014: T2 administration, central hypothyroidism, and effects on thyroid-sensitive tissues in rats.
⁠Read the study
Jonas and colleagues, 2015: T2's effects on thyroid regulation, body composition, energy metabolism, and heart weight in mice.
⁠Read the study
Thank you so much for listening! If you enjoyed exploring the science with us, please share this episode with a friend who loves learning about metabolism and body composition.
Join me on Friday for my solocast recap, where I'll revisit the key mechanisms, clarify what the studies do and don't show, and connect the discussion to practical takeaways for supporting muscle and metabolic health.
Guest disclosure and medical disclaimer
Dr. Amie Hornaman sells the T2-containing supplement discussed. This episode is educational and does not endorse or recommend purchasing or taking it. Some animal studies have raised concerns about thyroid suppression and heart effects; availability without a prescription does not establish safety.
Do not start T2, substitute it for prescribed treatment, or change your thyroid medication based on this episode. Consult a qualified healthcare professional about your individual circumstances.
Correction: In the mitochondrial uncoupling discussion, we meant DNP, not DMT.

Burn More Fat—But Are You Losing It? 7 Takeaways on Metabolic Flexibility & Protecting Muscle
Does becoming a better fat burner automatically mean you're losing more body fat? And do higher ketones mean better results?
In today's episode, I'm unpacking seven of my biggest takeaways from my conversation with Dr. Mike T. Nelson about metabolic flexibility, sustainable fat loss, and protecting your hard-earned muscle.
I'm sharing what I learned the hard way during my own keto journey—including how I gained weight despite having high ketones—and why understanding the difference between burning dietary fat and losing stored body fat can change how you approach your goals.
We're also exploring how to adjust carbohydrates to support your training, why fasted cardio is optional, and how small, manageable food changes can help you make progress while still enjoying your meals and your life!
In this episode, we explore:
What metabolic flexibility really means: Using fat and carbohydrates effectively and switching between fuels as your needs change.
Fat burning versus fat loss: Why increased fat oxidation and higher ketones don't automatically mean you're losing stored body fat.
Calories, hunger, and sustainability: Why an energy deficit matters—and why how you feel while creating it matters, too.
Matching carbohydrates to your training: How your activity, intensity, preferences, and recovery can guide your fueling choices.
Fasted cardio and the "fat-burning zone": Why the fuel you use during a workout doesn't tell the whole story about long-term fat loss.
Protecting muscle while losing weight: The combined importance of protein, resistance training, and recovery, plus a discussion of protein-sparing modified fasting and its limitations.
Building capacity beyond the scale: Tracking strength, aerobic fitness, energy, and recovery alongside changes in body weight.
I also share the gentle nutrition adjustments I'm making during breastfeeding and why this is a different approach from aggressive dieting or protein-sparing modified fasting.
You don't have to optimize everything at once. Choose one takeaway you can put into practice this week—whether that's tracking your weights and reps, making a simple food swap, or fueling your workouts in a way that helps you feel your best.
Listen to the full conversation
For the deeper dive, listen to my interview with Dr. Mike T. Nelson: Burning Fat vs. Losing Fat: Metabolic Flexibility Explained with Dr. Mike T. Nelson.
Resources & special offer
By popular request, the Back to School Sale has been extended for one more week! Save 40% sitewide at ketogenicgirl.com with code BACKTOSCHOOL40.
Explore:
The Protein Sparing Modified Fasting Library: High-protein recipes, grocery lists, meal frameworks, instant digital access, a premium printed edition, and community access.
Tone LUX Red Light Therapy: Discover the Sapphire, Diamond, and Gem panels, plus the Crystal mask and Contour neck and décolleté accessory.
Tone Device: Explore the breath ketone device discussed in the episode.
Let's connect
Which takeaway resonated with you most? Have you ever assumed higher ketones meant greater fat loss, or found that changing your fuel intake helped your training? I would love to hear from you!
If you enjoyed this episode, please follow the Optimal Protein Podcast and leave a rating or review. Thank you so much for listening and being part of this community!
Disclaimer: This podcast is for educational purposes only and is not medical advice. Consult your healthcare provider before changing your diet, fasting, or exercise routine. Aggressive calorie restriction and protein-sparing modified fasting are not presented as approaches for breastfeeding listeners. Individual results vary.

Does burning more fat for fuel mean you're actually losing more body fat? And if you're in ketosis, does that mean the fat you're burning is coming from your body—or from the food you just ate?
Today on the Optimal Protein Podcast, I'm joined by Dr. Mike T. Nelson to unpack this important distinction and explore what metabolic flexibility really means for fat loss, muscle preservation, and performance.
BACK-TO-SCHOOL SALE! For a limited time, save 40% sitewide at ketogenicgirl.com with code BACKTOSCHOOL40, including the Protein-Sparing Modified Fasting Library, ToneLUX Red Light Therapy Collection, and Tone Breath Ketone Analyzer.
Mike holds a PhD in exercise physiology and a master's degree in mechanical engineering with a focus on biomechanics. In this fascinating conversation, we explore your body's ability to use both carbohydrates and fat, switch between them, and adapt to different demands.
We discuss why burning more fat during a workout doesn't necessarily translate into greater body-fat loss, why calorie balance still matters, and how your nutrition and training can work together to support body recomposition. I also share my own experience gaining weight on keto despite high ketone readings—and what that taught me about dietary fat versus stored body fat.
In this episode, we discuss:
• The three components of metabolic flexibility—and why using carbohydrates effectively matters, too
• Burning fat versus losing fat: the distinction that can change how you approach your goals
• How insulin and fuel availability influence what your body burns
• Why higher ketone readings don't necessarily mean greater body-fat loss
• Fasted cardio: what the research suggests and where questions remain
• Long-term keto and the potential tradeoffs for high-intensity exercise
• Adjusting carbohydrates to support your training performance
• Protein-sparing modified fasting and the considerations around more aggressive calorie deficits
• Why stubborn lower-body fat can be especially frustrating for women
• Protein and resistance training: their roles in preserving lean mass while dieting
• Building aerobic fitness to support metabolic flexibility over time
• Heat, cold exposure, and Mike's broader framework of physiologic flexibility
• Lactate as a valuable fuel and the emerging interest in lactate supplements
• Tracking performance alongside the scale—and keeping maintenance in mind from the beginning
I loved Mike's emphasis on building a body that can perform well while you work toward your body-composition goals. This episode is full of thoughtful distinctions to help you better understand the science behind fat loss!
Connect with Dr. Mike T. Nelson:
Instagram: @drmiketnelson
Explore his newsletter for more on body composition, performance, and metabolic flexibility.
Special offers mentioned in this episode:
Save 40% sitewide at ⁠KetogenicGirl.com with code BACKTOSCHOOL40, including the Protein-Sparing Modified Fasting Library and Tone Device.
Australia and New Zealand listeners: save 75% during the warehouse moving sale with code WAREHOUSE75.
If you enjoyed this episode, please subscribe, leave a rating or review, and share it with a friend. Your support helps us continue bringing you conversations with leading researchers and experts in protein, metabolic health, and body composition.
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The content provided in this podcast is for informational purposes only and should not be construed as medical advice. Consult with a healthcare professional before making significant changes to your diet, supplements, or exercise regimen.

Can you gain lean tissue while losing body fat? And if two people eat the same number of protein grams, will they necessarily get the same body composition results?
In this episode, Vanessa shares six takeaways from her conversation with Dr. Drew Gonzalez on the science of fat loss, muscle retention, protein quality, creatine, and sustainable nutrition.
BACK-TO-SCHOOL SALE! For a limited time, save 40% sitewide at ketogenicgirl.com⁠ with code BACKTOSCHOOL40, including the Protein-Sparing Modified Fasting Library, ToneLUX Red Light Therapy Collection, and Tone Breath Ketone Analyzer.
A 12-week study discussed in the interview found that adults combining an exercise and weight-loss program with creatine gained lean tissue while reducing body fat. Vanessa unpacks why that result is exciting, what "lean tissue" actually measures, and why the change in body fat percentage needs careful interpretation.
In this episode:
Why the quality of weight loss matters more than the number on the scale alone
What the creatine study found about lean tissue and body fat during a weight-loss program
Whether protein quality may matter more when calories are limited
What a study comparing pork- and soy-based meals in military cadets found about recovery
How much protein Dr. Gonzalez suggests as a practical starting goal for people who resistance train
Why you don't need perfectly timed or evenly divided protein meals
What firefighter research can—and cannot—tell us about time-restricted eating
Where the evidence stands on creatine and cognition, probiotics, and other emerging supplements
The central question: How can you lose body fat while giving yourself the best chance of maintaining—or even gaining—lean tissue?
Listen to Vanessa's full interview with Dr. Drew Gonzalez for the complete conversation.
Follow @ketogenicgirl and @optimalproteinpodcast on Instagram, and join the Optimal Protein Podcast Facebook group to continue the discussion.
BACK-TO-SCHOOL SALE! For a limited time, save 40% sitewide at ketogenicgirl.com⁠ with code BACKTOSCHOOL40, including the Protein-Sparing Modified Fasting Library, ToneLUX Red Light Therapy Collection, and Tone Breath Ketone Analyzer.
The content provided in this podcast is for informational purposes only and should not be construed as medical advice. Consult with a healthcare professional before making significant changes to your diet, supplements, or exercise regimen.

Can you lose body fat while gaining lean tissue—even during a calorie deficit? And could the quality of your protein change how well you recover and protect muscle?
Vanessa is joined by exercise and nutrition researcher Dr. Drew Gonzalez to explore new research on creatine, body recomposition, protein quality, and what it takes to make weight loss more than a lower number on the scale.
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They begin with a 12-week study in middle-aged and older adults that tested creatine alongside exercise and a weight-loss diet. Vanessa and Dr. Gonzalez discuss the promising body-composition findings, why gaining lean tissue is not necessarily the same as gaining that amount of muscle, and what the study can—and cannot—tell us about fat loss and cognitive health.
They also explore research comparing pork- and soy-based meals during intense training, the role of essential amino acids and leucine when calories are limited, and practical protein targets for people who want to lose fat without unnecessarily losing muscle.
In this episode:
What a new creatine study found about lean tissue and body fat during weight loss
Whether someone eating plenty of meat still stands to benefit from creatine supplementation
What we know—and don't yet know—about higher creatine doses and brain health
Why two diets with the same protein grams may differ in essential amino acid content
What Dr. Gonzalez's military cadet study found about protein sources and recovery
How much protein to aim for while resistance training and losing body fat
Whether protein needs to be evenly distributed across meals
What firefighter research reveals about time-restricted eating in demanding real-world conditions
Whether probiotics and synbiotics meaningfully add to a structured fat-loss program
The goal isn't simply to lose weight. It's to improve what you lose—and what you keep.
BACK-TO-SCHOOL SALE! For a limited time, save 40% sitewide at ketogenicgirl.com with code BACKTOSCHOOL40, including the Protein-Sparing Modified Fasting Library, ToneLUX Red Light Therapy Collection, and Tone Breath Ketone Analyzer.
Follow @ketogenicgirl and @optimalproteinpodcast on Instagram, and join the Optimal Protein Podcast Facebook group for more discussion.
The content provided in this podcast is for informational purposes only and should not be construed as medical advice. Consult with a healthcare professional before making significant changes to your diet, supplements, or exercise regimen.