Podcasts > The Peter Attia Drive > #324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.

#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.

By Peter Attia, MD

On this edition of The Peter Attia Drive, Attia and Dr. Eric Ravussin delve into the challenges of accurately measuring energy expenditure and dietary intake. They unpack a study investigating whether varying macronutrient ratios impacts metabolic rate, discussing the potential adaptation over time.

The duo also examines a landmark study on calorie restriction and aging, detailing its methods and findings related to cardiometabolic health markers. While promising, Ravussin addresses limitations on long-term adherence and the need for continued follow-up. Throughout this scientific exploration, listeners gain insights into the complexities of assessing energy balance and the pursuit of metabolic health.

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#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.

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#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.

1-Page Summary

Measuring Energy Expenditure and Intake

Peter Attia and Eric Ravussin discuss the challenges in accurately measuring both energy expenditure and energy intake.

Techniques for Measuring Energy Expenditure

Ravussin explains that indirect calorimetry and metabolic chambers provide precise measurements of energy expenditure. Indirect calorimetry calculates expenditure from oxygen consumption and CO2 production with 2-3% accuracy, while metabolic chambers allow detailed monitoring in a controlled setting.

However, Ravussin acknowledges that precisely measuring energy intake remains difficult. Individuals often lack awareness or underreport actual food intake. Attia cites his own experiences with variable eating habits.

Challenges in Estimating Dietary Intake

While able to precisely quantify expended energy, researchers currently lack comparable methods for measuring energy intake, Ravussin notes. He suggests exploring AI image recognition and novel wearable technologies to improve dietary data collection outside research settings.

Macronutrient Composition and Energy Expenditure

Attia and Ravussin examine a study testing whether varying the carb-to-fat ratio, while keeping protein constant, could impact energy expenditure as proposed by the carbohydrate-[restricted term] model.

Initial Findings

In the first weeks, the low-carb diet group showed a modest but significant increase in energy expenditure of around 100 calories per day compared to the standard diet group.

Adaptation Over Time

However, Ravussin observed this expenditure increase diminished by the study's third and fourth weeks, suggesting the body may adapt to macronutrient changes over time. Attia proposed testing more extreme diet compositions.

Ravussin voiced skepticism about the carbohydrate-[restricted term] model's long-term efficacy, noting the body more readily matches carb oxidation to carb intake than high fat intake.

The Calorie Study on Caloric Restriction

This study explored how calorie restriction affects aging biomarkers over seven years.

Study Design

Researchers recruited over 200 non-obese adults, aiming for 10%+ weight loss via caloric deficit from diet, exercise, or very low-calorie diets. Strict screening, monitoring, and provided meals ensured adherence.

Key Findings

The calorie-restricted group lost 10-12% weight and improved cardiometabolic health markers like [restricted term] sensitivity, oxidative stress, and mitochondrial function - suggesting impacts on primary aging processes.

Limitations

Adherence over two years proved challenging despite intensive support. Concerns included bone density, menstrual cycles, and whether benefits extend into later decades, requiring continued follow-up.

1-Page Summary

Additional Materials

Counterarguments

  • Indirect calorimetry, while accurate, may not reflect real-world conditions where factors such as stress or illness can affect metabolism.
  • Metabolic chambers, though precise, are not practical for long-term or large-scale studies due to their cost and the artificial environment they create.
  • AI image recognition and wearable technologies for tracking intake are still in development and may not yet provide the accuracy needed for precise dietary assessment.
  • The initial increase in energy expenditure on a low-carb diet may be influenced by factors other than macronutrient composition, such as increased protein intake or overall calorie reduction.
  • The body's adaptation to macronutrient changes over time could be more complex than the study suggests, with individual variability in metabolic responses.
  • The carbohydrate-[restricted term] model may have some validity in certain contexts or populations, and dismissing it entirely could overlook potential benefits.
  • The study on caloric restriction, while showing positive results, may not be generalizable to all populations, especially those with different lifestyles or genetic backgrounds.
  • The long-term sustainability and health impacts of caloric restriction need more research, particularly regarding potential negative effects on mental health and social well-being.
  • Concerns about bone density and menstrual cycles with caloric restriction indicate that more research is needed to understand the trade-offs between weight loss and other health outcomes.

Actionables

  • You can track your energy expenditure by using a fitness tracker that estimates calorie burn based on heart rate and activity level, which can give you a rough idea of your daily energy output without the need for complex equipment. While not as accurate as indirect calorimetry, these devices are widely available and can help you monitor trends in your energy expenditure over time.
  • To better understand how different diets affect your body, experiment with a food diary app that allows you to log your meals and observe how varying your carb-to-fat ratio influences your hunger levels, energy, and weight over a few weeks. This can provide personal insights into how macronutrient changes affect you, which can be more relevant than general dietary advice.
  • If you're trying to adhere to a caloric restriction plan, consider forming a support group with friends or online communities where you can share challenges, strategies, and progress. Social support can enhance motivation and accountability, making it easier to stick to your goals and overcome the common difficulties associated with long-term dietary changes.

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#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.

Measuring energy expenditure and energy balance

Peter Attia and metabolic researcher Eric Ravussin delve deep into the complexities of measuring energy expenditure and the intricacies involved in maintaining energy balance, which pose technical and methodological challenges.

Techniques for precisely measuring energy expenditure, like indirect calorimetry and metabolic chambers

Indirect calorimetry measures oxygen consumption and carbon dioxide production to calculate energy expenditure and substrate utilization, with an accuracy of around 2-3%

Ravussin, who built one of the first metabolic chambers, discusses the use of indirect calorimetry in energy metabolism. This method, which estimates energy expenditure and substrate utilization through oxidative processes, has an accuracy of about 2-3%. By quantifying oxygen consumption and CO2 production, they calculate energy expenditure and determine which substrate, like carbohydrates or fats, is being oxidized.

Peter Attia compares the process to using an indirect calorimeter affixed to the face to measure VO2 max, praising the accuracy of the technology in measuring total energy consumption and substrate sources.

Metabolic chambers allow for extended, detailed monitoring of energy expenditure in a controlled environment, but have limitations in measuring energy intake accurately

Ravussin speaks highly of the precision of measurements in metabolic chambers, which function like hotel rooms to measure oxygen consumption and CO2 production in a comfortable, extended setting. However, he acknowledges that these chambers do not directly measure energy intake and their precision mainly applies to estimating energy output.

The study that Ravussin mentions took advantage of such chambers to assess energy expenditure, where subjects lived in a hospital for a month, periodically staying in the chambers.

Despite the precision in measuring expended energy, the methodology has limitations. While it provides an accurate assessment of energy lost as heat through direct calorimetry, it falls short in accurately accounting for energy intake.

Challenges in estimating energy intake in free-living conditions

Individuals often lack awareness or underreport their actual food intake

Despite the available tools to precisely measure energy expenditure and substrates, Ravussin acknowledges that there is currently no comparable method to accurately measure energy intake. He cites the unreliability of diet recalls and the challenges that free-living conditions pose to precise measurement. Participants often do not strictly follow dietary prescriptions in real life, making it difficult to estimate actual intake.

Peter Attia recognizes his own experiences with th ...

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Measuring energy expenditure and energy balance

Additional Materials

Counterarguments

  • While indirect calorimetry is accurate within 2-3%, this margin of error might still be significant for certain research applications or for tracking the progress of individuals with very specific metabolic goals.
  • Metabolic chambers, despite their controlled environment, may not accurately reflect an individual's typical behavior or energy expenditure in their natural, free-living environment.
  • Self-reporting of food intake, although often inaccurate, can be improved with better education on portion sizes and food composition, as well as with more user-friendly dietary tracking tools.
  • Strict control and monitoring of energy intake, while difficult outside of a research setting, can be somewhat mitigated by using meal delivery services that provide known quantities and compositions of food.
  • The lack of methods to accurately measure energy intake is a significant challenge, but it's worth noting that some emerging technologies and wearable devices are beginning to offer potential solutions, although they may not yet be widely validated or available.
  • The variability in individual eating habits, while challenging for measurement, can also be seen as an opportunity for personalized nutrition advice and interventions.
  • The comparison of indirect calorimetry to VO2 max measurement might oversimplify the complexities involved in each method and their respective contexts of use.
  • The enthusiasm for the precision of metabolic chambers migh ...

Actionables

  • You can track your energy expenditure by using a fitness tracker with a heart rate monitor to estimate your daily calorie burn. While not as precise as indirect calorimetry, modern fitness trackers use algorithms based on heart rate and movement to give you an approximation of your energy expenditure. Wear the tracker consistently and review your weekly averages to get a sense of your activity level and adjust your food intake accordingly.
  • Create a photo food diary using your smartphone to improve your awareness of actual food intake. Take a picture of everything you eat and drink throughout the day. At the end of each day, review the photos to recall and record your intake. This visual record can help you become more mindful of your eating habits and portions, potentially leading to more accurate self-reporting of food intake.
  • Engage in a weekly cooking challenge where you prepare all you ...

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#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.

The impact of macronutrient composition on energy expenditure

Peter Attia and Eric Ravussin delve into a study that manipulated the macronutrient ratios in participants' diets to see if it could alter their energy expenditure.

Hypothesis that varying the ratio of carbohydrate to fat, while holding protein constant, could influence energy expenditure

The researchers were curious to see if changing the macronutrient composition, specifically the ratio of carbohydrate to fat while keeping protein constant, affects non-deliberate energy expenditure. This question is pivotal when considering the carbohydrate-[restricted term] model that suggests lower carbohydrate intake can decrease [restricted term] secretion, reduce calorie storage, and induce a semi-starvation state in the systemic circulation, potentially increasing energy expenditure.

Previous studies suggested a potential effect, but the evidence was inconclusive

Ravussin emphasized the importance of isocaloric conditions to test this hypothesis, though replicating such conditions poses a challenge in real-world scenarios. Attia and Ravussin were proponents of an alternative hypothesis where significant changes in fat and carbohydrate intake could indeed alter energy expenditure. They focused on this in light of exploring the carbohydrate-[restricted term] model versus the traditional energy balance model.

The researchers designed an isocaloric study to test this hypothesis more definitively

The study followed an isocaloric diet, varying the ratios of carbohydrate to fat while keeping protein intake constant, to observe whether this would impact energy expenditure despite unchanged calorie intake. The diets were composed differently, with one being keto-centric (10% carbohydrate) and the other containing a standard amount of carbohydrates (45-50%).

Results of the macronutrient composition study

Initial findings showed a small but statistically significant increase in energy expenditure on the low-carbohydrate diet

In a controlled metabolic chamber, there was a slight increase in sleeping metabolic rate and 24-hour energy expenditure in the first couple of weeks under the ketogenic diet, typically just over 100 calories a day. This initial effect, while statistically significant, surprised researchers like Ravussin for its modesty.

This effect diminished over time, suggesting the body may adapt to the macronutrient changes

As the study progressed into the third and fourth weeks, Ravussin observed that the increased energy expenditure effect under the ...

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The impact of macronutrient composition on energy expenditure

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Clarifications

  • The carbohydrate-[restricted term] model suggests that obesity is primarily caused by high carbohydrate intake leading to increased [restricted term] levels, promoting fat storage. This model contrasts with the traditional view that obesity results from consuming more calories than expended. Proponents of the carbohydrate-[restricted term] model argue that reducing carbohydrate intake, particularly through low-carb diets, can be more effective for long-term weight loss. However, current evidence does not consistently support significant long-term advantages of low-carb diets for weight loss.
  • A metabolic chamber is a controlled environment used in scientific research to measure an individual's energy expenditure and metabolic processes. Participants stay in the chamber while their oxygen consumption, carbon dioxide production, and heat production are monitored to calculate energy expenditure. It allows researchers to study how different factors, such as diet composition, affect an individual's metabolism over a specific period. Metabolic chambers provide valuable insights into how the body processes nutrients and expends energy under controlled conditions.
  • The protein leverage theory suggests that humans prioritize consuming enough protein and may overeat to meet protein needs, even if it means consuming excess calories. This theory proposes that a lack of dietary protein can lead to increased hu ...

Counterarguments

  • The increase in energy expenditure observed in the low-carbohydrate diet may be too small to be of practical significance for weight management or metabolic health.
  • The study's controlled conditions may not accurately reflect real-world eating behaviors, which could limit the applicability of the findings.
  • The body's adaptation to macronutrient changes over time could indicate a homeostatic mechanism that maintains energy balance, challenging the idea that macronutrient manipulation can have a lasting impact on energy expenditure.
  • The protein leverage theory, while supported by some studies, may not fully explain human dietary behavior, as humans have more complex dietary patterns and environmental influences compared to insects and rodents.
  • Skepticism about the carbohydrate-[restricted term] model may not consider individual variability in metabolic responses to different macronutrient compositions.
  • Long-term ...

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#324 ‒ Metabolism, energy balance, and aging: How diet, calorie restriction, and macronutrients influence longevity and metabolic health | Eric Ravussin, Ph.D.

The Calorie Study on the effects of caloric restriction on aging

The Calorie Study, influenced by Biosphere 2 and various theories concerning calorie restriction, was a seven-year research endeavor to explore how calorie restriction affects biomarkers of aging in humans.

Rationale and design of the Calorie Study

Peter Attia and Eric Ravussin discuss the impetus and framework of the Calorie Study. The study, which spanned over a period of years including a pilot phase, aimed to investigate the impact of caloric restriction on primary and secondary aging. Researchers designed the study to recruit a screened population of non-obese adults and assigned them to various groups, including caloric restriction, ad libitum control, energy deficit through a combination of restriction and exercise, and weight loss through a very low-calorie diet.

Recruitment was selective—more than 5,000 individuals were screened to enroll 225 participants—all with the goal of a minimum 10% weight loss. The comprehensive design used doubly labeled water to measure energy requirements, accounting for metabolic adaptations and participants had access to lessons in cooking alongside provided meals.

Key findings from the Calorie Study

Participants in the caloric restriction group achieved an average of 10-12% weight loss and exhibited significant improvements in markers of cardiometabolic health. Evidence of enhanced mitochondrial function and turnover suggested potential benefits regarding primary aging processes. Participants enjoyed better health metrics, such as reduced body fat percentage, and showed evidence of metabolic adaptation and decreased oxidative stress, supporting the theory that lower metabolic rates might equate to longer lifespans.

The study found increased mitochondrial turnover with caloric restriction, linked to less energy requirement and the creation of more efficient mitochondria, implying positive impacts on aging. Improvements were observed in lipid profiles, [restricted term] sensitivity, body composition changes, and mitophagy. Moreover, a published paper by Bill Krauss indicated remarkable improvement across all these markers of secondary aging in originally healthy individuals.

Challenges and limitations of the Calorie Study

The study's replica ...

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The Calorie Study on the effects of caloric restriction on aging

Additional Materials

Counterarguments

  • The study's selective recruitment process may not reflect the broader population, potentially limiting the generalizability of the findings.
  • The intensive monitoring and support provided to participants are not typical in real-world settings, which may affect the feasibility of applying caloric restriction at a population level.
  • The high level of participant adherence required may not be realistic for the average person, questioning the practicality of long-term caloric restriction.
  • The study's focus on non-obese adults leaves unanswered questions about the effects of caloric restriction on obese populations, who may experience different outcomes.
  • The improvements in health metrics could be influenced by factors other than caloric restriction, such as increased physical activity or healthier food choices associated with the study's lifestyle interventions.
  • The potential negative impacts on bone mineral density and menstrual cycles suggest that caloric restriction may not be without risks, and these risks may outweigh the benefits for some individuals.
  • The long-term ...

Actionables

  • You can track your daily caloric intake and aim for a slight reduction using a food diary app to monitor the effects on your health metrics.
  • Start by calculating your current average daily calorie consumption and then reduce it by a small percentage, say 5-10%, to begin with. Use the app to log everything you eat and drink, ensuring you maintain a balanced diet. Over time, observe changes in your weight, energy levels, and overall well-being. This gradual approach helps you adjust to a lower calorie intake without the need for intensive support and minimizes the risk of negative side effects.
  • Incorporate a weekly check-in with a friend or family member who shares your goal of improving health through caloric management.
  • This creates a support system that can help maintain adherence to your new eating habits. During these check-ins, discuss your progress, challenges, and feelings about the dietary changes. Sharing your journey can provide motivation and accountability, which were key factors in the study's participant adherence.
  • Engage in regular, moderate exercise to complement caloric restriction and monitor i ...

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