#313 – AMA #62: Protein’s impact on appetite and weight management, and uric acid’s link to disease and how to manage levels

In this “Ask Me Anything” (AMA) episode, Peter dives into two important health topics: uric acid and protein, examining them from unique perspectives. For uric acid, he explores its metabolic role and connection to various diseases, focusing on the potential causal link with cardiovascular disease. He also discusses factors influencing uric acid levels, such as diet, genetics, and lifestyle, providing practical tips for effective management. Shifting to protein, Peter delves into its role in appetite and weight management, the consequences of insufficient protein, and the “protein leverage hypothesis” linking protein deficiency to obesity. He covers optimal protein intake and its impact on energy expenditure, and he compares the satiety effects of solid versus liquid protein. Finally, Peter shares his strategy for incorporating protein into a comprehensive weight management plan.

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We discuss:

• Overview of episode topics (and an important discussion on fanny packs) [2:00];
• Understanding uric acid: its role in metabolic processes, its association with gout and kidney stones, its impact on blood pressure, and more [6:00];
• Non-modifiable factors that influence uric acid levels [11:00];
• Modifiable factors that influence uric acid levels [14:15];
• Association between high uric acid levels and cardiovascular disease [20:00];
• Evidence suggesting a causal link between high uric acid levels and cardiovascular disease [24:00];
• Inconclusive evidence about the cardiovascular benefits of lowering uric acid pharmacologically [28:15];
• Exploring the potential risks of low uric acid levels in neurodegenerative diseases [37:00];
• Managing uric acid levels: dietary interventions and pharmacological approaches [42:00];
• The impact of protein on appetite and weight management [44:00];
• The consequences of insufficient protein on eating behaviors and satiety [52:15];
• The relationship between protein deficiency and obesity: exploring the “protein leverage hypothesis” [57:15];
• The impact of protein intake on energy expenditure [1:02:15];
• Determining optimal protein intake to avoid deficiency and support health [1:05:45];
• The role of different amino acids and protein sources in promoting satiety [1:08:15];
• Comparing the satiety effects of solid vs. liquid protein sources [1:10:30];
• Peter’s framework for incorporating protein intake into a strategy for controlling body weight [1:12:00]; and
• More.

Overview of episode topics (and an important discussion on fanny packs) [2:00]

Fanny packs

• Peter caused some “controversy” recently with his fashion choice of sporting a fanny pack
• Peter notes the large number of votes against the fanny pack, comparing it to other controversial health topics that require nuanced discussion.
• Peter’s rebuttal: 
  • “I would bet that the same number of people who think that the fanny pack is a faux pas are probably equal in proportion, not necessarily the same people, but equal in proportion to the number of people who think HRT causes breast cancer or TRT causes prostate cancer…
  • …And so it requires deep, thorough, nuanced discussion to explain the merits of certain approaches, and I think the fanny pack is no exception.”

Episode topics:

• Uric Acid Discussion: Nick mentions the renewed focus on uric acid due to new information, covering its relation to diseases and metrics for Peter and his patients.
• Protein Discussion: Nick introduces the discussion on protein and its relationship to appetite, energy expenditure, and weight control, highlighting new aspects not previously covered.

Understanding uric acid: its role in metabolic processes, its association with gout and kidney stones, its impact on blood pressure, and more [6:00]

What is uric acid? Why should people even care about this metric?

• Uric acid is often seen on blood tests, though not commonly ordered.
• Familiarity mainly comes from its association with gout.

But let’s just take a step back and talk about what it is…

• Metabolite Breakdown
  • Uric acid is a byproduct of purine breakdown.
  • Purines are DNA and RNA building blocks; their breakdown leads to uric acid production.
• Fructose connection
  • Uric acid is also a metabolite of fructose
  • In a previous convo with Rick Johnson, they talk at length and in great detail about the biochemical pathway that leads from the metabolism of fructose to uric acid.
• Evolutionary aspect: Genetic Mutation
  • A specific mutation in humans allows higher uric acid levels compared to ancestors.
  • Possibly linked to a survival advantage during extreme cold periods in Europe.

Uric acid and pathology

Gout

• Most of our understanding of it of course is associated with pathology and most of that pathology centers around gout.
• So when uric acid crystallizes, it can do so in joints, and because it is quite inflammatory when it crystallizes, this inflammatory condition within the joints is what is clinically known as gout.
• Commonly affects the big toe and requires potent anti-inflammatory drugs.

Kidney stones

• High uric acid levels can lead to urate-based kidney stones.
• Less common but significant in the types of kidney stones.

High blood pressure

• Hyperuricemia is linked to increased blood pressure.
• Established through experimental evidence and Mendelian randomization.

Mendelian Randomization (MR)

• MR is used to study causality between biomarkers and disease phenotypes.
• Helps clarify if lowering biomarkers like LDL or uric acid reduces disease risk.
• Example of causal relationships found:
  • Lowering LDL has been causally linked to reducing atherosclerotic cardiovascular disease. 
  • Similar MR studies show that uric acid levels correlate with blood pressure changes. 

Confounding factors

• All of this is confounded by the fact that things that are bad for you tend to raise uric acid and that association is a little difficult to tease out causality.
• For example, we know that patients with fatty liver disease and patients with type 2 diabetes usually have very high uric acid levels and it’s unclear exactly what the direction of causality is there.

Non-modifiable factors that influence uric acid levels [11:00]

Non-Modifiable Factors

Sex Differences

• Men generally have higher uric acid levels than women (0.5 to 1 mg/dL higher on average).

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