Sigma Nutrition Radio

This episode examines what we actually know (and importantly, what we do not know) about diet in relation to gallstones and gallbladder conditions. Much of the public-facing guidance around gallstones focuses on "avoiding fatty foods", yet Dr. Angela Madden explains that this long-standing practice sits on surprisingly weak direct evidence, particularly when judged against the standards typically expected for clinical dietary recommendations.
A central theme is the need to separate two distinct questions: dietary factors that influence the risk of developing gallstones (prevention), versus dietary strategies intended to reduce symptoms or complications once gallstones exist (management). While the prevention literature suggests plausible, consistent associations with overall diet quality and lifestyle factors, the specific question of prescribing a low-fat diet to manage symptomatic gallstones lacks robust randomized trial evidence.
Dr Angela Madden is a clinical researcher in nutrition and dietetics at the University of Hertfordshire, where she established and led the nutrition and dietetics subject group and now focuses her research on improving nutritional assessment, dietary interventions, and patient-centred outcomes in clinical and public health settings.
Timestamps
[02:09] Discussion with Dr. Angela Madden begins
[06:53] Understanding the gallbladder
[08:08] Gallbladder disorders and their prevalence
[13:42] Risk factors and pathophysiology
[22:15] Dietary factors and gallstone formation
[27:20] Exploring dietary fat and gallstones
[34:09] Broader dietary considerations
[45:44] Practical dietary recommendations
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Dr. Madden's univeristy page
Cochrane Review: Madden et al., 2024 – Modified dietary fat intake for treatment of gallstone disease in people of any age
Related episode: 513: Kidney Stones & Diet – Deepa Kariyawasam, RD

In this episode, Danny answers questions submitted by Premium subscribers.
Questions Answered in This Episode:
[00:05:13] Is eating too early (relative to chronotype) metabolically problematic?
[00:16:55] Can plant-based diets reverse cardiovascular disease?
[00:32:54] Are multivitamins useful insurance, or a waste with a good diet?
[00:44:56] Does coevolution with foods determine human compatibility and benefit?
[00:56:25] How should consumers choose supplement formulations and brands?
[01:04:46] Folate vs folic acid: differences and best choice for women of childbearing age?
[01:12:37] How reliable is omega-3 content in farmed salmon, especially imported frozen salmon?
[01:19:18] How accurate are food labels for metabolizable energy and absorption, especially across processing levels?
[01:23:58] Protein needs in breastfeeding and general rehabilitation (non-sport injury)?
To listen to the full episode, subscribe to Sigma Nutrition Premium.
Related Resources
Go to episode page (with full resource list)
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Resources for this episode: Eckel et al., 2015 – Morning Circadian Misalignment during Short Sleep Duration Impacts Insulin Sensitivity
Stothard et al., 2020 – Early Morning Food Intake as a Risk Factor for Metabolic Dysregulation
Ep. #470: Melatonin, Meal Timing & Glucose Tolerance
Ep. #579: Is Your Chronotype Hard-Wired or Modifiable?
Article: A Plant Based Diet Reverses Heart Disease: True or False?

"The more we learn about the world, and the deeper our learning, the more conscious, specific, and articulate will be our knowledge of what we do not know, our knowledge of our ignorance. For this, indeed, is the main source of our ignorance — the fact that our knowledge can be only finite, while our ignorance must necessarily be infinite." – Karl Popper
To mark Sigma Nutrition's milestone 600th episode (and 12-year anniversary), Danny and Alan examine several areas in which their views have changed, softened, strengthened, or remained stable over the lifespan of the podcast.
The discussion is therefore not only about nutrition itself, but also about the process of scientific reasoning: how positions are formed, what type of evidence can shift them, and why changing one's mind is often a sign of better thinking rather than inconsistency.
The episode therefore serves as both a review of several specific nutrition controversies and a lesson in scientific epistemology. They discuss topics such as red meat, protein, dietary cholesterol, omega-3s, flavonoids, and sodium.
Timestamps
[11:04] Time-restricted eating
[19:32] Protein intake, quality & dosing
[35:04] Cocoa flavanols and cognition
[51:38] Unprocessed red meat
[01:05:23] Omega-3 supplementation
[01:23:10] Dietary cholesterol
[01:44:41] Sodium J-curve myth
[01:53:41] Energy balance model
Links
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This episode examines whether unprocessed red meat has a causal role in (1) type 2 diabetes risk and intermediate measures of glucose intolerance (insulin resistance, beta cell dysfunction, glycemic markers) and (2) cardiovascular disease (CVD) risk.
While there is commonly observed risk signal from observational cohorts, there exist short-term randomized controlled trials (RCTs) that show largely null effects on glucose homeostasis. This had led to differing opinions and interpretations of the evidence base.
Some feel that in the context of an otherwise healthy diet, there isn't much to suggest concern about consuming unprocessed red meat. While others are of the view that there does exist a risk and that limiting or even avoiding consumption is prudent.
The crucial concept of replacement effects is discussed. Increasing red meat intake always means decreasing something else or increasing total energy intake. Therefore, interpreting evidence requires specifying the comparator food(s), the background dietary pattern, the dose, the cut (lean vs fatty), and how the meat is prepared.
To discuss their interpretations of this contentious evidence base, Dr. Mario Kratz and Dr. Gil Carvalho join the podcast to go through the studies most directly related to these questions.
Timestamps
[06:20] Red meat's impact is debated
[10:54] Mechanisms linking meat to diabetes
[15:31] Cohort evidence on diabetes risk
[24:43] Differences between cohorts and threshold effects
[33:13] RCT evidence and substitution trials
[45:49] Why comparator foods matter
[50:43] RCT examples and mixed results
[01:00:30] Is there cardiovascular risk beyond saturated fat?
[01:08:10] Epidemiology patterns and dose thresholds
[01:11:36] Personal recommendations and risk tolerance
[01:16:19] Key ideas
Related Resources
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Mario's YouTube channel: Nourished By Science
Gil's YouTube channel: Nutrition Made Simple!

This episode examines how exercise and nutrition interact to influence glycaemic control, with particular focus on the postprandial period (i.e., the hours after eating) and on "time-efficient" exercise strategies such as low-volume interval training.
Dr. Jenna Gillen outlines the physiological basis for why muscle contraction can acutely reduce post-meal glucose excursions, why repeated sessions can accumulate into longer-term improvements in insulin sensitivity, and why the nutrition context (pre- and post-exercise feeding, carbohydrate availability, and energy balance) can meaningfully alter observed outcomes.
A key translational thread is that many clinically relevant improvements may come from small, feasible doses of activity; especially post-meal walking and brief "exercise snacks" used to interrupt sedentary time.
However, the discussion considers who these interventions matter for most (and least). Postprandial glucose rises are normal in healthy individuals, whereas reducing exaggerated excursions is most relevant for those with insulin resistance, prediabetes, or type 2 diabetes (T2D).
Dr. Jenna Gillen is an Assistant Professor of Exercise Physiology in the Faculty of Kinesiology & Physical Education at the University of Toronto. 
Timestamps
[02:42] Dr. Gillen's research focus
[04:11] Understanding glycemic control
[10:07] Fasted vs. fed state exercise
[11:10] Post-meal exercise benefits
[20:10] Low volume interval training
[26:27] Interval training and blood glucose
[31:29] Energy balance and insulin sensitivity
[36:32] Exercise and nutrition interactions
[40:11] Practical exercise recommendations
[43:56] Key ideas segment (Premium-only)
Links
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See Sigma's recommended resources