In this episode I’m joined again by practising registered dietitian and senior research fellow at the University of Oxford, Dr Nicola Guess, to take a closer look at a study that drew a lot of attention online. Dr Samuel Klein’s group at Washington University assigned participants with prediabetes to one of three diets, tightly controlled their weight loss, and measured changes in liver fat. The arm labelled ketogenic showed the largest reduction, 67%, and the result was quickly shared as evidence that cutting carbohydrates is the best way to reduce liver fat.
Nicola offers a different interpretation. She argues the diet may have been mislabelled, as ketone levels in that arm were lower than you would expect on a ketogenic diet, and that protein intake, rather than carbohydrate restriction, is the more likely explanation for the result. This distinction matters. Roughly one in three adults has excess fat in their liver, often without symptoms, and advice built around “eat less carbohydrate” looks quite different from advice built around “eat more protein.”
What We Cover
- Why Nicola thinks this trial should never have been called a ketogenic diet study, and what she would call it instead
- The reason providing every meal, measuring urinary nitrogen, and tracking ketones makes this trial unusually worth taking seriously
- Why protein, not carbohydrate restriction, appears to be doing most of the work on liver fat
- The 23% of calories from saturated fat that everyone noticed, and why she thinks the weight loss masked its usual effect on ApoB
- What happens to liver fat when people stop losing weight and move into maintenance
- Whether liver fat causes insulin resistance, or is simply the clearest sign that something has already gone wrong
- Her practical target of 35 grams of protein per meal, and how she builds a plate around it
- Seed oils, fibre, and cooking potatoes to cool them: what actually moves the needle and what does not
What I took from this conversation is that the best answer here is not one diet beating another, it is combining them: the protein and lower carbohydrate load from the trial’s winning arm, with the olive oil, nuts, seeds, legumes, and plants that the Mediterranean evidence supports. Nicola is also refreshingly willing to say “I don’t know” when the mechanism has not been worked out, which is rarer than it should be in this field.
To connect with Nicola Guess, visit NicolaGuess.com or find her on Instagram and YouTube.
Resources and links:
- Effect of diet macronutrient content on the cardiometabolic response to weight loss: A randomized clinical trial
- Distinct effects of ketogenic and non-ketogenic weight-loss diets on hepatic steatosis and mitochondrial metabolism in MASLD
- Diets differing in carbohydrate cellularity and amount similarly reduced visceral fat in people with obesity – a randomized controlled trial (CARBFUNC)
- Relationship between Ketones, Ghrelin, and, Appetite on Isocaloric Diets with Varying Carbohydrate Quality and Amount: Results from a Randomized Controlled Trial in People with Obesity (CARBFUNC)
- Saturated Fat Is More Metabolically Harmful for the Human Liver Than Unsaturated Fat or Simple Sugars
- Overeating Saturated Fat Promotes Fatty Liver and Ceramides Compared With Polyunsaturated Fat: A Randomized Trial
- Effects of n-6 PUFAs compared with SFAs on liver fat, lipoproteins, and inflammation in abdominal obesity: a randomized controlled trial
- Sources of fatty acids stored in liver and secreted via lipoproteins in patients with nonalcoholic fatty liver disease
- Effects of the individual saturated fatty acids on serum lipids and lipoprotein concentrations
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More about Dr Nicola Guess
Dr Nicola Guess is a practicing Registered Dietitian and Senior Research Fellow at the University of Oxford, affiliated with the Nuffield Department of Primary Care Health Sciences. She holds a PhD, MPH, and RD, and her primary research and clinical interests are in conditions of glucose homeostasis – including type 2 diabetes, prediabetes and reactive hypoglycaemia. Dr Guess’s research investigates how dietary components, such as amino acids, affect beta-cell function and the underlying pathophysiology of metabolic diseases. She is also known for her work on evidence-based dietary guidelines and has led projects to develop clinician-friendly tools for dietary advice in clinical practice. Her work bridges the gap between research and practical application, aiming to improve patient care through informed nutritional strategies.
