Project Description

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The effects of a low-carbohydrate, high fat diet on diabetes related physiological mechanisms

Written by: Candice Spence 27 May 2019 Researcher: Emeritus Professor Tim Noakes, Dr James Smith, Dr Chris Webster, Dr Kate Larmuth

Institution: University of Cape Town

Background: Low carbohydrate high fat (LCHF) diets are an effective means for people with type 2 diabetes (T2D) to improve glucose control and reduce medication use, however there are still many unanswered questions about the diet. For example, there is much confusion as to what actually constitutes an effective LCHF diet in practice and little is known about the perceptions and experiences of T2D patients who follow an LCHF diet. The physiological mechanisms of how the diet improves glucose control and affects health are not clearly understood. Understanding these mechanisms is important if LCHF diets are to be widely accepted for managing T2D because there are still concerns that the high fat component of the diet will negatively impact other aspects of diabetes pathology.

Aim: To understand the nuances of an LCHF diet and its effect on diabetes related physiological mechanisms and cardiovascular disease risk

  • Study 1 is a multi-method study of patients with T2D who claimed to have followed a LCHF diet for longer than six months. The composition of the diet, diabetes medication use, and diabetes status was assessed (quantitative research) and participants were interviewed about their experiences with the diet and its effect on their health (qualitative research).
  • Study 2 will be used to develop and optimize our testing procedures to study advanced physiological mechanisms, including liver glucose production, muscle metabolism (mitochondrial function), and cardiovascular disease. These assessments will be piloted on twelve volunteers with a range of health and dietary characteristics to ensure that we can detect predictable differences amongst participants.
  • Study 3 will investigate the effect of an LCHF diet on diabetes related physiological mechanisms using the assessment methods from Study 2.

Summary of Study 1 (completed): 

The purpose of Study 1 was to learn as much as we could from the experiences of individuals with T2D who had already followed their own version of an LCHF diet, for longer than six months. An advantage of this approach is that we could study the nuances of a real world LCHF diet that was not influenced or incentivised by an intervention trial. We could also identify factors that participants felt were important for sustaining their diet and improving their health, and could identify real world challenges they faced. We interviewed and assessed the diet and health of 28 participants and compared their past medical records to the blood tests we performed. We then reassessed their diet and health status 15 months later but did not attempt to influence their diets in anyway during the study. 

Their average total carbohydrate intake (including fiber) was 61 g/day, and all but one participant followed either a very low (< 50 g/day) or low (< 130 g/day) carbohydrate diet. Commonly reported foods were full-fat dairy, non-starchy vegetables, coconut oil, eggs, nuts, olives and avocados, olive oil, and red meat and poultry with fat. The least commonly reported foods were: added sugar, fruits (with the exception of olives, avocados, and berries), grains, breakfast cereals, oats, breads, pasta, rice, beans and legumes, starchy vegetables, and vegetable and canola oil. Reported diets included predominantly unprocessed and minimally-processed whole foods and most participants said they spontaneously reduced snacking between meals and the number of meals they ate per day. Many said they were more active or could start exercising as a result of their weight-loss and feelings of increased energy levels that they associated with an LCHF diet. In order to recognize the above nuances, the term ‘LCHF lifestyle’ may be a more appropriate way to describe the interventions of participants in the current study.

A theme to emerge from the interviews was that participants associated carbohydrate rich foods, as well as sweet-tasting, packaged, and/or highly-processed foods, with hunger, cravings, and binging. They believed that by avoiding these foods, they had reduced their hunger and addictive eating behaviours, which gave them control over their eating, and in turn, gave them control of their health, weight and T2D. Indeed, our quantitative data showed that all participants had considerably reduced their HbA1c, weight and medication use while following an LCHF diet, with the majority of them sustaining complete or partial diabetes remission for more than a year.

Most participants also reported other unexpected health improvements that they associated with their ‘active LCHF lifestyle’ including: skin and skin conditions; headaches; general pain; joint pain; neuropathy pain; fertility; cramping; gout; sleep; and hypertension.  We specifically asked about negative aspects of their LCHF diets. A minority of participants associated an LCHF diet with constipation while many participants described certain social situations that made following an LCHF diet difficult. Many participants felt that their doctors did not support them in following an LCHF diet and some experienced hostility from their doctors. In summary, these observational data suggest that an LCHF diet can be sustainable and very effective for managing T2D in a real world setting, at least amongst certain individuals. 


Christopher C Webster, Tamzyn E Murphy, Kate M Larmuth, Timothy D Noakes, James A Smith. Diet, Diabetes Status, and Personal Experiences of Individuals with Type 2 diabetes Who Self-Selected and Followed a Low Carbohydrate High Fat diet.

Available here: 

Summary of Study 2 (data collection is complete): 

Study 1 highlighted the huge potential of an LCHF diet for reversing T2D and it taught us important lessons about prescribing an ‘LCHF lifestyle’ intervention. However, the effect of the diet on the physiological mechanisms of T2D and other co-morbidities like cardiovascular disease, are still unclear and therefore controversial. The physiological mechanisms that cause T2D are numerous and complex but include fat accumulation in multiple organs and altered liver glucose production and muscle metabolism. In study 2, we developed and/or optimised our testing protocol and procedures to assess these physiological mechanisms and validated them in 10 volunteers. 

In summary we: 

  • Pilot tested the participant testing protocol which included: Online questionnaires; medical history; blood tests; 3 tools to assess diet; DXA scan (body composition); MRI scan (muscle and liver fat); CAC score CT scan (cardiovascular risk); thigh muscle biopsy (for enzymes, metabolites, and mitochondrial function); and stable isotope tracers to measure liver glucose production after a meal.
  • Adapted and validated a technique to assess liver glucose production 5 hours after a meal, whereas previous research has only used this technique in over-night fasted participants.
  • Validated our protocols for assessing muscle mitochondrial function using high resolution respirometry. This technique requires advanced skills and controls to ensure sensitive and repeatable experiments.
  • Validated our protocol for analysing MRI images for muscle and liver fat content, including writing programs to analyse images automatically. 

Summary of Study 3 (planned): 

Study 3 will investigate the effect of an LCHF diet on physiological mechanisms of diabetes and cardiovascular disease using a 6 month randomised control trial. The lessons we learnt from study 1 will be used to design the interventions and the testing procedures we validated in study 2 will be used to assess outcomes. We are currently raising funds for this study. 

Updates on the project and its publications will first be shared via ResearchGate here

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