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Could the ketogenic diet induce a shift in thyroid function and support a metabolic advantage in healthy participants? A pilot randomized-controlled-crossover trial.
Iacovides, S, Maloney, SK, Bhana, S, Angamia, Z, Meiring, RM
PloS one. 2022;17(6):e0269440
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The ketogenic diet (KD) has been shown in several studies to result in weight loss compared to a conventional high-carbohydrate, low-fat diet (HCLF). It is thought that this sort of diet may inhibit the appetite and increase feelings of being fuller for longer. However, its effects on other biological functions which can lead to weight loss are unclear. This randomised control trial of 11 individuals aimed to determine the effect of the KD on thyroid function, which controls the conversion of calories into energy and therefore has a role in fat storage. The results showed that KD resulted in a higher loss of body mass than the HCLF diet and one of the thyroid hormones (T3) was decreased. However, hormones which stimulate thyroid function remained unchanged. It was concluded that changes in metabolism can occur following the KD, which may contribute to a greater loss of weight compared to a HCLF diet. This study could be used by healthcare professionals to understand that the ketogenic diet may be more effective at weight loss than a standard HCLF diet. However larger scale trials are warranted.
Abstract
BACKGROUND The ketogenic diet (KD) has been shown to result in body mass loss in people with disease as well as healthy people, yet the effect of the KD on thyroid function and metabolism are unknown. OBJECTIVE We aimed to determine the effects of a KD, compared with an isocaloric high-carbohydrate low-fat (HCLF) diet, on resting metabolic rate and thyroid function in healthy individuals. DESIGN Eleven healthy, normal-weight participants (mean(SD) age: 30(9) years) completed this randomized crossover-controlled study. For a minimum of three weeks on each, participants followed two isocaloric diets: a HCLF diet (55%carbohydrate, 20%fat, 25%protein) and a KD (15%carbohydrate, 60%fat, 25% protein), with a one-week washout period in-between. Importantly, while on the KD, the participants were required to remain in a state of nutritional ketosis for three consecutive weeks. Crossover analyses and linear mixed models were used to assess effect of diet on body mass, thyroid function and resting metabolic rate. RESULTS Both dietary interventions resulted in significant body mass loss (p<0.05) however three weeks of sustained ketosis (KD) resulted in a greater loss of body mass (mean (95%CI): -2.9 (-3.5, -2.4) kg) than did three weeks on the HCLF diet (-0.4 (-1.0, 0.1) kg, p < 0.0001). Compared to pre-diet levels, the change in plasma T3 concentration was significantly different between the two diets (p = 0.003), such that plasma T3 concentration was significantly lower following the KD diet (4.1 (3.8, 4.4) pmol/L, p<0.0001) but not different following the HCLF diet (4.8 (4.5, 5.2) pmol/L, p = 0.171. There was a significant increase in T4 concentration from pre-diet levels following the KD diet (19.3 (17.8, 20.9) pmol/L, p < 0.0001), but not following the HCLF diet (17.3 (15.7, 18.8) pmol.L, p = 0.28). The magnitude of change in plasma T4 concentration was not different between the two diets (p = 0.4). There was no effect of diet on plasma thyroid stimulating hormone concentration (p = 0.27). There was a significantly greater T3:T4 ratio following the HCLF diet (0.41 (0.27, 0.55), p < 0.0001) compared to pre-diet levels but not following the KD diet (0.25 (0.12, 0.39), p = 0.80). CONCLUSIONS Although the diets were isocaloric and physical activity and resting metabolic rate remained constant, the participants lost more mass after the KD than after the HCLF diet. The observed significant changes in triiodothyronine concentration suggest that unknown metabolic changes occur in nutritional ketosis, changes that warrant further investigation. TRIAL REGISTRATION Pan African Clinical Trial Registry: PACTR201707002406306 URL: https://pactr.samrc.ac.za/.
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Randomized crossover trial of a modified ketogenic diet in Alzheimer's disease.
Phillips, MCL, Deprez, LM, Mortimer, GMN, Murtagh, DKJ, McCoy, S, Mylchreest, R, Gilbertson, LJ, Clark, KM, Simpson, PV, McManus, EJ, et al
Alzheimer's research & therapy. 2021;13(1):51
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Most people with dementia have Alzheimer’s disease (AD), a disorder that characteristically results in progressive cognitive and functional decline. Brain energy metabolism is impaired in AD. Ketogenic diets can theoretically mitigate impaired brain energy metabolism in AD, leading to improved cognition, daily function, or quality of life. Ketogenic diets are high-fat, low-carbohydrate diets that shift the body towards fat metabolism. The aim of this study was to determine whether a 12-week modified ketogenic diet was well-tolerated and improved cognition, daily function, or quality of life in a hospital clinic of AD patients. This study is a single-phase, assessor-blinded, two-period randomised crossover trial. Participants (n=26) were randomised (1:1 allocation) to a modified ketogenic diet (intervention diet) or their usual diet supplemented with low-fat healthy-eating guidelines and optional recipes (control diet). Results show that high rates of retention and adherence are achievable by following a 12-week modified ketogenic diet to AD patients. Compared with a usual diet supplemented with low-fat healthy-eating guidelines, patients on the ketogenic diet improved in daily function and quality of life. Furthermore, changes in cardiovascular risk factors were mostly favourable and adverse effects were mild. Authors conclude that ketogenic diets may hold promise as viable and effective treatment strategies in AD, but larger and longer studies are needed in order to draw definitive conclusions.
Abstract
BACKGROUND Brain energy metabolism is impaired in Alzheimer's disease (AD), which may be mitigated by a ketogenic diet. We conducted a randomized crossover trial to determine whether a 12-week modified ketogenic diet improved cognition, daily function, or quality of life in a hospital clinic of AD patients. METHODS We randomly assigned patients with clinically confirmed diagnoses of AD to a modified ketogenic diet or usual diet supplemented with low-fat healthy-eating guidelines and enrolled them in a single-phase, assessor-blinded, two-period crossover trial (two 12-week treatment periods, separated by a 10-week washout period). Primary outcomes were mean within-individual changes in the Addenbrookes Cognitive Examination - III (ACE-III) scale, AD Cooperative Study - Activities of Daily Living (ADCS-ADL) inventory, and Quality of Life in AD (QOL-AD) questionnaire over 12 weeks. Secondary outcomes considered changes in cardiovascular risk factors and adverse effects. RESULTS We randomized 26 patients, of whom 21 (81%) completed the ketogenic diet; only one withdrawal was attributed to the ketogenic diet. While on the ketogenic diet, patients achieved sustained physiological ketosis (12-week mean beta-hydroxybutyrate level: 0.95 ± 0.34 mmol/L). Compared with usual diet, patients on the ketogenic diet increased their mean within-individual ADCS-ADL (+ 3.13 ± 5.01 points, P = 0.0067) and QOL-AD (+ 3.37 ± 6.86 points, P = 0.023) scores; the ACE-III also increased, but not significantly (+ 2.12 ± 8.70 points, P = 0.24). Changes in cardiovascular risk factors were mostly favourable, and adverse effects were mild. CONCLUSIONS This is the first randomized trial to investigate the impact of a ketogenic diet in patients with uniform diagnoses of AD. High rates of retention, adherence, and safety appear to be achievable in applying a 12-week modified ketogenic diet to AD patients. Compared with a usual diet supplemented with low-fat healthy-eating guidelines, patients on the ketogenic diet improved in daily function and quality of life, two factors of great importance to people living with dementia. TRIAL REGISTRATION This trial is registered on the Australia New Zealand Clinical Trials Registry, number ACTRN12618001450202 . The trial was registered on August 28, 2018.
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Ketogenic diet in the treatment of cancer - Where do we stand?
Weber, DD, Aminzadeh-Gohari, S, Tulipan, J, Catalano, L, Feichtinger, RG, Kofler, B
Molecular metabolism. 2020;33:102-121
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A literature review paper looking at complementary approaches to improve the efficacy of standard anticancer therapies – specifically the Ketogenic Diet (KD), characterised as a high-fat (90%), low-carbohydrate (2%) diet with adequate amounts of protein (8%). The KD is a low- cost adjuvant to cancer therapy and is considered promising due to its potential to target metabolic alterations in tumour cells. Research shows it potentially limits tumour growth, whilst protecting healthy cells from damage by chemotherapy or radiation and reducing inflammation. The ketones produced by the high ratio of fat in the diet are used to create ATP energy, which cancerous cells are unable to use. Preclinical studies show that in most cases the KD slowed tumour growth, prolonged survival rate, and delayed the initiation of tumours although this may be influenced by cancer type and genetic background. This implies it’s important to evaluate KD efficiency against each individual cancer rather than as a collective anticancer therapy. Gold standard therapy for some cancers is surgery, radiation, and chemotherapy. However aggressive cancer types with poor prognosis need new approaches where standard therapy is less successful. The authors recognise there is insufficient RCT evidence with large patient cohorts but smaller studies are emerging showing positive results for a KD with patients exceeding their expected lifespan, with reduced tumour growth and progression, reduced glucose up-take at the tumour site and overall improved quality of life. KD seemingly creates an environment in which cancer cells cannot thrive making it a promising adjuvant as a patient-specific multifactorial therapy.
Abstract
BACKGROUND Cancer is one of the greatest public health challenges worldwide, and we still lack complementary approaches to significantly enhance the efficacy of standard anticancer therapies. The ketogenic diet, a high-fat, low-carbohydrate diet with adequate amounts of protein, appears to sensitize most cancers to standard treatment by exploiting the reprogramed metabolism of cancer cells, making the diet a promising candidate as an adjuvant cancer therapy. SCOPE OF REVIEW To critically evaluate available preclinical and clinical evidence regarding the ketogenic diet in the context of cancer therapy. Furthermore, we highlight important mechanisms that could explain the potential antitumor effects of the ketogenic diet. MAJOR CONCLUSIONS The ketogenic diet probably creates an unfavorable metabolic environment for cancer cells and thus can be regarded as a promising adjuvant as a patient-specific multifactorial therapy. The majority of preclinical and several clinical studies argue for the use of the ketogenic diet in combination with standard therapies based on its potential to enhance the antitumor effects of classic chemo- and radiotherapy, its overall good safety and tolerability and increase in quality of life. However, to further elucidate the mechanisms of the ketogenic diet as a therapy and evaluate its application in clinical practice, more molecular studies as well as uniformly controlled clinical trials are needed.