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Skartun O, Smith CR, Laupsa-Borge J, Dankel SN. Symptoms during initiation of a ketogenic diet: a scoping review of occurrence rates, mechanisms and relief strategies. Front Nutr 2025; 12:1538266. [PMID: 40206956 PMCID: PMC11978633 DOI: 10.3389/fnut.2025.1538266] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2024] [Accepted: 03/05/2025] [Indexed: 04/11/2025] Open
Abstract
Background Evidence for the clinical utility of ketogenic diets (KD) is mounting. The transition to a KD (keto-induction) can however trigger unpleasant transient symptoms (≪keto-flu≫) which may deter continued adherence. Knowledge of strategies that mitigate symptoms during keto-induction may facilitate adoption of a KD. Aim We aimed to perform a scoping review of the available scientific literature with regards to symptom occurrence rates, possible mechanisms and proposed interventions for symptom relief during keto-induction. Methods Embase, Medline and Web of Science electronic databases were searched systematically using terms associated with the KD and keto-induction in conjunction with terms capturing adverse effects. In addition, additional relevant studies were retrieved from the identified articles' references. Results The available literature on keto-induction symptoms is highly heterogenous, but common transient symptoms are reported across multiple populations, including descriptions of "keto-flu," nausea, emesis, reduced appetite, hypoglycaemia, acidosis, increased risk of kidney stones, altered liver biochemistry, and skin rash. Mechanisms have been proposed based on general insights into physiology, but few have been empirically tested. However, approaches to reduce symptoms of keto-initiation are reported, including avoidance of the traditionally used fasted initiation and supplementation of medium-chain triglycerides (MCT) and ketone salts. There is a physiological rationale for supplementation with electrolytes and ketone esters, but a lack of clinical studies documenting their effect. Conclusion Several transient symptoms have been associated with keto-induction, although a limited number of studies have directly examined them, or the mechanisms and possible interventions for symptom alleviation. Further research is warranted to close knowledge gaps highlighted in this review.
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Biesiekierska M, Strigini M, Śliwińska A, Pirola L, Balcerczyk A. The Impact of Ketogenic Nutrition on Obesity and Metabolic Health: Mechanisms and Clinical Implications. Nutr Rev 2025:nuaf010. [PMID: 40036324 DOI: 10.1093/nutrit/nuaf010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/06/2025] Open
Abstract
The ketogenic diet (KD) has recently gained increasing popularity. This high-fat, adequate-protein, and carbohydrate-poor eating pattern leads to nutritional ketosis. The KD has long been known for its antidiabetic and antiepileptic effects and has been used therapeutically in these contexts. Recently, the KD, due to its effectiveness in inducing weight loss, has also been proposed as a possible approach to treat obesity. Likewise, a KD is currently explored as a supporting element in the treatment of obesity-associated metabolic disorders and certain forms of cancer. Here, we discuss the metabolic and biochemical mechanisms at play during the shift of metabolism to fatty acids and fatty acid-derived ketone bodies as main fuel molecules, in the substitution of carbohydrates, in ketogenic nutrition. Different sources of ketone bodies and KDs as alternatives to glucose and carbohydrates as main energy substrates are discussed, together with an attempt to weigh the benefits and risks posed by the chronic use of a KD in the context of weight loss, and also considering the molecular effects that ketone bodies exert on metabolism and on the endocrine system.
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Affiliation(s)
- Marta Biesiekierska
- Department of Oncobiology and Epigenetics, Faculty of Biology and Environmental Protection, University of Lodz, 90-236 Lodz, Poland
| | - Maura Strigini
- University Jean Monnet Saint-Etienne, INSERM, Mines Saint Etienne, SAINBIOSE U1059, F-42023 Saint-Etienne, France
| | - Agnieszka Śliwińska
- Department of Nucleic Acid Biochemistry, Medical University of Lodz, 92-213 Lodz, Poland
| | - Luciano Pirola
- INSERM Unit 1060, CarMeN Laboratory, Lyon 1 University, F-69495 Pierre Bénite, France
| | - Aneta Balcerczyk
- Department of Oncobiology and Epigenetics, Faculty of Biology and Environmental Protection, University of Lodz, 90-236 Lodz, Poland
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Lundanes J, Gårseth M, Taylor S, Crescenzi R, Pridmore M, Wagnild R, Hyldmo ÅA, Martins C, Nymo S. The effect of a low-carbohydrate diet on subcutaneous adipose tissue in females with lipedema. Front Nutr 2024; 11:1484612. [PMID: 39574523 PMCID: PMC11578713 DOI: 10.3389/fnut.2024.1484612] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2024] [Accepted: 10/28/2024] [Indexed: 11/24/2024] Open
Abstract
Introduction Lipedema is a common, yet underdiagnosed, subcutaneous adipose tissue (SAT) disorder. The main characteristics are SAT expansion in the lower extremities and arms, pain, and tenderness to palpation. It remains unknown if a low-carbohydrate diet (LCD) influences SAT in females with lipedema. Objectives To evaluate the effect of a LCD low-energy diet, compared to a low-fat isoenergetic control diet, on calf subcutaneous adipose tissue area, muscle area, SAT/muscle ratio, calf circumference and body composition in females with lipedema. Subjects/methods Adult females with obesity and lipedema were randomized to 1,200 kcal/day diets, either LCD or control (75 and 180 g/day of carbohydrates, respectively) for 8 weeks. Body composition was measured with bioelectrical impedance analysis, calf SAT area, muscle area, and circumference with magnetic resonance imaging and pain with brief pain inventory, before and after the intervention. Results Thirteen participants were included (five in the LCD group), with a mean age of 46 ± 12 years and a BMI of 37 ± 6 kg/m2. A significant reduction in calf SAT area, calf circumference, and pain was observed in the LCD group only. Both LCD and control groups experienced a significant reduction body weight, fat mass, fat free mass, and muscle area, with no differences between groups. No significant changes over time were found for SAT/muscle ratio. Conclusion A LCD has the potential to reduce SAT and pain in females with lipedema, despite a reduction in muscle mass in lipedema affected areas in both diet groups. Further studies are needed to confirm these findings and explore potential mechanisms. Clinical trial registration NCT04632810: Effect of ketosis on pain and quality of life in patients with lipedema (Lipodiet). https://clinicaltrials.gov/study/NCT04632810.
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Affiliation(s)
- Julianne Lundanes
- Obesity Research Group, Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU), Trondheim, Norway
- Nord-Trøndelag Hospital Trust, Clinic of Surgery, Namsos Hospital, Namsos, Norway
| | - Mari Gårseth
- Department of Diagnostic Imaging, Levanger Hospital, Nord-Trøndelag Hospital Trust, Levanger, Norway
| | - Shannon Taylor
- Department of Radiology and Radiological Sciences, Vanderbilt University Medical Center, Nashville, TN, United States
- Biomedical Engineering, Vanderbilt University, Nashville, TN, United States
| | - Rachelle Crescenzi
- Department of Radiology and Radiological Sciences, Vanderbilt University Medical Center, Nashville, TN, United States
- Biomedical Engineering, Vanderbilt University, Nashville, TN, United States
| | - Michael Pridmore
- Department of Radiology and Radiological Sciences, Vanderbilt University Medical Center, Nashville, TN, United States
| | - Rune Wagnild
- Department of Diagnostic Imaging, Levanger Hospital, Nord-Trøndelag Hospital Trust, Levanger, Norway
| | - Åsne Ask Hyldmo
- Obesity Research Group, Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU), Trondheim, Norway
- ObeCe, Department of Surgery, St. Olavs University Hospital, Trondheim, Norway
| | - Catia Martins
- Obesity Research Group, Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU), Trondheim, Norway
- ObeCe, Department of Surgery, St. Olavs University Hospital, Trondheim, Norway
- Department of Nutrition Sciences, University of Alabama at Birmingham (UAB), Birmingham, AL, United States
| | - Siren Nymo
- Obesity Research Group, Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU), Trondheim, Norway
- Nord-Trøndelag Hospital Trust, Clinic of Surgery, Namsos Hospital, Namsos, Norway
- ObeCe, Department of Surgery, St. Olavs University Hospital, Trondheim, Norway
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Volek JS, Kackley ML, Buga A. Nutritional Considerations During Major Weight Loss Therapy: Focus on Optimal Protein and a Low-Carbohydrate Dietary Pattern. Curr Nutr Rep 2024; 13:422-443. [PMID: 38814519 PMCID: PMC11327213 DOI: 10.1007/s13668-024-00548-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/01/2024] [Indexed: 05/31/2024]
Abstract
PURPOSE OF REVIEW Considering the high prevalence of obesity and related metabolic impairments in the population, the unique role nutrition has in weight loss, reversing metabolic disorders, and maintaining health cannot be overstated. Normal weight and well-being are compatible with varying dietary patterns, but for the last half century there has been a strong emphasis on low-fat, low-saturated fat, high-carbohydrate based approaches. Whereas low-fat dietary patterns can be effective for a subset of individuals, we now have a population where the vast majority of adults have excess adiposity and some degree of metabolic impairment. We are also entering a new era with greater access to bariatric surgery and approval of anti-obesity medications (glucagon-like peptide-1 analogues) that produce substantial weight loss for many people, but there are concerns about disproportionate loss of lean mass and nutritional deficiencies. RECENT FINDINGS No matter the approach used to achieve major weight loss, careful attention to nutritional considerations is necessary. Here, we examine the recent findings regarding the importance of adequate protein to maintain lean mass, the rationale and evidence supporting low-carbohydrate and ketogenic dietary patterns, and the potential benefits of including exercise training in the context of major weight loss. While losing and sustaining weight loss has proven challenging, we are optimistic that application of emerging nutrition science, particularly personalized well-formulated low-carbohydrate dietary patterns that contain adequate protein (1.2 to 2.0 g per kilogram reference weight) and achieve the beneficial metabolic state of euketonemia (circulating ketones 0.5 to 5 mM), is a promising path for many individuals with excess adiposity.
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Affiliation(s)
- Jeff S Volek
- Department of Human Sciences, The Ohio State University, 305 Annie & John Glenn Ave, Columbus, OH, 43210, USA.
| | - Madison L Kackley
- Department of Human Sciences, The Ohio State University, 305 Annie & John Glenn Ave, Columbus, OH, 43210, USA
| | - Alex Buga
- Department of Human Sciences, The Ohio State University, 305 Annie & John Glenn Ave, Columbus, OH, 43210, USA
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Lundanes J, Sandnes F, Gjeilo KH, Hansson P, Salater S, Martins C, Nymo S. Effect of a low-carbohydrate diet on pain and quality of life in female patients with lipedema: a randomized controlled trial. Obesity (Silver Spring) 2024; 32:1071-1082. [PMID: 38627016 DOI: 10.1002/oby.24026] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/30/2023] [Revised: 02/21/2024] [Accepted: 02/22/2024] [Indexed: 05/29/2024]
Abstract
OBJECTIVE The primary objective of this study was to evaluate the effect of a low-carbohydrate diet (LCD) compared with a control diet on pain in female patients with lipedema. The secondary objectives were to compare the impact of the two diets on quality of life (QoL) and investigate potential associations of changes in pain with changes in body weight, body composition, and ketosis. METHODS Adult female patients with lipedema and obesity were randomized to either the LCD or control diet (energy prescription: 1200 kcal/day) for 8 weeks. Body weight and body composition, pain (Brief Pain Inventory measured pain), and QoL (RAND 36-Item Health Survey [RAND-36], Impact of Weight on Quality of Life [IWQOL]-Lite, and Lymphoedema Quality of Life [LYMQOL]) were measured at baseline and at postintervention. RESULTS A total of 70 female patients (age, mean [SD], 47 [11] years; BMI 37 [5] kg/m2) were included. The LCD group had greater weight loss (-2.8 kg; 95% CI: -4.1 to -1.0; p < 0.001) and larger reduction in pain now (-1.1; 95% CI: -1.9 to -0.3; p = 0.009) compared with the control group. No association was found between changes in pain now and weight loss. Both groups experienced improvements in several QoL dimensions. CONCLUSIONS Diet-induced weight loss in women with lipedema can improve QoL. An energy-restricted LCD seems to be superior to a standard control diet in reducing pain.
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Affiliation(s)
- Julianne Lundanes
- Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway
- Clinic of Surgery, Nord-Trøndelag Hospital Trust, Namsos Hospital, Namsos, Norway
| | - Frida Sandnes
- Department of Clinical Medicine, UiT The Arctic University of Norway, Tromsø, Norway
- Department of Nutrition and Speech-Language Therapy, Clinic of Rehabilitation, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway
| | - Kari Hanne Gjeilo
- Clinic of Cardiology, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway
- Department of Public Health and Nursing, Norwegian University of Science and Technology, Trondheim, Norway
| | - Patrik Hansson
- Department of Clinical Medicine, UiT The Arctic University of Norway, Tromsø, Norway
- Department of Food and Nutrition and Sport Science, University of Gothenburg, Gothenburg, Sweden
| | - Sissel Salater
- Regional Center for Obesity Research and Innovation (ObeCe), Department of Surgery, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway
| | - Catia Martins
- Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway
- Regional Center for Obesity Research and Innovation (ObeCe), Department of Surgery, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway
- Department of Nutrition Sciences, University of Alabama at Birmingham (UAB), Birmingham, Alabama, USA
| | - Siren Nymo
- Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway
- Clinic of Surgery, Nord-Trøndelag Hospital Trust, Namsos Hospital, Namsos, Norway
- Regional Center for Obesity Research and Innovation (ObeCe), Department of Surgery, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway
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Tagliabue A, Armeno M, Berk KA, Guglielmetti M, Ferraris C, Olieman J, van der Louw E. Ketogenic diet for epilepsy and obesity: Is it the same? Nutr Metab Cardiovasc Dis 2024; 34:581-589. [PMID: 38326186 DOI: 10.1016/j.numecd.2024.01.014] [Citation(s) in RCA: 8] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/01/2023] [Revised: 01/09/2024] [Accepted: 01/10/2024] [Indexed: 02/09/2024]
Abstract
The term "ketogenic diet" (KD) is used for a wide variety of diets with diverse indications ranging from obesity to neurological diseases, as if it was the same diet. This terminology is confusing for patients and the medical and scientific community. The term "ketogenic" diet implies a dietary regimen characterized by increased levels of circulating ketone bodies that should be measured in blood (beta-hydroxybutyrate), urine (acetoacetate) or breath (acetone) to verify the "ketogenic metabolic condition". Our viewpoint highlights that KDs used for epilepsy and obesity are not the same; the protocols aimed at weight loss characterized by low-fat, low-CHO and moderate/high protein content are not ketogenic by themselves but may become mildly ketogenic when high calorie restriction is applied. In contrast, there are standardized protocols for neurological diseases treatment for which ketosis has been established to be part of the mechanism of action. Therefore, in our opinion, the term ketogenic dietary therapy (KDT) should be reserved to the protocols considered for epilepsy and other neurological diseases, as suggested by the International Study Group in 2018. We propose to adjust the abbreviations in VLCHKD for Very Low CarboHydrate Ketogenic Diet and VLEKD for Very Low Energy Ketogenic Diet, to clarify the differences in dietary composition. We recommend that investigators describe the researchers describing efficacy or side effects of KDs, to clearly specify the dietary protocol used with its unique acronym and level of ketosis, when ketosis is considered as a component of the diet's mechanism of action.
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Affiliation(s)
- A Tagliabue
- Ketogenic Metabolic Therapy Laboratory, Department of Public Health Experimental and Forensic Medicine, University of Pavia, Italy
| | - M Armeno
- Ketogenic Diet Team Unit, Clinical Nutrition Department, Hospital Pediatría Prof Dr JP Garrahan, Buenos Aires, Argentina
| | - K A Berk
- Department of Internal Medicine, Division of Dietetics, Erasmus MC University Medical Centre Rotterdam, Rotterdam, the Netherlands
| | - M Guglielmetti
- Ketogenic Metabolic Therapy Laboratory, Department of Public Health Experimental and Forensic Medicine, University of Pavia, Italy.
| | - C Ferraris
- Ketogenic Metabolic Therapy Laboratory, Department of Public Health Experimental and Forensic Medicine, University of Pavia, Italy
| | - J Olieman
- Department of Internal Medicine, Division of Dietetics, Erasmus MC University Medical Centre Rotterdam, Rotterdam, the Netherlands
| | - E van der Louw
- Department of Internal Medicine, Division of Dietetics, Erasmus MC University Medical Centre Rotterdam, Rotterdam, the Netherlands
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7
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Abstract
Despite the emergence of stronger nutritional science over the past two decades, fad diets remain highly popular. However, growing medical evidence has led to the endorsement of healthy eating patterns by medical societies. This thus allows fad diets to be compared to the emerging scientific evidence as to which diets promote or damage health. In this narrative review, the most popular current fad diets are critically analyzed, including low-fat diets, vegan and vegetarian diets, low-carbohydrate diets, ketogenic diets, Paleolithic diets, and intermittent fasting. Each of these diets has some scientific merit, but each has potential deficiencies relative to the findings of nutritional science. This article also presents the common themes that emerge among the dietary guidance of leading health organizations, such as the American Heart Association and the American College of Lifestyle Medicine. While there are important distinctions between dietary recommendations emanating from various medical societies, each recommends eating more unrefined, plant-based foods, while eating fewer highly processed foods and added sugars, and avoiding excessive calorie consumption as an important nutritional strategy for the prevention and management of chronic conditions and promotion of overall health.
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Affiliation(s)
- Kayli Anderson
- Food as Medicine Course, The American College of Lifestyle Medicine, PO Box 1188, Salida, CO 81201, United States of America.
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8
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Sørlie V, De Soysa AK, Hyldmo ÅA, Retterstøl K, Martins C, Nymo S. Effect of a ketogenic diet on pain and quality of life in patients with lipedema: The LIPODIET pilot study. Obes Sci Pract 2022; 8:483-493. [PMID: 35949278 PMCID: PMC9358738 DOI: 10.1002/osp4.580] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2021] [Revised: 11/23/2021] [Accepted: 12/06/2021] [Indexed: 11/06/2022] Open
Abstract
Background Lipedema is an underdiagnosed condition in women, characterized by a symmetrical increase in subcutaneous adipose tissue (SAT) in the lower extremities, sparing the trunk. The lipedema SAT has been found to be resistant to diet, exercise and bariatric surgery, in regard to both weight loss (WL) and symptom relief. Current experience indicates that a low carbohydrate and high fat (LCHF-diet) might have a beneficial effect on weight and symptom management in lipedema. Objective To assess the impact of an eucaloric low carbohydrate, high fat (LCHF)-diet on pain and quality of life (QoL) in patients with lipedema. Methods Women diagnosed with lipedema, including all types and stages affecting the legs, (age 18-75 years, BMI 30-45 kg/m2) underwent 7 weeks of LCHF-diet and, thereafter 6 weeks of a diet following the Nordic nutrition recommendations. Pain (visual analog scale) and QoL (questionnaire for lymphedema of the limbs), weight and body composition were measured at baseline, week seven and 13. Results Nine women (BMI: 36.7 ± 4.5 kg/m2 and age: 46.9 ± 7 years) were recruited. The LCHF diet induced a significant WL -4.6 ± 0.7 kg (-4.5 ± 2.4%), p < 0.001 for both, and reduction in pain (-2.3 ± 0.4 cm, p = 0.020). No correlation was found between WL and changes in pain at week seven (r = 0.283, p = 0.460). WL was maintained between week seven and 13 (0.3 ± 0.7 kg, p = 0.430), but pain returned to baseline levels at week 13 (4.2 ± 0.7 cm, p = 0.690). A significant increase in general QoL was found between baseline and week seven (1.0 (95% CI (2.0, 0.001)), p = 0.050) and 13 (1.0 95% CI (2.0, 0.001) p = 0.050), respectively. Conclusion A LCHF-diet is associated with reduction in perceived pain and improvement in QoL, in patients with lipedema. Larger randomized clinical trials are needed to confirm these findings.
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Affiliation(s)
- Vilde Sørlie
- Department of NutritionInstitute of Basic Medical SciencesFaculty of MedicineUniversity of OsloOsloNorway
| | - Ann Kristin De Soysa
- Department of Clinical Nutrition and Speech PathologyClinic of Clinical ServicesSt. Olav Hospital—Trondheim University HospitalTrondheimNorway
| | - Åsne Ask Hyldmo
- Centre of Obesity Research and InnovationClinic of SurgerySt. Olav Hospital —Trondheim University HospitalTrondheimNorway
| | - Kjetil Retterstøl
- Department of NutritionInstitute of Basic Medical SciencesFaculty of MedicineUniversity of OsloOsloNorway
| | - Catia Martins
- Centre of Obesity Research and InnovationClinic of SurgerySt. Olav Hospital —Trondheim University HospitalTrondheimNorway
- Department of Clinical and Molecular MedicineCentre for Obesity ResearchFaculty of MedicineNorwegian of Science and TechnologyTrondheimNorway
| | - Siren Nymo
- Centre of Obesity Research and InnovationClinic of SurgerySt. Olav Hospital —Trondheim University HospitalTrondheimNorway
- Department of Clinical and Molecular MedicineCentre for Obesity ResearchFaculty of MedicineNorwegian of Science and TechnologyTrondheimNorway
- Namsos HospitalClinic of SurgeryNord‐Trondelag Hospital TrustNamsosNorway
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9
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Abstract
Obesity remains a serious relevant public health concern throughout the world despite related countermeasures being well understood (i.e. mainly physical activity and an adjusted diet). Among different nutritional approaches, there is a growing interest in ketogenic diets (KD) to manipulate body mass (BM) and to enhance fat mass loss. KD reduce the daily amount of carbohydrate intake drastically. This results in increased fatty acid utilisation, leading to an increase in blood ketone bodies (acetoacetate, 3-β-hydroxybutyrate and acetone) and therefore metabolic ketosis. For many years, nutritional intervention studies have focused on reducing dietary fat with little or conflicting positive results over the long term. Moreover, current nutritional guidelines for athletes propose carbohydrate-based diets to augment muscular adaptations. This review discusses the physiological basis of KD and their effects on BM reduction and body composition improvements in sedentary individuals combined with different types of exercise (resistance training or endurance training) in individuals with obesity and athletes. Ultimately, we discuss the strengths and the weaknesses of these nutritional interventions together with precautionary measures that should be observed in both individuals with obesity and athletic populations. A literature search from 1921 to April 2021 using Medline, Google Scholar, PubMed, Web of Science, Scopus and Sportdiscus Databases was used to identify relevant studies. In summary, based on the current evidence, KD are an efficient method to reduce BM and body fat in both individuals with obesity and athletes. However, these positive impacts are mainly because of the appetite suppressive effects of KD, which can decrease daily energy intake. Therefore, KD do not have any superior benefits to non-KD in BM and body fat loss in individuals with obesity and athletic populations in an isoenergetic situation. In sedentary individuals with obesity, it seems that fat-free mass (FFM) changes appear to be as great, if not greater, than decreases following a low-fat diet. In terms of lean mass, it seems that following a KD can cause FFM loss in resistance-trained individuals. In contrast, the FFM-preserving effects of KD are more efficient in endurance-trained compared with resistance-trained individuals.
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10
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Naude CE, Brand A, Schoonees A, Nguyen KA, Chaplin M, Volmink J. Low-carbohydrate versus balanced-carbohydrate diets for reducing weight and cardiovascular risk. Cochrane Database Syst Rev 2022; 1:CD013334. [PMID: 35088407 PMCID: PMC8795871 DOI: 10.1002/14651858.cd013334.pub2] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
BACKGROUND Debates on effective and safe diets for managing obesity in adults are ongoing. Low-carbohydrate weight-reducing diets (also known as 'low-carb diets') continue to be widely promoted, marketed and commercialised as being more effective for weight loss, and healthier, than 'balanced'-carbohydrate weight-reducing diets. OBJECTIVES To compare the effects of low-carbohydrate weight-reducing diets to weight-reducing diets with balanced ranges of carbohydrates, in relation to changes in weight and cardiovascular risk, in overweight and obese adults without and with type 2 diabetes mellitus (T2DM). SEARCH METHODS We searched MEDLINE (PubMed), Embase (Ovid), the Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science Core Collection (Clarivate Analytics), ClinicalTrials.gov and WHO International Clinical Trials Registry Platform (ICTRP) up to 25 June 2021, and screened reference lists of included trials and relevant systematic reviews. Language or publication restrictions were not applied. SELECTION CRITERIA We included randomised controlled trials (RCTs) in adults (18 years+) who were overweight or living with obesity, without or with T2DM, and without or with cardiovascular conditions or risk factors. Trials had to compare low-carbohydrate weight-reducing diets to balanced-carbohydrate (45% to 65% of total energy (TE)) weight-reducing diets, have a weight-reducing phase of 2 weeks or longer and be explicitly implemented for the primary purpose of reducing weight, with or without advice to restrict energy intake. DATA COLLECTION AND ANALYSIS: Two review authors independently screened titles and abstracts and full-text articles to determine eligibility; and independently extracted data, assessed risk of bias using RoB 2 and assessed the certainty of the evidence using GRADE. We stratified analyses by participants without and with T2DM, and by diets with weight-reducing phases only and those with weight-reducing phases followed by weight-maintenance phases. Primary outcomes were change in body weight (kg) and the number of participants per group with weight loss of at least 5%, assessed at short- (three months to < 12 months) and long-term (≥ 12 months) follow-up. MAIN RESULTS We included 61 parallel-arm RCTs that randomised 6925 participants to either low-carbohydrate or balanced-carbohydrate weight-reducing diets. All trials were conducted in high-income countries except for one in China. Most participants (n = 5118 randomised) did not have T2DM. Mean baseline weight across trials was 95 kg (range 66 to 132 kg). Participants with T2DM were older (mean 57 years, range 50 to 65) than those without T2DM (mean 45 years, range 22 to 62). Most trials included men and women (42/61; 3/19 men only; 16/19 women only), and people without baseline cardiovascular conditions, risk factors or events (36/61). Mean baseline diastolic blood pressure (DBP) and low-density lipoprotein (LDL) cholesterol across trials were within normal ranges. The longest weight-reducing phase of diets was two years in participants without and with T2DM. Evidence from studies with weight-reducing phases followed by weight-maintenance phases was limited. Most trials investigated low-carbohydrate diets (> 50 g to 150 g per day or < 45% of TE; n = 42), followed by very low (≤ 50 g per day or < 10% of TE; n = 14), and then incremental increases from very low to low (n = 5). The most common diets compared were low-carbohydrate, balanced-fat (20 to 35% of TE) and high-protein (> 20% of TE) treatment diets versus control diets balanced for the three macronutrients (24/61). In most trials (45/61) the energy prescription or approach used to restrict energy intake was similar in both groups. We assessed the overall risk of bias of outcomes across trials as predominantly high, mostly from bias due to missing outcome data. Using GRADE, we assessed the certainty of evidence as moderate to very low across outcomes. Participants without and with T2DM lost weight when following weight-reducing phases of both diets at the short (range: 12.2 to 0.33 kg) and long term (range: 13.1 to 1.7 kg). In overweight and obese participants without T2DM: low-carbohydrate weight-reducing diets compared to balanced-carbohydrate weight-reducing diets (weight-reducing phases only) probably result in little to no difference in change in body weight over three to 8.5 months (mean difference (MD) -1.07 kg, (95% confidence interval (CI) -1.55 to -0.59, I2 = 51%, 3286 participants, 37 RCTs, moderate-certainty evidence) and over one to two years (MD -0.93 kg, 95% CI -1.81 to -0.04, I2 = 40%, 1805 participants, 14 RCTs, moderate-certainty evidence); as well as change in DBP and LDL cholesterol over one to two years. The evidence is very uncertain about whether there is a difference in the number of participants per group with weight loss of at least 5% at one year (risk ratio (RR) 1.11, 95% CI 0.94 to 1.31, I2 = 17%, 137 participants, 2 RCTs, very low-certainty evidence). In overweight and obese participants with T2DM: low-carbohydrate weight-reducing diets compared to balanced-carbohydrate weight-reducing diets (weight-reducing phases only) probably result in little to no difference in change in body weight over three to six months (MD -1.26 kg, 95% CI -2.44 to -0.09, I2 = 47%, 1114 participants, 14 RCTs, moderate-certainty evidence) and over one to two years (MD -0.33 kg, 95% CI -2.13 to 1.46, I2 = 10%, 813 participants, 7 RCTs, moderate-certainty evidence); as well in change in DBP, HbA1c and LDL cholesterol over 1 to 2 years. The evidence is very uncertain about whether there is a difference in the number of participants per group with weight loss of at least 5% at one to two years (RR 0.90, 95% CI 0.68 to 1.20, I2 = 0%, 106 participants, 2 RCTs, very low-certainty evidence). Evidence on participant-reported adverse effects was limited, and we could not draw any conclusions about these. AUTHORS' CONCLUSIONS: There is probably little to no difference in weight reduction and changes in cardiovascular risk factors up to two years' follow-up, when overweight and obese participants without and with T2DM are randomised to either low-carbohydrate or balanced-carbohydrate weight-reducing diets.
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Affiliation(s)
- Celeste E Naude
- Centre for Evidence-based Health Care, Division of Epidemiology and Biostatistics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa
| | - Amanda Brand
- Centre for Evidence-based Health Care, Division of Epidemiology and Biostatistics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa
| | - Anel Schoonees
- Centre for Evidence-based Health Care, Division of Epidemiology and Biostatistics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa
| | - Kim A Nguyen
- Centre for Evidence-based Health Care, Division of Epidemiology and Biostatistics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa
| | - Marty Chaplin
- Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, UK
| | - Jimmy Volmink
- Centre for Evidence-based Health Care, Division of Epidemiology and Biostatistics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa
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11
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Mass recovery following caloric restriction reverses lipolysis and proteolysis, but not gluconeogenesis, in insulin resistant OLETF rats. PLoS One 2021; 16:e0252360. [PMID: 34727112 PMCID: PMC8562784 DOI: 10.1371/journal.pone.0252360] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2021] [Accepted: 10/18/2021] [Indexed: 11/19/2022] Open
Abstract
Caloric restriction (CR) is one of the most important behavioral interventions to reduce excessive abdominal adiposity, which is a risk factor for the development of insulin resistance. Previous metabolomics studies have characterized substrate metabolism during healthy conditions; however, the effects of CR and subsequent mass recovery on shifts in substrate metabolism during insulin resistance (IR) have not been widely investigated. To assess the effects of acute CR and the subsequent mass recovery on shifts in substrate metabolism, a cohort of 15-week old Long Evans Tokushima Otsuka (LETO) and Otsuka Long Evans Tokushima Fatty (OLETF) rats were calorie restricted (CR: 50% × 10 days) with or without partial body mass recovery (PR; 73% x 7 days), along with their respective ad libitum controls. End-of-study plasma samples were analyzed for primary carbon metabolites by gas chromatography (GC) time-of-flight (TOF) mass spectrometry (MS) data acquisition. Data analysis included PCA, Pearson correlation vs previously reported variables (adipose and body masses, and insulin resistance index, IRI), and metabolomics maps (MetaMapp) generated for the most significant group comparisons. All treatments elicited a significant group differentiation in at least one principal component. CR improved TCA cycle in OLETF, and increased lipolysis and proteolysis. These changes were reversed after PR except for gluconeogenesis. Plasma lipid concentrations were inversely correlated to IRI in LETO, but not OLETF. These shifts in substrate metabolism suggest that the CR-induced decreases in adipose may not be sufficient to more permanently alter substrate metabolism to improve IR status during metabolic syndrome.
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12
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Volek JS, Phinney SD, Krauss RM, Johnson RJ, Saslow LR, Gower B, Yancy WS, King JC, Hecht FM, Teicholz N, Bistrian BR, Hamdy O. Alternative Dietary Patterns for Americans: Low-Carbohydrate Diets. Nutrients 2021; 13:3299. [PMID: 34684300 PMCID: PMC8537012 DOI: 10.3390/nu13103299] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2021] [Revised: 09/04/2021] [Accepted: 09/09/2021] [Indexed: 12/11/2022] Open
Abstract
The decades-long dietary experiment embodied in the Dietary Guidelines for Americans (DGA) focused on limiting fat, especially saturated fat, and higher carbohydrate intake has coincided with rapidly escalating epidemics of obesity and type 2 diabetes (T2D) that are contributing to the progression of cardiovascular disease (CVD) and other diet-related chronic diseases. Moreover, the lack of flexibility in the DGA as it pertains to low carbohydrate approaches does not align with the contemporary trend toward precision nutrition. We argue that personalizing the level of dietary carbohydrate should be a high priority based on evidence that Americans have a wide spectrum of metabolic variability in their tolerance to high carbohydrate loads. Obesity, metabolic syndrome, and T2D are conditions strongly associated with insulin resistance, a condition exacerbated by increased dietary carbohydrate and improved by restricting carbohydrate. Low-carbohydrate diets are grounded across the time-span of human evolution, have well-established biochemical principles, and are now supported by multiple clinical trials in humans that demonstrate consistent improvements in multiple established risk factors associated with insulin resistance and cardiovascular disease. The American Diabetes Association (ADA) recently recognized a low carbohydrate eating pattern as an effective approach for patients with diabetes. Despite this evidence base, low-carbohydrate diets are not reflected in the DGA. As the DGA Dietary Patterns have not been demonstrated to be universally effective in addressing the needs of many Americans and recognizing the lack of widely available treatments for obesity, metabolic syndrome, and T2D that are safe, effective, and sustainable, the argument for an alternative, low-carbohydrate Dietary Pattern is all the more compelling.
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Affiliation(s)
- Jeff S. Volek
- Department of Human Sciences, Ohio State University, Columbus, OH 43017, USA
| | | | - Ronald M. Krauss
- Departments of Pediatrics and Medicine, University of California, San Francisco, CA 94143, USA;
| | - Richard J. Johnson
- Division of Renal Diseases and Hypertension, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA;
| | - Laura R. Saslow
- Department of Behavior & Biological Sciences, University of Michigan, Ann Arbor, MI 48109, USA;
| | - Barbara Gower
- Department of Nutrition Sciences, University of Alabama, Birmingham, AL 35233, USA;
| | - William S. Yancy
- Department of Medicine, Lifestyle and Weight Management Center, Duke University, Durham, NC 27705, USA;
| | - Janet C. King
- Department of Nutritional Sciences & Toxicology, University of California, Berkley, CA 94720, USA;
| | - Frederick M. Hecht
- Osher Center for Integrative Medicine, University of California San Francisco, San Francisco, CA 94115, USA;
| | | | | | - Osama Hamdy
- Joslin Diabetes Center, Harvard Medical School, Boston, MA 02215, USA;
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13
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Guan D, Lazar MA. Interconnections between circadian clocks and metabolism. J Clin Invest 2021; 131:e148278. [PMID: 34338232 DOI: 10.1172/jci148278] [Citation(s) in RCA: 85] [Impact Index Per Article: 21.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
Circadian rhythms evolved through adaptation to daily light/dark changes in the environment; they are believed to be regulated by the core circadian clock interlocking feedback loop. Recent studies indicate that each core component executes general and specific functions in metabolism. Here, we review the current understanding of the role of these core circadian clock genes in the regulation of metabolism using various genetically modified animal models. Additionally, emerging evidence shows that exposure to environmental stimuli, such as artificial light, unbalanced diet, mistimed eating, and exercise, remodels the circadian physiological processes and causes metabolic disorders. This Review summarizes the reciprocal regulation between the circadian clock and metabolism, highlights remaining gaps in knowledge about the regulation of circadian rhythms and metabolism, and examines potential applications to human health and disease.
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Affiliation(s)
- Dongyin Guan
- Institute for Diabetes, Obesity, and Metabolism.,Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, and
| | - Mitchell A Lazar
- Institute for Diabetes, Obesity, and Metabolism.,Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, and.,Department of Genetics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA
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14
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Escalante G, Stevenson SW, Barakat C, Aragon AA, Schoenfeld BJ. Peak week recommendations for bodybuilders: an evidence based approach. BMC Sports Sci Med Rehabil 2021; 13:68. [PMID: 34120635 PMCID: PMC8201693 DOI: 10.1186/s13102-021-00296-y] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2021] [Accepted: 06/02/2021] [Indexed: 01/10/2023]
Abstract
Bodybuilding is a competitive endeavor where a combination of muscle size, symmetry, "conditioning" (low body fat levels), and stage presentation are judged. Success in bodybuilding requires that competitors achieve their peak physique during the day of competition. To this end, competitors have been reported to employ various peaking interventions during the final days leading to competition. Commonly reported peaking strategies include altering exercise and nutritional regimens, including manipulation of macronutrient, water, and electrolyte intake, as well as consumption of various dietary supplements. The primary goals for these interventions are to maximize muscle glycogen content, minimize subcutaneous water, and reduce the risk abdominal bloating to bring about a more aesthetically pleasing physique. Unfortunately, there is a dearth of evidence to support the commonly reported practices employed by bodybuilders during peak week. Hence, the purpose of this article is to critically review the current literature as to the scientific support for pre-contest peaking protocols most commonly employed by bodybuilders and provide evidence-based recommendations as safe and effective strategies on the topic.
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Affiliation(s)
- Guillermo Escalante
- Department of Kinesiology, California State University- San Bernardino, CA San Bernardino, USA
| | | | - Christopher Barakat
- Competitive Breed LLC, FL Tampa, USA
- Human Performance Laboratory, The University of Tampa, FL Tampa, USA
| | - Alan A. Aragon
- Department of Family and Consumer Sciences, California State University- Northridge, Los Angeles, CA USA
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15
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Wrzosek M, Woźniak J, Włodarek D. The effect of high-fat versus high-carb diet on body composition in strength-trained males. Food Sci Nutr 2021; 9:2541-2548. [PMID: 34026070 PMCID: PMC8116875 DOI: 10.1002/fsn3.2204] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2020] [Revised: 02/07/2021] [Accepted: 02/09/2021] [Indexed: 11/17/2022] Open
Abstract
Low-fat, high-carb (LFHC) and low-carb, high-fat (LCHF) diets change body composition as a consequence of the reduction of body fat of overweight persons. The aim of this study is the assessment of the impact of LFHC and LCHF diets on body composition of men of a healthy body mass who do strength sports while maintaining the appropriate calorific value in a diet and protein intake. The research involved 55 men aged 19-35, with an average BMI of 24.01 ± 1.17 (min. 20.1, max. 26.1). The participants were divided into two groups following two interventional diets: high-fat diet or high-carb diet, for 12 weeks. The body composition of the participants was measured using bioimpedance. After the 12-week-long experiment based on the low-carbohydrate diet, a significant body mass reduction of 1.5% was observed. In the group, following the LFHC diet, the parameters did not significantly change. In the group following LCHF diet, the body fat reduction of 8.6% from 14 (6.7-19.8) kg to 12.7 (3.9-19.2) was reported (p = 0.01) (in the absolute value of 1.2 kg). However, also in the LFHC group, the body fat mass was significantly reduced, that is, by 1.5% (p = 0.01) (by 0.4 kg). Nevertheless, it is worth emphasizing that despite significant changes within the groups, these changes were not statistically significant between the groups. Diets with different carbohydrate and fat intake and the energy value covering the energy needs of men training strength sports have similar impact on changes in body composition.
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Affiliation(s)
- Michał Wrzosek
- Department of DieteticsInstitute of Human Nutrition SciencesWarsaw University of Life Sciences (WULS—SGGW)WarsawPoland
| | - Jakub Woźniak
- Department of DieteticsInstitute of Human Nutrition SciencesWarsaw University of Life Sciences (WULS—SGGW)WarsawPoland
| | - Dariusz Włodarek
- Department of DieteticsInstitute of Human Nutrition SciencesWarsaw University of Life Sciences (WULS—SGGW)WarsawPoland
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16
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Buga A, Kackley ML, Crabtree CD, Sapper TN, Mccabe L, Fell B, LaFountain RA, Hyde PN, Martini ER, Bowman J, Pan Y, Scandling D, Brownlow ML, O'Connor A, Simonetti OP, Kraemer WJ, Volek JS. The Effects of a 6-Week Controlled, Hypocaloric Ketogenic Diet, With and Without Exogenous Ketone Salts, on Body Composition Responses. Front Nutr 2021; 8:618520. [PMID: 33869263 PMCID: PMC8044842 DOI: 10.3389/fnut.2021.618520] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2020] [Accepted: 02/23/2021] [Indexed: 01/16/2023] Open
Abstract
Background: Ketogenic diets (KDs) that elevate beta-hydroxybutyrate (BHB) promote weight and fat loss. Exogenous ketones, such as ketone salts (KS), also elevate BHB concentrations with the potential to protect against muscle loss during caloric restriction. Whether augmenting ketosis with KS impacts body composition responses to a well-formulated KD remains unknown. Purpose: To explore the effects of energy-matched, hypocaloric KD feeding (<50 g carbohydrates/day; 1.5 g/kg/day protein), with and without the inclusion of KS, on weight loss and body composition responses. Methods: Overweight and obese adults were provided a precisely defined hypocaloric KD (~75% of energy expenditure) for 6 weeks. In a double-blind manner, subjects were randomly assigned to receive ~24 g/day of a racemic BHB-salt (KD + KS; n = 12) or placebo (KD + PL; n = 13). A matched comparison group (n = 12) was separately assigned to an isoenergetic/isonitrogenous low-fat diet (LFD). Body composition parameters were assessed by dual x-ray absorptiometry and magnetic resonance imaging. Results: The KD induced nutritional ketosis (>1.0 mM capillary BHB) throughout the study (p < 0.001), with higher fasting concentrations observed in KD + KS than KD + PL for the first 2 weeks (p < 0.05). There were decreases in body mass, whole body fat and lean mass, mid-thigh muscle cross-sectional area, and both visceral and subcutaneous adipose tissues (p < 0.001), but no group differences between the two KDs or with the LFD. Urine nitrogen excretion was significantly higher in KD + PL than LFD (p < 0.01) and trended higher in KD + PL compared to KD + KS (p = 0.076), whereas the nitrogen excretion during KD + KS was similar to LFD (p > 0.05). Conclusion: Energy-matched hypocaloric ketogenic diets favorably affected body composition but were not further impacted by administration of an exogenous BHB-salt that augmented ketosis. The trend for less nitrogen loss with the BHB-salt, if manifested over a longer period of time, may contribute to preserved lean mass.
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Affiliation(s)
- Alex Buga
- Department of Human Sciences, The Ohio State University, Columbus, OH, United States
| | - Madison L. Kackley
- Department of Human Sciences, The Ohio State University, Columbus, OH, United States
| | | | - Teryn N. Sapper
- Department of Human Sciences, The Ohio State University, Columbus, OH, United States
| | - Lauren Mccabe
- Department of Human Sciences, The Ohio State University, Columbus, OH, United States
| | - Brandon Fell
- Department of Human Sciences, The Ohio State University, Columbus, OH, United States
| | - Rich A. LaFountain
- Department of Human Sciences, The Ohio State University, Columbus, OH, United States
| | - Parker N. Hyde
- Department of Human Sciences, The Ohio State University, Columbus, OH, United States
| | - Emily R. Martini
- Department of Human Sciences, The Ohio State University, Columbus, OH, United States
| | - Jessica Bowman
- Department of Human Sciences, The Ohio State University, Columbus, OH, United States
| | - Yue Pan
- Department of Radiology, Davis Heart & Lung Research Institute, The Ohio State University, Columbus, OH, United States
- Division of Cardiovascular Medicine, Department of Internal Medicine, The Ohio State University, Columbus, OH, United States
- Department of Radiology, Wexner Medical Center, The Ohio State University, Columbus, OH, United States
| | - Debbie Scandling
- Department of Radiology, Davis Heart & Lung Research Institute, The Ohio State University, Columbus, OH, United States
- Division of Cardiovascular Medicine, Department of Internal Medicine, The Ohio State University, Columbus, OH, United States
- Department of Radiology, Wexner Medical Center, The Ohio State University, Columbus, OH, United States
| | - Milene L. Brownlow
- Research and Development Department, Metagenics, Inc., Aliso Viejo, CA, United States
| | - Annalouise O'Connor
- Research and Development Department, Metagenics, Inc., Aliso Viejo, CA, United States
| | - Orlando P. Simonetti
- Department of Radiology, Davis Heart & Lung Research Institute, The Ohio State University, Columbus, OH, United States
- Division of Cardiovascular Medicine, Department of Internal Medicine, The Ohio State University, Columbus, OH, United States
- Department of Radiology, Wexner Medical Center, The Ohio State University, Columbus, OH, United States
| | - William J. Kraemer
- Department of Human Sciences, The Ohio State University, Columbus, OH, United States
| | - Jeff S. Volek
- Department of Human Sciences, The Ohio State University, Columbus, OH, United States
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17
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Petrisko M, Kloss R, Bradley P, Birrenkott E, Spindler A, Clayton ZS, Kern M. Biochemical, Anthropometric, and Physiological Responses to Carbohydrate-Restricted Diets Versus a Low-Fat Diet in Obese Adults: A Randomized Crossover Trial. J Med Food 2020; 23:206-214. [PMID: 32119803 DOI: 10.1089/jmf.2019.0266] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023] Open
Abstract
Some research supports high-fat carbohydrate (CHO)-restricted diets for weight and fat loss and improvement of cardiovascular disease risk factors. To test this, a randomized crossover study was designed. Subjects (17 obese men and women [BMI: 30-38 kg/m2]) were fed three diets (supplying 1600 and 2200 kilocalories (kcal)/day for women and men, respectively) for 4 weeks, with each trial separated by 4-week washout periods. One CHO-restricted diet (10% CHO, 50% fat, and 40% protein content) was rich in plant foods and mushrooms, while the other CHO-restricted diet included more animal foods (10% CHO, 60% fat, and 30% protein content). The third diet was lower in fat and protein content (LF) and higher in CHOs (61% CHO, 21% fat, and 18% protein content). Body composition was assessed through hydrostatic weighing before and after each diet trial. Fasting blood samples were collected weekly for analysis of hormones and lipids. Data were analyzed through repeated measures analysis of variance with post hoc paired comparison t-tests. Weight and fat loss were similar (P > .05) among trials. Subjects lost lean mass (P < .05) during CHO-restricted trials, but not in the LF trial. Insulin concentrations decreased (P < .05) during the CHO-restricted trial and tended (P = .05) to decrease during the LF trial. Total cholesterol decreased (P < .05) for all trials; however, high-density lipoprotein cholesterol decreased (P < .05) and triacylglycerols were higher (P < .05) following the LF trial. Taken together, energy restriction regardless of diet composition promoted similar weight loss; however, CHO-restricted diets based on either plants/mushrooms or animal foods elicited a more beneficial lipid-altering effect in comparison with the LF diet.
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Affiliation(s)
- Mayumi Petrisko
- School of Exercise and Nutritional Sciences, San Diego State University, San Diego, California, USA
| | - Rebecca Kloss
- School of Exercise and Nutritional Sciences, San Diego State University, San Diego, California, USA
| | - Patricia Bradley
- School of Exercise and Nutritional Sciences, San Diego State University, San Diego, California, USA
| | - Erika Birrenkott
- School of Exercise and Nutritional Sciences, San Diego State University, San Diego, California, USA
| | - Audrey Spindler
- School of Exercise and Nutritional Sciences, San Diego State University, San Diego, California, USA
| | - Zachary S Clayton
- School of Exercise and Nutritional Sciences, San Diego State University, San Diego, California, USA
| | - Mark Kern
- School of Exercise and Nutritional Sciences, San Diego State University, San Diego, California, USA
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18
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Kirkpatrick CF, Bolick JP, Kris-Etherton PM, Sikand G, Aspry KE, Soffer DE, Willard KE, Maki KC. Review of current evidence and clinical recommendations on the effects of low-carbohydrate and very-low-carbohydrate (including ketogenic) diets for the management of body weight and other cardiometabolic risk factors: A scientific statement from the National Lipid Association Nutrition and Lifestyle Task Force. J Clin Lipidol 2019; 13:689-711.e1. [PMID: 31611148 DOI: 10.1016/j.jacl.2019.08.003] [Citation(s) in RCA: 236] [Impact Index Per Article: 39.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2019] [Accepted: 08/13/2019] [Indexed: 02/06/2023]
Abstract
Historically, low-carbohydrate (CHO) and very-low-CHO diets have been used for weight loss. Recently, these diets have been promoted for type 2 diabetes (T2D) management. This scientific statement provides a comprehensive review of the current evidence base available from recent systematic reviews and meta-analyses on the effects of low-CHO and very-low-CHO diets on body weight, lipoprotein lipids, glycemic control, and other cardiometabolic risk factors. In addition, evidence on emerging risk factors and potential safety concerns of low-CHO and very-low-CHO diets, especially for high-risk individuals, such as those with genetic lipid disorders, was reviewed. Based on the evidence reviewed, low-CHO and very-low-CHO diets are not superior to other dietary approaches for weight loss. These diets may have advantages related to appetite control, triglyceride reduction, and reduction in the use of medication in T2D management. The evidence reviewed showed mixed effects on low-density lipoprotein cholesterol levels with some studies showing an increase. There was no clear evidence for advantages regarding effects on other cardiometabolic risk markers. Minimal data are available regarding long-term (>2 years) efficacy and safety. Clinicians are encouraged to consider the evidence discussed in this scientific statement when counseling patients on the use of low-CHO and very-low-CHO diets.
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Affiliation(s)
- Carol F Kirkpatrick
- Wellness Center, Kasiska Division of Health Sciences, Idaho State University, Pocatello, ID, USA.
| | - Julie P Bolick
- Dietitian Nutritionist Specialist II and Clinical Lipid Specialist, Intermountain Health Care, Live Well Center, Salt Lake City, UT, USA
| | - Penny M Kris-Etherton
- Distinguished Professor of Nutrition, Department of Nutritional Sciences, The Pennsylvania State University, University Park, PA, USA
| | - Geeta Sikand
- Associate Clinical Professor of Medicine (Cardiology Division) and Director of Nutrition, University of California Irvine Preventive Cardiology Program, Irvine, CA, USA
| | - Karen E Aspry
- Brown University Alpert Medical School, Lipid and Prevention Program, Lifespan Cardiovascular Institute, East Greenwich, RI, USA
| | - Daniel E Soffer
- University of Pennsylvania, Preventive Cardiology Heart and Vascular Center, Philadelphia, PA, USA
| | - Kaye-Eileen Willard
- Physician Advisor for Patient Quality and Safety, Ascension Wisconsin All Saints, Racine, WI, USA
| | - Kevin C Maki
- Midwest Biomedical Research, Center for Metabolic & Cardiovascular Health, Addison, IL, USA
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19
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Astley CM, Todd JN, Salem RM, Vedantam S, Ebbeling CB, Huang PL, Ludwig DS, Hirschhorn JN, Florez JC. Genetic Evidence That Carbohydrate-Stimulated Insulin Secretion Leads to Obesity. Clin Chem 2019; 64:192-200. [PMID: 29295838 DOI: 10.1373/clinchem.2017.280727] [Citation(s) in RCA: 60] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2017] [Accepted: 10/17/2017] [Indexed: 12/22/2022]
Abstract
BACKGROUND A fundamental precept of the carbohydrate-insulin model of obesity is that insulin secretion drives weight gain. However, fasting hyperinsulinemia can also be driven by obesity-induced insulin resistance. We used genetic variation to isolate and estimate the potentially causal effect of insulin secretion on body weight. METHODS Genetic instruments of variation of insulin secretion [assessed as insulin concentration 30 min after oral glucose (insulin-30)] were used to estimate the causal relationship between increased insulin secretion and body mass index (BMI), using bidirectional Mendelian randomization analysis of genome-wide association studies. Data sources included summary results from the largest published metaanalyses of predominantly European ancestry for insulin secretion (n = 26037) and BMI (n = 322154), as well as individual-level data from the UK Biobank (n = 138541). Data from the Cardiology and Metabolic Patient Cohort study at Massachusetts General Hospital (n = 1675) were used to validate genetic associations with insulin secretion and to test the observational association of insulin secretion and BMI. RESULTS Higher genetically determined insulin-30 was strongly associated with higher BMI (β = 0.098, P = 2.2 × 10-21), consistent with a causal role in obesity. Similar positive associations were noted in sensitivity analyses using other genetic variants as instrumental variables. By contrast, higher genetically determined BMI was not associated with insulin-30. CONCLUSIONS Mendelian randomization analyses provide evidence for a causal relationship of glucose-stimulated insulin secretion on body weight, consistent with the carbohydrate-insulin model of obesity.
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Affiliation(s)
- Christina M Astley
- Department of Medicine, Division of Endocrinology, Boston Children's Hospital, Boston, MA.,Departments of Medicine and Pediatrics, Harvard Medical School, Boston, MA.,Programs in Metabolism and Medical & Population Genetics, Broad Institute, Cambridge, MA
| | - Jennifer N Todd
- Department of Medicine, Division of Endocrinology, Boston Children's Hospital, Boston, MA.,Departments of Medicine and Pediatrics, Harvard Medical School, Boston, MA.,Programs in Metabolism and Medical & Population Genetics, Broad Institute, Cambridge, MA.,Diabetes Unit and Center for Genomic Medicine, Department of Medicine, Massachusetts General Hospital, Boston, MA
| | - Rany M Salem
- Department of Family Medicine and Public Health, University of California, San Diego, CA
| | - Sailaja Vedantam
- Department of Medicine, Division of Endocrinology, Boston Children's Hospital, Boston, MA.,Departments of Medicine and Pediatrics, Harvard Medical School, Boston, MA
| | - Cara B Ebbeling
- Department of Medicine, Division of Endocrinology, Boston Children's Hospital, Boston, MA.,Departments of Medicine and Pediatrics, Harvard Medical School, Boston, MA
| | - Paul L Huang
- Departments of Medicine and Pediatrics, Harvard Medical School, Boston, MA.,Cardiology Division, Department of Medicine, Massachusetts General Hospital, Boston, MA
| | - David S Ludwig
- Department of Medicine, Division of Endocrinology, Boston Children's Hospital, Boston, MA; .,Departments of Medicine and Pediatrics, Harvard Medical School, Boston, MA
| | - Joel N Hirschhorn
- Department of Medicine, Division of Endocrinology, Boston Children's Hospital, Boston, MA; .,Departments of Medicine and Pediatrics, Harvard Medical School, Boston, MA.,Programs in Metabolism and Medical & Population Genetics, Broad Institute, Cambridge, MA
| | - Jose C Florez
- Departments of Medicine and Pediatrics, Harvard Medical School, Boston, MA; .,Programs in Metabolism and Medical & Population Genetics, Broad Institute, Cambridge, MA.,Diabetes Unit and Center for Genomic Medicine, Department of Medicine, Massachusetts General Hospital, Boston, MA
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Ebbeling CB, Feldman HA, Klein GL, Wong JMW, Bielak L, Steltz SK, Luoto PK, Wolfe RR, Wong WW, Ludwig DS. Effects of a low carbohydrate diet on energy expenditure during weight loss maintenance: randomized trial. BMJ 2018; 363:k4583. [PMID: 30429127 PMCID: PMC6233655 DOI: 10.1136/bmj.k4583] [Citation(s) in RCA: 182] [Impact Index Per Article: 26.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 10/24/2018] [Indexed: 12/13/2022]
Abstract
OBJECTIVE To determine the effects of diets varying in carbohydrate to fat ratio on total energy expenditure. DESIGN Randomized trial. SETTING Multicenter collaboration at US two sites, August 2014 to May 2017. PARTICIPANTS 164 adults aged 18-65 years with a body mass index of 25 or more. INTERVENTIONS After 12% (within 2%) weight loss on a run-in diet, participants were randomly assigned to one of three test diets according to carbohydrate content (high, 60%, n=54; moderate, 40%, n=53; or low, 20%, n=57) for 20 weeks. Test diets were controlled for protein and were energy adjusted to maintain weight loss within 2 kg. To test for effect modification predicted by the carbohydrate-insulin model, the sample was divided into thirds of pre-weight loss insulin secretion (insulin concentration 30 minutes after oral glucose). MAIN OUTCOME MEASURES The primary outcome was total energy expenditure, measured with doubly labeled water, by intention-to-treat analysis. Per protocol analysis included participants who maintained target weight loss, potentially providing a more precise effect estimate. Secondary outcomes were resting energy expenditure, measures of physical activity, and levels of the metabolic hormones leptin and ghrelin. RESULTS Total energy expenditure differed by diet in the intention-to-treat analysis (n=162, P=0.002), with a linear trend of 52 kcal/d (95% confidence interval 23 to 82) for every 10% decrease in the contribution of carbohydrate to total energy intake (1 kcal=4.18 kJ=0.00418 MJ). Change in total energy expenditure was 91 kcal/d (95% confidence interval -29 to 210) greater in participants assigned to the moderate carbohydrate diet and 209 kcal/d (91 to 326) greater in those assigned to the low carbohydrate diet compared with the high carbohydrate diet. In the per protocol analysis (n=120, P<0.001), the respective differences were 131 kcal/d (-6 to 267) and 278 kcal/d (144 to 411). Among participants in the highest third of pre-weight loss insulin secretion, the difference between the low and high carbohydrate diet was 308 kcal/d in the intention-to-treat analysis and 478 kcal/d in the per protocol analysis (P<0.004). Ghrelin was significantly lower in participants assigned to the low carbohydrate diet compared with those assigned to the high carbohydrate diet (both analyses). Leptin was also significantly lower in participants assigned to the low carbohydrate diet (per protocol). CONCLUSIONS Consistent with the carbohydrate-insulin model, lowering dietary carbohydrate increased energy expenditure during weight loss maintenance. This metabolic effect may improve the success of obesity treatment, especially among those with high insulin secretion. TRIAL REGISTRATION ClinicalTrials.gov NCT02068885.
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Affiliation(s)
- Cara B Ebbeling
- New Balance Foundation Obesity Prevention Center, Division of Endocrinology, Boston Children's Hospital, 300 Longwood Avenue, Boston, MA 02115, USA
- Harvard Medical School, Boston, MA, USA
| | - Henry A Feldman
- Harvard Medical School, Boston, MA, USA
- Institutional Centers for Clinical and Translational Research, Boston Children's Hospital, Boston, MA, USA
| | - Gloria L Klein
- New Balance Foundation Obesity Prevention Center, Division of Endocrinology, Boston Children's Hospital, 300 Longwood Avenue, Boston, MA 02115, USA
| | - Julia M W Wong
- New Balance Foundation Obesity Prevention Center, Division of Endocrinology, Boston Children's Hospital, 300 Longwood Avenue, Boston, MA 02115, USA
- Harvard Medical School, Boston, MA, USA
| | - Lisa Bielak
- New Balance Foundation Obesity Prevention Center, Division of Endocrinology, Boston Children's Hospital, 300 Longwood Avenue, Boston, MA 02115, USA
| | - Sarah K Steltz
- New Balance Foundation Obesity Prevention Center, Division of Endocrinology, Boston Children's Hospital, 300 Longwood Avenue, Boston, MA 02115, USA
| | - Patricia K Luoto
- Department of Food and Nutrition, Framingham State University, Framingham, MA, USA
| | - Robert R Wolfe
- University of Arkansas for Medical Sciences, Little Rock, AR, USA
| | - William W Wong
- USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA
| | - David S Ludwig
- New Balance Foundation Obesity Prevention Center, Division of Endocrinology, Boston Children's Hospital, 300 Longwood Avenue, Boston, MA 02115, USA
- Harvard Medical School, Boston, MA, USA
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Abstract
Despite intensive research, the causes of the obesity epidemic remain incompletely understood and conventional calorie-restricted diets continue to lack long-term efficacy. According to the carbohydrate-insulin model (CIM) of obesity, recent increases in the consumption of processed, high-glycemic-load carbohydrates produce hormonal changes that promote calorie deposition in adipose tissue, exacerbate hunger, and lower energy expenditure. Basic and genetic research provides mechanistic evidence in support of the CIM. In animals, dietary composition has been clearly demonstrated to affect metabolism and body composition, independently of calorie intake, consistent with CIM predictions. Meta-analyses of behavioral trials report greater weight loss with reduced-glycemic load vs low-fat diets, though these studies characteristically suffer from poor long-term compliance. Feeding studies have lacked the rigor and duration to test the CIM, but the longest such studies tend to show metabolic advantages for low-glycemic load vs low-fat diets. Beyond the type and amount of carbohydrate consumed, the CIM provides a conceptual framework for understanding how many dietary and nondietary exposures might alter hormones, metabolism, and adipocyte biology in ways that could predispose to obesity. Pending definitive studies, the principles of a low-glycemic load diet offer a practical alternative to the conventional focus on dietary fat and calorie restriction.
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Affiliation(s)
- David S Ludwig
- The New Balance Foundation Obesity Prevention Center, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts
| | - Cara B Ebbeling
- The New Balance Foundation Obesity Prevention Center, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts
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Timeline of changes in adaptive physiological responses, at the level of energy expenditure, with progressive weight loss. Br J Nutr 2018; 120:141-149. [PMID: 29733003 PMCID: PMC6088538 DOI: 10.1017/s0007114518000922] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Diet-induced weight loss (WL) is associated with reduced resting and non-resting energy expenditure (EE), driven not only by changes in body composition but also potentially by adaptive thermogenesis (AT). When exactly this happens, during progressive WL, remains unknown. The aim of this study was to determine the timeline of changes in RMR and exercise-induced EE (EIEE), stemming from changes in body composition v. the presence of AT, during WL with a very-low-energy diet (VLED). In all, thirty-one adults (eighteen men) with obesity (BMI: 37 (sem 4·5) kg/m2; age: 43 (sem 10) years) underwent 8 weeks of a VLED, followed by 4 weeks of weight maintenance. Body weight and composition, RMR, net EIEE (10, 25 and 50 W) and AT (for RMR (ATRMR) and EIEE (ATEIEE)) were measured at baseline, day 3 (2 (sem 1) % WL), after 5 and 10 % WL and at weeks 9 (16 (sem 2) %) and 13 (16 (sem 1) %). RMR and fat mass were significantly reduced for the first time at 5 % WL (12 (sem 8) d) (P<0·01 and P<0·001, respectively) and EIEE at 10 % WL (32 (sem 8) d), for all levels of power (P<0·05), and sustained up to week 13. ATRMR was transiently present at 10 % WL (−460 (sem 690) kJ/d, P<0·01). A fall in RMR should be anticipated at ≥5 % WL and a reduction in EIEE at ≥10 % WL. Transient ATRMR can be expected at 10 % WL. These physiological adaptations may make progressive WL difficult and will probably contribute to relapse.
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A randomized controlled trial to evaluate the effects of high Protein Complete (l Acto) VEgeta Rian (PACER) diet in non-diabetic obese Asian Indians in North India. Heliyon 2018; 3:e00472. [PMID: 29387815 PMCID: PMC5772352 DOI: 10.1016/j.heliyon.2017.e00472] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2017] [Revised: 08/24/2017] [Accepted: 11/27/2017] [Indexed: 11/20/2022] Open
Abstract
In view of the increasing prevalence of obesity in largely vegetarian Asian Indians, it is important to research a high protein, low carbohydrate vegetarian diet. The present study was designed to evaluate the effects of a “High Protein Complete (lacto) VEgetaRian Diet (Acronym; ‘PACER diet’), on weight, body composition and metabolic profiles in non-diabetic obese Asian Indians living in north India. In this 8-week randomized control trial, 102 vegetarian subjects with body mass index (BMI) >25 kg/m2 were randomized to either a test diet (PACER diet; high protein, high fat and moderately low carbohydrate, lacto-vegetarian diet) or control diet (standard vegetarian diet formulated as the dietary guidelines for Asian Indians) after 4 weeks of diet and exercise run-in period. A standard exercise protocol was followed for both groups. Body weight, BMI, waist circumference (WC), blood pressure, fasting plasma glucose (FPG), fasting serum insulin and lipid profile were assessed before and after the intervention. There was significant weight loss along with improvements in cardio-metabolic risk factors among both the groups post intervention. Percent reductions in the intervention group for weight (6.1± 2.9; p < 0.001), WC (3.9 ± 1.7; p < 0.001), FPG (5.9 ± 3.2; p < 0.001), total cholesterol (10.2 ± 6.3: p < 0.001), serum triacylglycerol (13.6 ± 10.6; p < 0.001) and low-density lipoprotein cholesterol (11.9 ± 7.1; p < 0.001]) were significantly greater than the control diet group. In summary, intervention with a PACER diet (high protein, high fat and moderately low carbohydrate, lacto-vegetarian diet) showed significant improvement in weight loss, body composition and cardio-metabolic profile as compared to a standard vegetarian diet among obese Asian Indians in north India.
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24
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Dunn JP, Abumrad NN, Kessler RM, Patterson BW, Li R, Marks-Shulman P, Tamboli RA. Caloric Restriction-Induced Decreases in Dopamine Receptor Availability are Associated with Leptin Concentration. Obesity (Silver Spring) 2017; 25:1910-1915. [PMID: 28944597 PMCID: PMC5718041 DOI: 10.1002/oby.22023] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/30/2017] [Revised: 08/16/2017] [Accepted: 08/21/2017] [Indexed: 11/08/2022]
Abstract
OBJECTIVE It has been previously reported that early after Roux-en-Y-gastric bypass, dopamine (DA) type 2 and 3 receptor (D2/3R) binding potential (BPND ) was decreased from preoperative levels. The current study aimed to determine whether calorie restriction without weight loss modifies D2/3R BPND and whether such changes are explained by neuroendocrine regulation. METHODS Fifteen females with obesity (BMI = 39 ± 6 kg/m2 ) were studied before and after ∼10 days of a very-low-calorie-diet (VLCD). Outcome measures included fasting insulin, leptin, acyl ghrelin, and glucose, and insulin sensitivity and disposition index were estimated using the oral-minimal model (OMM) method. Participants underwent positron emission tomography scanning with the displaceable radioligand [18 F]fallypride to estimate available regional D2/3R levels. Regions of interest included the caudate, putamen, ventral striatum, hypothalamus, and substantia nigra (SN). RESULTS With the VLCD, weight decreased slightly (-3 kg). Insulin, glucose, and leptin decreased significantly, but there was no change in acyl ghrelin or measures from OMM. SN D2/3R BPND decreased significantly, with trends toward decreased levels in the remaining regions. The decrease in leptin concentration strongly predicted the change in D2/3R BPND in all regions (all P ≤ 0.004). CONCLUSIONS In obesity, reductions in regional D2/3R availability after VLCD are suggestive of increased endogenous DA competing with the radioligand. Changes in regional D2/3R availability were associated with decreases in leptin concentrations that occurred before clinically significant weight loss.
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Affiliation(s)
- Julia P. Dunn
- Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, U.S.A
- Veterans Administration St. Louis Health Care System, St. Louis, Missouri, U.S.A
| | - Naji N. Abumrad
- Department of Surgery, Vanderbilt University School of Medicine, Nashville, Tennessee, U.S.A
| | - Robert M. Kessler
- Department of Radiology, Vanderbilt University School of Medicine, Nashville, Tennessee, U.S.A
| | - Bruce W. Patterson
- Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, U.S.A
| | - Rui Li
- Department of Radiology, Vanderbilt University School of Medicine, Nashville, Tennessee, U.S.A
| | - Pamela Marks-Shulman
- Department of Surgery, Vanderbilt University School of Medicine, Nashville, Tennessee, U.S.A
| | - Robyn A. Tamboli
- Department of Surgery, Vanderbilt University School of Medicine, Nashville, Tennessee, U.S.A
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25
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Hall KD, Guo J. Obesity Energetics: Body Weight Regulation and the Effects of Diet Composition. Gastroenterology 2017; 152:1718-1727.e3. [PMID: 28193517 PMCID: PMC5568065 DOI: 10.1053/j.gastro.2017.01.052] [Citation(s) in RCA: 209] [Impact Index Per Article: 26.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/25/2016] [Revised: 01/19/2017] [Accepted: 01/23/2017] [Indexed: 12/14/2022]
Abstract
Weight changes are accompanied by imbalances between calorie intake and expenditure. This fact is often misinterpreted to suggest that obesity is caused by gluttony and sloth and can be treated by simply advising people to eat less and move more. Rather various components of energy balance are dynamically interrelated and weight loss is resisted by counterbalancing physiological processes. While low-carbohydrate diets have been suggested to partially subvert these processes by increasing energy expenditure and promoting fat loss, our meta-analysis of 32 controlled feeding studies with isocaloric substitution of carbohydrate for fat found that both energy expenditure (26 kcal/d; P <.0001) and fat loss (16 g/d; P <.0001) were greater with lower fat diets. We review the components of energy balance and the mechanisms acting to resist weight loss in the context of static, settling point, and set-point models of body weight regulation, with the set-point model being most commensurate with current data.
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26
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Coutinho SR, With E, Rehfeld JF, Kulseng B, Truby H, Martins C. The impact of rate of weight loss on body composition and compensatory mechanisms during weight reduction: A randomized control trial. Clin Nutr 2017; 37:1154-1162. [PMID: 28479016 DOI: 10.1016/j.clnu.2017.04.008] [Citation(s) in RCA: 41] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2016] [Revised: 03/29/2017] [Accepted: 04/10/2017] [Indexed: 11/29/2022]
Abstract
BACKGROUND & AIMS Rapid weight loss (WL) has been associated with a larger loss of fat free mass and a disproportional reduction in resting metabolic rate (RMR), but the evidence is inconclusive. We aimed to evaluate the impact of WL rate on body composition and compensatory mechanisms activated with WL (reduced RMR, increased exercise efficiency (ExEff) and appetite), both during negative and neutral energy balance (EB). METHODS Thirty-five participants with obesity were randomized to lose a similar weight rapidly (4 weeks) or gradually (8 weeks), and afterwards to maintain it (4 weeks). Body weight and composition, RMR, ExEff (10, 25 and 50 W), appetite feelings and appetite-regulating hormones (active ghrelin, cholecystokinin, total peptide YY (PYY), active glucagon-like peptide-1 and insulin), in fasting and every 30 min up to 2.5 h, were measured at baseline and after each phase. RESULTS Changes in body weight (≈9%) and composition were similar in both groups. With WL, RMR decreased and ExEff at 10 W increased significantly in the rapid WL group only. However, fasting hunger increased significantly with gradual WL only, while fasting and postprandial prospective food consumption, and postprandial hunger decreased (and postprandial fullness increased) significantly with rapid WL only. Basal total PYY, and basal and postprandial insulin decreased significantly, and similarly in both groups. After weight stabilization and no ketosis no differences between groups were found. CONCLUSIONS Despite differences while under negative EB, WL rate does not seem to have a significant impact on body composition or on compensatory mechanisms, once EB is reestablished. CLINICAL TRIAL REGISTRATION NUMBER NCT01912742 (the study was registered in clinicaltrial.gov).
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Affiliation(s)
- Sílvia Ribeiro Coutinho
- Obesity Research Group, Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
| | - Emilie With
- Obesity Research Group, Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway
| | - Jens F Rehfeld
- Department of Clinical Biochemistry, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
| | - Bård Kulseng
- Obesity Research Group, Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway; Centre for Obesity, Department of Surgery, St. Olav Hospital, Trondheim University Hospital, Trondheim, Norway
| | - Helen Truby
- Department of Food, Nutrition and Dietetics, Monash University, Melbourne, Australia
| | - Cátia Martins
- Obesity Research Group, Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway; Centre for Obesity, Department of Surgery, St. Olav Hospital, Trondheim University Hospital, Trondheim, Norway
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27
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Sipe LM, Yang C, Ephrem J, Garren E, Hirsh J, Deppmann CD. Differential sympathetic outflow to adipose depots is required for visceral fat loss in response to calorie restriction. Nutr Diabetes 2017; 7:e260. [PMID: 28394360 PMCID: PMC5436093 DOI: 10.1038/nutd.2017.13] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/23/2017] [Accepted: 02/01/2017] [Indexed: 01/10/2023] Open
Abstract
The sympathetic nervous system (SNS) regulates energy homeostasis in part by governing fatty acid liberation from adipose tissue. We first examined whether SNS activity toward discrete adipose depots changes in response to a weight loss diet in mice. We found that SNS activity toward each adipose depot is unique in timing, pattern of activation, and habituation with the most dramatic contrast between visceral and subcutaneous adipose depots. Sympathetic drive toward visceral epididymal adipose is more than doubled early in weight loss and then suppressed later in the diet when weight loss plateaued. Coincident with the decline in SNS activity toward visceral adipose is an increase in activity toward subcutaneous depots indicating a switch in lipolytic sources. In response to calorie restriction, SNS activity toward retroperitoneal and brown adipose depots is unaffected. Finally, pharmacological blockage of sympathetic activity on adipose tissue using the β3-adrenergic receptor antagonist, SR59230a, suppressed loss of visceral adipose mass in response to diet. These findings indicate that SNS activity toward discrete adipose depots is dynamic and potentially hierarchical. This pattern of sympathetic activation is required for energy liberation and loss of adipose tissue in response to calorie-restricted diet.
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Affiliation(s)
- L M Sipe
- Department of Biology, University of Virginia, Charlottesville, VA, USA
| | - C Yang
- Department of Biology, University of Virginia, Charlottesville, VA, USA
| | - J Ephrem
- Department of Biology, University of Virginia, Charlottesville, VA, USA
| | - E Garren
- Department of Biology, University of Virginia, Charlottesville, VA, USA
| | - J Hirsh
- Department of Biology, University of Virginia, Charlottesville, VA, USA
| | - C D Deppmann
- Department of Biology, University of Virginia, Charlottesville, VA, USA.,Department of Cell Biology, University of Virginia, Charlottesville, VA, USA.,Department of Biomedical Engineering, University of Virginia, Charlottesville, VA, USA.,Department of Neuroscience, University of Virginia, Charlottesville, VA, USA
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28
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Noakes TD, Windt J. Evidence that supports the prescription of low-carbohydrate high-fat diets: a narrative review. Br J Sports Med 2017; 51:133-139. [PMID: 28053201 DOI: 10.1136/bjsports-2016-096491] [Citation(s) in RCA: 102] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/21/2016] [Indexed: 12/15/2022]
Abstract
Low-carbohydrate high-fat (LCHF) diets are a highly contentious current topic in nutrition. This narrative review aims to provide clinicians with a broad overview of the effects of LCHF diets on body weight, glycaemic control and cardiovascular risk factors while addressing some common concerns and misconceptions. Blood total cholesterol and LDL-cholesterol concentrations show a variable, highly individual response to LCHF diets, and should be monitored in patients adhering to this diet. In contrast, available evidence from clinical and preclinical studies indicates that LCHF diets consistently improve all other markers of cardiovascular risk-lowering elevated blood glucose, insulin, triglyceride, ApoB and saturated fat (especially palmitoleic acid) concentrations, reducing small dense LDL particle numbers, glycated haemoglobin (HbA1c) levels, blood pressure and body weight while increasing low HDL-cholesterol concentrations and reversing non-alcoholic fatty liver disease (NAFLD). This particular combination of favourable modifications to all these risk factors is a benefit unique to LCHF diets. These effects are likely due in part to reduced hunger and decreased ad libitum calorie intake common to low-carbohydrate diets, allied to a reduction in hyperinsulinaemia, and reversal of NAFLD. Although LCHF diets may not be suitable for everyone, available evidence shows this eating plan to be a safe and efficacious dietary option to be considered. LCHF diets may also be particularly beneficial in patients with atherogenic dyslipidaemia, insulin resistance, and the frequently associated NAFLD.
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Affiliation(s)
- Timothy David Noakes
- Department of Human Biology, University of Cape Town, Sports Science Institute of South Africa, Newlands, Cape Town, South Africa
| | - Johann Windt
- Department of Experimental Medicine, University of British Columbia, Vancouver, British Columbia, Canada.,Centre for Hip Health and Mobility, University of British Columbia, Vancouver, British Columbia, Canada
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Urbain P, Strom L, Morawski L, Wehrle A, Deibert P, Bertz H. Impact of a 6-week non-energy-restricted ketogenic diet on physical fitness, body composition and biochemical parameters in healthy adults. Nutr Metab (Lond) 2017; 14:17. [PMID: 28239404 PMCID: PMC5319032 DOI: 10.1186/s12986-017-0175-5] [Citation(s) in RCA: 68] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2016] [Accepted: 02/16/2017] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND The ketogenic diet (KD) is a very low-carbohydrate, high-fat and adequate-protein diet that without limiting calories induces different metabolic adaptations, eg, increased levels of circulating ketone bodies and a shift to lipid metabolism. Our objective was to assess the impact of a 6-week non-energy-restricted KD in healthy adults beyond cohorts of athletes on physical performance, body composition, and blood parameters. METHODS Our single arm, before-and-after comparison study consisted of a 6-week KD with a previous preparation period including detailed instructions during classes and individual counselling by a dietitian. Compliance with the dietary regimen was monitored by measuring urinary ketones daily, and 7-day food records. All tests were performed after an overnight fast: cardiopulmonary exercise testing via cycle sprioergometry, blood samples, body composition, indirect calorimetry, handgrip strength, and questionnaires addressing complaints and physical sensations. RESULTS Forty-two subjects aged 37 ± 12 years with a BMI of 23.9 ± 3.1 kg/m2 completed the study. Urinary ketosis was detectable on 97% of the days, revealing very good compliance with the KD. Mean energy intake during the study did not change from the habitual diet and 71.6, 20.9, and 7.7% of total energy intake were from fat, protein, and carbohydrates, respectively. Weight loss was -2.0 ± 1.9 kg (P < 0.001) with equal losses of fat-free and fat mass. VO2peak and peak power decreased from 2.55 ± 0.68 l/min to 2.49 ± 0.69 l/min by 2.4% (P = 0.023) and from 241 ± 57 W to 231 ± 57 W by 4.1% (P < 0.001), respectively, whereas, handgrip strength rose slightly from 40.1 ± 8.8 to 41.0 ± 9.1 kg by 2.5% (P = 0.047). The blood lipids TG and HDL-C remained unchanged, whereas total cholesterol and LDL-C increased significantly by 4.7 and 10.7%, respectively. Glucose, insulin, and IGF-1 dropped significantly by 3.0, 22.2 and 20.2%, respectively. CONCLUSIONS We detected a mildly negative impact from this 6-week non-energy-restricted KD on physical performance (endurance capacity, peak power and faster exhaustion). Our findings lead us to assume that a KD does not impact physical fitness in a clinically relevant manner that would impair activities of daily living and aerobic training. However, a KD may be a matter of concern in competitive athletes. TRIAL REGISTRATION DRKS00009605, registered 08 January 2016.
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Affiliation(s)
- Paul Urbain
- Department of Medicine I, Section of Clinical Nutrition and Dietetics, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Hugstetterstr 55, 79106 Freiburg, Germany
| | - Lena Strom
- Department of Medicine I, Section of Clinical Nutrition and Dietetics, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Hugstetterstr 55, 79106 Freiburg, Germany.,Institute of Agricultural and Nutritional Sciences, Martin-Luther-University Halle-Wittenberg, Halle, Germany
| | - Lena Morawski
- Department of Sport and Sport Science, University of Freiburg, Freiburg, Germany
| | - Anja Wehrle
- Institute for Exercise- und Occupational Medicine, Center for Medicine, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Peter Deibert
- Institute for Exercise- und Occupational Medicine, Center for Medicine, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Hartmut Bertz
- Department of Medicine I, Section of Clinical Nutrition and Dietetics, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Hugstetterstr 55, 79106 Freiburg, Germany.,Department of Medicine I, Hematology, Oncology and Stem Cell Transplantation, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
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30
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Hall KD. A review of the carbohydrate-insulin model of obesity. Eur J Clin Nutr 2017; 71:323-326. [PMID: 28074888 DOI: 10.1038/ejcn.2016.260] [Citation(s) in RCA: 67] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2016] [Accepted: 10/10/2016] [Indexed: 02/07/2023]
Abstract
The carbohydrate-insulin model of obesity theorizes that diets high in carbohydrate are particularly fattening due to their propensity to elevate insulin secretion. Insulin directs the partitioning of energy toward storage as fat in adipose tissue and away from oxidation by metabolically active tissues and purportedly results in a perceived state of cellular internal starvation. In response, hunger and appetite increases and metabolism is suppressed, thereby promoting the positive energy balance associated with the development of obesity. Several logical consequences of this carbohydrate-insulin model of obesity were recently investigated in a pair of carefully controlled inpatient feeding studies whose results failed to support key model predictions. Therefore, important aspects of carbohydrate-insulin model have been experimentally falsified suggesting that the model is too simplistic. This review describes the current state of the carbohydrate-insulin model and the implications of its recent experimental tests.
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Affiliation(s)
- K D Hall
- National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, USA
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32
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Hall KD, Bemis T, Brychta R, Chen KY, Courville A, Crayner EJ, Goodwin S, Guo J, Howard L, Knuth ND, Miller BV, Prado CM, Siervo M, Skarulis MC, Walter M, Walter PJ, Yannai L. Calorie for Calorie, Dietary Fat Restriction Results in More Body Fat Loss than Carbohydrate Restriction in People with Obesity. Cell Metab 2015; 22:427-36. [PMID: 26278052 PMCID: PMC4603544 DOI: 10.1016/j.cmet.2015.07.021] [Citation(s) in RCA: 186] [Impact Index Per Article: 18.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/20/2015] [Revised: 07/06/2015] [Accepted: 07/23/2015] [Indexed: 10/23/2022]
Abstract
Dietary carbohydrate restriction has been purported to cause endocrine adaptations that promote body fat loss more than dietary fat restriction. We selectively restricted dietary carbohydrate versus fat for 6 days following a 5-day baseline diet in 19 adults with obesity confined to a metabolic ward where they exercised daily. Subjects received both isocaloric diets in random order during each of two inpatient stays. Body fat loss was calculated as the difference between daily fat intake and net fat oxidation measured while residing in a metabolic chamber. Whereas carbohydrate restriction led to sustained increases in fat oxidation and loss of 53 ± 6 g/day of body fat, fat oxidation was unchanged by fat restriction, leading to 89 ± 6 g/day of fat loss, and was significantly greater than carbohydrate restriction (p = 0.002). Mathematical model simulations agreed with these data, but predicted that the body acts to minimize body fat differences with prolonged isocaloric diets varying in carbohydrate and fat.
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Affiliation(s)
- Kevin D Hall
- National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
| | - Thomas Bemis
- National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA
| | - Robert Brychta
- National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA
| | - Kong Y Chen
- National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA
| | - Amber Courville
- Clinical Center Nutrition Department, National Institutes of Health, Bethesda, MD 20892, USA
| | - Emma J Crayner
- National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA
| | - Stephanie Goodwin
- National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA
| | - Juen Guo
- National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA
| | - Lilian Howard
- National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA
| | | | - Bernard V Miller
- National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA
| | | | - Mario Siervo
- Newcastle University, Newcastle upon Tyne NE4 5PL, UK
| | - Monica C Skarulis
- National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA
| | - Mary Walter
- National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA
| | - Peter J Walter
- National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA
| | - Laura Yannai
- National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA
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Heymsfield SB, Gonzalez MCC, Shen W, Redman L, Thomas D. Weight loss composition is one-fourth fat-free mass: a critical review and critique of this widely cited rule. Obes Rev 2014; 15:310-21. [PMID: 24447775 PMCID: PMC3970209 DOI: 10.1111/obr.12143] [Citation(s) in RCA: 175] [Impact Index Per Article: 15.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/16/2013] [Revised: 12/10/2013] [Accepted: 12/10/2013] [Indexed: 12/12/2022]
Abstract
Maximizing fat loss while preserving lean tissue mass and function is a central goal of modern obesity treatments. A widely cited rule guiding expected loss of lean tissue as fat-free mass (FFM) states that approximately one-fourth of weight loss will be FFM (i.e. ΔFFM/ΔWeight = ∼0.25), with the remaining three-fourths being fat mass. This review examines the dynamic relationships between FFM, fat mass and weight changes that follow induction of negative energy balance with hypocaloric dieting and/or exercise. Historical developments in the field are traced with the 'Quarter FFM Rule' used as a framework to examine evolving concepts on obesity tissue, excess weight and what is often cited as 'Forbes' Rule'. Temporal effects in the fractional contribution of FFM to changes in body weight are examined as are lean tissue moderating effects such as ageing, inactivity and exercise that frequently accompany structured low-calorie diet weight loss protocols. Losses of lean tissue with dieting typically tend to be small, raising questions about study design, power and applied measurement method reliability. Our review elicits important questions related to the fractional loss of lean tissues with dieting and provides a foundation for future research on this topic.
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Evaluation of Weight Loss on a Low-Calorie Meal Replacement Diet as a Potential Predictor of Weight Loss After Laparoscopic Adjustable Gastric Banding Surgery in Adolescents. Obes Surg 2013; 23:1384-8. [DOI: 10.1007/s11695-013-0935-x] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
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Abete I, Parra MD, Zulet MA, Martínez JA. Different dietary strategies for weight loss in obesity: role of energy and macronutrient content. Nutr Res Rev 2012; 19:5-17. [PMID: 19079872 DOI: 10.1079/nrr2006112] [Citation(s) in RCA: 51] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
Obesity is a chronic disorder caused by an imbalance of the energy metabolism with high associated burdens. Therefore, huge efforts are being currently devoted in studying new types of hypoenergetic diets and their composition, in order to characterise more specific, long-lasting and safe slimming protocols. A number of investigations are trying to determine the specific influence of the macronutrient distribution in energy-restricted diets on the management of excessive body weight. In this context, very-low-energy diets supplying between 1670 and 3350 kJ (400 and 800 kcal)/d have been beneficial in short-term treatments causing a weight loss of 300-500 g/d. Such strategies place more emphasis on energy restriction than on the macronutrient composition of the diet prescription. Weight loss produced by either low-carbohydrate or low-fat moderately energy-restricted diets ranges from 0.5 to 1.0 kg/week, while diets with high or moderately high protein content have also been applied in weight-reducing programmes by inducing losses of 0.2-0.4 kg/week. Other factors that determine weight loss by dieting are sex, age, initial body weight, race, genetics, regional fat deposition, etc, which must be taken into account to explain the variability in the outcomes of different low-energy diets. Therefore, more research is needed about the impact of diets with different fuel substrates and foods on the characteristics of the weight-loss process.
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Affiliation(s)
- I Abete
- Department of Physiology and Nutrition, University of Navarra, Irunlarrea s/n, 31008 Pamplona, Spain
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Miller BV, Bertino JS, Reed RG, Burrington CM, Davidson LK, Green A, Gartung AM, Nafziger AN. An evaluation of the atkins' diet. Metab Syndr Relat Disord 2012; 1:299-309. [PMID: 18370655 DOI: 10.1089/1540419031361426] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
Low-carbohydrate (LC) weight-reducing diets are popular choices for self-dieters. Eighteen adults (BMI >/= 25 kg/m(2)) were enrolled in this short-term longitudinal study to evaluate dietary intake and weight on their "usual" diets and LC diet. Subjects were instructed to follow the first two phases of the diet described in Dr. Atkins' New Diet Revolution (2 weeks each). Total daily intake of calories and nutrients were calculated from 3-day food diaries. Body weight was measured at the end of each 2-week diet session. All enrolled subjects completed the study (age = 39.8 +/- 8.1 years, BMI = 36.6 +/- 6.6 kg/m(2)). Mean caloric intakes were 1400 +/- 472 kcal/day (Induction diet) and 1558 +/- 490 kcal/day (Ongoing Weight Loss diet) both p </= 0.001 compared to "usual" (Baseline diet) 2481 +/- 723 kcal/day. Body weights were 107.4 +/- 24.2 kg, 103.6 +/- 23.0 kg and 102.1 +/- 22.6 kg at the conclusion of the Baseline, Induction, and Ongoing Weight Loss diets, respectively (both p </= 0.001). Decreases in daily caloric intake correlated with weight loss. Pearson correlation coefficients were, r = 0.64 (p </= 0.001) and r = 0.40 (p </= 0.001) for Induction and Ongoing Weight Loss diets versus "usual" diet. Caloric intake is decreased when otherwise healthy overweight and obese adults self-implement Atkins' Induction and Ongoing Weight Loss diets and significantly altered their dietary micronutrient intake. Weight loss can be explained by the self-selected lower caloric intake on The Atkins' Diet.
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Segal-Isaacson CJ, Johnson S, Tomuta V, Cowell B, Stein DT. A Randomized Trial Comparing Low-Fat and Low-Carbohydrate Diets Matched for Energy and Protein. ACTA ACUST UNITED AC 2012; 12 Suppl 2:130S-40S. [PMID: 15601961 DOI: 10.1038/oby.2004.278] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022]
Abstract
Several recent studies have found greater weight loss at 6 months among participants on a very-low-carbohydrate (VLC) weight-loss diet compared with a low-fat (LF) weight-loss diet. Because most of these studies were not matched for calories, it is not clear whether these results are caused by decreased energy intake or increased energy expenditure. It is hypothesized that several energy-consuming metabolic pathways are up-regulated during a VLC diet, leading to increased energy expenditure. The focus of this study was to investigate whether, when protein and energy are held constant, there is a significant difference in fat and weight loss when fat and carbohydrate are dramatically varied in the diet. The preliminary results presented in this paper are for the first four of six postmenopausal overweight or obese participants who followed, in random order, both a VLC and an LF diet for 6 weeks. Other outcome measures were serum lipids, glucose, and insulin, as well as dietary compliance and side effects. Our results showed no significant weight loss, lipid, serum insulin, or glucose differences between the two diets. Lipids were dramatically reduced on both diets, with a trend for greater triglyceride reduction on the VLC diet. Glucose levels were also reduced on both diets, with a trend for insulin reduction on the VLC diet. Compliance was excellent with both diets, and side effects were mild, although participants reported more food cravings and bad breath on the VLC diet and more burping and flatulence on the LF diet.
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Affiliation(s)
- C J Segal-Isaacson
- Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
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Speakman JR, Westerterp KR. A mathematical model of weight loss under total starvation: evidence against the thrifty-gene hypothesis. Dis Model Mech 2012; 6:236-51. [PMID: 22864023 PMCID: PMC3529354 DOI: 10.1242/dmm.010009] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
The thrifty-gene hypothesis (TGH) posits that the modern genetic predisposition to obesity stems from a historical past where famine selected for genes that promote efficient fat deposition. It has been previously argued that such a scenario is unfeasible because under such strong selection any gene favouring fat deposition would rapidly move to fixation. Hence, we should all be predisposed to obesity: which we are not. The genetic architecture of obesity that has been revealed by genome-wide association studies (GWAS), however, calls into question such an argument. Obesity is caused by mutations in many hundreds (maybe thousands) of genes, each with a very minor, independent and additive impact. Selection on such genes would probably be very weak because the individual advantages they would confer would be very small. Hence, the genetic architecture of the epidemic may indeed be compatible with, and hence support, the TGH. To evaluate whether this is correct, it is necessary to know the likely effects of the identified GWAS alleles on survival during starvation. This would allow definition of their advantage in famine conditions, and hence the likely selection pressure for such alleles to have spread over the time course of human evolution. We constructed a mathematical model of weight loss under total starvation using the established principles of energy balance. Using the model, we found that fatter individuals would indeed survive longer and, at a given body weight, females would survive longer than males, when totally starved. An allele causing deposition of an extra 80 g of fat would result in an extension of life under total starvation by about 1.1-1.6% in an individual with 10 kg of fat and by 0.25-0.27% in an individual carrying 32 kg of fat. A mutation causing a per allele effect of 0.25% would become completely fixed in a population with an effective size of 5 million individuals in 6000 selection events. Because there have probably been about 24,000 famine events since the evolution of hominins 4 million years ago, there has been ample time even for genes with only very minor impacts on adiposity to move to fixation. The observed polymorphic variation in the genes causing the predisposition to obesity is incompatible with the TGH, unless all these single nucleotide polymorphisms (SNPs) arose in the last 900,000 years, a requirement we know is incorrect. The TGH is further weakened by the observation of no link between the effect size of these SNPs and their prevalence, which would be anticipated under the TGH model of selection if all the SNPs had arisen in the last 900,000 years.
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Affiliation(s)
- John R Speakman
- Institute of Genetics and Developmental Biology, Key State Laboratory of Molecular Development, Chinese Academy of Sciences, Beijing, China.
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Abstract
Mathematical modeling of human energy regulation and body weight change has recently reached the level of sophistication required for accurate predictions. Mathematical models are beginning to provide a quantitative framework for integrating experimental data in humans and thereby help us better understand the dynamic imbalances of energy and macronutrients that give rise to changes in body weight and composition. This review provides an overview of the various approaches that have been used to model body weight dynamics and energy regulation in humans, highlights several insights that these models have provided, and suggests how mathematical models can serve as a guide for future experimental research.
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Affiliation(s)
- Kevin D Hall
- Laboratory of Biological Modeling, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
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Hall KD, Sacks G, Chandramohan D, Chow CC, Wang YC, Gortmaker SL, Swinburn BA. Quantification of the effect of energy imbalance on bodyweight. Lancet 2011; 378:826-37. [PMID: 21872751 PMCID: PMC3880593 DOI: 10.1016/s0140-6736(11)60812-x] [Citation(s) in RCA: 730] [Impact Index Per Article: 52.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
Abstract
Obesity interventions can result in weight loss, but accurate prediction of the bodyweight time course requires properly accounting for dynamic energy imbalances. In this report, we describe a mathematical modelling approach to adult human metabolism that simulates energy expenditure adaptations during weight loss. We also present a web-based simulator for prediction of weight change dynamics. We show that the bodyweight response to a change of energy intake is slow, with half times of about 1 year. Furthermore, adults with greater adiposity have a larger expected weight loss for the same change of energy intake, and to reach their steady-state weight will take longer than it would for those with less initial body fat. Using a population-averaged model, we calculated the energy-balance dynamics corresponding to the development of the US adult obesity epidemic. A small persistent average daily energy imbalance gap between intake and expenditure of about 30 kJ per day underlies the observed average weight gain. However, energy intake must have risen to keep pace with increased expenditure associated with increased weight. The average increase of energy intake needed to sustain the increased weight (the maintenance energy gap) has amounted to about 0·9 MJ per day and quantifies the public health challenge to reverse the obesity epidemic.
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Affiliation(s)
- Kevin D Hall
- National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
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Heymsfield SB, Thomas D, Nguyen AM, Peng JZ, Martin C, Shen W, Strauss B, Bosy-Westphal A, Muller MJ. Voluntary weight loss: systematic review of early phase body composition changes. Obes Rev 2011; 12:e348-61. [PMID: 20524998 DOI: 10.1111/j.1467-789x.2010.00767.x] [Citation(s) in RCA: 67] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
Weight loss follows when adult humans enter a phase of negative energy balance brought about by reducing energy intake and/or increasing energy expenditure. The weight loss period is usually viewed as a continuous process, ending when energy equilibrium is achieved at a lower weight or with death following depletion of fuel stores. However, growing evidence supports the expanded view that induction of negative energy balance leads to well-defined physiological effects characterized by three discrete phases (I-III). At present there are no comprehensive reviews of the 'early' phase of weight loss, a gap highlighted by recent interest in rapidly testing new treatments with short-term protocols. Herein we show from earlier reports and with new data that weight loss during phase I is: mathematically quantifiable with a t(1/2) < 1-week and 4- to 6-week duration; includes well-defined rapidly evolving body composition and energy expenditure changes; and is moderated by multiple factors including subject sex and activity level, nutrients ingested at baseline and during the negative energy balance period, and hormone and pharmacologic treatments. Our in depth review collectively characterizes phase I as a distinct weight loss period while revealing important knowledge gaps that can be filled with appropriately designed future studies.
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Affiliation(s)
- S B Heymsfield
- Merck Research Laboratories, Merck & Co., Inc., Rahway, NJ, USA.
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42
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Shikany JM, Vaughan LK, Baskin ML, Cope MB, Hill JO, Allison DB. Is Dietary Fat “Fattening”? A Comprehensive Research Synthesis. Crit Rev Food Sci Nutr 2010; 50:699-715. [DOI: 10.1080/10408398.2010.491057] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
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Foster GD, Wyatt HR, Hill JO, Makris AP, Rosenbaum DL, Brill C, Stein RI, Mohammed BS, Miller B, Rader DJ, Zemel B, Wadden TA, Tenhave T, Newcomb CW, Klein S. Weight and metabolic outcomes after 2 years on a low-carbohydrate versus low-fat diet: a randomized trial. Ann Intern Med 2010; 153:147-57. [PMID: 20679559 PMCID: PMC2949959 DOI: 10.7326/0003-4819-153-3-201008030-00005] [Citation(s) in RCA: 362] [Impact Index Per Article: 24.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
BACKGROUND Previous studies comparing low-carbohydrate and low-fat diets have not included a comprehensive behavioral treatment, resulting in suboptimal weight loss. OBJECTIVE To evaluate the effects of 2-year treatment with a low-carbohydrate or low-fat diet, each of which was combined with a comprehensive lifestyle modification program. DESIGN Randomized parallel-group trial. (ClinicalTrials.gov registration number: NCT00143936) SETTING 3 academic medical centers. PATIENTS 307 participants with a mean age of 45.5 years (SD, 9.7 years) and mean body mass index of 36.1 kg/m(2) (SD, 3.5 kg/m(2)). INTERVENTION A low-carbohydrate diet, which consisted of limited carbohydrate intake (20 g/d for 3 months) in the form of low-glycemic index vegetables with unrestricted consumption of fat and protein. After 3 months, participants in the low-carbohydrate diet group increased their carbohydrate intake (5 g/d per wk) until a stable and desired weight was achieved. A low-fat diet consisted of limited energy intake (1200 to 1800 kcal/d; <or=30% calories from fat). Both diets were combined with comprehensive behavioral treatment. MEASUREMENTS Weight at 2 years was the primary outcome. Secondary measures included weight at 3, 6, and 12 months and serum lipid concentrations, blood pressure, urinary ketones, symptoms, bone mineral density, and body composition throughout the study. RESULTS Weight loss was approximately 11 kg (11%) at 1 year and 7 kg (7%) at 2 years. There were no differences in weight, body composition, or bone mineral density between the groups at any time point. During the first 6 months, the low-carbohydrate diet group had greater reductions in diastolic blood pressure, triglyceride levels, and very-low-density lipoprotein cholesterol levels, lesser reductions in low-density lipoprotein cholesterol levels, and more adverse symptoms than did the low-fat diet group. The low-carbohydrate diet group had greater increases in high-density lipoprotein cholesterol levels at all time points, approximating a 23% increase at 2 years. LIMITATION Intensive behavioral treatment was provided, patients with dyslipidemia and diabetes were excluded, and attrition at 2 years was high. CONCLUSION Successful weight loss can be achieved with either a low-fat or low-carbohydrate diet when coupled with behavioral treatment. A low-carbohydrate diet is associated with favorable changes in cardiovascular disease risk factors at 2 years. PRIMARY FUNDING SOURCE National Institutes of Health.
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Affiliation(s)
- Gary D Foster
- Center for Obesity Research and Education, Temple University, Philadelphia, Pennsylvania 19140, USA.
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Foster GD, Wyatt HR, Hill JO, Makris AP, Rosenbaum DL, Brill C, Stein RI, Mohammed BS, Miller B, Rader DJ, Zemel B, Wadden TA, Tenhave T, Newcomb CW, Klein S. Weight and metabolic outcomes after 2 years on a low-carbohydrate versus low-fat diet: a randomized trial. Ann Intern Med 2010. [PMID: 20679559 PMCID: PMC2949959 DOI: 10.1059/0003-4819-153-3-201008030-00005] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
Abstract
BACKGROUND Previous studies comparing low-carbohydrate and low-fat diets have not included a comprehensive behavioral treatment, resulting in suboptimal weight loss. OBJECTIVE To evaluate the effects of 2-year treatment with a low-carbohydrate or low-fat diet, each of which was combined with a comprehensive lifestyle modification program. DESIGN Randomized parallel-group trial. (ClinicalTrials.gov registration number: NCT00143936) SETTING 3 academic medical centers. PATIENTS 307 participants with a mean age of 45.5 years (SD, 9.7 years) and mean body mass index of 36.1 kg/m(2) (SD, 3.5 kg/m(2)). INTERVENTION A low-carbohydrate diet, which consisted of limited carbohydrate intake (20 g/d for 3 months) in the form of low-glycemic index vegetables with unrestricted consumption of fat and protein. After 3 months, participants in the low-carbohydrate diet group increased their carbohydrate intake (5 g/d per wk) until a stable and desired weight was achieved. A low-fat diet consisted of limited energy intake (1200 to 1800 kcal/d; <or=30% calories from fat). Both diets were combined with comprehensive behavioral treatment. MEASUREMENTS Weight at 2 years was the primary outcome. Secondary measures included weight at 3, 6, and 12 months and serum lipid concentrations, blood pressure, urinary ketones, symptoms, bone mineral density, and body composition throughout the study. RESULTS Weight loss was approximately 11 kg (11%) at 1 year and 7 kg (7%) at 2 years. There were no differences in weight, body composition, or bone mineral density between the groups at any time point. During the first 6 months, the low-carbohydrate diet group had greater reductions in diastolic blood pressure, triglyceride levels, and very-low-density lipoprotein cholesterol levels, lesser reductions in low-density lipoprotein cholesterol levels, and more adverse symptoms than did the low-fat diet group. The low-carbohydrate diet group had greater increases in high-density lipoprotein cholesterol levels at all time points, approximating a 23% increase at 2 years. LIMITATION Intensive behavioral treatment was provided, patients with dyslipidemia and diabetes were excluded, and attrition at 2 years was high. CONCLUSION Successful weight loss can be achieved with either a low-fat or low-carbohydrate diet when coupled with behavioral treatment. A low-carbohydrate diet is associated with favorable changes in cardiovascular disease risk factors at 2 years. PRIMARY FUNDING SOURCE National Institutes of Health.
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Affiliation(s)
- Gary D Foster
- Center for Obesity Research and Education, Temple University, Philadelphia, Pennsylvania 19140, USA.
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Gardiner JV, Bataveljic A, Patel NA, Bewick GA, Roy D, Campbell D, Greenwood HC, Murphy KG, Hameed S, Jethwa PH, Ebling FJ, Vickers SP, Cheetham S, Ghatei MA, Bloom SR, Dhillo WS. Prokineticin 2 is a hypothalamic neuropeptide that potently inhibits food intake. Diabetes 2010; 59:397-406. [PMID: 19933997 PMCID: PMC2809973 DOI: 10.2337/db09-1198] [Citation(s) in RCA: 55] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
OBJECTIVE Prokineticin 2 (PK2) is a hypothalamic neuropeptide expressed in central nervous system areas known to be involved in food intake. We therefore hypothesized that PK2 plays a role in energy homeostasis. RESEARCH DESIGN AND METHODS We investigated the effect of nutritional status on hypothalamic PK2 expression and effects of PK2 on the regulation of food intake by intracerebroventricular (ICV) injection of PK2 and anti-PK2 antibody. Subsequently, we investigated the potential mechanism of action by determining sites of neuronal activation after ICV injection of PK2, the hypothalamic site of action of PK2, and interaction between PK2 and other hypothalamic neuropeptides regulating energy homeostasis. To investigate PK2's potential as a therapeutic target, we investigated the effect of chronic administration in lean and obese mice. RESULTS Hypothalamic PK2 expression was reduced by fasting. ICV administration of PK2 to rats potently inhibited food intake, whereas anti-PK2 antibody increased food intake, suggesting that PK2 is an anorectic neuropeptide. ICV administration of PK2 increased c-fos expression in proopiomelanocortin neurons of the arcuate nucleus (ARC) of the hypothalamus. In keeping with this, PK2 administration into the ARC reduced food intake and PK2 increased the release of alpha-melanocyte-stimulating hormone (alpha-MSH) from ex vivo hypothalamic explants. In addition, ICV coadministration of the alpha-MSH antagonist agouti-related peptide blocked the anorexigenic effects of PK2. Chronic peripheral administration of PK2 reduced food and body weight in lean and obese mice. CONCLUSIONS This is the first report showing that PK2 has a role in appetite regulation and its anorectic effect is mediated partly via the melanocortin system.
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Affiliation(s)
- James V. Gardiner
- Department of Investigative Medicine, Imperial College London, London, U.K
| | - Attia Bataveljic
- Department of Investigative Medicine, Imperial College London, London, U.K
| | - Neekhil A. Patel
- Department of Investigative Medicine, Imperial College London, London, U.K
| | - Gavin A. Bewick
- Department of Investigative Medicine, Imperial College London, London, U.K
| | - Debabrata Roy
- Department of Investigative Medicine, Imperial College London, London, U.K
| | - Daniel Campbell
- Department of Investigative Medicine, Imperial College London, London, U.K
| | | | - Kevin G. Murphy
- Department of Investigative Medicine, Imperial College London, London, U.K
| | - Saira Hameed
- Department of Investigative Medicine, Imperial College London, London, U.K
| | - Preeti H. Jethwa
- School of Biomedical Sciences, University of Nottingham, Nottingham, U.K
| | | | | | | | - Mohammad A. Ghatei
- Department of Investigative Medicine, Imperial College London, London, U.K
| | - Stephen R. Bloom
- Department of Investigative Medicine, Imperial College London, London, U.K
- Corresponding author: Stephen R. Bloom,
| | - Waljit S. Dhillo
- Department of Investigative Medicine, Imperial College London, London, U.K
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Boden G. High- or low-carbohydrate diets: which is better for weight loss, insulin resistance, and fatty livers? Gastroenterology 2009; 136:1490-2. [PMID: 19318102 PMCID: PMC2677123 DOI: 10.1053/j.gastro.2009.03.019] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Affiliation(s)
- Guenther Boden
- Division of Endocrinology, Diabetes and Metabolism, and the Clinical Research Center, Temple University School of Medicine, Philadelphia, PA
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47
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Dietary adherence and weight loss success among overweight women: results from the A TO Z weight loss study. Int J Obes (Lond) 2008; 32:985-91. [PMID: 18268511 DOI: 10.1038/ijo.2008.8] [Citation(s) in RCA: 153] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND Dietary adherence has been implicated as an important factor in the success of dieting strategies; however, studies assessing and investigating its association with weight loss success are scarce. OBJECTIVE We aimed to document the level of dietary adherence using measured diet data and to examine its association with weight loss success. DESIGN Secondary analysis was performed using data from 181 free-living overweight/obese women (mean+/-s.d. age=43+/-5 years, body mass index=31+/-4 kg m(-2)) participating in a 1-year randomized clinical trial (the A TO Z study) comparing popular weight loss diets (Atkins, Zone and Ornish). Participants' dietary adherence was assessed as the difference between their respective assigned diet's recommended macronutrient goals and their self-reported intake. Association between dietary adherence and 12-month weight change was computed using Spearman's correlations. Differences in baseline characteristics and macronutrient intake between the most and least adherent tertiles for diet groups were compared using t-tests. RESULTS Within each diet group, adherence score was significantly correlated with 12-month weight change (Atkins, r(s)=0.42, P=0.0003; Zone, r(s)=0.34, P=0.009 and Ornish, r(s)=0.38, P=0.004). Twelve-month weight change in the most vs least adherent tertiles, respectively, was -8.3+/-5.6 vs -1.9+/-5.8 kg, P=0.0006 (Atkins); -3.7+/-6.3 vs -0.4+/-6.8 kg, P=0.12 (Zone) and -6.5+/-6.8 vs -1.7+/-7.9 kg, P=0.06 (Ornish). CONCLUSIONS Regardless of assigned diet groups, 12-month weight change was greater in the most adherent compared to the least adherent tertiles. These results suggest that strategies to increase adherence may deserve more emphasis than the specific macronutrient composition of the weight loss diet itself in supporting successful weight loss.
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Johnstone AM, Horgan GW, Murison SD, Bremner DM, Lobley GE. Effects of a high-protein ketogenic diet on hunger, appetite, and weight loss in obese men feeding ad libitum. Am J Clin Nutr 2008; 87:44-55. [PMID: 18175736 DOI: 10.1093/ajcn/87.1.44] [Citation(s) in RCA: 239] [Impact Index Per Article: 14.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
Abstract
BACKGROUND Altering the macronutrient composition of the diet influences hunger and satiety. Studies have compared high- and low-protein diets, but there are few data on carbohydrate content and ketosis on motivation to eat and ad libitum intake. OBJECTIVE We aimed to compare the hunger, appetite, and weight-loss responses to a high-protein, low-carbohydrate [(LC) ketogenic] and those to a high-protein, medium-carbohydrate [(MC) nonketogenic] diet in obese men feeding ad libitum. DESIGN Seventeen obese men were studied in a residential trial; food was provided daily. Subjects were offered 2 high-protein (30% of energy) ad libitum diets, each for a 4-wk period-an LC (4% carbohydrate) ketogenic diet and an MC (35% carbohydrate) diet-randomized in a crossover design. Body weight was measured daily, and ketosis was monitored by analysis of plasma and urine samples. Hunger was assessed by using a computerized visual analogue system. RESULTS Ad libitum energy intakes were lower with the LC diet than with the MC diet [P=0.02; SE of the difference (SED): 0.27] at 7.25 and 7.95 MJ/d, respectively. Over the 4-wk period, hunger was significantly lower (P=0.014; SED: 1.76) and weight loss was significantly greater (P=0.006; SED: 0.62) with the LC diet (6.34 kg) than with the MC diet (4.35 kg). The LC diet induced ketosis with mean 3-hydroxybutyrate concentrations of 1.52 mmol/L in plasma (P=0.036 from baseline; SED: 0.62) and 2.99 mmol/L in urine (P<0.001 from baseline; SED: 0.36). CONCLUSION In the short term, high-protein, low-carbohydrate ketogenic diets reduce hunger and lower food intake significantly more than do high-protein, medium-carbohydrate nonketogenic diets.
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Affiliation(s)
- Alexandra M Johnstone
- Division of Obesity and Metabolic Health and Biomathematics and Statistics Scotland, Rowett Research Institute, Aberdeen, United Kingdom.
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Abstract
Adult humans often undertake acute fasts for cosmetic, religious or medical reasons. For example, an estimated 14% of US adults have reported using fasting as a means to control body weight and this approach has long been advocated as an intermittent treatment for gross refractory obesity. There are unique historical data sets on extreme forms of food restriction that give insight into the consequences of starvation or semi-starvation in previously healthy, but usually non-obese subjects. These include documented medical reports on victims of hunger strike, famine and prisoners of war. Such data provide a detailed account on how the body adapts to prolonged starvation. It has previously been shown that fasting for the biblical period of 40 days and 40 nights is well within the overall physiological capabilities of a healthy adult. However, the specific effects on the human body and mind are less clearly documented, either in the short term (hours) or in the longer term (days). This review asks the following three questions, pertinent to any weight-loss therapy, (i) how effective is the regime in achieving weight loss, (ii) what impact does it have on psychology? and finally, (iii) does it work long-term?
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Abstract
Antiobesity drugs that target peripheral metabolism may avoid some of the problems that have been encountered with centrally acting anorectic drugs. Moreover, if they cause weight loss by increasing fat oxidation, they not only address a cause of obesity but also should promote loss of fat rather than lean tissue and improve insulin sensitivity. Weight loss may be slow but more sustained than with anorectic drugs, and thermogenesis may be insufficient to cause any discomfort. Some thermogenic approaches are the activation of adrenergic, thyroid hormone or growth hormone receptors and the inhibition of glucocorticoid receptors; the modulation of transcription factors [e.g. peroxisome proliferator-activated receptor delta (PPARdelta) activators] or enzymes [e.g. glutamine fructose-6-phosphate amidotransferase (GFAT) inhibitors] that promote mitochondrial biogenesis, and the modulation of transcription factors (PPAR alpha activators) or enzymes (AMP-activated protein kinase) that promote fatty acid oxidation. More surprisingly, studies on genetically modified animals and with enzyme inhibitors suggest that inhibitors of fatty acid synthesis [e.g. ATP citrate lyase, fatty acid synthase, acetyl-CoA carboxylase (ACC)], fatty acid interconversion [stearoyl-CoA desaturase (SCD)] and triglyceride synthesis (e.g. acyl-CoA : diacylglycerol acyltransferase) may all be thermogenic. Some targets have been validated only by deleting genes in the whole animal. In these cases, it is possible that deletion of the protein in the brain is responsible for the effect on adiposity, and therefore a centrally penetrant drug would be required. Moreover, whilst a genetically modified mouse may display resistance to obesity in response to a high fat diet, it requires a tool compound to demonstrate that a drug might actually cause weight loss. Even then, it is possible that differences between rodents and humans, such as the greater thermogenic capacity of rodents, may give a misleading impression of the potential of a drug.
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Affiliation(s)
- J C Clapham
- Department of Molecular Pharmacology, AstraZeneca R & D Mölndal, Mölndal, Sweden
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