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      Self-reported menses physiology is positively modulated by a well-formulated, energy-controlled ketogenic diet vs. low fat diet in women of reproductive age with overweight/obesity

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          Abstract

          Weight loss can positively alter female physiology; however, whether dietary carbohydrate- or fat- restriction confer unique effects is less studied. Precisely designed, hypocaloric well-formulated ketogenic diets (KD; ~75% energy for weight maintenance) were compared to isocaloric/isonitrogenous low-fat diet (LFD) on self-reported menses in pre-menopausal overweight and obese women (mean ± SD: 34 ± 10 years, BMI: 32.3 ± 2.7 kg/m2). Women received a precisely-weighed and formulated KD with either twice-daily with ketone salts (KS; n = 6) or a flavor-matched placebo (PL; n = 7) daily for six-weeks. An age and BMI-matched cohort (n = 6) was later assigned to the LFD and underwent the same testing procedures as the KD. Self-reported menses fluctuations were assessed bi-weekly along with measures of body weight, body composition, and fasting serum clinical chemistries using repeated measures ANOVA with Bonferroni post-hoc corrections. Both diets elicited clinically-significant weight-loss (Δ: -7.0 ± 0.5 kg; p < 0.001), primarily from fat-mass (Δ: -4.6 ± 0.3 kg; p < 0.001), and improved insulin-sensitivity and serum lipids (all p < 0.05). Fasting plasma glucose and inflammatory markers were not different between diets. Fasting capillary beta-hydroxybutyrate (R-βHB) increased significantly during the KD, independent of supplementation (Δ: 1.2 ± 0.3 mM R-βHB; p < 0.001). Women randomized to the KD+KS (30%) and KD+PL (43%) reported subjective increases in menses frequency and intensity after 14 days, whereas another third reported a regain of menses (>1 year since the last period) after 28 days. No LFD participants reported menses changes. Nutrient-dense, whole-food KDs and LFD improved weight, BMI, body composition, and blood parameters in pre-menopausal women after six-weeks. Changes in self-reported menses were described by most of the KD participants, but none of the LFD women suggesting there may be unique effects of nutritional ketosis, independent of weight loss.

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          Most cited references35

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          Comparison of the Atkins, Zone, Ornish, and LEARN diets for change in weight and related risk factors among overweight premenopausal women: the A TO Z Weight Loss Study: a randomized trial.

          Popular diets, particularly those low in carbohydrates, have challenged current recommendations advising a low-fat, high-carbohydrate diet for weight loss. Potential benefits and risks have not been tested adequately. To compare 4 weight-loss diets representing a spectrum of low to high carbohydrate intake for effects on weight loss and related metabolic variables. Twelve-month randomized trial conducted in the United States from February 2003 to October 2005 among 311 free-living, overweight/obese (body mass index, 27-40) nondiabetic, premenopausal women. Participants were randomly assigned to follow the Atkins (n = 77), Zone (n = 79), LEARN (n = 79), or Ornish (n = 76) diets and received weekly instruction for 2 months, then an additional 10-month follow-up. Weight loss at 12 months was the primary outcome. Secondary outcomes included lipid profile (low-density lipoprotein, high-density lipoprotein, and non-high-density lipoprotein cholesterol, and triglyceride levels), percentage of body fat, waist-hip ratio, fasting insulin and glucose levels, and blood pressure. Outcomes were assessed at months 0, 2, 6, and 12. The Tukey studentized range test was used to adjust for multiple testing. Weight loss was greater for women in the Atkins diet group compared with the other diet groups at 12 months, and mean 12-month weight loss was significantly different between the Atkins and Zone diets (P<.05). Mean 12-month weight loss was as follows: Atkins, -4.7 kg (95% confidence interval [CI], -6.3 to -3.1 kg), Zone, -1.6 kg (95% CI, -2.8 to -0.4 kg), LEARN, -2.6 kg (-3.8 to -1.3 kg), and Ornish, -2.2 kg (-3.6 to -0.8 kg). Weight loss was not statistically different among the Zone, LEARN, and Ornish groups. At 12 months, secondary outcomes for the Atkins group were comparable with or more favorable than the other diet groups. In this study, premenopausal overweight and obese women assigned to follow the Atkins diet, which had the lowest carbohydrate intake, lost more weight at 12 months than women assigned to follow the Zone diet, and had experienced comparable or more favorable metabolic effects than those assigned to the Zone, Ornish, or LEARN diets [corrected] While questions remain about long-term effects and mechanisms, a low-carbohydrate, high-protein, high-fat diet may be considered a feasible alternative recommendation for weight loss. clinicaltrials.gov Identifier: NCT00079573.
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            Eight-Year Weight Losses with an Intensive Lifestyle Intervention: The Look AHEAD Study

            (2014)
            Objective To evaluate 8-year weight losses achieved with intensive lifestyle intervention (ILI) in the Look AHEAD (Action for Health in Diabetes) study. Design and Methods Look AHEAD assessed the effects of intentional weight loss on cardiovascular morbidity and mortality in 5,145 overweight/obese adults with type 2 diabetes, randomly assigned to ILI or usual care (i.e., diabetes support and education [DSE]). The ILI provided comprehensive behavioral weight loss counseling over 8 years; DSE participants received periodic group education only. Results All participants had the opportunity to complete 8 years of intervention before Look AHEAD was halted in September 2012; ≥88% of both groups completed the 8-year outcomes assessment. ILI and DSE participants lost (mean±SE) 4.7±0.2% and 2.1±0.2% of initial weight, respectively (p<0.001) at year 8; 50.3% and 35.7%, respectively, lost ≥5% (p<0.001), and 26.9% and 17.2%, respectively, lost ≥10% (p<0.001). Across the 8 years ILI participants, compared with DSE, reported greater practice of several key weight-control behaviors. These behaviors also distinguished ILI participants who lost ≥10% and kept it off from those who lost but regained. Conclusions Look AHEAD’s ILI produced clinically meaningful weight loss (≥5%) at year 8 in 50% of patients with type 2 diabetes and can be used to manage other obesity-related co-morbid conditions. Trial Registration clinicaltrials.gov Identifier: NCT00017953
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              Beyond weight loss: a review of the therapeutic uses of very-low-carbohydrate (ketogenic) diets

              Very-low-carbohydrate diets or ketogenic diets have been in use since the 1920s as a therapy for epilepsy and can, in some cases, completely remove the need for medication. From the 1960s onwards they have become widely known as one of the most common methods for obesity treatment. Recent work over the last decade or so has provided evidence of the therapeutic potential of ketogenic diets in many pathological conditions, such as diabetes, polycystic ovary syndrome, acne, neurological diseases, cancer and the amelioration of respiratory and cardiovascular disease risk factors. The possibility that modifying food intake can be useful for reducing or eliminating pharmaceutical methods of treatment, which are often lifelong with significant side effects, calls for serious investigation. This review revisits the meaning of physiological ketosis in the light of this evidence and considers possible mechanisms for the therapeutic actions of the ketogenic diet on different diseases. The present review also questions whether there are still some preconceived ideas about ketogenic diets, which may be presenting unnecessary barriers to their use as therapeutic tools in the physician's hand.
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                Author and article information

                Contributors
                Role: Data curationRole: Formal analysisRole: Project administrationRole: Writing – original draftRole: Writing – review & editing
                Role: Data curationRole: Formal analysisRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: MethodologyRole: ValidationRole: Writing – review & editing
                Role: ConceptualizationRole: MethodologyRole: ValidationRole: Writing – review & editing
                Role: Data curation
                Role: Formal analysis
                Role: Formal analysis
                Role: Formal analysis
                Role: Formal analysis
                Role: Writing – review & editing
                Role: ConceptualizationRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: Project administrationRole: ResourcesRole: SupervisionRole: ValidationRole: Writing – original draftRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS One
                plos
                PLOS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                16 August 2024
                2024
                : 19
                : 8
                : e0293670
                Affiliations
                [1 ] Department of Kinesiology, The Ohio State University, Columbus, Ohio, United States of America
                [2 ] Metagenics, Inc., Aliso Viejo, California, United States of America
                [3 ] Department of Obstetrics and Gynecology, The Ohio State University, Columbus, Ohio, United States of America
                University of Mississippi Medical Center, UNITED STATES OF AMERICA
                Author notes

                Competing Interests: JV receives royalties for low-carbohydrate nutrition books; is founder, consultant, and stockholder of Virta Health, Inc. and is a member of the advisory boards for Simply Good Foods. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

                Author information
                https://orcid.org/0000-0001-5527-9529
                https://orcid.org/0000-0001-8509-4330
                https://orcid.org/0000-0001-7284-3048
                https://orcid.org/0000-0001-7323-7357
                https://orcid.org/0000-0002-7701-9880
                Article
                PONE-D-23-11590
                10.1371/journal.pone.0293670
                11329152
                39150916
                d0003708-2d4c-464c-b8ff-a07d73e3fa8b
                © 2024 Kackley et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 7 June 2023
                : 11 March 2024
                Page count
                Figures: 4, Tables: 2, Pages: 14
                Funding
                Funded by: Metagenics, Inc.
                Award ID: #2017H0395
                Award Recipient :
                This work was funded by a research project grant received from Metagenics, Inc. The study sponsor was responsible for providing the study products (KS, MCT and protein powder samples), and contributed to study design, but was not involved in data collection, sample analysis, or result reporting.
                Categories
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