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A ketogenic diet consumed during radiotherapy improves several aspects of quality of life and metabolic health in women with breast cancer.
Klement, RJ, Weigel, MM, Sweeney, RA
Clinical nutrition (Edinburgh, Scotland). 2021;(6):4267-4274
Abstract
BACKGROUND & AIMS Ketogenic diets (KDs) have been proposed as complementary nutritional treatments for cancer patients. Because it is important to gain knowledge about the safety of KDs adopted during cancer therapy, we studied the effects of KDs on quality of life and blood parameters in women with early-stage breast cancer undergoing radiotherapy. METHODS A total of 29 patients consuming a KD were compared to 30 patients consuming their standard diet (SD) with respect to EORTC-QLQ30 questionnaire scores and different metabolic and hormonal blood parameters that were obtained prior to, in the middle of and at the end of radiotherapy. Baseline-to-end differences were assessed using Wilcoxon tests, and longitudinal changes were analyzed using linear mixed effects models. RESULTS Compared to the SD, women consuming a KD experienced significant improvements in emotional functioning, social functioning, sleep quality, future perspectives and systemic therapy side effects (all p-values <0.01). While breast symptoms increased significantly in both groups, the increase was less pronounced in the KD group. There was no hint of a detrimental effect of the KDs on either liver or kidney function; in contrast, biomarkers of metabolic health (gamma-glutamyl-transpeptidase, creatinine, triglycerides, IGF-1, free T3) significantly improved in the KD, but not the SD group. CONCLUSIONS These data support the hypothesis that consuming a KD during radiotherapy is safe for women with breast cancer and has the potential to improve quality of life and metabolic health. CLINICALTRIALS. GOV IDENTIFIER NCT02516501.
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The Role of the Gut Microbiota on the Beneficial Effects of Ketogenic Diets.
Attaye, I, van Oppenraaij, S, Warmbrunn, MV, Nieuwdorp, M
Nutrients. 2021;(1)
Abstract
The ketogenic diet is a dietary regime focused on strongly reducing carbohydrate intake and increasing fat intake; leading to a state of ketosis. The ketogenic diet has gained much popularity over the years due to its effects on promoting weight loss, increasing insulin sensitivity and reducing dyslipidaemia. All these factors play a crucial role in the development of cardio-metabolic diseases; one of the greatest health challenges of the time. Moreover, the ketogenic diet has been known to reduce (epileptic) seizure activity. It is still poorly understood how following a ketogenic diet can lead to these beneficial metabolic effects. However, in recent years it has become clear that diet and the gut microbiota interact with one another and thus influence host health. The goal of this review is to summarize the current state of knowledge regarding the beneficial metabolic effects of the ketogenic diet and the role of gut microbiota in these effects.
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Nutritional Ketosis in Parkinson's Disease - a Review of Remaining Questions and Insights.
Choi, A, Hallett, M, Ehrlich, D
Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics. 2021;(3):1637-1649
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Abstract
Nutritional ketosis has promise for treating Parkinson's disease. Three previous studies explored the use of a ketogenic diet in cohorts with Parkinson's disease, and, while not conclusive, the data suggest non-motor symptom benefit. Before the ketogenic diet can be considered as a therapeutic option, it is important to establish with greater certainty that there is a reliable symptomatic benefit: which symptoms or groups of symptoms are impacted (if non-motor symptoms, which ones, and by which mechanism), what timescale is needed to obtain benefit, and how large an effect size can be achieved? To accomplish this, further investigation into the disease mechanisms based on pre-clinical data and hints from the clinical outcomes to date is useful to understand target engagement and gauge which mechanism could lead to a testable hypothesis. We review research pertaining to ketogenic diet, exogenous ketones, fasting, clinical studies, and theoretical review papers regarding therapeutic mechanisms from direct ketone body signaling and indirect metabolic effects. Through discussion of these findings and consideration of whether the ketogenic diet can be regarded as therapeutically useful for adjunctive therapy for Parkinson's disease, we identify remaining questions for the clinician to consider prior to recommending this diet.
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Effect of a Ketogenic Diet on the Nutritional Parameters of Obese Patients: A Systematic Review and Meta-Analysis.
López-Espinoza, MÁ, Chacón-Moscoso, S, Sanduvete-Chaves, S, Ortega-Maureira, MJ, Barrientos-Bravo, T
Nutrients. 2021;(9)
Abstract
UNLABELLED The effect of a ketogenic diet (KD) on biochemical parameters and nutritional status has been the subject of debate over the years, as several randomized clinical trials (RCTs) obtained different results. METHOD A systematic review and random-effects meta-analysis of RCTs comparing KD with a balanced diet was performed by means of a search of PubMed, Cochrane Library, Scopus, and Web of Science. Trials where the method for measuring the response variables was unclear, those that considered pathologies other than chronic non-communicable diseases and those with participants receiving pharmacological treatment for obesity were excluded from the comparison. RESULTS Of the studies included in the meta-analysis, no statistically significant standardized mean differences were observed for body mass index (BMI) (d = -0.457, p = 0.359), total cholesterol, COL-T (d = 0.230, p = 0.591), high-density lipoprotein, HDL (d = -0.028, p = 0.934), low-density lipoprotein, LDL (d = 0.528, p = 0.173), or triglycerides, TG (d = -0.283, p = 0.222), with high values of heterogeneity. The percentage of women included in the studies is a significant moderating variable in terms of BMI ratio (z = -6.68, p < 0.001) and TG (z = -2.27, p = 0.023). CONCLUSION A KD shows no more benefits on nutritional parameters than a balanced diet, and adverse effects of being on the diet are sometimes reported.
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Effects of a Non-Energy-Restricted Ketogenic Diet on Clinical Oral Parameters. An Exploratory Pilot Trial.
Woelber, JP, Tennert, C, Ernst, SF, Vach, K, Ratka-Krüger, P, Bertz, H, Urbain, P
Nutrients. 2021;(12)
Abstract
Ketogenic diets (KDs) may be a helpful complement in the prevention of and therapy for several diseases. Apart from their non-cariogenic properties, it is still unclear how KDs affect oral parameters. The aim of this study was to investigate the influence of a KD on clinical periodontal parameters. Twenty generally healthy volunteers with an average age of 36.6 years underwent a KD for 6 weeks. Their compliance was monitored by measuring their urinary ketones daily and by keeping 7-day food records. Clinical oral parameters included plaque (PI), gingival inflammation (GI), a complete periodontal status (probing depths, bleeding on probing), and general physical and serologic parameters at baseline and after 6 weeks. The results showed a trend towards lower plaque values, but with no significant changes from baseline to the end of the study with regard to the clinical periodontal parameters. However, their body weight and BMI measurements showed a significant decrease. The regression analyses showed that the fat mass and the BMI were significantly positively correlated to periodontal inflammation, while HDL, fiber, and protein intake were negatively correlated to periodontal inflammation. The KD change did not lead to clinical changes in periodontal parameters in healthy participants under continued oral hygiene, but it did lead to a significant weight loss.
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Impact of a ketogenic diet intervention during radiotherapy on body composition: IV. Final results of the KETOCOMP study for rectal cancer patients.
Klement, RJ, Koebrunner, PS, Meyer, D, Kanzler, S, Sweeney, RA
Clinical nutrition (Edinburgh, Scotland). 2021;(7):4674-4684
Abstract
BACKGROUND & AIMS Obesity and low muscle mass are associated with worse outcomes of colorectal cancer patients. We conducted a controlled trial to study the impact of a ketogenic diet (KD) based on natural foods versus an unspecified standard diet (SD) on body composition in rectal cancer patients undergoing radiotherapy. METHODS Patients with non-metastasized rectal cancer were allocated to either the KD (N = 24) or the SD (N = 25) group during radiotherapy. Body composition was measured weekly by bioimpedance analysis and analyzed using linear mixed effects models. Pathologic response in patients undergoing neoadjuvant treatment was evaluated at the time of surgery. RESULTS A total of 18 KD and 23 SD patients completed the study and were eligible for analysis. The SD group experienced no noteworthy changes in any body composition parameter. In contrast, patients in the KD group lost significant amounts of body weight and fat mass, averaging 0.5 and 0.65 kg/week (p < 0.0001). There was a rapid loss of intracellular water consistent with initial intramuscular glycogen and water depletion, but skeletal muscle tissue was conserved. Pathological tumor responses were somewhat greater in the KD group, with a larger mean Dworak regression grade (p = 0.072) and larger percentage of near-complete (yT0N0 or yT1N1) responses (43 versus 15%, p = 0.116) that almost reached statistical significance in intention-to-treat analysis (50% versus 14%, p = 0.018). CONCLUSIONS In rectal cancer patients undergoing curative radiotherapy, a KD significantly reduced body weight and fat mass while preserving skeletal muscle mass. We could demonstrate a trend for KDs contributing synergistically to pathological tumor response, a finding in line with preclinical data that warrants future confirmation in larger studies. TRIAL REGISTRATION ClinicalTrials.gov identifier: NCT02516501, registered on August 06, 2015.
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Randomized Clinical Trial to Evaluate the Morphological Changes in the Adventitial Vasa Vasorum Density and Biological Markers of Endothelial Dysfunction in Subjects with Moderate Obesity Undergoing a Very Low-Calorie Ketogenic Diet.
Sánchez, E, Santos, MD, Nuñez-Garcia, M, Bueno, M, Sajoux, I, Yeramian, A, Lecube, A
Nutrients. 2021;(1)
Abstract
Weight loss after bariatric surgery decreases the earlier expansion of the adventitial vasa vasorum (VV), a biomarker of early atheromatous disease. However, no data are available regarding weight loss achieved by very low calorie ketogenic diets (VLCKD) on VV and lipid-based atherogenic indices. A randomized clinical trial was performed to examine changes in adventitial VV density in 20 patients with moderate obesity who underwent a 6-month very low calorie ketogenic diet (VLCKD, 600-800 kcal/day), and 10 participants with hypocaloric diet based on the Mediterranean Diet (MedDiet, estimated reduction of 500 kcal on the usual intake). Contrast-enhanced carotid ultrasound was used to assess the VV. Body composition analysis was also used. The atherogenic index of plasma (log (triglycerides to high-density lipoprotein cholesterol ratio)) and the triglyceride-glucose index were calculated. Serum concentrations of soluble intercellular adhesion molecule 1 (sICAM-1), and soluble vascular cell adhesion molecule 1 (sVCAM-1) were measured. The impact of weight on quality of life-lite (IWQOL-Lite) questionnaire was administered. Participants of intervention groups displayed a similar VV values. Significant improvements of BMI (-5.3 [-6.9 to -3.6] kg/m2, p < 0.001), total body fat (-7.0 [-10.7 to -3.3] %, p = 0.003), and IWQOL-Lite score (-41.4 [-75.2 to -7.6], p = 0.027) were observed in VLCKD group in comparison with MedDiet group. Although after a 6-months follow-up period VV density (mean, right and left sides) did not change significantly in any group, participants in the VLCKD exhibited a significantly decrease both in their atherogenic index of plasma and serum concentration of sICAM-1. A 6-month intervention with VLCKD do not impact in the density of the adventitial VV in subjects with moderate obesity, but induces significant changes in markers of endothelial dysfunction and CV risk.
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Effects of calorie restricted low carbohydrate high fat ketogenic vs. non-ketogenic diet on strength, body-composition, hormonal and lipid profile in trained middle-aged men.
Vidić, V, Ilić, V, Toskić, L, Janković, N, Ugarković, D
Clinical nutrition (Edinburgh, Scotland). 2021;(4):1495-1502
Abstract
BACKGROUND & AIMS The aim of this paper was to investigate and compare the effects of two iso-energetic hypo-caloric ketogenic hyper-ketonemic and non-ketogenic low carbohydrate high fat high cholesterol diets on body-composition, muscle strength and hormonal profile in experienced resistance-trained middle-aged men. METHODS Twenty non-competitive experienced resistance-trained middle-aged men were on the supervised calorie maintenance western diet and resistance-training regimen for 4 weeks and then divided into ketogenic and non-ketogenic groups for 8 weeks period. Keto bodies (β-hydroxybutyrate) levels were measured weekly, testosterone and insulin biweekly, strength and body-composition monthly, lipid profile and blood sugar level at the beginning and at the end of the study. RESULTS Both groups lost a similar amount of lean body mass and fat tissue (from F = 248.665, p < 0.001 to F = 21.943, p = 0.001), but preserved maximal upper and lower body strength (from F = 1.772, p = 0.238 to F = 0.595, p = 0.577). Basal testosterone and free testosterone increased (from F = 37.267, p = 0.001 to F = 16.261, p = 0.005) and insulin levels decreased significantly in both groups (F = 27.609, p = 0.001; F = 54.256, p < 0.001, respectively). No differences in lipid profile and blood sugar level were found (from F = 4.174, p = 0.058, to F = 0.065, p = 0.802). CONCLUSIONS Ketogenic diet with sustained hyper-ketonemia above 1 mol/l has the same impact as low carbohydrate non-ketogenic diet on muscle strength, body-composition, and hormonal and lipid profile in hypo-caloric dietary conditions in strength-trained middle-aged men.
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Very-Low-Calorie Ketogenic Diet as a Safe and Valuable Tool for Long-Term Glycemic Management in Patients with Obesity and Type 2 Diabetes.
Moriconi, E, Camajani, E, Fabbri, A, Lenzi, A, Caprio, M
Nutrients. 2021;(3)
Abstract
Obesity-related type 2 diabetes represents one of the most difficult challenges for the healthcare system. This retrospective study aims to determine the efficacy, safety and durability of a very-low-calorie ketogenic diet (VLCKD), compared to a standard low-calorie diet (LCD) on weight-loss, glycemic management, eating behavior and quality of life in patients with type 2 diabetes (T2DM) and obesity. Thirty patients with obesity and T2DM, aged between 35 and 75 years, who met the inclusion criteria and accepted to adhere to a VLCKD or a LCD nutritional program, were consecutively selected from our electronic database. Fifteen patients followed a structured VLCKD protocol, fifteen followed a classical LCD. At the beginning of the nutritional protocol, all patients were asked to stop any antidiabetic medications, with the exception of metformin. Data were collected at baseline and after 3 (T1) and 12 (T2) months. At T1 and T2, BMI was significantly reduced in the VLCKD group (p < 0.001), whereas it remained substantially unchanged in the LCD group. HbA1c was significantly reduced in the VLCKD group (p = 0.002), whereas a slight, although not significant, decrease was observed in the LCD group. Quality of life and eating behavior scores were improved in the VLCKD group, whereas no significant changes were reported in the LCD group, both at T1 and T2. At the end of the study, in the VLCKD group 26.6% of patients had stopped all antidiabetic medications, and 73.3% were taking only metformin, whereas 46.6% of LCD patients had to increase antidiabetic medications. The study confirms a valuable therapeutic effect of VLCKD in the long-term management of obesity and T2DM and its potential contribution to remission of the disease.
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The Effect of Exogenous Beta-Hydroxybutyrate Salt Supplementation on Metrics of Safety and Health in Adolescents.
Stefan, M, Sharp, M, Gheith, R, Lowery, R, Wilson, J
Nutrients. 2021;(3)
Abstract
The ketogenic diet is a high-fat, very low-carbohydrate, moderate-protein diet that will induce a state of ketosis, but because of its restrictive nature, it may be difficult to adhere to, especially in adolescents. Supplementing with exogenous beta-hydroxybutyrate salts may induce a state of temporary ketosis without any undesirable side effects, thereby promoting the benefits of ketosis and minimizing adherence requirements to a ketogenic diet. To date, beta-hydroxybutyrate supplementation in healthy adolescents has not been explored. Therefore, the purpose of this study was to examine the safety of exogenous beta-hydroxybutyrate salt supplementation in a healthy adolescent population. In the present study, 22 healthy male and female adolescents consumed 3.75 g of beta-hydroxybutyrate salts or maltodextrin placebo twice daily for 90 days. Comprehensive blood safety analysis, bone densitometry, happiness and emotional intelligence surveys, and blood pressure were assessed at Pre, Day 45, and Day 90. There were no significant differences detected in subjects supplementing with beta-hydroxybutyrate salts, indicating that exogenous beta-hydroxybutyrate salts had no detrimental impact on fasting blood safety metrics, bone density, happiness, emotional intelligence, or blood pressure. We conclude that supplementing with exogenous beta-hydroxybutyrate salts is safe and well-tolerated by healthy adolescents.