What is the Maximum Amount of Carbohydrates That is Still Able to Induce Ketosis and Suppress Appetite?

What is the Maximum Amount of Carbohydrates That is Still Able to Induce Ketosis and Suppress Appetite?

Ketosis and Appetite Suppression - What is the Maximum Carbohydrate Intake That is Still Associated With Appetite Suppression in a Low Energy Diet?

Two dietary approaches, very low energy diets (VLEDs) and ketogenic low carbohydrate diets (KLCDs), have the ability to suppress appetite. The suppression of appetite typically observed during these diets is believed (but not clinically proven) to be due to ketosis, a condition where circulating concentrations of ketone bodies are increased due to a higher production of ketones in the liver. Little is known about the potential mechanisms through which ketosis may lead to appetite suppression in VLEDs and KLCDs. A 'ketogenic diet' typically contains less than 50 grams carbohydrate per day, yet ketosis has been seen in subjects who consume diets with a carbohydrates ranging between 59-192 grams per day. Although an association between ketosis and appetite suppression has been established, the minimum level of ketosis and maximum carbohydrate intake that is still associated with appetite suppression remains unknown and should be explored. The ability to increase carbohydrate intake while maintaining a suppressed appetite will allow dieters to consume more carbohydrate-rich food that is beneficial for health without feeling more hungry. The study, 'can Appetite Suppression be achieved using KEtogenic Diets with more carbohydrates?' (ASKED) aimed to: to identify the maximum carbohydrate intake that is still associated with appetite suppression in a low energy diet and to determine the impact of a higher carbohydrate intake on appetite suppression, ketosis, body composition, and resting metabolic rate. A to evaluate the impact of weight loss while in and out of ketosis on markers of appetite (appetite related hormones and appetite sensations measured using visual analogue scales).

A total of 101 healthy, weight stable (< 2 kg variation in BW within the last 3 months), adult (18-65 years old) individuals with obesity (body mass index [BMI] 30-45 kg/m2) who were not actively trying to lose weight were recruited through advertisements in Facebook, Twitter and the intranet of St. Olavs Hospital and the Norwegian University of Science and Technology (NTNU) in Trondheim, Norway from May 2017 - August 2018. Informed consent was obtained from all participants before enrollment in the study, and participants were allowed to withdraw at any time. Study participants were randomized to one of three intervention arms: low, medium, or high CHO groups. Computer-generated randomization was performed using a block sampling (fixed block size) and stratification approach to account for the potential confounding factors of sex and BMI (< 35 and ≥ 35 kg/m2). (34, 35). Study participants were not made aware of which intervention arm they were allocated to until the end of the trial. All participants underwent an 8-week, supervised LED containing different amounts of CHO, followed by 4 weeks of gradual refeeding and weight stabilization. Measurements were taken before diet initiation (baseline), at the end of the WL phase (week 8) and at the end of the weight stabilization phase (week 12) to allow for the evaluation of the impact of WL in or out of ketosis on appetite markers.

Diet, Reducing, Hunger, Appetite Regulation, Ketogenic Diet, Caloric Restriction, Weight Loss, Ketosis

isocaloric 4128 kilojoules/day (1000 kilocalories/day) for men and women, low energy diet containing 70 gram carbohydrates for 8 weeks.

isocaloric (4128 kilojoules/day (1000 kilocalories/day) for men and women, low energy diet containing 100 gram carbohydrates for 8 weeks.

isocaloric 4128 kilojoules/day (1000 kilocalories/day) for men and women, low energy diet containing 130 gram carbohydrates for 8 weeks.

isocaloric 4128 kilojoules/day (1000 kilocalories/day) for men and women, low energy diet containing 70 gram carbohydrates

isocaloric 4128 kilojoules/day (1000 kilocalories/day) for men and women, low energy diet containing 130 gram carbohydrates

Assessed by an online version of Visual Analogue Scale (VAS), a validated scale used to measure appetite sensations in response to questions posed regarding feelings of hunger, fullness, desire to eat, prospective consumption. Study participants are asked questions such as 'How hungry do you feel right now?' and are asked to provide a response by marking across a 100 millimeter long line with sentences anchored at each end such as "I have never been more hungry/ or I am not hungry at all" corresponding to their feeling. VAS measurements are done in fasting, immediately after a meal and every 30 minutes for 2.5 hours. Measurements are quantified by measuring the distance from the left end of the line to the mark indicated by the participant.

12 weeks (at start of study (baseline), at week 9 (after diet induced weight loss period), and week 13 (after weight stabilization period)

Suppression of appetite indicated by appetite-related hormones Active Ghrelin, Total Glucagon Like Peptide-1, Total Peptide YY and Insulin

Measurement of plasma samples of appetite related hormones: Active ghrelin (AG), Total Glucagon Like Peptide-1 (Total GLP-1), Total Peptide YY (Total PYY) and Insulin measured in fasting, immediately after a meal and every 30 minutes for a period of 2.5 hours. Blood samples are first collected in Ethylenediaminetetraacetic acid (EDTA) tubes (72 milliliters in total) and centrifuged for 10 minutes at 18 degrees celsius with 3200 revolutions per minute (RPM). Plasma samples are then stored in -80 degree celsius freezer until analysis using a Metabolic Hormone Magnetic Bead Panel (Lincoplex Kit, Merck Millipore, USA). Results of plasma samples of these hormones will be presented in picograms (pg) per milliliter (ml).

12 weeks (at start of study (baseline), at week 9 (after diet induced weight loss period), and week 13 (after weight stabilization period)

Measurement of plasma samples of appetite related hormone Cholecystokinin (CCK) measured in fasting, immediately after a meal and every 30 minutes for a period of 2.5 hours. Blood samples are first collected in Ethylenediaminetetraacetic acid (EDTA) tubes (72 milliliters in total inclusive of blood collected for analysis of hormones listed above) and centrifuged for 10 minutes at 18 degrees celsius with 3200 revolutions per minute (RPM). Plasma samples are then stored in -80 degree celsius freezer until they are sent to the University of Copenhagen to be analyzed by the research group of Professor Jens F Rehfeld using his 'In-house Radioimmunoassay method'. The results of plasma CCK will be presented in picomoles (pmol) per liter (l).

12 weeks (at start of study (baseline), at week 9 (after diet induced weight loss period), and week 13 (after weight stabilization period)

Measured with beta hydroxybutyrate (BHB), a ketone body and indicator of ketosis in plasma form. Fasting blood samples are first collected in Ethylenediaminetetraacetic acid (EDTA) tubes (inclusive of the 72 milliliters of blood collected for analysis of appetite hormones listed above) and centrifuged for 10 minutes at 18 degrees celsius with 3200 revolutions per minute (RPM). Plasma samples are then stored in -80 degree celsius freezer until analysis using a Ketone Body Assay (MAK-134, Merck Millipore, USA). The results of plasma BHB will be presented in millimoles (mmol) per liter (l).

12 weeks (at start of study (baseline), at week 9 (after diet induced weight loss period), and week 13 (after weight stabilization period

Body composition measured with air displacement plethysmography (BodPod, COSMED, Italy). The output of the measurement of body composition using air displacement plethysmography provides absolute values in kilograms for body weight, fat mass and fat free mass.

12 weeks (at start of study (baseline), at week 9 (after diet induced weight loss period), and week 13 (after weight stabilization period)

Percent fat mass and fat free mass is measured with air displacement plethysmography (BodPod, COSMED, Italy). The output of the measurement of body composition using air displacement plethysmography provides fat mass and fat free mass as a percentage of total body weight.

12 weeks (at start of study (baseline), at week 9 (after diet induced weight loss period), and week 13 (after weight stabilization period)

Body composition measured using bioelectrical impedance analysis (BIA, Biospace, Korea). The output of the measurement of body composition using bioelectrical impedance analysis provides absolute values in kilograms for body weight, fat mass and fat free mass.

12 weeks (at start of study (baseline), at week 9 (after diet induced weight loss period), and week 13 (after weight stabilization period)

Percent fat mass and fat free mass is measured with bioelectrical impedance analysis (BIA, Biospace, Korea). The output of the measurement of body composition using bioelectrical impedance analysis provides fat mass and fat free mass as a percentage of total body weight.

12 weeks (at start of study (baseline), at week 9 (after diet induced weight loss period), and week 13 (after weight stabilization period)

Intracellular and extracellular water is measured with bioelectrical impedance analysis (BIA, Biospace, Korea). The output of the measurement of body composition using bioelectrical impedance analysis provides information on the amount total body water (made up of intracellular and extracellular water) in liters.

12 weeks (at start of study (baseline), at week 9 (after diet induced weight loss period), and week 13 (after weight stabilization period)

Waist and hip circumference will be measured with a measuring tape and the results will be provided in centimeters.

12 weeks (at start of study (baseline), at week 9 (after diet induced weight loss period), and week 13 (after weight stabilization period)

12 weeks (at start of study (Baseline), at week 9 (after diet induced weight loss period), and week 13 (after weight stabilization period)

Body mass index (BMI) will be calculated using the measurements of body weight (obtained using the weight in kilograms output provided by bioelectrical impedance analysis) and height in meters measured using the stadiometer using the following formula: (kilograms/meters)^2

12 weeks (at start of study (Baseline), at week 9 (after diet induced weight loss period), and week 13 (after weight stabilization period)

Measured through indirect calorimetry. Indirect calorimetry is a technique that measures oxygen consumption and carbon dioxide production during rest to estimate resting metabolic rate. Results will be presented in kilocalories per day.

12 weeks (at start of study (Baseline), at week 9 (after diet induced weight loss period), and week 13 (after weight stabilization period)

Inclusion Criteria: class I or II obesity (BMI 30-45 kg/m2) weight stable (<2 kg variation in weight within the last 3 months) not currently dieting to lose weight women who are either post-menopausal, taking oral contraceptives or with a normal cycle (28 ± 2 days) Exclusion Criteria: pregnant breast-feeding drug or alcohol abuse within the last two years currently taking medication known to affect appetite or induce weight loss enrolled in another obesity treatment program history of psychological disorders having had bariatric surgery metabolic diseases (such as hypo/hyperthyroidism and diabetes type 1 or 2) eating disorders lactose intolerance gastrointestinal (particularly cholelithiasis), kidney, liver, lung, cardiovascular disease malignancies

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Martins C, Nymo S, Aukan MI, Roekenes JA, Coutinho SR, Hunter GR, Gower BA. Association between ss-Hydroxybutyrate Plasma Concentrations after Hypocaloric Ketogenic Diets and Changes in Body Composition. J Nutr. 2023 Jul;153(7):1944-1949. doi: 10.1016/j.tjnut.2023.05.010. Epub 2023 May 12.

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