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NCT Number: NCT02944253

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

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).

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Key information

Conditions

Obesity Acid-Base Imbalance Acidosis Body Weight Body Weight Changes Ketosis Metabolic Diseases Nutrition Disorders Nutritional and Metabolic Diseases Overnutrition Overweight Pathological Conditions, Signs and Symptoms Signs and Symptoms Weight Loss

Age range

18 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

St Olavs Hospital

Trondheim, Norway

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Low energy diet 70 gram carbohydrates

Other

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

Low energy diet 100 gram carbohydrates

Other

isocaloric 4128 kilojoules/day (1000 kilocalories/day) for men and women

Low energy diet 130 gram carbohydrates

Other

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

Primary outcomes

  1. Suppression of appetite sensations measured using online visual analogue scales

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

    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.

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

    Time frame: 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 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).

  3. Suppression of appetite indicated by appetite-related hormone Cholecystokinin (CCK)

    Time frame: 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).

  4. Ketosis

    Time frame: 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).

Secondary outcomes

  1. Body composition (air displacement plethysmography)

    Time frame: 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.

  2. Percent fat/fat-free mass (air displacement plethysmography)

    Time frame: 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.

  3. Body composition (bioelectrical impedance)

    Time frame: 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.

  4. Percent fat/fat-free mass (bioelectrical impedance analysis)

    Time frame: 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.

  5. Intracellular and extracellular water measured using Bioelectrical impedance analysis

    Time frame: 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.

  6. Waist and hip circumference

    Time frame: 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.

  7. Height

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

    Height of the participant will be measured with a stadiometer and will be provided in meters.

  8. Body mass index (BMI)

    Time frame: 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

  9. Resting metabolic rate

    Time frame: 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.

Sponsors and collaborators

Lead sponsor

Norwegian University of Science and Technology

Other

Registry information

Official study title

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

Important dates

Study start
2017
Primary completion
2019
Study completion
2019
First posted
Oct 25, 2016
Registry last updated
Oct 4, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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