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

NCT02944253 | Completed

• 1 other identifier: 2016/1297
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

Obesity

Keywords

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

Outcome Measures

Primary Outcomes (4)

• Suppression of appetite sensations measured using online visual analogue scales

  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)

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

  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)

• Ketosis

  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

Secondary Outcomes (9)

• Body composition (air displacement plethysmography)

  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/fat-free mass (air displacement plethysmography)

  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 (bioelectrical impedance)

  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/fat-free mass (bioelectrical impedance analysis)

  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 measured using Bioelectrical impedance analysis

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

Study Arms (3)

Low energy diet 70 gram carbohydrates

EXPERIMENTAL

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

Other: Low energy diet 70 gram carbohydrates

Low energy diet 100 gram carbohydrates

EXPERIMENTAL

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

Other: Low energy diet 100 gram carbohydrates

Low energy diet 130 gram carbohydrates

EXPERIMENTAL

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

Other: Low energy diet 130 gram carbohydrates

Interventions

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 70 gram carbohydrates

Low energy diet 100 gram carbohydrates OTHER

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

Low energy diet 100 gram carbohydrates

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

Low energy diet 130 gram carbohydrates

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Norwegian University of Science and Technology: lead

Study Sites (1)

St Olavs Hospital

Trondheim, Norway

Location

Related Publications (6)

• Deemer SE, Plaisance EP, Martins C. Impact of ketosis on appetite regulation-a review. Nutr Res. 2020 May;77:1-11. doi: 10.1016/j.nutres.2020.02.010. Epub 2020 Feb 20.

  PMID: 32193016 BACKGROUND

• Martins C, Roekenes J, Salamati S, Gower BA, Hunter GR. Metabolic adaptation is an illusion, only present when participants are in negative energy balance. Am J Clin Nutr. 2020 Nov 11;112(5):1212-1218. doi: 10.1093/ajcn/nqaa220.

  PMID: 32844188 RESULT

• Martins C, Roekenes J, Gower BA, Hunter GR. Metabolic adaptation is associated with less weight and fat mass loss in response to low-energy diets. Nutr Metab (Lond). 2021 Jun 11;18(1):60. doi: 10.1186/s12986-021-00587-8.

  PMID: 34116675 RESULT

• 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.

  PMID: 37182692 RESULT

• Martins C, Roekenes J, Salamati S, Gower BA, Hunter GR. Reply to E Ravussin and L Redman. Am J Clin Nutr. 2020 Dec 10;112(6):1655-1656. doi: 10.1093/ajcn/nqaa309. No abstract available.

  PMID: 33301007 RESULT

• Martins C, Roekenes J, Hunter GR, Gower BA. Association between ketosis and metabolic adaptation at the level of resting metabolic rate. Clin Nutr. 2021 Aug;40(8):4824-4829. doi: 10.1016/j.clnu.2021.06.029. Epub 2021 Jul 6.

  PMID: 34358822 DERIVED

MeSH Terms

Conditions

Obesity; Weight Loss; Ketosis

Condition Hierarchy (Ancestors)

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

Study Officials

• Magne Børset, phd prof

  Norwegian University of Science and Technology

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 21, 2016
• First Posted: October 25, 2016
• Study Start: May 1, 2017
• Primary Completion: December 31, 2019
• Study Completion: December 31, 2019
• Last Updated: October 4, 2023

Record last verified: 2023-10

Locations

NO (1)