Clinical trial NCT02944253: What is the Maximum Amount of Carbohydrates That is Still Able to Induce Ketosis and Suppress Appetite?
Official title: Ketosis and Appetite Suppression - What is the Maximum Carbohydrate Intake That is Still Associated With Appetite Suppression in a Low Energy Diet?
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Obesity
Keywords: Diet, Reducing
Hunger
Appetite Regulation
Ketogenic Diet
Caloric Restriction
Weight Loss
Ketosis
Lead sponsor: Norwegian University of Science and Technology
Sponsor class: OTHER
First posted: 2016-10-25
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Suppression of appetite sensations measured using online visual analogue scales
timeFrame: 12 weeks (at start of study (baseline), at week 9 (after diet induced weight loss period), and week 13 (after weight stabilization period)
measure: Suppression of appetite indicated by appetite-related hormones Active Ghrelin, Total Glucagon Like Peptide-1, Total Peptide YY and Insulin
timeFrame: 12 weeks (at start of study (baseline), at week 9 (after diet induced weight loss period), and week 13 (after weight stabilization period)
measure: Suppression of appetite indicated by appetite-related hormone Cholecystokinin (CCK)
timeFrame: 12 weeks (at start of study (baseline), at week 9 (after diet induced weight loss period), and week 13 (after weight stabilization period)
measure: Ketosis
timeFrame: 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:
measure: Body composition (air displacement plethysmography)
timeFrame: 12 weeks (at start of study (baseline), at week 9 (after diet induced weight loss period), and week 13 (after weight stabilization period)
measure: Percent fat/fat-free mass (air displacement plethysmography)
timeFrame: 12 weeks (at start of study (baseline), at week 9 (after diet induced weight loss period), and week 13 (after weight stabilization period)
measure: Body composition (bioelectrical impedance)
timeFrame: 12 weeks (at start of study (baseline), at week 9 (after diet induced weight loss period), and week 13 (after weight stabilization period)
measure: Percent fat/fat-free mass (bioelectrical impedance analysis)
timeFrame: 12 weeks (at start of study (baseline), at week 9 (after diet induced weight loss period), and week 13 (after weight stabilization period)
measure: Intracellular and extracellular water measured using Bioelectrical impedance analysis
timeFrame: 12 weeks (at start of study (baseline), at week 9 (after diet induced weight loss period), and week 13 (after weight stabilization period)
measure: Waist and hip circumference
timeFrame: 12 weeks (at start of study (baseline), at week 9 (after diet induced weight loss period), and week 13 (after weight stabilization period)
measure: Height
timeFrame: 12 weeks (at start of study (Baseline), at week 9 (after diet induced weight loss period), and week 13 (after weight stabilization period)
measure: Body mass index (BMI)
timeFrame: 12 weeks (at start of study (Baseline), at week 9 (after diet induced weight loss period), and week 13 (after weight stabilization period)
measure: Resting metabolic rate
timeFrame: 12 weeks (at start of study (Baseline), at week 9 (after diet induced weight loss period), and week 13 (after weight stabilization period)
Other outcomes:
Locations:
city: Trondheim
country: Norway
facility: St Olavs Hospital
Study officials:
affiliation: Norwegian University of Science and Technology
name: Magne Børset, phd prof
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.