Alpha and Omega of Lifestyle Therapy - Resistance Training and Ingestion of n-3 Polyunsaturated Fatty Acids to Improve Health and Muscle Functions in Individuals With Obesity and Healthy Controls
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 150
- 试验地点
- 1
- 主要终点
- Muscle thickness, ultrasound
研究概览
简要总结
The study aims to investigate the effects of double-blinded, randomized placebo-controlled n3-fatty acid supplementation (1000 mg day-1) and 13 weeks of resistance training on muscle function/biology and systemic health in individuals with obesity (BMI>30) and lean individuals (BMI<30)
详细描述
Lifestyle therapy is important for treating lifestyle-related morbidities such as obesity. Such therapy often includes exercise and nutrition, and leads to improved health, functionality and quality of life. Unfortunately, obesity leads to adverse changes in the physiological milieu, including inflammation and altered nutritional status such as reduced omega-3:omega-6 ratios. Indeed, inadequate omega 3 levels are common even among lean individuals. This may negatively affect the outcome of lifestyle therapy with exercise, particularly those involving resistance training, contributing to the large heterogeneity seen in training responses. In accordance with this, many individuals (including both lean and obese subjects) fail to improve muscle biology/functions and health, including failure to increase muscle mass and strength, failure to improve glucose handling and inflammatory status. This makes general lifestyle therapy recommendations ineffective. Here, we investigate effects of double-blinded, randomized placebo-controlled n3-fatty acid supplementation (1000 mg day-1) and 13 weeks of low- and high-load resistance training on muscle growth/function/biology and health in individuals with obesity (BMI>30, n=60) and lean controls (BMI<30, n=60). Each participant will perform two different training protocols, one on each leg. The supplement period will commence 7 weeks prior to the onset of the strength training intervention to ensure adequate omega-3 biology at the onset of training. Analyses include assessment of the separate and combined effects of n3-supplementation and obesity on training responses to resistance training, measured as muscle mass, muscle strength/functionality, muscle biological traits, and systemic health variables such as hormone/inflammation/glucose biology, adipose tissue biology/mass, gut microbiome and health-related quality of life. The project will provide important insight into the feasibility of resistance training and n-3 fatty acid supplementation for treating individuals with obesity, paving the way for personalized lifestyle therapy.
The study has two defined main outcome measures, targeting the combined effects of omega-3 and strength training on i) muscle thickness of the thigh (measured using ultrasound; this main outcome measure targets the effects of the intervention on muscle growth), and ii) glucose tolerance (measured using an oral glucose test; this main outcome measure targets the effects of the intervention on improvements in health).
In our analytical approach, we will use a mixed model-approach to assess the main effects of the intervention, mainly defined as changes from before to after the resistance training intervention. Importantly, for health variables such as glucose tolerance, analyses will be performed by accounting for individual variation at baseline, as any beneficial effect can be expected to be higher/present only in individuals with a pathological/diseased starting point. Notably, for many variables, we will collect data from two additional time points (pre-supplementation and after two weeks of familiarization to training). These data will provide insight into additional perspectives, such as the effects of omega-3 intake-only on glucose tolerance, which will bring additional depth to our conclusions (these analyses are not necessarily specified in the Outcome Measures section). For other data, such as primary cultivation of skeletal muscle and muscle mitochondrial respiration, data will only be collected from a randomized subset of participants. For analyses of the effects of the intervention on obesity-related pathophysiologies and health-related quality of life, data from a group of non-intervention individuals will act as reference values (data sampled alongside the intervention). Finally, we will use regression analyses to explain individual differences in training responses, with particular emphasis on muscle hypertrophy/glucose tolerance and their mechanistic origin of nature.
2021/08: The number of anticipated participants was increased from 120 to 150 due to circumstances relating to the SARS-CoV-2 pandemic
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Factorial
- 主要目的
- Basic Science
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 30 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Untrained (less than 2 sessions of resistance exercise per month and less than 3 hours of endurance exercise per week)
排除标准
- •Unstable cardiovascular disease
- •Injuries affecting the ability to perform heavy resistance exercise
- •Mental illness
- •Allergy to local anesthesia
- •Use of medicine or drugs containing steroids the last two months prior to inclusion
结局指标
主要结局
Muscle thickness, ultrasound
时间窗: Changes from before to after the resistance training intervention (week 8 to 20)
Muscle thickness of vastus lateralis and vastus intermedius measured using ultrasound
Glucose tolerance
时间窗: Changes from before to after the resistance training intervention (week 8 to 20)
Glucose tolerance measured using an oral glucose tolerance test
次要结局
- Blood pressure at rest(Changes from before to after the resistance training intervention (week 8 to 20))
- Lean body mass(Changes from before to after the resistance training intervention (week 8 to 20))
- Muscle mass, MRI(Changes from before to after the resistance training intervention (week 8 to 20))
- Muscle mass, combined measure(Changes from before to after the resistance training intervention (week 8 to 20))
- Fat infiltration (muscle)(Changes from before to after the resistance training intervention (week 8 to 20))
- Peak power output during one-legged cycling(Changes from before to after the resistance training intervention (week 8 to 20))
- Unilateral lower body muscle endurance(Changes throughout the course of the resistance training intervention (weeks 8, 10 and 20))
- Waist circumference(Changes from before to after the resistance training intervention (week 8 to 20))
- Fat mass(Changes from before to after the resistance training intervention (week 8 to 20))
- Unilateral lower body maximal strength(Changes throughout the course of the resistance training intervention (weeks 8, 10 and 20))
- Visceral fat mass(Changes from before to after the resistance training intervention (week 8 to 20))
- Muscle quality(Changes from before to after the resistance training intervention (week 8 to 20))
- Fasting blood glucose(Changes throughout the course of the intervention (weeks 0, 8 and 20))
- N-3 PUFA (blood)(Changes throughout the course of the intervention (weeks 0, 8 and 20))
- Gene expression in subcutaneous fat(Changes from before to after the resistance training intervention (week 8 to 20))
- Gut microbiome (feces, N3-supplementation-only)(Changes from before to after N3-supplementation-only (week 0 to 8))
- Activities of daily living(Changes throughout the course of the intervention (week 0, 8 and 20))
- Musculoskeletal pain (Nordic Pain Questionnaire)(Changes throughout the course of the training intervention (weeks 0, 8 and 20))
- Muscle mass, immunohistochemistry(Changes from before to after the resistance training intervention (week 8 to 20))
- Muscle capillarization(Changes from before to after the resistance training intervention (week 8 to 20))
- Unilateral lower body isokinetic muscle strength(Changes throughout the course of the resistance training intervention (weeks 8, 10 and 20))
- Unilateral lower body isometric muscle strength(Changes throughout the course of the resistance training intervention (weeks 8, 10 and 20))
- Muscle fractional synthesis rate(Week 18 to 20)
- Musculoskeletal pain (VAS)(Changes throughout the course of the training intervention (weeks 0, 8 and 20))
- Fecal short-chained fatty acids (training intervention)(Changes from before to after the resistance training intervention (week 8 to 20))
- Health-related quality of life in overweight/obesity(Changes throughout the course of the intervention (week 0, 8 and 20))
- Muscle fibre type composition(Changes from before to after the resistance training intervention (week 8 to 20))
- Myonuclear number(Changes from before to after the resistance training intervention (week 8 to 20))
- Muscle satellite cell number(Changes throughout the course of the resistance training intervention (weeks 8, 10 and 20))
- Oxygen consumption during one-legged cycling(Changes from before to after the resistance training intervention (week 8 to 20))
- Nutritent concentrations in blood(Changes throughout the course of the intervention (weeks 0, 8 and 20))
- Concentrations of inflammatory factors in blood(Changes throughout the course of the intervention (weeks 0, 8 and 20))
- Gene expression in skeletal muscle (intervention)(Changes from before to after the resistance training intervention (week 8 to 20))
- Health-related quality of life (SF-36)(Changes throughout the course of the intervention (week 0, 8 and 20))
- Health-related quality of life (PANAS)(Changes throughout the course of the intervention (week 0, 8 and 20))
- Arterial stiffness(Throughout the course of the intervention (week 0, 8 and 20))
- Fecal short-chained fatty acids (N3-supplementation-only)(Changes from before to after N3-supplementation-only (week 0 to 8))
- Hemoglobin glycosylation (HbA1c)(Changes throughout the course of the intervention (weeks 0, 8 and 20))
- Lipid concentrations in blood(Changes throughout the course of the intervention (weeks 0, 8 and 20))
- Gene expression in skeletal muscle (familiarization)(Changes from before to after familiarization to resistance exercise (week 8 to 10))
- Gastrointestinal symptoms(Changes throughout the course of the training intervention (weeks 0, 8 and 20))
- Inflammatory characteristics of peripheral blood mononuclear cell (PBMC)(Throughout the course of the intervention (weeks 0, 8 and 20))
- Hormone concentrations in blood(Changes throughout the course of the intervention (weeks 0, 8 and 20))
- Protein abundance in skeletal muscle (intervention)(Changes from before to after the resistance training intervention (week 8 to 20))
- Protein abundance in skeletal muscle (familiarization)(Changes from before to after the resistance training intervention (week 8 to 10))
- Mitochondrial functions in muscle(Changes from before to after the resistance training intervention (week 8 to 20))
- Satellite cell proliferation and myotube growth (in vitro)(Changes from before to after N3-supplementation-only (week 0 to 8))
- Gut microbiome (feces, training intervention)(Changes from before to after the resistance training intervention (week 8 to 20))