Creatine, Carnitine and Carnosine in Vegetarians

Not Applicable

Completed

Conditions: Dietary Modification

Interventions: Behavioral: Vegetarian diet
Dietary Supplement: creatine
Dietary Supplement: Placebo
Dietary Supplement: Beta-alanine

Registration Number: NCT03194334

Lead Sponsor: University Ghent

Brief Summary: Balanced vegetarian diets are popular and contain health-promoting characteristics. A balanced lacto-ovo-vegetarian diet differs in nutrient intake from an omnivorous diet, e.g. by increased intake of fibre, magnesium and antioxidants, but lower intake of omega-3 fatty acids and vitamin B12. However, the impact of reduced to near absent intake of carnitine, carnosine and creatine in a vegetarian diet is less well established and could be relevant in relation to muscle function, exercise capacity and sports performance. Few longitudinal intervention studies investigating the effect of a vegetarian diet on the availability of these compounds currently exist.

This study aimed therefore to investigate the effect of of transiently switching omnivores onto a vegetarian diet for 6 months on muscle and plasma creatine, carnitine and carnosine homeostasis.

We hypothesized that homeostasis of creatine and carnosine would be disrupted when their dietary intake was missing. For carnitine, however, we hypothesized that homeostasis can be maintained given its slow turnover rate and its presence in some non-meat nutrients. A second aim was to investigate whether supplementation of creatine and beta-alanine (the rate-limiting precursor of carnosine synthesis), concurrently with a lacto-ovo-vegetarian diet, was able to correct for potentially emerging deficiencies.

Detailed Description: Forty healthy female omnivores will be included in this 6-month intervention study. Exclusion criteria are smoking, chronic use of medication, athletes participating in competitions, vegetarianism or eating meat or fish less than 5 times a week. The study is scheduled over a period of 6 months and measurements will be performed 1 week prior to the intervention (0M), after 3 months (3M) and within the last week (6M). Ten women will continue their omnivorous diet throughout the entire study (controls) and the other 30 subjects will switch to a lacto-ovo-vegetarian diet for 6 months. The vegetarian group will be split in 2 groups, matched for age, weight, height and baseline carnosine concentrations in soleus and gastrocnemius medialis muscles. Fifteen of them will be supplemented with beta-alanine and creatine (Veg+Suppl) and the other 15 women will receive a placebo (Veg+Pla). A co-worker, not involved in the study design and analysis, will perform the randomisation and will prepare the containers with supplements. With regard to supplementation, the study is double-blind placebo-controlled. The lacto-ovo-vegetarian diet consists of vegetables, fruits, seeds, grains, meat substitutes, eggs and dairy products and the exclusion of meat, poultry and fish. Subjects will complete a 3 day food diary at the start and after 3 months and will receive nutritional advice by a dietician during the study to prevent deficiencies in macronutrients and micronutrients. Furthermore, vegetarian recipes will be provided by email to support the subjects in their vegetarian diet.

The supplementation protocol includes simultaneously daily oral administration of creatine monohydrate (Creapure®, AlzChem AG, Germany) and slow-release beta-alanine (Carnosyn®, Natural Alternatives International, San Marcos, USA) or a placebo (maltodextrin, Natural spices, France). The supplements are considered as safe and efficacious. The Veg+Suppl group ingests 1 g of creatine monohydrate (2 capsules of 500 mg) and 0.8 g of beta-alanine (1 Carnosyn® tablet) each day during the intervention period. The Veg+Pla group will be supplemented with an identical number of capsules and tablets of maltodextrin. All subjects are asked not to take any other supplements than those provided by the current study. Compliance will be checked by asking the subjects to return the containers and counting the pills that are left. The control group, who will remain on an omnivorous diet, will not receive any supplements.

Before (0M), after 3 (3M) and 6 months (6M), subjects will perform an incremental cycling test, a fasted venous blood sample and 24hr urine will be collected, a muscle biopsy of the vastus lateralis muscle will be taken and muscle carnosine content will be determined by 1H-MRS.

A two-way analysis of variance (ANOVA) will be used to evaluate plasma and urinary metabolite concentrations, muscle carnosine, muscle biopsy metabolite concentrations, time to exhaustion (TTE) and VO2max with 'group' (Veg+Suppl; Veg+Pla; control) as between-subject factor and 'time' (0M; 3M; 6M) as within-subject factor (SPSS statistical software, SPSS Inc, Chicago, USA). For the analysis of capillary lactate and pH, measurements before and after the incremental cycling test were included as another within factor (start; end). In case of significance, analyses were repeated for each group separately and pairwise comparisons were used to compare the different time points. Values will be presented as mean ± SD and statistical significance threshold will be set at p ≤0.05.

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 40

Inclusion Criteria

women

Exclusion Criteria

smoking, chronic use of medication or taking supplements, athletes participating in competitions, vegetarianism or eating meat or fish less than 5 times a week

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Veg+ creatine and beta-alanine	creatine	switch to a lacto-ovo-vegetarian diet for 6 months and are supplemented with 1 g of creatine monohydrate (2 capsules of 500 mg) and 0.8 g of beta-alanine (1 Carnosyn® tablet) each day
Veg+ creatine and beta-alanine	Beta-alanine	switch to a lacto-ovo-vegetarian diet for 6 months and are supplemented with 1 g of creatine monohydrate (2 capsules of 500 mg) and 0.8 g of beta-alanine (1 Carnosyn® tablet) each day
Veg+Pla	Vegetarian diet	vegetarian + placebo: switch to a lacto-ovo-vegetarian diet for 6 months and are supplemented with placebo pills instead of beta-alanine and creatine
Veg+ creatine and beta-alanine	Vegetarian diet	switch to a lacto-ovo-vegetarian diet for 6 months and are supplemented with 1 g of creatine monohydrate (2 capsules of 500 mg) and 0.8 g of beta-alanine (1 Carnosyn® tablet) each day
Veg+Pla	Placebo	vegetarian + placebo: switch to a lacto-ovo-vegetarian diet for 6 months and are supplemented with placebo pills instead of beta-alanine and creatine

Primary Outcome Measures

Name	Time	Method
Fasted Plasma Beta-alanine Concentration	6 months	Fasted venous plasma beta-alanine concentration (precursor for carnosine) at 0, 3 and 6 months of the intervention
Gastrocnemius Carnosine Concentration	6 months	Gastrocnemius carnosine concentration at 0, 3 and 6 months of the intervention
Soleus Carnosine Concentration	6 months	Soleus carnosine concentration at 0, 3 and 6 months of the intervention
Plasma Creatine Concentration	6 months	Plasma creatine concentration at 0, 3 and 6 months of the intervention
Plasma Creatinine Concentration	6 months	Plasma creatinine at 0, 3 and 6 months of the intervention
Plasma Guanidinoacetate Concentration	6 months	Plasma guanidinoacetate at 0, 3 and 6 months of the intervention
Urinary Creatinine Concentration	6 months	Urinary creatinine at 0, 3 and 6 months of the intervention
Muscle Creatine Concentration	3 months	Muscle total creatine concentration in vastus lateralis muscle at 0 and 3 months of the intervention
Plasma Carnitine Concentration	6 months	plasma free carnitine concentration at 0, 3 and 6 months of the intervention
Plasma Acetylcarnitine Concentration	6 months	plasma acetylcarnitine concentration at 0, 3 and 6 months of the intervention
Plasma Total Carnitine Concentration	6 months	plasma total carnitine concentration (free + acetyl) at 0, 3 and 6 months of the intervention
Muscle Carnitine Concentration	3 months	muscle free carnitine concentration in vastus lateralis muscle at 0 and 3 months of the intervention
Muscle Acetylcarnitine Concentration	3 months	muscle acetylcarnitine concentration in vastus lateralis muscle at 0 and 3 months of the intervention
Muscle Total Carnitine Concentration	3 months	muscle total carnitine concentration (free + acetylcarnitine) in vastus lateralis muscle at 0 and 3 months of the intervention

Secondary Outcome Measures

Name	Time	Method
Vitamin D Status	6 months	Serum 25-Hydroxyvitamin D concentration at 0, 3 and 6 months of the intervention
Urinary Biomarker for Meat Intake: Pi-methyl-histidine	6 months	urinary pi-methyl-histidine concentration at 0, 3 and 6 months of the intervention
Urinary Biomarker for Meat Intake: Tau-methyl-histidine	6 months	urinary tau-methyl-histidine concentration at 0, 3 and 6 months of the intervention
Urinary Biomarker for Meat Intake: Anserine	6 months	urinary anserine concentration at 0, 3 and 6 months of the intervention
VO2max	6 months	VO2max during incremental cycling test performed at 0, 3 and 6 months
Time to Exhaustion	6 months	Time to exhaustion during incremental cycling test performed at 0, 3 and 6 months
Capillary Lactate	6 months	capillary lactate at the start and at the end of the incremental cycling test performed at 0, 3 and 6 months
Capillary pH	6 months	capillary pH at the start and at the end of the incremental cycling test performed at 0, 3 and 6 months