Clinical trial NCT03194334: Creatine, Carnitine and Carnosine in Vegetarians
Official title: Effect of a 6-month Vegetarian Diet in Omnivorous Women on Body Creatine, Carnitine and Carnosine Stores
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Dietary Modification
Keywords: vegetarianism
creatine
carnosine
carnitine
Lead sponsor: University Ghent
Sponsor class: OTHER
First posted: 2017-06-21
Enrollment: 40
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The study was scheduled over a period of 6 months. Of the 40 subjects, 10 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).
Primary purpose: BASIC_SCIENCE

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.

Eligibility criteria: 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

Primary outcomes:
measure: Fasted Plasma Beta-alanine Concentration
timeFrame: 6 months
measure: Gastrocnemius Carnosine Concentration
timeFrame: 6 months
measure: Soleus Carnosine Concentration
timeFrame: 6 months
measure: Plasma Creatine Concentration
timeFrame: 6 months
measure: Plasma Creatinine Concentration
timeFrame: 6 months
measure: Plasma Guanidinoacetate Concentration
timeFrame: 6 months
measure: Urinary Creatinine Concentration
timeFrame: 6 months
measure: Muscle Creatine Concentration
timeFrame: 3 months
measure: Plasma Carnitine Concentration
timeFrame: 6 months
measure: Plasma Acetylcarnitine Concentration
timeFrame: 6 months
measure: Plasma Total Carnitine Concentration
timeFrame: 6 months
measure: Muscle Carnitine Concentration
timeFrame: 3 months
measure: Muscle Acetylcarnitine Concentration
timeFrame: 3 months
measure: Muscle Total Carnitine Concentration
timeFrame: 3 months
Secondary outcomes:
measure: Vitamin D Status
timeFrame: 6 months
measure: Urinary Biomarker for Meat Intake: Pi-methyl-histidine
timeFrame: 6 months
measure: Urinary Biomarker for Meat Intake: Tau-methyl-histidine
timeFrame: 6 months
measure: Urinary Biomarker for Meat Intake: Anserine
timeFrame: 6 months
measure: VO2max
timeFrame: 6 months
measure: Time to Exhaustion
timeFrame: 6 months
measure: Capillary Lactate
timeFrame: 6 months
measure: Capillary pH
timeFrame: 6 months
Other outcomes:
Locations:
Study officials:
affiliation: University Ghent
name: Wim Derave, Professor
role: PRINCIPAL_INVESTIGATOR
References:
citation: Van Dyck D, Herman K, Poppe L, Crombez G, De Bourdeaudhuij I, Gheysen F. Results of MyPlan 2.0 on Physical Activity in Older Belgian Adults: Randomized Controlled Trial. J Med Internet Res. 2019 Oct 7;21(10):e13219. doi: 10.2196/13219.
citation: Blancquaert L, Baguet A, Bex T, Volkaert A, Everaert I, Delanghe J, Petrovic M, Vervaet C, De Henauw S, Constantin-Teodosiu D, Greenhaff P, Derave W. Changing to a vegetarian diet reduces the body creatine pool in omnivorous women, but appears not to affect carnitine and carnosine homeostasis: a randomised trial. Br J Nutr. 2018 Apr;119(7):759-770. doi: 10.1017/S000711451800017X.