The Influence of Nutrition Intervention on the P1NP and CTX-1 Response to an Acute Exercise Bout: A Systematic Review with Meta-Analysis.

Background: Although nutrition and exercise both influence bone metabolism, little is currently known about their interaction, or whether nutritional intervention can modulate the bone biomarker response to acute exercise. Improved understanding of the relationships between nutrition, exercise and bone metabolism may have substantial potential to inform nutritional interventions to protect the bone health of exercising individuals, and to elucidate mechanisms by which exercise and nutrition influence bone.

Objective: The aim was to synthesise available evidence related to the influence of nutrition on the response of the bone biomarkers procollagen type 1 N-terminal propeptide (P1NP) and C-terminal telopeptide of type 1 collagen (CTX-1) to acute exercise, using a systematic review and meta-analytic approach.

Methods: Studies evaluating the influence of nutritional status or intervention on the bone biomarker response to an acute exercise bout were included and separated into four categories: (1) feeding status and energy availability, (2) macronutrients, (3) micronutrients and (4) other. Studies conducted on healthy human populations of any age or training status were included. Meta-analysis was conducted when data from at least five studies with independent datasets were available. In the case of insufficient data to warrant meta-analysis, results from individual studies were narratively synthesised and standardised mean effect sizes visually represented.

Results: Twenty-two articles were included. Of these, three investigated feeding status or energy availability, eight macronutrients, eight micronutrients (all calcium) and six other interventions including dairy products or collagen supplementation. Three studies had more than one intervention and were included in all relevant outcomes. The largest and most commonly reported effects were for the bone resorption marker CTX-1. Meta-analysis indicated that calcium intake, whether provided via supplements, diet or infusion, reduced exercise-induced increases in CTX-1 (effect size - 1.1; 95% credible interval [CrI] -  2.2 to - 0.05), with substantially larger effects observed in studies that delivered calcium via direct infusion versus in supplements or foods. Narrative synthesis suggests that carbohydrate supplementation may support bone during acute exercise, via reducing exercise-induced increases in CTX-1. Conversely, a low-carbohydrate/high-fat diet appears to induce the opposite effect, as evidenced by an increased exercise associated CTX-1 response, and reduced P1NP response. Low energy availability may amplify the CTX-1 response to exercise, but it is unclear whether this is directly attributable to energy availability or to the lack of specific nutrients, such as carbohydrate.

Conclusion: Nutritional intervention can modulate the acute bone biomarker response to exercise, which primarily manifests as an increase in bone resorption. Ensuring adequate attention to nutritional factors may be important to protect bone health of exercising individuals, with energy, carbohydrate and calcium availability particularly important to consider. Although a wide breadth of data were available for this evidence synthesis, there was substantial heterogeneity in relation to design and intervention characteristics. Direct and indirect replication is required to confirm key findings and to generate better estimates of true effect sizes.