Nutrition, exercise and cardiometabolic health

This body of work examined the role of skeletal muscle, diet, and exercise in cardiovascular rehabilitation and risk reduction.

Early research showed that COVID-19 restrictions substantially disrupted cardiac rehabilitation participation and accelerated the shift toward home-based and digitally supported exercise delivery.

Complementary work highlighted the potential cardiometabolic consequences of reduced physical activity, including accelerated muscle loss and worsening metabolic health, emphasising resistance exercise and adequate protein intake as key strategies to preserve muscle mass.

Building on this, feasibility research investigated the implementation of a combined resistance training and high-protein Mediterranean-style dietary intervention in cardiac rehabilitation patients with sarcopenic obesity.

This work now underpins ongoing research exploring whether targeted lifestyle interventions aimed at improving skeletal muscle mass and dietary quality can enhance cardiometabolic health and support both rehabilitation and prehabilitation strategies in individuals at elevated cardiovascular risk.

This body of work has focused on the methodological development and biochemical characterisation of lipoprotein subclasses to better understand their role in cardiometabolic disease.

Initial work developed and validated an improved method for the rapid separation of LDL subclasses using iodixanol gradient ultracentrifugation, enabling more precise isolation of lipoprotein fractions for downstream biochemical analysis.

Subsequent research applied metabolomic approaches to characterise the metabolic composition of these LDL subclasses, revealing distinct metabolite signatures across lipoprotein fractions and providing new insight into the biochemical heterogeneity of LDL particles.

Building on this foundation, ongoing work is extending these approaches to HDL, comparing separation techniques including traditional salt gradients and iodixanol gradients to determine how methodological differences influence HDL metabolite profiles, apolipoprotein composition, and functional properties.

Together, this programme of work aims to refine analytical approaches for lipoprotein characterisation while improving our understanding of the structural and functional diversity of circulating lipoproteins in cardiometabolic health.

This project will investigate how contrasting dietary patterns influence lipoprotein metabolism and cardiovascular disease (CVD) risk.

Despite growing public interest in carnivore diets, there is currently a lack of randomised controlled trial evidence evaluating their cardiovascular effects. Emerging observational and short-term evidence suggests these diets may substantially increase LDL concentrations and are typically high in saturated fat, a dietary factor known to promote LDL aggregation (an important mechanistic step in the development of atherosclerosis).

This study will therefore compare the effects of a Mediterranean-style diet and a carnivore diet on LDL aggregation susceptibility and related lipoprotein profiles, including LDL, VLDL, and HDL, in individuals at elevated risk of CVD.

We will conduct a human study to determine whether these distinct dietary patterns produces differential effects on lipid metabolism and markers of CVD risk.

This project builds on existing community-based initiatives to improve cardiometabolic health through accessible dietary change.

Centred on the co-produced Kirkby Kitchen recipe resource, developed collaboratively by LJMU nutrition students and members of the Kirkby community and inspired by Mediterranean-style dietary principles, the project will examine how community-driven nutrition interventions can support healthier eating behaviours.

A key strength of this initiative is its co-production with residents and organisations, ensuring the resource is culturally relevant, practical, and community-owned.

Working alongside related studies, this project will seek to replicate this co-production approach and evaluate its impact on dietary behaviours and cardiometabolic health outcomes within the community.

This body of work investigated the metabolic and cardiovascular implications of carbohydrate restriction using a combination of systematic reviews, meta-analyses, and controlled human interventions.

Early work synthesised evidence from large randomised controlled trials examining carbohydrate-restricted diets in overweight and obese populations and found broadly comparable effects on LDL cholesterol relative to low-fat diets, alongside favourable changes in other lipid markers such as HDL cholesterol and triglycerides.

Complementing this population-level evidence, a randomised controlled trial examined the effects of contrasting dietary patterns on cardiometabolic health and demonstrated improvements in insulin sensitivity while identifying distinct metabolic adaptations associated with carbohydrate restriction, including shifts in lipid-related metabolites and circulating lipoprotein profiles.

In parallel, systematic review work explored the acute cardiometabolic effects of low-carbohydrate, high-fat meals in the postprandial state and found that such meals often increased postprandial triglyceride responses and may have transiently impaired endothelial function, although results across studies were heterogeneous.

Collectively, these studies highlighted the complexity of carbohydrate restriction and suggested that its cardiometabolic effects are context dependent, varying according to factors such as duration of exposure, dietary composition, and the populations studied.

This body of work investigated the determinants and clinical implications of discordance between LDL cholesterol (LDL-C) and apolipoprotein B (ApoB), a phenotype increasingly recognised in cardiovascular risk assessment.

Population-based analyses showed that individuals with discordantly high ApoB relative to LDL-C exhibited greater adiposity, insulin resistance and systemic inflammation.

Using Mendelian randomisation, this work also demonstrated for the first time that increased adiposity was genetically causal for elevated ApoB, but not LDL-C, highlighting a mechanistic link between body fat and atherogenic lipoprotein particle number.

Complementary analyses examining dietary patterns showed that this phenotype was associated with nutrient patterns higher in saturated fat and refined carbohydrates and lower in fibre and unsaturated fats.

Further analyses also showed that discordantly high ApoB was associated with markers of renal dysfunction and an increased likelihood of chronic kidney disease. Together, these studies highlighted that discordance between LDL-C and ApoB reflects a distinct cardiometabolic phenotype linked to adiposity, diet and metabolic dysfunction.

This body of work developed and evaluated a comprehensive research programme investigating how protein nutrition and resistance exercise influence skeletal muscle mass, cardiometabolic health, and cardiovascular outcomes in populations at elevated risk.

This included a systematic review and meta-analysis synthesised randomised controlled trials demonstrating that protein supplementation significantly augments the effects of resistance exercise on appendicular lean mass and handgrip strength in older adults compared to exercise alone.

Mendelian randomisation analyses demonstrating that increased appendicular lean mass and grip strength are causally associated with favourable lipoprotein particle profiles; an observational study of UK cardiac rehabilitation during COVID-19 restrictions. 

Through extensive patient and public involvement with clinical rehabilitation services, a randomised controlled trial protocol was designed integrating high-protein Mediterranean-style nutrition with progressive resistance training.

A subsequent mixed-methods feasibility and acceptability study involving service users in participatory co-design explored barriers and facilitators to intervention adoption and implementation in real-world rehabilitation settings. This culminated in a controlled trial in a phase 4 cardiac rehab population.

This body of work has investigated how different dietary lipid sources influence cardiometabolic risk, lipoprotein metabolism, and nutritional guidance for diverse populations.

Early research from the OPTILIP programme examined the metabolic effects of altering the dietary ratio of n-6 to n-3 polyunsaturated fatty acids, demonstrating that increasing long-chain n-3 fatty acid intake reduced fasting and postprandial triglycerides and shifted LDL particles toward a less atherogenic size profile.

Complementary studies also explored the effects of dietary lipid interventions on haemostatic pathways and cardiovascular risk markers, as well as the impact of cholesterol-rich seafood consumption, showing that prawns increased HDL cholesterol and improved lipoprotein ratios without adverse cardiometabolic effects.

More recent work has extended this research into plant-based omega-3 sources, synthesising evidence on the bioavailability and metabolic conversion of vegetarian n-3 fatty acids and highlighting microalgal oils as an effective source of preformed EPA and DHA for vegetarian and vegan populations.

Additional systematic review and meta-analysis work has further shown that plant-based omega-3 supplementation may improve triglycerides and liver-related biomarkers in patients with non-alcoholic fatty liver disease.

Collectively, this programme of research has contributed to understanding how both marine and plant-derived omega-3 fatty acids influence lipid metabolism and cardiometabolic health, while informing dietary strategies for populations with differing dietary preferences.

Kirwan, R., Mazidi, M., Butler, T., Perez de Heredia, F. P., Lip, G. Y. H., & Davies, I. G. (2024). The association of appendicular lean mass and grip strength with low-density lipoprotein, very low-density lipoprotein, and high-density lipoprotein particle diameter: a Mendelian randomization study of the UK Biobank cohort. European Heart Journal Open, 4(2), 1-10. doi:10.1093/ehjopen/oeae019.

Kirwan, R., Newson, L., McCullough, D., Butler, T., Davies, I. G., & Perez De Heredia Benedicte, F. (2023). Acceptability of a high-protein Mediterranean-style diet and resistance exercise protocol for cardiac rehabilitation patients: Involving service users in intervention design using a mixed-methods participatory approach. Frontiers in Nutrition, 10. doi:10.3389/fnut.2023.1043391.

Kirwan, R., Pérez de Heredia, F., McCullough, D., Butler, T., & Davies, I. G. (2022). Impact of COVID-19 lockdown restrictions on cardiac rehabilitation participation and behaviours in the United Kingdom. BMC Sports Science, Medicine and Rehabilitation, 14(1). doi:10.1186/s13102-022-00459-5.

Kirwan, R. P., Mazidi, M., García, C. R., Lane, K. E., Jafari, A., Butler, T., . . . Davies, I. G. (2021). Protein interventions augment the effect of resistance exercise on appendicular lean mass and handgrip strength in older adults: a systematic review and meta-analysis of randomized controlled trials.. The American journal of clinical nutrition. doi:10.1093/ajcn/nqab355.

McCullough, D., Kirwan, R., Butler, T., Pérez de Heredia, F., Thijssen, D. H. J., Lip, G. Y. H., . . . Davies, I. G. (2021). Feasibility of a high-PRotein Mediterranean-style diet and resistance Exercise in cardiac Rehabilitation patients with sarcopenic obesity (PRiMER): Study protocol for a randomised control trial. Clinical Nutrition ESPEN. doi:10.1016/j.clnesp.2021.08.001.

Webb, R. J., Lodge, J. K., Scott, S. S., & Davies, I. G. (2025). Metabolomic Characterisation of Low-Density Lipoproteins Isolated from Iodixanol and KBr-Based Density Gradient Ultracentrifugation. Metabolites, 15(2). doi:10.3390/metabo15020068.

Harman, N. L., Griffin, B. A., & Davies, I. G. (2013). Separation of the principal HDL subclasses using iodixanol ultracentrifugation. Journal of Lipid Research, (8), 2273-2281. doi:10.1194/jlr.D037432.

Lowe, G. M., Holmes, E., & Davies, I. (2009). Circulating ghrelin exists in both lipoprotein bound and free forms.. Ann Clin Biochem, 46, 514-516.

Davies, I. G., Graham, J. M., & Griffin, B. A. (2003). Rapid separation of LDL subclasses by iodixanol gradient ultracentrifugation. CLINICAL CHEMISTRY, 49(11), 1865-1872. doi:10.1373/clinchem.2003.023366.

Lowe, G. M., Bilton, R. F., Davies, I. G., Ford, T. C., Billington, D., & Young, A. J. (1999). Carotenoid composition and antioxidant potential in subfractions of human low-density lipoprotein.. Ann Clin Biochem, 36 ( Pt 3), 323-332. doi:10.1177/000456329903600304.

Wilson, M. L., Lane, K. E., Fadel, A., Dawson, E. A., Moore, E., Mazidi, M., . . . Davies, I. G. (2024). Effects of Single Low-Carbohydrate, High-Fat Meal Consumption on Postprandial Lipemia and Markers of Endothelial Dysfunction: A Systematic Review of Current Evidence. Nutrition reviews, 1-19. doi:10.1093/nutrit/nuae103.

McCullough, D., Harrison, T., Enright, K. J., Amirabdollahian, F., Mazidi, M., Lane, K. E., . . . Davies, I. G. (2023). The Effect of Carbohydrate Restriction on Lipids, Lipoproteins, and Nuclear Magnetic Resonance-Based Metabolites: CALIBER, a Randomised Parallel Trial. Nutrients, 15(13). doi:10.3390/nu15133002.

McCullough, D., Harrison, T., Boddy, L. M., Enright, K. J., Amirabdollahian, F., Schmidt, M. A., . . . Davies, I. G. (2022). The Effect of Dietary Carbohydrate and Fat Manipulation on the Metabolome and Markers of Glucose and Insulin Metabolism: A Randomised Parallel Trial. Nutrients, 14(18). doi:10.3390/nu14183691.

Gjuladin-Hellon, T., Davies, I. G., Penson, P., & Amiri Baghbadorani, R. (2018). Effects of carbohydrate restricted diets on low density lipoprotein-cholesterol levels in overweight and obese adults: a systematic review and meta-analysis of large randomised controlled trials of at least 6 months. Nutrition Reviews, 77(3), 161-180. Retrieved from https://doi.org/10.1093/nutrit/nuy049.

Mazidi, M., Webb, R. J., Lip, G. Y. H., Kengne, A. P., Banach, M., & Davies, I. G. (2022). Discordance between LDL-C and Apolipoprotein B Levels and Its Association with Renal Dysfunction: Insights from a Population-Based Study. Journal of Clinical Medicine, 11(2). doi:10.3390/jcm11020313.

Webb, R. J., Mazidi, M., Lip, G. Y. H., Kengne, A. P., Banach, M., & Davies, I. G. (2021). The role of adiposity, diet and inflammation on the discordance between LDL-C and apolipoprotein B. Nutrition, Metabolism and Cardiovascular Diseases. doi:10.1016/j.numecd.2021.12.004.

Mazidi, M., Webb, R. J., George, E. S., Shekoohi, N., Lovegrove, J. A., & Davies, I. G. (2021). Nutrient Patterns are Associated with Discordant Apolipoprotein B and Low-Density Lipoproteins: A Population-Based Analysis. British Journal of Nutrition. doi:10.1017/S000711452100369X.

Kirwan RP, Mazidi M, García CR, Lane KE, Jafari A, Butler T, Perez de Heredia F, Davies IG. (2022). Protein interventions augment the effect of resistance exercise on appendicular lean mass and handgrip strength in older adults: a systematic review and meta-analysis of randomized controlled trials. American Journal of Clinical Nutrition. 115(3):897-913. doi:10.1093/ajcn/nqab355 

Kirwan RP, Mazidi M, Butler T, Perez de Heredia F, Davies IG. The association of appendicular lean mass and grip strength with LDL, VLDL and HDL particle diameter: a Mendelian randomization study of the UK Biobank cohort. European Heart Journal Open. 4(2):1-10. doi:10.1093/ehjopen/oeae019 

Kirwan R, Perez de Heredia F, McCullough D, Butler T, Davies IG. (2022). Impact of COVID-19 lockdown restrictions on cardiac rehabilitation participation and behaviours in the United Kingdom. BMC Sports Science, Medicine and Rehabilitation. 14(1):67. doi:10.1186/s13102-022-00459-5 

McCullough D, Kirwan R, Butler T, Perez de Heredia F, Thijssen D, Lip GYH, Mills J, Davies IG. (2021). Feasibility of a high-PRotein Mediterranean-style diet and resistance Exercise in cardiac Rehabilitation patients with sarcopenic obesity (PRiMER): Study protocol for a randomised control trial. Clinical Nutrition ESPEN. 45:492-498. doi:10.1016/j.clnesp.2021.08.001 

Kirwan R, Newson L, McCullough D, Butler T, Davies IG, Perez de Heredia F. (2023). Acceptability of a high-protein Mediterranean-style diet and resistance exercise protocol for cardiac rehabilitation patients: Involving service users in intervention design using a mixed-methods participatory approach. Frontiers in Nutrition. 10:1043391. doi:10.3389/fnut.2023.1043391

Moore, E., Patanwala, I., Jafari, A., Davies, I. G., Kirwan, R., Newson, L., . . . Lane, K. E. (2023). A systematic review and meta-analysis of randomised controlled trials to evaluate plant-based omega-3 polyunsaturated fatty acids in non-alcoholic fatty liver disease patient biomarkers and paramete. Nutrition Reviews. doi:10.1093/nutrit/nuad054.

Lane, K. E., Wilson, M. G., Hellon, T. G., & Davies, I. G. (2021). Bioavailability and conversion of plant based sources of omega-3 fatty acids - a scoping review to update supplementation options for vegetarians and vegans.. Critical Reviews in Food Science and Nutrition. doi:10.1080/10408398.2021.1880364.

Isherwood, C., Wong, M., Jones, W. S., Davies, I. G., & Griffin, B. A. (2010). LACK OF EFFECT OF COLD WATER PRAWNS ON PLASMA CHOLESTEROL AND LIPOPROTEINS IN NORMO-LIPIDAEMIC MEN. CELLULAR AND MOLECULAR BIOLOGY, 56(1), 52-58.

Griffin, M. D., Sanders, T. A., Davies, I. G., Morgan, L. M., Millward, D. J., Lewis, F., . . . Griffin, B. A. (2006). Effects of altering the ratio of dietary n-6 to n-3 fatty acids on insulin sensitivity, lipoprotein size, and postprandial lipemia in men and postmenopausal women aged 45-70 y: the OPTILIP Study.. American Journal of Clinical Nutrition, 84(6), 1290-1298.

Sanders, T. A., Lewis F., Slaughter, S., Griffin, B. A., Griffin, M., Davies, I., . . . Miller, G. J. (2006). Effect of varying the ratio of n-6 to n-3 fatty acids by increasing the dietary intake of alpha-linolenic acid, eicosapentaenoic and docosahexaenoic acid, or both on fibrinogen and clotting factors VII and XII in persons aged 45-70 y: the OPTILIP study.. American Journal of Clinical Nutrition, 84(3), 513-522.