Publications

The latest list of publications from the NIHR Cambridge Biomedical Research Centre with a brief summary. 

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Publication: The Journal of Nutrition

Tong TYN, Koulman A, Griffin JL, Wareham NJ, Forouhi NG, Imamura F

26 October 2019


Cardiometabolic benefits of the Mediterranean diet have been recognized, but underlying mechanisms are not fully understood.

We aimed to investigate how the Mediterranean diet could influence circulating metabolites and how the metabolites could mediate the associations of the diet with cardiometabolic risk factors.

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Publication: PLoS ONE

Yerrakalva D, Wijndaele K, Hajna S, Westgate K, Khaw K, Wareham N, et al.

25 October 2019


Compensatory behaviours may be one of the reasons for the limited success of sedentary time interventions in older adults, but this possibility remains unexplored.

Activity compensation is the idea that if we change activity levels at one time we compensate for them at a later time to maintain a set point. We aimed to assess, among adults aged ≥60 years, whether sedentary time and time spent in prolonged sedentary bouts (≥30 mins) on one day were associated with sedentary time and time spent in prolonged sedentary bouts (≥30 mins) on the following day. We also sought to determine whether these associations varied by sociodemographic and comorbid factors.

Sedentary time was assessed for seven days using hip-worn accelerometers (ActiGraph GT1M) for 3459 adults who participated in the EPIC-Norfolk Study between 2004 and 2011. We assessed day-to-day associations in total and prolonged bouts of sedentary time using multi-level regressions. We included interaction terms to determine whether associations varied by age, sex, smoking, body mass index, social class, retirement, education and comorbid factors (stroke, diabetes, myocardial infarction and cancer).

Participants (mean age = 70.3, SD = 6.8 years) accumulated 540 sedentary mins/day (SD = 80.1). On any given day, every 60 minutes spent in sedentary time was associated with 9.9 extra sedentary minutes on the following day (95% CI 9.0, 10.2). This association was greater in non-retired compared to retired participants (non-retired 2.57 extra minutes, p = 0.024) and in current compared to former and never-smokers (5.26 extra mins for current vs former; 5.52 extra mins for current vs never, p = 0.023 and 0.017, respectively). On any given day, every 60 minutes spent in prolonged bouts was associated with 7.8 extra minutes in these bouts the following day (95% CI 7.6, 8.4). This association was greater in older individuals (0.18 extra minutes/year of age, 95% CI 0.061, 0.29), and for retired versus non-retired (retired 2.74 extra minutes, 95% CI 0.21, 5.74).

Conclusion Older adults did not display day-to-day compensation. Instead, individuals demonstrate a large stable component of day-to-day time spent sedentary and in prolonged bouts with a small but important capacity for positive variation. Therefore older adults appear to be largely habitual in their sedentary behaviour. Strategies to augment these patterns may be possible, given they may differ by age, smoking, and working status.

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Publication: Journal of the American Geriatrics Society

Bielemann RM, LaCroix AZ, Bertoldi AD, Tomasi E, Demarco FF, Gonzalez MC, et al.

8 October 2019


Use of objectively measured physical activity (PA) in older adults to assess relationship between PA and risk of all-causes mortality is scarce. This study evaluated the associations of PA based on accelerometry and a questionnaire with the risk of mortality among older adults from a city in Southern Brazil.

Overall physical activity (mg), light physical activity (LPA), and moderate to vigorous physical activity (MVPA) were estimated by raw accelerometer data. The International Physical Activity Questionnaire estimated leisure time and commuting PA. Hazard ratios (excluding deaths in the first 6 mo) stratified by sex were estimated by Cox regression analysis considering adjustment for confounders.

From the 1451 older adults interviewed in 2014, 145 died (10%) after a follow-up of an average 2.6 years. Men and women in the highest tertile of overall PA had on average a 77% and 92% lower risk of mortality than their less active counterparts. The highest tertile of LPA was also related to a lower risk of mortality in individuals of both sexes. MVPA statistically reduced the risk of mortality only among women. Self-reported leisure-time PA was statistically associated with a lower risk of mortality only among men. Women in the highest tertiles of commuting PA showed a lower risk of mortality than those in the reference group.

CONCLUSION Accelerometry-based PA was associated with a lower risk of mortality among Brazilian older adults. Older individuals should practice any type of PA.

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Publication: Metabolomics

Furse S, Billing G, Snowden SG, Smith J, Goldberg G, Koulman A.

25 September 2019


This study was motivated by the report that infant development correlates with particular lipids in infant plasma.

The hypothesis was that the abundance of these candidate biomarkers is influenced by the dietary intake of the infant.

A cohort of 30 exclusively-breastfeeding mother–infant pairs from a small region of West Africa was used for this observational study. Plasma and milk from the mother and plasma from her infant were collected within 24 h, 3 months post partum. The lipid, sterol and glyceride composition was surveyed using direct infusion MS in positive and negative ion modes. Analysis employed a combination of univariate and multivariate tests.

The lipid profiles of mother and infant plasma samples are similar but distinguishable, and both are distinct from milk. Phosphatidylcholines (PC), cholesteryl esters (CEs) and cholesterol were more abundant in mothers with respect to their infants. A latent structure model showed that four lipids in infant plasma previously shown to be biomarkers clustered with cholesteryl esters in the maternal circulation.

This study found evidence that the abundance of individual lipid isoforms associated with infant development are associated with the abundance of individual molecular species in the mother’s circulation.

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Publication: European Journal of Applied Physiology

Veijalainen A, Haapala EA, Väistö J, Leppänen MH, Lintu N, Tompuri T, et al.

18 September 2019


The researchers looked at the associations of physical activity (PA), sedentary time (ST), and cardiorespiratory fitness (CRF) with heart rate variability (HRV) in children.

The participants were a population sample of 377 children aged 6–9 years (49% boys). ST, light PA (LPA), moderate PA (MPA), vigorous PA (VPA), and moderate-to-vigorous PA (MVPA), and PA energy expenditure (PAEE) were assessed using a combined heart rate and movement sensor, maximal power output per kilograms of lean body mass as a measure of CRF by maximal cycle ergometer exercise test, and HRV variables (SDNN, RMSSD, LF, and HF) using 5 min resting electrocardiography. Data were analysed by linear regression adjusted for years from peak height velocity.

In boys, ST was inversely associated and MVPA, VPA, PAEE, and CRF were directly associated with HRV variables. CRF was directly associated with all HRV variables and PAEE was directly associated with RMSSD after mutual adjustment for ST, PAEE, and CRF.

In girls, ST was inversely associated and LPA, MPA, VPA, MVPA, and PAEE were directly associated with HRV variables. After mutual adjustment for ST, PAEE, and CRF, only the inverse associations of ST with HRV variables remained statistically significant.

Higher ST and lower PA and CRF were associated with poorer cardiac autonomic nervous system function in children. Lower CRF in boys and higher ST in girls were the strongest correlates of poorer cardiac autonomic function.

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Publication: Scientific Reports

Ottaviani JI, Fong R, Kimball J, Ensunsa JL, Gray N, Vogiatzoglou A, et al.

11 September 2019


Data from dietary intervention studies suggest that intake of (−)-epicatechin mediates beneficial vascular effects in humans. However, population-based investigations are required to evaluate associations between habitual intake and health and these studies rely on accurate estimates of intake, which nutritional biomarkers can provide.

Here, we evaluate a series of structurally related (−)-epicatechin metabolites (SREM), particularly (−)-epicatechin-3′-glucuronide, (−)-epicatechin-3′-sulfate and 3′-O-methyl-(−)-epicatechin-5-sulfate (SREMB), as flavan-3-ol and (−)-epicatechin intake. SREMB in urine proved to be a specific indicator of (−)-epicatechin intake, showing also a strong correlation with the amount of (−)-epicatechin ingested (R2: 0.86 (95% CI 0.8l; 0.92).

The median recovery of (−)-epicatechin as SREMB in 24 h urine was 10% (IQR 7–13%) and we found SREMB in the majority of participants of EPIC Norfolk (83% of 24,341) with a mean concentration of 2.4 ± 3.2 µmol/L.

Our results show that SREMB are suitable as biomarker of (−)-epicatechin intake. According to evaluation criteria from IARC and the Institute of Medicine, the results obtained support use of SREMB as a recovery biomarker to estimate actual intake of (−)-epicatechin.

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Publication: Journal of Nutritional Science

Foster E, Lee C, Imamura F, Hollidge SE, Westgate KL, Venables MC, et al.

30 August 2019


Online self-reported 24-h dietary recall systems promise increased feasibility of dietary assessment. Comparison against interviewer-led recalls established their convergent validity; however, reliability and criterion-validity information is lacking.

The validity of energy intakes (EI) reported using Intake24, an online 24-h recall system, was assessed against concurrent measurement of total energy expenditure (TEE) using doubly labelled water in ninety-eight UK adults (40–65 years). Accuracy and precision of EI were assessed using correlation and Bland–Altman analysis. Test–retest reliability of energy and nutrient intakes was assessed using data from three further UK studies where participants (11–88 years) completed Intake24 at least four times; reliability was assessed using intra-class correlations (ICC).

Compared with TEE, participants under-reported EI by 25 % (95 % limits of agreement −73 % to +68 %) in the first recall, 22 % (−61 % to +41 %) for average of first two, and 25 % (−60 % to +28 %) for first three recalls. Correlations between EI and TEE were 0·31 (first), 0·47 (first two) and 0·39 (first three recalls), respectively. ICC for a single recall was 0·35 for EI and ranged from 0·31 for Fe to 0·43 for non-milk extrinsic sugars (NMES). Considering pairs of recalls (first two v. third and fourth recalls), ICC was 0·52 for EI and ranged from 0·37 for fat to 0·63 for NMES. EI reported with Intake24 was moderately correlated with objectively measured TEE and underestimated on average to the same extent as seen with interviewer-led 24-h recalls and estimated weight food diaries.

Online 24-h recall systems may offer low-cost, low-burden alternatives for collecting dietary information.

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Publication: PLOS ONE

Cullerton K, Adams J, Francis O, Forouhi N, White M.

22 August 2019


Key to scientific integrity is ensuring that research findings are considered credible by scientific peers, practitioners, policymakers and the public.

Industry sponsorship of nutritional research can result in bias and raises significant professional, public and media concern. Yet, there is no international consensus on how to prevent or manage conflicts of interest for researchers considering engaging with the food industry.

This study aimed to determine internationally agreed principles to guide interactions between population health researchers and the food industry to prevent or manage conflicts of interest. We used a two-stage, online Delphi study for researchers, and an online survey for stakeholders. High levels of agreement on principles were achieved for both groups (researchers 68%; stakeholders 65%). Highest levels of agreement were with principles concerning research methods and governance.

More contentious were principles that required values-based decision-making, such as determining which elements of the commercial sector are acceptable to interact with. These results provide the basis for developing internationally-agreed guidelines for population health researchers governing interactions with the food industry.

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Publication: Advances in Nutrition

Aljuraiban G, Gibson R, Oude Griep L, Okuda N, Steffen L, Van Horn L et al.

18 June 2019


Healthy dietary habits are the cornerstone of cardiovascular disease (CVD) prevention.

Numerous researchers have developed diet quality indices to help evaluate and compare diet quality across and within various populations.

The availability of these new indices raises questions regarding the best selection relevant to a given population.

In this perspective, we critically evaluate a priori–defined dietary indices commonly applied in epidemiological studies of CVD risk and mortality.

A systematic literature search identified 59 observational studies that applied a priori–defined diet quality indices to CVD risk factors and/or CVD incidence and/or CVD mortality.

Among 31 different indices, these scores were categorized as follows: 1) those based on country-specific dietary patterns, 2) those adapted from distinct dietary guidelines, and 3) novel scores specific to key diet-related factors associated with CVD risk.

The strengths and limitations of these indices are described according to index components, calculation methods, and the application of these indices to different population groups. Also, the importance of identifying methodological challenges faced by researchers when applying an index are considered, such as selection and weighting of food groups within a score, since food groups are not necessarily equivalent in their associations with CVD.

The lack of absolute cutoff values, emphasis on increasing healthy food without limiting unhealthy food intake, and absence of validation of scores with biomarkers or other objective diet assessment methods further complicate decisions regarding the best indices to use.

Future research should address these limitations, consider cross-cultural and other differences between population groups, and identify translational challenges inherent in attempting to apply a relevant diet quality index for use in CVD prevention at a population level.

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Publication: The Journal of Endocrinology & Medicine

Martineau AR, Thummel KE, Wang Z, Jolliffe DA, Boucher BJ, Griffin SJ, et al.

14 June 2019


Vitamin D2 and vitamin D3 have been hypothesized to exert differential effects on vitamin D metabolism.

The objective of this study was to compare the influence of administering vitamin D2 vs vitamin D3 on metabolism of vitamin D3.

The researchers measured baseline and 4-month serum concentrations of vitamin D3, in 52 adults randomized to receive a total of four oral bolus doses of 2.5 mg vitamin D2 or vitamin D3 over four months. Metabolite-to-parent compound ratios were calculated to estimate hydroxylase activity. Pairwise before vs after comparisons were made to evaluate effects of vitamin D2 and vitamin D3 on metabolism of vitamin D. Mean postsupplementation metabolite-to-parent ratios were then compared between groups.

The researchers concluded that bolus-dose vitamin D2 is less effective than bolus-dose vitamin D3 in elevating total serum 25(OH)D concentration.

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Publication: Nutrients

Furse S, Koulman A.

20 May 2019


We tested the hypothesis that the lipid composition of infant formula is consistent between manufacturers, countries and target demographic. We developed techniques to profile the lipid and glyceride fraction of milk and formula in a high throughput fashion. Formula from principal brands in the UK (2017–2019; bovine-, caprine-, soya-based), the Netherlands (2018; bovine-based) and South Africa (2018; bovine-based) were profiled along with fresh British animal and soya milk and skimmed milk powder.

We found that the lipid and glyceride composition of infant formula differed by region, manufacturer and date of manufacture. The formulations within some brands, aimed at different target age ranges, differed considerably where others were similar across the range. Soya lecithin and milk lipids had characteristic phospholipid profiles. Particular sources of fat, such as coconut oil, were also easy to distinguish. Docosahexaenoic acid is typically found in triglycerides rather than phospholipids in formula.

The variety by region, manufacturer, date of manufacture and sub-type for target demographics lead to an array of lipid profiles in formula. This makes it impossible to predict its molecular profile. Without detailed profile of the formula fed to infants, it is difficult to characterise the relationship between infant nutrition and their growth and development.

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Publication: The Lancet

Forouhi NG, Unwin N

11 May 2019


Few, if any, would contest that diet and nutrition have a crucial and substantial impact on human health. But the devil is in the details. Common questions include: is there such a thing as an optimal diet? What is suboptimal? Which dietary components matter most? And given the necessity to take action on climate change and planetary health, what should the world eat?

The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) contributes towards answering these questions by estimating the burden of mortality and disability attributable to specific dietary risks, within a comparative risk assessment framework that currently considers 84 behavioural, environmental, occupational, and metabolic risks across 195 countries and territories.

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