Publications

Publication: European Heart Journal

Tammy Y N Tong, Paul N Appleby, Timothy J Key, Christina C Dahm, Kim Overvad, Anja Olsen, Anne Tjønneland, Verena Katzke, Tilman Kühn, Heiner Boeing, Anna Karakatsani, Eleni Peppa, Antonia Trichopoulou, Elisabete Weiderpass, Giovanna Masala, Sara Grioni, Salvatore Panico, Rosario Tumino, Jolanda M A Boer, W M Monique Verschuren, J Ramón Quirós, Antonio Agudo, Miguel Rodríguez-Barranco, Liher Imaz, María-Dolores Chirlaque, Conchi Moreno-Iribas, Gunnar Engström, Emily Sonestedt, Marcus Lind, Julia Otten, Kay-Tee Khaw, Dagfinn Aune, Elio Riboli, Nicholas J Wareham, Fumiaki Imamura, Nita G Forouhi, Emanuele di Angelantonio, Angela M Wood, Adam S Butterworth, Aurora Perez-Cornago

24 February 2020

Summary: 

This research looked at more than 418,000 people in nine European countries who were recruited to the European Prospective Investigation into Cancer and Nutrition (EPIC) study between 1992 and 2000. Researchers found that while higher intakes of fruit, vegetables, fibre, milk, cheese or yoghurt were each linked to a lower risk of ischaemic stroke, there was no significant association with a lower risk of haemorrhagic stroke.

As the study is observational, it cannot show that the foods studied cause an increase or decrease in risk of ischaemic or haemorrhagic stroke, only that they are associated with different risks.

Publication: Science

Jong-Eun Park, Rachel A. Botting, Cecilia Domínguez Conde, Dorin-Mirel Popescu, Marieke Lavaert, Daniel J. Kunz, Issac Goh, Emily Stephenson, Roberta Ragazzini, Elizabeth Tuck, Anna Wilbrey-Clark, Kenny Roberts, Veronika R. Kedlian, John R. Ferdinand, Xiaoling He, Simone Webb, Daniel Maunder, Niels Vandamme, Krishnaa T. Mahbubani, Krzysztof Polanski, Lira Mamanova, Liam Bolt, David Crossland, Fabrizio de Rita, Andrew Fuller, Andrew Filby, Gary Reynolds, David Dixon, Kourosh Saeb-Parsy, Steven Lisgo, Deborah Henderson, Roser Vento-Tormo, Omer A. Bayraktar, Roger A. Barker, Kerstin B. Meyer, Yvan Saeys, Paola Bonfanti, Sam Behjati, Menna R. Clatworthy, Tom Taghon, Muzlifah Haniffa, Sarah A. Teichmann

21 February 2020

Summary:

Human thymus tissue makes T-cells for adaptive immunity and this research made a comprehensive cell atlas of thymus tissue over the course of human life, from embryo to adult thus gaining new insights into human T-cell development.

Publication: Journal of Psychopharmacology

Kanen JW, Arntz FE, Yellowlees R, Cardinal RN, Price A, Christmas DM, Sahakian BJ, Apergis-Schoute AM, Robbins TW

18 February 2020

The involvement of serotonin in responses to negative feedback is well established. Acute serotonin reuptake inhibition has enhanced sensitivity to negative feedback (SNF), modelled by behaviour in probabilistic reversal learning (PRL) paradigms. Whilst experiments employing acute tryptophan depletion (ATD) in humans, to reduce serotonin synthesis, have shown no clear effect on SNF, sample sizes have been small.

The researchers studied a large sample of healthy volunteers, male and female, and found ATD had no effect on core behavioural measures in PRL.

These results indicate that ATD effects can differ from other manipulations of serotonin expected to have a parallel or opposing action.

Publication: Nature Immunology

Kylie R. James, Tomas Gomes, Rasa Elmentaite, Nitin Kumar, Emily L. Gulliver, Hamish W. King, Mark D. Stares, Bethany R. Bareham, John R. Ferdinand, Velislava N. Petrova, Krzysztof Polański, Samuel C. Forster, Lorna B. Jarvis, Ondrej Suchanek, Sarah Howlett, Louisa K. James, Joanne L. Jones, Kerstin B. Meyer, Menna R. Clatworthy, Kourosh Saeb-Parsy, Trevor D. Lawley, Sarah A. Teichmann

17 February 2020

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Summary:

This research surveyed the microbiome in different regions along the length of a healthy human colon, and in parallel surveyed the populations of immune cells.The map of the bacterial composition in the human colon showed that specific genera had preferences for colonising certain regions of the colon. B and T cells also changed along the length of the colon. This is the first survey to find out what constitutes a healthy homeostatic relationship between the microbiome in the human colon and host immune cells.

Publication: Food Science & Nutrition

Rachel M. Harris, Angela M. C. Rose, Nita G. Forouhi, Nigel Unwin

5 February 2020

The Caribbean island of Barbados has a high burden of diabetes and cardiovascular disease. Dietary habits were last described in 2005. A representative population-based sample provided two nonconsecutive 24-hr dietary recalls in this cross-sectional study. Mean daily nutrient intakes were compared with the Dietary Guidelines for Americans. Subgroup differences by age, sex, and educational level were examined using logistic regression. High sugar intakes exist for both sexes with 24% consuming less than the recommended <10% of energy from added sugars. Sugar-sweetened beverages provide 43% of total sugar intake. Inadequate dietary fiber intakes exist across all age groups. Inadequate micronutrient intake was found in women for calcium, folate, thiamine, zinc, and iron. Older persons (aged 45–64 years) were more likely to report adequacy of dietary fiber and iron than younger persons (aged 25–44). Older persons (aged 45–64 years) were less likely to have an adequate supply of riboflavin (OR = 0.4, 0.2, 0.6) than younger persons. Men were more likely to have adequate intakes of iron, folate, and thiamine than women. Education was not associated with nutrient intake. The Barbadian diet is characterized by high sugar intakes and inadequate dietary fiber; a nutrient profile associated with an increased risk of obesity, type 2 diabetes, and related noncommunicable diseases.

Publication: Nature Communications

Sanne Simone Kaalund, Luca Passamonti, Kieren S. J. Allinson, Alexander G. Murley, Trevor W. Robbins, Maria Grazia Spillantini and James B. Rowe

4 February 2020

Summary:

The locus coeruleus is the major source of noradrenaline to the brain and contributes to a wide range of physiological and cognitive functions. Neurodegeneration and pathological aggregation of tau protein in the locus coeruleus are early features of progressive supranuclear palsy (PSP). It is proposed to contribute to the clinical expression of the disease, including the PSP Richardson’s syndrome. Researchers investigated whether the tau and neuronal loss are associated with clinical heterogeneity and severity in PSP.

Publication: Acta Neuropathologica Communications

Sanne Simone Kaalund, Luca Passamonti, Kieren S. J. Allinson, Alexander G. Murley, Trevor W. Robbins, Maria Grazia Spillantini & James B. Rowe

4 February 2020

The noradrenergic deficit in the locus coeruleus is a candidate target for pharmacological treatment. Recent developments in ultra-high field magnetic resonance imaging to quantify in vivo structural integrity of the locus coeruleus may provide biomarkers for noradrenergic experimental medicines studies in Progressive supranuclear palsy (PSP).

Degeneration and tau pathology in the locus coeruleus are related to clinical heterogeneity of PSP. Integrity of the locus coeruleus may provide biomarkers for noradrenergic experimental medicines studies in PSP.

Publication: Acta Neuropathologica Communications

Sanne Simone Kaalund, Luca Passamonti, Kieren S. J. Allinson, Alexander G. Murley, Trevor W. Robbins, Maria Grazia Spillantini & James B. Rowe

4 February 2020

The locus coeruleus is the major source of noradrenaline to the brain and contributes to a wide range of physiological and cognitive functions including arousal, attention, autonomic control, and adaptive behaviour. Neurodegeneration and pathological aggregation of tau protein in the locus coeruleus are early features of progressive supranuclear palsy (PSP). This pathology is proposed to contribute to the clinical expression of disease, including the PSP Richardson’s syndrome. The researchers tested the hypothesis that tau pathology and neuronal loss are associated with clinical heterogeneity and severity in PSP.

They found an average 49% reduction of pigmented neurons in PSP patients relative to controls. The loss of pigmented neurons correlated with disease severity, even after adjusting for disease duration and the interval between clinical assessment and death. The degree of neuronal loss was negatively associated with tau-positive inclusions, with an average of 44% of pigmented neurons displaying tau-inclusions.

Degeneration and tau pathology in the locus coeruleus are related to clinical heterogeneity of PSP. The noradrenergic deficit in the locus coeruleus is a candidate target for pharmacological treatment. Recent developments in ultra-high field magnetic resonance imaging to quantify in vivo structural integrity of the locus coeruleus may provide biomarkers for noradrenergic experimental medicines studies in PSP.

Publication: Nutrition Reviews

Amoutzopoulos B, Page P, Roberts C, Roe M, Cade J, Steer T et al.

30 January 2020

Overestimation or underestimation of portion size leads to measurement error during dietary assessment.

Objective

To identify portion size estimation elements (PSEEs) and evaluate their relative efficacy in relation to dietary assessment, and assess the quality of studies validating PSEEs.

Data Selection and Extraction

Electronic databases, internet sites, and cross-references of published records were searched, generating 16 801 initial records, from which 334 records were reviewed and 542 PSEEs were identified, comprising 5% 1-dimensional tools (eg, food guides), 46% 2-dimensional tools (eg, photographic atlases), and 49% 3-dimensional tools (eg, household utensils). Out of 334 studies, 21 validated a PSEE (compared PSEE to actual food amounts) and 13 compared PSEEs with other PSEEs.

Conclusion

Quality assessment showed that only a few validation studies were of high quality. According to the findings of validation and comparison studies, food image–based PSEEs were more accurate than food models and household utensils. Key factors to consider when selecting a PSEE include efficiency of the PSEE and its applicability to targeted settings and populations.

Publication: Clinical Transplantation

John O. O. Ayorinde, Mazin Hamed, Mingzheng Aaron Goh, Dominic M. Summers, Anna Dare, Yining Chen, Kourosh Saeb‐Parsy

20 January 2020

Summary:

This research recorded donor and recipient data of kidney transplants and matched them with clinical outcomes, helping to build the Cambridge Kidney Assessment Tool (CKAT).

CKAT will assist surgeons to define macroscopic features of donor kidneys to help them better predict clinical outcome and help reduce unecessary discarding of donor kidneys offered for transplantion.

Publication: Journal of Neurology Neurosurgery and Psychiatry

Carolin Heller, Martha S Foiani, Katrina Moore, Rhian Convery, Martina Bocchetta, Mollie Neason, David M Cash, David Thomas, Caroline V Greaves, Ione OC Woollacott, Rachelle Shafei, John C Van Swieten, Fermin Moreno, Raquel Sanchez-Valle, Barbara Borroni, Robert Laforce Jr, Mario Masellis, Maria Carmela Tartaglia, Caroline Graff, Daniela Galimberti, James B Rowe et al

14 January 2020

There are few validated fluid biomarkers in frontotemporal dementia (FTD). Glial fibrillary acidic protein (GFAP) is a measure of astrogliosis, a known pathological process of FTD, but has yet to be explored as potential biomarker.

In this research, the team found out that plasma GFAP concentration was significantly increased in symptomatic GRN mutation carriers.

Raised GFAP concentrations appear to be unique to GRN-related FTD, with levels potentially increasing just prior to symptom onset, suggesting that GFAP may be an important marker of proximity to onset, and helpful for forthcoming therapeutic prevention trials.

Publication: Journal of Neurology

David J. Lewis-Smith, Noham Wolpe, Boyd C. P. Ghosh & James B. Rowe

9 January 2020

Alien limb refers to movements that seem purposeful but are independent of patients’ reported intentions. Alien limb often co-occurs with apraxia in the corticobasal syndrome, and anatomical and phenomenological comparisons have led to the suggestion that alien limb and apraxia may be causally related as failures of goal-directed movements. Here, the researchers characterised the nature of alien limb symptoms in patients with the corticobasal syndrome and their relationship to limb apraxia.

Twenty-eight patients with corticobasal syndrome (93%) demonstrated significant apraxia and this was often asymmetrical, with the left hand preferentially affected in 23/30 (77%) patients. Moreover, 25/30 (83%) patients reported one or more symptoms consistent with alien limb. The range of these phenomena was broad, including changes in the sense of ownership and control as well as unwanted movements.

Regression analyses showed no significant association between the severity of limb apraxia and either the occurrence of an alien limb or the number of alien limb phenomena reported. Bayesian estimation showed a low probability for a positive association between alien limb and apraxia, suggesting that alien limb phenomena are not likely to be related to severity apraxia. The results shed light on the phenomenology of these disabling and as yet untreatable clinical features, with relevance to theoretical models of voluntary action.

Publication: The American Journal of Clinical Nutrition

Trichia E, Luben R, Khaw K, Wareham NJ, Imamura F, Forouhi NG

8 January 2020

Background The consumption of some types of dairy products has been associated with lower cardiometabolic disease incidence. Knowledge remains limited about habitual dairy consumption and the pathways to cardiometabolic risk.

Objective We aimed to investigate associations of habitual consumption of total and types of dairy products with markers of metabolic risk and adiposity among adults in the United Kingdom.

Methods We examined associations of changes in dairy consumption (assessed with a food-frequency questionnaire) with parallel changes in cardiometabolic markers using multiple linear regression among 15,612 adults aged 40–78 y at baseline (1993–1997) and followed up over 1998–2000 (mean ± SD: 3.7±0.7 y) in the European Prospective Investigation into Cancer and Nutrition (EPIC)–Norfolk study.

Results For adiposity, an increase in fermented dairy products [yogurt (total or low-fat) or low-fat cheese] consumption was associated with a lower increase in body weight and body mass index (BMI). For example, over 3.7 y, increasing yogurt consumption by 1 serving/d was associated with a smaller increase in body weight by 0.23 kg (95% CI: −0.46, −0.01 kg). An increase in full-fat milk, high-fat cheese, and total high-fat dairy was associated with greater increases in body weight and BMI [e.g., for high-fat dairy: β = 0.13 (0.05, 0.21) kg and 0.04 (0.01, 0.07) kg/m2, respectively]. For lipids, an increase in milk (total and low-fat) or yogurt consumption was positively associated with HDL cholesterol. An increase in total low-fat dairy was negatively associated with LDL cholesterol (−0.03 mmol/L; −0.05, −0.01 mmol/L), whereas high-fat dairy (total, butter, and high-fat cheese) consumption was positively associated [e.g., 0.04 (0.02, 0.06) mmol/L for total high-fat dairy]. For glycemia, increasing full-fat milk consumption was associated with a higher increase in glycated hemoglobin (P = 0.027).

Conclusions The habitual consumption of different dairy subtypes may differently influence cardiometabolic risk through adiposity and lipid pathways.

Publication: Journal of Neuroscience

Natalie E. Adams, Laura E. Hughes, Holly N. Phillips, Alexander D. Shaw, Alexander G. Murley, David Nesbitt, Thomas E. Cope, W. Richard Bevan-Jones, Luca Passamonti and James B. Rowe

8 January 2020

To bridge the gap between preclinical cellular models of disease and in vivo imaging of human cognitive network dynamics, there is a pressing need for informative biophysical models. Here the researchers assessed dynamic causal models (DCM) of cortical network responses, as generative models of magnetoencephalographic observations during an auditory oddball roving paradigm in healthy adults.

They demonstrated the facility of conductance-based neural mass mean-field models, incorporating local synaptic connectivity, to investigate laminar-specific and GABAergic mechanisms of the auditory response. The neuronal model accurately recapitulated the observed magnetoencephalographic data. Using parametric empirical Bayes for optimal model inversion across both drug sessions, they identified the effect of tiagabine on GABAergic modulation of deep pyramidal and interneuronal cell populations and found a transition of the main GABAergic drug effects from auditory cortex in standard trials to prefrontal cortex in deviant trials.

The successful integration of pharmaco- magnetoencephalography with dynamic causal models of frontotemporal networks provides a potential platform on which to evaluate the effects of disease and pharmacological interventions.

Publication: Endocrine Connections

Janus C, Vistisen D, Amadid H, Witte DR, Lauritzen T, Brage S, et al.

31 December 2019

The hormone glucagon-like peptide-1 (GLP-1) decreases blood glucose and appetite. Greater physical activity (PA) is associated with lower incidence of type 2 diabetes. While acute exercise may increase glucose-induced response of GLP-1, it is unknown how habitual PA affects GLP-1 secretion. We hypothesised that habitual PA associates with greater glucose-induced GLP-1 responses in overweight individuals.

Methods

Cross-sectional analysis of habitual PA levels and GLP-1 concentrations in 1326 individuals (mean (s.d.) age 66 (7) years, BMI 27.1 (4.5) kg/m2) from the ADDITION-PRO cohort. Fasting and oral glucose-stimulated GLP-1 responses were measured using validated radioimmunoassay. PA was measured using 7-day combined accelerometry and heart rate monitoring. From this, energy expenditure (PAEE; kJ/kg/day) and fractions of time spent in activity intensities (h/day) were calculated. Cardiorespiratory fitness (CRF; mL O2/kg/min) was calculated using step tests. Age-, BMI- and insulin sensitivity-adjusted associations between PA and GLP-1, stratified by sex, were evaluated by linear regression analysis.

Results

In 703 men, fasting GLP-1 concentrations were 20% lower (95% CI: −33; −3%, P = 0.02) for every hour of moderate-intensity PA performed. Higher CRF and PAEE were associated with 1–2% lower fasting GLP-1 (P = 0.01). For every hour of moderate-intensity PA, the glucose-stimulated GLP-1 response was 16% greater at peak 30 min (1; 33%, P rAUC0-30 = 0.04) and 20% greater at full response (3; 40%, P rAUC0-120 = 0.02). No associations were found in women who performed PA 22 min/day vs 32 min/day for men.

Conclusion

Moderate-intensity PA is associated with lower fasting and greater glucose-induced GLP-1 responses in overweight men, possibly contributing to improved glucose and appetite regulation with increased habitual PA.

Publication: Genome Biology

E. Madissoon, A. Wilbrey-Clark, R. J. Miragaia, K. Saeb-Parsy, K. T. Mahbubani, N. Georgakopoulos, P. Harding, K. Polanski, N. Huang, K. Nowicki-Osuch, R. C. Fitzgerald, K. W. Loudon, J. R. Ferdinand, M. R. Clatworthy, A. Tsingene, S. van Dongen, M. Dabrowska, M. Patel, M. J. T. Stubbington, S. A. Teichmann, O. Stegle & K. B. Meyer

31 December 2019

Summary: 

The Human Cell Atlas, which is an international collaboration to map all the cell types in the human body.

However, delays between fresh sample collection and processing may lead to poor data and difficulties in experimental design.

This study looked at the effect of cold storage on fresh healthy spleen, esophagus, and lung from donors and concluded that cold storage of tissue works well and increases the time frame for processing samples; however robust protocols are needed for tissue preservation that can be used by all the research teams involved.

Publication: Nature

Duuamene Nyimanu, Richard G. Kay, Petra Sulentic, Rhoda E. Kuc, Philip Ambery, Lutz Jermutus, Frank Reimann, Fiona M. Gribble, Joseph Cheriyan, Janet J. Maguire, Anthony P. Davenport

27 December 2019

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Summary:

An LC-MS method was developed to measure Apelin in human plasma, and demonstrate apelin dosing achieved the correct concentration in volunteers. The extracts were also analysed on an LC-MS system to identify break-down products of the peptide that were produced in the body. The researchers found out that apelin is broken down from both ends of the peptide, but more so from the C-terminal. This information can be used to develop a better peptide that is stabilised against degradation, therefore improving its characteristics as a drug; and apelin-derived peptides may be potential new drugs for cardiovascular disease.

Publication: Nature

Anthony P. Coll, Michael Chen, Stephen O’Rahilly et al

25 December 2019

Cambridge scientists have discovered that metformin causes the cells of the intestine to make large amounts of a hormone, called GDF15, and secrete it into the bloodstream.

The high blood levels of GDF15 are sensed by a highly specific area of the brain where they suppress hunger and reduce food intake. When GDF15 is blocked, metformin has no effect on body weight.

The work was undertaken in the MRC Metabolic Diseases Unit at the University of Cambridge with collaborators at NGM Biopharmaceuticals, the University of Glasgow and elsewhere.

Dr Tony Coll, a lead author, said “We usually think that drugs have to pass through the intestine to have their effects in the body. In this case, though, the cells of the intestine themselves respond to the drug to create a hormonal signal which does the work.”

Metformin has been used to treat Type 2 diabetes for over 60 years and is the world’s most commonly prescribed anti-diabetic drug. It can also prevent the onset of diabetes in those at risk, doing so by helping people to lose and keep off weight. However, how metformin reduces body weight has been a mystery.

Professor Stephen O’Rahilly said: “How metformin keeps body weight down has been a mystery. This work shows that all of this effect is down to GDF15 acting on a tiny number of cells in the brain.”

These findings are supported  by an independent study from McMaster University published in Nature Metabolism  and should stimulate research into the use of GDF15 itself as an anti-obesity agent.

Publication: JAMA Neurology

Edwin Jabbari, Negin Holland, Viorica Chelban, P. Simon Jones, Ruth Lamb, Charlotte Rawlinson, Tong Guo, Alyssa A. Costantini, Manuela M. X. Tan, Amanda J. Heslegrave, Federico Roncaroli, Johannes C. Klein, Olaf Ansorge, Kieren S. J. Allinson, Zane Jaunmuktane, Janice L. Holton, Tamas Revesz, Thomas T. Warner, Andrew J. Lees, Henrik Zetterberg, Lucy L. Russell, Martina Bocchetta, Jonathan D. Rohrer, Nigel M. Williams, Donald G. Grosset, David J. Burn, Nicola Pavese, Alexander Gerhard, Christopher Kobylecki, P. Nigel Leigh, Alistair Church, Michele T. M. Hu, John Woodside, Henry Houlden,  James B. Rowe, Huw R. Morris

20 December 2019

This research looked at the distinguishing features of progressive supranuclear palsy and corticobasal syndrome subtypes and how they can be distinguished from Parkinson disease.

In this cohort study of 222 patients with atypical parkinsonian syndromes, recently defined progressive supranuclear palsy subtypes are almost as common as classic Richardson syndrome and share midbrain atrophy as a common hallmark. Distinct patterns of clinical trajectory, cognitive profile, serum neurofilament light chain level, genetic, and volumetric magnetic resonance imaging measures helped to distinguish the clinical subtypes of progressive supranuclear palsy and corticobasal syndrome; clinical trajectory and serum neurofilament light chain levels distinguished Parkinson disease from progressive supranuclear palsy and corticobasal syndrome

This study suggests that subtypes of progressive supranuclear palsy and corticobasal syndrome have distinct characteristics that may enhance their early diagnosis.

Publication: The Journal of Nutrition

Jones KS, Meadows SR, Schoenmakers I, Prentice A, Moore SE

13 December 2019

Vitamin D is important to maternal, fetal, and infant health, but quality data on vitamin D status in low- and middle-income countries and response to cholecalciferol supplementation in pregnancy are sparse.

We characterized vitamin D status and vitamin D metabolite change across pregnancy and in response to cholecalciferol supplementation in rural Gambia.

This study was a secondary analysis of samples collected in a 4-arm trial of maternal nutritional supplementation [iron folic acid (FeFol); multiple micronutrients (MMN); protein energy (PE) as lipid-based supplement; PE + MMN]; MMN included 10 μg/d cholecalciferol. Plasma 25-hydroxycholecalciferol [25(OH)D3], 24,25-dihydroxycholecalciferol [24,25(OH)2D3], and C3-epimer-25-hydroxycholecalciferol [3-epi-25(OH)D3] were measured by LC-MS/MS in 863 women [aged 30 ± 7 y (mean ± SD)] in early pregnancy (presupplementation) and late pregnancy, (gestational age 14 ± 3 and 30 ± 1 wk). Changes in 25(OH)D3 and vitamin D metabolite concentrations and associations with pregnancy stage and maternal age and anthropometry were tested.

Early pregnancy 25(OH)D3 concentration was 70 ± 15 nmol/L and increased according to pregnancy stage (82 ± 18 and 87 ± 17 nmol/L in the FeFol and PE-arms) and to cholecalciferol supplementation (95 ± 19 and 90 ± 20 nmol/L in the MMN and PE + MMN-arms) (P < 0.0001). There was no difference between supplemented groups. Early pregnancy 25(OH)D3 was positively associated with maternal age and gestational age. Change in 25(OH)D3 was negatively associated with late pregnancy, but not early pregnancy, triceps skinfold thickness. The pattern of change of 24,25(OH)2D3 mirrored that of 25(OH)D3 and appeared to flatten as pregnancy progressed, whereas 3-epi-25(OH)D3 concentration increased across pregnancy.

This study provides important data on the vitamin D status of a large cohort of healthy pregnant women in rural Africa. Without supplementation, vitamin D status increased during pregnancy, demonstrating that pregnancy stage should be considered when assessing vitamin D status. Nutritionally relevant cholecalciferol supplementation further increased vitamin D status. These data are relevant to the development of fortification and supplementation policies in pregnant women in West Africa.