Jonathan C.Y. Tang

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• PhD. MSc. BSc. FIBMS
• Senior Research Fellow in Metabolic Bone Disease and Clinical Biochemistry-Laboratory Medicine at University of East Anglia

Low vitamin D associated with high parathyroid hormone (PTH) is commonly reported in the context of HIV infection. We determined the association between total 25-hydroxyvitamin-D [25(OH)D] and PTH in adolescents living with HIV, in Zambia and Zimbabwe. Adolescents (11-19 years) perinatally-infected with HIV and established on antiretroviral therapy...

Calcium supplementation before exercise attenuates the decrease in serum calcium and increase in PTH and bone resorption. This study investigated the effect of calcium supplementation on calcium and bone metabolism during load carriage in women. A total of 48 women completed two load carriage sessions (load carriage 1 n = 48; load carriage 2 n = 40...

Objectives Automated immunoassays for 1,25-dihydroxyvitamin D (1,25(OH) 2 D) have increased the use of serum measurements in clinical and research settings, but disagreement with LC-MS/MS methods remains an issue. Methods In this study, we examined this problem using samples obtained from healthy young adults, n=80, mean age 21.7 (18–32) years, an...

The Mediterranean diet is associated with reduced mortality and cognitive decline, largely due to its polyphenol content. However, Western populations often do not meet recommended fruit and vegetable intakes. Polyphenols exert anti-inflammatory effects and may influence extracellular vesicle (EV) dynamics. DailyColors™ is a polyphenol-rich blend i...

Vitamin D dysregulation can occur in people living with HIV, disrupting calcium homeostasis and bone turnover. We aimed to investigate the potential mechanisms by which vitamin D regulates bone turnover in adolescents living with perinatally-acquired HIV (ALWH) in southern Africa. A pre-planned secondary analysis was performed of baseline data from...

Purpose: To investigate associations between hormonal contraceptive use and physical performance, body composition, and musculoskeletal injuries in basic military training. Methods: Female British Army recruits (n = 450) were grouped as non-users (n = 182), combined oral contraceptive users (COCP; n = 184), or progestin-only users (POC; n = 144). P...

PURPOSE: Women are at increased risk of stress fractures compared with men in military training. Exercise can decrease circulating serum calcium and increase parathyroid hormone (PTH) and bone resorption; these disturbances can be attenuated with calcium supplementation immediately before exercise, but this effect during load carriage in women is u...

Paget’s disease of bone (PDB) is characterised by increased and disorganised bone remodelling leading to various complications, such as bone deformity, deafness, secondary osteoarthritis, and pathological fracture. Pain is the most common presenting symptom of PDB, but it is unclear to what extent this is due to increased metabolic activity of the...

Objective To determine whether vitamin D supplementation influences grip strength, explosive leg power, cardiorespiratory fitness and risk of exercise-induced bronchoconstriction (EIB) in South African schoolchildren. Methods Substudy (n=450) in Cape Town schoolchildren aged 8–11 years nested within a phase 3 randomised placebo-controlled trial (V...

Resistance exercise (RE) increases collagen synthesis in young and older men, while hydrolyzed collagen (HC) ingestion improves this response to RE in a dose-response manner in young men. However, the collagen synthesis response to RE with and without HC in middle-aged men is unknown. Eight resistance-trained men (age: 49±8 years; height: 1.78±0.02...

Ovarian reserve is a reflection of the overall female reproductive potential. Vitamin D status has been suspected to influence fetal development and female fertility. As maternal diet during pregnancy can affect fetal development and future fertility, we hypothesised that periconceptional and gestational Vitamin D restriction could affect folliculo...

Montmorency cherry (MC) can improve endurance performance, but optimal pre‐exercise timing of supplementation and influence of training status on efficacy are unknown. We investigated the effect of MC concentrate ingestion between 30‐ and 150‐min pre‐exercise in trained and recreational cyclists on 15‐km time trial (TT) performance and exercise eco...

Purpose To test the hypothesis that training with reduced carbohydrate (CHO) availability increases bone resorption in adolescent soccer players. Methods In a randomised crossover design, ten male players (age: 17.4 ± 0.8 years) from an English Premier League academy completed an acute 90-min field-based training session (occurring between 10:30–1...

We have previously shown that high-dose vitamin D3 improved weight gain and neurodevelopmental indices in children receiving standard therapy for uncomplicated severe acute malnutrition (SAM). We conducted a randomised placebo-controlled trial to determine whether two oral doses of 200,000 international units (IU) vitamin D3 would benefit children...

Background Women of reproductive age experience cyclical variation in the female sex steroid hormones 17β-estradiol and progesterone during the menstrual cycle that is attenuated by some hormonal contraceptives. Estrogens perform a primary function in sexual development and reproduction but have nonreproductive effects on bone, muscle, and sinew ti...

We investigated the effects of resistance exercise (RE), hydrolysed collagen (HC) ingestion and circulating oestrogen concentration on collagen synthesis in a naturally menstruating female CrossFit athlete. In a double‐blind, randomised cross‐over design, the participant (36 years; height 1.61 m; mass 82.6 kg) consumed 0 or 30 g HC prior to perform...

BACKGROUND TB control requires the understanding and disruption of TB transmission. We describe prevalence, incidence and risk factors associated with childhood TB infection in Cape Town, South Africa. METHODS We report cross-sectional baseline and prospective incidence data from a large trial among primary school children living in high TB burden...

Vitamin D3 synthesis in human skin is initiated by solar ultraviolet radiation (UVR) exposure of precursor 7-dehydrocholesterol (7DHC), but influence of age on the early stage of vitamin D3 metabolism is uncertain. We performed a prospective standardised study in healthy ambulant adults aged ≥65 and ≤40 years examining (1) if baseline skin 7DHC con...

Objective To determine whether weekly oral vitamin D supplementation influences growth, body composition, pubertal development or spirometric outcomes in South African schoolchildren. Design Phase 3 double-blind randomised placebo-controlled trial. Setting Socioeconomically disadvantaged peri-urban district of Cape Town, South Africa. Participan...

Objective: To determine whether vitamin D supplementation influences grip strength, explosive leg power, cardiorespiratory fitness and risk of exercise-induced bronchoconstriciton (EIB) in South African schoolchildren. Methods: Sub-study (n=450) in Cape Town schoolchildren aged 8-11 years, nested within a phase 3 randomised placebo-controlled trial...

Background: Tuberculosis (TB) control requires the understanding and disruption of TB transmission. We describe prevalence, incidence and risk factors associated with childhood TB infection in Cape Town. Methods: We report cross-sectional baseline and prospective incidence data from a large trial among primary school children living in high TB-burd...

Randomised controlled trials (RCT) to determine the influence of vitamin D on bone mineral content (BMC) and fracture risk in children of Black African ancestry are lacking. We conducted a sub-study (n=450) nested within a Phase 3 RCT of weekly oral supplementation with 10,000 IU vitamin D3 vs. placebo for 3 years in HIV-uninfected Cape Town school...

Legumain is a lysosomal cysteine protease that has been implicated in an increasing amount of physiological and pathophysiological processes. However, the upstream mechanisms regulating the expression and function of legumain are not well understood. Here, we provide in vitro and in vivo data showing that vitamin D3 (VD3) enhances legumain expressi...

Introduction Paget’s disease of bone (PDB) frequently presents at an advanced stage with irreversible skeletal damage. Clinical outcomes might be improved by earlier diagnosis and prophylactic treatment. Methods We randomised 222 individuals at increased risk of PDB because of pathogenic SQSTM1 variants to receive 5 mg zoledronic acid (ZA) or plac...

Objective: To determine whether weekly oral vitamin D supplementation influences growth, body composition, pubertal development or spirometric outcomes in South African schoolchildren. Design: Phase 3 double-blind randomised placebo-controlled trial (clinicaltrials.gov registration no. NCT02880982). Setting: Socio-economically disadvantaged peri-ur...

Background: Zoledronate is a nitrogen-containing bisphosphonate (BP) recognised for its antiresorptive potency. The pharmacokinetic/pharmacodynamic of zoledronate remains unclear. Although adverse events from overuse of BP is rare, there have been reports of over-treatment resulting in pathophysiological consequences. The current administration reg...

We investigated the association between vitamin D metabolites and incidence of lower body (pelvis and lower limb) overuse musculoskeletal and bone stress injury in 1637 men and 530 women (22.6 ± 7.5 years), undergoing 12 weeks initial military training. We measured serum 25-hydroxyvitamin D (25(OH)D) and 24,25-dihydroxyvitamin D (24,25(OH)2D) by hi...

Background: Resistance exercise (RE) stimulates collagen synthesis in skeletal muscle and tendon but there is limited and equivocal evidence regarding an effect of collagen supplementation and exercise on collagen synthesis. Furthermore, it is not known if a dose-response exists regarding the effect of hydrolyzed collagen (HC) ingestion and RE on c...

Purpose The primary aim of this study was to examine whether a glycine-rich collagen peptides (CP) supplement could enhance sleep quality in physically active men with self-reported sleep complaints. Methods In a randomized, crossover design, 13 athletic males (age: 24 ± 4 years; training volume; 7 ± 3 h·wk ¹ ) with sleep complaints (Athens Insomn...

This study investigated sex differences in iron status, and associations between iron status and endurance and musculoskeletal outcomes, in military training. 2,277 British Army trainees (581 women) participated. Iron markers and endurance performance (2.4 km run) were measured at the start (week 1) and end (week 13) of training. Whole-body areal b...

The relationship between vitamin D metabolites and lower body (pelvis and lower limb) overuse injury is unclear. In a prospective cohort study, we investigated the association between vitamin D metabolites and incidence of lower body overuse musculoskeletal and bone stress injury in young adults undergoing initial military training during all seaso...

Skin exposure to ultraviolet radiation (UVR) triggers conversion of precursor 7-dehydrocholesterol (7DHC) to vitamin D3, which then enters the bloodstream. The aim of this study was to assess if skin 7DHC concentration differs between younger and older adults, and to explore the impact of solar-simulated UVR (SSR) on 7DHC (in skin) and vitamin D3 (...

BACKGROUND Women of reproductive age experience cyclical variation in the female sex steroid hormones 17β-estradiol and progesterone during the menstrual cycle that is attenuated by some hormonal contraceptives. Estrogens perform a primary function in sexual development and reproduction but have nonreproductive effects on bone, muscle, and sinew ti...

Unlabelled: This study assessed whether vitamin K, given with oral bisphosphonate, calcium and/or vitamin D has an additive effect on fracture risk in post-menopausal women with osteoporosis. No difference in bone density or bone turnover was observed although vitamin K1 supplementation led to a modest effect on parameters of hip geometry. Purpos...

Background Military field exercises are characterised by high volumes of exercise and prolonged periods of load carriage. Exercise can decrease circulating serum calcium and increase parathyroid hormone and bone resorption. These disturbances to calcium and bone metabolism can be attenuated with calcium supplementation immediately before exercise....

BACKGROUND Randomised controlled trials (RCT) to determine the influence of vitamin D on bone mineral content (BMC) and fracture risk in children of Black African ancestry are lacking. METHODS We conducted a sub-study nested within a Phase 3 RCT of weekly oral supplementation with 10,000 IU vitamin D3 in HIV-uninfected Cape Town schoolchildren of B...

This study investigated sex differences in, and the effect of protein supplementation on, bone metabolism during a 36-hour military field exercise. Forty-four British Army Officer cadets (14 women) completed a 36-hour field exercise. Participants consumed their habitual diet (n = 14 women [Women] and n = 15 men [Men Controls]) or the habitual diet...

Background: Vitamin D metabolites induce innate antimycobacterial responses in vitro. Observational studies consistently report independent associations between vitamin D deficiency and increased susceptibility to Mycobacterium tuberculosis infection. Methods: We conducted a randomised placebo-controlled trial to determine whether weekly oral su...

Vitamin D is essential for musculoskeletal health at all stages of human life. However, older adults can be prone to a lower vitamin D status [1]. With the growing population of > 65-year-olds [2], it is essential to better understand the functions of the ageing skin, and the early vitamin D pathway is a crucial area. Solar ultraviolet radiation (U...

Anabolic treatment options for osteoporosis remain limited. One approach to discovering novel anabolic drug targets is to identify genetic causes of extreme high bone mass (HBM). We investigated a pedigree with unexplained HBM within the UK HBM study, a national cohort of probands with HBM and their relatives. Whole exome sequencing (WES) in a fami...

Bone and renal metabolism are regulated by common factors and there is extensive cross-talk between these organs (the 'renal-bone-axis'). Ageing is associated with physiological changes including reduced bone mass, renal function and tissue sensitivity to regulatory hormones, impacting the renal-bone axis. We aimed to investigate the influence of e...

Loss‐of‐function mutations in the CYP24A1 protein‐coding region causing reduced 25OHD and 1,25(OH)2D catabolism have been observed in some cases of Infantile hypercalcaemia type 1 (HCINF1), which can manifest as nephrocalcinosis, hypercalcaemia and adult‐onset hypercalciuria and renal stone formation. Some cases present with apparent CYP24A1 phenot...

Purpose We examined the effects of collagen peptides (CP) supplementation on exercise-induced gastrointestinal (GI) stress. Methods In a randomized, crossover design, 20 volunteers (16 males: $$\dot{V}$$ V ˙ O 2max , 53.4 ± 5.9 ml·kg ⁻¹ ) completed 3 trials: a non-exercise rest trial, with no supplement (REST) and then an exercise trial with CP (1...

Objectives Vitamin D deficiency in neonates can have life-threatening consequences, hence the knowledge of risk factors is essential. This study aimed to explore the effect of maternal socioeconomic status (SES) on newborn 25-hydroxyvitamin D (25OHD) concentrations. Design Over two 1-week periods (winter and summer of 2019), 3000 newborn heel pric...

Background: Melatonin and cortisol production demonstrate circadian rhythms; disruption of these rhythms feature in endocrine and neurodegenerative disorders, such as Addison’s disease, Huntington’s disease (HD) and Alzheimer’s disease (AD). Measuring serum and saliva concentrations at nadir is challenging using immunoassays. We have developed LC-M...

Background: Volumetric absorbent microsampling (VAMS) provides a less intrusive alternative to venepuncture when collecting blood samples for diagnostic testing. A small, precisely determined amount of capillary blood from a single finger-prick is absorbed into a medium for storage, from which it can later be extracted and analysed. In this study,...

Introduction: The role of vitamin D and calcium metabolism has long been implicated in the clinical manifestation of primary hyperparathyroidism (PHPT). The skeletal response to the overproduction of PTH is less predictable, and the effect on bone loss can be greater in some patients. In this study, we established associations between vitamin D met...

Objectives: Examine the effect of maternal Index of Multiple Deprivation (IMD) on newborn 25-hydroxyvitaminD (25OHD) levels in a multi-ethnic newborn cohort. Design: 3000 dried blood spots (DBS) were gathered from newborns at a regional newborn screening laboratory over two 1-week periods [February 2019 (winter) and August 2019 (summer)]. Data on...

Purpose: To determine vitamin D metabolites and vitamin D receptor (VDR) single-nucleotide polymorphisms (SNPs) relationships with physical performance. Methods: In 1205 men and 322 women (94.8% white Caucasian, 22.0 ± 2.8 years) commencing military training, we measured: serum vitamin D metabolites (25-hydroxyvitamin D (25(OH)D) and 24,25-dihyd...

Military training increases tibial density and size, but it is unknown if men and women adapt similarly to the same arduous training. Seventy-seven men and 57 women not using hormonal contraceptives completed this study. Tibial volumetric bone mineral density (vBMD) and geometry were measured by peripheral quantitative computed tomography (4%, 14%,...

ABSTRACT Vitamin D status and supplementation regulates bone metabolism and may modulate Wnt signaling. We studied the response of hormonal regulators of bone metabolism, markers of Wnt signaling and bone turnover and bone mineral density (BMD) and bone mineral content (BMC) in a randomized vitamin D intervention trial (12,000 IU, 24,000 IU, 48,000...

Vitamin D deficiency (25-hydroxyvitamin D[25(OH)D] <50 nmol/L) is common among adults in Cape Town, South Africa, but studies investigating vitamin D status of children in this setting are lacking. We conducted a cross-sectional study to determine the prevalence and determinants of vitamin D deficiency in 1825 Cape Town schoolchildren aged 6–11 yea...

Oral delivery of peptides and proteins is hindered by their rapid proteolysis in the gastrointestinal tract and their inability to permeate biological membranes. Various drug delivery approaches are being investigated and implemented to overcome these obstacles. In the discussed study conducted in pigs, an investigation was un-dertaken to assess th...

Shatavari has long been used as an Ayurvedic herb for women’s health, but empirical evidence for its effectiveness has been lacking. Shatavari contains phytoestrogenic compounds that bind to the estradiol receptor. Postmenopausal estradiol deficiency contributes to sarcopenia and osteoporosis. In a randomised double-blind trial, 20 postmenopausal w...

Introduction: Montmorency cherry concentrate (MCC) supplementation enhances functional recovery from exercise, potentially due to antioxidant and anti-inflammatory effects. However, to date, supporting empirical evidence for these mechanistic hypotheses is reliant on indirect blood biomarkers. This study is the first to investigate functional reco...

Background Vitamin D deficiency in infancy can have devastating health consequences such as hypocalcaemic seizures and dilated cardiomyopathy. It is therefore imperative to ensure adherence to national antenatal and infant supplementation policies. The effectiveness of antenatal supplementation in preventing newborn vitamin D deficiency in the UK h...

Background Shatavari has long been used as an Ayurvedic herb for women’s health, but empirical evidence for its effectiveness has been lacking. Shatavari contains phytoestrogenic compounds that bind to the estradiol receptor, and may therefore benefit postmenopausal women since postmenopausal estradiol deficiency contributes to sarcopenia and osteo...

A 33-year-old gentleman of Egyptian heritage presented with a 21 years history of unexplained and recurrent hypercalcaemia, nephrolithiasis, nephrocalcinosis, and myocarditis. A similar history was also found in two first-degree relatives. Further investigation into the vitamin D metabolism pathway identified the biochemical hallmarks of infantile...

Sulforaphane (SFN), an isothiocyanate (ITCs) derived from glucosinolate that is found in cruciferous vegetables, has been reported to exert a promising anticancer effect in a substantial amount of scientific research. However, epidemical studies showed inconsistencies between cruciferous vegetable intake and bladder cancer risk. In this study, huma...

Background Seasonal variations have been reported for immune markers. However, the relative contributions of sunlight and vitamin D variability on such seasonal changes are unknown. Objective This double-blind, randomized, placebo-controlled trial tested whether daily 400 IU vitamin D3 supplementation affected short-term (12 weeks) and long-term (...

In patients with phenylketonuria (PKU), treated by diet therapy only, evidence suggests that areal bone mineral density (BMDa) is within the normal clinical reference range but is below the population norm. Aims: To study longitudinal bone density, mass, and geometry over 36 months in children with PKU taking either amino acid (L-AA) or casein gl...

Introduction Hormonal contraceptive use might impair bone health and increase the risk of stress fracture by decreasing endogenous oestrogen production, a central regulator of bone metabolism. This cross-sectional study investigated bone density and biochemical markers of bone metabolism in women taking hormonal contraceptives on entry to basic mil...

The standard treatment of primary hypoparathyroidism (hypoPT) with oral calcium supplementation and calcitriol (or an analog), intended to control hypocalcemia and hyperphosphatemia and avoid hypercalciuria, remains challenging for both patients and clinicians. In 2015, human parathyroid hormone (hPTH) (1‐84) administered as a daily subcutaneous in...

Older adults spend more than 8 h/day in sedentary behaviours. Detrimental effects of sedentary behaviour (SB) on health are established, yet little is known about SB and bone health (bone mineral density; BMD) in older adults. The purpose of this review is to examine associations of SB with BMD in older adults. Five electronic databases were search...

PurposeTo determine serum 25(OH)D and 1,25(OH)2D relationship with hepatitis B vaccination (study 1). Then, to investigate the effects on hepatitis B vaccination of achieving vitamin D sufficiency (serum 25(OH)D ≥ 50 nmol/L) by a unique comparison of simulated sunlight and oral vitamin D3 supplementation in wintertime (study 2).Methods Study 1 invo...

There is a need to further understand the impact of the menstrual cycle and phase of combined oral contraceptive (COC) use on the pre-analytical variability of markers of bone metabolism in order to improve standardisation procedures for clinical practice and research. The aim of this study was to assess bone metabolism marker concentrations across...

Purpose: To determine the relationship between vitamin D status and upper respiratory tract infection (URTI) of physically active men and women across seasons (study 1). Then, to investigate the effects on URTI and mucosal immunity of achieving vitamin D sufficiency (25(OH)D ≥50 nmol·L-1) by a unique comparison of safe, simulated-sunlight or oral...

To date, no research has explored the effects of low energy availability on cognitive performance using dietary and exercise regimens relevant to athletes. Twenty female participants (10 eumenorrheic, 10 oral contraceptive [OC] users) completed three 3-day conditions: 1) controlled-balanced energy availability without exercise (BAL; 45 kcal·kg lean...

Introduction. Sarcoidosis is a chronic granulomatous disease of unknown aetiology with a variable clinical course and prognosis. There is an urgent need to identify new and novel biomarkers to help differentiate between clinical phenotypes and guide clinical decisions with respect to commencing and monitoring treatment. Across the spectrum of respi...

Objectives To determine the prevalence of vitamin D deficiency on dried blood spots (DBS) obtained at newborn blood spot screening (NBS) and thereby test the efficacy of the UK national antenatal supplementation programme in an increasingly ethnically diverse English population. To evaluate the seasonal and ethnic variation in neonatal plasma 25 hy...

Introduction: Exercise acutely alters markers of bone resorption and formation. As risk of fracture is increased in patients with type 1 diabetes, understanding if exercise-induced bone turnover is affected within this population is prudent. We assessed bone turnover responses to acute exercise in individuals with long-duration type 1 diabetes and...

Purpose: To investigate the effect of supplementary energy on bone formation and resorption during arduous military training in energy deficit. Methods: Thirty male soldiers completed an 8-week military combat course (mean ± SD, age 25 ± 3 years, height 1.78 ± 0.05 m, body mass 80.9 ± 7.7 kg). Participants received either the habitual diet (cont...

The prevalence of vitamin D deficiency in the general population has become a major public health problem. Vitamin D deficiency might have significant consequences not only to bone health but possible to other autoimmune, infectious, cancer and cardiovascular diseases. The explosion of interests in vitamin D had sparked a massive increase in the nu...

Objectives: Mutations in SQSTM1 are strongly associated with Paget's disease of bone (PDB) but little is known about the clinical characteristics of those with early disease. Methods: Radionuclide bone scans, biochemical markers of bone turnover and clinical characteristics were analysed in SQSTM1 mutation carriers who took part in the Zoledroni...

The demand for measurement of vitamin D metabolites for clinical diagnosis and to advance our understanding of the role of vitamin D in human health has significantly increased in the last decade. New developments in technologies employed have enabled the separation and quantification of additional metabolites and interferences. Also, developments...

A 33 year-old man was referred to the endocrine bone clinic following presentation with a 4 mm kidney stone and hypercalcaemia. Apart from mild fatigue, he had no other hypercalcaemic or concerning symptoms. He was not on any medications or supplements. He had a positive family history for kidney stones and reported that his grandmother had been no...