Paul Lips

VU University Medical Center, Amsterdamo, North Holland, Netherlands

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Publications (211)1312.04 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Advanced glycation endproducts (AGEs) are a heterogeneous group of compounds formed nonenzymatically by glycation and oxidation of proteins. AGEs are suggested as one of the major agents in the pathogenesis and progression of diabetic-associated microvascular and macrovascular complications.
    11/2015; 11(4):141-141. DOI:10.1007/s12467-013-0076-9
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    ABSTRACT: Elevated homocysteine concentrations are associated with a decline in physical function in elderly persons. Homocysteine-lowering therapy may slow down this decline. This study aimed to examine the effect of a 2-year intervention of vitamin B12 and folic acid supplementation on physical performance, handgrip strength, and risk of falling in elderly subjects in a double-blind, randomized placebo-controlled trial. Participants aged ≥65 years with elevated plasma homocysteine concentrations [12-50 µmol/L (n = 2919)] were randomly assigned to daily supplementation of 500 µg vitamin B12, 400 µg folic acid, and 600 IU vitamin D3, or to placebo with 600 IU vitamin D3. Physical performance (range 0-12) and handgrip strength (kg) were measured at baseline and after 2 years. Falls were reported prospectively on a research calendar. Intention-to-treat (primary) and per-protocol (secondary) analyses were performed. Physical performance level and handgrip strength significantly decreased during the follow-up period, but this decline did not differ between groups. Moreover, time to first fall was not significantly different (HR: 1.0, 95 % CI 0.9-1.2). Secondary analyses on a per-protocol base identified an interaction effect with age on physical performance. In addition, the treatment was associated with higher follow-up scores on the walking test (cumulative OR: 1.3, 95 % CI 1.1-1.5). Two-year supplementation of vitamin B12 and folic acid was neither effective in reducing the age-related decline in physical performance and handgrip strength, nor in the prevention of falling in elderly persons. Despite the overall null-effect, the results provide indications for a positive effect of the intervention on gait, as well as on physical performance among compliant persons >80 years. These effects should be further tested in future studies.
    Calcified Tissue International 09/2015; DOI:10.1007/s00223-015-0059-5 · 3.27 Impact Factor
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    ABSTRACT: Background Vitamin D is well known for its function in calcium homeostasis and bone mineralisation, but is increasingly studied for its potential immunomodulatory properties. Vitamin D deficiency is a common problem in patients with COPD. Previous studies have not demonstrated a beneficial effect of vitamin D on exacerbation rate in COPD patients. However, subgroup analyses suggested protective effects in vitamin D deficient patients. Our objective is to assess the effect of vitamin D supplementation on exacerbation rate specifically in vitamin D deficient COPD patients. Methods/Design We will perform a randomised, multi-center, double-blind, placebo-controlled intervention study. The study population consists of 240 COPD patients aged 40 years and older with vitamin D deficiency (25-hydroxyvitamin D concentration < 50 nmol/L). Participants will be recruited after an exacerbation and will be randomly allocated in a 1:1 ratio to receive vitamin D3 16800 IU or placebo orally once a week during 1 year. Participants will receive a diary card to register the incidence of exacerbations and changes in medication during the study period. Visits will be performed at baseline, at 6 months and at 12 months after randomisation. Participants will undergo spirometry, measurement of total lung capacity and assessment of maximal respiratory mouth pressure. Several physical performance and hand grip strength tests will be performed, questionnaires on quality of life and physical activity will be filled in, a nasal secretion sample and swab will be obtained and blood samples will be taken. The primary outcome will be exacerbation rate. Discussion This study will be the first RCT aimed at the effects of vitamin D supplementation on exacerbation rate in vitamin D deficient COPD patients. Also, in contrast to earlier studies that used infrequent dosing regimens, our trial will study effects of a weekly dose of vitamin D supplementation. Secondly, the immunomodulatory effects of vitamin D on host immune response of COPD patients and underlying mechanisms will be studied. Finally, the effects on physical functioning will be examined. Trial registration This trial is registered in, ID number NCT02122627. Date of Registration April 2014.
    BMC Pulmonary Medicine 09/2015; 15(1). DOI:10.1186/s12890-015-0101-4 · 2.40 Impact Factor
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    ABSTRACT: Background/objectives: The prevalence of vitamin D deficiency among seniors is high. Whereas sun exposure, vitamin D intake, genes, demographics, and lifestyle have been identified as being important determinants of vitamin D status, the impact of these factors is expected to differ across populations. To improve current prevention and treatment strategies, this study aimed to explore the main determinants of vitamin D status and its relative importance in a population of community-dwelling Dutch older adults. Methods/subjects: Serum 25-hydroxyvitamin D (25(OH)D) was measured in 2857 adults aged ≥65 years. Sun exposure was assessed with a structured questionnaire (n=1012), vitamin D intake using a Food Frequency Questionnaire (n=596), and data on genetic variation that may affect 25(OH)D status was obtained for 4 genes, DHCR7 (rs12785878), CYP2R1 (rs10741657), GC (rs2282679), and CYP24A1 (rs6013897) (n=2530). Results: Serum 25(OH)D concentrations <50nmol/L were observed in 45% of the population; only 6% of these participants used vitamin D supplements. Sun exposure (being outside daily during summer: 66±25nmol/L vs not being outside daily during summer: 58±27nmol/L, P=0.02) and vitamin D intake (per unit μg/day during winter/spring: 3.1±0.75nmol/L, P<0.0001) were associated with higher 25(OH)D concentrations. Major allele carriers of SNPs related to DHCR7, CYP24A1, and GC, as well as CYP2R1 minor allele carriers had the highest 25(OH)D concentrations. Together, sun (R(2)=0.29), vitamin D intake (R(2)=0.24), and genes (R(2)=0.28) explained 35% (R(2)=0.35) of the variation in 25(OH)D concentrations during summer/autumn period, when adjusted for age, sex, BMI, education, alcohol consumption, smoking, physical activity, and self-rated health status (n=185). Conclusion: The investigated determinants explained 35% of 25(OH)D status. Of the three main determinants under study, sun exposure still appeared to be an important determinant of serum 25(OH)D in older individuals, closely followed by genes, and vitamin D intake. Given the low frequency of vitamin D supplement use in this population, promoting supplement use may be an inexpensive, easy, and effective strategy to fight vitamin D deficiency.
    The Journal of steroid biochemistry and molecular biology 08/2015; DOI:10.1016/j.jsbmb.2015.08.008 · 3.63 Impact Factor
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    ABSTRACT: Elevated systemic levels of pro-inflammatory cytokines are thought to be involved in the pathogenesis of osteoporosis. Our objective was to investigate whether low grade systemic inflammation was associated with bone markers, bone quality, bone mass and fracture risk in a population of older persons. Serum interleukin 6 (IL-6), high-sensitivity C-reactive protein (hsCRP) and erythrocyte sedimentation rate (ESR) were measured in 1287 participants of the Longitudinal Aging Study Amsterdam (LASA), a population based study in a representative sample of older men and women (age 76±6.7years). Bone quality was measured by quantitative ultrasound measurements (QUS) at baseline and after 3years at the calcaneus, and bone mineral density was measured by dual-energy x-ray absorptiometry (DXA) at the spine and hip in a subpopulation. Furthermore, the bone markers osteocalcin (OC) and urinary excretion of deoxypyridinoline (DPD) were determined. Incident clinical fractures were recorded during 6years of follow-up. Multivariable regression analyses revealed higher IL-6 and ESR levels were associated with lower quantitative ultrasound values in older men (β=-0.98; 95%CI -57.72- -6.42, p<0.05) and (β=-0.221; 95%CI -15.39- -3.27, p<0.05) respectively at baseline, but not in women. No significant associations were found between inflammatory markers and bone markers, bone loss at the spine or hips, fracture rate or time to fracture. Elevated inflammatory markers are associated with impaired bone quality in older men, but not in women. No associations were found with the risk for fractures. Copyright © 2015. Published by Elsevier Inc.
    Bone 07/2015; 81. DOI:10.1016/j.bone.2015.07.017 · 3.97 Impact Factor
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    ABSTRACT: Hyperhomocysteinemia is an important cardiovascular risk indicator in the oldest old, and is associated with elevated arterial stiffness in this age group. Since several intervention trials reported a lack of benefit of B-vitamin supplementation on cardiovascular outcomes, we aimed to investigate the effect of B-vitamin supplementation on arterial stiffness and atherosclerosis in hyperhomocysteinemic elderly patients. The B-PROOF study is a double-blind, randomized controlled trial, including 2919 elderly aged at least 65 years, with hyperhomocysteinemia (12-50 μmol/l), treated with B-vitamins (500 μg vitamin B12 and 400 μg folic acid) or placebo for 2 years. In a subgroup (n = 569), the effect of B-vitamins on pulse wave velocity (PWV) was investigated as a measurement of arterial stiffness. To measure atherosclerosis, carotid intima-media thickness (IMT) measures had been used. Incidents of cardiovascular and cerebrovascular events were determined via structured questionnaires, and blood pressure was also measured. Compared to placebo, B-vitamin supplementation lowered serum homocysteine by 3.6 μmol/l (P < 0.001). Analysis of covariance showed no effect of supplementation on PWV levels, and this was not different for patients without increased arterial stiffness at baseline. Furthermore, no effect on carotid IMT was observed. Vitamin B12 and folic acid supplementation in hyperhomocysteinemic elderly patients have no effect on PWV or carotid IMT. Further research will still be necessary to unravel the effects and pathways of homocysteine-lowering treatment on cardiovascular outcomes.
    Journal of Hypertension 06/2015; 33(9). DOI:10.1097/HJH.0000000000000647 · 4.72 Impact Factor
  • 05/2015; DOI:10.1530/endoabs.37.OC3.2
  • 05/2015; DOI:10.1530/endoabs.37.GP.11.08
  • 05/2015; DOI:10.1530/endoabs.37.GP.10.05
  • 05/2015; DOI:10.1530/endoabs.37.GP.20.02
  • 05/2015; DOI:10.1530/endoabs.37.EP734
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    ABSTRACT: Introduction: Patients with differentiated thyroid cancer (DTC) are treated with (near)-total thyroidectomy followed by remnant ablation. Optimal radioiodine-131 (131I) uptake is achieved by withholding thyroid hormone (THW), pretreatment with recombinant human Thyrotropin Stimulating Hormone (rhTSH) is an alternative. Six randomized trials have been published comparing THW and rhTSH, however comparison is difficult because an uniform definition of ablation success is lacking. Using a strict definition, we performed an observational study aiming to determine the efficacy of rhTSH as preparation for remnant ablation. Patients and methods: Adult DTC patients with, tumor stage T1b to T3, Nx, N0 and N1, M0 were included in a prospective multicenter observational study with a fully sequential design, using a stopping rule. All patients received remnant ablation with 131I using rhTSH. Ablation success was defined as no visible uptake in the original thyroid bed on a rhTSH stimulated 150 MBq 131I whole body scan (WBS) 9 months after remnant ablation, or no visible uptake in the original thyroid bed on a post therapeutic WBS when a second high dose was necessary. Results: After interim analysis of the first 8 patients, the failure rate was estimated to be 69% (90% confidence interval (CI) 20-86%) and the inclusion of new patients had to be stopped. Final analysis resulted in an ablation success in 11 out of 17 patients (65%, 95% CI 38-86%). Conclusion: According to this study, the efficacy of rhTSH in the preparation of 131I ablation therapy is inferior, when using a strict definition of ablation success. The current lack of agreement as to the definition of successful remnant ablation, makes comparison between different ablation strategies difficult. Our results point to the need for an international consensus on the definition of ablation success, not only in routine patient's care but also for scientific reasons. Trial registration: Dutch Trial Registration NTR2395.
    PLoS ONE 03/2015; 10(3). DOI:10.1371/journal.pone.0120184 · 3.23 Impact Factor
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    ABSTRACT: Beyond the established roles of vitamin D in bone and mineral homeostasis, we are becoming increasingly aware of its diverse effects in skeletal muscle. Subjects with severe vitamin D deficiency or mutations of the vitamin D receptor develop generalized atrophy of muscle and bone, suggesting coordinated effects of vitamin D in musculoskeletal physiology. At a mechanistic level, vitamin D exerts wide-ranging effects in muscle and bone calcium handling, differentiation and development. Vitamin D also modulates muscle and bone-derived hormones, facilitating cross-talk between these tissues. In this review, we discuss emerging evidence that vitamin D regulates bone and muscle in a direct, integrated fashion, positioning the vitamin D pathway as a potential therapeutic target for musculoskeletal diseases. Copyright © 2015. Published by Elsevier Inc.
    Bone 03/2015; DOI:10.1016/j.bone.2015.02.029 · 3.97 Impact Factor
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    ABSTRACT: Objectives: First, the association between serum 25-hydroxyvitamin D (25[OH]D) and cognitive performance was examined. Second, we assessed whether there was evidence for an interplay between 25(OH)D and glucose homeostasis in the association with cognitive performance. Design, setting, and participants: Associations were studied using cross-sectional data of 776 (3 domains) up to 2722 (1 domain) Dutch community-dwelling older adults, aged 65 years or older. Measurements: Serum 25(OH)D, plasma glucose, and insulin concentrations were obtained. Cognitive performance was assessed with an extensive cognitive test battery. Prevalence ratios (PRs) were calculated to quantify the association between 25(OH)D and cognition; poor performance was defined as the worst 10% of the distribution of the cognitive scores. Results: The overall median MMSE score was 29 (IQR 28-30). Higher serum 25(OH)D was associated with better attention and working memory, PR 0.50 (95% CI 0.29-0.84) for the third serum 25(OH)D tertile, indicating a 50% lower probability of being a poor performer than participants in the lowest tertile. Beneficial trends were shown for 25(OH)D with executive function and episodic memory. Serum 25(OH)D was not associated with plasma glucose or insulin. Plasma insulin only modified the association between serum 25(OH)D and executive function (P for interaction: .001), suggesting that the improvement in executive function with high 25(OH)D concentrations is stronger in participants with high plasma insulin concentrations compared with those with low plasma insulin concentrations. Conclusion: Higher 25(OH)D concentrations significantly associated with better attention and working memory performance. This study does not demonstrate an interplay between serum 25(OH)D and glucose homeostasis in the association with cognitive performance.
    Journal of the American Medical Directors Association 03/2015; 16(7). DOI:10.1016/j.jamda.2015.02.013 · 4.94 Impact Factor
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    ABSTRACT: High plasma homocysteine (Hcy) levels are associated with increased osteoporotic fracture incidence. However, the mechanism remains unclear. We investigated the effect of Hcy-lowering vitamin B12 and folic acid treatment on bone mineral density (BMD) and calcaneal quantitative ultrasound (QUS) parameters. This randomized, double-blind, placebo-controlled trial included participants aged ≥65 years with plasma Hcy levels between 12 and 50 µmol/L. The intervention comprised 2-year supplementation with either a combination of 500 µg B12, 400 µg folic acid, and 600 IU vitamin D or placebo with 600 IU vitamin D only. In total, 1111 participants underwent repeated dual-energy X-ray assessment and 1165 participants underwent QUS. Femoral neck (FN) BMD, lumbar spine (LS) BMD, calcaneal broadband ultrasound attenuation (BUA), and calcaneal speed of sound (SOS) were assessed. After 2 years, FN-BMD and BUA had significantly decreased, while LS-BMD significantly increased (all p < 0.01) and SOS did not change in either treatment arm. No statistically significant differences between the intervention and placebo group were present for FN-BMD (p = 0.24), LS-BMD (p = 0.16), SOS (p = 0.67), and BUA (p = 0.96). However, exploratory subgroup analyses revealed a small positive effect of the intervention on BUA at follow-up among compliant persons >80 years (estimated marginal mean 64.4 dB/MHz for the intervention group and 61.0 dB/MHz for the placebo group, p = 0.04 for difference). In conclusion, this study showed no overall effect of treatment with vitamin B12 and folic acid on BMD or QUS parameters in elderly, mildly hyperhomocysteinemic persons, but suggests a small beneficial effect on BUA in persons >80 years who were compliant in taking the supplement.
    Calcified Tissue International 02/2015; 96(5). DOI:10.1007/s00223-015-9968-6 · 3.27 Impact Factor
  • JoEllen Welsh · Daniel D Bikle · Paul Lips
    The Journal of Steroid Biochemistry and Molecular Biology 01/2015; 148. DOI:10.1016/j.jsbmb.2015.01.024 · 3.63 Impact Factor
  • Haakon E Meyer · Kristin Holvik · Paul Lips
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    ABSTRACT: This is one of a series of occasional articles that highlight areas of practice where management lacks convincing supporting evidence. The series adviser is David Tovey, editor in chief, the Cochrane Library. To suggest a topic for this series, please email us at uncertainties{at} authors would like to thank Julie Whittle Johansen for proofreading the manuscript.Contributors: HEM wrote the manuscript draft, assisted by KH and PL. HEM conducted the literature review. All authors approved the final version of the manuscript. HEM is guarantor.Competing interests: We have read and understood BMJ policy on declaration of interests and declare the following interests: KH received payment for performing independent food safety assessments concerning vitamin D as a member of the Norwegian Scientific Committee for Food Safety’s panel on nutrition, dietetic products, novel food and allergy. She also received an honorarium from Renapharma for a lecture in an educational symposium for general practitioners in November 2012. The funding company had no influence on the content of the lecture. PL and HEM have none.Provenance and peer review: Commissioned; externally peer reviewed.
    BMJ Clinical Research 01/2015; 350(jan29 10):h321. DOI:10.1136/bmj.h321 · 14.09 Impact Factor
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    ABSTRACT: Ambulatory measurements of trunk accelerations can provide valuable information on the amount and quality of daily-life activities and contribute to the identification of individuals at risk of falls. We compared associations between retrospective and prospective falls with potential risk factors as measured by daily-life accelerometry. In addition, we investigated predictive value of these parameters for 6-month prospective falls. One week of trunk accelerometry (DynaPort MoveMonitor) was obtained in 169 older adults (mean age 75). The amount of daily activity and quality of gait were determined and validated questionnaires on fall-risk factors, grip strength, and trail making test were obtained. Six-month fall incidence was obtained retrospectively by recall and prospectively by fall diaries and monthly telephone contact. Among all participants, 35.5% had a history of ≥1 falls and 34.9% experienced ≥1 falls during 6-month follow-up. Logistic regressions showed that questionnaires, grip strength, and trail making test, as well as the amount and quality of gait, were significantly associated with falls. Significant associations differed between retrospective and prospective analyses although odds ratios indicated similar patterns. Predictive ability based on questionnaires, grip strength, and trail making test (area under the curve .68) improved substantially by accelerometry-derived parameters of the amount of gait (number of strides), gait quality (complexity, intensity, and smoothness), and their interactions (area under the curve .82). Daily-life accelerometry contributes substantially to the identification of individuals at risk of falls, and can predict falls in 6 months with good accuracy. © The Author 2015. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail:
    The Journals of Gerontology Series A Biological Sciences and Medical Sciences 01/2015; 70(5). DOI:10.1093/gerona/glu225 · 5.42 Impact Factor
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    ABSTRACT: ObjectiveA possible association between serum 25-hydroxyvitamin D and testosterone levels has been reported, however, contradictory results have emerged.DesignTo investigate a causal link between vitamin D and testosterone status, we studied the effect of vitamin D supplementation on serum testosterone concentrations in three independent intervention studies including male patients with heart failure (study 1), male nursing home residents (study 2) and male non-western immigrants in the Netherlands (study 3).Methods In study 1, 92 subjects were randomized to either vitamin D (2000 IU cholecalciferol daily) or control. Blood was drawn at baseline, after 3 and 6 weeks. In study 2, 49 vitamin D deficient subjects received either vitamin D (600IU daily) or placebo. Blood was drawn at baseline and after 8 and 16 weeks. In study 3, 43 vitamin D deficient subjects received either vitamin D (1200IU daily) or placebo. Blood was drawn at baseline and after 8 and 16 weeks.Serum 25-hydroxyvitamin D levels were measured using LC-MS/MS or radioimmunoassay. Testosterone levels were measured using a 2nd generation immunoassay.ResultsSerum 25-hydroxyvitamin D levels significantly increased in all treatment groups (median increase of 27, 30, and 36 nmol/L in study 1, 2, 3, respectively) but not in the control groups. The documented increase in 25-hydroxyvitamin D levels, however, did not affect mean testosterone concentrations at the end of the study (median increase of 0, 0.5, and 0 nmol/L in study 1, 2, and 3, respectively) .Conclusions In this post-hoc analysis of 3 small clinical trials of limited duration in men with normal baseline testosterone concentrations, vitamin D supplementation was not associated with an increase in circulating testosterone concentrations.This article is protected by copyright. All rights reserved.
    Clinical Endocrinology 01/2015; 83(1). DOI:10.1111/cen.12711 · 3.46 Impact Factor
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    ABSTRACT: We investigated the reliability of physical activity monitoring based on trunk accelerometry in older adults and assessed the number of measured days required to reliably assess physical activity. Seventy-nine older adults (mean age 79.1±7.9) wore an accelerometer (DynaPort MoveMonitor, McRoberts) at the lower back during two non-consecutive weeks. The duration of locomotion, lying, sitting, standing and shuffling, movement intensity, the number of locomotion bouts and transitions to standing and the median and maximum duration of locomotion were determined per day. Using data of week 2 as reference, intraclass correlations and smallest detectable differences were calculated over an increasing number of consecutive days from week 1. Reliability was good to excellent when whole weeks were assessed. Our results indicate that a minimum of 2 days of observation are required to obtain an ICC≥0.7 for most activities, except for lying and median duration of locomotion bouts, which required up to 5 days.
    Journal of aging and physical activity 01/2015; 23(1):9-17. DOI:10.1123/japa.2013-0103 · 1.97 Impact Factor

Publication Stats

14k Citations
1,312.04 Total Impact Points


  • 2001–2015
    • VU University Medical Center
      • • Department of Internal Medicine
      • • Department of Endocrinology
      • • Department of Pediatrics
      Amsterdamo, North Holland, Netherlands
  • 1995–2015
    • VU University Amsterdam
      • • Faculty of Human Movement Sciences
      • • Academic Centre for Dentistry Amsterdam (ACTA)
      • • IHS-Institute of Health Sciences
      • • Department of Social Gerontology
      Amsterdamo, North Holland, Netherlands
  • 1998–2010
    • Academisch Medisch Centrum Universiteit van Amsterdam
      • • Department of Internal Medicine
      • • Department of Endocrinology and Metabolism
      Amsterdamo, North Holland, Netherlands
  • 1998–2009
    • University of Amsterdam
      • Department of Endocrinology
      Amsterdamo, North Holland, Netherlands
  • 2006
    • University of Florence
      Florens, Tuscany, Italy
    • Erasmus MC
      • Department of Internal Medicine
      Rotterdam, South Holland, Netherlands