Vascular effects of sodium and potassium intake
Gijsbers, Lieke - \ 2017
Wageningen University. Promotor(en): J.M. Geleijnse; Pieter van 't Veer. - Wageningen : Wageningen University - ISBN 9789463436267 - 161
sodium - potassium - vascular system - hypertension - blood pressure - mineral supplements - endothelium - blood vessels - heart rate - osmoregulation - human nutrition research - randomized controlled trials - cardiovascular diseases - natrium - kalium - vaatsysteem - hypertensie - bloeddruk - minerale supplementen - endotheel - bloedvaten - hartfrequentie - osmoregulatie - voedingsonderzoek bij de mens - gestuurd experiment met verloting - hart- en vaatziekten
Cardiovascular diseases (CVD) are the main cause of death worldwide. Annually, about 17.5 million people die from CVD, accounting for ~30% of deaths worldwide. Elevated blood pressure (BP) is a major risk factor for CVD and the largest single contributor to global mortality. BP is a modifiable risk factor that is largely determined by lifestyle factors, including diet. Dietary minerals, in particular sodium and potassium, play an important role in BP regulation. While adverse effects of sodium and beneficial effects of potassium on BP have repeatedly been shown in human intervention studies, evidence on other vascular effects of these dietary minerals is still scarce. Therefore, we investigated the BP effects of sodium and potassium intake in healthy humans in a broader (patho)physiological context, focusing also on endothelial function, arterial stiffness, fluid regulation and heart rate.
In Chapter 2, the effects of sodium and potassium supplementation on BP and arterial stiffness were examined by means of a randomized placebo-controlled crossover trial. Thirty-six untreated Dutch individuals with mildly elevated BP on a fully controlled diet that was relatively low in sodium (2-3 g/d) and potassium (2-3 g/d) received capsules with sodium (3 g/d), potassium (3 g/d) or placebo, for 4 weeks each, in random order. After each intervention, fasting office BP, 24-h ambulatory BP and measures of arterial stiffness were assessed. The results of this study showed that increased sodium intake strongly raised office and ambulatory systolic BP (7-8 mmHg) whereas increased potassium intake lowered systolic BP (3-4 mmHg). Potassium supplementation increased ambulatory HR, but office HR was not affected. Measures of arterial stiffness were not materially affected by increased sodium or potassium intake, possibly due to the relatively short intervention period.
In the same study we investigated the effects of increased sodium and potassium intake on the functional measure of endothelial function (flow-mediated dilation), and on a comprehensive set of biomarkers of endothelial dysfunction and low-grade inflammation (Chapter 3). Four weeks of supplemental sodium had no effect on brachial flow-mediated dilation, or on the blood biomarkers of endothelial dysfunction and low-grade inflammation, except for an increase in serum endothelin-1 (a biomarker of endothelial dysfunction). Potassium supplementation improved flow-mediated dilation by 1.2% and tended to lower the low-grade inflammation marker interleukin-8. This suggests that potassium may beneficially influence vascular health by improving endothelial function.
In a post-hoc analysis of the same study in 35 untreated individuals, the humoral effects of supplemental sodium and potassium were assessed using a panel of markers that are involved in osmoregulation and volume regulation (Chapter 4). Results showed that supplemental sodium increased plasma natriuretic peptides and plasma copeptin, and suppressed the renin-angiotensin system. Supplemental potassium decreased plasma MR-pro-ANP, increased plasma copeptin, and stimulated the renin-angiotensin system. These findings suggest that the mineral-induced changes in BP elicit several counter regulatory mechanisms to maintain volume homeostasis.
In Chapter 5, the effect of potassium supplementation on heart rate was assessed in a meta-analysis of 22 randomized, placebo-controlled trials in healthy adults. Overall, increasing potassium intake by 2-3 g/d for at least two weeks did not affect resting heart rate. 24-h Ambulatory heart rate was not significantly affected in subgroup analysis of 4 RCTs, including ours. Other subgroup analyses for characteristics of the study and study population also showed no significant effects, and there was no evidence for a dose-response relationship. These results suggest that increasing potassium intake is not expected to adversely affect heart rate in apparently healthy adults.
In Chapter 6, BP associations for sodium and potassium intake using different dietary assessment methods were examined. Data of 993 healthy Dutch adults not on antihypertensive medication were analyzed using a cross-sectional approach. Sodium and potassium intake were estimated from two non-consecutive 24-h urinary samples (considered as the gold standard), two non-consecutive web-based 24-h recalls, and a validated 180-item food frequency questionnaire (FFQ). This study showed no significant associations of sodium intake with BP, regardless of the dietary assessment method used. Potassium intake estimated from 24-h urine and FFQ was inversely associated with BP (~1.5 mmHg reduction per 1 g/d increment). This suggests that dietary assessment methods in cross-sectional studies may be inadequate for estimating the association of sodium intake with BP, but may yield reliable results for potassium intake.
As discussed in Chapter 7, the studies presented in this thesis indicate that increasing sodium intake from a recommended level to a level that is common in Western societies for four weeks strongly raises BP in individuals with an untreated mildly elevated BP. The results for endothelial function and arterial stiffness are inconclusive, and hence more (longer-term) studies are warranted. Increasing the intake of potassium lowers BP and improves endothelial function, even in individuals on a relatively low-sodium diet. Both sodium and potassium intake affected fluid parameters, likely indicating that compensatory responses are stimulated to maintain body fluid balance. Although in our RCT ambulatory heart rate was increased after supplemental potassium, the meta-analysis showed that increasing potassium intake is unlikely to affect heart rate in apparently healthy adults. When evaluating the effectiveness of sodium and potassium intake on cardiovascular health, results obtained from observational studies should be interpreted with caution, particularly for sodium intake.
Around the world people consume on average 9-12 g of salt and 2-4 g of potassium on a daily basis. A more optimal intake of sodium and potassium can be achieved through adherence to dietary guidelines and product reformulation by food industry. This could reduce BP by more than 10 mmHg and lower the number of cardiovascular deaths by at least one-quarter in Western populations.
Vitamin D for older adults : Determinants of status, supplementation strategies and its role in muscle function
Vaes, Anouk M.M. - \ 2017
Wageningen University. Promotor(en): C.P.G.M. de Groot, co-promotor(en): M. Tieland. - Wageningen : Wageningen University - ISBN 9789463436144 - 164
vitamin d - deficiency - aging - vitamin supplements - dosage effects - musculoskeletal system - literature reviews - food enrichment - skeletal muscle - food supplements - randomized controlled trials - vitamine d - deficiëntie - verouderen - vitaminetoevoegingen - doseringseffecten - skeletspierstelsel - literatuuroverzichten - voedselverrijking - skeletspier - voedselsupplementen - gestuurd experiment met verloting
Vitamin D has been identified as an important factor in healthy aging and is receiving growing attention in clinical research. Vitamin D is a fat-soluble molecule, which is synthesized by hepatic and renal or extra-renal hydroxylation into the active hormone 1,25-dihydroxyvitamin D (1,25(OH)2D). The main function of this metabolite is to regulate calcium and phosphorus homeostasis and to support bone mineralization. In the circulation, the 25-hydroxyvitamin D metabolite (25(OH)D) is most stable and thus, considered the best marker of vitamin D status. A serum 25(OH)D concentration <30-50 nmol/L is considered deficient. Given the increased risk of deficiency and the potential beneficial effect of supplementation on musculoskeletal health, older adults present a specific target group for vitamin D interventions. However, the optimal serum 25(OH)D concentration is a matter of ongoing debate as randomized trials show conflicting results.
With the research presented in this thesis, we aimed to gain insight in the prevalence and main determinants of a low vitamin D status, to investigate strategies to prevent or reverse vitamin D deficiency, and to study the effect of vitamin D supplementation on muscle strength and physical performance in Dutch older adults.
In chapter 2, we examined the prevalence and the main determinants of a low vitamin D status in a large population of community-dwelling older adults (n=2857). Vitamin D deficiency was highly prevalent, with serum 25(OH)D concentrations <50 nmol/L in 45%, and <30 nmol/L in 14% of the population. When exploring the main determinants of serum 25(OH)D status, significant associations were observed with age, BMI, dietary intake, sun exposure behavior, and genetic polymorphisms encoding for enzymes in the vitamin D pathway. Combined, these factors explained 35% of the variation in serum 25(OH)D concentrations.
To explore potential strategies that prevent vitamin D deficiency, we investigated the contribution of dietary vitamin D intake and specific food groups to serum 25(OH)D concentration in chapter 3. Daily vitamin D intake from dietary sources showed a median (25-75th percentile) intake of 4.0 (3.0-5.4) µg/day (n=595) and only 12-20% of older adults reported to take vitamin D supplements. These findings are in sharp contrast with the current nutrient guidelines and show that the vast majority of older adults do not meet the reference intakes for vitamin D. Nevertheless, significant associations were observed between the highest tertile of dietary vitamin D intake and serum 25(OH)D concentration, suggesting that regular intake of foods rich in vitamin D can support the prevention of modest insufficiency.
For the majority of older adults, supplementation is required to ensure sufficient serum 25(OH)D concentrations throughout the year. Currently, supplementation with vitamin D3 is the most common strategy. However, alternative treatment regimens exist that require further investigation. In chapter 4, we report on a dose-response trial (n=59) that investigated the efficacy of calcifediol (5, 10 or 15 µg/d) as a supplementation strategy. Compared to vitamin D3, calcifediol is more hydrophilic, does not require hepatic hydroxylation, and binds with higher affinity to its binding proteins. In our study, we observed that calcifediol was safe and well tolerated in the supplemented doses over the entire study period of 6-months. We concluded that a dose of 10 µg/day resulted in sustained serum 25(OH)D concentrations between 75-100 nmol/L. Furthermore, calcifediol had a ~3 times higher potency when compared to vitamin D3, in increasing serum 25(OH)D concentrations. All in all, calcifediol may offer a valuable supplementation regimen to rapidly correct deficiency.
Vitamin D presents an important endocrine regulator in the musculoskeletal health of older adults. Besides its role in bone health, low serum 25(OH)D concentrations have been linked to impaired physical performance and increased risk of falling. The active metabolite 1,25-dihydroxyvitamin D is suggested to act upon a wide variety of cells throughout the body, including muscle cells. Although the exact mechanisms by which vitamin D acts on muscle are unclear, several indirect or direct regulatory pathways have been described, including effects of 1,25-dihyroxyvitamin D through intracellular calcium and phosphate homeostasis, or via activation of transcription factors when binding to the vitamin D receptor in muscle cells.
In chapter 5 we observed significant associations between low serum 25(OH)D concentrations, physical performance and frailty in community-dwelling older adults (n=494-756). However, randomized trials are needed to define the causality of the observed associations. A previous pilot study indicated plausible beneficial effects of calcifediol over vitamin D3 on performance and strength. As such, we aimed to further explore the potential role of calcifediol or vitamin D3 on muscle function in chapter 6. We performed a placebo-controlled trial in pre-frail and frail, vitamin D deficient older adults, supplementing either 10 µg/d calcifediol or 20 µg/d vitamin D3, compared to placebo over a 6-month period (n=78). Again, calcifediol induced a faster and higher increase in serum 25(OH)D status when compared to vitamin D3. However, we observed no effect of either supplementation regimen on lower extremity strength or physical performance. Current literature suggests positive effects on strength and balance when supplementing with vitamin D, however, results are inconsistent. Meta-analyses of randomized trials indicate that the beneficial effects of vitamin D supplementation might be more pronounced in vulnerable populations with more severe vitamin D deficiencies.
All in all, the high prevalence of vitamin D deficiency is alarming. Promoting adequate vitamin D status is important considering the beneficial effects on bone health. In the last decade, research has come a long way in exploring the role of vitamin D in muscle function. However, the evidence base remains uncertain and further research on the optimal vitamin D status for older adults is needed to guide clinical practice. Until then, focus should be placed on prevention and identification of deficiency.
Cater with Care : impact of protein-enriched foods and drinks for elderly people
Beelen, J. - \ 2016
Wageningen University. Promotor(en): Lisette de Groot; Frans Kok, co-promotor(en): Nicole de Roos. - Wageningen : Wageningen University - ISBN 9789462578814 - 142
undernutrition - hospital catering - hospitals - protein - elderly - protein intake - food - beverages - diet studies - dietetics - dietitians - randomized controlled trials - ondervoeding - ziekenhuiscatering - ziekenhuizen - eiwit - ouderen - eiwitinname - voedsel - dranken - dieetstudies - diëtetiek - diëtisten - gestuurd experiment met verloting
Protein undernutrition is a major health concern for older adults, especially for those who are ill. There is growing consensus for a protein intake target of 1.2 - 1.5 gram per kg bodyweight per day (g/kg/d) for these older adults. However, this target is not reached by the majority of older adults. Therefore, more effective and novel strategies to increase protein intake are warranted, including the use of protein-enriched foods and drinks. This thesis evaluated the impact of the developed protein-enriched foods and drinks on protein intake and physical performance among older adults. The studies in this thesis were done as part of the Cater with Care® project; a collaboration between the university, care organizations, and partners from the food industry. The industrial partners developed the products, focusing each on different product categories: Carezzo Nutrition developed bread, pastry, and fresh juices and soups; The Kraft Heinz Company focused on long shelf-life and convenience foods; and the Veal Promotion Foundation produced veal meat.
To fit the products to the needs of the target group, interviews with undernourished older adults (at home or hospitalized) and with dietitians were conducted (chapter 2). These interviews showed that undernutrition awareness is low among older adults. To treat undernutrition by changing their eating habits, older adults need to be aware of their health problem, they need to be willing to change, and they need to be able to understand and implement the dietitian’s advices. This process takes time while undernutrition should be treated immediately. For immediate treatment, enriched products could be used, without first creating awareness. According to the interviewees, enriched products should fit within older adults’ eating habits, and have small portion sizes.
To gain insights in food choices of hospitalized older adults (65 years and older) an observational study was conducted. In this study, energy and protein intakes of 80 hospitalized older patients at low and high risk of undernutrition were assessed (chapter 3). Patients who received an energy- and protein-rich menu, because of their risk of undernutrition, were better able to reach the protein and energy targets than patients with a low risk of undernutrition receiving a standard menu. Based on these results we proposed that all hospitalized older adults – both at low and high risk of undernutrition – should receive an energy- and protein-rich menu.
Subsequently, a pilot study was done in a care home and a rehabilitation center with the aim to explore the potential of the developed protein-enriched products to increase protein intake (chapter 4). Participants did not compensate their consumption of regular protein-rich foods (e.g. dairy, cheese) upon the introduction of protein-enriched foods and drinks. The 22 institutionalized elderly (mean age 83 years) consumed 12 gram protein per day more than they did before the intervention. Consequently, more people met the protein target of 1.2 g/kg/d than before the intervention. We concluded that protein-enriched products enabled institutionalized elderly to reach protein intake targets. Furthermore, we gained valuable feedback to improve the assortment of protein-enriched products for the effectiveness study.
In the final study, effects of the protein-enriched products on protein intake and physical performance were studied in a randomized controlled trial during hospitalization and subsequent recovery at home. During the hospital period in which 147 older patients participated, patients that received protein-enriched products increased their protein intake compared to the control group that already received a protein-rich hospital menu (chapter 5). As a result, 79% of the intervention group reached a protein intake of 1.2 g/kg/d, compared to 48% of the control group. Finally, effects of the protein-enriched products were tested at home, for a longer period (chapter 6). Half of the hospital phase participants (n = 75) continued the intervention at home for 12 weeks. The protein-enriched products were successfully implemented in the daily menu of the older adults: the intervention group had a higher average protein intake (1.5 ± 0.6 g/kg/d) than the control group (1.0 ± 0.4 g/kg/d) during the 12-week intervention period. Seventy-two percent of the intervention group reached a protein intake of 1.2 g/kg/d during the 12-week intervention, compared to 31% of the control group. Protein intake of the intervention group was mainly increased by the following protein-enriched products: bread, dairy drinks, dairy desserts, soups, and fruit juices. However, despite the successful improvement of protein intake, we found no added value on physical performance in the first 6 months after hospitalization.
It was concluded that with the protein-enriched familiar foods and drinks, we have a feasible, acceptable, and appetizing long-term strategy to increase protein intake of older adults in various settings. We envisage a beneficial role of these protein-enriched products in combination with physical activity in older adults with lower protein intakes.
Impact of odour-baited mosquito traps for malaria control : design and evaluation of a trial using solar-powered mosquito trapping systems in western Kenya
Homan, T. - \ 2016
Wageningen University. Promotor(en): Willem Takken; T.A. Smith. - Wageningen : Wageningen University - ISBN 9789462577435 - 224
016-3935 - culicidae - mosquito-borne diseases - vector control - malaria - bait traps - odours - solar energy - randomized controlled trials - kenya - culicidae - ziekten overgebracht door muskieten - vectorbestrijding - malaria - vallen met lokaas - geurstoffen - zonne-energie - gestuurd experiment met verloting - kenya
The parasites belonging to the genus Plasmodium are the cause of the second deadliest infectious disease in the world, malaria. Sub Saharan Africa harbours more than 90% of malaria attributable mortality and morbidity, and most deaths occur in children under 18 years old. Malaria is transmitted to humans by a bite of a Plasmodium infected arthropod vector from the genus Anopheles. Halfway the 20th century malaria was successfully eliminated from most developed countries, nonetheless in the third world effective control remains a laborious challenge. Intensive efforts undertaken to control and eventually eradicate malaria during the past decade have led to substantial reductions in morbidity and mortality. Conversely, scientists became increasingly aware that with the current preventative and curative tools against malaria successful eradication seems unlikely. Not only do current tools not suffice to attain that goal, their efficacy to control malaria as it is, maybe severely threatened. Proper treatment and diagnosis are becoming increasingly less effective because of the adaptive nature of the parasite. Parasites get resistance against drugs and carriers are more often found to have subclinical infections. Likewise prevention of malaria, by vector control, becomes less effective. Malaria vectors become resistant to insecticides and transmission patterns are shifting away from where preventive measures are functional: outside and during the day. It this gap where the SolarMal project experimented with a novel malaria vector control tool, complimentary to existing malaria control methods: odour-baited mosquito traps that mimic human beings to lure and kill mosquitoes to eventually reduce malaria. The ultimate aim of this thesis was to seek proof of principle of the effect of mass trapping of malaria vectors on malaria and mosquito densities by rolling out over 4000 odour-baited mosquito traps at household level on Rusinga Island, Kenya.
Chapter 2 is a study protocol of the SolarMal project and provides a general understanding of how the objectives of the project are translated into a research design. The study comprises of a medical, an entomological and a sociological discipline. A multidisciplinary strategy is presented in which the intervention is explained. Experimental designs of all disciplines are introduced including time frames, participant eligibility, and randomisation. Furthermore, a general overview of the data collected and how it is evaluated and analysed using health and demographic surveillance and monitoring is provided.
In chapter 3 a novel data collection and management platform is presented. The health and demographic surveillance as well as other disciplines in the project are an example of one of the first fully digital data collection systems in a low and middle income country. The development of digital questionnaires and the conducting of these by means of Open Data Kit software enabled the project to efficiently collect data. All residential structures were documented by GPS, and data of individuals attached. Converting the geo-located data to a geodatabase and displayed with Google Earth mobile made navigating from house to house an easy task. By daily uploading of data to the server at the project campus, scientists have access to a near real time database. Once uploaded to the server, data is transferred to the OpenHDS database in which the demography of the study population is updated accordingly. Data quality was further increased by a tool that looked for inconsistencies.
In chapter 4 we explore what experimental design would fit the SolarMal project best. A stepped wedge cluster-randomized trial [SWCRT] design was chosen to make sure that the whole area would cross over from the control to the intervention arm over a period of two years. As elimination was the goal, universal coverage was required. Subsequently, strategies for randomization and crossover of clusters that could measure a possible intervention effect best were simulated with a generic model of disease transmission. Considering sufficient numbers and sizes of clusters a hierarchical SWCRT would best measure a possible effect of OBTs on Rusinga Island. Special care was given to quantifying spill over effects into the control arm. Finally, two new measures of intervention effectiveness are proposed.
Chapter 5 reports on the outcomes of the health and demographic surveillance system on Rusinga Island. Running an HDSS is a thorough but complex method to monitor intervention effects in an area where health surveillance is minimal. As part of the overarching HDSS institution, INDEPTH, data collection methods and reporting are harmonious with many other HDSSs around the world. Demographic parameters are calculated and the HDSS practices are described.
Chapter 6 uses the baseline cross sectional prevalence surveys to elucidate how the epidemiology of malaria on Rusinga Island. Firstly, the malaria distribution and hot spots are identified. Consequently, a standard epidemiological model and a geographically weighted regression are compared, and used to identify risk factors for malaria. The latter model, taking into account non-stationarity, performs better and is able to produce geographically varying risk factors. The strength of the relationship of risk factors for malaria are heterogeneous over the whole island, and for instance social economic status and occupation are strong predictors of malaria in some areas but less in other areas. Considering these risk factor distributions can aid in guiding the implementation of malaria intervention methods.
Chapter 7 presents the main outcomes of the SolarMal project. The impact of OBTs on the prevalence of malaria is pronounced in the contemporaneous comparison between the intervened and the intervened arm. Comparison of baseline data with the intervened clusters does not yield significant effects. A strong decline in cases of clinical malaria was observed starting already in the baseline period, and therefore we cannot attribute this decline to the intervention. Effects on the most prominent malaria vector were large, whereas other vectors did not suffer under the intervention.
Chapter 8 is a general discussion of the work provided. The most important implications of the thesis are discussed underscoring the societal and scientific relevance, and putting the research in a wider perspective. Unaddressed issues are raised and recommendations for further research are provided.
Zuivelconsumptie, bloeddruk en hypertensie : observationele studies en interventieonderzoek
Engberink, M.F. - \ 2009
Wageningen University. Promotor(en): Evert Schouten; Frans Kok, co-promotor(en): Marianne Geleijnse. - [S.l. : S.n. - ISBN 9789085853619 - 143
melkproducten - bloeddruk - hypertensie - gestuurd experiment met verloting - epidemiologische onderzoeken - maatregel op voedingsgebied - voedselopname - dieetrichtlijnen - nederland - milk products - blood pressure - hypertension - randomized controlled trials - epidemiological surveys - nutritional intervention - food intake - dietary guidelines - netherlands
Diet and lifestyle play an important role in maintaining a healthy blood pressure. Whether intake of dairy products could reduce population blood pressure remains to be established. We examined the association of (specific types of) dairy food intake with blood pressure and risk of hypertension using data from two Dutch population-based cohort studies; i.e. the MORGEN study and the Rotterdam study. Blood pressure level was not consistently associated with overall dairy intake or intake of specific dairy foods in 21,553 Dutch adults from the MORGEN study. However, both in the MORGEN study and in the Rotterdam study, the risk of hypertension was reduced by ~20% in subjects who consumed more than 150 mL of low-fat dairy per day. Other dairy foods, i.e. fermented dairy, high-fat dairy, milk and milk products, and cheese, were not consistently associated with risk of hypertension. In addition, we assessed the effect of two dairy components on human blood pressure, i.e. lactotripeptides and cis-9, trans-11 conjugated linoleic acid, in controlled intervention studies. These dairy components did not affect blood pressure.