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.
High fat challenges and detection of early perturbations in endothelial health : the use of a comprehensive phenotyping approach
Esser, D. - \ 2013
Wageningen University. Promotor(en): Michael Muller, co-promotor(en): Lydia Afman. - S.l. : s.n. - ISBN 9789461735911 - 168
endotheel - vetconsumptie - voedingsvet - lipidenmetabolisme - chocolade - endothelium - fat consumption - dietary fat - lipid metabolism - chocolate
Background:Cardiovascular disease (CVD) is one of the leading causes of morbidity and mortality worldwide. One of the pathophysiology’s that play a pivotal role in the development and progression of CVD is a dysfunctional endothelium. An important lifestyle risk factor for endothelial dysfunction is the diet and several nutrients have been classified to be either beneficial or harmful for the endothelium. Although CVD usually affects middle-aged or older adults, the onset of endothelial dysfunction begins in early life, emphasising the need for primary prevention. We therefore aimed to identify markers of early perturbations in endothelial health by using dietary stressors, e.g. high fat (HF) challenge test. Thereafter we aimed to evaluate if the potential early markers are reversible and can be improved after an intervention with a dietary anti-stressor.
Methods:First we validated the HF challenge test as a tool to trigger the endothelial response capacity. For that purpose, we compared the postprandial response after a HF shake with an average breakfast shake in young healthy men by assessing several plasma markers and functional measures of endothelial function. To identify new markers for early perturbations in endothelial health and to optimized the HF challenge test we applied three HF challenges differing in fatty acid type in two populations of middle-aged men, i.e. one at high- and one at low risk for developing CVD and characterized the postprandial response by applying high-throughput metabolomic and transcriptomic tools next to an extensive phenotyping of vascular function and vascular health parameters. Lastly, we evaluated if the, in the studies above, identified potential early biomarker profile is reversible and can be improved after an intervention with a dietary anti-stressor by means of a high flavanol chocolate intervention.
Results:In young men, we observed that a HF challenge decreased flow mediated dilation (FMD), but this decrease was also found after the consumption of an average breakfast shake. IL-8 concentrations were more pronouncedly increased after HF shake consumption compared to an average breakfast control shake. In middle-aged men, a HF challenge decreased the augmentation index (AIX) and elicited an activated state of cellular adherence in the circulation as determined by increased plasma soluble adhesion molecules, increased leukocyte cell surface integrin and selectin expression and increased number of leukocytes. A challenge high in mono-unsaturated fatty acids (MUFAs) elicited the highest postprandial triglyceride (TG) concentrations and the most pronounced effects on AIX. By applying high-throughput metabolomic tools, we observed that oxylipin profiles were affected by the HF challenge and that these changes were depended on dietary fatty acid composition. Application of transcriptome profiling revealed that changes in peripheral blood mononuclear cell (PBMC) gene expression profiles after a HF challenge test were different between lean and obese subjects, with the most deviating effect after MUFA intake. The saturated fatty acid (SFA) shake decreased the expression of genes involved in cholesterol uptake and cholesterol biosynthesis and increased expression of genes involved in cholesterol efflux. MUFA increased expression of inflammatory genes and of peroxisome proliferator-activated receptor α (PPARα) target genes involved in β-oxidation. 4-week daily intake of a dietary anti-stressor, e.g. dark chocolate, increased fasting FMD and decreased AIX, and elicited a less activated state of cellular adherence, as determined by a decrease in plasma soluble adhesion molecules, a decrease in leukocyte cell surface integrin and selectin expression and a decrease in the number of leukocytes.
Conclusions:In this thesis we extensively characterized the postprandial response to a HF challenge in human subjects with different disease risk profiles and optimized the HF challenge test. We identified MUFAs as most potent fatty acids to trigger the vascular and cellular response capacity, which makes it the optimal fatty acid type to use in a HF challenge test. We demonstrated that besides functional measures of vascular function, also plasma and cellular factors involved in leukocyte adhesion to the endothelium are adversely affected by dietary stressors and are beneficially affected by a dietary anti-stressor. Therefore, we conclude that endothelial health can be more comprehensively measured by means of a biomarker profile consisting not only of the vascular function measures FMD and AIX, but also of a subset of soluble adhesion molecules in the plasma, leukocyte counts and cell surface integrin and selectin expression. To identify potential new leads for biomarkers, we applied whole genome gene expression profiling, combined with the HF challenge test which enabled us to detect small differences in health status. Furthermore, we identified metabolic and inflammatory pathways that are specifically affected by either MUFAs or SFAs. These findings increased our understanding on how a SFA or MUFA challenge exert their distinct effects on stress related and metabolic compensatory cellular processes and provided us with new potential leads to detect early perturbations in endothelial health.
Nutritional zinc deficiency, immune capacity and malaria : a study on mediators of immunity to malaria caused by Plasmodium falciparum in African children
Mbugi, E.V. - \ 2009
Wageningen University. Promotor(en): Huub Savelkoul; J.F. Shao, co-promotor(en): Hans Verhoef. - [S.l. : S.n. - ISBN 9789085855316 - 174
malaria - plasmodium falciparum - immuniteit - zink - kinderen - geneesmiddelresistentie - immuniteitsreactie - mineraaltekorten - voedingsstoffentekorten - cytokinen - antilichamen - endotheel - anemie - tropische ziekten - tanzania - malaria - plasmodium falciparum - immunity - zinc - children - drug resistance - immune response - mineral deficiencies - nutrient deficiencies - cytokines - antibodies - endothelium - anaemia - tropical diseases - tanzania
This thesis aimed at investigating the role of genetic and nutritional factors that affect the immune response to malaria in Tanzanian children. The introductory chapter (Chapter 1) reviews the importance of nutritional deficiencies, particularly of zinc, and presents the hypothesis that such deficiencies lead to impaired immunity and contribute to the burden of malaria. The chapter also describes current efforts to prevent malaria through intermittent preventive treatment, both in infants (IPTi) and pregnant women (IPTp). Sulfadoxinepyrimethamine is still used for first-line treatment of uncomplicated malaria, or, in many countries, to prevent malaria and anaemia in pregnancy. In malaria endemic areas, development of resistance to previously valuable antimalarial drugs has been continuously reported for decades. Thus our initial longitudinal study aimed at measuring the prevalence of resistance-associated mutations on dihydrofolate reductase (DHFR) and dihydropteroate synthase (DHPS) genes (dhfr and dhps) that confer parasite resistance to sulphadoxinepyrimethamine (SP) that was used as an interim antimalarial drug after chloroquine resistance. Although SP resistance-associated point mutations were highly prevalent, we observed an adequate parasite response to SP (Chapter 2). We speculated that the impact of the dhfr and dhps mutations on SP resistance may be dependent at least in part on the protective immunity that has developed in response to frequent exposure to infection and may be weighed down by host immunity in endemic areas and thus impacts in the continued use of the drug for treatment of malaria. The impact of other drugs with similar mechanisms of action used as antibiotics in selecting mutations responsible for SP resistance needs therefore to be studied for their modulating activity of the immune response. These findings underscore the relevance to further study the crucial involvement of the immune system in the development of protection against malaria but also affecting the efficacy of treatment modalities of malaria in various African conditions.
In the subsequent cross-sectional studies, we assessed the effect of deficiencies of zinc and magnesium as well as iron deficiency anaemia on malaria-specific cytokine responses indicative of innate immunity to Plasmodium falciparum (Chapter 3). In this study, we used Plasmodium falciparum-parasitised red blood cells (pRBCs) as antigens for in vitro stimulation of peripheral blood mononuclear cells (PBMCs). Cytokines were measured in the supernatant of cultured PBMCs after 24 hours of stimulation. Zinc deficiency was associated with a marked increase in monocyte-derived TNF-α concentration in children with malarial infection but not in their uninfected peers. In children with malarial infection, iron deficiency anaemia was associated with elevated concentrations of TNF-α, whereas magnesium deficiency in children without malaria seemed to be associated with increased concentrations of IL-10. Our findings reflected plasticity in cytokine profiles of monocytes reacting to malaria infection under conditions of different nutrient deficiencies. Following the observation of the variable impact of micronutrients on innate cytokines, we evaluated the profile of both type I and type II cytokines and whether they were influenced by nutritional and malaria status (Chapter 4). The cytokine measurements were performed at day 7 of stimulation anticipating that this timing was optimal for measuring effects on these cytokines mainly derived from activated T-cells. The results indicated a variable influence of nutrient deficiencies on increased cytokine response with zinc deficiency and iron deficiency anemia having greater impact on type I and magnesium deficiency on type II cytokines. The subsequent study evaluated the plasma levels of naturally acquired antimalarial antibodies of variousIgG subclasses plus the total IgG and IgM levels and whether they were associated with zinc deficiency based on preceding chapters (Chapter 5). The results indicated a high variability in antibody levels with zinc deficiency, varying with age of the affected child. IgG3 appeared to be predominant across all age subgroups within < 5 yrs aged children providing clues that IgG3 might confer immune protection to malaria under conditions of zinc deficiency. Chapter 6 explored the association between CD36 deficiency, P. falciparum in vitro adherence on purified CD36 and anemia in children. CD36 is a receptor that occurs on the surface of activated immune cells and vascular endothelial cells and participates in phagocytosis and lipid metabolism. We hypothesized that it could play a fundamental role in cytoadherence of erythrocytes that are parasitized by Plasmodium. Our results showed that CD36 deficiency was associated with protection against the development of malarial anemia in children and that it may be mediated through reduced cytoadherence of infected red blood cells to vascular endothelium.
These studies demonstrate that despite antimalarial drug resistance, there is a potential for optimizing the immunological protective capacity in the population to confer parasite clearance that can be variably influenced by micronutrient status. Improving nutritional status in this population could be rewarding not only to increase protection to malaria but possibly also to other infections.
Does vitamin C supplementation influence the levels of circulating oxidized LDL, slCAM-1, sVCAM-1 and vWF-antigen in healthy male smokers?
Hoydonck, P.G.A. ; Schouten, E.G. ; Manuel-y-Keenoy, B. ; Campenhout, A. van; Hoppenbrouwers, K.P.M. ; Temme, E.H.M. - \ 2004
European Journal of Clinical Nutrition 58 (2004)12. - ISSN 0954-3007 - p. 1587 - 1593.
low-density-lipoprotein - ascorbic-acid - lipid-peroxidation - cigarette-smoking - alpha-tocopherol - heart-disease - plasma - endothelium - oxidation - nonsmokers
Objective: To examine the effects of vitamin C supplementation on the concentration of oxidation markers, in particular, circulating oxidized LDL ( OxLDL) and on endothelial activation markers. Design: Randomized double-blind, placebo-controlled crossover trial. Setting: Belgian population of the city of Leuven. Subjects: A total of 34 healthy male smokers aged 26 - 73 y. Intervention: Smokers were randomly assigned to receive either vitamin C (250 mg twice daily) or placebo capsules, each to be taken for 4 weeks. After a 1-week washout period, participants then crossed over to the alternative capsules for further 4 weeks. Mean outcome measures: Markers of oxidation (bilirubin, uric acid, alpha-tocopherol, retinol, malondialdehyde, circulating Oxidized LDL ( OxLDL)) and markers of endothelial activation (sICAM-1, sVCAM-1, vWF-antigen) were analysed. Results: Plasma ascorbate concentrations significantly increased from 46.6 +/- 17.6 to 70.1 +/- 21.2 mumol/l after a 4-week treatment with 500 mg vitamin C per day. The other plasma antioxidants concentrations, including bilirubin, uric acid, alpha-tocopherol and retinol, were similar in both treatment periods. Vitamin C did not change plasma malondialdehyde and circulating OxLDL compared with placebo (vitamin C 0.73 +/- 0.25 mg/dl OxLDL; placebo 0.72 +/- 0.21 mg/dl OxLDL). After vitamin C supplementation, neither sICAM-1 and sVCAM-1 levels nor the concentration of vWF-antigen significantly differed from placebo condition. Conclusions: Oral supplementation of vitamin C is not associated with changes in markers of oxidation or endothelial activation in healthy male smokers. Sponsorship: The Unilever Chair in Nutritional Epidemiology, University of Leuven, Belgium.