No effect of multivitamin supplementation on central blood pressure in healthy older people: A randomized controlled trial
Introduction
Age is a major risk factor for cardiovascular disease, and it has been demonstrated that those with established hypertension also exhibit higher measures of central blood pressure, including augmentation index and central augmentation pressure, relative to healthy controls [11]. Augmentation index provides a measure of pulse wave reflection which can be used as an estimate of arterial stiffness [19], [39]. Potentially serious consequences of high arterial stiffness include increased central blood pressure, left ventricular hyperplasia and failure, increased atherosclerosis and plaque rupture, and end-organ damage due to increased pressure pulsations [23]. Augmentation index increases with age in a curvilinear fashion and is an independent predictor of cardiovascular risk [12], cardiovascular events and mortality [26]. Therefore it is important to consider how to counteract arterial stiffness and associated central blood pressures, particularly in susceptible older adults.
Vitamins including antioxidant and B-group vitamins have numerous effects on the cardiovascular system including arterial effects [4], [6]. There are relatively few trials examining the effects of vitamin supplementation on augmentation index, however existing studies suggest there might be beneficial effects.
For example, trials of antioxidant vitamins have demonstrated reductions in augmentation index [1]. Four randomized, double-blind, placebo-controlled studies have investigated augmentation index after a single 2 g dose of vitamin C in healthy adults; three of these have demonstrated a beneficial effect [42], [41], [24], and one observed no effect [14]. Longer term supplementation may also be beneficial. Two randomized, placebo-controlled studies have investigated the effects of four weeks of vitamin E supplementation in healthy young males, with improved augmentation index observed in one study [30], but not another [31]. Studies in patient groups have also indicated possible benefits of antioxidant vitamin supplements. For instance, improved augmentation index was observed in patients with type II diabetes following daily supplementation with 500 mg vitamin C for six weeks, but not with placebo, in a randomized, double blind study [25]. In hypertensive adults, a randomized crossover study of combined vitamin C (1 g) and vitamin E (400 IU) supplement compared with placebo improved cardiovascular measures and there was a trend to reduction in augmentation index over four weeks [29].
Several randomized controlled trials of B vitamins and augmentation index have been conducted in patients with renal disease. The largest of the studies, conducted in patients with chronic renal failure, found no effect on augmentation index after 3.6 years of daily folic acid supplementation compared with placebo [43]. An open-label study found an improvement in carotid augmentation index with a combination of folate and vitamin B12 compared with folate only [16]. In a randomized, open-label, crossover study, improved augmentation index was observed in patients with end-stage renal disease receiving folic acid during haemodialysis, although this was not observed when administered prior to hemodialysis [37].
At least ten studies have examined the effects of vitamin D supplementation on augmentation index in various populations. One randomized, double-blind, placebo-controlled study observed a reduction in augmentation index in diabetic patients with one year of supplementation [2]. Another randomized study in vitamin D-deficient elderly people demonstrated an improvement in augmentation index after a single high-dose supplement of 100,000 IU of intramuscular vitamin D3 but not with a lower dose of 50,000 IU [22]. However the majority of studies, including well-powered randomized, double-blind, placebo-controlled trials, have not demonstrated improvements in augmentation index with vitamin D [7], [8], [18], [34].
Overall, these vitamin studies offer cautious support that some vitamin supplements have potential to lower augmentation index. To date there have been no studies investigating the effects of multivitamins on augmentation index. This is important because multivitamins are widely consumed in the general population [15], [35], [36]. Augmentation index increases with age, and is associated with increased risk of cardiovascular events and mortality [38], so a beneficial effect of supplementation in older adults is particularly relevant. The studies reported here are the first to investigate the effects of multivitamin supplementation on augmentation index and other central blood pressure measures in healthy elderly adults.
The current investigation examines secondary cardiovascular outcomes from studies which assessed the effects of 16-weeks multivitamin supplementation in healthy older male and female participants. The outcome measures of interest include augmentation index, augmentation pressure and central pulse pressure. While augmentation index is more commonly used in research, it has been proposed that augmentation pressure might be a better index of arterial stiffness in older adults as it continues to increase after age 55 whereas augmentation index levels out [5]. Central pulse pressure was also assessed as it is strongly associated with vascular health [33]. It was hypothesized that augmentation index, augmentation pressure and central pulse pressure would decrease after multivitamin supplementation. Central and brachial systolic, diastolic and pulse pressures were also assessed for comparison.
Section snippets
Method
This paper reports the cardiovascular findings of a combined sample of participants from three parallel, double-blind, placebo-controlled studies; each investigating the effects of 16-weeks supplementation with multivitamin, mineral and herbal supplements. The studies were registered with the Australian New Zealand Clinical Trials Registry, trial IDs ACTRN12608000117314, ACTRN12608000256370 and ACTRN12612000334808. The studies were conducted between 2008 and 2012. Ethics approvals were obtained
Results
A total of 249 participants were randomized across the three studies and cardiovascular data was collected from 239 of these individuals (160 females, 79 males). A total of 17 females (seven assigned multivitamin, ten assigned placebo) and three males (one assigned multivitamin, two assigned placebo) withdrew from the trials prior to study completion for details see [10]. Cardiovascular measures were not collected at post treatment from one female and three male participants. Participant
Discussion
The present research demonstrated no effect of multivitamin supplements on augmentation index, augmentation pressure or brachial blood pressures in adults aged 50 years and above. These findings are secondary cardiovascular outcomes from three studies investigating the effects of 16-weeks of multivitamin supplementation. In the same studies beneficial effects were observed for cognition and neural efficiency [20], [21], as well as for blood biomarkers [10], [20]. However the present results
Conclusions
Arterial hemodynamics play a crucial role in cardiovascular health during aging, where higher central blood pressure measures are associated with increased cardiovascular risk. However further research is needed to establish multivitamin supplementation as a potential method to improve central blood pressure measures. The present research does not support such a function in healthy older adults over the short term.
Conflict of interest statement
Andrew Pipingas is currently a member of the Scientific Advisory Panel for Swisse Wellness Pty Ltd.
Acknowledgements
The studies were sponsored by Swisse Wellness Pty Ltd. (formerly Swisse Vitamins Pty Ltd) under contract to Swinburne University of Technology and performed independently by the Brain Sciences Institute and Centre for Human Psychopharmacology. Supplements used in this study were provided by Swisse Wellness.
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