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Abstract
We have investigated the effect on blood pressure of treatment with vitamin C (an antioxidant and free radical scavenger) in patients with both systolic and essential hypertension. Following a 2-week run-in phase, two age- and sex-matched groups of untreated hypertensive subjects were randomised in a double-blind study to receive 6 weeks' oral treatment with either vitamin C, 250 mg twice daily (n = 22; 8M/14F, mean age 73.7 +/- 4.9 years) or placebo, one capsule twice daily (n = 26; 10M/16F, mean age 73.8 +/- 5.3 years). Blood pressure was measured in the sitting position using a random zero sphygmomanometer on three occasions during the run-in phase, and again at 2, 4 and 6 weeks after commencing treatment. Venous blood samples for measurement of plasma ascorbic acid (AA) and lipid peroxides (LP) were measured in all subjects at baseline and at 4 and 6 weeks after the start of vitamin C or placebo treatment. During the study period, significant falls in both systolic (vitamin C group, mean change -10.3 (95% CI 0.7-20.0) mm Hg, p = 0.05) and diastolic (vitamin C group, mean change -5.9 (95% CI 0.2-11.5) mm Hg, p = 0.03; placebo group, mean change -4.7 (95% CI 0.3-9.1) mm Hg, p = 0.05) blood pressure occurred. However, no statistical difference between the effects of either treatment on blood pressure was observed. At baseline, AA concentrations were lower in the vitamin C-treated group compared with the placebo group (44.6 +/- 2.4 vs. 57.7 +/- 4.2 mumol/l, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
... As mentioned above, hypertension is associated with decreased serum vitamin C levels, so it is logical to propose supplementation of vitamin C to treat hypertension. Several clinical studies have been published using vitamin C with mixed outcomes [47,48]. A study published in 2012 performed a Meta-Analysis of Randomized Controlled Trials investigating the effects of vitamin C supplementation on blood pressure from 1966 to 2011 (included 29 clinical trials) and showed a positive outcome of vitamin C treatment in reducing SBP and DBP. ...
... However, after analyzing the data from the trials, it was noted that the average change in blood pressure was small (> 5 mm hg) [48]. Ghosh et al. (1994) performed aged and sex-match randomized double-blind study to treat hypertensive subjects with vitamin C supplementation in aged patients [47]. The participants received either oral Vitamin C 250 mg once or twice daily or a placebo for 6 weeks, followed by analysis on plasma vitamin C and lipid peroxidase. ...
... However, after analyzing the data from the trials, it was noted that the average change in blood pressure was small (> 5 mm hg) [48]. Ghosh et al. (1994) performed aged and sex-match randomized double-blind study to treat hypertensive subjects with vitamin C supplementation in aged patients [47]. The participants received either oral Vitamin C 250 mg once or twice daily or a placebo for 6 weeks, followed by analysis on plasma vitamin C and lipid peroxidase. ...
The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has been spreading around the world at an exponential pace, leading to millions of individuals developing the associated disease called COVID-19. Due to the novel nature and the lack of immunity within humans, there has been a collective global effort to find effective treatments against the virus. This has led the scientific community to repurpose Food and Drug Administration (FDA) approved drugs with known safety profiles. Of the many possible drugs, vitamin C has been on the shortlist of possible interventions due to its beneficial role as an immune booster and inherent antioxidant properties. Within this manuscript, a detailed discussion regarding the intracellular function and inherent properties of vitamin C is conducted. It also provides a comprehensive review of published research pertaining to the differences in expression of the vitamin C transporter under several pathophysiologic conditions. Finally, we review recently published research investigating the efficacy of vitamin C administration in treating viral infection and life-threatening conditions. Overall, this manuscript aims to present existing information regarding the extent to which vitamin C can be an effective treatment for COVID-19 and possible explanations as to why it may work in some individuals but not in others.
... SBP and diastolic BP (DBP) ⬇ [159]. Humans, elderly patients with hypertension [160]. ...
... Small ⬇ in BP and antioxidant capacity ⬆ [160]. ...
As a major cause of morbidity and mortality globally, hypertension remains a serious threat to global public health. Despite the availability of many antihypertensive medications, several hypertensive individuals are resistant to standard treatments, and are unable to control their blood pressure. Regulation of the renin-angiotensin-aldosterone system (RAAS) controlling blood pressure, activation of the immune system triggering inflammation and production of reactive oxygen species, leading to oxidative stress and redox-sensitive signaling, have been implicated in the pathogenesis of hypertension. Thus, besides standard antihypertensive medications, which lower arterial pressure, antioxidant medications were tested to improve antihypertensive treatment. We review and discuss the role of oxidative stress in the pathophysiology of hypertension and the potential use of antioxidants in the management of hypertension and its associated organ damage.
... Nevertheless, sBP in the dwa group tended to be higher than in the Hwa group. to date, several clinical trials on the effect of vitamin C supplements on BP have yielded inconsistent findings with respect to hypertension in humans [43,44]. the lack of an antihypertensive effect in studies using supplementation with vitamin C alone could be due to the decreased bioavailability of nitric oxide under conditions of oxidative stress [36]. ...
Hydrogen-rich water (HW) has been suggested to possess antioxidant properties of value in treatments of lifestyle diseases and for prevention of latent pathologies. To date, the potential benefits of HW against the deleterious effects of excessive salt intake and hypertension have not been investigated. Here, we first examined the effects of HW or HW supplemented with 0.1% ascorbic acid (HWA) on spontaneously hypertensive rats (SHR) that had been fed a normal diet. In comparison to control rats given distilled water (DW), we found that HW did not significantly influence systolic blood pressure (SBP) or diastolic blood pressure (DBP) in SHR; however, the increase in SBP and DBP were inhibited in the HWA group. Next, four groups of SHR were given DW, 0.1% ascorbic acid-added DW (DWA), HW, or HWA in combination with a 4% NaCl-added diet. SHR fed the 4% NaCl-added diet showed increased hypertension; HWA treatment resulted in a significant reduction in blood pressure. The HWA group tended to have lower plasma angiotensin II levels than the DW group. In addition, urinary volumes and urinary sodium levels were significantly lower in the HWA group than the DW group. Urinary isoprostane, an oxidative stress marker, was also significantly lower in the HWA group, suggesting that the inhibitory effect of HWA on blood pressure elevation was caused by a reduction in oxidative stress. These findings suggest a synergistic interaction between HW and ascorbic acid, and also suggest that HWA ingestion has potential for prevention of hypertension.
... Vitamin C may have favorable effects on vascular dilation, possibly through its antioxidant effects on NO ( Duffy et al., 2001;Jackson et al., 1998;Vita et al., 1998). Nevertheless, there are several small and short-term clinical tri- als in which the effect of vitamin C supplements on blood pres- sure have yielded inconsistent findings ( Block et al., 2001;Duffy et al., 1999;Fotherby et al., 2000; Galley et al., 1997;Ghosh et al., 1994;Mullan et al., 2002). The lack of antihypertensive efficacy observed in studies using supplementation with vitamin C alone could be due to the decreased bioavailability of NO under condi- tions of oxidative stress. ...
Hypertension is a highly prevalent disease worldwide. It is known for being one of the most important risk factors for developing cardiovascular disease, including acute myocardial infarction and stroke. Therefore, during the last decades there have been multiple efforts to fully understand the mechanisms underlying hypertension, and then develop effective therapeutic interventions to attenuate the morbidity and mortality associated with this condition. In this regard, oxidative stress has been proposed as a key mechanistic mediator of hypertension, which is an imbalance between oxidant species and the antioxidant defense systems. A large amount of evidence supports the role of vascular wall as a major source of reactive oxygen species. These include the activation of enzymes, such as NADPH oxidase and xanthine oxidase, the uncoupling eNOS and mitochondrial dysfunction, having as a major product the superoxide anion. Among the stimuli that increase the production of oxidative species can be found the action of some vasoactive peptides, such as angiotensin II, endothelin-1 and urotensin II. The oxidative stress state generated leads to a decrease in the biodisponibility of nitric oxide and prostacyclin, key factors in maintaining the vascular tone. The knowledge of the mechanisms mentioned above has allowed generating some therapeutic strategies using antioxidants as antihypertensives with different results. Further studies are required to position antioxidants as key agents in the treatment of hypertension. The current review summarize evidence of the role of oxidative stress in hypertension, emphasizing in therapeutic targets that can be consider in antioxidant therapy.
© Georg Thieme Verlag KG Stuttgart · New York.
... Nutrient intake and electrolyte level are complex and varied, but studies revealed a relationship between vitamin C and blood pressure that hypertensive patients present a lower intake and serum vitamin C [25]. A variety of observational and interventional studies has additionally reported that vitamin C intake and its concentration status were significantly related to a reduction of resting blood pressure [26][27][28]. Given the potential oxidation resistance function of vitamin C, researchers attributed this association to that vitamin C could prevent the formation of free radicals, thereby reducing the vascular oxidative in the progress of hypertension [29]. ...
Aims
Exercise and food supplement of vitamin C (VC) are beneficial to human health, especially for those who suffer from hypertension. Here we tend to explore if gut microflora is involved in the anti-hypertensive effects of exercise and VC-supplement therapies.
Materials and Methods: With the spontaneously hypertensive rat (SHR) model, the small intestine pathology and the fecal microbiota was analyzed along with the pro- and anti-inflammatory cytokines (PICs and AICs) and reactive oxygen species (ROS) in the hypothalamus paraventricular nucleus (PVN) and intestine.
Key findings
We found that both exercise and VC intake, individually or combined, were able to alleviate the blood pressure in the SHRs comparing to the normotensive control Wistar-kyoto (WKY) rats. The expression level of PICs in the PVN and intestine of the SHRs was down-regulated while the AICs were up-regulated after treatments, together with down-regulation of ROS in the PVN. At meantime, the gut pathology was dramatically improved in the SHRs with exercise training or VC intake. Analysis of the gut microflora revealed significant changes in their composition. Several important micro-organisms that were deficient in the SHRs were found up-regulated by the treatments, including Turicibacter and Romboutsia which are involved in the short-chain fatty acid production.
Significance
Exercise training and VC intake individually can modify the gut microflora composition and improve the inflammatory state in both PVN and intestine, which contribute to their anti-hypertensive function. Combination of the two treatments enhanced their effects and worth to be considered as a non-medical aid for the hypertensive patients.
... The synthesis of free radicals have been identified to influence BP [11]; whilst exogenous administration of antioxidants has been used in animal models and in humans with hypertension to counteract the hypertensive effect of reactive oxygen species (ROS), due to their potential role in improving vascular function and reducing BP [12]. While several studies have suggested an inverse association between dietary antioxidants and BP [13][14][15][16][17][18][19][20][21][22], published results from randomized controlled clinical trials do not support the hypothesis that vitamin E or β-carotene supplementation has a protective effect on BP [23,24]. Relatedly, diets consist of a variety of foods, with complex combinations of antioxidant nutrients. ...
The association between dietary antioxidant quality score (DAQS) and cardiovascular risk factors such as low cardiovascular fitness (CRF) and elevated blood pressure (BP) has rarely been investigated. To investigate the association between DAQS, CRF, and BP. This cross-sectional study was conducted on 270 adult subjects living in Tehran, Iran. Dietary intake was evaluated using a validated food frequency questionnaire. The DAQS was calculated using antioxidant-nutrient intake. Socio-economic status, anthropometric measures, and BP were recorded by a trained interviewer, using standard methods. A significant increase was found in maximal oxygen uptake (p value = 0.01) across tertiles of DAQS. After adjusting for confounders, the association remained unchanged (p value = 0.02). Participants in the highest tertile of DAQS had higher systolic BP (SBP) (p value = 0.01) and diastolic BP (DBP) (p value = 0.03), although adjustment for confounding factors attenuated the results (p value = 0.3 for DBP and p value = 0.6 for SBP). Our results revealed that higher DAQS is associated with better CRF in Iranian adults. Further studies are needed to establish the veracity of our results.
... Other studies also revealed the relationship between vitamin C and BP, one of which was that hypertensive patients present a lower intake and serum vitamin C [23]. A variety of observational and interventional studies has additionally reported that vitamin C intake and its concentration status were significantly related to a reduction of resting BP [24]. For example, Kamran et al. [25] found that the correlation between vitamin C intake and systolic BP was -0.02 in uncontrolled hypertensive patients. ...
Background:
Hypertension is regarded as a major and independent risk factor of cardiovascular diseases, and numerous studies observed an inverse correlation between vitamin C intake and blood pressure.
Aim:
Our aim is to investigate the relationship between serum vitamin C and blood pressure, including the concentration differences and the correlation strength.
Method:
Two independent researchers searched and screened articles from the National Library of Medicine, Cochrane Library, Web of Science, China National Knowledge Infrastructure, VIP databases, and WANFANG databases. A total of 18 eligible studies were analyzed in the Reviewer Manager 5.3 software, including 14 English articles and 4 Chinese articles.
Results:
In the evaluation of serum vitamin C levels, the concentration in hypertensive subjects is 15.13 μmol/L lower than the normotensive ones (mean difference = -15.13, 95% CI [-24.19, -6.06], and P = 0.001). Serum vitamin C has a significant inverse relation with both systolic blood pressure (Fisher's Z = -0.17, 95% CI [-0.20, -0.15], P < 0.00001) and diastolic blood pressure (Fisher's Z = -0.15, 95% CI [-0.20, -0.10], P < 0.00001).
Conclusions:
People with hypertension have a relatively low serum vitamin C, and vitamin C is inversely associated with both systolic blood pressure and diastolic blood pressure.
... This could suggest that although oxidative stress may be able to disrupt CBF regulation, additional pathological processes that follow in consequence, such as inflammation, could also have a prominent role later on. This could also explain why antioxidant treatment has not proven efficacious to control blood pressure in hypertensive patients, 27 where multiple pathological processes affect CBF in parallel. ...
Background
Immune cells are key regulators of the vascular inflammatory response characteristic of hypertension. In hypertensive rodents, regulatory T lymphocytes (Treg, CD4⁺CD25⁺) prevented vascular injury, cardiac damage, and endothelial dysfunction of mesenteric arteries. Whether Treg modulate the cerebrovascular damage induced by hypertension is unknown.
Methods and Results
C57BL/6 mice were perfused with angiotensin II (Ang II; 1000 ng/kg per minute) for 14 days and adoptive transfer of 3×10⁵CD4⁺CD25⁺ T cells was performed via 2 intravenous injections. Control mice received a sham surgery and PBS. Treg prevented Ang II‐induced neurovascular uncoupling (P<0.05) and endothelial impairment (P<0.05), evaluated by laser Doppler flowmetry in the somatosensory cortex. The neuroprotective effect of Treg was abolished when they were isolated from mice deficient in interleukin‐10. Administration of interleukin‐10 (60 ng/d) to hypertensive mice prevented Ang II‐induced neurovascular uncoupling (P<0.05). Treg adoptive transfer also diminished systemic inflammation induced by Ang II (P<0.05), examined with a peripheral blood cytokine array. Mice receiving Ang II + Treg exhibited reduced numbers of Iba‐1+ cells in the brain cortex (P<0.05) and hippocampus (P<0.001) compared with mice infused only with Ang II. Treg prevented the increase in cerebral superoxide radicals. Overall, these effects did not appear to be directly modulated by Treg accumulating in the brain parenchyma, because only a nonsignificant number of Treg were detected in brain. Instead, Treg penetrated peripheral tissues such as the kidney, inguinal lymph nodes, and the spleen.
Conclusions
Treg prevent impaired cerebrovascular responses in Ang II‐induced hypertension. The neuroprotective effects of Treg involve the modulation of inflammation in the brain and periphery.
... One of the possible justifications perhaps free constrictive reactions to NE is elevated in hypertensive patients, ascorbic acid could reduce this response. However, there are some clinical experiments in which the outcome of ascorbic acid supplements on blood pressure have given unpredictable effects [49][50][51][52][53][54]. The lack of antihypertensive efficiency noted in trials by supplementation with ascorbic acid alone might be due to the reduced bioavailability of NO in conditions of oxidative damage. ...
Hypertension is considered as the most common risk factor for cardiovascular diseases, also is regarded as a leading cause of the mortality and morbidity worldwide. The mechanisms underlying the pathological process of hypertension are not completely explained. However, there is growing evidence that increased oxidative stress plays an important role in the pathophysiology of hypertension. Several preclinical studies and clinical trials have indicated that antioxidant therapy is important for management of hypertension, using antioxidants compounds such as alpha tocopherol (Vit E) and ascorbic acid (Vit C), polyphenols with others and some antihypertensive drugs that are now in clinical use (e.g., ACEIs, ARBs, novel B-blockers, dihydropyridine CCBs) which have antioxidative pleiotropic effects. The purpose of this review is to highlight the importance of antioxidant therapy for management of oxidative stress induced hypertension. Furthermore, reviewing the current knowledge in the oxidative stress and its significance in hypertension.
... Low levels of ascorbic acid have been observed in patients with hypertension as compared to normals. However, Ghosh and coworkers (1994) reported no statistical differences between blood pressure of ascorbic acid-treated and placebo-treated patients with essential hypertension [38]. Given before ischemia, dehydroascorbic acid, a blood brain barrier transportable form of vitamin C causes dose-dependant increase in postreperfusion cerebral blood flow with reductions in neurological deficit and mortality [27]. ...
... An interesting study by Mullan et al. (2002) showed that an oral administration of ascorbic acid (500 mg/day) for 1 month lowered blood pressure and reduced systemic arterial stiffness; conversely, other two randomized controlled trials failed to prove a blood pressure-lowering effect of vitamin C supplementation (Lovat et al., 1993;Ghosh et al., 1994). ...
Oxidative stress is generally considered as the consequence of an imbalance between pro- and antioxidants species, which often results into indiscriminate and global damage at the organismal level. Elderly people are more susceptible to oxidative stress and this depends, almost in part, from a decreased performance of their endogenous antioxidant system. As many studies reported an inverse correlation between systemic levels of antioxidants and several diseases, primarily cardiovascular diseases, but also diabetes and neurological disorders, antioxidant supplementation has been foreseen as an effective preventive and therapeutic intervention for aging-associated pathologies. However, the expectations of this therapeutic approach have often been partially disappointed by clinical trials. The interplay of both endogenous and exogenous antioxidants with the systemic redox system is very complex and represents an issue that is still under debate. In this review a selection of recent clinical studies concerning antioxidants supplementation and the evaluation of their influence in aging-related diseases is analyzed. The controversial outcomes of antioxidants supplementation therapies, which might partially depend from an underestimation of the patient specific metabolic demand and genetic background, are presented.
... However, antioxidant-based therapies have failed to show therapeutic impact in human patients with hypertension. 50,51 Although the reasons for these failures are not completely known, it might, at least, be related with the following: (1) antioxidants used; (2) patients included in trials; and (3) the trial design, itself. With respect to antioxidants, it is possible that agents used were ineffective, not appropriate, or that the dosing and duration of therapy were insufficient. ...
Oxidative stress plays an important role in the pathogenesis of hypertension, especially in obesity-related hypertension. The natriuretic and antinatriuretic components of the renal renin angiotensin system (RAS) maintain sodium homeostasis and blood pressure. Here, we test the hypothesis that increased oxidative stress leads to the imbalance of RAS components and hypertension in obese Zucker rats.
Lean and obese rats received vehicle or tempol, a superoxide dismutase mimetic in the drinking water for 4 weeks. Compared with vehicle-treated lean rats, vehicle-treated obese rats exhibited higher blood pressure and increased renal oxidative stress, accompanied by increased diuretic and natriuretic responses to AT1R antagonist (Candesartan) and AT2R agonist (CGP-42112A) and reduced diuretic and natriuretic response to MasR agonist (Ang-[1 to 7]). Moreover, obese rats had higher ACE, AT1R and AT2R, lower ACE2 and MasR expressions in the kidney. All of the above-mentioned abnormalities were reversed to some degree by tempol treatment. In primary cultures of renal proximal tubular (RPT) cells from lean and obese rats, tempol treatment also increased AT2R, ACE2, and MasR expressions but decreased AT1R and ACE expressions in obese rats.
Taken together, our study indicated that the imbalance of renal RAS components was associated with increased oxidative stress in obese rats. Furthermore, antioxidant treatment with tempol reversed the imbalance of renal RAS components and led to diuresis and natriuresis, which, at least in part, explains the blood pressure-lowering effect of antioxidant supplementation in obesity-related hypertension.
© 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.
... Studies in human hypertensives are few. Generally, study design did not exclude confounding variables such as diabetes, concomitant antihypertensive treatment, and advanced age [125][126][127][128][129][130][131], making it difficult to assess the antihypertensive effect of vitamin C. Although indirect, evidence from population-based studies indicates that plasma vitamin C levels are inversely correlated to blood pressure [8][9][10][11]. ...
Hypertension is a major health problem worldwide. Individuals with hypertension are at an increased risk for stroke, heart
disease, and kidney failure. Although the etiology of essential hypertension has a genetic component, lifestyle factors such
as diet play an important role. Insulin resistance and glucose intolerance are common features of hypertension in humans and
in animal models. Altered glucose metabolism leads to an increased production of the reactive aldehyde, methylglyoxal. Methylglyoxal
binds sulfhydryl and amino groups of proteins forming conjugates/advanced glycation end products (AGEs). This alters protein
structure and function and can affect vascular calcium channels, enzymes, and tissue proteins leading to increased oxidative
stress. These alterations impair endothelial function leading to an increase in intracellular free calcium, peripheral vascular
resistance, and hypertension. Supplementation with antioxidants, including vitamin C, E, or B6, thiols such as lipoic acid
and cysteine, and the quinone enzyme Q10, have been shown to lower blood pressure in animal models and humans with essential
hypertension. The Dietary Approaches to Stop Hypertension (DASH) studies demonstrated that a well-balanced diet, rich in these
nutrients, was effective in lowering blood pressure. These antioxidants may achieve their antihypertensive effects by reducing
aldehyde conjugate/AGE formation and oxidative stress, by improving insulin resistance and endothelial function, or by normalizing
calcium channels and peripheral vascular resistance. In essential hypertension, deficiencies of antioxidants may exist or
a higher than normal amount may be required to correct metabolic abnormalities. Dietary supplementation with antioxidants
may be a beneficial, inexpensive, first-line alternate treatment modality for hypertension.
... 100,101 Vitamin C may have favorable effects on vascular dilation, possibly through its antioxidant effects on NO. [102][103][104] Nevertheless, several small and short-term clinical trials on the effect of vitamin C supplements on blood pressure have yielded inconsistent findings. [105][106][107][108][109][110][111] The lack of antihypertensive efficacy observed in studies using supplementation with vitamin C alone could be due to the decreased bioavailability of NO under conditions of oxidative stress. It was shown that these effects are mediated in part by the ability of vitamin C to protect BH 4 from oxidation and thereby increase the enzymatic activity of eNOS. ...
Hypertension is considered to be the most important risk factor in the development of cardiovascular disease. An increasing body of evidence suggests that oxidative stress, which results in an excessive generation of reactive oxygen species (ROS), has a key role in the pathogenesis of hypertension. The modulation of the vasomotor system involves ROS as mediators of vasoconstriction induced by angiotensin II, endothelin-1 and urotensin-II, among others. The bioavailability of nitric oxide (NO), which is a major vasodilator, is highly dependent on the redox status. Under physiological conditions, low concentrations of intracellular ROS have an important role in the normal redox signaling maintaining vascular function and integrity. However, under pathophysiological conditions, increased levels of ROS contribute to vascular dysfunction and remodeling through oxidative damage. In human hypertension, an increase in the production of superoxide anions and hydrogen peroxide, a decrease in NO synthesis and a reduction in antioxidant bioavailability have been observed. In turn, antioxidants are reducing agents that can neutralize these oxidative and otherwise damaging biomolecules. The use of antioxidant vitamins, such as vitamins C and E, has gained considerable interest as protecting agents against vascular endothelial damage. Available data support the role of these vitamins as effective antioxidants that can counteract ROS effects. This review discusses the mechanisms involved in ROS generation, the role of oxidative stress in the pathogenesis of vascular damage in hypertension, and the possible therapeutic strategies that could prevent or treat this disorder.
... Thirteen trials 8–20 making up 14 separate group populations were identified and analyzed providing a total pooled population of 284 hypertensive patients (52% female), with a weighted mean age of 58.8 ± 9.5 years and a weighted mean body mass index of 28.5 ± 1.9 Kg/m 2 . Median vitamin C dose and study intervention duration was 500mg/day and 6 weeks respectively (Table 1).9,11,14,16,17,19 The baseline plasma vitamin C levels ranged between 44 to 74 µmol, while the range in post treatment levels ranged between 78 to 122 µmol. ...
Hypertension is a common condition with high mortality from associated diseases. Epidemiological evidence suggests that a dietary deficiency of vitamin C may be a risk factor for hypertension. However the literature on vitamin C interventional trials appears divided on the efficacy of vitamin C utilization clinically.
A literature search and review of published trials using vitamin C in treating patients with hypertension was undertaken. Relevant references were located using MEDLINE (1966-2005) and the bibliographies of located articles.
Thirteen trials making up 14 separate groups were identified and analyzed providing a pooled population of 284 hypertensive patients (52% female), with a weighted mean age of 58.8 +/- 9.5 years. Median vitamin C dose and study intervention duration was 500mg/day and 6 weeks respectively. The weighted mean baseline and post treatment systolic blood pressures across all 14 groups were 149.6 +/- 11.1 and 145.7 +/- 11.0 mmHg respectively. This represented a systolic blood pressure decrease of 3.9 mmHg. Seven of the 14 groups ascertained statistically significant reductions (p < .05) in systolic blood pressures. However only 2 of the 14 groups found significant reductions in diastolic blood pressure. The weighted mean baseline and post treatment diastolic blood pressures across all 14 groups were 84.6 +/- 4.4 and 82.5 +/- 4.1 mmHg respectively. This represented a diastolic blood pressure decrease of 2.1 mmHg.
Vitamin C supplementation in hypertensive patients appears to possess modest effects on reducing systolic blood and diastolic blood pressure.
... Intervention trials have been less consistent2425262728293031323334353637. Many of the studies that failed to find a treatment effect have had design limitations such as no control group or no placebo control, short duration, small sample size, concomitant use of non-study dietary supplements containing vitamin C, and varying or inadequately described methods for measuring BP; or they were post-hoc analyses where change in BP was not a primary endpoint of the trial. ...
The prevalence of hypertension and its contribution to cardiovascular disease risk makes it imperative to identify factors that may help prevent this disorder. Extensive biological and biochemical data suggest that plasma ascorbic acid may be such a factor. In this study we examined the association between plasma ascorbic acid concentration and blood pressure (BP) in young-adult women.
Participants were 242 Black and White women aged 18-21 yr from the Richmond, CA, cohort of the National Heart, Lung and Blood Institute Growth and Health Study. We examined the associations of plasma ascorbic acid with BP at follow-up year 10, and with change in BP during the previous year.
In cross-sectional analysis, plasma ascorbic acid at year 10 was inversely associated with systolic BP and diastolic BP after adjusting for race, body mass index, education, and dietary intake of fat and sodium. Persons in the highest one-fourth of the plasma ascorbic acid distribution had 4.66 mmHg lower systolic BP (95% CI 1.10 to 8.22 mmHg, p = 0.005) and 6.04 mmHg lower diastolic BP (95% CI 2.70 to 9.38 mmHg, p = 0.0002) than those in the lowest one-fourth of the distribution. In analysis of the change in BP, plasma ascorbic acid was also inversely associated with change in systolic BP and diastolic BP during the previous year. While diastolic blood pressure among persons in the lowest quartile of plasma ascorbic acid increased by 5.97 mmHg (95% CI 3.82 to 8.13 mmHg) from year 9 to year 10, those in the highest quartile of plasma vitamin C increased by only 0.23 mmHg (95% CI -1.90 to +2.36 mmHg) (test for linear trend: p < 0.0001). A similar effect was seen for change in systolic BP, p = 0.005.
Plasma ascorbic acid was found to be inversely associated with BP and change in BP during the prior year. The findings suggest the possibility that vitamin C may influence BP in healthy young adults. Since lower BP in young adulthood may lead to lower BP and decreased incidence of age-associated vascular events in older adults, further investigation of treatment effects of vitamin C on BP regulation in young adults is warranted.
... If the relationship between vitamin C and blood pressure is causal, it has implications for dietary intervention; however, dietary intervention trials have been inconclusive. The effect of vitamin C supplementation, even when decreasing blood pressure, was not quite unequivocal (Feldman et al. 1992;Lovat et al. 1993;Ghosh et al. 1994). In the Finnish study with smokers, where a controlled trial of mixed antioxidants including ascorbic acid, organic Se, vitamin E and -carotene was undertaken, there was a significant reduction in systolic blood pressure (Salonen et al. 1994). ...
This review attempts to delineate the underlying mechanisms leading to the development of hypertension as well as the function of vitamins and minerals in the regulation of blood pressure. Physiological processes that regulate cardiac output and systemic vascular resistance impact on the control of blood pressure. Metabolic abnormalities associated with the tetrad of hypertension, dyslipidaemia, glucose intolerance and obesity share insulin resistance, which might be organ or cell specific, as an underlying feature representing different tissue manifestation of a common cellular ionic defect. As Ca is at the centre of ionic regulation of cellular functions, vitamins involved in Ca regulation have a significant role in the control of blood pressure. The endothelium-dependent vasodilator, NO, is susceptible to oxidative damage. Hence, antioxidant vitamins and related factors regulate blood pressure through protection of NO. Robust evidence for the involvement of vitamin B6 (pyridoxine), vitamin C, vitamin D and vitamin E in the regulation of blood pressure have been reported. The well-known roles of Na, K, Ca, Mg and Cl have been explored further. The action of various vitamins on blood pressure regulation cannot always be explained on the basis of their conventionally recognised "vitamin function". The non-traditional functions of vitamins and their derivatives can be exploited as an adjunct to available pharmacological modalities in the treatment of hypertension.
Objectives
The objective of the current study is to compare the treatment effects of different vitamins on essential hypertension to provide an initial basis for developing evidence-based practices.
Design
Systematic review and network meta-analysis.
Data sources
Five electronic databases (PubMed, Embase, Web of Science, Cochrane Central Register of Controlled Trials and ClinicalTrials.gov) were searched from their inception to 25 September 2023.
Outcomes
The primary outcomes were the difference between the intervention group and the control group in changes in office systolic blood pressure (SBP) and office diastolic blood pressure (DBP) from baseline. The secondary outcomes were the difference between the intervention group and the control group in changes in 24-hour mean ambulatory systolic blood pressure (24 hours SBP), 24-hour mean ambulatory diastolic blood pressure (24 hours DBP) and heart rate (HR) from baseline.
Results
A total of 23 studies comparing five vitamins (vitamin B2, vitamin C, vitamin D, vitamin E, folic acid) and involving 2218 participants were included. The included trials were all vitamin versus placebo, so the network was star-shaped. Among the five vitamins, only vitamin E was significantly more effective at reducing SBP (mean difference: −14.14 mm Hg, 95% credible intervals: −27.62 to –0.88) than placebo. In addition, no evidence was found that any of the five vitamins influenced DBP, 24 hours SBP, 24 hours DBP, or HR. The dose of vitamins, geographical region and percentage of males (only SBP) might be sources of heterogeneity. Sensitivity and subgroup analysis revealed that the effect of vitamin intervention on blood pressure varies according to different doses of vitamins.
Conclusions
According to the results, vitamin E might be an effective measure to reduce SBP, but more research is needed to validate this finding.
PROSPERO registration number
CRD42022352332.
Background:
Vitamin C as a supplement to treat hypertension has been proposed. However, it remains controversial whether vitamin C can improve blood pressure in patients with primary hypertension.
Objectives:
To analyze the effect of vitamin C (VitC) supplementation on systolic (SBP) and diastolic (DBP) blood pressure in patients with essential hypertension.
Methods:
We searched the Chinese Knowledge Infrastructure, VIP Database for Chinese Technical Periodicals, WANFANG Data, Cochrane Library, National Library of Medicine's PubMed, EMBASE, and other databases until June 2019. Eight RCTs involving 614 participants were analyzed. SBP and DBP before and after VitC supplementation were compared between the intervention and control groups. The risk of bias of individual studies was assessed using the Cochrane Collaboration risk of bias tool. Two reviewers selected studies independently of each other. The Cochrane Collaboration Review Manager 5.3 was used to perform the meta-analysis.
Results:
There was a significant difference in the change of SBP (weighted mean difference [WMD] = -4.09; 95% confidence interval [CI] -5.56, -2.62; P < .001) and DBP (WMD = -2.30; 95% CI -4.27, -.331; P = .02) between the groups. Further, there was a significant difference in the SBP (WMD = -3.75, 95% CI -6.24, -1.26, P = .003) and DBP (WMD = -3.29, 95% CI -5.98, -.60, P = .02) for the subgroup with an age ≥60 years and that with ≥35 participants. In the subgroup analysis, result for SBP with a study duration ≥6 weeks was statistically significant different (WMD = -4.77; 95% CI -6.46, -3.08; P < .001). For an intervention dose of VitC ≥500 mg daily, SBP was statistically significant (WMD = -5.01; 95% CI -8.55, -1.48; P = .005).
Conclusion:
VitC supplementation resulted in a significant reduction of blood pressure in patients with essential hypertension.
Background:
Vitamin C is an essential micronutrient and powerful antioxidant. Observational studies have shown an inverse relationship between vitamin C intake and major cardiovascular events and cardiovascular disease (CVD) risk factors. Results from clinical trials are less consistent.
Objectives:
To determine the effectiveness of vitamin C supplementation as a single supplement for the primary prevention of CVD.
Search methods:
We searched the following electronic databases on 11 May 2016: the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library; MEDLINE (Ovid); Embase Classic and Embase (Ovid); Web of Science Core Collection (Thomson Reuters); Database of Abstracts of Reviews of Effects (DARE); Health Technology Assessment Database and Health Economics Evaluations Database in the Cochrane Library. We searched trial registers on 13 April 2016 and reference lists of reviews for further studies. We applied no language restrictions.
Selection criteria:
Randomised controlled trials of vitamin C supplementation as a single nutrient supplement lasting at least three months and involving healthy adults or adults at moderate and high risk of CVD were included. The comparison group was no intervention or placebo. The outcomes of interest were CVD clinical events and CVD risk factors.
Data collection and analysis:
Two review authors independently selected trials for inclusion, abstracted the data and assessed the risk of bias.
Main results:
We included eight trials with 15,445 participants randomised. The largest trial with 14,641 participants provided data on our primary outcomes. Seven trials reported on CVD risk factors. Three of the eight trials were regarded at high risk of bias for either reporting or attrition bias, most of the 'Risk of bias' domains for the remaining trials were judged as unclear, with the exception of the largest trial where most domains were judged to be at low risk of bias.The composite endpoint, major CVD events was not different between the vitamin C and placebo group (hazard ratio (HR) 0.99, 95% confidence interval (CI) 0.89 to 1.10; 1 study; 14,641 participants; low-quality evidence) in the Physicians Health Study II over eight years of follow-up. Similar results were obtained for all-cause mortality HR 1.07, 95% CI 0.97 to 1.18; 1 study; 14,641 participants; very low-quality evidence, total myocardial infarction (MI) (fatal and non-fatal) HR 1.04 (95% CI 0.87 to 1.24); 1 study; 14,641 participants; low-quality evidence, total stroke (fatal and non-fatal) HR 0.89 (95% CI 0.74 to 1.07); 1 study; 14,641 participants; low-quality evidence, CVD mortality HR 1.02 (95% 0.85 to 1.22); 1 study; 14,641 participants; very low-quality evidence, self-reported coronary artery bypass grafting (CABG)/percutaneous transluminal coronary angioplasty (PTCA) HR 0.96 (95% CI 0.86 to 1.07); 1 study; 14,641 participants; low-quality evidence, self-reported angina HR 0.93 (95% CI 0.84 to 1.03); 1 study; 14,641 participants; low-quality evidence.The evidence for the majority of primary outcomes was downgraded (low quality) because of indirectness and imprecision. For all-cause mortality and CVD mortality, the evidence was very low because more factors affected the directness of the evidence and because of inconsistency.Four studies did not state sources of funding, two studies declared non-commercial funding and two studies declared both commercial and non-commercial funding.
Authors' conclusions:
Currently, there is no evidence to suggest that vitamin C supplementation reduces the risk of CVD in healthy participants and those at increased risk of CVD, but current evidence is limited to one trial of middle-aged and older male physicians from the USA. There is limited low- and very low-quality evidence currently on the effect of vitamin C supplementation and risk of CVD risk factors.
In the next 30 to 40 years, the population of adults over the age of 65 years of age is estimated to double [1]. As the population of the United States ages, there is a concurrent need to address the morbidity associated with ageing. Rudman et al. [2], examined a population of nursing home residents and found that nearly 70% of the residents had a reduced body mass index (BMI), a 50% incidence of anemia, and a majority had a serum albumin 003C3.5 g/dl. They also found that all of the study group had a dietary intake 003C50% of the recommended dietary allowance (RDA) of several essential nutrients including: zinc, magnesium, manganese, copper, vitamin E retinol, nicotinic acid, pyridoxine, and folic acid. With this in mind, it is important to consider that institutionalized elderly may be deficient in their dietary intake of several essential vitamins. This dietary deficiency may lead to further health complications.
From Pauling researches several authors have argued potentially favourable actions of supplementation with high doses of vitamin C on health problems. Nowadays, after discovering of free radicals as an important pathological agent, interest has been pointed on ascorbic acid, considering its strong antioxidant effect. This effect could be especially relevant in sport activities, subject to a bigger oxidation risk, mainly in aerobic and endurance sports. Information flux is daily increasing on these aspects and for this reason we think is now seasonable to review the more relevant aspects on this field, considering the new published data relative to vitamin C supplementation and their actions on different health problems as cardiovascular illness, ocular and respiratory disorders, infections, etc. We discuss also its importance and use as an ergogenic aid, with possible positive effects on aerobic capacity and muscular strength, muscular nuisance and pain in the eccentric contraction, management of some problems related to fatigue and over training and, as a new concept, better hormonal adaptation to exercise. As data are very relevant and abundant, we have structured this review in two different parts. In this first part, we review general actions and effects of vitamin C, being second part specifically focused on supplementation results and strategies in sports performance.
Vitamin C is a potent water-soluble antioxidant in humans. Although this six-carbon lactone is derived from glucose in most mammalian species, where it is formed mainly in the liver, humans do not possess the enzymes for its synthesis. It is present in various foods, particularly of plant origin, in quantities that are several orders of magnitude higher than those of other vitamins. At the cell level, vitamin C exerts a protective effect against the oxidation of biomolecules, by many agents such reactive oxygen species produced in both physiological and pathophysiological processes. This protection involves proteins, lipids and DNA. The growing evidence of the involvement of oxidative stress in the mechanism of non-infectious, chronic and degenerative disorders makes the antioxidant supplementation with vitamin C, an attractive strategy in the prevention and attenuation of progression of these diseases. In the present chapter we are aimed to provide evidence of vitamin C supplementation in the treatment and prevention of important human diseases, such as preeclampsia, hypertension, atherosclerosis, diabetes, among others. In addition, although this antioxidant vitamin is well tolerated, we include some studies related with its side effects, such as kidney stones formation, diarrhea and indigestion. The underlying mechanisms accounting for these undesirable effects remain to be determined, whereas the prevailing viewpoints consider vitamin C as a safety supplement.
Hypertension is considered the most important risk factor in the development ofcardiovascular disease. An increasing body of evidence suggests that oxidative stress,which results in an excessive generation of reactive oxygen species (ROS), plays a keyrole in the pathogenesis of hypertension. The modulation of the vasomotor systeminvolves ROS as mediators of vasoconstriction induced by angiotensin II, endothelin-1and urotensin-II, among other factors. The bioavailability of nitric oxide (NO), a majorvasodilator, is modulated by the cellular redox status. Under physiological conditions,low concentrations of intracellular ROS are important in normal redox signaling tomaintain vascular function and integrity. However, under pathological conditions, ROScontribute to vascular dysfunction and remodeling through oxidative injury. Increasedproduction of superoxide anion and hydrogen peroxide, decreased NO synthesis anddiminished antioxidant capacity have been found in patients with essential hypertension.Antioxidants are reducing agents that can neutralize these oxidative compounds, whichotherwise damage biomolecules and thereby cause functional and even structuralimpairment of the end-organs. The use of antioxidant vitamins such as vitamins C and Efor protection against vascular endothelial injury has gained considerable interest.Available data support the role of these vitamins as effective antioxidants to counteractthe effects of ROS. In this chapter, the following core hypothesis is evaluated: essentialhypertension is a manifestation of subtle vascular inflammation brought about byheightened oxidative stress. For this purpose, the mechanisms involved in the generation of vascular ROS are discussed, as well as the role of oxidative stress in the pathogenesisof hypertension. Possible therapeutic strategies to overcome the heightened oxidativestress in essential hypertension are suggested.
Essential hypertension is a highly prevalent pathological condition that is considered as one of the most relevant cardiovascular risk factors and is an important cause of morbidity and mortality around the world. Despite the fact that mechanisms underlying hypertension are not yet fully elucidated, a large amount of evidence shows that oxidative stress plays a central role in its pathophysiology. Oxidative stress can be defined as an imbalance between oxidant agents, such as superoxide anion, and antioxidant molecules, and leads to a decrease in nitric oxide bioavailability, which is the main factor responsible for maintaining the vascular tone. Several vasoconstrictor peptides, such as angiotensin II, endothelin-1 and urotensin II, act through their receptors to stimulate the production of reactive oxygen species, by activating enzymes like NADPH oxidase and xanthine oxidase. The knowledge of the mechanism described above has allowed generating new therapeutic strategies against hypertension based on the use of antioxidants agents, including vitamin C and E, N-Acetylcysteine, polyphenols and selenium, among others. These substances have different therapeutic targets, but all represent antioxidant reinforcement. Several clinical trials using antioxidants have been made. The aim of the present review is to provide new insights about the key role of oxidative stress in the pathophysiology of essential hypertension and new clinical attempts to demonstrate the usefulness of antioxidant therapy in the treatment of hypertension.
Except for drugs eliminated predominantly by renal excretion, it is not possible to generalize on the type, magnitude, or
importance of age-related differences in pharmacokinetics. Conflicting data in the literature for various drugs may be attributed
to small numbers of subjects studied, differences in selection criteria for subjects, and variation in protocol design. Apparent
age-related differences in drug disposition are multifactorial and influenced by environmental, genetic, physiological, and
pathological factors.
No class of drugs has been more popular than the angiotensin-receptor blockers (ARBs). Their side-effect profile has resulted
in increasing prescriptions because they are better tolerated than any other class of antihypertensive drugs. The outcome
trials (Table 1) with these drugs are now being reported and are showing benefits for target organ protection (1–15). ARBs are proven to be effective in reducing the rate of renal insufficiency among diabetic hypertensives (3,5), reducing strokes for elderly patients (10) and hypertensive patients with left ventricular hypertrophy (7), and reducing cardiovascular mortality and total mortality compared to atenolol in diabetic hypertensive patients (9). Valsartan is as effective as captopril in patients sustaining a myocardial infarction complicated by heart failure, left
ventricular dysfunction, or both (15).
The arterial pressure is regulated by changes in cardiac output and/or systemic vascular resistance. Effective perfusion of
body organs requires appropriate resistance to blood flow to maintain arterial pressure. In the systemic vasculature, the
major factor of vascular resistance is smooth muscle tone, which helps regulate the most important determinant of resistance
to flow, the cross-sectional area of a vessel. There are two major neurohormonal systems that regulate cardiovascular function,
including smooth muscle tone: the autonomic nervous system and the renin-angiotensin system. The peripheral autonomic nervous
system has three main components: (a) the sympathetic nervous system (SNS), which comprises the autonomic outflow from the
thoracic and high lumbar segments of the spinal cord; (b) the parasympathetic nervous system, which includes the outflow from
the cranial nerves and the low lumbar and sacral spinal cord; and (c) the enteric nervous system, which is intrinsic neurons
in the wall of the gut. In addition to the blood vessels, the urinary bladder, penis, and prostate also have smooth muscle
cells (SMCs) innervated by SNS and parasympathetic nervous system neurons to help regulate micturition, erection, and ejaculation
(1).
The prevalence of both renal parenchymal and renovascular hypertension (RVH) increases sharply with age, making these the
two most common causes of secondary hypertension in the elderly (1). The main causes of renal parenchymal disease in the elderly are diabetes mellitus and hypertension (2); the main contributor to RVH is atherosclerosis.
Accurate measurement of blood pressure (BP) in older patients is vitally important for prognosis and intervention; however,
obtaining reliable measurement data in this population is not always an easy task. The office BP in older patients is often
difficult to measure for a variety of reasons. For example, in older patients accurate BP measurement is challenging because
alterations in cardiovascular physiology with the aging process produce an increase in BP variability. Furthermore, certain
structural changes in the blood vessel can add to the imprecision of many types of BP determination.
Acute hemorrhage is associated with a decrease in cardiac function and contractility, increase in heart rate and fall in blood pressure. Decreased myocardial function and contractility have been shown to be caused by generation of free radicals in the ischemic myocardium. These toxic effects can be significantly attenuated by pretreatment of animals with superoxide dismutase and catalase, suggesting the involvement of free radicals in the depression of cardiovascular function. In the present study, the role of ascorbic acid as a free radical scavenger in protection from the deleterious effects of excess blood loss was examined. The study was conducted on healthy mongrel dogs anesthetized with _-chloralose (80mg / kg, intravenous) maintained on artificial ventilation using a respiratory pump. Catheterisation was done to measure arterial blood pressure, left ventricular pressure, cardiac output, cardiac contractility, right atrial pressure and heart rate. All parameters were recorded on a polygraph. Cardiac output was measured by the thermodilution technique. Hemorrhage was induced by withdrawing 40% of estimated total blood volume in steps of 10% each at 10 min intervals. Arterial blood samples were withdrawn at each step for malondialdehyde (MDA) estimation. After inducing 40% hemorrhage, ascorbic acid was given as a bolus injection (70 mg / kg) in one group whereas, the other group received a continuous slow infusion of ascorbic acid (15 mg / min for an hour). After treatment, all the above-mentioned cardiovascular parameters were recorded and MDA estimation was done at 1, 15, 30, 45 and 60 min in both the groups. A fall in all the cardiovascular parameters was observed on hemorrhage. MDA rose from the basal level of 2.56 ± 0.7 nmol / dl to 3.3 ± 1.0 nmol / dl (p<0.05). Immediately after treatment, MDA level fell to 0.76 ± 0.03 nmol / min. This transient rise in MDA level observed at 40% blood loss suggests involvement of free radicals in the pathogenesis of the consequences of hemorrhage. Administration of ascorbic acid resulted in the recovery of hemodynamic parameters, which were adversely influenced by the induction of hemorrhage. Our results demonstrate the involvement of oxidants in hemorrhage-induced cardiovascular depression and cardioprotection by ascorbic acid, an antioxidant. The restoration of cardiovascular parameters towards normalcy by ascorbic acid was largely due to its antioxidant activity with a smaller contribution by the auto regulatory compensatory mechanisms.
Be cautious about the association until large randomised trials havebeen done
Stroke, coronary heart disease, and peripheral vascular disease have many risk factors, or risk indicators, in common, yet some factors are more important for one vascular bed than another. Cigarette smoking is a stronger determinant of peripheral vascular disease than of stroke, high blood pressure is more important for stroke than for coronary artery disease, and a high serum cholesterol concentration has a greater effect on coronary heart disease than on stroke. Other factors may be equally important in all these conditions, and Meade has argued that this is the case for a high plasma concentration of fibrinogen.1 In this week's BMJ Khaw and Woodhouse examine the association between a low vitamin C concentration in elderly people and a high fibrinogen concentration (p 1559)2 and Gale and colleagues report cardiovascular mortality according to vitamin C intake (p 1563).3
Khaw and Woodhouse followed up 96 men and women every two months for over a year.2 They …
Within the past few years, the paradigm in hypertension has shifted from an emphasis on diastolic blood pressure (DBP) to
one that emphasizes the importance of systolic blood pressure (SBP), especially in individuals over age 50 years (1–4). The rationale for this shift is based on a large body of observational and clinical trial data demonstrating that SBP is
a better risk predictor, and that SBP control markedly reduces cardiovascular morbidity and mortality. At the same time, there
has been relatively little information available to practitioners about the many new concepts that underlie this new approach
to cardiovascular patho-physiology. Most important is the notion that age-related changes in vascular stiffness are at the
center of future efforts to provide important new diagnostic and therapeutic advances in hypertension care.
Musculoskeletal disorders such as osteoarthritis, rheumatoid arthritis, and gouty arthritis are common problems among the
elderly (over 65 years old) population and have an impact on functional status and disability. The National Health and Nutrition
Examination Survey reported a greater than 80% incidence of osteoarthritis in people over the age of 55 years (1–3). Far less common is rheumatoid arthritis, with an incidence of 30 per 100,000 persons; this disease has a peak onset between
ages 30 and 55 years, with symptoms progressing later into life (4).
Although certain classes of medications provide additional benefits beyond blood pressure (BP) reduction in older patients
with comorbid conditions, the greatest factor in reduction of cardiovascular and cerebrovascular events and preservation of
renal function is BP reduction. The Hypertension Detection and Follow-up Program demonstrated that a reduction in systolic
blood pressure (SBP) of 1 mmHg correlated with a 1% decline in mortality (1). However, to achieve newly targeted BP levels based on the Seventh Report of the Joint National Committee on the Prevention,
Detection, Evaluation, and Treatment of High Blood Pressure, the majority of individuals will require two to four agents (2,3).
When confronted with an elevation in blood pressure (BP) in an elderly patient, additional measurements are necessary because
of increased variability in older persons possibly caused by impaired baroreceptor sensitivity (Fig. 1) (1). In addition to lability of BP, there should be consideration given to the presence of an auscultatory gap (2), orthostatic hypotension (3), and pseudohypertension (4).
In the treatment of hypertension and cardiovascular disease (CVD), multiple treatment strategies have come and gone over the
last several decades. The stepped care approach was popular for some time. However, adopting a stepped care approach to the
treatment of hypertension per se neglected the diverse individualized pathophysiology of hypertension. Its advocates appreciated the purity of a standardization
of hypertension treatment; others were disenchanted with its rigid nature. Yet, the stepped care approach to hypertension
therapy, with diuretics and/or β-blockers, was supported by strong outcomes data from numerous randomized controlled trials
(RCTs) (1).
A 50% increase in the 1995 US population size by the year 2050 has been projected (1). Although 12.5% of the population was 65 years or older in 1990, it is estimated the percentage will increase to 20% by
2050 (Fig. 1). The number of elderly will increase from 39 million in 2010 to 69 million by 2030 (1). The projected population growth of older patients will certainly increase the prevalence of hypertension in the elderly,
which accounts for two-thirds of the elderly population (2). The prevalence of hypertension has increased since 1988 (Fig. 2) (3).
Awareness, treatment, and control of hypertension in the United States have been improving for geriatric patients (1). However, awareness, treatment, and control remain the lowest among the oldest age group (2). This is ironic given the fact that the largest body of outcomes trials documents the reduction of morbidity and mortality
in the elderly population. These trials are reviewed in detail in Chapter 7.
Lifestyle modification (Table 1) is recommended for adults with prehypertension (120–139/80–89 mmHg) for the primary prevention of hypertension (1). However, lifestyle changes are also adjunctive to anti-hypertensive drug therapy (2,3). The National High Blood Pressure Education Program Working Group included reduced alcohol intake, tobacco abstinence, reduction
of saturated fat, and adequate dietary intake of potassium, calcium, and magnesium as nonpharmacological modalities in the
elderly (4).
In observational studies, increased vitamin C intake, vitamin C supplementation, and higher blood concentrations of vitamin C are associated with lower blood pressure (BP). However, evidence for blood pressure-lowering effects of vitamin C in clinical trials is inconsistent.
The objective was to conduct a systematic review and meta-analysis of clinical trials that examined the effects of vitamin C supplementation on BP.
We searched Medline, EMBASE, and Central databases from 1966 to 2011. Prespecified inclusion criteria were as follows: 1) use of a randomized controlled trial design; 2) trial reported effects on systolic BP (SBP) or diastolic BP (DBP) or both; 3) trial used oral vitamin C and concurrent control groups; and 4) trial had a minimum duration of 2 wk. BP effects were pooled by random-effects models, with trials weighted by inverse variance.
Twenty-nine trials met eligibility criteria for the primary analysis. The median dose was 500 mg/d, the median duration was 8 wk, and trial sizes ranged from 10 to 120 participants. The pooled changes in SBP and DBP were -3.84 mm Hg (95% CI: -5.29, -2.38 mm Hg; P < 0.01) and -1.48 mm Hg (95% CI: -2.86, -0.10 mm Hg; P = 0.04), respectively. In trials in hypertensive participants, corresponding reductions in SBP and DBP were -4.85 mm Hg (P < 0.01) and -1.67 mm Hg (P = 0.17). After the inclusion of 9 trials with imputed BP effects, BP effects were attenuated but remained significant. Conclusions: In short-term trials, vitamin C supplementation reduced SBP and DBP. Long-term trials on the effects of vitamin C supplementation on BP and clinical events are needed.
Hypertension reigns as a leading cause of cardiovascular morbidity and mortality worldwide. Excessive reactive oxygen species (ROS) have emerged as a central common pathway by which disparate influences may induce and exacerbate hypertension. Potential sources of excessive ROS in hypertension include nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, mitochondria, xanthine oxidase, endothelium-derived NO synthase, cyclooxygenase 1 and 2, cytochrome P450 epoxygenase, and transition metals. While a significant body of epidemiological and clinical data suggests that antioxidant-rich diets reduce blood pressure and cardiovascular risk, randomized trials and population studies using natural antioxidants have yielded disappointing results. The reasons behind this lack of efficacy are not completely clear, but likely include a combination of (1) ineffective dosing regimens, (2) the potential pro-oxidant capacity of some of these agents, (3) selection of subjects less likely to benefit from antioxidant therapy (too healthy or too sick), and (4) inefficiency of nonspecific quenching of prevalent ROS versus prevention of excessive ROS production. Commonly used antioxidants include Vitamins A, C and E, L-arginine, flavanoids, and mitochondria-targeted agents (Coenzyme Q10, acetyl-L-carnitine, and alpha-lipoic acid). Various reasons, including incomplete knowledge of the mechanisms of action of these agents, lack of target specificity, and potential interindividual differences in therapeutic efficacy preclude us from recommending any specific natural antioxidant for antihypertensive therapy at this time. This review focuses on recent literature evaluating naturally occurring antioxidants with respect to their impact on hypertension.
Growing evidence indicates that insulin resistance and oxidative stress are involved in the pathogenesis of essential hypertension. In insulin-resistant states, like obesity and type 2 diabetes, altered glucose metabolism may lead to increased formation of methylglyoxal and other ketoaldehydes. Animal studies have shown that increased levels of endogenous aldehydes may lead to hypertension and oxidative stress. In animal models, the administration of vitamin C, vitamin B6 or alpha-lipoic acid reduced tissue levels of aldehydes, prevented oxidative stress, and lowered blood pressure. The purpose of this review article is to critically evaluate the available evidence for the role of dietary supplements in hypertension treatment.
Prehypertension has been recently described as an independent category of blood pressure. Mounting evidence suggests that blood pressure in the prehypertensive range is associated with an increased risk of developing hypertension and cardiovascular disease. Several reports have assigned a critical role for oxidative stress in these disease processes. This review focuses on the clinical and experimental studies done in prehypertension and hypertension within the context of oxidative stress. This article also provides insights into why diverse therapeutic interventions, which have in common the ability to reduce oxidative stress, can impede or delay the onset of hypertension in prehypertension subjects.
A total of 3,318 men and women from a region in rural China were randomized to receive daily either a multiple vitamin/mineral
supplement or a placebo. Deaths that occurred in the participants were ascertained and classified according to cause over
the 6-year period from 1985 to 1991. At the end of supplementation, blood pressure readings were taken, and the prevalence
of hypertension was determined. There was a slight reduction in overall mortality in the supplement group (relative risk (RR)
= 0.93, 95% confidence interval (Cl) 0.75–1.16), with the decreased relative risk most pronounced for cerebrovascular disease
deaths (RR = 0.63, 95% Cl 0.37–1.07). This benefit was greater for men (RR = 0.42, 95% Cl 0.19–0.93) than for women (RR =
0.93, 95% Cl 0.44–1.98). Among the survivors, the presence of elevations in both systolic and diastolic blood pressures was
less common in those who received the supplement (RR for men = 0.43, 95% Cl 0.28–0.65; RR for women = 0.92, 95% Cl 0.68–1.24).
This study indicates that supplementation with a multivitamin/mineral combination may have reduced mortality from cerebrovascular
disease and the prevalence of hypertension in this rural population with a micronutrient-poor diet.
Many painful disorders, including joint dysfunctions such as rheumatoid arthritis (RA) or temporomandibular joint disorders (TMD), are associated with hyperthermia of the overlying skin. The same is true of certain intractable chronic pain conditions, such as chronic orofacial pain, which may be associated with TMD. We suggest that this skin hyperthermia, caused by regional vasodilation, is induced by extravascular nitric oxide (NO). Extravascular NO can be produced in the affected joint by osteoblasts, chondrocytes, and macrophages, by mechanical stimulation of endothelial cells, or by stimulated neurons. In view of a strong correlation between pain and skin hyperthermia in these disorders, and the evidence that NO enhances the sensitivity of peripheral nociceptors, we also suggest that at least this kind of pain is associated with excessive local level of NO. This hypothesis can be verified by dynamic area telethermometry, assessing the effect of NO on the sympathetic nervous function. This mechanism, which is in line with the general role of NO as a mediator between different organ systems, also may be relevant to any pain associated with enhanced immune response. Clinical implications of the proposed mechanism are discussed.
Vitamin supplementation in large dosages is increasingly common in the older population. Often, such supplementation is used in an attempt to improve an individual’s health status. There have been claims that the effects of vitamins halt the normal aging process or prevent and cure disease.
However, several recent studies have failed to demonstrate the efficacy of vitamin supplementation in preventing several types of cancer. In moderate dosages, supplementation with vitamin E (tocopherols) shows promise as a lipid antioxidant, and may reduce the risk of coronary heart disease. However, before vitamin E becomes an accepted medical therapy, further long term studies must be undertaken to examine the safety and efficacy of such therapy.
An adequate intake of vitamins should be ensured by adherence to a well balanced diet. However, the elderly are prone to circumstances that may prevent them from eating a balanced diet. In addition, there are several age-related medical conditions that may predispose individuals to dietary and vitamin deficiencies. To prevent vitamin deficiency diseases and their associated morbidity, modest vitamin supplementation may be necessary. However, supplementation should be reserved for individuals with documented deficiency or who are at risk of developing such deficiencies, especially those who are homebound or institutionalised.
Vitamins taken in large dosages should be considered as drugs. These medicines, which are obtainable over-the-counter, should be carefully regulated to prevent toxicity.
Data accumulated from epidemiological observations, intervention trials and studies on experimental animals provide a growing body of evidence of the influence of various dietary components on blood pressure. Dietary sodium, usually taken in the form of sodium chloride (common salt), is positively associated with blood pressure, and in many hypertensive patients reduction in sodium intake lowers blood pressure. On the other hand, in certain patients potassium, calcium and magnesium may be protective electrolytes against hypertension. Dietary fats, especially n-3 polyunsaturated fatty acids, may also influence blood pressure, whereas the possible role of other macronutrients, such as proteins and carbohydrates, or vitamins in the regulation of blood pressure is less well understood. Occasional ingestion of coffee transiently increases blood pressure, but the effects of habitual coffee consumption are controversial. Excessive use of alcohol on a regular basis has been associated with elevated blood pressure. It has also been shown in case reports that large amounts of liquorice lead to the development of hypertension. Thus, with appropriate dietary modifications, it is possible to prevent the development of high blood pressure and to treat hypertensive patients with fewer drugs and with lower doses. In some patients antihypertensive medication may not be at all necessary.
Albumin and immunoglobulin G (IgG) show increased visible fluorescence in diabetic patients, IgG fluorescence being correlated with the presence of diabetic retinopathy. Captopril, an angiotensin converting enzyme (ACE) inhibitor, has free radical scavenging ability, attributable to its thiol group. We compared the scavenging effect of captopril (at doses between 0.5 and 100 microM) with perindoprilat, enalapril and enalaprilat (ACE inhibitors without scavenging ability) and two thiol-containing compounds, mercaptopropionylglycine (MPG) and N-acetylcysteine (NAC) (scavengers with no effect on ACE). Three systems were used to generate visible fluorescence in albumin and IgG; glycation, exposure to copper/hydrogen peroxide and gamma radiation. All three thiol-containing compounds inhibited fluorescence development in IgG and albumin, when fluorescence was generated by glycation or gamma radiation. Other ACE inhibitors had no effect with IgG. Enalapril and perindoprilat showed less effect than captopril with albumin; enalaprilat had no effect. No compound had any effect on fluorescence generation by copper/hydrogen peroxide. Captopril may have an additional antioxidant effect compared to other ACE inhibitors.