Evidence on the use of alternative substances and therapies in hypertension

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Heras Benito" "autores" => array:1 [ 0 => array:2 [ "nombre" => "M." "apellidos" => "Heras Benito" ] ] ] ] ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1889183724000035?idApp=UINPBA00004N" "url" => "/18891837/0000004100000001/v1_202403190601/S1889183724000035/v1_202403190601/es/main.assets" ] "en" => array:19 [ "idiomaDefecto" => true "cabecera" => "Review" "titulo" => "Evidence on the use of alternative substances and therapies in hypertension" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "40" "paginaFinal" => "57" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "E. Martín-Riobóo, M. Turégano-Yedro, J.R. Banegas" "autores" => array:3 [ 0 => array:4 [ "nombre" => "E." "apellidos" => "Martín-Riobóo" "email" => array:1 [ 0 => "martinriobooenrique@gmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "M." "apellidos" => "Turégano-Yedro" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "J.R." "apellidos" => "Banegas" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "c" "identificador" => "aff0015" ] ] ] ] "afiliaciones" => array:3 [ 0 => array:3 [ "entidad" => "Especialista en Medicina Familiar y Comunitaria, UGC Poniente, Distrito Sanitario Córdoba-Guadalquivir, Córdoba, IMIBIC, Hospital Reina Sofía Córdoba, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Especialista en Medicina Familiar y Comunitaria, Centro de Salud Casar de Cáceres, Cáceres, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Especialista en Medicina Preventiva y Salud Pública, Departamento de Medicina Preventiva y Salud Pública, Facultad de Medicina, Universidad Autónoma de Madrid/IdiPaz y CIBERESP, Madrid, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Evidencias sobre el uso de sustancias y terapias alternativas en hipertensión" ] ] "textoCompleto" => "IntroductionComplementary and alternative medicine (CAM) is defined as practices, products, substances, or healthcare systems that that do not conform to the standards of mainstream medicine.<a class="elsevierStyleCrossRef" href="#bib0935">1</a> They are commonly used around the world by diverse populations and ethnicities, but they remain largely unregulated. Patients give varied reasons for using CAM. A systematic review of 231 studies found that the three main reasons were: expectations of benefits, dissatisfaction with conventional medicine, and the perception that CAM is completely safe.<a class="elsevierStyleCrossRef" href="#bib0940">2</a> Geographic, socio-demographic, economic, and cultural connotations have also been described. While in African countries, considerations such as the easy accessibility of these therapies, the high economic cost of conventional medicine, and the history of traditions and beliefs are noteworthy,<a class="elsevierStyleCrossRef" href="#bib0940">2</a> in Europe it has been documented that the use of CAM is higher in women, with higher socio-economic levels and more severe disease.<a class="elsevierStyleCrossRefs" href="#bib0945">3,4</a> In the United States (US), it is used more frequently by Caucasians than Black people, and by patients who perceive the quality of their medical care as poor.<a class="elsevierStyleCrossRef" href="#bib0955">5</a> However, CAM forms part of the cultural and religious heritage of certain Asian countries (traditional Chinese medicine, Ayurvedic medicine, traditional Chinese herbs) or of specific practices of certain racial groups.<a class="elsevierStyleCrossRef" href="#bib0960">6</a> In fact, the World Health Organisation (WHO) reminds us that certain countries in this geographical area, such as China and South Korea, partially finance CAM through their health systems.<a class="elsevierStyleCrossRef" href="#bib0965">7</a>In general, these therapies are increasingly widely used. A review of surveys in 21 countries found that 21–74% of the surveyed population had used CAM in the past 12 months.<a class="elsevierStyleCrossRef" href="#bib0970">8</a> Other studies in the US population found that more than 50% had used a vitamin or mineral complex, and patients with chronic diseases were more likely to use these supplements.<a class="elsevierStyleCrossRef" href="#bib0975">9</a> In Europe, a review found that 25.9% of the general population had used CAM in the last 12 months, although this varied greatly from country to country, from 10% in Hungary to almost 40% in Germany.<a class="elsevierStyleCrossRef" href="#bib0950">4</a>It is recognised that healthcare system users rarely inform their healthcare team about the use of supplements or other alternative therapies despite potential drug-drug interactions or significant health harms.<a class="elsevierStyleCrossRef" href="#bib0935">1</a> These misconceptions regarding their purported efficacy have largely driven the popularity of these products, while adverse effects have been grossly underestimated and silenced.Objective and search strategyIn this narrative review we will consider two sources of data, primarily focussing on the effects on blood pressure (BP) and hypertension (HTN). On the one hand, published systematic reviews and meta-analyses (general reviews on CAM and systematic reviews of individual therapies) and, on the other, the most recent clinical trials (mainly within the last 10 years) in the field of CAM. The authors have independently selected the aspects considered most relevant by consensus.Selection of studiesFor the review we undertook a search in EMBASE, MEDLINE, the Cochrane Library, and Google Scholar.A total of 4336 articles were obtained with the keywords Alternative, Therapies, Hypertension. After applying filters for Meta-Analysis, Clinical Trials, Systematic Review, and Randomised controlled trial, we were limited to 908 searches, of which 181 were finally reviewed for the document.We chose to divide CAM therapies into two sections:<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005">1.Alternative medicines based on non-biological or mind-body therapies, such as, acupuncture, yoga, meditation, mindfulness, qigong, chiropractic, osteopathy, Tai Chi, music therapy, etc.</li><li class="elsevierStyleListItem" id="lsti0010">2.Biologically based practices including botanicals, animal extracts, vitamins, minerals, fatty acids, amino acids, proteins, prebiotics, etc.</li></ul>Non-biological therapiesIn this section we will review body-based therapies, mind-body therapies, and other alternatives unrelated to substance intake or restriction.There are a multitude of techniques that could be divided into: body-based therapies (chiropractic or osteopathic manipulation, massage, acupuncture, and movement therapy); mind-body techniques (yoga, meditation, Tai-Chi, qigong, mindfulness, energy healing therapy, transcendental meditation, hypnosis, and biofeedback); other therapies and alternative medicines to Western medicine (Ayurvedic medicine, chelation therapy, craniosacral therapy, homoeopathy, naturopathy, and traditional healing). Of these, we highlight the following, as they are the most studied:Acupuncture and hypertensionAcupuncture is a traditional Chinese form of alternative medicine that is gaining attention in our country and in the rest of the world. Although its popularity is progressively increasing, little is still known about this therapy and its potential beneficial effects on chronic disease risk factors, such as hypertension.<a class="elsevierStyleCrossRef" href="#bib0980">10</a> There is no evidence available currently to demonstrate the sustained effect of acupuncture on reducing BP, as the available evidence does not show a clear effect, and its quality is low, with considerable biases.<a class="elsevierStyleCrossRefs" href="#bib0985">11,12</a> Several systematic reviews have concluded that acupuncture significantly reduced systolic BP (SBP) and diastolic BP (DBP), although in populations and methods that are widely heterogeneous between studies.<a class="elsevierStyleCrossRefs" href="#bib0990">12,13</a> In Spain, another study showed that acupuncture was effective in reducing BP levels in patients already receiving pharmacological therapy, with the reduction occurring in the first 3 weeks and being maintained until at least week 8.<a class="elsevierStyleCrossRef" href="#bib1000">14</a> Therefore, robust studies are needed to determine the efficacy and safety of acupuncture in the treatment of HTN and to provide a useful scientific basis for clinical decision-making.<a class="elsevierStyleCrossRef" href="#bib1005">15</a>Yoga and hypertensionYoga is a traditional Indian practice that has been adapted for use as a CAM. It mainly involves physical poses, breathing techniques, and meditation.<a class="elsevierStyleCrossRef" href="#bib1010">16</a> Yoga seems to exert its antihypertensive effect mainly through its breathing and meditation techniques and less through the postures.<a class="elsevierStyleCrossRef" href="#bib1015">17</a> These practices appear to increase parasympathetic activity and decrease sympathetic activity, possibly by increasing gamma-aminobutyric acid (GABA) activity, thus counteracting the overactivity of the sympathetic nervous system that is associated with HTN.<a class="elsevierStyleCrossRef" href="#bib1010">16</a>A systematic review and meta-analysis of the use of yoga in HTN found emerging, but very low quality, evidence that yoga may be a useful tool and adjunct treatment in the management of HTN. The impact of yoga can reduce SBP by 10mmHg and DBP by 8mmHg.<a class="elsevierStyleCrossRef" href="#bib1015">17</a> However, these positive effects disappeared when the effects of antihypertensive drugs were introduced. Although most studies have shown that yoga effectively reduces BP in the hypertensive population, and for some authors it should be proposed as a complementary therapy to be included in clinical guidelines,<a class="elsevierStyleCrossRef" href="#bib1020">18</a> the heterogeneity of yoga practices and poses and the quality of some research make it difficult to systematically recommend any specific yoga practice for hypertensive patients. In addition to yoga's efficacy on blood pressure control, some studies have shown benefits on lipid profile.<a class="elsevierStyleCrossRef" href="#bib1025">19</a>Meditation, mindfulness, and hypertensionSeveral neurophysiological and neuroanatomical studies have shown that meditation can have long-lasting effects at the brain level, with beneficial consequences on baseline physiological state and cardiovascular risk, as well as other benefits such as lowering BP, and reducing insulin resistance or metabolic syndrome.<a class="elsevierStyleCrossRef" href="#bib1030">20</a>Additional benefits of meditation in hypertension have been documented.<a class="elsevierStyleCrossRefs" href="#bib1030">20–22</a> Thus, its implementation may be an attractive and cost-effective adjunct to currently known medical therapies.<a class="elsevierStyleCrossRef" href="#bib1030">20</a> An 8-week randomised trial with ambulatory BP monitoring (ABPM) demonstrated the benefits of meditation (in the mindfulness modality) on BP control and on levels of stress, anxiety, and depression in a Mediterranean population.<a class="elsevierStyleCrossRef" href="#bib1035">21</a> Another study, which conducted a systematic review and meta-analysis on the effectiveness of mindfulness-based stress reduction programmes for HTN, showed significant improvements in patients with HTN or prehypertension,<a class="elsevierStyleCrossRef" href="#bib1040">22</a> above all reducing SBP.<a class="elsevierStyleCrossRef" href="#bib1045">23</a> Therefore, some reviews have considered that in addition to aerobic exercise, isometric training, use of low-sodium and high-potassium salt, comprehensive lifestyle changes, and low-calorie diet, meditation, mindfulness, and breath control should be useful alternative therapies to consider in patients with HTN.<a class="elsevierStyleCrossRef" href="#bib1045">23</a>Qigong and hypertensionQigong is a traditional fitness method that originated in ancient China and focuses on body movement, mind guidance, and breath control to achieve physical and mental well-being adjustment through a combination of these.<a class="elsevierStyleCrossRef" href="#bib1050">24</a> It also helps to lower BP levels, control complications, and reduce mortality.<a class="elsevierStyleCrossRef" href="#bib1055">25</a> Several meta-analyses and systematic reviews have highlighted<a class="elsevierStyleCrossRefs" href="#bib1050">24–26</a> that compared to no intervention, qigong significantly reduces SBP and DBP, and the combination of Qigong and antihypertensive drugs are more effective than antihypertensive drugs alone,<a class="elsevierStyleCrossRef" href="#bib1060">26</a> a combination that may also reduce stroke incidence, mortality, and the dose of antihypertensive drugs.<a class="elsevierStyleCrossRef" href="#bib1065">27</a>Qigong has also been shown to be useful in combination with another traditional Chinese wellness technique, such as Tai Chi. A meta-analysis evaluated mixed Tai Chi and qigong therapy on BP, concluding that it could be an effective complementary and alternative therapy in the control of HTN, alone or in combination with antihypertensive drugs.<a class="elsevierStyleCrossRef" href="#bib1070">28</a> This reduction in BP may be related to increased nitric oxide levels and decreased endothelin-1 levels.<a class="elsevierStyleCrossRef" href="#bib1070">28</a> The limitations of the studies are that almost all of them were conducted exclusively in Asian populations.Chiropractic care and hypertensionChiropractic care is often associated with frequent use of high velocity, low amplitude spinal manipulation/manual impulses directed at segments of the spine with the goal of restoring motion and function.<a class="elsevierStyleCrossRef" href="#bib1075">29</a> While spinal manipulation is often applied to intentionally targeted areas of the spine, the clinical relevance of such practice is unclear.<a class="elsevierStyleCrossRef" href="#bib1080">30</a> Several neurophysiological pathways have been proposed to explain the mechanisms of action of spinal manipulation in musculoskeletal disorders,<a class="elsevierStyleCrossRef" href="#bib1085">31</a> including its potential effect on the autonomic nervous system. The autonomic nervous system is a central component in blood pressure regulation, and some studies have suggested that 20–30% of hypertensives resistant to conventional pharmacological treatment may benefit from alternative therapies such as spinal manipulation.<a class="elsevierStyleCrossRef" href="#bib1090">32</a> However, several systematic reviews agree on the lack of evidence to support the use of spinal manipulation for HTN and other non-musculoskeletal disorders,<a class="elsevierStyleCrossRefs" href="#bib1090">32,34,35</a> including a recent landmark analysis (“global summit”) in the academic chiropractic community.<a class="elsevierStyleCrossRef" href="#bib1095">33</a> Furthermore, given the lack of systematicity in data regarding adverse effects related to spinal manipulation in hypertensive patients, possible contraindications, including severe hypotension and stroke, cannot be ruled out.<a class="elsevierStyleCrossRefs" href="#bib1090">32,34,37,38</a>Based on the body of evidence, the use of spinal manipulation in hypertension treatment protocols, as well as in other non-musculoskeletal disorders, is hardly justifiable, although these protocols should consider contextual elements and patient preferences.Bakris et al.<a class="elsevierStyleCrossRef" href="#bib1110">36</a> proved in grade I hypertensives without antihypertensive treatment that restoration of atlas vertebra misalignment was associated with marked and sustained reductions in BP comparable to the use of two-drug combination therapy. However, other papers conclude that there is a lack of evidence for spinal manipulation as an additional therapy in HT.<a class="elsevierStyleCrossRef" href="#bib1100">34</a> Therefore, more research is needed on the potential short-, medium-, and long-term benefits of this technique, taking the potential adverse effects of these practices into account, especially in non-professional hands.Osteopathy and arterial hypertensionOsteopathy is a philosophy of medicine that uses manual techniques to treat and alleviate discomfort through the restoration of organic balance.<a class="elsevierStyleCrossRef" href="#bib1125">39</a> Although it has been used in the management of medical pathologies, its use in hypertension is uncertain. One study showed that, in patients with cardiovascular disorders, osteopathic treatment after one year was significantly associated with improved SBP.<a class="elsevierStyleCrossRef" href="#bib1130">40</a> In contrast, other reviews<a class="elsevierStyleCrossRef" href="#bib1135">41</a> did not find a positive relationship between the practice and a decrease in BP. Therefore, larger, and more consistent studies are needed to support its use in hypertension.<a class="elsevierStyleCrossRef" href="#bib1140">42</a>Tai Chi and hypertensionTai Chi, one of the most widely used traditional Chinese arts, helps to relax both body and mind, and has been shown to relax blood vessels, lower BP,<a class="elsevierStyleCrossRef" href="#bib1145">43</a> and improve quality of life.<a class="elsevierStyleCrossRef" href="#bib1150">44</a>Several systematic reviews indicate its benefit in preventing falls, improving cognitive ability in older adults and benefits in other pathological processes, such as osteoarthritis, Parkinson's disease, chronic obstructive pulmonary disease rehabilitation, depression, cardiac rehabilitation, and dementia.<a class="elsevierStyleCrossRefs" href="#bib1155">45,46</a> However, the role of Tai Chi in HTN was more limited. Chan et al.<a class="elsevierStyleCrossRef" href="#bib1165">47</a> reported that Tai Chi is better than brisk walking in helping to control cardiovascular risk factors and improve psychosocial well-being, and could be considered a viable and safe alternative exercise in patients with HT.<a class="elsevierStyleCrossRefs" href="#bib1155">45,47</a> In terms of Tai Chi form, the Wu style had a better effect on HT in middle-aged and elderly people (significantly higher mean improvement in SBP), thus offering greater protection to the cardiovascular system.<a class="elsevierStyleCrossRef" href="#bib1170">48</a>Thus, any form of Tai Chi could be useful in the control of CVRFs such as hypertension, and in improving the quality of life of patients, it is also safe and has a minimal rate of adverse effects.Music therapy and hypertensionMusic therapy can be considered an important part of the non-pharmacological treatment of HTN. It can have positive effects on the mind and body that can help control BP levels,<a class="elsevierStyleCrossRef" href="#bib1175">49</a> with beneficial results in hypertensive patients.<a class="elsevierStyleCrossRefs" href="#bib1175">49–51</a> A controlled trial evaluated the effects of music therapy, showing significant reductions in BP, heart rate (HR), and anxiety levels in older adults living in a nursing home.<a class="elsevierStyleCrossRefs" href="#bib1175">49–51</a> Cao et al.<a class="elsevierStyleCrossRef" href="#bib1180">50</a> also reported improvements in BP (up to 9mmHg SBP and 6.5 DBP), HR, and depression and anxiety rating scales, and in sleep quality in hypertensive patients. These benefits suggest that music therapy could be a promising tool for preventing the progression of prehypertension,<a class="elsevierStyleCrossRef" href="#bib1185">51</a> although more specific studies are needed. A systematic review and meta-analysis corroborated the reduction in BP after music therapy used for hypertension, although a cause-effect relationship was not established.<a class="elsevierStyleCrossRefs" href="#bib1190">52,53</a> Therefore, randomised, well-designed, high-quality studies could be designed, that significantly evaluate the efficacy of musical interventions, although it would be difficult to systematise these results in the general population, as most studies lack double-blind implementation, and thus incur selection biases.<a class="elsevierStyleCrossRef" href="#bib1180">50</a>Biological therapiesThis category includes substances or foods obtained directly from nature, chemical substances, functional foods, and nutraceuticals. According to Functional Food Science in Europe (FUFOSE) a functional food is a food that, beyond its nutritional value, measurably influences physiological functions in terms of health promotion or disease prevention.Several reviews have assessed its value in terms of cardiovascular outcomes,<a class="elsevierStyleCrossRef" href="#bib1200">54</a> lipid levels,<a class="elsevierStyleCrossRef" href="#bib1205">55</a> and in HTN.<a class="elsevierStyleCrossRef" href="#bib1210">56</a> The results obtained have not always been neutral or positive, but some recent studies have reported adverse results with the consumption of some types of algae, posing potential risks to human health.<a class="elsevierStyleCrossRef" href="#bib1215">57</a>A recent review of 884 studies on a total of 27 micronutrients assessed the relationship between consumption and reduced cardiovascular disease, showing that n−3 and n−6 fatty acids, l-arginine, l-citrulline, folic acid, vitamin D, magnesium, zinc, α-lipoic acid, coenzyme Q10, melatonin, catechin, curcumin, flavanol, genistein, and quercetin showed moderate to high quality evidence for reducing cardiovascular risk factors.<a class="elsevierStyleCrossRef" href="#bib1220">58</a> Specifically, supplementation with n−3 fatty acids decreased cardiovascular mortality, myocardial infarction, and coronary events. Folic acid supplementation decreased stroke risk, and coenzyme Q10 supplementation decreased all-cause mortality events, while vitamins C, D, E, and selenium showed no effect on cardiovascular disease or type 2 diabetes risk. Other substances, such as β-carotenes increased all-cause mortality, cardiovascular mortality events, and stroke risk.In terms of their potential hypotensive effect, which is the main reason for our review, numerous substances have been analysed, most notably fish oil and monounsaturated fatty acids (omega-3 and 6), garlic, artichoke, oats, berberine, calcium, co-enzyme Q10, coffee, cocoa (dark chocolate), cinnamon, turmeric, spirulina, soluble viscous fibre, l-arginine, flax, magnesium, melatonin, quercetin, potassium, beetroot, milk-derived peptides (dietary amino acids), red pepper, salicornia, tea (green, red and bitter), vitamin C, vitamin D, and zinc.Fatty acidsA short-term study with very small numbers of elderly patients found a possible decrease in BP in those taking omega-3 and 6 fatty acids,<a class="elsevierStyleCrossRef" href="#bib1225">59</a> but a retrospective review of the NHANES study found no association between higher intakes of n−3 or n−6 fatty acids and a lower risk of hypertension.<a class="elsevierStyleCrossRef" href="#bib1230">60</a>Folic acidSome studies in US adults have found associations between multiple vitamin supplementation with vitamin B complex and folate and the prevalence of HTN retrospectively,<a class="elsevierStyleCrossRef" href="#bib1235">61</a> suggesting a protective effect against HTN.A recent review of pooled results with 22 studies analysed found that folic acid supplementation slightly, but significantly, reduced both SBP and DBP.<a class="elsevierStyleCrossRef" href="#bib1240">62</a>GarlicGarlic (Allium sativum L.) belongs to the Liliaceae family along with the onion. Its benefits are due to its high content of sulphur compounds, of which allicin is the substance with the greatest biological activity, although other substances with a hypotensive effect are of note, such as adenosine and saponins. Some meta-analyses have shown that garlic can reduce SBP and DBP,<a class="elsevierStyleCrossRefs" href="#bib1245">63–65</a> and beneficial effects have also been attributed to the intestinal probiota,<a class="elsevierStyleCrossRef" href="#bib1260">66</a> and lipid and immune parameters.<a class="elsevierStyleCrossRef" href="#bib1265">67</a>ArtichokeArtichoke (Cynara scolymus L.) has been linked to the Mediterranean diet. Artichoke leaves contain polyphenolic compounds, prebiotics (inulin), minerals, ascorbic acid, and folic acid, and its leaf extract is rich in dietary fibre and antioxidant components, with a proposed mechanism of hypotensive action based on increased expression of the endothelial nitric oxide synthase (eNOS) gene and therefore the production of nitric oxide (NO) in cultured human vascular endothelial cells, improving endothelium-dependent vasodilation, with positive effects both on insulin resistance and on other lipid metabolic parameters, or somatometric parameters (waist circumference or visceral adipose tissue).<a class="elsevierStyleCrossRef" href="#bib1270">68</a>Although not all meta-analyses and systematic reviews have been able to document a hypotensive effect,<a class="elsevierStyleCrossRef" href="#bib1275">69</a> a recent review has documented a significant decrease in both SBP and DBP.<a class="elsevierStyleCrossRef" href="#bib1280">70</a>OatsOats provide several beneficial dietary components with putative beneficial effects on BP or endothelial function, such as β-glucans, γ-amino butyric acid (GABA), and phytochemicals such as avenanthramides.<a class="elsevierStyleCrossRef" href="#bib1285">71</a>A systematic review<a class="elsevierStyleCrossRef" href="#bib1290">72</a> found that oat consumption is effective in reducing SBP levels, particularly in individuals whose baseline BP is in the HTN range, and no such effect was found in normotensive individuals. However, research in this area is limited and further studies are needed to elucidate the antihypertensive potential of oats.<a class="elsevierStyleCrossRef" href="#bib1295">73</a>BerberineBerberine is a natural plant alkaloid used in eastern countries (Chunghyul-dan herbal extract contains berberine). Some studies have linked berberine consumption to metabolic benefits at the cardiovascular level (improvement of diabetes and lipids) and to hypotensive effects,<a class="elsevierStyleCrossRefs" href="#bib1300">74,75</a> although the quality of the studies was very low (high heterogeneity, short duration, and low number of participants).Cocoa (and dark chocolate)The polyphenols contained in cocoa (mainly flavonoids and epicatechin) antagonise angiotensin-converting enzyme (ACE) and activate the enzyme nitric oxide synthase, which increases nitric oxide synthesis, promotes vasodilation and thus BP reduction. This hypotensive effect has been documented when the daily dose of flavonols in cocoa was ≥900mg (equivalent to 100–500g chocolate) or epicatechin≥100mg (equivalent to 50–200g chocolate).<a class="elsevierStyleCrossRef" href="#bib1310">76</a> One study compared cocoa intake in beverage form with cocoa and dark chocolate, finding that the decrease in BP was greater with consumption of dark chocolate.<a class="elsevierStyleCrossRef" href="#bib1310">76</a> A Cochrane review<a class="elsevierStyleCrossRef" href="#bib1315">77</a> analysed this blood pressure lowering effect providing moderate quality evidence that chocolate and flavonol-rich cocoa products caused a small (2mmHg) blood pressure lowering effect in mainly healthy adults and short-term, which was substantially greater in the subgroup of hypertensive patients, although the results were limited by the large heterogeneity of the studies. On a practical level, a review conducted for general practitioners in 2013<a class="elsevierStyleCrossRef" href="#bib1320">78</a> claimed that consumption of 50g cocoa per day could reduce BP in hypertensive patients by 2–3mmHg, although with a grade C recommendation.CoffeeThere are over 1000 chemical compounds in coffee, the most documented being caffeine, chlorogenic acid, trigonelline, kahweol, cafestol, ferulic acid, and melanoidins. Numerous studies and systematic reviews/meta-analyses have examined a possible hypotensive effect of caffeine, with varying results.<a class="elsevierStyleCrossRefs" href="#bib1325">79–85</a> A j-shaped curve was documented for regular coffee consumption and long-term risk of hypertension.<a class="elsevierStyleCrossRef" href="#bib1325">79</a> While moderate and regular coffee consumption did not increase, and might even reduce, the risk of developing HTN, occasional coffee consumption would have hypertensive effects and might even decrease cancer mortality.<a class="elsevierStyleCrossRef" href="#bib1360">86</a> Regarding the different types of coffee (instant, ground, and decaffeinated) and their relationship with cardiovascular disease and arrhythmias, decaffeinated, ground, and instant coffee, particularly at doses of 2–3 cups/day, were associated with significant reductions in mortality and incident cardiovascular disease. It has been documented that it is caffeinated coffee, not decaffeinated coffee, which has been associated with a hypotensive effect.<a class="elsevierStyleCrossRef" href="#bib1360">86</a> Ground and instant coffee, but not decaffeinated, were associated with a reduced risk of arrhythmia.<a class="elsevierStyleCrossRef" href="#bib1365">87</a>In summary, moderate, and regular coffee consumption (1–3cups/day) does not adversely affect blood pressure in most people, including those with HTN. While acute administration of coffee may induce an increase in BP, regular consumption of coffee in medium-high doses (3–5cups/day) has a neutral or even beneficial impact on BP values and new onset of HTN; the same long-term intake significantly reduces the incidence of cardiovascular disease as well as all-cause mortality.<a class="elsevierStyleCrossRefs" href="#bib1360">86,87</a> Current evidence excludes a significant effect of coffee consumption on the development of HTN and BP control in treated and untreated hypertensives, all of which supports a protective role of the antioxidant components of coffee that may counteract the claimed negative effect of caffeine. Therefore, coffee consumption is compatible with a correct and balanced lifestyle and should not be discouraged in hypertensive subjects or those with cardiovascular disease.<a class="elsevierStyleCrossRef" href="#bib1370">88</a>Calcium and vitamin DDecreased levels of vitamin D and calcium have been linked to elevated BP and cardiovascular complications. A meta-analysis reviewed the combined effects of calcium and vitamin D on BP, finding a non-significant reduction in SBP and a significant decrease in DBP.<a class="elsevierStyleCrossRef" href="#bib1375">89</a> In contrast, another review studied the effect of calcium and vitamin D supplementation in normotensive and hypertensive patients, detecting no significant effect on daytime office BP, although subgroup analysis found a decrease in SBP in men.<a class="elsevierStyleCrossRef" href="#bib1380">90</a>A recent systematic review from the Cochrane library<a class="elsevierStyleCrossRef" href="#bib1385">91</a> found that increased calcium intake slightly reduced SBP and DBP in normotensive individuals, particularly in young people, which may suggest a role in the prevention of HTN. Similarly, another publication noted how high dietary calcium was associated with a lower risk of all-cause mortality, cardiovascular disease, and cancer; in terms of dosage, a dietary intake between 1000 and 1200mg per day in people with HTN could be considered cost-effective.<a class="elsevierStyleCrossRef" href="#bib1390">92</a>Several reviews have addressed calcium supplementation with the prevention of pre-eclampsia<a class="elsevierStyleCrossRefs" href="#bib1395">93–95</a> with positive results, especially in women with low calcium intake.<a class="elsevierStyleCrossRef" href="#bib1405">95</a>Isolated vitamin D3 intake has been associated with some cardioprotective effect, although one review found no such association.<a class="elsevierStyleCrossRef" href="#bib1410">96</a> It has also been studied in relation to a possible hypotensive effect without positive results, although a decrease in SBP and DBP was observed in men<50 years and with intake>800units/day and with trials lasting<6 months, which considerably limits its value.<a class="elsevierStyleCrossRef" href="#bib1415">97</a>CinnamonSome reviews have studied the blood pressure lowering effect of cinnamon,<a class="elsevierStyleCrossRefs" href="#bib1420">98–101</a>with decreases in both SBP and DBP.<a class="elsevierStyleCrossRef" href="#bib1420">98</a> However, the small number of publications, the absence of long-term results, the great heterogeneity, and the small number of patients included make these conclusions inconsistent, if not partially incongruent.Coenzyme Q10Although some reviews have associated the consumption of coenzyme Q10 with a hypotensive effect, several Cochrane reviews have found no evidence for this.<a class="elsevierStyleCrossRef" href="#bib1440">102</a>Another review looked at the hypotensive effect in patients with metabolic diseases, documenting a slight decrease in SBP, but not in DBP.<a class="elsevierStyleCrossRef" href="#bib1445">103</a> A potential U-shaped dose–response relationship between CoQ10 supplementation and SBP level has been documented at a dose of approximately 100–200mg/day, mainly in patients with cardiovascular disease (SBP-lowering effects were more pronounced in patients with diabetes and dyslipidaemia and in studies lasting longer than 12 weeks).<a class="elsevierStyleCrossRef" href="#bib1450">104</a> Its definitive effect on BP is therefore not yet well established.TurmericCurcumin, first used 3000 years ago as an anti-inflammatory agent, is a well-known bioactive compound derived from the active ingredient of turmeric (Curcuma longa) and has been described as having a potential therapeutic effect on a variety of diseases through antioxidant, anti-apoptotic and anti-inflammatory pathways.<a class="elsevierStyleCrossRef" href="#bib1455">105</a> The results on HTN are inconsistent. Thus, while one systematic review/metaanalysis,<a class="elsevierStyleCrossRef" href="#bib1460">106</a> showed that turmeric consumption did not reduce SBP/DBP (although it did in studies lasting>12 weeks), another review did show a decrease in DBP in subgroup analysis, also in studies lasting more than 12 weeks.<a class="elsevierStyleCrossRef" href="#bib1465">107</a>Spirulina (Arthrospira platensis)This micro-alga of the proanthocyanidin family is actually a group of single-celled bacterial micro-organisms of the genus Arthrospira that has become a superfood for combating anaemia and malnutrition. Recommendations on the beneficial effects of algae in the diet are becoming increasingly widespread, identified with responsible and ecological consumption, and spirulina is one of the most widely used,<a class="elsevierStyleCrossRef" href="#bib1470">108</a> with supposed hypotensive effects.<a class="elsevierStyleCrossRef" href="#bib1475">109</a> The components of Spirulina platensis matrix have been investigated for their potential cardiovascular benefits, and a decameric peptide (peptide fraction 6 – SP6–) was found to produce endothelium-dependent vasodilation.<a class="elsevierStyleCrossRef" href="#bib1480">110</a>A recent review analysed the short-term blood pressure lowering effect, finding a decrease of 4.5mmHg SBP and 2.5mmHg DBP; and even greater decreases of up to 7mmHg DBP in other meta-analyses (mainly in hypertensive patients). However, more evidence is needed, although it could be considered a potential hypotensive adjunct in the future.<a class="elsevierStyleCrossRef" href="#bib1485">111</a>Viscous soluble fibreThere are numerous recommendations to increase the consumption of dietary fibre, due to its beneficial effects on the cardiovascular system and cancer prevention. With regard to its potential hypotensive effect, several types of fibre have been described as likely to be beneficial, including β-glucan from oats and barley, guar gum, konjac, pectin, and psyllium. Several reviews have found decreases in both SBP and DBP,<a class="elsevierStyleCrossRefs" href="#bib1490">112–114</a> especially psyllium.<a class="elsevierStyleCrossRefs" href="#bib1495">113,114</a>l-Argininel-Arginine is an amino acid obtained by the body from dietary sources or endogenous metabolism. It is the substrate for numerous enzyme pathways involved in the regulation of vascular tone, immune activation, and cell growth. l-Arginine supplementation has been shown to exert several beneficial effects on cardiometabolic markers, including BP. A recent review has shown how l-arginine supplementation leads to a significant decrease in SBP. In non-linear dose–response analysis, the effective dose of l-arginine supplementation was found to be ≥4g/day.<a class="elsevierStyleCrossRef" href="#bib1505">115</a>MagnesiumAlthough a Cochrane review<a class="elsevierStyleCrossRef" href="#bib1510">116</a> had previously found insufficient evidence for the hypotensive effect of magnesium, a review of clinical trials showed that an average intake of 368mg/day of magnesium lowered SBP by 2mmHg and DBP by 1.8mmHg<a class="elsevierStyleCrossRef" href="#bib1515">117</a>; however, its long-term effect requires further evidence to be demonstrated. In addition, antihypertensive effects have been reported in certain patient subgroups, such as those with insulin resistance, pre-diabetes, or diabetes, and very recently in diabetic patients in improving BP and lipid levels.<a class="elsevierStyleCrossRef" href="#bib1520">118</a>In January 2022, the FDA (<a href="https://www.fda.gov/food/cfsan-constituent-updates/fda-announces-qualified-health-claim-magnesium-and-reduced-risk-high-blood-pressure">https://www.fda.gov/food/cfsan-constituent-updates/fda-announces-qualified-health-claim-magnesium-and-reduced-risk-high-blood-pressure</a>) announced that companies can make certain health claims regarding magnesium intake and a reduced risk of high blood pressure. However, food companies and dietary supplement manufacturers wishing to include such claims on their packaging must add some caveats. Specifically, the wording should make it clear that the evidence to support the claim is “inconsistent and inconclusive”, with more research needed to provide further evidence.<a class="elsevierStyleCrossRef" href="#bib1525">119</a>MelatoninMelatonin is a hormone secreted in the pineal gland that has a sleep cycle modulating effect and has demonstrated cardiovascular beneficial effects. The hypotensive effect has been studied in several meta-analyses,<a class="elsevierStyleCrossRefs" href="#bib1530">120–125</a> extended-release melatonin (and not immediate-release) been significantly associated with BP decreases of approximately 3.5mmHg in SBP and DBP, consistently. A study evaluating hypertensive diabetics found that more than 30% of non-dippers with type 2 diabetes treated with melatonin regained normal circadian BP rhythm with reductions of 3–5mmHg at night.<a class="elsevierStyleCrossRef" href="#bib1560">126</a>Milk peptides and probioticsThe hypotensive effect of some biologically active peptides and probiotics from lactic acid fermentation of milk, namely isoleucine-proline-proline (IPP) and valine-proline-proline (VPP), has been studied for decades. Numerous recent reviews with these peptides have found a hypotensive effect,<a class="elsevierStyleCrossRefs" href="#bib1560">126–132</a> primarily through inhibition of angiotensin-converting enzyme or ACE (activating ACE-2), mainly in hypertensive patients<a class="elsevierStyleCrossRef" href="#bib1560">126</a> or in patients with hypertension and diabetes mellitus,<a class="elsevierStyleCrossRef" href="#bib1565">127</a> although this has not been demonstrated in all studies.<a class="elsevierStyleCrossRef" href="#bib1570">128</a> Human clinical trials have shown that the consumption of probiotics can improve BP control and improve vascular function,<a class="elsevierStyleCrossRef" href="#bib1575">129</a> both in multi-component and single-component (Lactobacillus plantarum) studies.<a class="elsevierStyleCrossRef" href="#bib1580">130</a> However, although the results are encouraging, more research is still needed to clarify the exact mechanism and efficiency of the intake of these antihypertensive peptides, and their potential benefit on health in general and on hypertension in particular.<a class="elsevierStyleCrossRef" href="#bib1585">131</a> A summary of marketed products containing these products can be found in a recent review.<a class="elsevierStyleCrossRef" href="#bib1590">132</a> A recent meta-analysis evaluated the blood pressure lowering effect of whey protein, finding a significant decrease in SBP of −1.5mmHg.<a class="elsevierStyleCrossRef" href="#bib1595">133</a>PotassiumAlthough numerous studies on the blood pressure lowering effect of potassium intake have been conducted for decades, it was not until the beginning of this century that potassium supplementation was recommended in clinical practice guidelines. The Canadian guidelines on HTN have been the most explicit in their recommendation, obtaining a maximum level of evidence (A)<a class="elsevierStyleCrossRef" href="#bib1600">134</a> given that potassium is a fundamental pillar of the DASH diet (Dietary Approaches to Stop Hypertension) and the Mediterranean diet. Several reviews and meta-analyses have documented how a supplement of 3500–5000mg/day can reduce SBP by up to 4mmHg and DBP by 2mmHg, with consumption preferably with a diet (such as locally available fruits and vegetables) rich in potassium.<a class="elsevierStyleCrossRefs" href="#bib1605">135–141</a>A recent meta-analysis documented how potassium supplementation as a salt substitute was able to lower BP and total mortality.<a class="elsevierStyleCrossRef" href="#bib1630">140</a> Similarly, another meta-analysis found that for every 10% lower proportion of sodium chloride in the salt substitute, a 1.5mmHg reduction in SBP and a .95mmHg reduction in DBP was associated with a 1.5mmHg reduction in SBP and a .95mmHg reduction in DBP.<a class="elsevierStyleCrossRef" href="#bib1635">141</a> However, despite the results shown, caution should be exercised regarding the use of these potassium supplements, especially in patients with chronic kidney disease or on ACE inhibitors or potassium-sparing diuretics due to the risk of hyperkalaemia.BeetrootSeveral studies<a class="elsevierStyleCrossRefs" href="#bib1640">142–145</a> have documented that both beetroot juice (beetroot) and capsules with dry extract (nitrate) can lower BP, given the high nitrate content which is converted to nitric oxide after ingestion of this plant. The effect has been shown mainly in decreasing SBP, and not so clearly for DBP.<a class="elsevierStyleCrossRef" href="#bib1545">123</a>In any case, the properties of beetroot may go beyond its nitrate content, as other reviews have found no positive cardiovascular effects with inorganic nitrate consumption,<a class="elsevierStyleCrossRef" href="#bib1655">145</a> and the BP-lowering effects of beetroot juice appear to be independent of NO3. In any case, potential health risks must be highlighted because possible carcinogenic effects of its N-nitroso compounds (nitrosamides and nitrosamines)<a class="elsevierStyleCrossRef" href="#bib1640">142</a> have been described, although a review by Spanish authors reminded us that the beneficial effects of the consumption of beetroot and other vegetables outweigh the possible potential risk to human health.<a class="elsevierStyleCrossRef" href="#bib1660">146</a>SalicorniaSalicornia sp. is a halophyte plant, tolerant to water salinity, which grows in salt marshes. The way it defends itself against these adverse stress conditions (seawater salinity, UV rays, etc.) is to produce large quantities of polyphenols. The number of polyphenols in B-Salicornia is very high (29mgGAE/g), which may partly explain its beneficial effects. It has a wide geographical distribution, and its identified effects include lowering BP, lowering homocysteine, and its anti-adipogenic effect due to its main component, transferulic acid.<a class="elsevierStyleCrossRefs" href="#bib1665">147–149</a> It is currently being marketed as another natural salt in parts of our country (Salicornia® extract and B-Salicornia® are registered trademarks). Some studies and research are underway to assess the effect of this marine plant as a salt substitute<a class="elsevierStyleCrossRef" href="#bib1680">150</a> and its neurovascular effects (<a href="http://proyectosalicornia.com/wp-content/uploads/2022/05/18.04.22-peiba_HALOFITAS_modF.pdf">http://proyectosalicornia.com/wp-content/uploads/2022/05/18.04.22-peiba_HALOFITAS_modF.pdf</a>), although there is no conclusive data as yet.TeaTea is a beverage prepared by pouring hot or boiling water over the cured leaves or leaf buds of the tea plant Camellia sinensis. Prolonged consumption appears to be associated with cardiovascular and hypotensive benefits.<a class="elsevierStyleCrossRefs" href="#bib1685">151,152</a> It is particularly used by Asian and Middle Eastern populations, from where most of the studies on the substance originate.Caffeine in tea is known to have a short-term pressor effect after immediate ingestion of tea, which is neutralised in the medium and long term, and has been shown in many epidemiological studies to reduce both SBP and DBP.<a class="elsevierStyleCrossRef" href="#bib1690">152</a>There are numerous types of tea (green tea, black tea, matcha tea, sour tea, white tea, sour or red tea, sweet tea, dark tea, corn silk tea, etc.). The main phenolic compounds found in tea are flavonoids, which account for almost 70% of its polyphenols. Catechins and their derivatives especially epigallocatechin-3-gallate (EGCG) are the most abundant flavonoids in green tea which are responsible for the potential preventive effect on oxidative stress caused by diseases such as cancer, cardiovascular diseases, and neurodegenerative diseases.<a class="elsevierStyleCrossRef" href="#bib1695">153</a> Among the many varieties of tea, it is mainly green tea, red tea, black tea, and bitter tea (sour tea, or hibiscus sabdariffa, or Jamaican rose) that have been most studied for their potential hypotensive effect.<a class="elsevierStyleCrossRefs" href="#bib1700">154–159</a> One review compared green tea and black tea and found that both reduced overall SBP and DBP by 2 and 1mmHg respectively, slightly more for green tea, suggesting that long-term tea intake (≥12 weeks) could contribute to a significant reduction in BP.<a class="elsevierStyleCrossRef" href="#bib1730">160</a>Finally, it has been reported in a Chinese population that prolonged tea consumption could reduce the risk of HTN by 10%,<a class="elsevierStyleCrossRef" href="#bib1735">161</a> and that higher tea consumption, especially green tea, was associated with a lower risk of ischaemic and haemorrhagic stroke.<a class="elsevierStyleCrossRef" href="#bib1740">162</a>In short, it is possible that tea consumption, especially in the long term, may contribute to a small decrease in BP levels. However, given the lack of homogeneous clinical trials with sufficient numbers of patients and in populations outside Asia and the Middle East, as well as the absence of reliable data on morbidity and mortality, this recommendation is of very low quality.Vitamin CVitamin C has been consistently associated with a decrease in BP. Several systematic reviews support this, with SBP/DBP decreases of approximately 4 and 2mmHg in both normotensive and hypertensive patients.<a class="elsevierStyleCrossRefs" href="#bib1745">163,164</a> However, short duration, heterogeneity, large differences in doses used, and lack of trials with clinical events limit their conclusions for the time being.<a class="elsevierStyleCrossRef" href="#bib1750">164</a>ZincSome studies have evaluated zinc intake with BP lowering in normotensive and hypertensive patients. One study linked zinc intake to lower SBP, but not DBP, although there was controversy regarding the doses used.<a class="elsevierStyleCrossRef" href="#bib1755">165</a> Further clinical trials using different doses of zinc at various durations are therefore required to confirm this finding.Finally, for other substances that have been evaluated for a possible hypotensive effect, either because of the heterogeneity of their composition or the paucity of studies, we did not consider a specific breakdown of them. These would include herbal supplements,<a class="elsevierStyleCrossRef" href="#bib1760">166</a> flax seeds,<a class="elsevierStyleCrossRef" href="#bib1765">167</a> quercetin,<a class="elsevierStyleCrossRef" href="#bib1770">168</a> and other Asian herbs such as angelica sinensis (red sage or dong quai), and salvia miltiorrhiza (Danshen).Synthesis of resultsThe evaluation of alternative medicines based on mind-body therapies has enabled us to confirm a small but positive benefit of some techniques, such as acupuncture, Tai Chi, meditation, or yoga, similar to that already reflected in other previous work.<a class="elsevierStyleCrossRefs" href="#bib0990">12–14,17,22,47</a> In contrast, others such as chiropractic have very limited evidence, and also present a negative risk–benefit balance on BP, by exerting pressure on affected joints.<a class="elsevierStyleCrossRef" href="#bib1080">30</a> We cannot report any benefits on BP levels for the other therapies we analysed.With regard to orally consumed biological substances, as detailed above, numerous products have shown apparent efficacy in reducing BP levels. However, in most cases, the magnitude has been small and the evidence weak or moderate, which may limit their application as adjunct therapy in the management of HTN. The beneficial effects of potassium followed by coffee, in that order, and hypotensive effects, with less evidence, of other substances such as cocoa, calcium, garlic, folic acid, artichoke, magnesium, beetroot, spirulina, milk peptides, and melatonin, should be highlighted. The results for the remaining substances are very limited, controversial, or negative.With regard to potassium, several clinical practice guidelines have made express recommendations to increase potassium intake, such as the Canadian recommendations<a class="elsevierStyleCrossRef" href="#bib1600">134</a> or the European guidelines,<a class="elsevierStyleCrossRef" href="#bib1775">169</a> with evidence A, similar to the recommendation for sodium restriction, which we endorse in this review. In general, whenever possible, this should be supplementation in the form of foods with high potassium content and to a lesser extent external prepared supplements (due to doubts regarding doses, preparation, excipients, and systematisation of the preparations generating concern).<a class="elsevierStyleCrossRef" href="#bib1780">170</a> Thus, the European recommendations<a class="elsevierStyleCrossRef" href="#bib1775">169</a> specify the need to increase potassium intake to 3500mg/day, preferably in the form of a Mediterranean or DASH diet rich in fruit and vegetables. A recent editorial in the journal Hypertension<a class="elsevierStyleCrossRef" href="#bib1785">171</a> encourages this substitution based on two studies of salt substitutes with potassium in rural China<a class="elsevierStyleCrossRefs" href="#bib1790">172,173</a> and a model of sodium substitution with potassium in table salt with very encouraging results. Although at the population level the cardiovascular and BP benefits may outweigh the risks associated with hyperkalaemia, in our view, we suggest that health authorities should place warning labels on these products for vulnerable individuals (people with chronic renal failure and those taking potassium-sparing diuretics or renin–angiotensin system blockers).With regard to coffee, although the recommendations in the clinical practice guidelines are not yet as explicit as with potassium,<a class="elsevierStyleCrossRefs" href="#bib1600">134,169</a> it is currently documented that, because there is a possible j-shaped curve, taking 3–4 cups of coffee per day could be permitted in patients who are already doing so<a class="elsevierStyleCrossRef" href="#bib1800">174</a> due to its corroborated positive effect on BP and other cardiovascular diseases (atrial fibrillation, diabetes, heart failure, etc.).<a class="elsevierStyleCrossRef" href="#bib1805">175</a><a class="elsevierStyleCrossRefs" href="#tbl0005">Tables 1 and 2</a> summarise the conclusions reached by the authors of this review on the efficacy and evidence for recommending this CAM, showing differences according to the therapy chosen.<elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0010"></elsevierMultimedia>Limitations and perspectivesWe found numerous limitations in the studies and reviews that limit their external validity: great heterogeneity of the reviews, poorly defined doses of substances, small number of patients, very short follow-up time, lack of adequate methods to control bias (randomisation, confounding, etc.). The current paucity of clinical trial evidence demonstrating that the typically modest BP reduction associated with these approaches translates into a reduction in hard cardiovascular events is a major shortcoming. However, we must accept that at present it is unlikely that event-based trials will be conducted because of the prohibitive sample size required to demonstrate a benefit with small reductions in BP in relatively healthy individuals with mild hypertension, let alone in the non-hypertensive population.<a class="elsevierStyleCrossRef" href="#bib1835">178</a> In the absence of such trials, we would have to base our deliberations on the surrogacy of intermediate targets, such as BP reduction “per se”, bearing in mind that even small reductions in BP at the population level can translate into substantial public health benefits.<a class="elsevierStyleCrossRef" href="#bib1840">179</a> Therefore, we believe that the risk–benefit ratio may support some reasonable recommendations for individuals to use these alternative, or complementary, approaches, provided they are used in appropriate circumstances and under the guidance of a reputable healthcare provider, and should in no way replace the reasoned, conventional use of drugs when they are indicated.We were able to document at least two other previous reviews<a class="elsevierStyleCrossRefs" href="#bib1820">180,181</a> that made a critical appraisal of the evidence with the aim of describing the most commonly used therapeutic modalities and reviewing the current level of evidence attributable to each modality, with some divergences between them.Patients, for the reasons described above, are increasingly using alternative non-pharmacological therapies, which are often unregulated. In addition, the information available on networks and in cyberspace is often poor. Thus, in a study carried out in Australia, Canada, the USA, and the UK, 90 pages and 40 websites were evaluated using the DISCERN score, with disparate and not always appropriate results on the risks of treatment and the impact on quality of life.<a class="elsevierStyleCrossRef" href="#bib1850">182</a> Therefore, we believe it is essential to ask our patients explicitly about the searches they make, the reason they do so, and to guide them in identifying high quality resources on the web on the problem to be solved.In 2020, the Spanish Foundation for Science and Technology (FECYT) conducted a qualitative study in Spain on the use of and confidence in therapies without scientific evidence, including homoeopathy, acupuncture, phytotherapy, reiki, and Bach flowers, with the aim of better understanding the perspectives of the users of these treatments.<a class="elsevierStyleCrossRef" href="#bib1855">183</a> This study describes that the users of these pseudo-therapies think that current medicine is corrupted by the interests of big pharma and has become excessively technical, industrialised (chemical), and detached from human needs, and, although the majority of users continue to trust traditional medicine (especially in cases of serious illnesses), they remain hesitant and highly critical towards it. Therefore, the most common access route to alternative medicine is corroborated to be “word of mouth” (work colleagues, friends, family network, etc.) followed by specialised books and the Internet.The limitations of our review are that it is a narrative review with no pretensions of being systematic and, therefore, there is no table to provide levels of evidence. However, the non-pharmacological therapies that have supposedly been studied are considerable in number. As early as 2011, a first official document on alternative therapies was drawn up in Spain (<a href="https://www.sanidad.gob.es/novedades/docs/analisisSituacionTNatu.pdf">https://www.sanidad.gob.es/novedades/docs/analisisSituacionTNatu.pdf</a>), to ascertain their impact and use, documenting up to 139 techniques, recognising that at that time there was no global regulation on natural therapies in any Western country. Of these, 73 lacked a randomised clinical trial and were considered pseudo-therapies. It is therefore necessary to sound a warning bell against the growing indiscriminate use of “pseudotherapies” without any scientific basis and which are not sufficiently accredited (if not discredited) by official bodies. In this regard, in 2018 the Ministry of Health and Consumer Affairs drew up a “Plan for protection against pseudotherapies” <a href="https://www.sanidad.gob.es/gabinetePrensa/notaPrensa/pdf/20181141118135247771.pdf">https://www.sanidad.gob.es/gabinetePrensa/notaPrensa/pdf/20181141118135247771.pdf</a>), the principles of which are the evaluation of pseudotherapies based on the most up-to-date and robust scientific knowledge and evidence, dissemination and transparency of information, and ensuring regulatory compliance. Since then, the #CoNprueba portal has been created to inform and raise awareness about pseudotherapies and pseudosciences and to contribute to the dissemination of science and critical thinking.A third limitation of the results would be that they may be subject to multiple confounding factors and, specifically in this field, many of the techniques and complementary measures analysed may be being used by people who already follow healthy lifestyle patterns (vegetarian diets, physical exercise)<a class="elsevierStyleCrossRefs" href="#bib1860">184–186</a> and, therefore, would not extend to the rest of the population.A final consideration is that our review was based on decreases in BP produced by CAM, and we only flag up other beneficial effects for some CAM; at the vascular level (vasodilatation, activation of nitric oxide, improvement of endothelium, etc.), metabolic (insulin resistance, lipid parameters, glycaemia, etc.), and somatometric parameters (adiposity, weight, waist circumference, etc.), the potential of all of which could increase in the prevention of cardiovascular and cerebrovascular diseases.Conclusions<ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0015">•After this review, the multiple alternative practices and therapies are very difficult to assess and require further wider studies.</li><li class="elsevierStyleListItem" id="lsti0020">•There is a lack of clear and forceful legislation on the use of these therapies and their potential marketing, which should be regulated.</li><li class="elsevierStyleListItem" id="lsti0025">•We recommend increasing potassium intake and gradually replacing sea salt, preferably in the form of potassium-rich foods, although the use of potassium salt supplements is widely available and could be recommended, subject to warnings and limitations in vulnerable individuals.</li><li class="elsevierStyleListItem" id="lsti0030">•Moderate coffee consumption (3–4cups/day) is advisable in patients who already drink coffee.</li><li class="elsevierStyleListItem" id="lsti0035">•Mind-body therapies based on meditation and safe exercise provide a reasonable basis for discreetly reducing blood pressure and the stress levels of everyday life.</li><li class="elsevierStyleListItem" id="lsti0040">•There are few CAMs that are worthwhile in practice (yes in research), but these are associated with “bad science, but good medicine” (complementary), i.e., with little evidential support but some utility, especially as part of healthy lifestyles and beliefs, which are more personal than collective.</li><li class="elsevierStyleListItem" id="lsti0045">•Major limitations are detected in most of the studies analysed and subsequent systematic reviews/meta-analyses concerning their methodology (duration, sample, randomisation, confounding factors) and their external validity, which remain considerable shortcomings that limit their results.</li><li class="elsevierStyleListItem" id="lsti0050">•Therefore, the results of this review suggest that certain non-conventional therapies could be slightly effective in treating hypertension and improving cardiac, cerebral, and vascular function in general, and could form part of non-pharmacological measures as adjunct treatment in future guidelines for the management of hypertension, but never replacing pharmacological treatments. However, the heterogeneity of the studies and the multiple biases in them preclude any other level of recommendation at the present time.</li></ul>FundingThis work was partially supported by Fondo de Investigación Sanitaria (FIS)22/1164 (Instituto de Salud Carlos III and FEDER/FSE).Conflict of interestThe authors have no conflict of interests to declare." "textoCompletoSecciones" => array:1 [ "secciones" => array:15 [ 0 => array:3 [ "identificador" => "xres2110301" "titulo" => "Abstract" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Objective" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Search strategy" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Selection of studies" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Synthesis of results" ] 4 => array:2 [ "identificador" => "abst0025" "titulo" => "Conclusions" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1797744" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres2110300" "titulo" => "Resumen" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "abst0030" "titulo" => "Objetivo" ] 1 => array:2 [ "identificador" => "abst0035" "titulo" => "Estrategia de búsqueda" ] 2 => array:2 [ "identificador" => "abst0040" "titulo" => "Selección de estudios" ] 3 => array:2 [ "identificador" => "abst0045" "titulo" => "Síntesis de resultados" ] 4 => array:2 [ "identificador" => "abst0050" "titulo" => "Conclusiones" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1797743" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Objective and search strategy" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Selection of studies" ] 7 => array:3 [ "identificador" => "sec0020" "titulo" => "Non-biological therapies" "secciones" => array:8 [ 0 => array:2 [ "identificador" => "sec0025" "titulo" => "Acupuncture and hypertension" ] 1 => array:2 [ "identificador" => "sec0030" "titulo" => "Yoga and hypertension" ] 2 => array:2 [ "identificador" => "sec0035" "titulo" => "Meditation, mindfulness, and hypertension" ] 3 => array:2 [ "identificador" => "sec0040" "titulo" => "Qigong and hypertension" ] 4 => array:2 [ "identificador" => "sec0045" "titulo" => "Chiropractic care and hypertension" ] 5 => array:2 [ "identificador" => "sec0050" "titulo" => "Osteopathy and arterial hypertension" ] 6 => array:2 [ "identificador" => "sec0055" "titulo" => "Tai Chi and hypertension" ] 7 => array:2 [ "identificador" => "sec0060" "titulo" => "Music therapy and hypertension" ] ] ] 8 => array:3 [ "identificador" => "sec0065" "titulo" => "Biological therapies" "secciones" => array:24 [ 0 => array:2 [ "identificador" => "sec0070" "titulo" => "Fatty acids" ] 1 => array:2 [ "identificador" => "sec0075" "titulo" => "Folic acid" ] 2 => array:2 [ "identificador" => "sec0080" "titulo" => "Garlic" ] 3 => array:2 [ "identificador" => "sec0085" "titulo" => "Artichoke" ] 4 => array:2 [ "identificador" => "sec0090" "titulo" => "Oats" ] 5 => array:2 [ "identificador" => "sec0095" "titulo" => "Berberine" ] 6 => array:2 [ "identificador" => "sec0100" "titulo" => "Cocoa (and dark chocolate)" ] 7 => array:2 [ "identificador" => "sec0105" "titulo" => "Coffee" ] 8 => array:2 [ "identificador" => "sec0110" "titulo" => "Calcium and vitamin D" ] 9 => array:2 [ "identificador" => "sec0115" "titulo" => "Cinnamon" ] 10 => array:2 [ "identificador" => "sec0120" "titulo" => "Coenzyme Q10" ] 11 => array:2 [ "identificador" => "sec0125" "titulo" => "Turmeric" ] 12 => array:2 [ "identificador" => "sec0130" "titulo" => "Spirulina (Arthrospira platensis)" ] 13 => array:2 [ "identificador" => "sec0135" "titulo" => "Viscous soluble fibre" ] 14 => array:2 [ "identificador" => "sec0140" "titulo" => "l-Arginine" ] 15 => array:2 [ "identificador" => "sec0145" "titulo" => "Magnesium" ] 16 => array:2 [ "identificador" => "sec0150" "titulo" => "Melatonin" ] 17 => array:2 [ "identificador" => "sec0155" "titulo" => "Milk peptides and probiotics" ] 18 => array:2 [ "identificador" => "sec0160" "titulo" => "Potassium" ] 19 => array:2 [ "identificador" => "sec0165" "titulo" => "Beetroot" ] 20 => array:2 [ "identificador" => "sec0170" "titulo" => "Salicornia" ] 21 => array:2 [ "identificador" => "sec0175" "titulo" => "Tea" ] 22 => array:2 [ "identificador" => "sec0180" "titulo" => "Vitamin C" ] 23 => array:2 [ "identificador" => "sec0185" "titulo" => "Zinc" ] ] ] 9 => array:3 [ "identificador" => "sec0190" "titulo" => "Synthesis of results" "secciones" => array:1 [ 0 => array:2 [ "identificador" => "sec0195" "titulo" => "Limitations and perspectives" ] ] ] 10 => array:2 [ "identificador" => "sec0200" "titulo" => "Conclusions" ] 11 => array:2 [ "identificador" => "sec0205" "titulo" => "Funding" ] 12 => array:2 [ "identificador" => "sec0210" "titulo" => "Conflict of interest" ] 13 => array:2 [ "identificador" => "xack735001" "titulo" => "Acknowledgements" ] 14 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2023-11-08" "fechaAceptado" => "2023-11-10" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1797744" "palabras" => array:3 [ 0 => "Alternative" 1 => "Therapies" 2 => "Hypertension" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1797743" "palabras" => array:3 [ 0 => "Alternativas" 1 => "Terapias" 2 => "Hipertensión" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "ObjectiveReview of some of the best-known biological and non-biological complementary/alternative therapies/medicines (CAM) and their relationship with blood pressure (BP) and hypertension (HT). Search strategyNarrative review assessing a recent series of systematic reviews, meta-analyses, and clinical trials published in recent years, focusing on the effects of CAM on BP and HT. Selection of studiesWe searched EMBASE, MEDLINE, Cochrane Library and Google Scholar, obtaining a total of 4336 articles, finally limiting the search to 181 after applying filters. Synthesis of resultsSome studies on biological therapies show some usefulness in BP reduction with an adequate benefit–risk balance, although there is a scarcity of high-quality trials that support these results. Some mind-body therapies have shown hypothetical benefit; in contrast, others lack robust evidence. ConclusionsAlthough some therapies present a reasonable risk–benefit ratio, they should in no case replace pharmacological treatment when indicated." "secciones" => array:5 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Objective" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Search strategy" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Selection of studies" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Synthesis of results" ] 4 => array:2 [ "identificador" => "abst0025" "titulo" => "Conclusions" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "ObjetivoRevisar algunas de las más conocidas terapias/medicinas biológicas y no biológicas complementarias/alternativas (MCA), y su relación con la presión arterial (PA) e hipertensión arterial (HTA). Estrategia de búsquedaRevisión narrativa en la que se valoraron una serie reciente de revisiones sistemáticas, metaanálisis y ensayos clínicos publicados en los últimos años, centrada en los efectos de la MCA sobre la PA y HTA. Selección de estudiosSe realizaron búsquedas en EMBASE, MEDLINE, Cochrane Library y Google Scholar, obteniéndose un total de 4.336 artículos, limitándose finalmente a 181 tras aplicar filtros. Síntesis de resultadosAlgunos trabajos sobre terapias biológicas parecen demostrar cierta utilidad en reducción de la PA con adecuado balance beneficio/riesgo, aunque existe escasez de ensayos de alta calidad que avalen estos resultados. Algunas terapias cuerpo/mente han mostrado un hipotético beneficio; en cambio, otras carecen de evidencia robusta. ConclusionesAunque algunas terapias presentan una relación riesgo/beneficio razonable, no deberían sustituir en ningún caso al tratamiento farmacológico cuando este esté indicado." "secciones" => array:5 [ 0 => array:2 [ "identificador" => "abst0030" "titulo" => "Objetivo" ] 1 => array:2 [ "identificador" => "abst0035" "titulo" => "Estrategia de búsqueda" ] 2 => array:2 [ "identificador" => "abst0040" "titulo" => "Selección de estudios" ] 3 => array:2 [ "identificador" => "abst0045" "titulo" => "Síntesis de resultados" ] 4 => array:2 [ "identificador" => "abst0050" "titulo" => "Conclusiones" ] ] ] ] "multimedia" => array:4 [ 0 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "We used Ernst's assessment criteria (Ernst E. Alternative Medicine. A Critical Assessment of 202 Modalities. Second Edition. Springer, 2022), plus quality of evidence, but judged assessment based on our revision of the scientific literature. Plausibility: assumptions of the measures are consistent with established knowledge of the human body. Efficacy: performance according to the available scientific evidence and its quality. Safety: production of harm. Cost: estimation of associated expenditure. Risk–benefit balance: combination of efficacy and safety. With the sign “-” we want to indicate lack of sufficient evidence to judge; if efficacy is negative or debated, the risk–benefit balance and the benefits to blood pressure do not merit assessment, and in any case, would be “negative” at present. The cost may be high if the measure is assisted and continued.Prepared using references cited in the text, especially Mancia et al.,<a class="elsevierStyleCrossRef" href="#bib1775">169</a> Jones et al.,<a class="elsevierStyleCrossRef" href="#bib1785">171</a> and Wolf and Bisognano.<a class="elsevierStyleCrossRef" href="#bib1825">176</a>" "tablatextoimagen" => array:2 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><elsevierMultimedia ident="202403190601350261"></elsevierMultimedia> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab3490045.png" ] ] 1 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Plausibilidad biológicaCalidad/cantidad evidenciaEficaciaSeguridadCosteBalance riesgo-beneficioBeneficios en PA/HTAOtros efectos beneficiosos \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Biological plausibilityQuality/quantity of evidenceEfficacySafetyCostRisk–benefit balanceBenefits to BP/HTAOther beneficial effects \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">AcupunturaManipulación espinal/quiroprácticaMindfulness, meditación, quigongMúsicoterapiaTai ChiYoga \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">AcupunctureSpinal manipulation/chiropracticMindfulness, meditation, qigongMusic therapyTai ChiYoga \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; 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entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">BajoAlto \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">LowHigh \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Bueno \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Good \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Dolor crónico, estrésDolor espalda y cuelloMental, depresión, cardiovascularEstrés, depresiónOsteoporosis, caídas, cardiovascularDepresión, estrés, lípidos \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Chronic pain, stressBack and neck painMental, depression, cardiovascularStress, depressionOsteoporosis, falls, cardiovascularDepression, stress, lipids \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab3490046.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Assessment of selected non-biological alternative measures relating to blood pressure and hypertension." ] ] 1 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at2" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "The scientific evidence supporting each measure, its efficacy and potency in lowering blood pressure considers the number and quality of studies reviewed. 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"etiqueta" => "186" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ …2] ] "host" => array:1 [ 0 => array:2 [ …2] ] ] ] ] ] ] ] ] "agradecimientos" => array:1 [ 0 => array:4 [ "identificador" => "xack735001" "titulo" => "Acknowledgements" "texto" => "We would like to thank Javier Muñoz-Laguna (Universidad of Zurich and Autonomous University of Madrid) for advice on chiropractic care.And Joan Montaner Villalonga, neurologist and Head of the Andalusian stroke plan. Hospital Virgen Macarena, Seville, for his advice on salicornia." "vista" => "all" ] ] ] "idiomaDefecto" => "en" "url" => "/18891837/0000004100000001/v1_202403190601/S188918372300065X/v1_202403190601/en/main.assets" "Apartado" => array:4 [ "identificador" => "9111" "tipo" => "SECCION" "es" => array:2 [ "titulo" => "Revisión" "idiomaDefecto" => true ] "idiomaDefecto" => "es" ] "PDF" => "https://static.elsevier.es/multimedia/18891837/0000004100000001/v1_202403190601/S188918372300065X/v1_202403190601/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S188918372300065X?idApp=UINPBA00004N"]

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Evidence on the use of alternative substances and therapies in hypertension

Evidencias sobre el uso de sustancias y terapias alternativas en hipertensión

E. Martín-Riobóoa,

Corresponding author

martinriobooenrique@gmail.com

Corresponding author.

, M. Turégano-Yedrob, J.R. Banegasc

a Especialista en Medicina Familiar y Comunitaria, UGC Poniente, Distrito Sanitario Córdoba-Guadalquivir, Córdoba, IMIBIC, Hospital Reina Sofía Córdoba, Spain

b Especialista en Medicina Familiar y Comunitaria, Centro de Salud Casar de Cáceres, Cáceres, Spain

c Especialista en Medicina Preventiva y Salud Pública, Departamento de Medicina Preventiva y Salud Pública, Facultad de Medicina, Universidad Autónoma de Madrid/IdiPaz y CIBERESP, Madrid, Spain

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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Complementary and alternative medicine &#40;CAM&#41; is defined as practices&#44; products&#44; substances&#44; or healthcare systems that that do not conform to the standards of mainstream medicine&#46;<a class="elsevierStyleCrossRef" href="#bib0935"><span class="elsevierStyleSup">1</span></a> They are commonly used around the world by diverse populations and ethnicities&#44; but they remain largely unregulated&#46; Patients give varied reasons for using CAM&#46; A systematic review of 231 studies found that the three main reasons were&#58; expectations of benefits&#44; dissatisfaction with conventional medicine&#44; and the perception that CAM is completely safe&#46;<a class="elsevierStyleCrossRef" href="#bib0940"><span class="elsevierStyleSup">2</span></a> Geographic&#44; socio-demographic&#44; economic&#44; and cultural connotations have also been described&#46; While in African countries&#44; considerations such as the easy accessibility of these therapies&#44; the high economic cost of conventional medicine&#44; and the history of traditions and beliefs are noteworthy&#44;<a class="elsevierStyleCrossRef" href="#bib0940"><span class="elsevierStyleSup">2</span></a> in Europe it has been documented that the use of CAM is higher in women&#44; with higher socio-economic levels and more severe disease&#46;<a class="elsevierStyleCrossRefs" href="#bib0945"><span class="elsevierStyleSup">3&#44;4</span></a> In the United States &#40;US&#41;&#44; it is used more frequently by Caucasians than Black people&#44; and by patients who perceive the quality of their medical care as poor&#46;<a class="elsevierStyleCrossRef" href="#bib0955"><span class="elsevierStyleSup">5</span></a> However&#44; CAM forms part of the cultural and religious heritage of certain Asian countries &#40;traditional Chinese medicine&#44; Ayurvedic medicine&#44; traditional Chinese herbs&#41; or of specific practices of certain racial groups&#46;<a class="elsevierStyleCrossRef" href="#bib0960"><span class="elsevierStyleSup">6</span></a> In fact&#44; the World Health Organisation &#40;WHO&#41; reminds us that certain countries in this geographical area&#44; such as China and South Korea&#44; partially finance CAM through their health systems&#46;<a class="elsevierStyleCrossRef" href="#bib0965"><span class="elsevierStyleSup">7</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">In general&#44; these therapies are increasingly widely used&#46; A review of surveys in 21 countries found that 21&#8211;74&#37; of the surveyed population had used CAM in the past 12 months&#46;<a class="elsevierStyleCrossRef" href="#bib0970"><span class="elsevierStyleSup">8</span></a> Other studies in the US population found that more than 50&#37; had used a vitamin or mineral complex&#44; and patients with chronic diseases were more likely to use these supplements&#46;<a class="elsevierStyleCrossRef" href="#bib0975"><span class="elsevierStyleSup">9</span></a> In Europe&#44; a review found that 25&#46;9&#37; of the general population had used CAM in the last 12 months&#44; although this varied greatly from country to country&#44; from 10&#37; in Hungary to almost 40&#37; in Germany&#46;<a class="elsevierStyleCrossRef" href="#bib0950"><span class="elsevierStyleSup">4</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">It is recognised that healthcare system users rarely inform their healthcare team about the use of supplements or other alternative therapies despite potential drug-drug interactions or significant health harms&#46;<a class="elsevierStyleCrossRef" href="#bib0935"><span class="elsevierStyleSup">1</span></a> These misconceptions regarding their purported efficacy have largely driven the popularity of these products&#44; while adverse effects have been grossly underestimated and silenced&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Objective and search strategy</span><p id="par0020" class="elsevierStylePara elsevierViewall">In this narrative review we will consider two sources of data&#44; primarily focussing on the effects on blood pressure &#40;BP&#41; and hypertension &#40;HTN&#41;&#46; On the one hand&#44; published systematic reviews and meta-analyses &#40;general reviews on CAM and systematic reviews of individual therapies&#41; and&#44; on the other&#44; the most recent clinical trials &#40;mainly within the last 10 years&#41; in the field of CAM&#46; The authors have independently selected the aspects considered most relevant by consensus&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Selection of studies</span><p id="par0025" class="elsevierStylePara elsevierViewall">For the review we undertook a search in EMBASE&#44; MEDLINE&#44; the Cochrane Library&#44; and Google Scholar&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">A total of 4336 articles were obtained with the keywords Alternative&#44; Therapies&#44; Hypertension&#46; After applying filters for Meta-Analysis&#44; Clinical Trials&#44; Systematic Review&#44; and Randomised controlled trial&#44; we were limited to 908 searches&#44; of which 181 were finally reviewed for the document&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">We chose to divide CAM therapies into two sections&#58;<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">1&#46;</span><p id="par0040" class="elsevierStylePara elsevierViewall">Alternative medicines based on non-biological or mind-body therapies&#44; such as&#44; acupuncture&#44; yoga&#44; meditation&#44; mindfulness&#44; qigong&#44; chiropractic&#44; osteopathy&#44; Tai Chi&#44; music therapy&#44; etc&#46;</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">2&#46;</span><p id="par0045" class="elsevierStylePara elsevierViewall">Biologically based practices including botanicals&#44; animal extracts&#44; vitamins&#44; minerals&#44; fatty acids&#44; amino acids&#44; proteins&#44; prebiotics&#44; etc&#46;</p></li></ul></p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Non-biological therapies</span><p id="par0050" class="elsevierStylePara elsevierViewall">In this section we will review body-based therapies&#44; mind-body therapies&#44; and other alternatives unrelated to substance intake or restriction&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">There are a multitude of techniques that could be divided into&#58; body-based therapies &#40;chiropractic or osteopathic manipulation&#44; massage&#44; acupuncture&#44; and movement therapy&#41;&#59; mind-body techniques &#40;yoga&#44; meditation&#44; Tai-Chi&#44; qigong&#44; mindfulness&#44; energy healing therapy&#44; transcendental meditation&#44; hypnosis&#44; and biofeedback&#41;&#59; other therapies and alternative medicines to Western medicine &#40;Ayurvedic medicine&#44; chelation therapy&#44; craniosacral therapy&#44; homoeopathy&#44; naturopathy&#44; and traditional healing&#41;&#46; Of these&#44; we highlight the following&#44; as they are the most studied&#58;</p><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Acupuncture and hypertension</span><p id="par0060" class="elsevierStylePara elsevierViewall">Acupuncture is a traditional Chinese form of alternative medicine that is gaining attention in our country and in the rest of the world&#46; Although its popularity is progressively increasing&#44; little is still known about this therapy and its potential beneficial effects on chronic disease risk factors&#44; such as hypertension&#46;<a class="elsevierStyleCrossRef" href="#bib0980"><span class="elsevierStyleSup">10</span></a> There is no evidence available currently to demonstrate the sustained effect of acupuncture on reducing BP&#44; as the available evidence does not show a clear effect&#44; and its quality is low&#44; with considerable biases&#46;<a class="elsevierStyleCrossRefs" href="#bib0985"><span class="elsevierStyleSup">11&#44;12</span></a> Several systematic reviews have concluded that acupuncture significantly reduced systolic BP &#40;SBP&#41; and diastolic BP &#40;DBP&#41;&#44; although in populations and methods that are widely heterogeneous between studies&#46;<a class="elsevierStyleCrossRefs" href="#bib0990"><span class="elsevierStyleSup">12&#44;13</span></a> In Spain&#44; another study showed that acupuncture was effective in reducing BP levels in patients already receiving pharmacological therapy&#44; with the reduction occurring in the first 3 weeks and being maintained until at least week 8&#46;<a class="elsevierStyleCrossRef" href="#bib1000"><span class="elsevierStyleSup">14</span></a> Therefore&#44; robust studies are needed to determine the efficacy and safety of acupuncture in the treatment of HTN and to provide a useful scientific basis for clinical decision-making&#46;<a class="elsevierStyleCrossRef" href="#bib1005"><span class="elsevierStyleSup">15</span></a></p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Yoga and hypertension</span><p id="par0065" class="elsevierStylePara elsevierViewall">Yoga is a traditional Indian practice that has been adapted for use as a CAM&#46; It mainly involves physical poses&#44; breathing techniques&#44; and meditation&#46;<a class="elsevierStyleCrossRef" href="#bib1010"><span class="elsevierStyleSup">16</span></a> Yoga seems to exert its antihypertensive effect mainly through its breathing and meditation techniques and less through the postures&#46;<a class="elsevierStyleCrossRef" href="#bib1015"><span class="elsevierStyleSup">17</span></a> These practices appear to increase parasympathetic activity and decrease sympathetic activity&#44; possibly by increasing gamma-aminobutyric acid &#40;GABA&#41; activity&#44; thus counteracting the overactivity of the sympathetic nervous system that is associated with HTN&#46;<a class="elsevierStyleCrossRef" href="#bib1010"><span class="elsevierStyleSup">16</span></a></p><p id="par0070" class="elsevierStylePara elsevierViewall">A systematic review and meta-analysis of the use of yoga in HTN found emerging&#44; but very low quality&#44; evidence that yoga may be a useful tool and adjunct treatment in the management of HTN&#46; The impact of yoga can reduce SBP by 10<span class="elsevierStyleHsp" style=""></span>mmHg and DBP by 8<span class="elsevierStyleHsp" style=""></span>mmHg&#46;<a class="elsevierStyleCrossRef" href="#bib1015"><span class="elsevierStyleSup">17</span></a> However&#44; these positive effects disappeared when the effects of antihypertensive drugs were introduced&#46; Although most studies have shown that yoga effectively reduces BP in the hypertensive population&#44; and for some authors it should be proposed as a complementary therapy to be included in clinical guidelines&#44;<a class="elsevierStyleCrossRef" href="#bib1020"><span class="elsevierStyleSup">18</span></a> the heterogeneity of yoga practices and poses and the quality of some research make it difficult to systematically recommend any specific yoga practice for hypertensive patients&#46; In addition to yoga&#39;s efficacy on blood pressure control&#44; some studies have shown benefits on lipid profile&#46;<a class="elsevierStyleCrossRef" href="#bib1025"><span class="elsevierStyleSup">19</span></a></p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Meditation&#44; mindfulness&#44; and hypertension</span><p id="par0075" class="elsevierStylePara elsevierViewall">Several neurophysiological and neuroanatomical studies have shown that meditation can have long-lasting effects at the brain level&#44; with beneficial consequences on baseline physiological state and cardiovascular risk&#44; as well as other benefits such as lowering BP&#44; and reducing insulin resistance or metabolic syndrome&#46;<a class="elsevierStyleCrossRef" href="#bib1030"><span class="elsevierStyleSup">20</span></a></p><p id="par0080" class="elsevierStylePara elsevierViewall">Additional benefits of meditation in hypertension have been documented&#46;<a class="elsevierStyleCrossRefs" href="#bib1030"><span class="elsevierStyleSup">20&#8211;22</span></a> Thus&#44; its implementation may be an attractive and cost-effective adjunct to currently known medical therapies&#46;<a class="elsevierStyleCrossRef" href="#bib1030"><span class="elsevierStyleSup">20</span></a> An 8-week randomised trial with ambulatory BP monitoring &#40;ABPM&#41; demonstrated the benefits of meditation &#40;in the mindfulness modality&#41; on BP control and on levels of stress&#44; anxiety&#44; and depression in a Mediterranean population&#46;<a class="elsevierStyleCrossRef" href="#bib1035"><span class="elsevierStyleSup">21</span></a> Another study&#44; which conducted a systematic review and meta-analysis on the effectiveness of mindfulness-based stress reduction programmes for HTN&#44; showed significant improvements in patients with HTN or prehypertension&#44;<a class="elsevierStyleCrossRef" href="#bib1040"><span class="elsevierStyleSup">22</span></a> above all reducing SBP&#46;<a class="elsevierStyleCrossRef" href="#bib1045"><span class="elsevierStyleSup">23</span></a> Therefore&#44; some reviews have considered that in addition to aerobic exercise&#44; isometric training&#44; use of low-sodium and high-potassium salt&#44; comprehensive lifestyle changes&#44; and low-calorie diet&#44; meditation&#44; mindfulness&#44; and breath control should be useful alternative therapies to consider in patients with HTN&#46;<a class="elsevierStyleCrossRef" href="#bib1045"><span class="elsevierStyleSup">23</span></a></p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Qigong and hypertension</span><p id="par0085" class="elsevierStylePara elsevierViewall">Qigong is a traditional fitness method that originated in ancient China and focuses on body movement&#44; mind guidance&#44; and breath control to achieve physical and mental well-being adjustment through a combination of these&#46;<a class="elsevierStyleCrossRef" href="#bib1050"><span class="elsevierStyleSup">24</span></a> It also helps to lower BP levels&#44; control complications&#44; and reduce mortality&#46;<a class="elsevierStyleCrossRef" href="#bib1055"><span class="elsevierStyleSup">25</span></a> Several meta-analyses and systematic reviews have highlighted<a class="elsevierStyleCrossRefs" href="#bib1050"><span class="elsevierStyleSup">24&#8211;26</span></a> that compared to no intervention&#44; qigong significantly reduces SBP and DBP&#44; and the combination of Qigong and antihypertensive drugs are more effective than antihypertensive drugs alone&#44;<a class="elsevierStyleCrossRef" href="#bib1060"><span class="elsevierStyleSup">26</span></a> a combination that may also reduce stroke incidence&#44; mortality&#44; and the dose of antihypertensive drugs&#46;<a class="elsevierStyleCrossRef" href="#bib1065"><span class="elsevierStyleSup">27</span></a></p><p id="par0090" class="elsevierStylePara elsevierViewall">Qigong has also been shown to be useful in combination with another traditional Chinese wellness technique&#44; such as Tai Chi&#46; A meta-analysis evaluated mixed Tai Chi and qigong therapy on BP&#44; concluding that it could be an effective complementary and alternative therapy in the control of HTN&#44; alone or in combination with antihypertensive drugs&#46;<a class="elsevierStyleCrossRef" href="#bib1070"><span class="elsevierStyleSup">28</span></a> This reduction in BP may be related to increased nitric oxide levels and decreased endothelin-1 levels&#46;<a class="elsevierStyleCrossRef" href="#bib1070"><span class="elsevierStyleSup">28</span></a> The limitations of the studies are that almost all of them were conducted exclusively in Asian populations&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Chiropractic care and hypertension</span><p id="par0095" class="elsevierStylePara elsevierViewall">Chiropractic care is often associated with frequent use of high velocity&#44; low amplitude spinal manipulation&#47;manual impulses directed at segments of the spine with the goal of restoring motion and function&#46;<a class="elsevierStyleCrossRef" href="#bib1075"><span class="elsevierStyleSup">29</span></a> While spinal manipulation is often applied to intentionally targeted areas of the spine&#44; the clinical relevance of such practice is unclear&#46;<a class="elsevierStyleCrossRef" href="#bib1080"><span class="elsevierStyleSup">30</span></a> Several neurophysiological pathways have been proposed to explain the mechanisms of action of spinal manipulation in musculoskeletal disorders&#44;<a class="elsevierStyleCrossRef" href="#bib1085"><span class="elsevierStyleSup">31</span></a> including its potential effect on the autonomic nervous system&#46; The autonomic nervous system is a central component in blood pressure regulation&#44; and some studies have suggested that 20&#8211;30&#37; of hypertensives resistant to conventional pharmacological treatment may benefit from alternative therapies such as spinal manipulation&#46;<a class="elsevierStyleCrossRef" href="#bib1090"><span class="elsevierStyleSup">32</span></a> However&#44; several systematic reviews agree on the lack of evidence to support the use of spinal manipulation for HTN and other non-musculoskeletal disorders&#44;<a class="elsevierStyleCrossRefs" href="#bib1090"><span class="elsevierStyleSup">32&#44;34&#44;35</span></a> including a recent landmark analysis &#40;&#8220;global summit&#8221;&#41; in the academic chiropractic community&#46;<a class="elsevierStyleCrossRef" href="#bib1095"><span class="elsevierStyleSup">33</span></a> Furthermore&#44; given the lack of systematicity in data regarding adverse effects related to spinal manipulation in hypertensive patients&#44; possible contraindications&#44; including severe hypotension and stroke&#44; cannot be ruled out&#46;<a class="elsevierStyleCrossRefs" href="#bib1090"><span class="elsevierStyleSup">32&#44;34&#44;37&#44;38</span></a></p><p id="par0100" class="elsevierStylePara elsevierViewall">Based on the body of evidence&#44; the use of spinal manipulation in hypertension treatment protocols&#44; as well as in other non-musculoskeletal disorders&#44; is hardly justifiable&#44; although these protocols should consider contextual elements and patient preferences&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">Bakris et al&#46;<a class="elsevierStyleCrossRef" href="#bib1110"><span class="elsevierStyleSup">36</span></a> proved in grade I hypertensives without antihypertensive treatment that restoration of atlas vertebra misalignment was associated with marked and sustained reductions in BP comparable to the use of two-drug combination therapy&#46; However&#44; other papers conclude that there is a lack of evidence for spinal manipulation as an additional therapy in HT&#46;<a class="elsevierStyleCrossRef" href="#bib1100"><span class="elsevierStyleSup">34</span></a> Therefore&#44; more research is needed on the potential short-&#44; medium-&#44; and long-term benefits of this technique&#44; taking the potential adverse effects of these practices into account&#44; especially in non-professional hands&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Osteopathy and arterial hypertension</span><p id="par0110" class="elsevierStylePara elsevierViewall">Osteopathy is a philosophy of medicine that uses manual techniques to treat and alleviate discomfort through the restoration of organic balance&#46;<a class="elsevierStyleCrossRef" href="#bib1125"><span class="elsevierStyleSup">39</span></a> Although it has been used in the management of medical pathologies&#44; its use in hypertension is uncertain&#46; One study showed that&#44; in patients with cardiovascular disorders&#44; osteopathic treatment after one year was significantly associated with improved SBP&#46;<a class="elsevierStyleCrossRef" href="#bib1130"><span class="elsevierStyleSup">40</span></a> In contrast&#44; other reviews<a class="elsevierStyleCrossRef" href="#bib1135"><span class="elsevierStyleSup">41</span></a> did not find a positive relationship between the practice and a decrease in BP&#46; Therefore&#44; larger&#44; and more consistent studies are needed to support its use in hypertension&#46;<a class="elsevierStyleCrossRef" href="#bib1140"><span class="elsevierStyleSup">42</span></a></p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Tai Chi and hypertension</span><p id="par0115" class="elsevierStylePara elsevierViewall">Tai Chi&#44; one of the most widely used traditional Chinese arts&#44; helps to relax both body and mind&#44; and has been shown to relax blood vessels&#44; lower BP&#44;<a class="elsevierStyleCrossRef" href="#bib1145"><span class="elsevierStyleSup">43</span></a> and improve quality of life&#46;<a class="elsevierStyleCrossRef" href="#bib1150"><span class="elsevierStyleSup">44</span></a></p><p id="par0120" class="elsevierStylePara elsevierViewall">Several systematic reviews indicate its benefit in preventing falls&#44; improving cognitive ability in older adults and benefits in other pathological processes&#44; such as osteoarthritis&#44; Parkinson&#39;s disease&#44; chronic obstructive pulmonary disease rehabilitation&#44; depression&#44; cardiac rehabilitation&#44; and dementia&#46;<a class="elsevierStyleCrossRefs" href="#bib1155"><span class="elsevierStyleSup">45&#44;46</span></a> However&#44; the role of Tai Chi in HTN was more limited&#46; Chan et al&#46;<a class="elsevierStyleCrossRef" href="#bib1165"><span class="elsevierStyleSup">47</span></a> reported that Tai Chi is better than brisk walking in helping to control cardiovascular risk factors and improve psychosocial well-being&#44; and could be considered a viable and safe alternative exercise in patients with HT&#46;<a class="elsevierStyleCrossRefs" href="#bib1155"><span class="elsevierStyleSup">45&#44;47</span></a> In terms of Tai Chi form&#44; the Wu style had a better effect on HT in middle-aged and elderly people &#40;significantly higher mean improvement in SBP&#41;&#44; thus offering greater protection to the cardiovascular system&#46;<a class="elsevierStyleCrossRef" href="#bib1170"><span class="elsevierStyleSup">48</span></a></p><p id="par0125" class="elsevierStylePara elsevierViewall">Thus&#44; any form of Tai Chi could be useful in the control of CVRFs such as hypertension&#44; and in improving the quality of life of patients&#44; it is also safe and has a minimal rate of adverse effects&#46;</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Music therapy and hypertension</span><p id="par0130" class="elsevierStylePara elsevierViewall">Music therapy can be considered an important part of the non-pharmacological treatment of HTN&#46; It can have positive effects on the mind and body that can help control BP levels&#44;<a class="elsevierStyleCrossRef" href="#bib1175"><span class="elsevierStyleSup">49</span></a> with beneficial results in hypertensive patients&#46;<a class="elsevierStyleCrossRefs" href="#bib1175"><span class="elsevierStyleSup">49&#8211;51</span></a> A controlled trial evaluated the effects of music therapy&#44; showing significant reductions in BP&#44; heart rate &#40;HR&#41;&#44; and anxiety levels in older adults living in a nursing home&#46;<a class="elsevierStyleCrossRefs" href="#bib1175"><span class="elsevierStyleSup">49&#8211;51</span></a> Cao et al&#46;<a class="elsevierStyleCrossRef" href="#bib1180"><span class="elsevierStyleSup">50</span></a> also reported improvements in BP &#40;up to 9<span class="elsevierStyleHsp" style=""></span>mmHg SBP and 6&#46;5 DBP&#41;&#44; HR&#44; and depression and anxiety rating scales&#44; and in sleep quality in hypertensive patients&#46; These benefits suggest that music therapy could be a promising tool for preventing the progression of prehypertension&#44;<a class="elsevierStyleCrossRef" href="#bib1185"><span class="elsevierStyleSup">51</span></a> although more specific studies are needed&#46; A systematic review and meta-analysis corroborated the reduction in BP after music therapy used for hypertension&#44; although a cause-effect relationship was not established&#46;<a class="elsevierStyleCrossRefs" href="#bib1190"><span class="elsevierStyleSup">52&#44;53</span></a> Therefore&#44; randomised&#44; well-designed&#44; high-quality studies could be designed&#44; that significantly evaluate the efficacy of musical interventions&#44; although it would be difficult to systematise these results in the general population&#44; as most studies lack double-blind implementation&#44; and thus incur selection biases&#46;<a class="elsevierStyleCrossRef" href="#bib1180"><span class="elsevierStyleSup">50</span></a></p></span></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Biological therapies</span><p id="par0135" class="elsevierStylePara elsevierViewall">This category includes substances or foods obtained directly from nature&#44; chemical substances&#44; functional foods&#44; and nutraceuticals&#46; According to Functional Food Science in Europe &#40;FUFOSE&#41; a functional food is a food that&#44; beyond its nutritional value&#44; measurably influences physiological functions in terms of health promotion or disease prevention&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">Several reviews have assessed its value in terms of cardiovascular outcomes&#44;<a class="elsevierStyleCrossRef" href="#bib1200"><span class="elsevierStyleSup">54</span></a> lipid levels&#44;<a class="elsevierStyleCrossRef" href="#bib1205"><span class="elsevierStyleSup">55</span></a> and in HTN&#46;<a class="elsevierStyleCrossRef" href="#bib1210"><span class="elsevierStyleSup">56</span></a> The results obtained have not always been neutral or positive&#44; but some recent studies have reported adverse results with the consumption of some types of algae&#44; posing potential risks to human health&#46;<a class="elsevierStyleCrossRef" href="#bib1215"><span class="elsevierStyleSup">57</span></a></p><p id="par0145" class="elsevierStylePara elsevierViewall">A recent review of 884 studies on a total of 27 micronutrients assessed the relationship between consumption and reduced cardiovascular disease&#44; showing that <span class="elsevierStyleItalic">n</span>&#8722;3 and <span class="elsevierStyleItalic">n</span>&#8722;6 fatty acids&#44; <span class="elsevierStyleSmallCaps">l</span>-arginine&#44; <span class="elsevierStyleSmallCaps">l</span>-citrulline&#44; folic acid&#44; vitamin D&#44; magnesium&#44; zinc&#44; &#945;-lipoic acid&#44; coenzyme Q10&#44; melatonin&#44; catechin&#44; curcumin&#44; flavanol&#44; genistein&#44; and quercetin showed moderate to high quality evidence for reducing cardiovascular risk factors&#46;<a class="elsevierStyleCrossRef" href="#bib1220"><span class="elsevierStyleSup">58</span></a> Specifically&#44; supplementation with <span class="elsevierStyleItalic">n</span>&#8722;3 fatty acids decreased cardiovascular mortality&#44; myocardial infarction&#44; and coronary events&#46; Folic acid supplementation decreased stroke risk&#44; and coenzyme Q10 supplementation decreased all-cause mortality events&#44; while vitamins C&#44; D&#44; E&#44; and selenium showed no effect on cardiovascular disease or type 2 diabetes risk&#46; Other substances&#44; such as &#946;-carotenes increased all-cause mortality&#44; cardiovascular mortality events&#44; and stroke risk&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall">In terms of their potential hypotensive effect&#44; which is the main reason for our review&#44; numerous substances have been analysed&#44; most notably fish oil and monounsaturated fatty acids &#40;omega-3 and 6&#41;&#44; garlic&#44; artichoke&#44; oats&#44; berberine&#44; calcium&#44; co-enzyme Q10&#44; coffee&#44; cocoa &#40;dark chocolate&#41;&#44; cinnamon&#44; turmeric&#44; spirulina&#44; soluble viscous fibre&#44; <span class="elsevierStyleSmallCaps">l</span>-arginine&#44; flax&#44; magnesium&#44; melatonin&#44; quercetin&#44; potassium&#44; beetroot&#44; milk-derived peptides &#40;dietary amino acids&#41;&#44; red pepper&#44; salicornia&#44; tea &#40;green&#44; red and bitter&#41;&#44; vitamin C&#44; vitamin D&#44; and zinc&#46;</p><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Fatty acids</span><p id="par0155" class="elsevierStylePara elsevierViewall">A short-term study with very small numbers of elderly patients found a possible decrease in BP in those taking omega-3 and 6 fatty acids&#44;<a class="elsevierStyleCrossRef" href="#bib1225"><span class="elsevierStyleSup">59</span></a> but a retrospective review of the NHANES study found no association between higher intakes of <span class="elsevierStyleItalic">n</span>&#8722;3 or <span class="elsevierStyleItalic">n</span>&#8722;6 fatty acids and a lower risk of hypertension&#46;<a class="elsevierStyleCrossRef" href="#bib1230"><span class="elsevierStyleSup">60</span></a></p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0145">Folic acid</span><p id="par0160" class="elsevierStylePara elsevierViewall">Some studies in US adults have found associations between multiple vitamin supplementation with vitamin B complex and folate and the prevalence of HTN retrospectively&#44;<a class="elsevierStyleCrossRef" href="#bib1235"><span class="elsevierStyleSup">61</span></a> suggesting a protective effect against HTN&#46;</p><p id="par0165" class="elsevierStylePara elsevierViewall">A recent review of pooled results with 22 studies analysed found that folic acid supplementation slightly&#44; but significantly&#44; reduced both SBP and DBP&#46;<a class="elsevierStyleCrossRef" href="#bib1240"><span class="elsevierStyleSup">62</span></a></p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0150">Garlic</span><p id="par0170" class="elsevierStylePara elsevierViewall">Garlic &#40;<span class="elsevierStyleItalic">Allium sativum L</span>&#46;&#41; belongs to the Liliaceae family along with the onion&#46; Its benefits are due to its high content of sulphur compounds&#44; of which allicin is the substance with the greatest biological activity&#44; although other substances with a hypotensive effect are of note&#44; such as adenosine and saponins&#46; Some meta-analyses have shown that garlic can reduce SBP and DBP&#44;<a class="elsevierStyleCrossRefs" href="#bib1245"><span class="elsevierStyleSup">63&#8211;65</span></a> and beneficial effects have also been attributed to the intestinal probiota&#44;<a class="elsevierStyleCrossRef" href="#bib1260"><span class="elsevierStyleSup">66</span></a> and lipid and immune parameters&#46;<a class="elsevierStyleCrossRef" href="#bib1265"><span class="elsevierStyleSup">67</span></a></p></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0155">Artichoke</span><p id="par0175" class="elsevierStylePara elsevierViewall">Artichoke &#40;<span class="elsevierStyleItalic">Cynara scolymus L</span>&#46;&#41; has been linked to the Mediterranean diet&#46; Artichoke leaves contain polyphenolic compounds&#44; prebiotics &#40;inulin&#41;&#44; minerals&#44; ascorbic acid&#44; and folic acid&#44; and its leaf extract is rich in dietary fibre and antioxidant components&#44; with a proposed mechanism of hypotensive action based on increased expression of the endothelial nitric oxide synthase &#40;eNOS&#41; gene and therefore the production of nitric oxide &#40;NO&#41; in cultured human vascular endothelial cells&#44; improving endothelium-dependent vasodilation&#44; with positive effects both on insulin resistance and on other lipid metabolic parameters&#44; or somatometric parameters &#40;waist circumference or visceral adipose tissue&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib1270"><span class="elsevierStyleSup">68</span></a></p><p id="par0180" class="elsevierStylePara elsevierViewall">Although not all meta-analyses and systematic reviews have been able to document a hypotensive effect&#44;<a class="elsevierStyleCrossRef" href="#bib1275"><span class="elsevierStyleSup">69</span></a> a recent review has documented a significant decrease in both SBP and DBP&#46;<a class="elsevierStyleCrossRef" href="#bib1280"><span class="elsevierStyleSup">70</span></a></p></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0160">Oats</span><p id="par0185" class="elsevierStylePara elsevierViewall">Oats provide several beneficial dietary components with putative beneficial effects on BP or endothelial function&#44; such as &#946;-glucans&#44; &#947;-amino butyric acid &#40;GABA&#41;&#44; and phytochemicals such as avenanthramides&#46;<a class="elsevierStyleCrossRef" href="#bib1285"><span class="elsevierStyleSup">71</span></a></p><p id="par0190" class="elsevierStylePara elsevierViewall">A systematic review<a class="elsevierStyleCrossRef" href="#bib1290"><span class="elsevierStyleSup">72</span></a> found that oat consumption is effective in reducing SBP levels&#44; particularly in individuals whose baseline BP is in the HTN range&#44; and no such effect was found in normotensive individuals&#46; However&#44; research in this area is limited and further studies are needed to elucidate the antihypertensive potential of oats&#46;<a class="elsevierStyleCrossRef" href="#bib1295"><span class="elsevierStyleSup">73</span></a></p></span><span id="sec0095" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0165">Berberine</span><p id="par0195" class="elsevierStylePara elsevierViewall">Berberine is a natural plant alkaloid used in eastern countries &#40;Chunghyul-dan herbal extract contains berberine&#41;&#46; Some studies have linked berberine consumption to metabolic benefits at the cardiovascular level &#40;improvement of diabetes and lipids&#41; and to hypotensive effects&#44;<a class="elsevierStyleCrossRefs" href="#bib1300"><span class="elsevierStyleSup">74&#44;75</span></a> although the quality of the studies was very low &#40;high heterogeneity&#44; short duration&#44; and low number of participants&#41;&#46;</p></span><span id="sec0100" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0170">Cocoa &#40;and dark chocolate&#41;</span><p id="par0200" class="elsevierStylePara elsevierViewall">The polyphenols contained in cocoa &#40;mainly flavonoids and epicatechin&#41; antagonise angiotensin-converting enzyme &#40;ACE&#41; and activate the enzyme nitric oxide synthase&#44; which increases nitric oxide synthesis&#44; promotes vasodilation and thus BP reduction&#46; This hypotensive effect has been documented when the daily dose of flavonols in cocoa was &#8805;900<span class="elsevierStyleHsp" style=""></span>mg &#40;equivalent to 100&#8211;500<span class="elsevierStyleHsp" style=""></span>g chocolate&#41; or epicatechin<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>100<span class="elsevierStyleHsp" style=""></span>mg &#40;equivalent to 50&#8211;200<span class="elsevierStyleHsp" style=""></span>g chocolate&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib1310"><span class="elsevierStyleSup">76</span></a> One study compared cocoa intake in beverage form with cocoa and dark chocolate&#44; finding that the decrease in BP was greater with consumption of dark chocolate&#46;<a class="elsevierStyleCrossRef" href="#bib1310"><span class="elsevierStyleSup">76</span></a> A Cochrane review<a class="elsevierStyleCrossRef" href="#bib1315"><span class="elsevierStyleSup">77</span></a> analysed this blood pressure lowering effect providing moderate quality evidence that chocolate and flavonol-rich cocoa products caused a small &#40;2<span class="elsevierStyleHsp" style=""></span>mmHg&#41; blood pressure lowering effect in mainly healthy adults and short-term&#44; which was substantially greater in the subgroup of hypertensive patients&#44; although the results were limited by the large heterogeneity of the studies&#46; On a practical level&#44; a review conducted for general practitioners in 2013<a class="elsevierStyleCrossRef" href="#bib1320"><span class="elsevierStyleSup">78</span></a> claimed that consumption of 50<span class="elsevierStyleHsp" style=""></span>g cocoa per day could reduce BP in hypertensive patients by 2&#8211;3<span class="elsevierStyleHsp" style=""></span>mmHg&#44; although with a grade C recommendation&#46;</p></span><span id="sec0105" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0175">Coffee</span><p id="par0205" class="elsevierStylePara elsevierViewall">There are over 1000 chemical compounds in coffee&#44; the most documented being caffeine&#44; chlorogenic acid&#44; trigonelline&#44; kahweol&#44; cafestol&#44; ferulic acid&#44; and melanoidins&#46; Numerous studies and systematic reviews&#47;meta-analyses have examined a possible hypotensive effect of caffeine&#44; with varying results&#46;<a class="elsevierStyleCrossRefs" href="#bib1325"><span class="elsevierStyleSup">79&#8211;85</span></a> A j-shaped curve was documented for regular coffee consumption and long-term risk of hypertension&#46;<a class="elsevierStyleCrossRef" href="#bib1325"><span class="elsevierStyleSup">79</span></a> While moderate and regular coffee consumption did not increase&#44; and might even reduce&#44; the risk of developing HTN&#44; occasional coffee consumption would have hypertensive effects and might even decrease cancer mortality&#46;<a class="elsevierStyleCrossRef" href="#bib1360"><span class="elsevierStyleSup">86</span></a> Regarding the different types of coffee &#40;instant&#44; ground&#44; and decaffeinated&#41; and their relationship with cardiovascular disease and arrhythmias&#44; decaffeinated&#44; ground&#44; and instant coffee&#44; particularly at doses of 2&#8211;3 cups&#47;day&#44; were associated with significant reductions in mortality and incident cardiovascular disease&#46; It has been documented that it is caffeinated coffee&#44; not decaffeinated coffee&#44; which has been associated with a hypotensive effect&#46;<a class="elsevierStyleCrossRef" href="#bib1360"><span class="elsevierStyleSup">86</span></a> Ground and instant coffee&#44; but not decaffeinated&#44; were associated with a reduced risk of arrhythmia&#46;<a class="elsevierStyleCrossRef" href="#bib1365"><span class="elsevierStyleSup">87</span></a></p><p id="par0210" class="elsevierStylePara elsevierViewall">In summary&#44; moderate&#44; and regular coffee consumption &#40;1&#8211;3<span class="elsevierStyleHsp" style=""></span>cups&#47;day&#41; does not adversely affect blood pressure in most people&#44; including those with HTN&#46; While acute administration of coffee may induce an increase in BP&#44; regular consumption of coffee in medium-high doses &#40;3&#8211;5<span class="elsevierStyleHsp" style=""></span>cups&#47;day&#41; has a neutral or even beneficial impact on BP values and new onset of HTN&#59; the same long-term intake significantly reduces the incidence of cardiovascular disease as well as all-cause mortality&#46;<a class="elsevierStyleCrossRefs" href="#bib1360"><span class="elsevierStyleSup">86&#44;87</span></a> Current evidence excludes a significant effect of coffee consumption on the development of HTN and BP control in treated and untreated hypertensives&#44; all of which supports a protective role of the antioxidant components of coffee that may counteract the claimed negative effect of caffeine&#46; Therefore&#44; coffee consumption is compatible with a correct and balanced lifestyle and should not be discouraged in hypertensive subjects or those with cardiovascular disease&#46;<a class="elsevierStyleCrossRef" href="#bib1370"><span class="elsevierStyleSup">88</span></a></p></span><span id="sec0110" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0180">Calcium and vitamin D</span><p id="par0215" class="elsevierStylePara elsevierViewall">Decreased levels of vitamin D and calcium have been linked to elevated BP and cardiovascular complications&#46; A meta-analysis reviewed the combined effects of calcium and vitamin D on BP&#44; finding a non-significant reduction in SBP and a significant decrease in DBP&#46;<a class="elsevierStyleCrossRef" href="#bib1375"><span class="elsevierStyleSup">89</span></a> In contrast&#44; another review studied the effect of calcium and vitamin D supplementation in normotensive and hypertensive patients&#44; detecting no significant effect on daytime office BP&#44; although subgroup analysis found a decrease in SBP in men&#46;<a class="elsevierStyleCrossRef" href="#bib1380"><span class="elsevierStyleSup">90</span></a></p><p id="par0220" class="elsevierStylePara elsevierViewall">A recent systematic review from the Cochrane library<a class="elsevierStyleCrossRef" href="#bib1385"><span class="elsevierStyleSup">91</span></a> found that increased calcium intake slightly reduced SBP and DBP in normotensive individuals&#44; particularly in young people&#44; which may suggest a role in the prevention of HTN&#46; Similarly&#44; another publication noted how high dietary calcium was associated with a lower risk of all-cause mortality&#44; cardiovascular disease&#44; and cancer&#59; in terms of dosage&#44; a dietary intake between 1000 and 1200<span class="elsevierStyleHsp" style=""></span>mg per day in people with HTN could be considered cost-effective&#46;<a class="elsevierStyleCrossRef" href="#bib1390"><span class="elsevierStyleSup">92</span></a></p><p id="par0225" class="elsevierStylePara elsevierViewall">Several reviews have addressed calcium supplementation with the prevention of pre-eclampsia<a class="elsevierStyleCrossRefs" href="#bib1395"><span class="elsevierStyleSup">93&#8211;95</span></a> with positive results&#44; especially in women with low calcium intake&#46;<a class="elsevierStyleCrossRef" href="#bib1405"><span class="elsevierStyleSup">95</span></a></p><p id="par0230" class="elsevierStylePara elsevierViewall">Isolated vitamin D3 intake has been associated with some cardioprotective effect&#44; although one review found no such association&#46;<a class="elsevierStyleCrossRef" href="#bib1410"><span class="elsevierStyleSup">96</span></a> It has also been studied in relation to a possible hypotensive effect without positive results&#44; although a decrease in SBP and DBP was observed in men<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>50 years and with intake<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>800<span class="elsevierStyleHsp" style=""></span>units&#47;day and with trials lasting<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>6 months&#44; which considerably limits its value&#46;<a class="elsevierStyleCrossRef" href="#bib1415"><span class="elsevierStyleSup">97</span></a></p></span><span id="sec0115" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0185">Cinnamon</span><p id="par0235" class="elsevierStylePara elsevierViewall">Some reviews have studied the blood pressure lowering effect of cinnamon&#44;<a class="elsevierStyleCrossRefs" href="#bib1420"><span class="elsevierStyleSup">98&#8211;101</span></a>with decreases in both SBP and DBP&#46;<a class="elsevierStyleCrossRef" href="#bib1420"><span class="elsevierStyleSup">98</span></a> However&#44; the small number of publications&#44; the absence of long-term results&#44; the great heterogeneity&#44; and the small number of patients included make these conclusions inconsistent&#44; if not partially incongruent&#46;</p></span><span id="sec0120" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0190">Coenzyme Q10</span><p id="par0240" class="elsevierStylePara elsevierViewall">Although some reviews have associated the consumption of coenzyme Q10 with a hypotensive effect&#44; several Cochrane reviews have found no evidence for this&#46;<a class="elsevierStyleCrossRef" href="#bib1440"><span class="elsevierStyleSup">102</span></a></p><p id="par0245" class="elsevierStylePara elsevierViewall">Another review looked at the hypotensive effect in patients with metabolic diseases&#44; documenting a slight decrease in SBP&#44; but not in DBP&#46;<a class="elsevierStyleCrossRef" href="#bib1445"><span class="elsevierStyleSup">103</span></a> A potential U-shaped dose&#8211;response relationship between CoQ10 supplementation and SBP level has been documented at a dose of approximately 100&#8211;200<span class="elsevierStyleHsp" style=""></span>mg&#47;day&#44; mainly in patients with cardiovascular disease &#40;SBP-lowering effects were more pronounced in patients with diabetes and dyslipidaemia and in studies lasting longer than 12 weeks&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib1450"><span class="elsevierStyleSup">104</span></a> Its definitive effect on BP is therefore not yet well established&#46;</p></span><span id="sec0125" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0195">Turmeric</span><p id="par0250" class="elsevierStylePara elsevierViewall">Curcumin&#44; first used 3000 years ago as an anti-inflammatory agent&#44; is a well-known bioactive compound derived from the active ingredient of turmeric &#40;<span class="elsevierStyleItalic">Curcuma longa</span>&#41; and has been described as having a potential therapeutic effect on a variety of diseases through antioxidant&#44; anti-apoptotic and anti-inflammatory pathways&#46;<a class="elsevierStyleCrossRef" href="#bib1455"><span class="elsevierStyleSup">105</span></a> The results on HTN are inconsistent&#46; Thus&#44; while one systematic review&#47;metaanalysis&#44;<a class="elsevierStyleCrossRef" href="#bib1460"><span class="elsevierStyleSup">106</span></a> showed that turmeric consumption did not reduce SBP&#47;DBP &#40;although it did in studies lasting<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>12 weeks&#41;&#44; another review did show a decrease in DBP in subgroup analysis&#44; also in studies lasting more than 12 weeks&#46;<a class="elsevierStyleCrossRef" href="#bib1465"><span class="elsevierStyleSup">107</span></a></p></span><span id="sec0130" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0200">Spirulina &#40;<span class="elsevierStyleItalic">Arthrospira platensis</span>&#41;</span><p id="par0255" class="elsevierStylePara elsevierViewall">This micro-alga of the proanthocyanidin family is actually a group of single-celled bacterial micro-organisms of the genus <span class="elsevierStyleItalic">Arthrospira</span> that has become a superfood for combating anaemia and malnutrition&#46; Recommendations on the beneficial effects of algae in the diet are becoming increasingly widespread&#44; identified with responsible and ecological consumption&#44; and spirulina is one of the most widely used&#44;<a class="elsevierStyleCrossRef" href="#bib1470"><span class="elsevierStyleSup">108</span></a> with supposed hypotensive effects&#46;<a class="elsevierStyleCrossRef" href="#bib1475"><span class="elsevierStyleSup">109</span></a> The components of <span class="elsevierStyleItalic">Spirulina platensis matrix</span> have been investigated for their potential cardiovascular benefits&#44; and a decameric peptide &#40;peptide fraction 6 &#8211; SP6&#8211;&#41; was found to produce endothelium-dependent vasodilation&#46;<a class="elsevierStyleCrossRef" href="#bib1480"><span class="elsevierStyleSup">110</span></a></p><p id="par0260" class="elsevierStylePara elsevierViewall">A recent review analysed the short-term blood pressure lowering effect&#44; finding a decrease of 4&#46;5<span class="elsevierStyleHsp" style=""></span>mmHg SBP and 2&#46;5<span class="elsevierStyleHsp" style=""></span>mmHg DBP&#59; and even greater decreases of up to 7<span class="elsevierStyleHsp" style=""></span>mmHg DBP in other meta-analyses &#40;mainly in hypertensive patients&#41;&#46; However&#44; more evidence is needed&#44; although it could be considered a potential hypotensive adjunct in the future&#46;<a class="elsevierStyleCrossRef" href="#bib1485"><span class="elsevierStyleSup">111</span></a></p></span><span id="sec0135" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0205">Viscous soluble fibre</span><p id="par0265" class="elsevierStylePara elsevierViewall">There are numerous recommendations to increase the consumption of dietary fibre&#44; due to its beneficial effects on the cardiovascular system and cancer prevention&#46; With regard to its potential hypotensive effect&#44; several types of fibre have been described as likely to be beneficial&#44; including &#946;-glucan from oats and barley&#44; guar gum&#44; konjac&#44; pectin&#44; and psyllium&#46; Several reviews have found decreases in both SBP and DBP&#44;<a class="elsevierStyleCrossRefs" href="#bib1490"><span class="elsevierStyleSup">112&#8211;114</span></a> especially psyllium&#46;<a class="elsevierStyleCrossRefs" href="#bib1495"><span class="elsevierStyleSup">113&#44;114</span></a></p></span><span id="sec0140" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0210"><span class="elsevierStyleSmallCaps">l</span>-Arginine</span><p id="par0270" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleSmallCaps">l</span>-Arginine is an amino acid obtained by the body from dietary sources or endogenous metabolism&#46; It is the substrate for numerous enzyme pathways involved in the regulation of vascular tone&#44; immune activation&#44; and cell growth&#46; <span class="elsevierStyleSmallCaps">l</span>-Arginine supplementation has been shown to exert several beneficial effects on cardiometabolic markers&#44; including BP&#46; A recent review has shown how <span class="elsevierStyleSmallCaps">l</span>-arginine supplementation leads to a significant decrease in SBP&#46; In non-linear dose&#8211;response analysis&#44; the effective dose of <span class="elsevierStyleSmallCaps">l</span>-arginine supplementation was found to be &#8805;4<span class="elsevierStyleHsp" style=""></span>g&#47;day&#46;<a class="elsevierStyleCrossRef" href="#bib1505"><span class="elsevierStyleSup">115</span></a></p></span><span id="sec0145" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0215">Magnesium</span><p id="par0275" class="elsevierStylePara elsevierViewall">Although a Cochrane review<a class="elsevierStyleCrossRef" href="#bib1510"><span class="elsevierStyleSup">116</span></a> had previously found insufficient evidence for the hypotensive effect of magnesium&#44; a review of clinical trials showed that an average intake of 368<span class="elsevierStyleHsp" style=""></span>mg&#47;day of magnesium lowered SBP by 2<span class="elsevierStyleHsp" style=""></span>mmHg and DBP by 1&#46;8<span class="elsevierStyleHsp" style=""></span>mmHg<a class="elsevierStyleCrossRef" href="#bib1515"><span class="elsevierStyleSup">117</span></a>&#59; however&#44; its long-term effect requires further evidence to be demonstrated&#46; In addition&#44; antihypertensive effects have been reported in certain patient subgroups&#44; such as those with insulin resistance&#44; pre-diabetes&#44; or diabetes&#44; and very recently in diabetic patients in improving BP and lipid levels&#46;<a class="elsevierStyleCrossRef" href="#bib1520"><span class="elsevierStyleSup">118</span></a></p><p id="par0280" class="elsevierStylePara elsevierViewall">In January 2022&#44; the FDA &#40;<a href="https://www.fda.gov/food/cfsan-constituent-updates/fda-announces-qualified-health-claim-magnesium-and-reduced-risk-high-blood-pressure">https&#58;&#47;&#47;www&#46;fda&#46;gov&#47;food&#47;cfsan-constituent-updates&#47;fda-announces-qualified-health-claim-magnesium-and-reduced-risk-high-blood-pressure</a>&#41; announced that companies can make certain health claims regarding magnesium intake and a reduced risk of high blood pressure&#46; However&#44; food companies and dietary supplement manufacturers wishing to include such claims on their packaging must add some caveats&#46; Specifically&#44; the wording should make it clear that the evidence to support the claim is &#8220;inconsistent and inconclusive&#8221;&#44; with more research needed to provide further evidence&#46;<a class="elsevierStyleCrossRef" href="#bib1525"><span class="elsevierStyleSup">119</span></a></p></span><span id="sec0150" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0220">Melatonin</span><p id="par0285" class="elsevierStylePara elsevierViewall">Melatonin is a hormone secreted in the pineal gland that has a sleep cycle modulating effect and has demonstrated cardiovascular beneficial effects&#46; The hypotensive effect has been studied in several meta-analyses&#44;<a class="elsevierStyleCrossRefs" href="#bib1530"><span class="elsevierStyleSup">120&#8211;125</span></a> extended-release melatonin &#40;and not immediate-release&#41; been significantly associated with BP decreases of approximately 3&#46;5<span class="elsevierStyleHsp" style=""></span>mmHg in SBP and DBP&#44; consistently&#46; A study evaluating hypertensive diabetics found that more than 30&#37; of non-dippers with type 2 diabetes treated with melatonin regained normal circadian BP rhythm with reductions of 3&#8211;5<span class="elsevierStyleHsp" style=""></span>mmHg at night&#46;<a class="elsevierStyleCrossRef" href="#bib1560"><span class="elsevierStyleSup">126</span></a></p></span><span id="sec0155" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0225">Milk peptides and probiotics</span><p id="par0290" class="elsevierStylePara elsevierViewall">The hypotensive effect of some biologically active peptides and probiotics from lactic acid fermentation of milk&#44; namely isoleucine-proline-proline &#40;IPP&#41; and valine-proline-proline &#40;VPP&#41;&#44; has been studied for decades&#46; Numerous recent reviews with these peptides have found a hypotensive effect&#44;<a class="elsevierStyleCrossRefs" href="#bib1560"><span class="elsevierStyleSup">126&#8211;132</span></a> primarily through inhibition of angiotensin-converting enzyme or ACE &#40;activating ACE-2&#41;&#44; mainly in hypertensive patients<a class="elsevierStyleCrossRef" href="#bib1560"><span class="elsevierStyleSup">126</span></a> or in patients with hypertension and diabetes mellitus&#44;<a class="elsevierStyleCrossRef" href="#bib1565"><span class="elsevierStyleSup">127</span></a> although this has not been demonstrated in all studies&#46;<a class="elsevierStyleCrossRef" href="#bib1570"><span class="elsevierStyleSup">128</span></a> Human clinical trials have shown that the consumption of probiotics can improve BP control and improve vascular function&#44;<a class="elsevierStyleCrossRef" href="#bib1575"><span class="elsevierStyleSup">129</span></a> both in multi-component and single-component &#40;<span class="elsevierStyleItalic">Lactobacillus plantarum</span>&#41; studies&#46;<a class="elsevierStyleCrossRef" href="#bib1580"><span class="elsevierStyleSup">130</span></a> However&#44; although the results are encouraging&#44; more research is still needed to clarify the exact mechanism and efficiency of the intake of these antihypertensive peptides&#44; and their potential benefit on health in general and on hypertension in particular&#46;<a class="elsevierStyleCrossRef" href="#bib1585"><span class="elsevierStyleSup">131</span></a> A summary of marketed products containing these products can be found in a recent review&#46;<a class="elsevierStyleCrossRef" href="#bib1590"><span class="elsevierStyleSup">132</span></a> A recent meta-analysis evaluated the blood pressure lowering effect of whey protein&#44; finding a significant decrease in SBP of &#8722;1&#46;5<span class="elsevierStyleHsp" style=""></span>mmHg&#46;<a class="elsevierStyleCrossRef" href="#bib1595"><span class="elsevierStyleSup">133</span></a></p></span><span id="sec0160" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0230">Potassium</span><p id="par0295" class="elsevierStylePara elsevierViewall">Although numerous studies on the blood pressure lowering effect of potassium intake have been conducted for decades&#44; it was not until the beginning of this century that potassium supplementation was recommended in clinical practice guidelines&#46; The Canadian guidelines on HTN have been the most explicit in their recommendation&#44; obtaining a maximum level of evidence &#40;A&#41;<a class="elsevierStyleCrossRef" href="#bib1600"><span class="elsevierStyleSup">134</span></a> given that potassium is a fundamental pillar of the DASH diet &#40;Dietary Approaches to Stop Hypertension&#41; and the Mediterranean diet&#46; Several reviews and meta-analyses have documented how a supplement of 3500&#8211;5000<span class="elsevierStyleHsp" style=""></span>mg&#47;day can reduce SBP by up to 4<span class="elsevierStyleHsp" style=""></span>mmHg and DBP by 2<span class="elsevierStyleHsp" style=""></span>mmHg&#44; with consumption preferably with a diet &#40;such as locally available fruits and vegetables&#41; rich in potassium&#46;<a class="elsevierStyleCrossRefs" href="#bib1605"><span class="elsevierStyleSup">135&#8211;141</span></a></p><p id="par0300" class="elsevierStylePara elsevierViewall">A recent meta-analysis documented how potassium supplementation as a salt substitute was able to lower BP and total mortality&#46;<a class="elsevierStyleCrossRef" href="#bib1630"><span class="elsevierStyleSup">140</span></a> Similarly&#44; another meta-analysis found that for every 10&#37; lower proportion of sodium chloride in the salt substitute&#44; a 1&#46;5<span class="elsevierStyleHsp" style=""></span>mmHg reduction in SBP and a &#46;95<span class="elsevierStyleHsp" style=""></span>mmHg reduction in DBP was associated with a 1&#46;5<span class="elsevierStyleHsp" style=""></span>mmHg reduction in SBP and a &#46;95<span class="elsevierStyleHsp" style=""></span>mmHg reduction in DBP&#46;<a class="elsevierStyleCrossRef" href="#bib1635"><span class="elsevierStyleSup">141</span></a> However&#44; despite the results shown&#44; caution should be exercised regarding the use of these potassium supplements&#44; especially in patients with chronic kidney disease or on ACE inhibitors or potassium-sparing diuretics due to the risk of hyperkalaemia&#46;</p></span><span id="sec0165" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0235">Beetroot</span><p id="par0305" class="elsevierStylePara elsevierViewall">Several studies<a class="elsevierStyleCrossRefs" href="#bib1640"><span class="elsevierStyleSup">142&#8211;145</span></a> have documented that both beetroot juice &#40;beetroot&#41; and capsules with dry extract &#40;nitrate&#41; can lower BP&#44; given the high nitrate content which is converted to nitric oxide after ingestion of this plant&#46; The effect has been shown mainly in decreasing SBP&#44; and not so clearly for DBP&#46;<a class="elsevierStyleCrossRef" href="#bib1545"><span class="elsevierStyleSup">123</span></a></p><p id="par0310" class="elsevierStylePara elsevierViewall">In any case&#44; the properties of beetroot may go beyond its nitrate content&#44; as other reviews have found no positive cardiovascular effects with inorganic nitrate consumption&#44;<a class="elsevierStyleCrossRef" href="#bib1655"><span class="elsevierStyleSup">145</span></a> and the BP-lowering effects of beetroot juice appear to be independent of NO<span class="elsevierStyleInf">3</span>&#46; In any case&#44; potential health risks must be highlighted because possible carcinogenic effects of its <span class="elsevierStyleItalic">N</span>-nitroso compounds &#40;nitrosamides and nitrosamines&#41;<a class="elsevierStyleCrossRef" href="#bib1640"><span class="elsevierStyleSup">142</span></a> have been described&#44; although a review by Spanish authors reminded us that the beneficial effects of the consumption of beetroot and other vegetables outweigh the possible potential risk to human health&#46;<a class="elsevierStyleCrossRef" href="#bib1660"><span class="elsevierStyleSup">146</span></a></p></span><span id="sec0170" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0240">Salicornia</span><p id="par0315" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Salicornia</span> sp&#46; is a halophyte plant&#44; tolerant to water salinity&#44; which grows in salt marshes&#46; The way it defends itself against these adverse stress conditions &#40;seawater salinity&#44; UV rays&#44; etc&#46;&#41; is to produce large quantities of polyphenols&#46; The number of polyphenols in B-Salicornia is very high &#40;29<span class="elsevierStyleHsp" style=""></span>mg<span class="elsevierStyleHsp" style=""></span>GAE&#47;g&#41;&#44; which may partly explain its beneficial effects&#46; It has a wide geographical distribution&#44; and its identified effects include lowering BP&#44; lowering homocysteine&#44; and its anti-adipogenic effect due to its main component&#44; transferulic acid&#46;<a class="elsevierStyleCrossRefs" href="#bib1665"><span class="elsevierStyleSup">147&#8211;149</span></a> It is currently being marketed as another natural salt in parts of our country &#40;Salicornia&#174; extract and B-Salicornia&#174; are registered trademarks&#41;&#46; Some studies and research are underway to assess the effect of this marine plant as a salt substitute<a class="elsevierStyleCrossRef" href="#bib1680"><span class="elsevierStyleSup">150</span></a> and its neurovascular effects &#40;<a href="http://proyectosalicornia.com/wp-content/uploads/2022/05/18.04.22-peiba_HALOFITAS_modF.pdf">http&#58;&#47;&#47;proyectosalicornia&#46;com&#47;wp-content&#47;uploads&#47;2022&#47;05&#47;18&#46;04&#46;22-peiba&#95;HALOFITAS&#95;modF&#46;pdf</a>&#41;&#44; although there is no conclusive data as yet&#46;</p></span><span id="sec0175" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0245">Tea</span><p id="par0320" class="elsevierStylePara elsevierViewall">Tea is a beverage prepared by pouring hot or boiling water over the cured leaves or leaf buds of the tea plant <span class="elsevierStyleItalic">Camellia sinensis</span>&#46; Prolonged consumption appears to be associated with cardiovascular and hypotensive benefits&#46;<a class="elsevierStyleCrossRefs" href="#bib1685"><span class="elsevierStyleSup">151&#44;152</span></a> It is particularly used by Asian and Middle Eastern populations&#44; from where most of the studies on the substance originate&#46;</p><p id="par0325" class="elsevierStylePara elsevierViewall">Caffeine in tea is known to have a short-term pressor effect after immediate ingestion of tea&#44; which is neutralised in the medium and long term&#44; and has been shown in many epidemiological studies to reduce both SBP and DBP&#46;<a class="elsevierStyleCrossRef" href="#bib1690"><span class="elsevierStyleSup">152</span></a></p><p id="par0330" class="elsevierStylePara elsevierViewall">There are numerous types of tea &#40;green tea&#44; black tea&#44; matcha tea&#44; sour tea&#44; white tea&#44; sour or red tea&#44; sweet tea&#44; dark tea&#44; corn silk tea&#44; etc&#46;&#41;&#46; The main phenolic compounds found in tea are flavonoids&#44; which account for almost 70&#37; of its polyphenols&#46; Catechins and their derivatives especially epigallocatechin-3-gallate &#40;EGCG&#41; are the most abundant flavonoids in green tea which are responsible for the potential preventive effect on oxidative stress caused by diseases such as cancer&#44; cardiovascular diseases&#44; and neurodegenerative diseases&#46;<a class="elsevierStyleCrossRef" href="#bib1695"><span class="elsevierStyleSup">153</span></a> Among the many varieties of tea&#44; it is mainly green tea&#44; red tea&#44; black tea&#44; and bitter tea &#40;sour tea&#44; or hibiscus sabdariffa&#44; or Jamaican rose&#41; that have been most studied for their potential hypotensive effect&#46;<a class="elsevierStyleCrossRefs" href="#bib1700"><span class="elsevierStyleSup">154&#8211;159</span></a> One review compared green tea and black tea and found that both reduced overall SBP and DBP by 2 and 1<span class="elsevierStyleHsp" style=""></span>mmHg respectively&#44; slightly more for green tea&#44; suggesting that long-term tea intake &#40;&#8805;12 weeks&#41; could contribute to a significant reduction in BP&#46;<a class="elsevierStyleCrossRef" href="#bib1730"><span class="elsevierStyleSup">160</span></a></p><p id="par0335" class="elsevierStylePara elsevierViewall">Finally&#44; it has been reported in a Chinese population that prolonged tea consumption could reduce the risk of HTN by 10&#37;&#44;<a class="elsevierStyleCrossRef" href="#bib1735"><span class="elsevierStyleSup">161</span></a> and that higher tea consumption&#44; especially green tea&#44; was associated with a lower risk of ischaemic and haemorrhagic stroke&#46;<a class="elsevierStyleCrossRef" href="#bib1740"><span class="elsevierStyleSup">162</span></a></p><p id="par0340" class="elsevierStylePara elsevierViewall">In short&#44; it is possible that tea consumption&#44; especially in the long term&#44; may contribute to a small decrease in BP levels&#46; However&#44; given the lack of homogeneous clinical trials with sufficient numbers of patients and in populations outside Asia and the Middle East&#44; as well as the absence of reliable data on morbidity and mortality&#44; this recommendation is of very low quality&#46;</p></span><span id="sec0180" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0250">Vitamin C</span><p id="par0345" class="elsevierStylePara elsevierViewall">Vitamin C has been consistently associated with a decrease in BP&#46; Several systematic reviews support this&#44; with SBP&#47;DBP decreases of approximately 4 and 2<span class="elsevierStyleHsp" style=""></span>mmHg in both normotensive and hypertensive patients&#46;<a class="elsevierStyleCrossRefs" href="#bib1745"><span class="elsevierStyleSup">163&#44;164</span></a> However&#44; short duration&#44; heterogeneity&#44; large differences in doses used&#44; and lack of trials with clinical events limit their conclusions for the time being&#46;<a class="elsevierStyleCrossRef" href="#bib1750"><span class="elsevierStyleSup">164</span></a></p></span><span id="sec0185" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0255">Zinc</span><p id="par0350" class="elsevierStylePara elsevierViewall">Some studies have evaluated zinc intake with BP lowering in normotensive and hypertensive patients&#46; One study linked zinc intake to lower SBP&#44; but not DBP&#44; although there was controversy regarding the doses used&#46;<a class="elsevierStyleCrossRef" href="#bib1755"><span class="elsevierStyleSup">165</span></a> Further clinical trials using different doses of zinc at various durations are therefore required to confirm this finding&#46;</p><p id="par0355" class="elsevierStylePara elsevierViewall">Finally&#44; for other substances that have been evaluated for a possible hypotensive effect&#44; either because of the heterogeneity of their composition or the paucity of studies&#44; we did not consider a specific breakdown of them&#46; These would include herbal supplements&#44;<a class="elsevierStyleCrossRef" href="#bib1760"><span class="elsevierStyleSup">166</span></a> flax seeds&#44;<a class="elsevierStyleCrossRef" href="#bib1765"><span class="elsevierStyleSup">167</span></a> quercetin&#44;<a class="elsevierStyleCrossRef" href="#bib1770"><span class="elsevierStyleSup">168</span></a> and other Asian herbs such as angelica sinensis &#40;red sage or dong quai&#41;&#44; and salvia miltiorrhiza &#40;Danshen&#41;&#46;</p></span></span><span id="sec0190" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0260">Synthesis of results</span><p id="par0360" class="elsevierStylePara elsevierViewall">The evaluation of alternative medicines based on mind-body therapies has enabled us to confirm a small but positive benefit of some techniques&#44; such as acupuncture&#44; Tai Chi&#44; meditation&#44; or yoga&#44; similar to that already reflected in other previous work&#46;<a class="elsevierStyleCrossRefs" href="#bib0990"><span class="elsevierStyleSup">12&#8211;14&#44;17&#44;22&#44;47</span></a> In contrast&#44; others such as chiropractic have very limited evidence&#44; and also present a negative risk&#8211;benefit balance on BP&#44; by exerting pressure on affected joints&#46;<a class="elsevierStyleCrossRef" href="#bib1080"><span class="elsevierStyleSup">30</span></a> We cannot report any benefits on BP levels for the other therapies we analysed&#46;</p><p id="par0365" class="elsevierStylePara elsevierViewall">With regard to orally consumed biological substances&#44; as detailed above&#44; numerous products have shown apparent efficacy in reducing BP levels&#46; However&#44; in most cases&#44; the magnitude has been small and the evidence weak or moderate&#44; which may limit their application as adjunct therapy in the management of HTN&#46; The beneficial effects of potassium followed by coffee&#44; in that order&#44; and hypotensive effects&#44; with less evidence&#44; of other substances such as cocoa&#44; calcium&#44; garlic&#44; folic acid&#44; artichoke&#44; magnesium&#44; beetroot&#44; spirulina&#44; milk peptides&#44; and melatonin&#44; should be highlighted&#46; The results for the remaining substances are very limited&#44; controversial&#44; or negative&#46;</p><p id="par0370" class="elsevierStylePara elsevierViewall">With regard to potassium&#44; several clinical practice guidelines have made express recommendations to increase potassium intake&#44; such as the Canadian recommendations<a class="elsevierStyleCrossRef" href="#bib1600"><span class="elsevierStyleSup">134</span></a> or the European guidelines&#44;<a class="elsevierStyleCrossRef" href="#bib1775"><span class="elsevierStyleSup">169</span></a> with evidence A&#44; similar to the recommendation for sodium restriction&#44; which we endorse in this review&#46; In general&#44; whenever possible&#44; this should be supplementation in the form of foods with high potassium content and to a lesser extent external prepared supplements &#40;due to doubts regarding doses&#44; preparation&#44; excipients&#44; and systematisation of the preparations generating concern&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib1780"><span class="elsevierStyleSup">170</span></a> Thus&#44; the European recommendations<a class="elsevierStyleCrossRef" href="#bib1775"><span class="elsevierStyleSup">169</span></a> specify the need to increase potassium intake to 3500<span class="elsevierStyleHsp" style=""></span>mg&#47;day&#44; preferably in the form of a Mediterranean or DASH diet rich in fruit and vegetables&#46; A recent editorial in the journal Hypertension<a class="elsevierStyleCrossRef" href="#bib1785"><span class="elsevierStyleSup">171</span></a> encourages this substitution based on two studies of salt substitutes with potassium in rural China<a class="elsevierStyleCrossRefs" href="#bib1790"><span class="elsevierStyleSup">172&#44;173</span></a> and a model of sodium substitution with potassium in table salt with very encouraging results&#46; Although at the population level the cardiovascular and BP benefits may outweigh the risks associated with hyperkalaemia&#44; in our view&#44; we suggest that health authorities should place warning labels on these products for vulnerable individuals &#40;people with chronic renal failure and those taking potassium-sparing diuretics or renin&#8211;angiotensin system blockers&#41;&#46;</p><p id="par0375" class="elsevierStylePara elsevierViewall">With regard to coffee&#44; although the recommendations in the clinical practice guidelines are not yet as explicit as with potassium&#44;<a class="elsevierStyleCrossRefs" href="#bib1600"><span class="elsevierStyleSup">134&#44;169</span></a> it is currently documented that&#44; because there is a possible j-shaped curve&#44; taking 3&#8211;4 cups of coffee per day could be permitted in patients who are already doing so<a class="elsevierStyleCrossRef" href="#bib1800"><span class="elsevierStyleSup">174</span></a> due to its corroborated positive effect on BP and other cardiovascular diseases &#40;atrial fibrillation&#44; diabetes&#44; heart failure&#44; etc&#46;&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib1805"><span class="elsevierStyleSup">175</span></a></p><p id="par0380" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRefs" href="#tbl0005">Tables 1 and 2</a> summarise the conclusions reached by the authors of this review on the efficacy and evidence for recommending this CAM&#44; showing differences according to the therapy chosen&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><span id="sec0195" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0265">Limitations and perspectives</span><p id="par0385" class="elsevierStylePara elsevierViewall">We found numerous limitations in the studies and reviews that limit their external validity&#58; great heterogeneity of the reviews&#44; poorly defined doses of substances&#44; small number of patients&#44; very short follow-up time&#44; lack of adequate methods to control bias &#40;randomisation&#44; confounding&#44; etc&#46;&#41;&#46; The current paucity of clinical trial evidence demonstrating that the typically modest BP reduction associated with these approaches translates into a reduction in hard cardiovascular events is a major shortcoming&#46; However&#44; we must accept that at present it is unlikely that event-based trials will be conducted because of the prohibitive sample size required to demonstrate a benefit with small reductions in BP in relatively healthy individuals with mild hypertension&#44; let alone in the non-hypertensive population&#46;<a class="elsevierStyleCrossRef" href="#bib1835"><span class="elsevierStyleSup">178</span></a> In the absence of such trials&#44; we would have to base our deliberations on the surrogacy of intermediate targets&#44; such as BP reduction &#8220;per se&#8221;&#44; bearing in mind that even small reductions in BP at the population level can translate into substantial public health benefits&#46;<a class="elsevierStyleCrossRef" href="#bib1840"><span class="elsevierStyleSup">179</span></a> Therefore&#44; we believe that the risk&#8211;benefit ratio may support some reasonable recommendations for individuals to use these alternative&#44; or complementary&#44; approaches&#44; provided they are used in appropriate circumstances and under the guidance of a reputable healthcare provider&#44; and should in no way replace the reasoned&#44; conventional use of drugs when they are indicated&#46;</p><p id="par0390" class="elsevierStylePara elsevierViewall">We were able to document at least two other previous reviews<a class="elsevierStyleCrossRefs" href="#bib1820"><span class="elsevierStyleSup">180&#44;181</span></a> that made a critical appraisal of the evidence with the aim of describing the most commonly used therapeutic modalities and reviewing the current level of evidence attributable to each modality&#44; with some divergences between them&#46;</p><p id="par0395" class="elsevierStylePara elsevierViewall">Patients&#44; for the reasons described above&#44; are increasingly using alternative non-pharmacological therapies&#44; which are often unregulated&#46; In addition&#44; the information available on networks and in cyberspace is often poor&#46; Thus&#44; in a study carried out in Australia&#44; Canada&#44; the USA&#44; and the UK&#44; 90 pages and 40 websites were evaluated using the DISCERN score&#44; with disparate and not always appropriate results on the risks of treatment and the impact on quality of life&#46;<a class="elsevierStyleCrossRef" href="#bib1850"><span class="elsevierStyleSup">182</span></a> Therefore&#44; we believe it is essential to ask our patients explicitly about the searches they make&#44; the reason they do so&#44; and to guide them in identifying high quality resources on the web on the problem to be solved&#46;</p><p id="par0400" class="elsevierStylePara elsevierViewall">In 2020&#44; the Spanish Foundation for Science and Technology &#40;FECYT&#41; conducted a qualitative study in Spain on the use of and confidence in therapies without scientific evidence&#44; including homoeopathy&#44; acupuncture&#44; phytotherapy&#44; reiki&#44; and Bach flowers&#44; with the aim of better understanding the perspectives of the users of these treatments&#46;<a class="elsevierStyleCrossRef" href="#bib1855"><span class="elsevierStyleSup">183</span></a> This study describes that the users of these pseudo-therapies think that current medicine is corrupted by the interests of big pharma and has become excessively technical&#44; industrialised &#40;chemical&#41;&#44; and detached from human needs&#44; and&#44; although the majority of users continue to trust traditional medicine &#40;especially in cases of serious illnesses&#41;&#44; they remain hesitant and highly critical towards it&#46; Therefore&#44; the most common access route to alternative medicine is corroborated to be &#8220;word of mouth&#8221; &#40;work colleagues&#44; friends&#44; family network&#44; etc&#46;&#41; followed by specialised books and the Internet&#46;</p><p id="par0405" class="elsevierStylePara elsevierViewall">The limitations of our review are that it is a narrative review with no pretensions of being systematic and&#44; therefore&#44; there is no table to provide levels of evidence&#46; However&#44; the non-pharmacological therapies that have supposedly been studied are considerable in number&#46; As early as 2011&#44; a first official document on alternative therapies was drawn up in Spain &#40;<a href="https://www.sanidad.gob.es/novedades/docs/analisisSituacionTNatu.pdf">https&#58;&#47;&#47;www&#46;sanidad&#46;gob&#46;es&#47;novedades&#47;docs&#47;analisisSituacionTNatu&#46;pdf</a>&#41;&#44; to ascertain their impact and use&#44; documenting up to 139 techniques&#44; recognising that at that time there was no global regulation on natural therapies in any Western country&#46; Of these&#44; 73 lacked a randomised clinical trial and were considered pseudo-therapies&#46; It is therefore necessary to sound a warning bell against the growing indiscriminate use of &#8220;pseudotherapies&#8221; without any scientific basis and which are not sufficiently accredited &#40;if not discredited&#41; by official bodies&#46; In this regard&#44; in 2018 the Ministry of Health and Consumer Affairs drew up a &#8220;Plan for protection against pseudotherapies&#8221; <a href="https://www.sanidad.gob.es/gabinetePrensa/notaPrensa/pdf/20181141118135247771.pdf">https&#58;&#47;&#47;www&#46;sanidad&#46;gob&#46;es&#47;gabinetePrensa&#47;notaPrensa&#47;pdf&#47;20181141118135247771&#46;pdf</a>&#41;&#44; the principles of which are the evaluation of pseudotherapies based on the most up-to-date and robust scientific knowledge and evidence&#44; dissemination and transparency of information&#44; and ensuring regulatory compliance&#46; Since then&#44; the &#35;CoNprueba portal has been created to inform and raise awareness about pseudotherapies and pseudosciences and to contribute to the dissemination of science and critical thinking&#46;</p><p id="par0410" class="elsevierStylePara elsevierViewall">A third limitation of the results would be that they may be subject to multiple confounding factors and&#44; specifically in this field&#44; many of the techniques and complementary measures analysed may be being used by people who already follow healthy lifestyle patterns &#40;vegetarian diets&#44; physical exercise&#41;<a class="elsevierStyleCrossRefs" href="#bib1860"><span class="elsevierStyleSup">184&#8211;186</span></a> and&#44; therefore&#44; would not extend to the rest of the population&#46;</p><p id="par0415" class="elsevierStylePara elsevierViewall">A final consideration is that our review was based on decreases in BP produced by CAM&#44; and we only flag up other beneficial effects for some CAM&#59; at the vascular level &#40;vasodilatation&#44; activation of nitric oxide&#44; improvement of endothelium&#44; etc&#46;&#41;&#44; metabolic &#40;insulin resistance&#44; lipid parameters&#44; glycaemia&#44; etc&#46;&#41;&#44; and somatometric parameters &#40;adiposity&#44; weight&#44; waist circumference&#44; etc&#46;&#41;&#44; the potential of all of which could increase in the prevention of cardiovascular and cerebrovascular diseases&#46;</p></span></span><span id="sec0200" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0270">Conclusions</span><p id="par0420" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">&#8226;</span><p id="par0425" class="elsevierStylePara elsevierViewall">After this review&#44; the multiple alternative practices and therapies are very difficult to assess and require further wider studies&#46;</p></li><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">&#8226;</span><p id="par0430" class="elsevierStylePara elsevierViewall">There is a lack of clear and forceful legislation on the use of these therapies and their potential marketing&#44; which should be regulated&#46;</p></li><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel">&#8226;</span><p id="par0435" class="elsevierStylePara elsevierViewall">We recommend increasing potassium intake and gradually replacing sea salt&#44; preferably in the form of potassium-rich foods&#44; although the use of potassium salt supplements is widely available and could be recommended&#44; subject to warnings and limitations in vulnerable individuals&#46;</p></li><li class="elsevierStyleListItem" id="lsti0030"><span class="elsevierStyleLabel">&#8226;</span><p id="par0440" class="elsevierStylePara elsevierViewall">Moderate coffee consumption &#40;3&#8211;4<span class="elsevierStyleHsp" style=""></span>cups&#47;day&#41; is advisable in patients who already drink coffee&#46;</p></li><li class="elsevierStyleListItem" id="lsti0035"><span class="elsevierStyleLabel">&#8226;</span><p id="par0445" class="elsevierStylePara elsevierViewall">Mind-body therapies based on meditation and safe exercise provide a reasonable basis for discreetly reducing blood pressure and the stress levels of everyday life&#46;</p></li><li class="elsevierStyleListItem" id="lsti0040"><span class="elsevierStyleLabel">&#8226;</span><p id="par0450" class="elsevierStylePara elsevierViewall">There are few CAMs that are worthwhile in practice &#40;yes in research&#41;&#44; but these are associated with &#8220;bad science&#44; but good medicine&#8221; &#40;complementary&#41;&#44; i&#46;e&#46;&#44; with little evidential support but some utility&#44; especially as part of healthy lifestyles and beliefs&#44; which are more personal than collective&#46;</p></li><li class="elsevierStyleListItem" id="lsti0045"><span class="elsevierStyleLabel">&#8226;</span><p id="par0455" class="elsevierStylePara elsevierViewall">Major limitations are detected in most of the studies analysed and subsequent systematic reviews&#47;meta-analyses concerning their methodology &#40;duration&#44; sample&#44; randomisation&#44; confounding factors&#41; and their external validity&#44; which remain considerable shortcomings that limit their results&#46;</p></li><li class="elsevierStyleListItem" id="lsti0050"><span class="elsevierStyleLabel">&#8226;</span><p id="par0460" class="elsevierStylePara elsevierViewall">Therefore&#44; the results of this review suggest that certain non-conventional therapies could be slightly effective in treating hypertension and improving cardiac&#44; cerebral&#44; and vascular function in general&#44; and could form part of non-pharmacological measures as adjunct treatment in future guidelines for the management of hypertension&#44; but never replacing pharmacological treatments&#46; However&#44; the heterogeneity of the studies and the multiple biases in them preclude any other level of recommendation at the present time&#46;</p></li></ul></p></span><span id="sec0205" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0275">Funding</span><p id="par0465" class="elsevierStylePara elsevierViewall">This work was partially supported by <span class="elsevierStyleGrantSponsor" id="gs1">Fondo de Investigaci&#243;n Sanitaria &#40;FIS&#41;</span><span class="elsevierStyleGrantNumber" refid="gs1">22&#47;1164</span> &#40;Instituto de Salud Carlos III and FEDER&#47;FSE&#41;&#46;</p></span><span id="sec0210" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0280">Conflict of interest</span><p id="par0470" class="elsevierStylePara elsevierViewall">The authors have no conflict of interests to declare&#46;</p></span></span>"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Objective</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Review of some of the best-known biological and non-biological complementary&#47;alternative therapies&#47;medicines &#40;CAM&#41; and their relationship with blood pressure &#40;BP&#41; and hypertension &#40;HT&#41;&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Search strategy</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Narrative review assessing a recent series of systematic reviews&#44; meta-analyses&#44; and clinical trials published in recent years&#44; focusing on the effects of CAM on BP and HT&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Selection of studies</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">We searched EMBASE&#44; MEDLINE&#44; Cochrane Library and Google Scholar&#44; obtaining a total of 4336 articles&#44; finally limiting the search to 181 after applying filters&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Synthesis of results</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Some studies on biological therapies show some usefulness in BP reduction with an adequate benefit&#8211;risk balance&#44; although there is a scarcity of high-quality trials that support these results&#46; Some mind-body therapies have shown hypothetical benefit&#59; in contrast&#44; others lack robust evidence&#46;</p></span> <span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Conclusions</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Although some therapies present a reasonable risk&#8211;benefit ratio&#44; they should in no case replace pharmacological treatment when indicated&#46;</p></span>"
        "secciones" => array:5 [
          0 => array:2 [
            "identificador" => "abst0005"
            "titulo" => "Objective"
          ]
          1 => array:2 [
            "identificador" => "abst0010"
            "titulo" => "Search strategy"
          ]
          2 => array:2 [
            "identificador" => "abst0015"
            "titulo" => "Selection of studies"
          ]
          3 => array:2 [
            "identificador" => "abst0020"
            "titulo" => "Synthesis of results"
          ]
          4 => array:2 [
            "identificador" => "abst0025"
            "titulo" => "Conclusions"
          ]
        ]
      ]
      "es" => array:3 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Objetivo</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Revisar algunas de las m&#225;s conocidas terapias&#47;medicinas biol&#243;gicas y no biol&#243;gicas complementarias&#47;alternativas &#40;MCA&#41;&#44; y su relaci&#243;n con la presi&#243;n arterial &#40;PA&#41; e hipertensi&#243;n arterial &#40;HTA&#41;&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Estrategia de b&#250;squeda</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Revisi&#243;n narrativa en la que se valoraron una serie reciente de revisiones sistem&#225;ticas&#44; metaan&#225;lisis y ensayos cl&#237;nicos publicados en los &#250;ltimos a&#241;os&#44; centrada en los efectos de la MCA sobre la PA y HTA&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Selecci&#243;n de estudios</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Se realizaron b&#250;squedas en EMBASE&#44; MEDLINE&#44; Cochrane Library y Google Scholar&#44; obteni&#233;ndose un total de 4&#46;336 art&#237;culos&#44; limit&#225;ndose finalmente a 181 tras aplicar filtros&#46;</p></span> <span id="abst0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">S&#237;ntesis de resultados</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Algunos trabajos sobre terapias biol&#243;gicas parecen demostrar cierta utilidad en reducci&#243;n de la PA con adecuado balance beneficio&#47;riesgo&#44; aunque existe escasez de ensayos de alta calidad que avalen estos resultados&#46; Algunas terapias cuerpo&#47;mente han mostrado un hipot&#233;tico beneficio&#59; en cambio&#44; otras carecen de evidencia robusta&#46;</p></span> <span id="abst0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Conclusiones</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Aunque algunas terapias presentan una relaci&#243;n riesgo&#47;beneficio razonable&#44; no deber&#237;an sustituir en ning&#250;n caso al tratamiento farmacol&#243;gico cuando este est&#233; indicado&#46;</p></span>"
        "secciones" => array:5 [
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            "identificador" => "abst0030"
            "titulo" => "Objetivo"
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            "identificador" => "abst0035"
            "titulo" => "Estrategia de b&#250;squeda"
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          2 => array:2 [
            "identificador" => "abst0040"
            "titulo" => "Selecci&#243;n de estudios"
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          3 => array:2 [
            "identificador" => "abst0045"
            "titulo" => "S&#237;ntesis de resultados"
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            "identificador" => "abst0050"
            "titulo" => "Conclusiones"
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          "leyenda" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">We used Ernst&#39;s assessment criteria &#40;Ernst E&#46; Alternative Medicine&#46; A Critical Assessment of 202 Modalities&#46; Second Edition&#46; Springer&#44; 2022&#41;&#44; plus quality of evidence&#44; but judged assessment based on our revision of the scientific literature&#46; Plausibility&#58; assumptions of the measures are consistent with established knowledge of the human body&#46; Efficacy&#58; performance according to the available scientific evidence and its quality&#46; Safety&#58; production of harm&#46; Cost&#58; estimation of associated expenditure&#46; Risk&#8211;benefit balance&#58; combination of efficacy and safety&#46; With the sign &#8220;-&#8221; we want to indicate lack of sufficient evidence to judge&#59; if efficacy is negative or debated&#44; the risk&#8211;benefit balance and the benefits to blood pressure do not merit assessment&#44; and in any case&#44; would be &#8220;negative&#8221; at present&#46; The cost may be high if the measure is assisted and continued&#46;</p><p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Prepared using references cited in the text&#44; especially Mancia et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib1775"><span class="elsevierStyleSup">169</span></a> Jones et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib1785"><span class="elsevierStyleSup">171</span></a> and Wolf and Bisognano&#46;<a class="elsevierStyleCrossRef" href="#bib1825"><span class="elsevierStyleSup">176</span></a></p>"
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                  \t\t\t\t  " align="" valign="\n
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                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Plausibilidad biol&#243;gicaCalidad&#47;cantidad evidenciaEficaciaSeguridadCosteBalance riesgo-beneficioBeneficios en PA&#47;HTAOtros efectos beneficiosos&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Biological plausibilityQuality&#47;quantity of evidenceEfficacySafetyCostRisk&#8211;benefit balanceBenefits to BP&#47;HTAOther beneficial effects&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">AcupunturaManipulaci&#243;n espinal&#47;quiropr&#225;cticaMindfulness&#44; meditaci&#243;n&#44; quigongM&#250;sicoterapiaTai ChiYoga&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">AcupunctureSpinal manipulation&#47;chiropracticMindfulness&#44; meditation&#44; qigongMusic therapyTai ChiYoga&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">DebatidaD&#233;bilS&#237;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">DebatedWeakYes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Baja&#47;EscasaMedia&#47;ModeradaMedia&#47;EscasaBaja&#47;Moderada&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Low&#47;PoorMedium&#47;ModerateMedium&#47;PoorLow&#47;Moderate&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Riesgos ocasionalesAlta&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Occasional riskHigh&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">BajoAlto&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">LowHigh&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Bueno&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Good&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dolor cr&#243;nico&#44; estr&#233;sDolor espalda y cuelloMental&#44; depresi&#243;n&#44; cardiovascularEstr&#233;s&#44; depresi&#243;nOsteoporosis&#44; ca&#237;das&#44; cardiovascularDepresi&#243;n&#44; estr&#233;s&#44; l&#237;pidos&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Chronic pain&#44; stressBack and neck painMental&#44; depression&#44; cardiovascularStress&#44; depressionOsteoporosis&#44; falls&#44; cardiovascularDepression&#44; stress&#44; lipids&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
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          "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Assessment of selected non-biological alternative measures relating to blood pressure and hypertension&#46;</p>"
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          "leyenda" => "<p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">The scientific evidence supporting each measure&#44; its efficacy and potency in lowering blood pressure considers the number and quality of studies reviewed&#46; Safety&#58; &#8220;-&#8221; denotes no special risks&#46;</p><p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">Prepared using several references from the text in addition to Willett et al&#46;<a class="elsevierStyleCrossRef" href="#bib1830"><span class="elsevierStyleSup">177</span></a></p>"
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">FormaSuplementoDietaF&#225;rmaco&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">FormSupplementDietDrug&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">EficaciaS&#237;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">EfficacyYes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">MagnitudPeque&#241;aModeradaEscasa&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">MagnitudeSmallModeratePoor&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">Evidencia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Evidence&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">EvidenciaEscasaModeradaBuena&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">EvidencePoorModerateGood&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">SeguridadPrecauci&#243;n por hiperpotasemiaToxicidad por nitratos&#47;nitrosos&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">SafetyCaution for hyperkalaemiaNitrate&#47;n-nitroso toxicity&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#193;cido f&#243;licoAjoAlcachofaCacao&#44; chocolate negroCaf&#233;Coenzima Q10EspirulinaL-ArgininaMagnesioMelatoninaP&#233;ptidos y Probi&#243;ticos en lechePotasioRemolachaSalicorniaT&#233;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Folic acidGarlicArtichokeCocoa&#44; dark chocolateCoffeeCoenzyme Q10Spirulina<span class="elsevierStyleSmallCaps">l</span>-ArginineMagnesiumMelatoninPeptides and Probiotics in milkPotassiumBeetrootSalicorniaTea&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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        "descripcion" => array:1 [
          "en" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Blood pressure lowering effects with various orally consumed biological substances&#46;</p>"
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        "texto" => "<p id="par0480" class="elsevierStylePara elsevierViewall">We would like to thank Javier Mu&#241;oz-Laguna &#40;Universidad of Zurich and Autonomous University of Madrid&#41; for advice on chiropractic care&#46;</p><p id="par0485" class="elsevierStylePara elsevierViewall">And Joan Montaner Villalonga&#44; neurologist and Head of the Andalusian stroke plan&#46; Hospital Virgen Macarena&#44; Seville&#44; for his advice on salicornia&#46;</p>"
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Article information

ISSN: 18891837
Original language: English

DOI:10.1016/j.hipert.2023.11.001

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