{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,19]],"date-time":"2026-07-19T10:08:33Z","timestamp":1784455713936,"version":"3.55.0"},"reference-count":33,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2020,3,3]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              High blood pressure (\n              <jats:styled-content style=\"fixed-case\">BP<\/jats:styled-content>\n              ) has long been recognized as a major health threat and, particularly, a major risk factor for stroke, cardiovascular disease, and end\u2010organ damage. However, the identification of a novel, alternative, integrative approach for the control of\n              <jats:styled-content style=\"fixed-case\">BP<\/jats:styled-content>\n              and cardiovascular protection is still needed.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              Sixty\u2010nine uncontrolled hypertension patients, aged 40 to 68\u00a0years, on antihypertensive medication were enrolled in 2 double\u2010blind studies. Forty\u2010five were randomized to placebo or a new nutraceutical combination named AkP05, and\n              <jats:styled-content style=\"fixed-case\">BP<\/jats:styled-content>\n              , endothelial function, and circulating nitric oxide were assessed before and at the end of 4\u00a0weeks of treatment. Twenty\u2010four patients were randomized to diuretic or AkP05 for 4\u00a0weeks and underwent a cardiopulmonary exercise test to evaluate the effects of AkP05 on functional capacity of the cardiovascular, pulmonary, and muscular systems. Vascular and molecular studies were undertaken on mice to characterize the action of the single compounds contained in the AkP05 nutraceutical combination. AkP05 supplementation reduced\n              <jats:styled-content style=\"fixed-case\">BP<\/jats:styled-content>\n              , improved endothelial function, and increased nitric oxide release; cardiopulmonary exercise test revealed that AkP05 increased maximum O\n              <jats:sub>2<\/jats:sub>\n              uptake, stress tolerance, and maximal power output. In mice, AkP05 reduced\n              <jats:styled-content style=\"fixed-case\">BP<\/jats:styled-content>\n              and improved endothelial function, evoking increased nitric oxide release through the\n              <jats:styled-content style=\"fixed-case\">PKC<\/jats:styled-content>\n              \u03b1\/Akt\/endothelial nitric oxide synthase pathway and reducing reactive oxygen species production via\n              <jats:styled-content style=\"fixed-case\">NADPH<\/jats:styled-content>\n              \u2010oxidase inhibition. These effects were mediated by synergism of the single compounds of AkP05.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              This is the first study reporting positive effects of a nutraceutical combination on the vasculature and exercise tolerance in treated hypertensive patients. Our findings suggest that AkP05 may be used as an adjunct for the improvement of cardiovascular protection and to better control\n              <jats:styled-content style=\"fixed-case\">BP<\/jats:styled-content>\n              in uncontrolled hypertension.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.119.014923","type":"journal-article","created":{"date-parts":[[2020,2,21]],"date-time":"2020-02-21T00:00:11Z","timestamp":1582243211000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":21,"title":["New Nutraceutical Combination Reduces Blood Pressure and Improves Exercise Capacity in Hypertensive Patients Via a Nitric Oxide\u2013Dependent Mechanism"],"prefix":"10.1161","volume":"9","author":[{"given":"Albino","family":"Carrizzo","sequence":"first","affiliation":[{"name":"IRCCS Neuromed Pozzilli Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ornella","family":"Moltedo","sequence":"additional","affiliation":[{"name":"Department of Pharmacy University of Salerno Fisciano Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Damato","sequence":"additional","affiliation":[{"name":"IRCCS Neuromed Pozzilli Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katiuscia","family":"Martinello","sequence":"additional","affiliation":[{"name":"IRCCS Neuromed Pozzilli Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Di Pietro","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery University of Salerno Baronissi Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Oliveti","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery University of Salerno Baronissi Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fausto","family":"Acernese","sequence":"additional","affiliation":[{"name":"Department of Pharmacy University of Salerno Fisciano Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Giugliano","sequence":"additional","affiliation":[{"name":"Department of Advanced Biomedical Sciences University Federico II of Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raffaele","family":"Izzo","sequence":"additional","affiliation":[{"name":"Department of Advanced Biomedical Sciences University Federico II of Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduardo","family":"Sommella","sequence":"additional","affiliation":[{"name":"Department of Pharmacy University of Salerno Fisciano Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serena","family":"Migliarino","sequence":"additional","affiliation":[{"name":"Department of Clinical and Molecular Medicine School of Medicine and Psychology Sapienza University of Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ornella","family":"Piazza","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery University of Salerno Baronissi Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmine","family":"Izzo","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery University of Salerno Baronissi Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"Virtuoso","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine A.O.U. 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