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Current Pharmaceutical Design


ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Mini-Review Article

Effects of Drugs, Phytoestrogens, Nutrients and Probiotics on Endothelial Dysfunction in the Estrogen-Deficient State

Author(s): Phablo Wendell C. Oliveira, Mariana R. Couto, Glauciene J. de Sousa, Pollyana Peixoto, Flávia S.A. Moraes, Tadeu U. de Andrade and Nazaré S. Bissoli*

Volume 26, Issue 30, 2020

Page: [3711 - 3722] Pages: 12

DOI: 10.2174/1381612826666200331084338

Price: $65


Background: Endothelial dysfunction is commonly present in estrogen-deficient states, e.g., after menopause. In the search for alternatives to hormone replacement therapy (HRT), treatments based on phytoestrogens or in non-hormonal mechanisms have been under evaluation.

Objective: Here we aim to present an overview of innovative potential treatments for endothelial dysfunction in estrogen-deficient states, introducing our own preliminary data about the probiotic kefir.

Methods: We conducted a review based on a PubMed database search for keywords of interest (Menopause, Ovariectomy, Vascular dysfunction, Hot flashes, Metformin, Statins, Phytoestrogens, Omega-3, Vitamin D, Probiotics).

Results: Vascular parameters were found to be improved by both metformin and statins through pleiotropic effects, being related to a decrease in oxidative stress and restoration of the nitric oxide pathway. Phytoestrogens such as genistein and resveratrol have also been shown to improve vascular dysfunction, which seems to involve their estrogenic-like actions. Omega-3, vitamin D and its analogues, as well as probiotics, have shown similar vascular beneficial effects in both postmenopausal women and an animal model of ovariectomy (OVX), which could be related to antioxidant and/or anti-inflammatory effects. Moreover, our preliminary data on the probiotic kefir treatment in OVX rats suggested a vascular antioxidant effect. In particular, some evidence points to statins and vitamin D having anti-atherogenic effects.

Conclusion: Pleiotropic effects of common medications and natural compounds could have therapeutic potential for endothelial dysfunction in estrogen-deficient states. They could, therefore, work as future complementary or alternative treatments to HRT.

Keywords: Menopause, ovariectomy, metformin, statins, phytoestrogens, Omega-3, Vitamin D, probiotics.

Iorga A, Cunningham CM, Moazeni S, Ruffenach G, Umar S, Eghbali M. The protective role of estrogen and estrogen receptors in cardiovascular disease and the controversial use of estrogen therapy. Biol Sex Differ 2017; 8(1): 33.
[] [PMID: 29065927]
Agarwal S, Alzahrani FA, Ahmed A. Hormone replacement therapy: would it be possible to replicate a functional ovary? Int J Mol Sci 2018; 19(10): E3160.
[] [PMID: 30322209]
Manson JE, Hsia J, Johnson KC, et al. Estrogen plus progestin and the risk of coronary heart disease. N Engl J Med 2003; 349(6): 523-34.
[] [PMID: 12904517]
Oliveira PWC, de Sousa GJ, Caliman IF, et al. Metformin ameliorates ovariectomy-induced vascular dysfunction in non-diabetic Wistar rats. Clin Sci (Lond) 2014; 127(4): 265-75.
[] [PMID: 24521306]
Caliman IF, Lamas AZ, Dalpiaz PL, et al. Endothelial relaxation mechanisms and oxidative stress are restored by atorvastatin therapy in ovariectomized rats. PLoS One 2013; 8(11): e80892.
[] [PMID: 24278341]
Gencel VB, Benjamin MM, Bahou SN, Khalil RA. Vascular effects of phytoestrogens and alternative menopausal hormone therapy in cardiovascular disease. Mini Rev Med Chem 2012; 12(2): 149-74.
[] [PMID: 22070687]
Gortan Cappellari G, Losurdo P, Mazzucco S, et al. Treatment with n-3 polyunsaturated fatty acids reverses endothelial dysfunction and oxidative stress in experimental menopause. J Nutr Biochem 2013; 24(1): 371-9.
[] [PMID: 23159066]
Dong J, Wong SL, Lau CW, et al. Calcitriol restores renovascular function in estrogen-deficient rats through downregulation of cyclooxygenase- 2 and the thromboxane-prostanoid receptor. Kidney Int 2013; 84(1): 54-63.
[] [PMID: 23423254]
Szulińska M, Łoniewski I, Skrypnik K, et al. Multispecies probiotic supplementation favorably affects vascular function and reduces arterial stiffness in obese postmenopausal women-a 12-week placebocontrolled and randomized clinical study. Nutrients 2018; 10(11): E1672.
[] [PMID: 30400570]
Jurrissen TJ, Olver TD, Winn NC, et al. Endothelial dysfunction occurs independently of adipose tissue inflammation and insulin resistance in ovariectomized Yucatan miniature-swine. Adipocyte 2018; 7(1): 35-44.
[] [PMID: 29283284]
Moreau KL, Hildreth KL. Vascular Aging across the Menopause Transition in Healthy Women. Adv Vasc Med 2014; 2014: 204390.
[] [PMID: 25984561]
Vanhoutte PM, Shimokawa H, Feletou M, Tang EH. Endothelial dysfunction and vascular disease - a 30th anniversary update. Acta Physiol (Oxf) 2017; 219(1): 22-96.
[] [PMID: 26706498]
Lamas AZ, Caliman IF, Dalpiaz PL, et al. Comparative effects of estrogen, raloxifene and tamoxifen on endothelial dysfunction, inflammatory markers and oxidative stress in ovariectomized rats. Life Sci 2015; 124: 101-9.
[] [PMID: 25623855]
Camporez JP, Akamine EH, Davel AP, Franci CR, Rossoni LV, Carvalho CR. Dehydroepiandrosterone protects against oxidative stress-induced endothelial dysfunction in ovariectomized rats. J Physiol 2011; 589(Pt 10): 2585-96.
[] [PMID: 21486789]
Yazğan Y, Nazıroğlu M. Ovariectomy-induced mitochondrial oxidative stress, apoptosis, and calcium ion influx through TRPA1, TRPM2, and TRPV1 are prevented by 17β-Estradiol, Tamoxifen, and Raloxifene in the hippocampus and dorsal root ganglion of rats. Mol Neurobiol 2017; 54(10): 7620-38.
[] [PMID: 27832523]
Valencia AP, Schappal AE, Morris EM, Thyfault JP, Lowe DA, Spangenburg EE. The presence of the ovary prevents hepatic mitochondrial oxidative stress in young and aged female mice through glutathione peroxidase 1. Exp Gerontol 2016; 73: 14-22.
[] [PMID: 26608809]
Seo SY, Kang SY, Kwon OS, et al. A mechanical acupuncture instrument mitigates the endoplasmic reticulum stress and oxidative stress of ovariectomized rats. Integr Med Res 2019; 8(3): 187-94.
[] [PMID: 31463191]
Zhou Y, Liu X, Li W, Sun X, Xie Z. Endoplasmic reticulum stress contributes to the pathogenesis of stress urinary incontinence in postmenopausal women. J Int Med Res 2018; 46(12): 5269-77.
[] [PMID: 30426803]
Bansal R, Aggarwal N. Menopausal hot flashes: a concise review. J Midlife Health 2019; 10(1): 6-13.
[] [PMID: 31001050]
Thurston RC, Chang Y, Barinas-Mitchell E, et al. Physiologically assessed hot flashes and endothelial function among midlife women. Menopause 2017; 24(8): 886-93.
[] [PMID: 28399007]
Silveira JS, Clapauch R,. Souza Md, Bouskela E. Hot flashes: emerging cardiovascular risk factors in recent and late postmenopause and their association with higher blood pressure. Menopause 2016; 23(8): 846-55.
[] [PMID: 27219834]
Marshall SM. 60 years of metformin use: a glance at the past and a look to the future. Diabetologia 2017; 60(9): 1561-5.
[] [PMID: 28776085]
Lee SH, Min KJ. Caloric restriction and its mimetics. BMB Rep 2013; 46(4): 181-7.
[] [PMID: 23615258]
Zilov AV, Abdelaziz SI, AlShammary A, et al. Mechanisms of action of metformin with special reference to cardiovascular protection. Diabetes Metab Res Rev 2019; 35(7): e3173.
[] [PMID: 31021474]
Zhou J, Massey S, Story D, Li L. Metformin: An old drug with new applications. Int J Mol Sci 2018; 19(10): 2863.
[] [PMID: 30241400]
Luo F, Das A, Chen J, Wu P, Li X, Fang Z. Metformin in patients with and without diabetes: a paradigm shift in cardiovascular disease management. Cardiovasc Diabetol 2019; 18(1): 54.
[] [PMID: 31029144]
Matzinger M, Fischhuber K, Heiss EH. Activation of Nrf2 signaling by natural products-can it alleviate diabetes? Biotechnol Adv 2018; 36(6): 1738-67.
[] [PMID: 29289692]
Nafisa A, Gray SG, Cao Y, et al. Endothelial function and dysfunction: Impact of metformin. Pharmacol Ther 2018; 192: 150-62.
[] [PMID: 30056057]
Jadhav S, Ferrell W, Greer IA, Petrie JR, Cobbe SM, Sattar N. Effects of metformin on microvascular function and exercise tolerance in women with angina and normal coronary arteries: a randomized, double-blind, placebo-controlled study. J Am Coll Cardiol 2006; 48(5): 956-63.
[] [PMID: 16949486]
Maudar V, Winters SJ, Villafuerte BC. Hot flashes and fatigue relieved by metformin. Endocr Pract 2009; 15(1): 30-4.
[] [PMID: 19211394]
Forouzandeh F, Salazar G, Patrushev N, et al. Metformin beyond diabetes: pleiotropic benefits of metformin in attenuation of atherosclerosis. J Am Heart Assoc 2014; 3(6): e001202.
[] [PMID: 25527624]
Jialal I, Devaraj S. AHA/ACC/Multisociety Cholesterol Guidelines: highlights. Ther Adv Cardiovasc Dis 2019; 13: 1753944719881579.
[] [PMID: 31590600]
Sirtori CR. The pharmacology of statins. Pharmacol Res 2014; 88: 3-11.
[] [PMID: 24657242]
Taylor F, Huffman MD, Macedo AF, et al. Statins for the primary prevention of cardiovascular disease. Cochrane Database Syst Rev 2013; (1): : CD004816.
[] [PMID: 23440795]
Oesterle A, Laufs U, Liao JK. Pleiotropic Effects of Statins on the Cardiovascular System. Circ Res 2017; 120(1): 229-43.
[] [PMID: 28057795]
Mollazadeh H, Atkin SL, Butler AE, Ruscica M, Sirtori CR, Sahebkar A. The effect of statin therapy on endoplasmic reticulum stress. Pharmacol Res 2018; 137: 150-8.
[] [PMID: 30312664]
Bouitbir J, Singh F, Charles AL, et al. Statins trigger mitochondrial reactive oxygen species-induced apoptosis in glycolytic skeletal muscle. Antioxid Redox Signal 2016; 24(2): 84-98.
[] [PMID: 26414931]
Zhou Q, Liao JK. Statins and cardiovascular diseases: from cholesterol lowering to pleiotropy. Curr Pharm Des 2009; 15(5): 467-78.
[] [PMID: 19199975]
Shuto H, Tominaga K, Yamauchi A, et al. The statins fluvastatin and pravastatin exert anti-flushing effects by improving vasomotor dysfunction through nitric oxide-mediated mechanisms in ovariectomized animals. Eur J Pharmacol 2011; 651(1-3): 234-9.
[] [PMID: 21114974]
Cetinkaya Demir B, Uyar Y, Ozbilgin K, Köse C. Effect of raloxifene and atorvastatin in atherosclerotic process in ovariectomized rats. J Obstet Gynaecol Res 2013; 39(1): 229-36.
[] [PMID: 22845341]
Pitha J, Bobková D, Kovár J, Havlícková J, Poledne R. Antiatherogenic effect of simvastatin is not due to decrease of LDL cholesterol in ovariectomized golden Syrian hamster. Physiol Res 2010; 59(3): 401-6.
[PMID: 19681658]
Marchesi S, Lupattelli G, Siepi D, et al. Short-term atorvastatin treatment improves endothelial function in hypercholesterolemic women. J Cardiovasc Pharmacol 2000; 36(5): 617-21.
[] [PMID: 11065222]
Igase M, Kohara K, Tabara Y, et al. Low-dose rosuvastatin improves the functional and morphological markers of atherosclerosis in asymptomatic postmenopausal women with dyslipidemia. Menopause 2012; 19(12): 1294-9.
[] [PMID: 22850442]
Ridker PM, Pradhan A, MacFadyen JG, Libby P, Glynn RJ. Cardiovascular benefits and diabetes risks of statin therapy in primary prevention: an analysis from the JUPITER trial. Lancet 2012; 380(9841): 565-71.
[] [PMID: 22883507]
Pinal-Fernandez I, Casal-Dominguez M, Mammen AL. Statins: pros and cons. Med Clin (Barc) 2018; 150(10): 398-402.
[] [PMID: 29292104]
Stachowiak G, Pertyński T, Pertyńska-Marczewska M. Metabolic disorders in menopause. Przegl Menopauz 2015; 14(1): 59-64.
[] [PMID: 26327890]
Tournadre A. Statins, myalgia, and rhabdomyolysis. Joint Bone Spine 2019; 87(1): 37-42.
Desmawati D, Sulastri D. Phytoestrogens and Their Health Effect. Open Access Maced J Med Sci 2019; 7(3): 495-9.
[] [PMID: 30834024]
Park YJ, Jang YM, Kwon YH. Isoflavones prevent endoplasmic reticulum stress-mediated neuronal degeneration by inhibiting tau hyperphosphorylation in SH-SY5Y cells. J Med Food 2009; 12(3): 528-35.
[] [PMID: 19627200]
Huang YH, Zhang QH. Genistein reduced the neural apoptosis in the brain of ovariectomised rats by modulating mitochondrial oxidative stress. Br J Nutr 2010; 104(9): 1297-303.
[] [PMID: 20579403]
Lissin LW, Oka R, Lakshmi S, Cooke JP. Isoflavones improve vascular reactivity in post-menopausal women with hypercholesterolemia. Vasc Med 2004; 9(1): 26-30.
[] [PMID: 15230485]
Vera R, Jiménez R, Lodi F, et al. Genistein restores caveolin-1 and AT-1 receptor expression and vascular function in large vessels of ovariectomized hypertensive rats. Menopause 2007; 14(5): 933-40.
[] [PMID: 17667142]
Crisafulli A, Altavilla D, Marini H, et al. Effects of the phytoestrogen genistein on cardiovascular risk factors in postmenopausal women. Menopause 2005; 12(2): 186-92.
[] [PMID: 15772566]
Villa P, Costantini B, Suriano R, et al. The differential effect of the phytoestrogen genistein on cardiovascular risk factors in postmenopausal women: relationship with the metabolic status. J Clin Endocrinol Metab 2009; 94(2): 552-8.
[] [PMID: 19017760]
Squadrito F, Altavilla D, Crisafulli A, et al. Effect of genistein on endothelial function in postmenopausal women: a randomized, double-blind, controlled study. Am J Med 2003; 114(6): 470-6.
[] [PMID: 12727580]
Squadrito F, Altavilla D, Morabito N, et al. The effect of the phytoestrogen genistein on plasma nitric oxide concentrations, endothelin- 1 levels and endothelium dependent vasodilation in postmenopausal women. Atherosclerosis 2002; 163(2): 339-47.
[] [PMID: 12052481]
D’Anna R, Cannata ML, Marini H, et al. Effects of the phytoestrogen genistein on hot flushes, endometrium, and vaginal epithelium in postmenopausal women: a 2-year randomized, double-blind, placebo- controlled study. Menopause 2009; 16(2): 301-6.
[] [PMID: 19034051]
Irace C, Marini H, Bitto A, et al. Genistein and endothelial function in postmenopausal women with metabolic syndrome. Eur J Clin Invest 2013; 43(10): 1025-31.
[] [PMID: 23899172]
Kulkarni SS, Cantó C. The molecular targets of resveratrol. Biochim Biophys Acta 2015; 1852(6): 1114-23.
[] [PMID: 25315298]
Renaud S, de Lorgeril M. Wine, alcohol, platelets, and the French paradox for coronary heart disease. Lancet 1992; 339(8808): 1523-6.
[] [PMID: 1351198]
Catalgol B, Batirel S, Taga Y, Ozer NK. Resveratrol: French paradox revisited. Front Pharmacol 2012; 3: 141.
[] [PMID: 22822401]
Wallerath T, Deckert G, Ternes T, et al. Resveratrol, a polyphenolic phytoalexin present in red wine, enhances expression and activity of endothelial nitric oxide synthase. Circulation 2002; 106(13): 1652-8.
[] [PMID: 12270858]
Klinge CM, Blankenship KA, Risinger KE, et al. Resveratrol and estradiol rapidly activate MAPK signaling through estrogen receptors alpha and beta in endothelial cells. J Biol Chem 2005; 280(9): 7460-8.
[] [PMID: 15615701]
Marques BCAA, Trindade M, Aquino JCF, et al. Beneficial effects of acute trans-resveratrol supplementation in treated hypertensive patients with endothelial dysfunction. Clin Exp Hypertens 2018; 40(3): 218-23.
[] [PMID: 29431520]
Mizutani K, Ikeda K, Kawai Y, Yamori Y. Resveratrol attenuates ovariectomy-induced hypertension and bone loss in stroke-prone spontaneously hypertensive rats. J Nutr Sci Vitaminol (Tokyo) 2000; 46(2): 78-83.
[] [PMID: 10885794]
Petit M, Guihot AL, Grimaud L, et al. Resveratrol improved flow-mediated outward arterial remodeling in ovariectomized rats with hypertrophic effect at high dose. PLoS One 2016; 11(1): e0146148.
[] [PMID: 26734763]
Fabricio V, Oishi JC, Biffe BG, et al. Resveratrol treatment normalizes the endothelial function and blood pressure in ovariectomized rats. Arq Bras Cardiol 2017; 108(2): 116-21.
[] [PMID: 28327868]
Majumdar AS, Joshi PA, Giri PR. Resveratrol attenuated smokeless tobacco-induced vascular and metabolic complications in ovariectomized rats. Menopause 2013; 20(8): 869-76.
[] [PMID: 23884055]
Li Y, Huang J, Yan Y, et al. Preventative effects of resveratrol and estradiol on streptozotocin-induced diabetes in ovariectomized mice and the related mechanisms. PLoS One 2018; 13(10): e0204499.
[] [PMID: 30273360]
Wong RHX, Evans HM, Howe PRC. Resveratrol supplementation reduces pain experience by postmenopausal women. Menopause 2017; 24(8): 916-22.
[] [PMID: 28350759]
Wong RH, Howe PR, Buckley JD, Coates AM, Kunz I, Berry NM. Acute resveratrol supplementation improves flow-mediated dilatation in overweight/obese individuals with mildly elevated blood pressure. Nutr Metab Cardiovasc Dis 2011; 21(11): 851-6.
[] [PMID: 20674311]
Cruz MN, Agewall S, Schenck-Gustafsson K, Kublickiene K. Acute dilatation to phytoestrogens and estrogen receptor subtypes expression in small arteries from women with coronary heart disease. Atherosclerosis 2008; 196(1): 49-58.
[] [PMID: 17367797]
Leo L, Surico D, Deambrogio F, et al. Preliminary data on the effectiveness of resveratrol in a new formulation in treatment of hot flushes. Minerva Ginecol 2015; 67(5): 475-83.
[PMID: 26491826]
Brito P, Almeida LM, Dinis TC. The interaction of resveratrol with ferrylmyoglobin and peroxynitrite; protection against LDL oxidation. Free Radic Res 2002; 36(6): 621-31.
[] [PMID: 12180187]
Wang Z, Zou J, Cao K, Hsieh TC, Huang Y, Wu JM. Dealcoholized red wine containing known amounts of resveratrol suppresses atherosclerosis in hypercholesterolemic rabbits without affecting plasma lipid levels. Int J Mol Med 2005; 16(4): 533-40.
[PMID: 16142383]
Henry LA, Witt DM. Resveratrol: phytoestrogen effects on reproductive physiology and behavior in female rats. Horm Behav 2002; 41(2): 220-8.
[] [PMID: 11855907]
Jargin SV. Soy and phytoestrogens: possible side effects. Ger Med Sci 2014; 12: Doc18.
[PMID: 25587246]
Elagizi A, Lavie CJ, Marshall K, DiNicolantonio JJ, O’Keefe JH, Milani RV. Omega-3 polyunsaturated fatty acids and cardiovascular health: a comprehensive review. Prog Cardiovasc Dis 2018; 61(1): 76-85.
[] [PMID: 29571892]
Zanetti M, Grillo A, Losurdo P, et al. Omega-3 Polyunsaturated Fatty Acids: Structural and Functional Effects on the Vascular Wall. BioMed Res Int 2015; 2015: 791978.
[] [PMID: 26301252]
Sheikh O, Vande Hei AG, Battisha A, Hammad T, Pham S, Chilton R. Cardiovascular, electrophysiologic, and hematologic effects of omega-3 fatty acids beyond reducing hypertriglyceridemia: as it pertains to the recently published REDUCE-IT trial. Cardiovasc Diabetol 2019; 18(1): 84.
[] [PMID: 31234885]
Okada LSDRR, Oliveira CP, Stefano JT, et al. Omega-3 PUFA modulate lipogenesis, ER stress, and mitochondrial dysfunction markers in NASH - Proteomic and lipidomic insight. Clin Nutr 2018; 37(5): 1474-84.
[] [PMID: 29249532]
Losurdo P, Grillo A, Panizon E, et al. Supplementation of omega-3 polyunsaturated fatty acids prevents increase in arterial stiffness after experimental menopause. J Cardiovasc Pharmacol Ther 2014; 19(1): 114-20.
[] [PMID: 24038017]
lareva NV, Govorin AV, Luzina EV. The role of imbalance of fatty acids in formation of endothelium dysfunction in women in menopause. Klin Lab Diagn 2012; (8): 11-4.
[PMID: 23097984]
Rhee Y, Paik MJ, Kim KR, et al. Plasma free fatty acid level patterns according to cardiovascular risk status in postmenopausal women. Clin Chim Acta 2008; 392(1-2): 11-6.
[] [PMID: 18328818]
Ciappolino V, Mazzocchi A, Enrico P, et al. N-3 Polyunsatured fatty acids in menopausal transition: a systematic review of depressive and cognitive disorders with accompanying vasomotor symptoms. Int J Mol Sci 2018; 19(7): 1849.
[] [PMID: 29937484]
Cesari M, Incalzi RA, Zamboni V, Pahor M. Vitamin D hormone: a multitude of actions potentially influencing the physical function decline in older persons. Geriatr Gerontol Int 2011; 11(2): 133-42.
[] [PMID: 21134097]
Jablonski NG, Chaplin G. The roles of vitamin D and cutaneous vitamin D production in human evolution and health. Int J Paleopathol 2018; 23: 54-9.
[] [PMID: 29606375]
Lai YH, Fang TC. The pleiotropic effect of vitamin d. ISRN Nephrol 2013; 2013: 898125.
[] [PMID: 24967240]
Palacios C, Gonzalez L. Is vitamin D deficiency a major global public health problem? J Steroid Biochem Mol Biol 2014; 144(Pt A): 138-45.
Wang H, Chen W, Li D, et al. Vitamin D and Chronic Diseases. Aging Dis 2017; 8(3): 346-53.
[] [PMID: 28580189]
Carlberg C. The physiology of vitamin D-far more than calcium and bone. Front Physiol 2014; 5: 335.
[] [PMID: 25228886]
Zhang R, Naughton DP. Vitamin D in health and disease: current perspectives. Nutr J 2010; 9: 65.
[] [PMID: 21143872]
Schnatz PF, Nudy M, O’Sullivan DM, et al. Coronary artery vitamin D receptor expression and plasma concentrations of 25- hydroxyvitamin D: their association with atherosclerosis. Menopause 2012; 19(9): 967-73.
[] [PMID: 22617336]
Muhammad MH, Hussien NI, Elwia SK, Vitamin D. Replacement mitigates menopause-associated dyslipidaemia and atherogenic indices in ovariectomized rats; a biochemical study. Exp Clin Endocrinol Diabetes 2019; 128(3)
[PMID: 31234220]
Stach K, Kälsch AI, Nguyen XD, et al. 1α,25-dihydroxyvitamin D3 attenuates platelet activation and the expression of VCAM-1 and MT1-MMP in human endothelial cells. Cardiology 2011; 118(2): 107-15.
[] [PMID: 21546774]
Rostkowska-Nadolska B, Sliupkas-Dyrda E, Potyka J, et al. Vitamin D derivatives: calcitriol and tacalcitol inhibits interleukin-6 and interleukin-8 expression in human nasal polyp fibroblast cultures. Adv Med Sci 2010; 55(1): 86-92.
[] [PMID: 20439185]
Pfeifer M, Begerow B, Minne HW, Nachtigall D, Hansen C. Effects of a short-term vitamin D(3) and calcium supplementation on blood pressure and parathyroid hormone levels in elderly women. J Clin Endocrinol Metab 2001; 86(4): 1633-7.
[PMID: 11297596]
Wood AD, Secombes KR, Thies F, et al. Vitamin D3 supplementation has no effect on conventional cardiovascular risk factors: a parallel- group, double-blind, placebo-controlled RCT. J Clin Endocrinol Metab 2012; 97(10): 3557-68.
[] [PMID: 22865902]
LeBlanc ES, Hedlin H, Qin F, et al. Calcium and vitamin D supplementation do not influence menopause-related symptoms: Results of the Women’s Health Initiative Trial. Maturitas 2015; 81(3): 377-83.
[] [PMID: 26044075]
He M, Shi B. Gut microbiota as a potential target of metabolic syndrome: the role of probiotics and prebiotics. Cell Biosci 2017; 7: 54.
[] [PMID: 29090088]
Lerner A, Shoenfeld Y, Matthias T. Probiotics: If it does not help it does not do any harm. really? Microorganisms 2019; 7(4): E104.
[] [PMID: 30979072]
Mashaqi S, Gozal D. Obstructive sleep apnea and systemic hypertension: gut dysbiosis as the mediator? J Clin Sleep Med 2019; 15(10): 1517-27.
[] [PMID: 31596218]
Cao W, Chin Y, Chen X, et al. The role of gut microbiota in the resistance to obesity in mice fed a high fat diet. Int J Food Sci Nutr 2019; 27: 1-11.
[] [PMID: 31774018]
Raizada MK, Joe B, Bryan NS, et al. Report of the national heart, lung, and blood institute working group on the role of microbiota in blood pressure regulation: current status and future directions. Hypertension 2017; 70: 479-85.
[] [PMID: 28760940]
Yang T, Santisteban MM, Rodriguez V, et al. Gut dysbiosis is linked to hypertension. Hypertension 2015; 65(6): 1331-40.
[] [PMID: 25870193]
Vieira AT, Castelo PM, Ribeiro DA, Ferreira CM. Influence of oral and gut microbiota in the health of menopausal women. Front Microbiol 2017; 8: 1884.
[] [PMID: 29033921]
Rezazadeh L, Gargari BP, Jafarabadi MA, Alipour B. Effects of probiotic yogurt on glycemic indexes and endothelial dysfunction markers in patients with metabolic syndrome. Nutrition 2019; 62: 162-8.
[] [PMID: 30921552]
Mauricio MD, Serna E, Fernández-Murga ML, et al. Bifidobacterium pseudocatenulatum CECT 7765 supplementation restores altered vascular function in an experimental model of obese mice. Int J Med Sci 2017; 14(5): 444-51.
[] [PMID: 28539820]
Friques AG, Arpini CM, Kalil IC, et al. Chronic administration of the probiotic kefir improves the endothelial function in spontaneously hypertensive rats. J Transl Med 2015; 13: 390.
[] [PMID: 26715471]
Lambert MNT, Thorup AC, Hansen ESS, Jeppesen PB. Combined Red Clover isoflavones and probiotics potently reduce menopausal vasomotor symptoms. PLoS One 2017; 12(6): e0176590.
[] [PMID: 28591133]
Park KY, Kim B, Hyun CK. Lactobacillus rhamnosus GG improves glucose tolerance through alleviating ER stress and suppressing macrophage activation in db/db mice. J Clin Biochem Nutr 2015; 56(3): 240-6.
[] [PMID: 26060355]
Ren T, Zhu L, Shen Y, Mou Q, Lin T, Feng H. Protection of hepatocyte mitochondrial function by blueberry juice and probiotics via SIRT1 regulation in non-alcoholic fatty liver disease. Food Funct 2019; 10(3): 1540-51.
[] [PMID: 30785444]
Klippel BF, Duemke LB, Leal MA, et al. Effects of Kefir on the cardiac autonomic tones and baroreflex sensitivity in spontaneously hypertensive rats. Front Physiol 2016; 7: 211.
[] [PMID: 27375490]
Santanna AF, Filete PF, Lima EM, et al. Chronic administration of the soluble, nonbacterial fraction of kefir attenuates lipid deposition in LDLr-/- mice. Nutrition 2017; 35: 100-5.
[] [PMID: 28241975]
Brasil GA, Silva-Cutini MA, Moraes FSA, et al. The benefits of soluble non-bacterial fraction of kefir on blood pressure and cardiac hypertrophy in hypertensive rats are mediated by an increase in baroreflex sensitivity and decrease in angiotensin-converting enzyme activity. Nutrition 2018; 51-52: 66-72.
[] [PMID: 29605766]
Silva-Cutini MA, Almeida SA, Nascimento AM, et al. Long-term treatment with kefir probiotics ameliorates cardiac function in spontaneously hypertensive rats. J Nutr Biochem 2019; 66: 79-85.
[] [PMID: 30776608]
Qin J, Li Y, Cai Z, et al. A metagenome-wide association study of gut microbiota in type 2 diabetes. Nature 2012; 490(7418): 55-60.
[] [PMID: 23023125]
Yu F, Han W, Zhan G, et al. Abnormal gut microbiota composition contributes to the development of type 2 diabetes mellitus in db/db mice. Aging (Albany NY) 2019; 11(22): 10454-67.
[] [PMID: 31760385]
Bengoa AA, Iraporda C, Garrote GL, Abraham AG. Kefir micro organisms: their role in grain assembly and health properties of fermented milk. J Appl Microbiol 2019; 126(3): 686-700.
[] [PMID: 30218595]
John SM, Deeseenthum S. Properties and benefits of kefir - A review. Songklanakarin J Sci Technol 2015; 37(3): 275-82.
Fathi Y, Ghodrati N, Zibaeenezhad MJ, Faghih S. Kefir drink causes a significant yet similar improvement in serum lipid profile, compared with low-fat milk, in a dairy-rich diet in overweight or obese premenopausal women: A randomized controlled trial. J Clin Lipidol 2017; 11(1): 136-46.
[] [PMID: 28391880]
Fathi Y, Faghih S, Zibaeenezhad MJ, Tabatabaei SH. Kefir drink leads to a similar weight loss, compared with milk, in a dairy-rich non-energy-restricted diet in overweight or obese premenopausal women: a randomized controlled trial. Eur J Nutr 2016; 55(1): 295-304.
[] [PMID: 25648739]
Mulvany MJ, Halpern W. Contractile properties of small arterial resistance vessels in spontaneously hypertensive and normotensive rats. Circ Res 1977; 41(1): 19-26.
[] [PMID: 862138]
Friques AGF, Santos FDN, Angeli DB, et al. Bisphenol A contamination in infant rats: molecular, structural, and physiological cardiovascular changes and the protective role of kefir. J Nutr Biochem 2020; 75: 108254.
[] [PMID: 31707283]

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