Go to our Partner website

07/03/2024

Vascular Vitality and Boosting Endothelial Function

Heart and vessles

In arteries, the gradual accumulation of plaque causes the blood vessels to narrow over time. However, the plaque itself can also become unstable and rupture. This can potentially damage the inner lining of the arteries (endothelium) and block blood flow. 

Despite extensive research and medication, cardiovascular disease remains a leading killer. Statins, while beneficial for high-risk patients, come with side effects and limitations. 

The risk of a cardiovascular event is highest for those with arterial plaques at the most advanced level. Commonly, there are no symptoms until this process triggers a stroke or heart attack. A standardized extract derived from French Maritime Pine Bark has been shown to halt plaque accumulation.

Supporting this, the plant extract Centella Asiatica has been shown to help preserve the hard cap on existing atherosclerotic plaques, making them less likely to rupture and cause a fatal cardiovascular event. 


What is Atherosclerosis? 

Atherosclerosis is a major challenge that comes with the ageing process. It is the dangerous plaque buildup in arteries (1,2). This heightens the risk of heart attacks or strokes without warning symptoms (3). 

Both the French maritime pine bark and Centella asiatica extracts have been found to prevent plaque growth and stabilize it. This particularly reduces the likelihood of cardiovascular incidents. 

Studies show that together, they offer enhanced protection, potentially cut the plaque progression by 95% (4).


What is Endothelial Function? 

Endothelial function is like the health check-up of the inner walls of your blood vessels. 

These inner walls, called the endothelium, have several jobs: 

  • They help control how wide or narrow your blood vessels are, which affects blood pressure and how much blood gets to different parts of your body. 
  • They help prevent unnecessary blood clots from forming inside your vessels, ensuring blood flows smoothly. They can call in white blood cells to fight off infections or heal injuries. 
  • They act like bouncers at the door, deciding what gets into the blood and what stays out. 
  • They assist in creating new pathways for blood flow, which is important for healing wounds or growing new tissues. 

When the endothelium is not working well ("endothelial dysfunction"), it's like the body's internal traffic system breaking down. 

This can lead to: 

  • Narrowed blood vessels.
  • Unwanted blood clots.
  • A higher risk for heart problems.

It's important for our health to keep this endothelial layer functioning properly to prevent diseases, especially those related to the heart and blood vessels.


French Maritime Pine Bark Extract and Centalla Asiatica

What does french maritime pine bark extract do?

French maritime pine bark extract helps slow arterial plaque (5)

It does this by altering fat metabolism and reducing inflammation, crucial in atherosclerosis prevention (6,7). 

It has been shown in studies to: 

  • Decrease plaque and cholesterol levels.
  • Improve HDL ('good' cholesterol) (8). 
  • It can also enhance endothelial function by boosting nitric oxide production (9,10), essential for keeping arteries open and reducing clot risks (11). 

Clinical trials have further validated its potential to prevent artery constriction and promote better blood flow: 

  • A study was conducted on 23 patients with coronary artery disease, assessing the effects of French maritime pine bark extract (200 mg daily for eight weeks) on endothelial function and blood flow. 
  • The treatment significantly improved endothelial function by 32% and reduced oxidative stress, indicating its potential to slow plaque formation (12). 
  • Another study in Italy with 93 volunteers at risk of coronary artery disease due to elevated blood pressure, lipids, and sugar levels showed that 150 mg of the extract daily increased blood flow significantly, highlighting its preventive benefits for early-stage cardiovascular risks (13). 
  • This research stresses that French maritime pine bark extract as a promising option for preventing and managing early arterial changes and coronary artery disease.

What is Centella Asiatica?

Centella asiatica, known as gotu kola, has been shown to stabilize arterial plaques by enhancing collagen synthesis. This is crucial for maintaining the hard caps of plaques and preventing rupture (14,15). 

In studies, participants with soft plaques taking 60 mg of this extract thrice daily saw a 30% denser plaque over 12 months, reducing the risk of strokes or heart attacks (16).

Further research confirmed its efficacy in improving plaque stability and preventing cardiovascular events (16).

Dual Compound Clinical Research

To explore the effects of combining French maritime pine bark and centella asiatica on atherosclerosis, a study involved individuals aged 45 to 60 with class IV plaques (4). 

Over 30 months, those taking both extracts saw a 95% lower plaque progression than controls (4). Further research on subjects with advanced atherosclerosis (class V) showed a significant reduction in progression to symptomatic class VI, highlighting a dramatic decrease in cardiovascular risks and hospitalization rates (17). 

Another trial with patients aged 45 to 60 with 50%-60% arterial occlusion (a blockage of blood to limbs) confirmed these compounds stabilize and reduce plaque accumulation effectively without adverse effects, outperforming standard management (18).

Over four years, both treatments showed significant benefits in reducing plaque size and angina, with the combination formula notably decreasing the incidence of heart attacks (19). 

Additional research on asymptomatic patients (20) with risk factors demonstrated that supplementation improved plaque stability and reduced oxidative stress without adverse effects, showing the formula’s role in comprehensive cardiovascular protection.


The Four Main Heart Nutrients

What Are The Most Important Supplements for Heart Health? 

The four go-to nutrients for a healthy heart are:


Further Natural Ways to Benefit Heart Health

Pomegranete

Pomegranate extract significantly protects against cardiovascular disease by targeting endothelial health. It exhibits multiple mechanisms like:

  • Reducing cholesterol accumulation.
  • Protecting LDL ('bad' cholesterol) from oxidation.
  • Shrinking atherosclerotic plaque (21-23). 

Importantly, it enhances artery elasticity to improve blood flow and pressure (23,24).  

In ageing individuals, both diminished nitric oxide production and increased levels of oxidative stress lead to endothelial dysfunction being common. This in turn results in heart attacks and strokes (25,26,27-29).  

Thus, pomegranate can fight these issues by supporting antioxidant defenses and protecting LDL from oxidative damage (22,23), contributing to cardiovascular health (24-26). 

Additionally, pomegranate boosts superoxide dismutase (SOD), further aiding endothelial function (30-34). 

Amla

Oxidative stress, high cholesterol, and elevated glucose combined also lead to endothelial dysfunction and arterial stiffness, majorly contributes to cardiovascular disease (41-57), amla can help. 

Amla, an Ayrdurrvic staple shown to reduce arterial stiffness, can protect endothelial function, and offer cardioprotective benefits in various studies, making it an effective natural aid for heart health (58-86).

Studies on amla confirm this efficacy in reducing risk factors associated with cardiovascular disease, including: 

  • Stress-induced arterial stiffness. 
  • Endothelial dysfunction in smokers.
  • Individuals with metabolic syndrome or diabetes (87-92).

Black Tea

Amla and black tea extracts work synergistically to: 

  • Improve endothelial health by reducing oxidative stress.
  • Enhancing nitric oxide production. 
  • Improving lipid profiles (58-60). 

Black tea can help in improving endothelial function, reducing cholesterol, inflammation, oxidative stress, and blood pressure variations (93-109). 

Together, these extracts provide natural defense against cardiovascular disease, offering a safer alternative to statins and addressing the complex factors contributing to heart health (110).


Read More Blog Posts


References

  1. Bentzon JF, Otsuka F, Virmani R, et al. Mechanisms of plaque formation and rupture. Circ Res. 2014 Jun 6;114(12):1852-66.
  2. Fava C, Montagnana M. Atherosclerosis Is an Inflammatory Disease which Lacks a Common Anti-inflammatory Therapy: How Human Genetics Can Help to This Issue. A Narrative Review. Front Pharmacol. 2018;9:55.
  3. Available at: https://www.nhlbi.nih.gov/health-topics/atherosclerosis#signs,-symptoms,-and-complications. Accessed August 21, 2018.
  4. Belcaro G, Dugall M, Hosoi M, et al. Pycnogenol(R) and Centella Asiatica for asymptomatic atherosclerosis progression. Int Angiol. 2014 Feb;33(1):20-6.
  5. D'Andrea G. Pycnogenol: a blend of procyanidins with multifaceted therapeutic applications? Fitoterapia. 2010 Oct;81(7):724-36.
  6. Rohdewald P. A review of the French maritime pine bark extract (Pycnogenol), a herbal medication with a diverse clinical pharmacology. Int J Clin Pharmacol Ther. 2002 Apr;40(4):158-68.
  7. Gu JQ, Ikuyama S, Wei P, et al. Pycnogenol, an extract from French maritime pine, suppresses Toll-like receptor 4-mediated expression of adipose differentiation-related protein in macrophages. Am J Physiol Endocrinol Metab. 2008 Dec;295(6):E1390-400.
  8. Luo H, Wang J, Qiao C, et al. Pycnogenol attenuates atherosclerosis by regulating lipid metabolism through the TLR4-NF-kappaB pathway. Exp Mol Med. 2015 Oct 23;47:e191.
  9. Badimon L, Hernandez Vera R, Vilahur G. Atherothrombotic risk in obesity. Hamostaseologie. 2013;33(4):259-68.
  10. Chistiakov DA, Revin VV, Sobenin IA, et al. Vascular endothelium: functioning in norm, changes in atherosclerosis and current dietary approaches to improve endothelial function. Mini Rev Med Chem. 2015;15(4):338-50.
  11. Fitzpatrick DF, Bing B, Rohdewald P. Endothelium-dependent vascular effects of Pycnogenol. J Cardiovasc Pharmacol. 1998 Oct;32(4):509-15.
  12. Enseleit F, Sudano I, Periat D, et al. Effects of Pycnogenol on endothelial function in patients with stable coronary artery disease: a double-blind, randomized, placebo-controlled, cross-over study. Eur Heart J. 2012 Jul;33(13):1589-97.
  13. Hu S, Belcaro G, Cornelli U, et al. Effects of Pycnogenol(R) on endothelial dysfunction in borderline hypertensive, hyperlipidemic, and hyperglycemic individuals: the borderline study. Int Angiol. 2015 Feb;34(1):43-52.
  14. Cheruvu PK, Finn AV, Gardner C, et al. Frequency and distribution of thin-cap fibroatheroma and ruptured plaques in human coronary arteries: a pathologic study. J Am Coll Cardiol. 2007 Sep 4;50(10):940-9.
  15. Leskinen MJ, Kovanen PT, Lindstedt KA. Regulation of smooth muscle cell growth, function and death in vitro by activated mast cells--a potential mechanism for the weakening and rupture of atherosclerotic plaques. Biochem Pharmacol. 2003 Oct 15;66(8):1493-8.
  16. Cesarone MR, Belcaro G, Nicolaides AN, et al. Increase in echogenicity of echolucent carotid plaques after treatment with total triterpenic fraction of Centella asiatica: a prospective, placebo-controlled, randomized trial. Angiology.2001 Oct;52 Suppl 2: S19-25.
  17. Belcaro G, Ippolito E, Dugall M, et al. Pycnogenol(R) and Centella asiatica in the management of asymptomatic atherosclerosis progression. Int Angiol. 2015 Apr;34(2):150-7.
  18. Luzzi R, Belcaro G, Ippolito E. Carotid plaque stabilization induced by the supplement association Pycnogenol(R) and centella asiatica (Centellicum(R)). Minerva Cardioangiol. 2016 Dec;64(6):603-9.
  19. Belcaro G, Dugall M, Ippolito E, et al. Pycnogenol(R) and Centella asiatica to prevent asymptomatic atherosclerosis progression in clinical events. Minerva Cardioangiol. 2017 Feb;65(1):24-31.
  20. Belcaro G, Cornelli U. Variations in Echogenicity in Carotid and Femoral Atherosclerotic Plaques with Pycnogenol + Centella Asiatica Supplementation. Int J Angiol. 2017 Jun;26(2): 95-101
  21. Kaplan M, Hayek T, Raz A, et al. Pomegranate juice supplementation to atherosclerotic mice reduces macrophage lipid peroxidation, cellular cholesterol accumulation and development of atherosclerosis. J Nutr. 2001 Aug;131(8):2082-9.
  22. Rosenblat M, Volkova N, Aviram M. Pomegranate juice (PJ) consumption antioxidative properties on mouse macrophages, but not PJ beneficial effects on macrophage cholesterol and triglyceride metabolism, are mediated via PJ-induced stimulation of macrophage PON2. Atherosclerosis. 2010 Sep;212(1):86-92.
  23. Aviram M, Rosenblat M. Pomegranate for your cardiovascular health. Rambam Maimonides Med J. 2013 Apr;4(2):e0013.
  24. Asgary S, Sahebkar A, Afshani MR, Keshvari M, Haghjooyjavanmard S, Rafieian-Kopaei M. Clinical evaluation of blood pressure lowering, endothelial function improving, hypolipidemic and anti-Inflammatory effects of pomegranate juice in hypertensive subjects. Phytother Res. 2014 Feb;28)2)193-9.
  25. Houston M. The role of nutrition and nutraceutical supplements in the treatment of hypertension. World J Cardiol. 2014 Feb 26;6(2):38-66.
  26. Stoltz JF, Muller S, Kadi A, Decot V, Menu P, Bensoussan D. Introduction to endothelial cell biology. Clin Hemorheol Microcirc. 2007;37(1-2):5-8.
  27. Puddu GM, Cravero E, Arnone G, Muscari A, Puddu P. Molecular aspects of atherogenesis: new insights and unsolved questions. J Biomed Sci. 2005 Dec;12(6):839-53.
  28. Lee WJ, Ou HC, Hsu WC, et al. Ellagic acid inhibits oxidized LDL-mediated LOX-1 expression, ROS generation, and inflammation in human endothelial cells. J Vasc Surg. 2010 Nov;52(5):1290-300.
  29. Seals DR, Jablonski KL, Donato AJ. Aging and vascular endothelial function in humans. Clin Sci (London). 2011 May;120(9):357-75.
  30. Dong S, Tong X, Liu H, Gao Q. Protective effects of pomegranate polyphenols on cardiac function in rats with myocardial ischemia/reperfusion injury. Nan Fang Yi Ke Da Xue Xue Bao. 2012 Jun;32(7):924-7.
  31. Mohan M, Waghulde H, Kasture S. Effect of pomegranate juice on Angiotensin II-induced hypertension in diabetic Wistar rats. Phytother Res. 2010 Jun;24 Suppl 2:S196-203.
  32. Shaban NZ, El-Kersh MA, El-Rashidy FH, Habashy NH. Protective role of Punica granatum (pomegranate) peel and seed oil extracts on diethylnitrosamine and phenobarbital-induced hepatic injury in male rats. Food Chem. 2013 Dec 1;141(3):1587-96.
  33. Vouldoukis I, Conti M, Krauss P, et al. Supplementation with gliadin-combined plant superoxide dismutase extract promotes antioxidant defences and protects against oxidative stress. Phytother Res. 2004 Dec;18(12):957-62.
  34. Cook-Mills JM, Marchese ME, Abdala-Valencia H. Vascular cell adhesion molecule-1 expression and signaling during disease: regulation by reactive oxygen species and antioxidants. Antioxid Redox Signal. 2011 Sep 15;15(6):1607-38.
  35. Available at: http://www.nytimes.com/2013/11/14/opinion/dont-give-more-patients-statins.html. Accessed December 17, 2013.
  36. Abramson JD, Rosenberg HG, Jewell N, Wright JM. Should people at low risk of cardiovascular disease take a statin? Bmj. 2013;347:f6123.
  37. Mansi I, Mortensen E. The controversy of a wider statin utilization: why? Expert Opin Drug Saf. 2013 May;12(3):327-37.
  38. Antony B, Benny M, Kaimal TN. A Pilot clinical study to evaluate the effect of Emblica officinalis extract (Amlamax™) on markers of systemic inflammation and dyslipidemia. Indian J Clin Biochem. 2008 Oct;23(4):378-81.
  39. van Duynhoven J, Vaughan EE, van Dorsten F, et al. Interactions of black tea polyphenols with human gut microbiota: implications for gut and cardiovascular health. Am J Clin Nutr. 2013 Dec;98(6):1631S-41S.
  40. Available at: http://www.ncbi.nlm.nih.gov/books/nbk92768. Accessed December 18, 2013.
  41. Mottillo S, Filion KB, Genest J, et al. The metabolic syndrome and cardiovascular risk a systematic review and meta-analysis. J Am Coll Cardiol. 2010 Sep 28;56(14):1113-32.
  42. Available at: http://www.heart.org/heartorg/conditions/diabetes/whydiabetesmatters/cardiovascular-disease-diabetes_ucm_313865_article.jsp# Accessed December 18, 2013.
  43. Cheung YF, O K, Woo CW, et al. Oxidative stress in children late after Kawasaki disease: relationship with carotid atherosclerosis and stiffness. BMC Pediatr. 2008;8:20.
  44. Delles C, Zimmerli LU, McGrane DJ, et al. Vascular stiffness is related to superoxide generation in the vessel wall. J Hypertens. 2008 May;26(5):946-55.
  45. Kim JH, Bugaj LJ, Oh YJ, et al. Arginase inhibition restores NOS coupling and reverses endothelial dysfunction and vascular stiffness in old rats. J Appl Physiol (1985). 2009 Oct;107(4):1249-57.
  46. Soucy KG, Lim HK, Attarzadeh DO, et al. Dietary inhibition of xanthine oxidase attenuates radiation-induced endothelial dysfunction in rat aorta. J Appl Physiol (1985). 2010 May;108(5):1250-8.
  47. Hata K, Nakagawa T, Mizuno M, et al. Relationship between smoking and a new index of arterial stiffness, the cardio-ankle vascular index, in male workers: a cross-sectional study. Tob Induc Dis. 2012;10(1):11.
  48. Heffernan KS, Karas RH, Patvardhan EA, Kuvin JT. Endothelium-dependent vasodilation is associated with exercise capacity in smokers and non-smokers. Vasc Med. 2010 Apr;15(2):119-25.
  49. Shimosato T, Geddawy A, Tawa M, Imamura T, Okamura T. Chronic administration of nicotine-free cigarette smoke extract impaired endothelium-dependent vascular relaxation in rats via increased vascular oxidative stress. J Pharmacol Sci. 2012;118(2):206-14.
  50. Sikka G, Pandey D, Bhuniya AK, et al. Contribution of arginase activation to vascular dysfunction in cigarette smoking. Atherosclerosis. 2013 Nov;231(1):91-4.
  51. Toda N, Toda H. Nitric oxide-mediated blood flow regulation as affected by smoking and nicotine. Eur J Pharmacol. 2010 Dec 15;649(1-3):1-13.
  52. Varela-Carver A, Parker H, Kleinert C, Rimoldi O. Adverse effects of cigarette smoke and induction of oxidative stress in cardiomyocytes and vascular endothelium. Curr Pharm Des. 2010;16(23):2551-8.
  53. Peluso I, Morabito G, Urban L, Ioannone F, Serafini M. Oxidative stress in atherosclerosis development: the central role of LDL and oxidative burst. Endocr Metab Immune Disord Drug Targets. 2012 Dec;12(4):351-60.
  54. Farmer DG, Kennedy S. RAGE, vascular tone and vascular disease. Pharmacol Ther. 2009 Nov;124(2):185-94.
  55. Neves D. Advanced glycation end-products: a common pathway in diabetes and age-related erectile dysfunction. Free Radic Res. 2013 Aug;47 Suppl 1:49-69.
  56. Sena CM, Matafome P, Crisostomo J, et al. Methylglyoxal promotes oxidative stress and endothelial dysfunction. Pharmacol Res. 2012 May;65(5):497-506.
  57. Stirban A, Negrean M, Gotting C, et al. Dietary advanced glycation endproducts and oxidative stress: in vivo effects on endothelial function and adipokines. Ann N Y Acad Sci. 2008 Apr;1126:276-9.
  58. Usha Rani P, Sravanti IV. Study of CAPROS®500mg and placebo in modifying cardiovascular risk with special reference to endothelial dysfunction in patients with type 2 diabetes mellitus: Natreon; 2012.
  59. Grassi D, Mulder TP, Draijer R, Desideri G, Molhuizen HO, Ferri C. Black tea consumption dose-dependently improves flow-mediated dilation in healthy males. J Hypertens. 2009 Apr;27(4):774-81.
  60. Fujita H, Yamagami T. Antihypercholesterolemic effect of Chinese black tea extract in human subjects with borderline hypercholesterolemia. Nutr Res. 2008 Jul;28(7):450-6.
  61. Nain P, Saini V, Sharma S, Nain J. Antidiabetic and antioxidant potential of Emblica officinalis Gaertn. leaves extract in streptozotocin-induced type-2 diabetes mellitus (T2DM) rats. J Ethnopharmacol. 2012 Jun 26;142(1):65-71.
  62. Golechha M, Bhatia J, Arya DS. Studies on effects of Emblica officinalis (Amla) on oxidative stress and cholinergic function in scopolamine induced amnesia in mice. J Environ Biol. 2012 Jan;33(1):95-100.
  63. Wongpradabchai S, Chularojmontri L, Phornchirasilp S, Wattanapitayakul SK. Protective effect of Phyllanthus emblica fruit extract against hydrogen peroxide-induced endothelial cell death. J Med Assoc Thai. 2013 Jan;96 Suppl 1:S40-8.
  64. Khanom F, Kayahara H, Tadasa K. Superoxide-scavenging and prolyl endopeptidase inhibitory activities of Bangladeshi indigenous medicinal plants. Biosci Biotechnol Biochem. 2000 Apr;64(4):837-40.
  65. Sai Ram M, Neetu D, Yogesh B, et al. Cyto-protective and immunomodulating properties of Amla (Emblica officinalis) on lymphocytes: an in-vitro study. J Ethnopharmacol. 2002 Jun;81(1):5-10.
  66. Damodara Reddy V, Padmavathi P, Gopi S, Paramahamsa M, Varadacharyulu N. Protective Effect of Emblica officinalis Against Alcohol-Induced Hepatic Injury by Ameliorating Oxidative Stress in Rats. Indian J Clin Biochem. 2010 Oct;25(4):419-24.
  67. Shivananjappa MM, Joshi MK. Influence of Emblica officinalis aqueous extract on growth and antioxidant defense system of human hepatoma cell line (HepG2). Pharm Biol. 2012 Apr;50(4):497-505.
  68. Kim HJ, Yokozawa T, Kim HY, Tohda C, Rao TP, Juneja LR. Influence of amla (Emblica officinalis Gaertn.) on hypercholesterolemia and lipid peroxidation in cholesterol-fed rats. J Nutr Sci Vitaminol (Tokyo). 2005 Dec;51(6):413-8.
  69. Yokozawa T, Kim HY, Kim HJ, Okubo T, Chu DC, Juneja LR. Amla (Emblica officinalis Gaertn.) prevents dyslipidaemia and oxidative stress in the ageing process. Br J Nutr. 2007 Jun;97(6):1187-95.
  70. Ling LT, Palanisamy UD, Cheng HM. Prooxidant/antioxidant ratio (ProAntidex) as a better index of net free radical scavenging potential. Molecules. 2010 Nov;15(11):7884-92.
  71. Kim HY, Okubo T, Juneja LR, Yokozawa T. The protective role of amla (Emblica officinalis Gaertn.) against fructose-induced metabolic syndrome in a rat model. Br J Nutr. 2010 Feb;103(4):502-12.
  72. Koshy SM, Bobby Z, Hariharan AP, Gopalakrishna SM. Amla (Emblica officinalis) extract is effective in preventing high fructose diet-induced insulin resistance and atherogenic dyslipidemic profile in ovariectomized female albino rats. Menopause. 2012 Oct;19(10):1146-55.
  73. Balakumar P, Mahadevan N. Interplay between statins and PPARs in improving cardiovascular outcomes: a double-edged sword? Br J Pharmacol. 2012 Jan;165(2):373-9.
  74. Ling H, Burns TL, Hilleman DE. Novel strategies for managing dyslipidemia: treatment beyond statins. Postgrad Med. 2012 Nov;124(6):43-54.
  75. Tenenbaum A, Fisman EZ. Balanced pan-PPAR activator bezafibrate in combination with statin: comprehensive lipids control and diabetes prevention? Cardiovasc Diabetol. 2012;11:140.
  76. Patel SS, Goyal RK. Prevention of diabetes-induced myocardial dysfunction in rats using the juice of the Emblica officinalis fruit. Exp Clin Cardiol. 2011 Fall;16(3):87-91.
  77. Puppala M, Ponder J, Suryanarayana P, Reddy GB, Petrash JM, LaBarbera DV. The isolation and characterization of beta-glucogallin as a novel aldose reductase inhibitor from Emblica officinalis. PLoS One. 2012;7(4):e31399.
  78. Suryanarayana P, Kumar PA, Saraswat M, Petrash JM, Reddy GB. Inhibition of aldose reductase by tannoid principles of Emblica officinalis: implications for the prevention of sugar cataract. Mol Vis. 2004 Mar 12;10:148-54.
  79. Ananthakrishnan R, Li Q, Gomes T, Schmidt AM, Ramasamy R. Aldose reductase pathway contributes to vulnerability of aging myocardium to ischemic injury. Exp Gerontol. 2011 Sep;46(9):762-7.
  80. Ramasamy R, Goldberg IJ. Aldose reductase and cardiovascular diseases, creating human-like diabetic complications in an experimental model. Circ Res. 2010 May 14;106(9):1449-58.
  81. Tang WH, Martin KA, Hwa J. Aldose reductase, oxidative stress, and diabetic mellitus. Front Pharmacol. 2012;3:87.
  82. Bhatia J, Tabassum F, Sharma AK, et al. Emblica officinalis exerts antihypertensive effect in a rat model of DOCA-salt-induced hypertension: role of (p) eNOS, NO and oxidative stress. Cardiovasc Toxicol. 2011 Sep;11(3):272-9.
  83. Yokozawa T, Kim HY, Kim HJ, et al. Amla (Emblica officinalis Gaertn.) attenuates age-related renal dysfunction by oxidative stress. J Agric Food Chem. 2007 Sep 19;55(19):7744-52.
  84. Chatterjee A, Chatterjee S, Biswas A, Bhattacharya S, Chattopadhyay S, Bandyopadhyay SK. Gallic acid enriched fraction of Phyllanthus emblica potentiates indomethacin-induced gastric ulcer healing via e-NOS-dependent pathway. Evid Based Complement Alternat Med. 2012;2012:487380.
  85. Chularojmontri L, Suwatronnakorn M, Wattanapitayakul SK. Phyllanthus emblica L. enhances human umbilical vein endothelial wound healing and sprouting. Evid Based Complement Alternat Med. 2013;2013:720728.
  86. Ojha S, Golechha M, Kumari S, Arya DS. Protective effect of Emblica officinalis (amla) on isoproterenol-induced cardiotoxicity in rats. Toxicol Ind Health. 2012 Jun;28(5):399-411.
  87. Usha Rani P. Evaluation of Emblica officinalis (CAPROS®) on cold pressor induced cardiovascular changes in healthy human subjects. Natreon;2012.
  88. Rozanski A, Blumenthal JA, Kaplan J. Impact of psychological factors on the pathogenesis of cardiovascular disease and implications for therapy. Circulation. 1999 Apr 27;99(16):2192-217.
  89. Kjaer A, Meyer C, Nielsen FS, Parving HH, Hesse B. Dipyridamole, cold pressor test, and demonstration of endothelial dysfunction: a PET study of myocardial perfusion in diabetes. J Nucl Med. 2003 Jan;44(1):19-23.
  90. Muller MD, Sauder CL, Ray CA. Mental stress elicits sustained and reproducible increases in skin sympathetic nerve activity. Physiol Rep. 2013 Mar;1(1).
  91. Soares-Filho GL, Mesquita CT, Mesquita ET, et al. Panic attack triggering myocardial ischemia documented by myocardial perfusion imaging study. A case report. Int Arch Med. 2012;5(1):24.
  92. Usha Rani P, Sravanti IV. Evaluation of effect of Emblica officinalis (Capros) on mental stress induced cardiovascular changes in healthy human subjects: Natreon;2012.
  93. Chen D, Milacic V, Chen MS, et al. Tea polyphenols, their biological effects and potential molecular targets. Histol Histopathol. 2008 Apr;23(4):487-96.
  94. Available at: http://www.wjgnet.com/2220-3168/full/v3/i4/32.htm. Accessed December 31, 2013.
  95. Arts IC, Hollman PC, Feskens EJ, Bueno de Mesquita HB, Kromhout D. Catechin intake might explain the inverse relation between tea consumption and ischemic heart disease: the Zutphen Elderly Study. Am J Clin Nutr. 2001 Aug;74(2):227-32.
  96. Chen Z, Li Y, Zhao LC, et al. A study on the association between tea consumption and stroke. Zhonghua Liu Xing Bing Xue Za Zhi. 2004 Aug;25(8):666-70.
  97. Larsson SC, Virtamo J, Wolk A. Black tea consumption and risk of stroke in women and men. Ann Epidemiol. 2013 Mar;23(3):157-60.
  98. Yi D, Tan X, Zhao Z, et al. Reduced risk of dyslipidemia with oolong tea consumption: a population-based study in southern China. Br J Nutr. 2013 Nov 14:1-9.
  99. Duffy SJ, Keaney JF, Jr., Holbrook M, et al. Short- and long-term black tea consumption reverses endothelial dysfunction in patients with coronary artery disease. Circulation. 2001 Jul 10;104(2):151-6.
  100. Hodgson JM, Puddey IB, Burke V, Watts GF, Beilin LJ. Regular ingestion of black tea improves brachial artery vasodilator function. Clin Sci (Lond). 2002 Feb;102(2):195-201.
  101. Hirata K, Shimada K, Watanabe H, et al. Black tea increases coronary flow velocity reserve in healthy male subjects. Am J Cardiol. 2004 Jun 1;93(11):1384-8,a6.
  102. Jochmann N, Lorenz M, Krosigk A, et al. The efficacy of black tea in ameliorating endothelial function is equivalent to that of green tea. Br J Nutr. 2008 Apr;99(4):863-8.
  103. Davies MJ, Judd JT, Baer DJ, et al. Black tea consumption reduces total and LDL cholesterol in mildly hypercholesterolemic adults. J Nutr. 2003 Oct;133(10):3298s-302s.
  104. Bahorun T, Luximon-Ramma A, Neergheen-Bhujun VS, et al. The effect of black tea on risk factors of cardiovascular disease in a normal population. Prev Med. 2012 May;54 Suppl:S98-102.
  105. Bahorun T, Luximon-Ramma A, Gunness TK, et al. Black tea reduces uric acid and C-reactive protein levels in humans susceptible to cardiovascular diseases. Toxicology. 2010 Nov 28;278(1):68-74.
  106. Neyestani TR, Shariatzade N, Kalayi A, et al. Regular daily intake of black tea improves oxidative stress biomarkers and decreases serum C-reactive protein levels in type 2 diabetic patients. Ann Nutr Metab. 2010;57(1):40-9.
  107. Avolio AP, Xu K, Butlin M. Effect of large arteries on blood pressure variability. Conf Proc IEEE Eng Med Biol Soc. 2013 Jul;2013:4078-81.
  108. Parati G, Liu X, Ochoa JE. Clinical relevance of visit-to-visit blood pressure variability: impact on renal outcomes. J Hum Hypertens. 2013 Oct 17.
  109. Hodgson JM, Croft KD, Woodman RJ, et al. Black tea lowers the rate of blood pressure variation: a randomized controlled trial. Am J Clin Nutr. 2013 May;97(5):943-50.
  110. Taylor F, Huffman MD, Macedo AF, et al. Statins for the primary prevention of cardiovascular disease. Cochrane Database Syst Rev. 2013;1:Cd004816.