Enhance Endothelial Function and Reduce Arterial Stiffness

 

Despite years of research and billions of dollars spent on lipid-lowering medications, cardiovascular disease remains the number one killer in the United States.

“Statin” drugs have undergone intense scrutiny, with evidence of over-prescribing, the potential for side effects, and somewhat exaggerated claims about effectiveness.^1-3 Statin drugs reduce the risk of heart attack in high-risk patients, such as preventing a second heart attack in those individuals having already experienced a first heart attack.The benefit of reducing the risk of a heart attack in otherwise low-risk patients, however, is not clear.

Furthermore, a recent, controversial guideline change on statin drug prescribing for optimal lipid management has been met with deep skepticism by many experts in cardiology.^1,2

Many aging individuals who seek to support healthy blood lipid management look for natural products with evidence of support.

Studies show that extracts from an Ayurvedic herbal plant called Amla (Emblica officinalis) can provide support for some of the important aspects of vascular and cardiac health.⁴

In addition, black tea extracts may offer more benefit for vascular health.⁵ These natural ingredients, used for centuries in Asian medicine, are available without the need for prescription.⁶

If you are concerned about vascular and cardiac health, and seek natural strategies to support cardiovascular health as you age, you’ll want to learn more about Amla and black tea extracts.

Endothelial Dysfunction And Stiff Arteries Are Killing You

 

By now most of us understand that elevated levels of cholesterol and other fats put us at risk of heart attacks, strokes, and other serious cardiovascular outcomes. We also know that having elevated blood glucose, metabolic syndrome, or outright diabetes adds to that risk.^7,8 But few people outside of the halls of academia really understand how these factors work together to put your health—and your life—at risk.

In a nutshell, here’s how it works:

Your blood vessels are lined with an ultra-thin layer of sensitive cells called endothelial cells (or simply, “the endothelium”). The endothelium normally regulates blood flow and pressure, assuring that vital tissues always get just the right amount of oxygen- and nutrient-rich blood.

You want to have a healthy endothelium.

But the modern lifestyle works against endothelial health. One culprit is oxidative stress, which arises from a number of exposure sources.^9-18

Oxidative stress damages the endothelium and impairs its ability to regulate blood flow, in part, by reducing endothelial production of nitric oxide, a signaling molecule that tells the artery when to dilate to improve flow.¹¹ Oxidative stress acts on elevated cholesterol levels to produce dangerous oxidized LDL, a key component of artery-clogging plaque.¹⁹

Add to that elevated blood sugar, which produces dangerous advanced glycation end products (AGEs) that chemically cross-link proteins in vessels, and physical and emotional stress, which impairs endothelial function still further, and you have the “perfect storm” of factors that damage endothelial function and ultimately lead to stiffening of the arteries.^20-23

A result of thickened, stiff arteries is rising blood pressure, an overworked heart, and restricted blood flow. This ultimately leads to the catastrophes we see as heart attacks, heart failure, and strokes.^24-27

So the bottom line is you want to do everything possible to protect your endothelial function and prevent arterial stiffening, long before you develop warning signs of cardiovascular disease.

To do that, it’s wise to attack all of the factors that add up to stiffened arteries and poor endothelial function. The ideal cardiovascular protective pill, therefore, would simultaneously reduce oxidative damage, control lipid and blood sugar levels, improve platelet function, and lower blood pressure.

In clinical studies, that pill would markedly improve endothelial function and reduce arterial stiffening in healthy people and those at high risk for cardiovascular disease, such as diabetics, smokers, and those with the metabolic syndrome. And that pill would do all of this, without imposing its own risks to your health.

That’s what Amla extract has now been shown to do.²⁸ Black tea extract provides an interesting complement, improving the same risk factors by similar as well as different mechanisms.^29,30

What You Need to Know

Guard Heart Health With Botanical Power Duo

• Your heart health is threatened by arterial stiffening, the result of a host of factors that damage your endothelial function and reduce your body’s ability to respond to changes in blood flow and pressure.
• Mainstream medicine uses “statins” to address this problem. “Statins” are increasingly under scrutiny for being over-prescribed and potentially dangerous—and they primarily address lipids, which is only one part of the entire picture.
• Amla has undergone dozens of basic lab and clinical trials related to cardiovascular disease.
• All of these studies point to the idea that Amla fruit extract represents the “perfect heart pill,” because it addresses not only lipid levels, but also the oxidant stress, glucose damage, platelet dysfunction, and blood pressure abnormalities that contribute to endothelial dysfunction and arterial stiffening.
• The addition of black tea extract rounds out Amla’s benefits, complementing them to assure you of comprehensive heart health promotion.

How Amla Functions

The fruit of the Amla has long been used in traditional Indian medical systems.³¹ More recently, interest has grown in the fruit’s impact on blood glucose, lipid profiles, and, increasingly, other risk factors for cardiovascular disease. Let’s see how it stacks up as a supplement for reducing some of the risk factors that produce endothelial dysfunction and ultimately arterial stiffening.

Amla is a potent antioxidant. ³² Amla reduces overall oxidant stress by three separate pathways: it inhibits production of the oxidizing free radicals that damage endothelial cells, it scavenges and neutralizes those reactive oxygen species that have already been produced, and it enhances production and activity of natural cellular antioxidant enzyme systems.^33-37 The result is a significant decrease in oxidant damage, as measured by biochemical markers of oxidation.^38,39 Amla has very little pro-oxidant activity, ensuring a low rate of undesirable effects.⁴⁰

Amla lowers cholesterol. Animal studies show that, while a high-fat or high-fructose diet will produce signs of the metabolic syndrome and unhealthy lipid profiles, treatment with Amla extract has been shown to help reduce total cholesterol and triglycerides.^38,39,41,42 Importantly, this effect was especially noticeable in a rat model of menopause; at menopause, women’s risk for heart disease rapidly rises to become similar to men’s.⁴²

It was recently discovered that Amla lowers serum lipids through an important pathway.⁴³ Amla activates the “metabolic sensor” molecule called PPAR-alpha; the PPARs lower both blood lipids and glucose by increasing their consumption in cells.³⁹ PPAR-activating drugs are increasingly being recommended for use in combination with statins, especially for diabetics. Amla may provide this benefit with less potential for the side effects seen with the two drugs.^39,44,45

Amla fights diabetes. Diabetes is a disaster for endothelial function and arterial stiffness, and substantially raises the odds for a heart attack or stroke. When rats are made diabetic in the laboratory, Amla administration prevents rises in blood sugar and insulin resistance; it also prevents diabetes-associated increases in food intake.^42,46

A unique anti-diabetic property of Amla is that it inhibits an enzyme called aldose reductase.^47,48 This enzyme produces a toxic chemical called sorbitol, which damages proteins in the eye to cause cataracts, and which more recently has been implicated in production of arterial stiffening and cardiovascular disease.^47-51

Amla lowers blood pressure. Elevated blood pressure is both a cause and a consequence of arterial stiffening; it can be produced in the laboratory by inducing the metabolic syndrome in rats through high-fructose diets, eventually resulting in damage to the heart and kidneys, exactly as in humans.⁴¹ But if the animals are supplemented with Amla extracts, blood pressure and elevated heart rates return to near-normal levels, heart and kidney swelling are reduced, and elevated sodium and depressed potassium levels are normalized.^52,53 And in animals with full-blown diabetes, Amla prevents blood pressure-induced heart muscle dysfunction as well.⁴⁶ Anyone using Amla to help with hypertension should have regular blood pressure checks, ideally using an at-home blood pressure monitor to ensure that blood pressure readings stay at the optimal range, which we at Life Extension have long argued are around 115/75 mm Hg.

Amla protects endothelial function. Poor endothelial function, as we’ve seen, underlies the arterial thickening and stiffening that ultimately leads to cardiovascular disease. Laboratory studies using cultured endothelial cells and experimental models show that treatment with Amla extract enhances production of nitric oxide, the signaling molecule that the endothelium uses to “tell” arterial walls to relax and maintain normal blood flow.^52,54,55

Amla is cardioprotective. The sum of all of Amla’s beneficial effects in the laboratory can be seen in studies that demonstrate how it protects heart muscle from damage. A laboratory model of the overworked, underfed, diseased heart can be produced by treating animals with the drug isoproterenol, a powerful heart stimulant that eventually impairs cardiac muscle function by excessive oxidative stress. In a study, rats treated with isoproterenol developed decreased heart rate, poor contractility (“squeeze”) and increased pressure inside the heart, which leads to heart failure.⁵⁶ But treatment with Amla extract restored normal heart function and pumping pressures, preserved antioxidant levels, reduced enzyme markers of heart muscle damage, and prevented microscopically-visible injury to heart muscle.⁵⁶ And in another study with diabetic rats, Amla also reduced ominous increases in heart size and muscle damage.⁴⁶

Human Clinical Trials Using Amla

 

Laboratory studies show that Amla may rectify many problems associated with the endothelial dysfunction that conspire to cause cardiovascular disease. Now there’s exciting new evidence from a series of clinical studies that shows just how powerful these effects are in humans.

The first of these clinical trials examined the effects of Amla fruit extract supplementation on acute physical stress in healthy volunteers.⁵⁷ Both acute and chronic stress are known risk factors for coronary artery disease, acting through oxidative mechanisms to damage the endothelium and stiffen arteries.^57,58 Subjects received either a placebo or 500 mg Amla fruit extract twice daily for 14 days.⁵⁷ Before and after supplementation, subjects underwent a “cold pressor” test that required placing the hand in ice water for a set period.^57,59

All patients showed the same increases in blood pressure (10-12%) and arterial stiffness (12-20%) before treatment was started, but; after 14 days, while placebo patients had those same increases, supplemented patients had decreases in both blood pressure (3-5% less than baseline) and arterial stiffness (8%), a marked and significant difference compared with placebo.⁵⁷

In a similarly-designed study, researchers looked at the impact of Amla supplementation on mitigating the effects of mental stress on arterial stiffness. Mental stress is known to produce increased risk for acute cardiovascular disease, including even heart attacks.^60,61 Here, healthy subjects took placebo or 500 mg Amla fruit extract twice daily for 14 days, and were subjected to a series of stressful mental math exercises before and after the supplementation period.⁶² Subjects taking Amla had a decrease in their aortic blood pressure compared with baseline values, while no such change was seen in placebo patients. No significant change in arterial stiffening occurred in either group.⁶²

Because smoking is known to threaten endothelial function,^13-18,63 another study was done to compare markers of endothelial dysfunction in smokers who received either placebo or 250 mg Amla extract twice daily for 60 days.⁶⁴ Participants indicated their status on a group of smoking-related health parameters (e.g., of mouth hygiene, productive cough, painful breathing with exertion, sleep, and palpitations), while objective parameters of endothelial function and cardiovascular risk (including blood counts, lipid profiles, platelet aggregation, C-reactive protein, antioxidant status, and lung function) were measured at baseline and the end of the study. With the exception of lung function (which remained constant and showed no signs of further deterioration), the supplemented group had significant improvement on all subjective and all objective measurements, demonstrating the broad-spectrum efficacy of Amla at reducing endothelial risk in one of the most challenging groups, namely smokers.

People with metabolic syndrome are also at increased risk for cardiovascular disease as a result of endothelial dysfunction and increased arterial stiffness.^27,65 Scientists studied placebo vs. Amla fruit extract (250 and 500 mg twice daily for 12 weeks) in metabolic syndrome patients with known endothelial dysfunction.²⁸ They used the same proven technique for measuring arterial stiffness as in the previous studies. The placebo group had a small increase (1.3%) in stiffness after 12 weeks, while both Amla doses produced significant decreases (-6.6 and -7.5% for the 250 and 500 mg doses, respectively). Both Amla groups, but not the placebo group, also had significant increases in beneficial nitric oxide which helps arteries dilate to allow increased blood flow. And both Amla doses produced significant increases in endogenous antioxidants such as glutathione, and reduced markers of oxidative damage and inflammation such as C-reactive protein. Finally, both dose levels of Amla caused drops in triglycerides, total cholesterol and LDL, with no change in the placebo group.

People with diabetes (types I or II) are at massively increased risk of endothelial dysfunction and stiffening of their arteries.^23,65 Researchers have now studied the impact of Amla extract (500 mg twice daily for 12 weeks) vs. placebo in a group of diabetics, using the same measures of arterial stiffness as in the other studies.²⁸ Supplemented subjects had a 7.6% drop in stiffness, compared with a 1.3% increase in placebo recipients.²⁸ Amla also produced drops in total cholesterol, LDL and triglycerides, with beneficial increases in HDL and native antioxidant enzymes. An additional benefit of Amla was a drop in hemoglobin A1c , a measure of chronic glucose exposure and a contributor to cardiovascular risk. Again, virtually every measured outcome was improved in this very high-risk population.²⁸

Together, these studies seem to validate the idea that Amla, particularly at doses of 500 mg twice daily, provides meaningful cardiovascular protective benefits.

Black Tea: The Ideal Complement To Amla

 

The world’s second most popular beverage after water is tea, which contains more than 4,000 chemical constituents, many of which have proven health benefits, especially the catechins and theaflavins found in black (and green) tea.^67,68 Higher catechin consumption is associated with a 51% reduction in the risk of dying from cardiovascular disease, a 40% reduction in stroke risk, and a 90% reduction in lipid disturbances. ^69-72

Clinical trials of black tea or its components have shown substantial benefits on the risk factors for arterial stiffening and cardiovascular disease:

• Endothelial function is improved by consumption of black tea for both short- and long-term intervals in healthy volunteers as well as in patients with known coronary artery disease or elevated lipid profiles.^29,73,74 Black tea consumption also increased the function of the essential coronary arteries by increasing blood flow in a group of healthy volunteers.⁷⁵ These effects are similar to those of green tea, also known for its endothelial function-improving properties.⁷⁶
• Cholesterol levels (LDL and total cholesterol) were lowered by black tea consumption in adults with mildly elevated levels, with reductions in total cholesterol of 6.5% and LDL of 11.1%.⁷⁷ Black tea extract showed similar effects in other studies.^30,78
• Inflammatory changes and metabolic toxins that promote endothelial dysfunction can be reduced by black tea consumption, as shown in studies of C-reactive protein (a marker of inflammation) and uric acid, an ammonia-like toxin produced in the liver. Levels of both were significantly reduced by consumption of black tea for 12 weeks.^79,80
• Oxidative stress, another major contributor to endothelial dysfunction, is also reduced by black tea extract consumption in patients with type II diabetes and in healthy volunteers.^78,80
• Large variations in blood pressure are an independent risk factor for cardiovascular disease, and recent evidence suggests that these variations are reflections of increased arterial stiffness.^81,82 Regular black tea consumption can reduce the rate of blood pressure variation and so lower the risk.⁸³

Statins: Potential Benefits, But With Potential Risks, Too

“Statin” drugs have been tremendous money makers for Big Pharma for more than 2 decades; during that time recommendations for who should take them have, with few exceptions, been broadened. A recent review of the subject, in fact, suggested that even people at less than a 10% risk of cardiovascular disease are candidates for drug treatment.⁸⁴ Critics have commented upon the potential for bias given that the review included many studies funded by statin manufacturers.^2,84

Some prominent researchers continue to question the need for more widespread use of statins in the general population.

For example, distinguished Harvard professor John D. Abramson and colleagues argue in an editorial published in the prestigious British Medical Journal that the evidence of benefit for statins in lower-risk patients comes nowhere near the known risks that these drugs produce.

In a startling calculation, the researchers show that one needs to treat 140 or more low-risk people for five years to prevent a single heart attack or stroke, and even then there’s no reduction in the long-term risk of dying.² By comparison, treating as few as 19 patients will produce at least one episode of the severe muscle pain known as “myopathy.”²

And that’s not to mention the potential increase in the incidence of diabetes or liver and kidney dysfunction, cataracts, cognitive symptoms, nerve disorders, and sexual dysfunction, and other potentially debilitating effects.²

Abramson has publically made the plea to stop giving statins indiscriminately to more and more patients, and it’s time for all physicians to reevaluate their prescribing habits.²

Statins are imperfect drugs; and although they do have a role in cardiovascular disease risk managem ent, a careful risk/benefit analysis must occur for each individual patient, always using the lowest possible drug dose to achieve the desired treatment effect. Life Extension has long argued that half doses of drugs like Lipitor^® work as well as full dose in many patients requiring statins.

Summary

Your heart and blood vessels are under constant attack from oxidants, inflammation, elevated blood sugar, high cholesterol, and a host of internal and environmental toxins.

These effects add up to diminished endothelial function and its major consequence, arterial stiffening, which in turn dramatically raise risk for heart attack, stroke, and other disastrous outcomes.

Mainstream medicine is almost slavishly devoted to statin drugs in attempts to bring down risk, but these drugs are just a small piece of the complex puzzle that represents cardiovascular disease. Statins, which more and more experts feel are over-prescribed, also carry with them a list of serious side effects. They are certainly far short of a perfect heart pill.

Extracts of Amla fruit on the other hand, attack endothelial dysfunction and arterial stiffening on a wide front, improving not only lipid profiles but also blood glucose, platelet function, blood pressure, and the oxidant stress that produces them. Studies in animals and now humans demonstrate the broad-spectrum benefits of Amla, which has now been shown to produce potentially life-saving reductions in the arterial stiffening that raises risk for cardiovascular disease.

The addition of black tea extracts would appear to complement the biological benefits of Amla.

If you have any questions on the scientific content of this article, please call a Life Extension^® Wellness Specialist at 1-866-864-3027.

References

1. Available at: http://www.nytimes.com/2013/11/14/opinion/dont-give-more-patients-statins.html?_r=0. Accessed December 17, 2013.
2. Abramson JD, Rosenberg HG, Jewell N, Wright JM. Should people at low risk of cardiovascular disease take a statin? Bmj. 2013;347:f6123.
3. Mansi I, Mortensen E. The controversy of a wider statin utilization: why? Expert Opin Drug Saf. 2013 May;12(3):327-37.
4. 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.
5. 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.
6. Available at: http://www.ncbi.nlm.nih.gov/books/nbk92768. Accessed December 18, 2013.
7. 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.
8. Available at: http://www.heart.org/heartorg/conditions/diabetes/whydiabetesmatters/cardiovascular-disease-diabetes_ucm_313865_article.jsp#. Accessed December 18, 2013.
9. 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.
10. 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.
11. 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.
12. 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.
13. 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.
14. 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.
15. 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.
16. 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.
17. 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.
18. 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.
19. 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.
20. Farmer DG, Kennedy S. RAGE, vascular tone and vascular disease. Pharmacol Ther. 2009 Nov;124(2):185-94.
21. 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.
22. Sena CM, Matafome P, Crisostomo J, et al. Methylglyoxal promotes oxidative stress and endothelial dysfunction. Pharmacol Res. 2012 May;65(5):497-506.
23. 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.
24. Garg N, Senthilkumar A, Nusair MB, Goyal N, Garg RK, Alpert MA. Heart failure with a normal left ventricular ejection fraction: epidemiology, pathophysiology, diagnosis and management. Am J Med Sci. 2013 Aug;346(2):129-36.
25. Hoefer IE, den Adel B, Daemen MJ. Biomechanical factors as triggers of vascular growth. Cardiovasc Res. 2013 Jul 15;99(2):276-83.
26. Tian L, Chesler NC. In vivo and in vitro measurements of pulmonary arterial stiffness: A brief review. Pulm Circ. 2012 Oct;2(4):505-17.
27. Dabelea D, Talton JW, D’Agostino R, Jr., et al. Cardiovascular Risk Factors Are Associated With Increased Arterial Stiffness in Youth With Type 1 Diabetes: The SEARCH CVD study. Diabetes Care. 2013 Oct 7.
28. 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.
29. 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.
30. 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.
31. 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.
32. 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.
33. 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.
34. 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.
35. 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.
36. 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.
37. 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.
38. 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.
39. 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.
40. 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.
41. 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.
42. 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.
43. 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.
44. Ling H, Burns TL, Hilleman DE. Novel strategies for managing dyslipidemia: treatment beyond statins. Postgrad Med. 2012 Nov;124(6):43-54.
45. Tenenbaum A, Fisman EZ. Balanced pan-PPAR activator bezafibrate in combination with statin: comprehensive lipids control and diabetes prevention? Cardiovasc Diabetol. 2012;11:140.
46. 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.
47. 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.
48. 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.
49. 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.
50. 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.
51. Tang WH, Martin KA, Hwa J. Aldose reductase, oxidative stress, and diabetic mellitus. Front Pharmacol. 2012;3:87.
52. 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.
53. 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.
54. 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.
55. 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.
56. 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.
57. Usha Rani P. Evaluation of Emblica officinalis (CAPROS^®) on cold pressor induced cardiovascular changes in healthy human subjects. Natreon;2012.
58. 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.
59. 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.
60. Muller MD, Sauder CL, Ray CA. Mental stress elicits sustained and reproducible increases in skin sympathetic nerve activity. Physiol Rep. 2013 Mar;1(1).
61. 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.
62. Usha Rani P, Sravanti IV. Evaluation of effect of Emblica officinalis (Capros) on mental stress induced cardiovascular changes in healthy human subjects: Natreon;2012.
63. Yao FJ, Huang YP, Lin H, et al. Smoking impairs endothelial function in ED patients. Zhonghua Nan Ke Xue. 2011 May;17(5):414-7.
64. Biswas TK, Cakrabarti S, Pandit S, Jana U, Dey SK. Clinical evaluation of a Standardized extract of Emblica officinalis fruits for improvement of cardio-respiratory and antioxidant status of volunteers with long smoking history: Natreon;2012.
65. Della-Morte D, Gardener H, Denaro F, et al. Metabolic syndrome increases carotid artery stiffness: the Northern Manhattan Study. Int J Stroke. 2010 Jun;5(3):138-44.
66. Usha Rani P, Sravanti IV. Study of CAPROS^®250mg, CAPROS^®500mg and placebo on endothelial dysfunction in metabolic syndrome. Natreon;2012.
67. 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.
68. Available at: http://www.wjgnet.com/2220-3168/full/v3/i4/32.htm. Accessed December 31, 2013.
69. 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.
70. 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.
71. 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.
72. 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.
73. 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.
74. 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.
75. 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.
76. 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.
77. 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.
78. 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.
79. 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.
80. 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.
81. 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.
82. 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.
83. 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.
84. Taylor F, Huffman MD, Macedo AF, et al. Statins for the primary prevention of cardiovascular disease. Cochrane Database Syst Rev. 2013;1:Cd004816.