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Life Extension Magazine May 2011

Natural Ways to Thwart a Stealth Killer

By Kirk Stokel

The lifetime risk of developing high blood pressure is greater than 90% in adults 55 years and older.1 You may be one of them. Experts estimate that this silent killer accounts for 40.5 million doctor visits each year.1

Natural Ways to Thwart a Stealth Killer

Sadly, those visits often come too late.

Poorly controlled blood pressure slowly damages kidneys and the vasculature, often culminating in heart attack, stroke, or kidney failure.2,3

Tens of thousands of deaths attributable to hypertension occur each year,1 yet most could have been prevented had corrective action been taken earlier in life. Published studies show that aging individuals who achieve a mere 5-point decrease in diastolic blood pressure can reduce their risk for lethal hypertension-related conditions by as much as 16%.4

In this article, you will learn of a discovery by a team of Cambridge researchers showing how to better manage hypertension using low-cost and readily available nutrient compounds.

A Fascinating Discovery

A recent study by researchers at the Cambridge Institute for Medical Research reveals the dangerous relationship between oxidative stress and angiotensin, a hormone that boosts blood pressure often to dangerous levels. Aiwu Zhou and colleagues decided to focus on angiotensin’s parent molecule, angiotensinogen.5 Using ultra-high resolution X-ray crystallography, Zhou’s team examined the underlying mechanisms driving high blood pressure.

When oxidative stress is present, the angiotensinogen molecule shifts its shape and floods the system with angiotensin!5 This led to the discovery of an “oxidative switch” that impacts blood pressure status in the body. What Zhou’s team has done is to identify an entirely new mechanism between oxidative stress and hypertension.

But nutritional scientists have long known that antioxidants confer some protection against hypertension. So Zhou’s work is fueling renewed interest in nutrients that fight oxidation and tip the balance away from angiotensin release. Recent discoveries show that a small handful of antioxidant compounds can inhibit the angiotensin-converting enzyme (ACE) itself, contributing to their antihypertensive effects. Let’s examine some of nature’s own antihypertensive interventions and how they can work to keep you healthy.

Whey proteins derived from milk are antioxidants that may contribute to their antihypertensive properties.

Whey Protein

Whey proteins derived from milk are antioxidants that may contribute to their antihypertensive properties.6-8 They also contribute to blood vessel relaxation and reduced “stiffness.”9 Professor Zhou’s discovery that antioxidant status directly affects angiotensin availability further explains how whey proteins may fight elevated blood pressure.5 Human studies of whey-rich or whey-enriched milk products demonstrate convincing reductions in blood pressure compared with placebo- or casein-supplemented patients.9-11

Whey Protein

In recent years, scientists have found that whey proteins exert substantial direct angiotensin-converting enzyme (ACE)-inhibiting effects.12-14 In the human stomach and intestine, whey proteins break down into very specific short amino acid chains (peptides) that makes them efficient ACE-inhibitors.15-19 Laboratory studies consistently show that blood pressure is reduced in hypertensive animals given whey protein derivatives.20,21 That effect is attributed at least in part to ACE inhibition.21 The ACE-inhibitory effect is substantially less powerful than those of prescription drugs, but some people encounter side effects with those drugs.4,20 Whey protein derivatives, by contrast, can be used for long periods of time without significant problems.9 Recent work suggests that these active milk components also inhibit the release of other vessel-constricting molecules such as endothelin-1, offering a second pathway for blood pressure control.22

Together, all of these findings suggest that whey proteins can reduce the risk of hypertension-related disease.4,23 Let’s now look at other natural antihypertensive nutrients that can work together with whey to promote your cardiovascular health.

Grape Seed Extract and Resveratrol

Grapes contain many biologically active compounds, most notably multitargeted polyphenols such as resveratrol and proanthocyanidins, which are associated with improvements in cardiovascular risk factors.24

Extracts of grape seed are rich in beneficial compounds. Their constituents include antioxidants that reduce markers of oxidative stress, such as oxidized low-density lipoprotein (LDL), that are associated with atherosclerosis.25 Those antioxidant effects can directly prevent or treat elevations in blood pressure in laboratory animals.26

Grape seed extracts operate at multiple additional targets to achieve their beneficial effects on blood pressure. They fight advanced glycation end product (AGE) formation,27 an early step in producing inflammation associated with cardiovascular disease and cancer.28 This means that grape seed extracts hold promise not only in preventing hypertension, but also in fighting some of its deleterious effects, such as kidney damage.29

Grape Seed Extract and Resveratrol

The effects of grape seed extract may also protect the heart. In an experimental model of heart attack, cardiac tissue from animals that had received grape seed extract was better able to recover from lack of blood flow (ischemia), compared with the heart tissue of animals that did not receive grape seed extract.30

Grape seed polyphenols can also reduce salt sensitive-hypertension in an animal model, which may further help push blood pressure into the normal range.31 Finally, grape seed extracts have been shown to induce cognitive improvements in impaired hypertensive rats.32

All of these mechanisms contribute to improved blood pressure control and result in the clinically relevant drops seen in blood pressure in human studies.33 Recent discoveries about resveratrol, a main component of the extracts, shed additional light on their mechanism and their potential.

Resveratrol is one of the more fascinating biologically active molecules known to science. It has a plethora of beneficial effects, acting at several key metabolic switches to promote longevity and fight chronic disease. A powerful antioxidant in its own right, resveratrol also enhances activity of the SIRT-1 regulatory complex, which is associated with prolonged life span in a host of experimental models.34-36 Resveratrol also inhibits signaling molecules expressed by blood vessel cells that are implicated in hypertension.37 The polyphenol improves the way vascular endothelial lining cells react and respond to factors that control blood pressure.34

Preliminary research suggests that resveratrol may have ACE-inhibitory capabilities, adding to its potential for maintaining healthy blood pressure.38 Additionally, resveratrol may suppress some of the adverse effects of angiotensin II, such as vascular smooth muscle cell overgrowth (hypertrophy).39-43

In an animal model, resveratrol has also been found to help prevent cardiac hypertrophy induced by high blood pressure.44,45 Chronic cardiac hypertrophy can lead to cardiac dysfunction and heart failure.46 Angiotensin’s effects have been implicated in that process, and resveratrol can block those effects by its action on multiple pathways.45,47,48

In animal studies, resveratrol reduces pulmonary hypertension, the elevated pressure in arteries of the lungs that dramatically impairs quality of life in people with chronic heart disease.49

What You Need to Know: Hypertension
  • Hypertension
    High blood pressure threatens millions of Americans each year, despite medications and recommendations about diet and exercise.
  • Antioxidants have long been known to provide protection against hypertension by a variety of mechanisms.
  • In late 2010, landmark research revealed that oxidative stress directly increases production of the potent blood pressure-increasing hormone angiotensin. This discovery lends new urgency to the quest for therapies that can restore normal antioxidant function.
  • Nutrients such as whey protein and peptides, grape seed extract, and pomegranate extracts all have superior antihypertensive effects in human and animal studies.
  • All three nutrients restore antioxidant function, and each also fights angiotensin’s deadly effects both by reducing its production and by blocking its deleterious impact on vulnerable tissues.


The pomegranate has demonstrated benefits for cardiovascular health and blood pressure control.50 Pomegranate juice and extracts are rich in some of nature’s most powerful polyphenols.51 Those molecules contribute to a reduction in cellular oxidative stress and help restore natural antioxidants to effective values. As we’ve seen, ameliorating oxidative stress in cells, particularly those of the vascular system, shows promise as an effective means of combating hypertension, because it limits production of angiotensin.5

Like whey proteins and grape seed extracts, however, pomegranate extracts also directly inhibit activity of the angiotensin-converting enzyme (ACE), helping to lower blood pressure.52 And like resveratrol, pomegranate extracts are effective at blocking some of the downstream damage induced by angiotensin in tissues vulnerable to hypertensive changes.53


In still a third line of defense, pomegranate supplements can increase levels of the antioxidant protective complexes called paraoxonases (PON).54 PONs are major components of high-density lipoprotein (HDL) and are widely recognized as providing much of the benefit we see from HDL.54,55

A fourth avenue of benefit from pomegranate extracts is their effect on vessel wall function. Oxidative damage leaves vessels vulnerable to damage at points where blood pressure is markedly increased by so-called shear stress. Pomegranate juice mitigates that damage by improving activity of endothelial nitric oxide synthase (eNOS), thus making more vessel-dilating nitric oxide available.56

The clinical benefits of pomegranate consumption on cardiovascular disease and blood pressure are undeniable. A landmark 2004 study from Israel demonstrated that pomegranate juice consumption for 3 years reduced carotid artery wall thickness in patients with narrowing of those arteries.57 The carotids are the major blood supplier to the brain, and thickening of those walls is a precursor to devastating strokes. That thickening is itself a direct result of chronic exposure to elevated blood pressure as well as abnormal lipid profiles. The patients in the Israeli study experienced an average of 12% reduction in systolic blood pressure by the end of the first year.

Subsequent human studies have demonstrated improvements in blood flow to the heart and the brain in patients with cardiovascular disease, following pomegranate supplementation.58,59 And flow-mediated dilation, a measure of vessels’ ability to respond to pressure changes, is improved after consumption of pomegranate juice.60

Oxidant Stress, Hypertension, and Angiotensin
Oxidant Stress, Hypertension, and Angiotensin

Over the past decade, scientists have come to recognize the extreme importance of oxidative stress in the causation of hypertension.61 In animal studies, oxidative stress increases blood pressure; if that stress is corrected, blood pressure normalizes.62 The root cause is an imbalance between production and elimination of reactive oxygen species (ROS), which triggers damage to the tissues most directly involved in maintenance of blood pressure.63-65

The kidney and the blood vessels are two primary target tissues of ROS damage.64 Both are intimately involved in regulation of blood flow and pressure, and are themselves rich sources of ROS, which makes them especially vulnerable.64 ROS damage reduces blood vessels’ ability to relax in the face of increased flow, which raises blood pressure.61,65 ROS also trigger inflammatory responses within and around vessels that threaten flow and elevate pressure.65,66 And ROS change the signaling characteristics of the vital endothelial cells that both line blood vessels and relay information about pressure to other structures in the vessel.65 Finally, ROS in the brain disrupt central nervous system signaling, further elevating blood pressure.67

It is in the kidney that the worst mischief is done. The kidney is the primary blood pressure control organ, largely through a molecular signaling network called the renin-angiotensin system.

When the kidney perceives a drop in blood flow, it secretes an enzyme called renin. Renin in turn acts on a molecule called angiotensinogen, which is produced throughout the body.68 Renin snips off a small portion of the angiotensinogen molecule, producing a short amino acid chain called angiotensin I.5 Another enzyme, angiotensin-converting enzyme (ACE), then makes one final snip to produce the active peptide hormone angiotensin II.5,68 Angiotensin II is a powerful constrictor of blood vessels, producing an immediate rise in blood pressure upon its release.68

About 30 years ago researchers developed a powerful category of drugs known as ACE-inhibitors. These drugs prevent that final step in which angiotensin I is converted to active angiotensin II.5 Used correctly they can help to lower blood pressure, although they also carry substantial risk of side effects.4

But most ACE-inhibitors work at only one molecular target, leaving them ineffective against the onslaught of oxidative stress, which is a powerful stimulant of angiotensin production. And, in a vicious cycle, increased amounts of active angiotensin further promote production of ROS.65 That has left hypertension researchers avidly seeking an alternative means of reducing the oxidative stress-induced effects of angiotensin on blood vessels.


Blood pressure elevations continue to threaten our longevity and our quality of life. We’ve known for years that people with a high intake of antioxidants tend to have lower blood pressures and to suffer less from cardiovascular disease in general. It’s only in the past decade, however, that we have begun to understand the biochemical underpinnings of that cardioprotective effect. We now understand that oxidative stress induces inflammation in blood vessels that impairs their ability to safely regulate blood pressure.

Only in late 2010 did we learn that a state of high oxidative stress causes the blood pressure-boosting hormone angiotensin to become more readily available in the body. That discovery has set off a storm of interest in researchers aiming to control blood pressure by modifying oxidative stress in the body. Fortunately, solid scientific evidence abounds for the protective effects of three nutrients. Whey protein, grape seed extracts, and pomegranate extracts all work by restoring healthy antioxidant levels. We’ve learned that they each also prevent both activation of angiotensin and its destructive effects by a series of related but complementary mechanisms. Using all three together simply makes sense as a way to optimize your cardiovascular health.

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

Do What It Takes to Maintain Optimal Blood Pressure 24-Hours a Day
Do What It Takes to Maintain Optimal Blood Pressure 24-Hours a Day

Life Extension has long advocated that optimal blood pressure readings over a 24-hour period should be at or below 115/75 mmHg for most people.

When blood pressure is chronically above this level, or when upward spikes in blood pressure occur during certain periods of the day, risk of vascular disease and kidney injury increases.

As humans age, blood pressure tends to rise above optimal ranges, often necessitating a multi-modal approach.

Having one’s blood pressure periodically monitored in a doctor’s office can fail to detect periods of the day when blood pressure may be sharply increased, such as when the effects of a blood pressure drug wear off. The best defense is a home blood pressure monitoring device that is sold over-the-counter in pharmacies or can be ordered directly from Life Extension.

Some people require blood pressure lowering drugs to achieve optimal control. A generic drug called losartan is often prescribed at a starting dose of 50 mg once a day. This drug does not always provide 24-hour blood pressure control, sometimes necessitating twice-a-day dosage (up to 50 mg two times a day).

A more expensive drug called Benicar® consistently shows better 24-hour blood pressure control, and is usually prescribed at a starting dose of 20 mg once a day.

An advantage to using nutrients that help support healthy blood pressure levels is that the dose of prescription drugs may be reduced. Nutrients and lifestyle changes (reduced calorie/sodium intake and increased physical activity) can also reduce the dosage or need for prescriptive anti-hypertensive drugs.

Whatever intervention you select, the ultimate objective is not to exceed a blood pressure level of 115/75 at rest throughout the day. With a home blood pressure monitoring device, you can check your blood pressure at intervals throughout the day to ensure that whatever program you select is achieving optimal results.


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