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Health Protocols

Atherosclerosis and Cardiovascular Disease

The Remarkable Lifesaving Benefits of Aspirin

Oftentimes, the benefits of aspirin are overlooked in light of the numerous nutritional ingredients that convey cardio-protective effects. This is unfortunate because maturing individuals can utilize aspirin, along with these nutritional ingredients, to significantly enhance their defense against cardiovascular disease.

Studies indicate that aspirin may protect against heart disease in part by improving endothelial function. In a study involving 41 patients with hypertension and high cholesterol, 100 mg of aspirin daily was shown to lower both systolic and diastolic blood pressure and to increase flow-mediated dilation, a maker of endothelial function (Magen, 2005).

The heart depends on its coronary arteries for the oxygen supply that fuels this most vital of organs. Coronary heart disease occurs when normal blood flow through the arteries that feed the heart is slowed or interrupted by factors such as blood clots or plaque.

Preventing clots is another way that aspirin helps prevent heart attacks. By irreversibly blocking production of clot-promoting compounds known as thromboxanes, aspirin prevents platelets in the blood from latching on to each other and forming a clot. A platelet has a life span of 10 days, and aspirin irreversibly impairs the platelet’s clotting ability. Aspirin helps blood flow more smoothly past any plaque that is narrowing an artery, and if a plaque ruptures, aspirin will reduce the likelihood of a clot clinging to it (Steinhubl, 2005).

Aspirin can also help prevent heart disease through its anti-inflammatory action. Inflammation participates in many disease processes in the body, including plaque accumulation in the arteries (Libby, 2002). The growth of plaque can obstruct blood flow through the arteries. If a plaque ruptures due to inflammation, it can trigger a heart attack.

A 2003 meta-analysis examined aspirin’s effects on primary heart-attack prevention (that is, the prevention of first heart attacks). In more than 55,000 men and women, aspirin use was associated with a 32% reduction in the risk of having a first heart attack, and with a 15% reduction in the risk of all major vascular events (Eidelman, 2003).

A study presented at the 2005 meeting of the American Heart Association reported on the lifesaving benefits of aspirin therapy. This study examined nearly 9,000 women with stable heart disease, ranging in age from 50 to 79. During more than six years of follow-up, women taking aspirin were 25% less likely to die from heart disease and 17% less likely to die from any cause. Some women took 81 mg of aspirin daily, while others took 325 mg. The study authors stated that the two doses appeared to be similarly effective, but that higher doses of aspirin are associated with a greater risk of certain side effects, such as stomach bleeding (American Heart Association).

A meta-analysis published in 2006 examined the effects of aspirin therapy in preventing cardiovascular events in women and men. Examining data from more than 50,000 women, investigators determined that aspirin therapy was associated with a significant 12% reduction in cardiovascular events in women. Among more than 44,000 men, aspirin therapy produced a significant 14% reduction in all cardiovascular events and an even more impressive 32% reduction in heart attacks (Berger, 2006).

According to the US Preventive Services Task Force, aspirin’s proven benefits are reason enough for people to start using it if they have at least a 6% chance of developing coronary heart disease in the next 10 years. By contrast, the American Heart Association recommends aspirin for people whose 10-year risk of developing coronary heart disease is 10% or higher, as long they have no medical contraindications for taking the drug. A doctor can help you calculate your cardiovascular risk based on factors such as tobacco use, cholesterol, and blood pressure. You can also assess your cardiovascular risk by using online risk factor calculators available at the American Heart Association website.

Life Extension strongly recommends that people who have already had a heart attack (or other episode of heart disease) discuss aspirin therapy with their doctor as part of a strategy to prevent future problems. Life Extension also suggests that people with no previous history of cardiovascular disease—but who are nevertheless at high risk for heart disease—strongly consider aspirin therapy in consultation with their personal physician. The recommended dose for preventing heart-related problems is 81-325 mg daily. Speak with your doctor about your personal needs before beginning aspirin therapy.

Hormones and Cardiovascular Health

Testosterone and estrogen balance (men). Recent studies suggest that testosterone-replacement may improve the symptoms of vascular disease. A placebo-controlled crossover study in men with ischemic heart disease and low testosterone levels reported that exercise time and the time to development of ischemic changes on a treadmill test were both increased with testosterone-replacement therapy (Malkin, 2004).

It has been shown that men with lower levels of testosterone have poorer endothelial function. In a study of 187 males, researchers found that those men in the highest quartile of testosterone levels had 1.7 fold greater flow mediated dilation, a marker of endothelial function (Akishita, 2007).

In another study, researchers examined the correlation between testosterone levels and mortality in over 900 men with coronary heart disease. The team found that the mortality rate in patients with testosterone deficiency was 21%, while only 12% of subjects with normal testosterone levels died. The authors of the study concluded that “in patients with coronary disease testosterone deficiency is common and impacts significantly negatively on survival” (Malkin, 2010).

Researchers analyzed 30-day survival data for 126 men who had suffered a heart attack. All of the men who did not survive were found to have low total testosterone levels (<= 300 ng/dL). The team went on to conclude that “a low level of testosterone was independently related to total short-term [post-heart attack] mortality (Militaru, 2010).

Testosterone levels are also inversely associated with the development of coronary artery disease. In a study of men 45 years of age or younger, researchers found that subjects with diagnosed coronary artery disease had significantly lower levels of free testosterone than did healthy, age-matched controls. The researchers went on to caution that, based on their findings, “a low level of free testosterone may be related to the development of premature coronary artery disease” (Turhan, 2007).

Italian researchers compared plasma testosterone levels of 119 elderly men with isolated systolic hypertension to those of 106 nonhypertensive elderly men. All the study participants were 60 to 79 years old, non-obese, nondiabetic, and nonsmokers. The hypertensive men were found to have 14% lower levels of testosterone compared to the nonhypertensive men. In both the hypertensive and nonhypertensive men, low testosterone levels correlated with higher blood pressure values (Fogari, 2003).

In a study of over 11,000 men, followed for up to 10 years, baseline testosterone concentrations were inversely associated with cardiovascular and all-cause mortality. Men with total testosterone levels of 481 ng/dL or greater at baseline were significantly less likely to die of cardiovascular disease or any cause during the follow-up period compared to men with testosterone levels below 481 ng/dL. The correlation held even after adjustment for various other confounding factors. The authors of this study declared that “low testosterone may be a predictive marker for those at high risk of cardiovascular disease” (Khaw, 2007).

A study published in the Journal of the American Medical Association (JAMA) measured blood estradiol (a dominant estrogen) in 501 men with chronic heart failure. Compared to men in the balanced estrogen quintile, men in the lowest estradiol quintile were 317% more likely to die during a 3-year follow-up, while men in the highest estradiol quintile were 133% more likely to die (Jankowska, 2009).

The men in the balanced quintile—with the fewest deaths—had serum estradiol levels between 21.80 and 30.11 pg/mL. This is very similar to the optimal range that Life Extension has long recommended for aging men. The men in the highest quintile who suffered 133% increased death rates had serum estradiol levels of 37.40 pg/mL or above. The lowest estradiol group that suffered a 317% increased death rate had serum estradiol levels under 12.90 pg/mL.

For more information on optimizing male hormone levels in order to prevent not only vascular disease, but many other age-related diseases as well, please review the chapter on Male Hormone Restoration Therapy.

Testosterone Protects Women Too

Testosterone is often thought to be beneficial only for men. However, a study of nearly 3,000 women reveals that maintaining optimal testosterone levels is important for females as well. After assessing testosterone levels at baseline, researchers found that, over a 4.5 year follow-up period, those women with the lowest levels of testosterone were more likely to experience a cardiovascular event and to die of any cause than women with the highest testosterone. The authors concluded “low baseline testosterone in women is associated with increased all-cause mortality and incident cardiovascular events independent of traditional risk factors” (Sievers, 2010).

DHEA (men and women). DHEA is a precursor to sex hormones such as testosterone and estrogen. Levels of steroid hormones, including DHEA, decline with the age-associated onset of a variety of medical conditions, including chronic inflammation, hypertension, and atherosclerosis. Higher levels of DHEA in humans are associated with lower levels of inflammatory biomarkers (Sondergaard HP et al 2004).

A study showed that men with high levels of DHEA tended to have greater protection against aortic atherosclerosis progression (Hak AE et al 2002). Similarly, another study of 419 Japanese individuals found that those with the highest circulating levels of DHEA-sulfate (form of DHEA commonly measured on blood tests) were much less likely to have carotid atherosclerosis (Yoshida, 2010).

Animal studies show a protective role for DHEA in preventing atherosclerosis. Providing DHEA to human vascular endothelial cells in culture increases nitric oxide synthesis, which boosts blood flow (Simoncini T et al 2003).

Progesterone (women). Several studies have determined that non-bioidentical progestin promotes the formation of atherosclerosis (Register, 1998; Levine, 1996). The story is quite different for bioidentical progesterone, where multiple animal studies have shown that bioidentical progesterone inhibits the process of atherosclerosis (Morey, 1997; Houser, 2000). To illustrate, scientists fed postmenopausal monkeys a diet which is known to cause atherosclerosis for 30 months. The scientists then divided the monkeys into groups that received estrogen alone, estrogen plus non-bioidentical progestin, or a control group that did not receive hormones. The control group developed substantial atherosclerotic plaque. The administration of estrogen resulted in a 72% decrease in atherosclerotic plaque, compared to the control group. Treatment with non-bioidentical progestin yielded disturbing results. The group that received estrogen combined with non-bioidentical progestin had a similar amount of atherosclerotic plaque as the control group, meaning that non-bioidentical progestin completely reversed estrogen’s inhibitory effects on the formation of atherosclerosis (Adams, 1997). In contrast, when the same investigators administered bioidentical progesterone along with estrogen, no such inhibition of estrogen’s cardiovascular benefit was seen (Adams, 1990).

In a trial published in the Journal of the American College of Cardiology, researchers studied postmenopausal women with a history of heart attack or coronary artery disease. The women were given estrogen in combination with either bioidentical progesterone or non-bioidentical progestin. After 10 days of treatment the women underwent exercise treadmill tests. Compared to the non-bioidentical progestin group, the amount of time it took to produce myocardial ischemia (reduced blood flow to the heart) on the exercise treadmill was substantially improved in the bioidentical progesterone group (Rosano, 2000).

Estriol (women). Growing evidence suggests that estriol may offer benefits to the cardiovascular system. For instance, Japanese scientists found that a group of menopausal women given estriol for 12 months had a significant decrease in both systolic and diastolic blood pressure (Takahashi, 2000). Another study compared the use of estriol for 10 months in 20 postmenopausal and 29 elderly women. Some of the elderly women had decreases in total cholesterol and triglycerides and an increase in beneficial HDL (Nishibe, 1996).

To examine the effects of estriol on atherosclerosis, researchers conducted an experiment in which female rabbits were fed a high cholesterol diet with or without supplemental estriol. The rabbits had their ovaries removed surgically to mimic menopause. Remarkably, the group receiving estriol had 75% less atherosclerosis than the group fed the high cholesterol diet alone (without estriol) (Kano, 2002).

Phytoestrogens (women). Following menopause, circulating levels of estrogen are depleted. Phytoestrogens are plant hormones with estrogenic activity. In postmenopausal women, phytoestrogens appear to have estrogen-like benefits such as protection against osteoporosis (Atkinson C et al 2004; Crisafulli A et al 2004a) and possibly hot flashes (Crisafulli A et al 2004b). Phytoestrogens have also been shown to improve vascular function, which tends to decline with age. In one study genistein, a phytoestrogen, provided in a daily 54 mg supplement for one year, significantly improved endothelium-dependent vasodilation in postmenopausal women. Moreover, its benefits were as substantial as those observed in women receiving an estrogen-progestin regimen (Squadrito F et al 2003).

For more information on optimizing female hormone levels in order to prevent not only cardiovascular disease, but other age-related diseases as well, please review the chapter on Female Hormone Restoration Therapy.


Atherosclerosis is a serious threat to the health of a staggering number of individuals across the globe. Its progression has been linked to increased risk of heart attack, stroke, atrial fibrillation and dementia, among other potentially fatal conditions. Since it may begin as early as childhood and aging has been identified as the greatest risk factor for its development, it is vital to combat this disease as early—and as aggressively—as possible. Unfortunately, if aging individuals leave the health of their arteries in the hands of mainstream medicine, they cannot expect conventional approaches to address all the risk factors that lead to atherosclerosis and cardiovascular disease.

Comprehensive blood testing helps aging individuals identify and target their specific risk factors, allowing for the development of a personalized, targeted treatment regimen that can be used to preserve and improve cardiovascular health.

In contrast to the methods of mainstream medicine, which address only very few heart disease risk factors, Life Extension has identified numerous scientifically validated ways by which aging individuals can improve the function of their endothelial cells and greatly reduce their risk of developing deadly atherosclerotic plaque buildup in their blood vessels.

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The protocols raise many issues that are subject to change as new data emerge. None of our suggested protocol regimens can guarantee health benefits. The publisher has not performed independent verification of the data contained herein, and expressly disclaim responsibility for any error in literature.