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Life Extension Magazine

LE Magazine July 2006
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Aspirin

Remarkable Research Uncovers Lifesaving Benefits Beyond Cardiovascular Protection

Life Extension, always at the forefront in uncovering the latest scientific and medical breakthroughs for our members, recommended aspirin therapy for cardiovascular protection long before this practice became a standard treatment by cardiologists and other doctors. Life Extension continues to closely scrutinize ongoing scientific research associated with aspirin. Recently, scientists have uncovered tantalizing evidence suggesting that aspirin may help prevent skin cancer and reduce the risk of Alzheimer's disease.

The common thread linking aspirin’s beneficial effects on colorectal cancer, skin cancer, and Alzheimer's appears to be its remarkable ability to reduce excess inflammation and promote healthy blood flow. Today, medical science is confirming what Life Extension members have known for some time—that chronic inflammation underlies many of the most lethal degenerative diseases.

Cells throughout the body manufacture hormone-like substances called prostaglandins, which are involved in fever, inflammation, and pain, as well as thromboxanes, which help regulate blood vessel tone, platelet aggregation, and clot formation.1,2

The fatty acid arachidonic acid is transformed into prostaglandins and thromboxanes through the action of the cyclooxygenase (COX) enzymes. Aspirin works by irreversibly disabling the COX enzymes so that they can no longer produce prosta-glandins and thromboxanes.3-5

By reducing prostaglandin and thromboxane production, aspirin decreases inflammation, pain, fever, and blood clotting. As people grow older, they commonly experience increased inflammation as well as a greater prevalence of undesirable blood-clotting tendencies. Scientists believe that increased oxidative stress and greater levels of pro-inflammatory mediators may induce these changes in aging adults.6,7 Aspirin’s demonstrated ability to reduce inflammation may play a key role in helping to counteract many of the adverse biochemical changes that accompany aging. These very same properties also make aspirin a powerful weapon against many major diseases, including cardiovascular disease and cancer.

HOW ASPIRIN DIFFERS FROM OTHER NONSTEROIDAL ANTI-INFLAMMATORY DRUGS (NSAIDS)

Aspirin is perhaps the best-known member of the family of nonsteroidal anti-inflammatory drugs (NSAIDs). These drugs works by inhibiting the cyclooxygenase (COX) enzymes, which are responsible for the production of hormone-like biochemicals called prostaglandins and thromboxanes.

The COX-1 enzyme produces thromboxanes that support platelet function and prostaglandins that protect the stomach lining. By contrast, the COX-2 enzyme produces prostaglandins that may contribute to inflammation and cancer. Agents that inhibit the COX-2 enzyme may help protect against certain cancers.8-10

Because it inhibits both COX-1 and COX-2, aspirin is considered a non-specific NSAID. Other non-specific NSAIDs include ibuprofen, naproxen, and indomethacin. However, aspirin is distinct from these other non-specific NSAIDs because its inhibition of the COX enzymes is irreversible. This may make aspirin particularly beneficial for inhibiting undesirable blood clotting that can contribute to heart attack and stroke. Aspirin’s ability to block the COX-2 enzyme may help protect against certain cancers. Side effects associated with non-specific NSAIDs like aspirin include stomach irritation and increased bleeding tendency.8-10

Selective COX-2 inhibitors, such as celecoxib (Celebrex®), make up another class of NSAID drugs. COX-2 inhibitors were initially hailed as breakthrough drugs for treating conditions such as arthritis, because they reduce inflammation while producing fewer gastrointestinal side effects than the non-specific NSAIDs. However, alarming research in recent years has shown that while some selective COX-2 inhibitors may lower the risk for certain cancers, they also may increase the risk of adverse cardiovascular outcomes.8-10 (See “Arthritis After Vioxx®,” Life Extension, February 2005.)

These startling research findings concerning the potential cardiovascular risks of selective COX-2 inhibitors have shifted the spotlight back to aspirin, a potent therapeutic that both inhibits inflammation and provides protection against cardiovascular events.

Aspirin and Cancer Prevention

Life Extension has long warned that chronic inflammation can pave the way for many deadly diseases, including cancer. Inflammation plays many roles in encouraging normal cells to become cancerous. For example, inflammation generates free radicals that can damage the genetic material responsible for regulating normal cell death and reproduction.11 While the bulk of the research examining aspirin’s effects against cancer has focused on colorectal cancer, emerging evidence indicates that aspirin may also markedly reduce the risk of cancers of the skin, breast, ovary, lung, and other organs.12

Aspirin offers protection against cancer through its effects on the COX enzymes. While the COX-1 enzyme promotes blood clotting and helps protect the stomach lining, COX-2 participates in harmful inflammation and cancer. Aspirin inhibits both types of COX enzymes, which may account for its protective effects against various cancers.12 Life Extension has long advocated the use of anti-inflammatory therapies, including natural therapeutics such as curcumin and green tea, as strategies to help prevent and fight cancer.13

Aspirin lowers skin cancer risk. A recent study out of sun-drenched Australia offers compelling evidence that aspirin use protects against skin cancer. This study found that people who regularly used aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) were less likely to develop squamous cell carcinoma and actinic keratosis (a pre-cancerous skin condition linked to excessive sun exposure). The lead investigator reported that people who had used aspirin or other NSAIDs at least twice a week for five years reduced their risk of skin cancer by a remarkable 60%, while those who used aspirin daily for five years saw an astounding decrease of nearly 90% in their risk of developing skin cancer. The benefits from regular use of NSAIDs were evident after as little as one year of use, according to the study authors.14,15

Aspirin reduces breast cancer risk. Aspirin may offer protection against two cancers that afflict women: breast cancer and ovarian cancer. A study reported in late 2005 noted that women who used more than 100 mg of aspirin on a frequent basis (for 90 days or more) during the year prior to mammogram testing had a lower risk of breast cancer than infrequent users or non-users of aspirin.16 In 2006, researchers reported the findings of a population-based, case-controlled study of women with ovarian cancer. They noted that women who used any NSAIDs such as aspirin within the previous five years had a reduced risk of developing ovarian cancer. Their data suggests that greater use of NSAIDs correlates with a lower risk of ovarian cancer.17

Aspirin protects against colon cancer. In a double-blind study reported in 2003, researchers gave groups of more than 350 adults a daily dose of either 81 or 325 mg of aspirin, or a placebo pill, for three years. All the subjects had had colon polyps removed in the past, but were free of polyps at the study’s onset. Many colon cancers are thought to develop from polyps. After approximately three years, the subjects underwent another colonoscopy to determine how many growths were present. Subjects who took the 81-mg dose of aspirin had 19% fewer polyps than those in the placebo group. The researchers concluded that low-dose aspirin had a modest effect in reducing the incidence of potentially pre-cancerous polyps.18

Another study examined 635 patients with a history of colorectal cancer. Half took 325 mg of aspirin a day, while half took a placebo. After roughly a year, each group underwent a colonoscopy to check for polyps. The results were even more impressive: subjects in the aspirin group had a 35% lower risk of polyps than those who took placebo. In addition, it took longer for polyps to develop in the subjects who took aspirin.19 These findings suggest an important role for aspirin in preventing colon cancer.

Aspirin and Alzheimer's Disease

Alzheimer's disease not only changes people’s mental abilities, but also alters the physical appearance of their brains. In people who have Alzheimer's, the brain tissue literally shrinks.20

This condition is also marked by scattered, abnormal structures called beta-amyloid plaques and neurofibrillary tangles. In Alzheimer's disease, beta-amyloid plaques are found around the cerebral cortex, as well as in a structure deeper in the brain called the hippocampus, which plays a role in memory storage. Neurofibrillary tangles are found inside the neurons, where they can cause the neuron to have difficulty communicating with other neurons, and later to die. Although many healthy older people have some plaques and tangles in their brains, people with Alzheimer's disease have far more. Substances involved in inflammation have been found in these plaques, and scientists suspect this inflammation contributes to neuronal death.21

One potentially dangerous substance that has been found in the brains of Alzheimer's sufferers is the COX-2 enzyme. Some research has shown a link between excess COX enzymes and prostaglandins with more beta-amyloid in brains. Elevated COX-2 has also been found in hippocampal neurons of people with Alzheimer's, and has been correlated with the withering of neurons and more dense plaques in that region of the brain.22

Another theory suggests that prostaglandins produced by the COX enzymes may also increase the effects of a neurotransmitter called glutamate. Neurotransmitters such as glutamate help nerve cells communicate. If too much glutamate lingers in the space between neurons, it can overstimulate the cells, causing them to die. Researchers have proposed that inhibiting the COX enzymes and thus reducing prostaglandins could reduce the excess stimulation caused by glutamate, thus protecting cells against inflammation and neurodegenerative disease.23-25

Regular use of anti-inflammatory drugs, particularly aspirin, has been associated with a lower prevalence of Alzheimer's disease, along with improved preservation of cognitive function. For example, a meta-analysis examined the use of NSAIDs in relation to the development of Alzheimer's disease in adults over the age of 55. Individuals who regularly used anti-inflammatory drugs had a decreased risk of developing Alzheimer's, and the risk reduction increased as the duration of anti-inflammatory use lengthened. People who used the anti-inflammatory medications for 24 months, for example, had an amazing 73% reduced risk of developing Alzheimer's.26 An analysis of more than 700 individuals over the age of 80 showed that those who regularly used aspirin had a markedly lower prevalence of Alzheimer's dementia. Furthermore, this group maintained better cognitive function than those who did not use aspirin.27

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