Health Benefits of Aspirin: Miscellaneous Benefits

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Aspirin use may help prevent bile duct cancer

A team of current and former Mayo Clinic researchers has discovered that aspirin use is associated with a significantly reduced risk of developing bile duct cancer, also called cholangiocarcinoma. The results are published in Hepatology.

"Our study found that individuals who took aspirin had a more than a two-and-a-half to three-and-a-half-fold lesser chance of developing bile duct cancer, compared to individuals who did not take aspirin," says Lewis Roberts, M.B. Ch.B., Ph.D., the study's senior author and a gastroenterologist and hepatologist at Mayo Clinic.

Bile duct cancer is an uncommon cancer that forms in the slender tubes (bile ducts) that carry digestive fluid through the liver. The disease occurs mostly in people over 50 and can cause symptoms, such as yellowing of the skin and eyes, intense itchiness of the skin, and white stools. Bile duct cancer is an aggressive type of cancer that progresses quickly and is difficult to treat.

"We know that continuous unremitting inflammation is one of the main factors that promotes cancer of the bile ducts," Dr. Roberts says. "Aspirin, with it's an anti-inflammatory properties, may reduce the risk of bile duct cancer by lessening inflammation through inhibition of an enzyme called cyclo-oxygenase (COX), which is known to promote inflammation."

In addition to the COX enzyme pathway, Dr. Roberts says other studies have shown that aspirin blocks additional cell-signaling cascades that promote cancer development. "The evidence has been accumulating that regular, long-term use of aspirin is associated with a decreased risk of a number of different cancer types, particularly gastrointestinal cancers," he says.

But, it is not certain that aspirin is safe to use for cancer prevention. Dr. Roberts and his colleagues say additional confirmatory studies are needed before aspirin can be recommended for use in preventing bile duct cancer. Future plans will include population-based studies designed to confirm the associations of aspirin with decreased risk of developing bile duct cancer and clinical trials of aspirin in people at high risk for developing bile duct cancer.

 

Aspirin use = lower risk of death from chronic liver disease

Aspirin use is associated with a decreased risk of developing hepatocellular carcinoma and death from chronic liver disease (CLD), according to a study published November 28, 2012 in the Journal of the National Cancer Institute.

Hepatocellular carcinoma (HCC), the most common type of primary liver cancer, occurs mainly among patients with CLD. Previous reports have linked chronic inflammation due to CLD to cellular processes that could promote carcinogenesis. Because of their anti-inflammatory properties and widespread use to prevent cardiovascular and cerebrovascular disease, nonsteroidal anti-inflammatory drugs (NSAIDs) including aspirin and nonaspirin NSAIDs are being investigated as cancer chemopreventive agents. NSAIDs have been shown to have a beneficial effect in observational studies and clinical trials on risk of some cancers. However, the relationship between NSAID use and risk of HCC and death from CLD is unclear.

To investigate this relationship, Vikrant V. Sahasrabuddhe, M.B.B.S., Dr.P.H, from the Division of Cancer Epidemiology and Genetics at the National Cancer Institute, and colleagues, performed an observational study of 300,504 men and women aged 50 to 71 years enrolled in the National Institutes of Health-AARP Diet and Health Study who reported their aspirin and nonaspirin NSAID use and were followed-up for 10-12 years. The researchers linked the self-reported use of aspirin and nonaspirin NSAIDs to registry data on diagnoses of 250 cases of HCC and 428 deaths due to CLD to perform their study.

The researchers found that the use of NSAIDs was associated with a reduced risk of HCC and a reduced risk of death from CLD compared to non-users. Study participants who used aspirin had a 41% reduced risk of HCC and a 45% reduced risk of death from CLD, whereas those who used non-aspirin NSAIDs experienced a 26% reduced risk of CLD mortality but no reduced risk of HCC. The authors conclude that "these associations are prominent with the use of aspirin, and if confirmed, might open new vistas for chemoprevention of HCC and CLD."

In an accompanying editorial, Isra G. Levy, M.B., BCh., MSc., and Carolyn P. Pim, M.D., both from the Department of Epidemiology and Community Medicine at the University of Ottawa in Canada discuss how the known causes of chronic liver disease and primary liver cancer are hepatitis B and C virus infections, alcohol use, and a link between obesity and diabetes has been suggested. "We already have cheap, readily available interventions," such as vaccines for hepatitis B and C virus but "effective strategies for reduction of HBV and HCV are not always available or fully applied." Also, alcohol abuse and obesity are complex and multifactorial challenges that require interventions at the individual and system levels." They conclude that although we should study the potential of new chemopreventive strategies such as NSAID use, we should also continue to focus on improving the established practices and interventions.

Aspirin can prevent liver damage that afflicts millions, Yale study finds

Simple aspirin may prevent liver damage in millions of people suffering from side effects of common drugs, alcohol abuse, and obesity-related liver disease, a new Yale University study suggests.

The study in the January 26, 2009 edition of Journal of Clinical Investigation documents that in mice, aspirin reduced mortality caused by an overdose of acetaminophen, best known by the brand name Tylenol. It further showed that a class of molecules known as TLR antagonists, which block receptors known to activate inflammation, have a similar effect as aspirin. Since these agents seem to work by reducing injury-induced inflammation, the results suggest aspirin may help prevent and treat liver damage from a host of non-infectious causes, said Wajahat Mehal, M.D., of the Section of Digestive Diseases and Department of Immunobiology at Yale School of Medicine.

"Many agents such as drugs and alcohol cause liver damage, and we have found two ways to block a central pathway responsible for such liver injury," Mehal said. "Our strategy is to use aspirin on a daily basis to prevent liver injury, but if it occurs, to use TLR antagonists to treat it."

Promising drugs that have failed clinical trials because of liver toxicity might be resurrected if combined with aspirin, Mehal said.

  

Benefits of aspirin for treating osteoporosis

Researchers at the University of Southern California, School of Dentistry have uncovered the health benefits of aspirin in the fight against osteoporosis. Forty-four million Americans, 68 percent of whom are women, suffer from the debilitating effects of osteoporosis according to the National Institute of Health. One out of every two women and one in four men over 50 will have an osteoporosis-related fracture in their lifetime.

This latest study identifies aspirin's medicinal role on two fronts. In mice, the drug appears to prevent both improper bone resorption and the death of bone-forming stem cells. The findings were published in PLoS ONE http://www.plosone.org/doi/pone.0002615 on Wednesday, July 9, 2007.

An aspirin regimen appears to help mice recover from osteoporosis in two useful ways, striking a balance between bone formation and resorption, according to Associate Professor Songtao Shi and Research Associate Takayoshi Yamaza of the USC School of Dentistry's Center for Craniofacial Molecular Biology (CCMB).

The silent disease affects both men and women. In women, bone loss is greatest during the first few years after menopause. Osteoporosis occurs when bone resorption (loss of bone) occurs too quickly or when formation (replacement) occurs to slowly.

According to Shi, the removal of the ovaries and the resulting decrease in estrogen induces osteoporosis in mice, much like the onset of the disease in post-menopausal women. It is commonly thought that T-lymphocytes, a type of immune system cell, play a pivotal part in this process by over-activating osteoclasts, the bone cells that reabsorb bone material from the skeleton. Most current osteoporosis therapies aim to curb overactive osteoclasts.

However, there seems to be another side to the T-lymphocytes', or T-cells', role in osteoporosis, Yamaza says. While the immune cells typically attack disease cells and other foreign entities, the T-cells can mistakenly attack healthy stem cells.

"After infusing the mice with T-cells, the T-cells impaired the function of bone marrow mesenchymal stem cells as well as caused osteoclast numbers to increase," he says.

The bone marrow mesenchymal stem cells, or BMMSC, differentiate to become many different cells including osteoblasts, the cells responsible for bone formation. If this processed is impaired by T-cells, bone formation cannot keep up with bone resorption caused by osteoclasts, and bone mineral density decreases – the hallmark of osteoporosis that leads to skeletal structural deterioration and fractures.

An aspirin regimen has been linked in earlier epidemiological studies to better bone mineral density, but the mechanisms of its interactions in regards to bone health had not yet been studied extensively, Shi said.

"We've shown how aspirin both inhibits bone resorption and promotes osteoblast formation," Shi says.

Another exciting aspect of the aspirin treatment is that the dose administered to the mice in order to increase their bone mineral density is the same as that of a typical human aspirin regimen when adjusted for body weight differences, he adds. While the species difference is still a factor, the results are promising.

"When we gave a large amount of aspirin to the mouse by injection, it did not work," Shi says, "but when we gave a low dose in the mice's water for a long period of time, similar to a human dosage, the bone mineral density increased."

Shi and Yamaza hope that their work will translate into new clinical strategies for osteoporosis.

"We have opened a door," Shi says. "We hope other scientists can confirm what we've found and move the treatment forward."

The use of aspirin offers hope to patients and doctors searching for a potential alternative to bisphophonates currently being used as a means of prevention and treatment for osteoporosis. This latest study opens up the possibility that aspirin some day will not only be prescribed to ward off heart disease but also osteoporosis.

Aspirin and omega-3 fatty acids work together to fight inflammation

Experts tout the health benefits of low-dose aspirin and omega-3 fatty acids found in foods like flax seeds and salmon, but the detailed mechanisms involved in their effects are not fully known. Researchers reporting in the February 21, 2013 issue of the Cell Press journal Chemistry & Biology show that aspirin helps trigger the production of molecules called resolvins that are naturally made by the body from omega-3 fatty acids. These resolvins shut off, or "resolve," the inflammation that underlies destructive conditions such as inflammatory lung disease, heart disease, and arthritis.

"In this report, we found that one resolvin, termed resolvin D3 from the omega-3 fatty acid DHA, persists longer at sites of inflammation than either resolvin D1 or resolvin D2 in the natural resolution of inflammation in mice," explains senior author Dr. Charles Serhan of Brigham and Women's Hospital and Harvard Medical School. "This finding suggests that this late resolution phase resolvin D3 might display unique properties in fighting uncontrolled inflammation."

The researchers also confirmed that aspirin treatment triggered the production of a longer acting form of resolvin D3 through a different pathway. "Aspirin is able to modify an inflammatory enzyme to stop forming molecules that propagate inflammation and instead produce molecules from omega-3 fatty acids, like resolvin D3, that help inflammation to end," explains coauthor Dr. Nicos Petasis of the University of Southern California.

Aspirin before heart surgery reduces the risk of post-operative acute kidney failure

Aspirin taken for five days before a heart operation can halve the numbers of patients developing post-operative acute kidney failure, according to research presented at the European Anaesthesiology Congress in Paris June 10, 2012.

Professor Jianzhong Sun (MD, PhD), professor and attending anaesthesiologist at Jefferson Medical College, Thomas Jefferson University (Philadelphia, USA), told the meeting that in a study of 3,219 patients, pre-operative aspirin therapy was associated with a reduction in acute renal failure of about three in every 100 patients undergoing coronary artery bypass graft (CABG), valve surgery or both.

The patients were divided into two groups: those taking aspirin within five days before their operation (2,247 patients) and those not taking it (972 patients) [1]. Although the researchers had no record of the precise dose taken, doses of between 80-325mg per day is the normal dose for aspirin that is taken over a period of time.

After adjusting their results for various differing characteristics such as age, disease, and other medications, the researchers found that pre-operative aspirin was associated with a significant decrease in the incidence of post-operative kidney failure,

Acute renal failure occurred in 86 out of 2247 patients (3.8%) taking aspirin, and in 65 out of 972 patients (6.7%) not taking it. This represented an approximate halving in the risk of acute renal failure.

Prof Sun said: "Thus, the results of this clinical study showed that pre-operative therapy with aspirin is associated with preventing about an extra three cases of acute renal failure per 100 patients undergoing CABG or/and valve surgery."

Acute renal failure or injury is a common post-operative complication and has a significant impact on the survival of patients undergoing heart surgery. "It significantly increases hospital stay, the incidence of other complications and mortality," said Prof Sun. "From previous reports, up to 30% of patients who undergo cardiac surgery develop acute renal failure. In our studies, about 16-40% of cardiac surgery patients developed it in various degrees, depending upon how their kidneys were functioning before the operation. Despite intensive studies we don't understand yet why kidney failure can develop after cardiac surgery, but possible mechanisms could involve inflammatory and neurohormonal factors, reduced blood supply, reperfusion injury, kidney toxicity and/or their combinations."

He continued: "For many years, aspirin as an anti-platelet and anti-inflammatory agent has been one of the major medicines in prevention and treatment of cardiovascular disease in non-surgical settings. Now its applications have spread to surgical fields, including cardiac surgery, and further, to non-cardiovascular diseases, such as the prevention of cancer. Looking back and ahead, I believe we can say that aspirin is really a wonder drug, and its wide applications and multiple benefits are truly beyond what we could expect and certainly worthy of further studies both in bench and bedside research."

Prof Sun said that more observational and randomised controlled clinical trials were required to investigate the role played by aspirin in preventing post-operative kidney failure, but he believed that the effect might also be seen in patients undergoing non-cardiac surgeries.

"For instance, the PeriOperative ISchemic Evaluation-2 trial (POISE-2) [2] is ongoing and aims to test whether small doses of aspirin, given individually for a short period before and after major non-cardiac surgeries, could prevent major cardiovascular complications such as heart attacks and death, around the time of surgery."

Other findings from Prof Sun's research showed that diabetes, high blood pressure, heart disease, heart failure, and diseases of the vascular system were all independent risk factors for post-operative acute kidney failure.

Low-dose aspirin offers lower chance of asthma

In a large, randomized, placebo-controlled study of 22,071 healthy male physicians, taking a low-dose of aspirin every other day lowered the risk of receiving an initial asthma diagnosis by 22 percent.

These findings, based on data from the double-blind Physicians' Health Study, appear in the second issue for January 2007 of the American Journal of Respiratory and Critical Care Medicine, published by the American Thoracic Society.

Tobias Kurth, M.D., Sc.D., of the Division of Aging at Brigham and Women's Hospital in Massachusetts, and five associates studied physicians, ages 40 to 84, over a period of 4.9 years. Among the 11,037 individuals who took aspirin, 113 new cases of asthma were diagnosed, as contrasted to 145 in the placebo group.

"Aspirin reduced the risk by 22 percent of newly-diagnosed adult-onset asthma," said Dr. Kurth. "These results suggest that aspirin may reduce the development of asthma in adults. They do not imply that aspirin improves symptoms in patients with asthma."

"Indeed, asthma can cause severe bronchospasm in some patients who have asthma," he continued. "Because asthma was not the primary endpoint of the U. S. Public Health Service study, additional randomized trials would be helpful to confirm the apparent reduction in asthma incidence caused by aspirin."

The Physicians Health Study, which began in 1982, was terminated after 4.9 years when results showed a 44-percent reduction in the risk of a first heart attack among those randomly assigned to aspirin.

"Physicians could self-report an asthma diagnosis on questionnaires at baseline, at six months and annually thereafter," said Dr. Kurth. "Asthma was not the original deductive endpoint of the trial."

According to the authors, the 22-percent lower risk of newly-diagnosed asthma among those assigned to the low-dose aspirin group was not affected by participant characteristics like smoking, body mass index or age.

They noted that aspirin-intolerant asthma, a problem in which aspirin exacerbates the disease, affects only a small minority of asthma patients. In three large population-based studies, that difficulty affected only four to 11 percent of the groups. In children, however, the proportion affected by aspirin intolerant asthma was significantly smaller.

Daily low-dose aspirin may protect against preeclampsia complications

Daily low-dose aspirin beginning as early as the second trimester of pregnancy may prevent complications from preeclampsia, according to an article being published in Annals of Internal Medicine. Preeclampsia is a condition characterized by high blood pressure and proteinuria during the second half of pregnancy. Poor perinatal health outcomes are associated with preeclampsia, primarily due to increased risk for intrauterine growth restriction (IUGR) or medically initiated preterm delivery. Preeclampsia is the leading cause of maternal deaths and is responsible for more than one third of serious maternal morbidities and 15 percent of preterm births.

Predicting which patients will develop preeclampsia is not possible but some conditions, such as preeclampsia in a previous pregnancy or chronic illnesses such as diabetes, hypertension, and renal disease put women at high risk. Prevention is imperative because the only effective treatment for preeclampsia is delivery, which may have serious neonatal harms before 34 weeks of gestation.

Researchers  found that when women at high-risk for preeclampsia started taking a daily low-dose aspirin after their first trimester their risk of developing preeclampsia during the pregnancy dropped by 24-percent. In addition, the risk for preterm birth dropped by 14 percent and the risk for IUGR dropped by 20 percent.

Aspirin has double benefits in fighting inflammation

Hugely popular non-steroidal anti-inflammation drugs like aspirin, naproxen (marketed as Aleve) and ibuprofen (Advil, Motrin) all work by inhibiting or killing an enzyme called cyclooxygenase – a key catalyst in production of hormone-like lipid compounds called prostaglandins that are linked to a variety of ailments, from headaches and arthritis to menstrual cramps and wound sepsis.

In a new paper, published August 2014 in the online early edition of PNAS, researchers at the University of California, San Diego School of Medicine conclude that aspirin has a second effect: Not only does it kill cyclooxygenase, thus preventing production of the prostaglandins that cause inflammation and pain, it also prompts the enzyme to generate another compound that hastens the end of inflammation, returning the affected cells to homeostatic health.

"Aspirin causes the cyclooxygenase to make a small amount of a related product called 15-HETE," said senior author Edward A. Dennis, PhD, Distinguished Professor of Pharmacology, Chemistry and Biochemistry. "During infection and inflammation, the 15-HETE can be converted by a second enzyme into lipoxin, which is known to help reverse inflammation and cause its resolution – a good thing."

Specifically, Dennis and colleagues looked at the function of a type of white blood cells called macrophages, a major player in the body's immune response to injury and infection. They found that macrophages contain the biochemical tools to not just initiate inflammation, a natural part of the immune response, but also to promote recovery from inflammation by releasing 15-HETE and converting it into lipoxin as the inflammation progresses.

Dennis said the findings may open new possibilities for anti-inflammatory therapies by developing new drugs based on analogues of lipoxin and other related molecules that promote resolution of inflammation. "If we can find ways to promote more resolution of inflammation, we can promote health," he said.

Aspirin shown to benefit schizophrenia treatment

A new study shows that some anti-inflammatory medicines, such as aspirin, estrogen, and Fluimucil, can improve the efficacy of existing schizophrenia treatments. This work is being presented at the 2014 European College of Neuropsychopharmacology conference in Berlin.

For some time, doctors have believed that helping the immune system may benefit the treatment of schizophrenia, but until now there has been no conclusive evidence that this would be effective. Now a group of researchers at the University of Utrecht in the Netherlands has carried out a comprehensive meta-analysis of all robust studies on the effects of adding anti-inflammatories to antipsychotic medication. This has allowed them to conclude that anti-inflammatory medicines, such as aspirin, can add to the effective treatment of schizophrenia.

Research has shown that the immune system is linked to certain psychiatric disorders, such as schizophrenia and bipolar disorder. Schizophrenia in particular is linked to the HLA gene system, which is found on chromosome 6 in humans. The HLA system controls many of the characteristics of the immune system.

According to lead researcher, Professor Iris Sommer (Psychiatry Department, University Medical Centre, Utrecht, Netherlands):

"The picture on anti-inflammatory agents in schizophrenia has been mixed, but this analysis pulls together the data from 26 double-blind randomised controlled trials, and provides significant evidence that some (but not all) anti-inflammatory agents can improve symptoms of patients with schizophrenia. In particular, aspirin, estrogens (in women) and the common antioxidant N-acetylcysteine (fluimicil) show promising results. Other anti-inflammatory agents, including celecoxib, minocycline, davunetide, and fatty acids showed no significant effect".

In spite the fact that schizophrenia affects around 24 million people worldwide1, treatment has not changed much in over 50 years, and largely relies on correcting the regulation of dopamine in the brain of schizophrenia sufferers. This has been shown to help symptoms such as hallucinations and delusions, but has been unable to help many other symptoms such as decreased energy, lack of motivation and poor concentration. In addition, around 20 to 30% of all patients don't respond to antipsychotic treatment. Co-treatment with anti-inflammatory agents holds the possibility of improving patient's response to treatment.

Professor Sommer continued:

"The study makes us realise that we need to be selective about which anti-inflammatory we use. Now that we know that some effects are replicated, we need to refine our methods to see if we can turn it into a real treatment. We have just started a multicenter trial using simvastatine to reduce inflammation in the brain of patients with schizophrenia. Studies like these will provide the proof-of-concept for targeting the immune system in schizophrenia".

Commenting for the ECNP, Professor Celso Arango (Hospital General Universitario Gregorio Marañón, Madrid) said:

"Inflammation and oxidative stress seem to be important factors in different mental disorders. Patients with different mental conditions, including schizophrenia, have been shown to have reduced antioxidants in the brain as well as excess inflammatory markers. Animal models and clinical trials have shown that antioxidants and anti-inflammatory drugs could not only reduce symptoms associated with the disorders but also prevent the appearance of neurobiological abnormalities and transition to psychosis if given early during brain development. This work is a step towards the possibility of better treatment, but we need more research in this area, especially with younger subjects where we might expect more brain plasticity".