Effects of Aspirin on COX-2 and Inflammation: Benefits and Side Effects
A Useful Medication With Some Drawbacks
When aspirin was first created it was hailed as a wonder drug for inflammation, pain, and fever. It's still a very useful medication today. It has many health benefits and is a staple in many people's medicine cabinets. However, some people have moved to a different medication because aspirin has drawbacks as well as advantages.
Aspirin relieves inflammation due to its ability to inhibit an enzyme in the body called COX-2. Unfortunately, aspirin also inhibits the COX-1 enzyme. This inhibition can lead to stomach irritation and bleeding problems. Aspirin increases bleeding by decreasing the formation of blood clots. The reduction of blood clots may actually be helpful in people with cardiovascular disease. Aspirin may also be helpful in reducing the risk of some types of cancer, although this benefit is still being investigated.
Salicin in Willow Bark: The Forerunner of Aspirin
Aspirin is chemically related to salicin, a chemical found in the inner bark of willow trees and also in some other plants. Willow bark has been used to treat pain and fever since ancient times. Salicin is turned into salicylic acid in our digestive tracts.
In the 1800s, scientists isolated salicin from willow trees. They converted it to salicylic acid, which was used as a medicine. However, the acid often caused severe stomach pain. German chemist Felix Hoffman, who worked for the Bayer company, is credited with the creation of aspirin in 1897. He converted salicylic acid into acetylsalicylic acid, also known as ASA or aspirin. Aspirin was found to cause less stomach pain than salicylic acid while still relieving other body pains and fever.
Types of White Blood Cells (Colorized)
Inflammation is a normal body response to injury. When tissue is damaged by an infection, chemicals, physical trauma, heat, or radiation, inflammation begins. Extra blood flows to the injured area, causing fluid to leak out of the blood vessels, resulting in heat, redness, swelling, and pain. The blood and fluids contain white blood cells and proteins that destroy infectious organisms, such as bacteria and viruses. Inflammation helps to seal off the injured area from the rest of the body. In addition, damaged cells are destroyed and the repair of injured tissues begins.
Inflammation is uncomfortable but is normally a temporary process. This short-lived inflammatory response is known as acute inflammation. Acute inflammation subsides as pathogens are killed and body tissue is repaired. However, acute inflammation in certain parts of the body, such as in the brain, is very dangerous. Inflammation that lasts a long time (chronic inflammation) can also be serious and may lead to a variety of health problems.
The Heart and Blood Vessels
How Aspirin Reduces Inflammation
There are several versions of the COX (cyclooxygenase) enzyme. The best known forms of the enzyme are COX-1 and COX-2. COX-1 is found in most of our cells. COX-2 is much less common but is found in increased amounts in inflamed areas.
The COX enzymes stimulate the body to make chemicals called prostaglandins. Different prostaglandins produce different effects. Some maintain normal body function, but others cause inflammation, pain, and fever. COX-2 stimulates the production of inflammatory prostaglandins. Aspirin inhibits the manufacture of COX-2, thereby decreasing inflammation.
Side Effects of Aspirin Use
Aspirin inhibits the COX-1 enzyme as well as the COX-2 enzyme. COX-1 stimulates the production of prostaglandins that maintain the mucus layer inside the stomach. The mucus protects the stomach lining from being attacked by the hydrochloric acid and digestive enzymes that are present in the cavity of the stomach. Without enough mucus in the stomach, a person taking aspirin may develop an inflamed stomach lining (gastritis) and ulcers (sores) on the lining.
Another function of COX-1 is to stimulate blood platelets to make thromboxane A2. This chemical triggers platelets to stick together around a wound, starting the clotting process. Since aspirin inhibits the production of COX-1, it also inhibits blood clotting. Wounds on the stomach lining and elsewhere may bleed more freely during treatment with aspirin.
Aspirin may have other effects in the body. It can cause kidney problems, since COX-1 is needed for normal kidney function. In addition, up to twenty percent of adults with asthma experience an asthma attack when they take aspirin. Aspirin can also cause tinnitus (ringing or other sounds in the ears in the absence of external sounds) or make existing tinnitus worse. In children with a viral disease, aspirin use may cause Reye’s syndrome, a very dangerous condition in which the brain and liver swell.
Aspirin and Cardiovascular Problems
Aspirin’s ability to reduce blood clotting can be a harmful side effect of the medication. It may be a helpful feature in some people, however. These include people at risk for developing blood clots in the heart, resulting in a heart attack, or blood clots in the carotid arteries traveling up the neck to the brain, which could lead to a stroke. Some doctors recommend that patients who have an increased likelihood of developing these disorders take a low dose of aspirin every day.
Some people with peripheral artery disease, or PAD, take aspirin to help their disorder. PAD usually affects arteries travelling to the legs. It's a condition in which an artery is narrowed by fatty deposits on the arterial lining. The narrowed passageway for blood flow increases the chance of blood clot formation.
If you are at risk for developing a cardiovascular problem, talk to your doctor about the advisability of taking aspirin and about a suitable dose. Don't take the medication without your doctor's advice.
Aspirin and Cancer Risk
There is another possible benefit of aspirin which may be related to its ability to decrease inflammation. Aspirin may reduce the risk of some types of cancer, especially colorectal cancer. The picture is far from clear, however. In addition, as the video below points out, we shouldn’t expect aspirin to protect us from getting cancer if we perform activities known to promote the disease, such as smoking.
In March 2015, the Fred Hutchinson Cancer Research Center published their analysis of ten large population studies. They concluded that regular aspirin intake is protective against colorectal cancer in most people. However, 9% of the people in their study who had a particular genetic makeup received no benefit from taking aspirin with respect to cancer risk. In 4% of the people with another type of genetic makeup, aspirin actually increased the risk of colorectal cancer. The center concludes that more research is needed and that they can't yet make a blanket recommendation that we all take aspirin to prevent cancer.
It will be interesting to see if researchers discover how aspirin works to protect people from cancer (if in fact it does) and whether this protection results from its ability to reduce inflammation, as has been speculated. There is evidence linking chronic inflammation to cancer development. It will also be interesting to discover why aspirin's action seems to depend on genetics.
Aspirin May Help to Prevent Cancer
NSAIDs (Nonsteroidal Anti-Inflammatory Drugs) are a group of chemicals that include aspirin and ibuprofen. Like aspirin, ibuprofen inhibits both COX-1 and COX-2. Acetaminophen (paracetamol) is not an NSAID. It's used to treat pain and fever, but unlike aspirin and ibuprofen, it only weakly inhibits the COX-2 enzyme and is not anti-inflammatory. Acetaminophen is believed to exert its effects by acting on the central nervous system.
New drugs have been created that inhibit COX-2 but not COX-1. These drugs don’t create stomach problems since they don’t inhibit the COX-1 enzyme. Unfortunately, some of them have been found to cause serious health problems, including an increased risk of heart attack, stroke, and liver damage, and have been withdrawn from the market.
A Dietitian Discusses the Anti-Inflammatory Diet
An Anti-Inflammatory Diet and Inflammation
Over the long-term, an anti-inflammatory diet may help to decrease chronic inflammation and reduce the need for certain medications. In an anti-inflammatory diet, foods that are believed to reduce inflammation are emphasized while those that are thought to increase inflammation are avoided, or at least limited. In general, vegetables, fruits, legumes (pulses), whole grains, fish, nuts, and seeds are considered to anti-inflammatory, provided they are eaten in an unprocessed form. On the other hand, refined grains, sugar, saturated fats, hydrogenated fats, and alcohol are thought to increase inflammation.
Chronic inflammation contributes to many health problems. Some of these problems include rheumatoid arthritis, asthma, and inflammatory bowel disease. If you have a disorder that involves inflammation, it’s certainly worth following an anti-inflammatory diet. This diet is healthy for everyone, whether or not a person is experiencing inflammation. Following the diet may enable you to reduce or even eliminate certain medications and their side effects. Don't stop taking a medication without a doctor's advice, though!
Specific Foods That May Reduce Inflammation
Fats containing omega-3 fatty acids have been shown to reduce inflammation. Oily fish such as wild salmon and sardines are good sources of omega-3 fatty acids known as EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid). Foods such as walnuts and flax seeds contain a different form of omega-3 fatty acid. Our bodies can convert this form into EPA and DHA, although in limited amounts.
Extra virgin olive oil contains oleocanthal, which produces a stinging sensation in the throat just like ibuprofen does. It also lowers the levels of COX-1 and COX-2 like ibuprofen, reducing inflammation. The amount of olive oil that is normally ingested each day is equivalent to a weak dose of ibuprofen, but it’s believed that over time the regular consumption of extra virgin olive oil can decrease inflammation. Other substances that have been shown to reduce inflammation are green vegetables, berries, herbs, and certain spices, especially ginger and turmeric.
DO NOT start taking daily aspirin for any reason without consulting your doctor. Some people experience unpleasant and potentially dangerous side effects from aspirin use. People with certain medical conditions shouldn't take the medication. In addition, there are drugs that shouldn't be combined with aspirin. The dose that's taken is also an important point to consider.
It's very interesting that such an old medication as aspirin still has important uses, despite the creation of newer drugs. It's not ideal for everyone, but for some people it's a very helpful medicine.
Harvard Health Publications has information about aspirin.
WebMD has information about the anti-inflammatory diet.
The National Cancer Institute has created a webpage about the link between aspirin and cancer risk.
The institute also has a page about the link between chronic inflammation and cancer.
The Fred Hutchinson Cancer Research Center website has a report on the links between aspirin, genetics, and cancer risk.
Questions & Answers
© 2011 Linda Crampton