Free Radicals and Joint Pain

Oxidative stress is a term that is commonly used interchangably with free radical stress. They both describe a natural process in the human body in which a molecule is rendered unstable by one of many biochemical events. These unstable molecules (free radicals) go in search of a partner molecule, in order to "calm down." In science jargon, it's called quenching--not unlike quenching a fire.

It is a little like when someone in a group is itching for a fight, and a friend takes him by the arm and walks him out of harm's way. In this case, the free radical is the one itching for a fight and the friend is the antioxidant. If the free radical finds someone to fight with, a fight may break out and even spread to a larger group of people. We've all heard of fights on the football field, hockey rink, or bar that began with two people and exploded into a mob of fist-fighting ruffians. In a similar way, a single free radical can set up biochemical chain reactions that can spread far and wide. Osteoarthritis is a bit like a bar fight going on in our joints. A vivid metaphor, perhaps, but it does convey a point.

The human body uses free radicals to its advantage every minute of every day. The problem arises when free radical production becomes excessive or persists within certain tissues. In the joint environment, free radicals can lead to persistent, ongoing damage, especially if the antioxidant protection cannot keep pace.

We'll look at a couple of examples of free radical activity in painful joints, because controlling free radical activity in joints appears to be crucial to maintaining joint integrity. We'll then discuss the diet and lifestyle factors that help contain excessive free radical activity.

Free Radicals in Painful Joints

Doctors have been suspicious of free radicals as a contributor to joint damage for some time. In one study, doctors looked at 26 people with various forms of arthritis and 42 healthy people without arthritis. These doctors used needle biopsy to extract fluid from the knee joint, so they could determine whether the joint contained molecules called isoprostanes. Isoprostanes are footprints of damaged fatty acids that tell us two important things. First, they tell us that the cell membranes within the joint capsule are being damaged. Second, they tell us that there is free radical activity (which is one of the things triggering the damage). Those with osteoarthritis had much higher levels of isoprostanes in their joint fluid, as summarized below:

Type of Arthritis Amount of Isoprostane in Joint Fluid (pg/ml)

Osteoarthritis 494

Reactive Arthritis 192

Rheumatoid Arthritis 119

In this same study, doctors also looked at the amount of isoprostanes in the blood. People with osteoarthritis also had higher blood levels of this free radical damaged molecule.

Blood (Serum) Isoprostanes in Osteoarthritis (pg/ml)

Osteoarthritis 187

Control 33

[Basu, S, et al. Ann Rheum Dis 2001;60:627-31]

Joint tissue also contains an abundance of cells called synoviocytes. These are the cells that make up the joint capsule. They are not cartilage, but they help form the integrity of the structure that surrounds the entire joint. Damage here would lead to inflammation, swelling, and poor joint function. Damage here could also lead to increased pain signalling. This is important to understand, because it highlights the fact that joints can be painful due to reasons other than cartilage injury.

So, what did they find in the synovial cells? In one study of synovial cells, doctors looked for two other footprints of free radical-damaged fatty acids. These are called MDA (malondialdehyde) and HNE (hydroxynonenal). HNE is particularly troublesome. These doctors compared people who had osteoarthritis with people who had rheumatoid arthritis and no arthritis (called controls). They found that people with osteoarthritis had much higher levels of this damaged fatty acid (HNE) in their joint cells than the other two groups. This is strong evidence of free radical injury to these important cells.

Type of Arthritis Degree of HNE Elevation Concentration of HNE in Cells

Osteoarthritis ++++ 4.2 μM/L x 106 cells

Rheumatoid arthritis ++ 2.9 μM/L x 106 cells

No Arthritis ++ 2.9 μM/L x 106 cells

So, what does this mean. Quite simply, it suggests that in osteoarthritis, free radical activity can be fairly high. This results in damage to some of the cellular structures that make up the joint. It also suggests that things like antioxidants might hold promise in osteoarthritis. But before we discuss antioxidants, we must look at one other bit of evidence surrounding free radicals and joints. That is, how free radicals might affect the chromosomes within joint cells and speed up the joint aging process.

Is Arthritis a Sign of Accelerated Aging?

While there is agreement that arthritis is not caused by aging, there is now evidence that osteoarthritis might be a sign of accelerated biological aging. Doctors recently examined almost 1,100 people, mostly female twins, taking x-rays of the hands and samples of white blood cells. They wanted to see how osteoarthritis might be linked to a shortening of the tail end of their chromosomes (a part called telomeres). This shortening of telomomeres, found at the tips of our DNA, has long been linked to biological aging. Shortened telmomeres are linked, in part, to free radical damage, such as that due to smoking, alcohol, sunlight, and other factors.

These doctors found that the older the person was, the shorter the telomeres. In other words, telomere length was associated with chronological age. This is not uncommon and has been shown in other studies. However, among the 160 people with osteoarthritis of the hand, the telomere length was significantly shorter than those without arthritis. Telomere length was also associated with the severity of the hand arthritis.

These findings led doctors to suspect that the osteoarthritis was actually a sign of of accelerated biological aging. But what causes premature shortening of the telomeres on our DNA? There is now a lot of evidence that free radical stress can cause premature aging of our DNA.

[Osteoarthritis May be Sign of Faster Biological Aging. ScienceDaily, Oct. 2, 2006]

Assessment of paraoxonase activities in patients with knee osteoarthritis

Do Antioxidants Help?

Whenever we talk about free radicals, we naturally wonder whether antioxidants might be helpful. This is a lengthy subject, so we'll just look at a couple of examples. The first is with green tea, which contains powerful antioxidants called catechins.

Doctors interested in how antioxidants might protect joints put green tea to the test. They first took snipets of cartilage and put them into a test tube environment. Next, they added IL-1, a highly inflammatory immune protein that ravages joints. In some of the test tubes they also added varying amounts of green tea. After only 28 days, the IL-1 had almost completely disolved the uprotected cartilage. However, when components of green tea were added (such as EGCG), the cartilage was spared to a significant degree. A more recent study also showed that green tea catechins were protective against cartilage breakdown when the inflammatory immume protein IL-1 was present.

[Adcocks, C, et al. Catechins from gree tea (Camellia sinensis) inhibit bovine and human cartilage protoglycan and type II collagen degradation in vitro. 2002 J Nutr;132(3):341-6.]

[Ahmed, S, et al. Green Tea Polyphenol Epigallocatechin-3-gallate (EGCG) Differentially Inhibits Interleukin-1-Induced Expression of Matrix Metalloproteinase-1 and -13 in Human Chondrocytes. J Pharmacol Exp Ther 2004;308(2):767-773.]

Doctors at the University of Iowa subjected cartilage to repeated stresses in the laboratory. They found that the antioxidants vitamin E and N-acetylcysteine had a pronounced effect on protecting cartilage from wear and tear damage.

[Beecher, BR, Martin, JA, Pedersen, DR, et al. Antioxidants block cyclic loading induced chondrocyte death. Iowa Orthop J 2007;27:108.]