Do hyaluronic acid injections help knee pain? Don't waste your money.

As spring turns into summer, we spend more time outdoors, exercising, gardening, or just walking around. And for many people, more exercise means knee pain. Count me among the afflicted.

Several people, including my orthopedic specialist, have suggested that I try injections of hyaluronic acid to treat my knee pain. Many people swear by it, and even though I looked into this two years ago (and rejected it as ineffective), I thought I would look again. Perhaps the evidence had changed.

It hadn't.

Superficially, these injections sound reasonable. Hyaluronic acid is already inside your knee and helps to lubricate and cushion the joint. Adding more lubricant seems like a good idea; after all, it works for cars, bicycles, door hinges, or any other creaky joint.

But not for knees. Just recently, Anne Rutjes, Peter Jüni and their colleagues published a very large review of the evidence on knee injections. They looked at 89 trials involving over 12,000 adults and found that in the trials that were properly controlled (blinded), hyaluronic acid injections had either no effect or a “clinically irrelevant effect”; that is, too small a difference to matter to the patient. (They also found five unpublished trials that showed no effect at all; this is a good example of the so-called “file drawer effect”, where studies that don’t have the desired outcome are stashed away in a drawer and never published.)

Rutjes and colleagues also pointed out that there’s a real risk of harm when you inject something deep into the knee joint. To quote their summary for patients (published along with the article),

“Viscosupplementation [injection of hyaluronic acid] may provide little if no pain relief or function improvement in patients with knee osteoarthritis. It also seems to increase the risk for adverse events."

If you don’t believe Rutjes, perhaps you’ll believe the American Academy of Orthopaedic Surgeons (AAOS), who reviewed a large body of evidence and wrote: 

“We cannot recommend using hyaluronic acid for patients with symptomatic osteoarthritis of the knee. Strength of recommendation: Strong.”

After looking at numerous studies, the AAOS concluded that there was no clinically meaningful benefit from these injections. This document is their official recommendation for physicians.

I was disturbed, though, to find that the AAOS information for patients directly contradicts their own recommendations to clinicians, and suggests that knee injections might work. On their patient-oriented web page, they offer the wishy-washy comment that “hyaluronic acid does seem to have anti-inflammatory and pain-relieving properties … [that] may last for several months,” though “not all patients will have relief of pain.”

What the heck? Are they orthopedists trying to hide the truth from their patients? Why would they do that?

I checked to see if the AAOS patient information was merely out of date, but no, it was reviewed in 2014, and the clinical recommendations appeared in 2013. I have to assume that the authors of the patient information page are not the same doctors who established the official recommendations for clinicians–but it seems unlikely that they are ignorant of their own organizations official guidelines. So why don’t they warn patients that hyaluronic acid injections don’t work? Is it because hyaluronic acid treatments are a significant money-maker for some orthopedists? 

I can hear the response from some doctors already: "In my experience," they say, "this works for some patients." Sorry, but one doctor's experience (or "clinical judgment", as some call it) doesn't trump science. That's why we do experiments, to determine whether or not our subjective impression is correct. In this case, the science is clear.

Incidentally, the Mayo Clinic also fails on this topic. Their site states that hyaluronic acid 

“can be injected into your knee to improve mobility and ease pain. Relief may last as long as six months to a year.” 

They cite no evidence to back this up. Patients looking at either the Mayo site or the AAOS site will be misled into thinking that these injections might be worth a try.

WebMD does a much better job, writing that 

“one study published in Rheumatology found that hyaluronan was no better at reducing joint pain than a placebo injection of salt water. An analysis of seven different studies published in the Journal of Family Practice did not recommend the treatment, since the benefits–if it had any at all–were so slight.”

Note that unlike the Mayo Clinic page,  the WebMD page mentions specific studies and names the journals.

So what does work for knee pain? Physical therapy and exercise to strengthen the muscles around the knee is still the best course, according to the AAOS's clinical guide. Weight loss also helps, by reducing the load on the knee. The only medical intervention that helps is an NSAID pain reliever such as ibuprofen. (See my 2013 article for other treatments that don’t work, including acupuncture (not even close) and glucosamine-condroitin supplements).

As for me, I bought a knee brace even though the AAOS says it doesn’t help. But it feels like it’s helping, and it was cheap. And my knee is definitely feeling better. Why not take advantage of a placebo effect once in a while?

A true fountain-of-youth drug combo?

This is really, really interesting. Can we alleviate the effects of aging by getting rid of "bad" cells in the body?

A new study from the Mayo Clinic and the Scripps Research Institute reports that a novel cocktail of two unrelated drugs 

“dramatically slows the aging process—alleviating symptoms of frailty, improving cardiac function and extending a healthy lifespan.” 

The scientists who conducted the study, led by James Kirkland, Laura Niedernhofer, and Paul Robbins, screened 46 different compounds to find ones that would interfere with the ability of senescent cells to survive. The two that seemed to work best were quercetin and dasatinib. They call these drugs "senolytic" for their ability to kill senescent cells.

Old cells are supposed to die and let the body replace them. Most of them do, but some cells become senescent: old geezers who just won’t go away. The problem is, these cells just don’t sit quietly in the living room reading a book. Instead, they make lots of noise, throwing things around that can mess up the living room and make all the other cells miserable. At a molecular level, they secrete enzymes that cause inflammation and other problems, which may explain the relationship between these cells and age-related chronic diseases such as heart disease and osteoporosis. 

This current line of research started about four years ago, when the Mayo Clinic's Jan van Deursen published a study (in mice) showing that if you could selectively destroy senescent cells, the mice had fewer age-related diseases and lived up to 25% longer. Senescent cells, it seems, are definitely a problem.

The challenge is that very few cells are senescent, even in very old people, and it's difficult to destroy these cells without harming all the healthy cells around them. In the new study, Kirkland and his team screened 46 different compounds to find ones that could interfere with what they called “pro-survival” genes in senescent cells. The theory is that the senescent cells have a special ability to survive, and if we can interfere with that ability, the cells will die.

The two compounds they found are very different. Quercetin is a common plant extract, found in a wide variety of fruits and vegetables, especially capers, red onions, plums, and cranberries. Dasatinib, in contrast, is a highly specialized cancer drug made by Bristol-Myers Squibb (NYSE:BMY) and sold under the name Sprycel®. Dasatinib is used to treat CML, a form of leukemia. Quercetin is cheap and easily available, while dasatinib is very expensive and cannot be obtained without a prescription.

The study results were very impressive: after a single dose, mice had improved heart function that lasted up to 7 months. Periodic doses worked too: mice showed improvements in a wide range of age-related symptoms, including bone loss, tremors, grip strength, and overall body condition.

Before everyone runs out and buys a giant bag of red onions (or a quercetin supplement), I should inject a dose of skepticism. Quercetin’s effect on lifespan has been studied before, and it came up short. A study in 2013 by Stephen Spindler and colleagues looked at extracts of blueberry, pomegranate, green tea, black tea, quercetin, and other plants, feeding each of them to mice in a controlled experiment. None of the mice lived longer, and Spindler reported that 

“our results do not support the idea that isolated phytonutrient anti-oxidants and anti-inflammatories are potential longevity therapeutics.”

However, the method of delivery for quercetin and dasatinib in the new experiment was different, and the combination of the two might have benefits that quercetin alone does not offer. As Kirkland point out, dasatinib and quercetin “are both approved for use in humans and appear to be relatively safe,” although they then go on to point out a variety of possible side effects, some of them harmful. They end, though, on a remarkably optimistic note: 

“If senolytic agents can indeed be brought into clinical application, they could be transformative. With intermittent short treatments, it may eventually become feasible to delay, prevent, alleviate, or even reverse multiple chronic diseases and disabilities as a group, instead of one at a time.”

Of course, results in mice often fail when we try them out in humans–but not always. Let’s hope this drug combination shows the same effects in humans that Kirkland and colleagues observed in mice. None of us are getting any younger.

Those fish oil supplements might cause cancer

Eating fish is good for you, especially fish that contain omega-3 fatty acids.  So I was surprised last week to read a new study in the Journal of the National Cancer Institute that found that omega-3 fatty acids increase the risk of prostate cancer.  The risk for both high-grade and low-grade cancer was increased with higher levels of omega-3 fatty acids.  This is a carefully done study, and the results should make anyone who is taking fish oil pills reconsider.

One reason this study caught many people off guard is that there has been much evidence showing that a diet rich in fish that contain omega-3 oils is good for you.  The Mayo Clinic says that  "eating fish helps your heart", especially fish like salmon that contain omega-3 fatty acids.  The American Heart Association (AHA) elaborates:

"Omega-3 fatty acids benefit the heart of healthy people, and those at high risk of — or who have — cardiovascular disease. Research has shown that omega-3 fatty acids decrease risk of arrhythmias (abnormal heartbeats), which can lead to sudden death. Omega-3 fatty acids also decrease triglyceride levels, slow growth rate of atherosclerotic plaque, and lower blood pressure (slightly)."

This all sounds great.  Because of the evidence about the benefits of fatty fish, supplement manufacturers have been marketing and selling fish oil pills for years, with great success.  As I described back in 2010, GlaxoSmithKline even created a high-dose omega-3 fatty acid pill called Lovaza that has FDA approval.

But the evidence for that you can get the same benefit from supplemental omega-3 fatty acids — taking a pill, that is — is much weaker.  In fact, a large review published last year in the Journal of the American Medical Association found no connection at all between supplemental omega-3 and a lower risk of heart attacks, strokes, or death in general.  Other studies have reported similarly negative results.  So it appears that fish oil pills may not have any heart benefits.

And now, with this new study, we learn that supplemental fish oil might increase the risk of prostate cancer.

The bottom line: the AHA recommendations about eating fish are probably still good ones.  The AHA website says:

"We recommend eating fish (particularly fatty fish) at least two times (two servings) a week. Each serving is 3.5 oz. cooked, or about ¾ cup of flaked fish.  Enjoy fish baked or grilled, not fried." 

But popping a fish oil pill is not going to cut it. As we've seen before, supplements often fail to show the benefits that a healthy diet offers.  So save your money and stop buying those fish oil pills — and fire up the grill and throw on a few salmon fillets for this weekend's barbecue.