If you’ve been told you have osteoarthritis in your knee and your doctor mentioned hyaluronic acid injections, you’re not alone. More than 32 million adults in the U.S. live with this condition, and about 1 in 7 of them get these shots every year. But here’s the thing: while millions are getting them and Medicare spends over $300 million annually on them, many experts still aren’t sure if they actually work better than a placebo.

What Are Hyaluronic Acid Injections?

Hyaluronic acid (HA) is a natural substance found in your joints. It’s part of the synovial fluid-the slippery liquid that cushions and lubricates your knees. In a healthy joint, this fluid is thick and springy, like gelatin. But with osteoarthritis, that fluid breaks down. The hyaluronic acid concentration drops by 30-50%, and the fluid becomes thin and watery. That’s when your knee starts to grind, ache, and swell.

Viscosupplementation is the medical term for injecting extra hyaluronic acid into the joint to restore that cushioning. It’s not a cure. It doesn’t rebuild cartilage. But the idea is simple: if your joint’s natural lubricant is running low, why not add some back in?

The first FDA-approved product, Hyalgan, came from rooster combs-which is why some people still call these shots “rooster comb injections.” Today, most HA is made in labs using bacterial fermentation, not animal parts. Still, the name sticks.

Who Gets These Injections?

These aren’t for everyone. You’re a good candidate if:

• You have mild to moderate knee osteoarthritis (Kellgren-Lawrence grades 1-3)
• Over-the-counter painkillers like ibuprofen or acetaminophen haven’t helped enough
• You’ve tried weight loss, physical therapy, or walking regularly and still have pain
• You’re not a good candidate for surgery yet

If you have “bone-on-bone” arthritis (grade 4), studies show these injections won’t help. Henry Ford Health and the Arthritis Foundation both say the same thing: if your X-ray shows no space left between your bones, don’t expect relief from HA shots.

How Many Shots Do You Need?

There’s no single answer. Different products work differently:

• Single-injection options: Gel-One, Monovisc. One shot, done.
• Three-injection series: Euflexxa, Synvisc, Orthovisc. One shot per week for three weeks.
• Five-injection series: Some older protocols, less common now.

The Arthritis Foundation says three doses are more effective than one or two. But here’s the twist: some studies say single shots work just as well. A 2022 review by Vincent et al. found no big difference in pain relief between one shot and three.

The bottom line? If your doctor recommends three shots, it’s probably because they’re using a product designed for that schedule. Stick with it. Don’t skip one because you’re feeling better after the first.

How Long Does It Last?

If it works, you’ll start noticing changes in 2-4 weeks. Peak relief usually hits around 6-8 weeks. For many, the effect lasts 6 months or longer. Some report relief for up to a year.

But here’s the catch: the benefits are modest. In a large NIH study, HA injections showed only a small improvement in pain compared to placebo. That’s about a 9% difference on pain scales-barely enough for most people to notice.

Compare that to corticosteroid shots. Those work faster-often within days-but the relief fades after 4-6 weeks. HA doesn’t kick in as quickly, but when it does, it lasts longer. That’s why some doctors recommend HA for patients who need longer-lasting relief and can’t handle frequent steroid injections.

What Are the Side Effects?

Most people tolerate these injections fine. But side effects happen:

• Temporary pain or swelling: 10-20% of people feel more discomfort right after the shot. It usually goes away in a day or two.
• Swelling: About 5-10% develop noticeable swelling. Ice and rest help.
• Allergic reactions: Extremely rare-less than 0.1% of cases. Most are linked to older, rooster-comb-derived products.

You shouldn’t get these shots if you have:

• An infection in or near your knee
• A known allergy to hyaluronic acid or bird proteins (if using avian-derived HA)
• A bleeding disorder or are on blood thinners (unless cleared by your doctor)

The procedure itself takes less than 10 minutes. Your doctor will clean the area, numb the skin (sometimes), and inject the gel using a thin needle. You can walk out right after.

Do They Actually Work?

This is where it gets messy.

On one side: dozens of studies show HA injections provide statistically better pain relief than saline (salt water) injections. A 2022 meta-analysis by Concoff et al. found that 2-4 shots delivered real, measurable improvement.

On the other side: a 2022 STAT News review of 50 years of research concluded these injections are “barely more effective than the placebo effect.” That’s not a small critique-it’s a major one. The NIH’s 2015 review said the same thing: “modest effect,” “doubtful effect at 6 months.”

Even the high molecular weight HA products-marketed as “better,” “longer-lasting,” or “more effective”-have failed to prove superiority in multiple trials. One study tested HA with 100,000 kDa molecular weight and found no benefit over placebo on pain and function scores.

So why do so many people still get them?

Because for some, they work. And when you’ve tried everything else and your knee still hurts, you’ll try almost anything. The Arthritis Foundation says “some patients experience meaningful relief,” even if the science is mixed.

HA vs. Other Treatments

Let’s put this in context:

Comparison of Osteoarthritis Treatments

Treatment	Onset of Relief	Duration	Side Effects
Hyaluronic Acid Injections	2-4 weeks	Up to 6-12 months	Mild swelling, temporary pain
Corticosteroid Injections	1-3 days	4-8 weeks	Joint damage with frequent use, blood sugar spikes
NSAIDs (e.g., ibuprofen)	30-60 minutes	4-6 hours	Stomach ulcers, kidney strain, high blood pressure
Physical Therapy + Exercise	4-8 weeks	Long-term, if maintained	None
Weight Loss (5-10% body weight)	3-6 months	Long-term	None

Physical therapy and weight loss aren’t flashy, but they’re the only treatments with strong evidence of slowing disease progression. HA injections? They just manage symptoms.

Who Might Benefit Most?

Not everyone responds. But research suggests certain people do better:

• Those with early-stage OA (grades 1-2)
• People under 65
• Patients with less joint deformity
• Those who respond well to placebo in clinical trials (yes, that’s a real thing)

There’s also emerging research into biomarkers-blood or joint fluid tests-that might predict who will respond. Right now, it’s not available outside of research labs. But in the future, we might be able to test your joint before the shot and know if it’s worth it.

What’s Next?

The field is evolving. New HA products are being developed with longer-lasting effects, better cross-linking, and even combinations with anti-inflammatory drugs. Some trials are testing HA with platelet-rich plasma (PRP) or stem cells, though those are still experimental.

Meanwhile, insurance companies and health systems are starting to push back. Medicare still covers it, but some private insurers now require proof you’ve tried physical therapy first.

What Should You Do?

If you’re considering HA injections:

• Ask your doctor to confirm your OA stage with an X-ray. No point getting shots if you’re grade 4.
• Make sure you’ve tried exercise and weight management. Even 5% weight loss can cut knee pain by 50%.
• Ask which product they’re using and why. Is it single or multi-dose? What’s the molecular weight?
• Set realistic expectations. You’re not getting a miracle. You’re looking for a few extra months of manageable pain.
• Track your pain before and after. Use a simple 0-10 scale. If you don’t feel better after 8 weeks, it probably didn’t work for you.

And if it doesn’t help? That’s okay. You’re not failing. You’re just learning what doesn’t work for your body. There are other options-knee braces, assistive devices, even surgery down the road. But for now, you’ve got more control than you think.