Synvisc Injections: Should You Avoid Them?

Synvisc – Treatment Potency Rating (TPR)

We have developed a bespoke treatment scoring system called Treatment Potency Rating (TPR) which allows you to preview how efficacious each treatment is, at a glance.

This is our Treatment Potency Rating (TPR) of Synvisc in a table format:

Synvisc Rating:	6.8 / 10.0
How it works? (Mechanism of Action, MoA):	Supplements the synovial joint fluid.
What proof is there? (Evidence For Efficacy):	Clinical trials and anecdotal reports.
Date to market? (Longitudinal Data):	Since 1997.
Risks? (Side Effect Profile):	Mild but potential allergic reactions.
Treatment Duration:	Depends on Synvisc or Synvisc-One.
Recovery Time:	Minimal. A day, or less than a week.
Cost-effectiveness:	More expensive than other brands.
Provider Expertise:	Moderate expertise is required.
Best Suited For:	Osteoarthritis (OA).

How Do Synvisc Injections Work?

Synvisc is just the brand name for a hyaluronic acid, injection-based, osteoarthritis (OA) medication.

It is administered into the joint capsule with the aim of replenishing the synovial fluid.

Synovial fluid is a viscous (thick), slippery fluid that naturally occurs in our joints. It acts as a lubricant and shock absorber, allowing for smooth movement while protecting the cartilage from wear and tear. And the main component of synovial fluid is hyaluronic acid (HA), which gives it these unique, cartilage-preserving properties.

The process of injecting hyaluronic acid into the joint is often referred to as viscosupplementation.

Hence the name Synvisc – (Syn)ovial fluid & (Visc)osupplmentation. In case you were wondering why such a name.

So in simple terms, how do Synvisc injections work?

Well, osteoarthritis is a multi-factorial condition with a rather complex aetiology (root cause).

But one of the main culprits is the diminished quantity and quality of synovial fluid. This leads to pain and decreased joint function.

Synvisc works primarily by supplementing the synovial fluid of the target joint with Hylan G-F 20. This can reduce friction within the joint, provide better cushioning during movement and restore joint function.

Hylan G-F 20 is a proprietary, cross-linked, high molecular-weight hyaluronic acid of avian origin. It is created by combining hylan A and hylan B.

These are hyaluronan chains extracted from chicken combs (the fleshy crest on top of chickens’ heads) in which the carboxylic and N-acetyl groups remain unaffected (1).

And what does that mean exactly?

Well, hyaluronic acid (HA) is an endogenously produced glycosaminoglycan. A type of long, unbranched polysaccharide.

Basically a naturally derived, complex sugar molecule.

And in its natural form, HA is composed of repeating disaccharide units of N-acetylglucosamine and glucuronic acid. The carboxylic groups on the glucuronic acid and the N-acetyl groups on the N-acetylglucosamine are key functional groups that contribute to HA’s joint-protecting properties.

So when we said above, that these two groups remain unaffected, we mean that during the extraction and processing of the Synvisc hyaluronic acid, these essential chemical structures are preserved.

This is what makes Synvisc rather unique when compared to other brands.

And why is this important?

Because these two groups are responsible for many of the HA’s beneficial properties. Specifically its ability to attract and retain water which, in turn, provides lubrication and shock-absorption within the joint.

These two functional groups can be found in Hylan A and Hylan B.

Hylan A is a fluid substance that imparts increased viscosity, enhancing the elastic properties of the synovial fluid. In contrast, hylan B is a more elastic, gel-like substance that provides additional cushioning support within the joint. The combination of these two forms in Synvisc and Synvisc-One effectively mimics the consistency and functionality of healthy synovial fluid, which is naturally found in joints (2).

Differences Between Synvisc & Synvisc-One

Synvisc injections come in two formulations, Synvisc and Synvisc-One.

Both are hyaluronic-acid-based treatments for osteoarthritis, but differ in terms of volume and treatment duration.

Synvisc:

• Requires 3 injections, typically administered once per week, for three weeks.
• Each injection contains 2 mL of Hylan G-F 20, totaling 6 mL over the course of treatment.

Synvisc-One:

• Requires 1 injection, administered all at once.
• A single 6 mL injection of Hylan G-F 20.

For both formulations, each mL of Hylan G-F 20 contains 16 mg of Hylan (8 mg each of Hylan A and Hylan B).

So both deliver a total of 96 mg of Hylan.

In simple terms:

Synvisc-One is basically 3 Synvisc injections combined into 1, for convenience purposes.

We found in a study by Chevalier et al. (3) that a single Synvisc-One injection demonstrated comparable efficacy to the traditional three-injection regimen of Synvisc. And both formulations aim to provide relief for up to six months. But it’s important to note that, just like any other medication, individual responses can vary.

Some patients report quicker pain relief with Synvisc-One, possibly due to the higher initial dose of hyaluronic acid. However, we found in a more recent study by Conrozier et al. (4) that the overall efficacy over time is comparable between the two formulations.

Synvisc-One does offer the advantage of requiring fewer office visits, making it slightly more convenient. A study by Stitik et al. (5) highlighted improved patient adherence with the single-injection regimen.

In medicine, this is often the case. Usually, the more convenient a treatment is, the higher the patient adherence rate, which indirectly increases its efficacy.

Also, while the total amount of Hylan G-F 20 is the same in both formulations, pricing structures may differ. We found that insurance coverage policies can vary between single and multiple injection regimens, potentially affecting out-of-pocket costs for patients. To learn more about the pricing of Synvisc, check out the pricing section of this article by (clicking here).

Finally, how do Synvisc and Synvisc-One differ in terms of side effect profiles?

Well, in theory, the single-injection approach of Synvisc-One might reduce the overall risk of injection-related adverse events. Simply due to having only one injection, instead of three consecutive. From a purely statistical standpoint, this reduces the probability of doctor error and infection.

However, we reviewed a meta-analysis by Rutjes et al. (6) which showed that the risk profile for both formulations is generally similar when considering the entire treatment course. To learn more about the side effects of Synvisc, check out the side effects section of this article by (clicking here).

So the choice between Synvisc and Synvisc-One should be made in consultation with your healthcare provider, taking into account the severity of osteoarthritis, lifestyle, and personal preferences.

Both Synvisc vs Synvisc-One have shown efficacy in managing osteoarthritis symptoms, with the main differences being the administration protocol and potential convenience factors.

Is Synvisc or Synvisc-One a steroid?

No, Synvisc or Synvisc-One aren’t corticosteroids or any steroid for that matter.

They contain Hylan G-F 20, a form of synthetic, cross-linked Hyaluronic Acid designed to supplement the natural hyaluronic acid of our joints.

The Problem With Cross-Linked HA

Many hyaluronic acid injection brands, such as Synvisc, contain cross-linked Hyaluronic Acid.

Even though cross-linked Hyaluronic Acid is more durable, and in theory, should provide prolonged joint lubrication, there are downsides that should be considered.

Cross-linked HA isn’t naturally found in the human body. The HA we have in our joints, skin, connective tissue and even the vitreous of the eye is typically linear without complex, network-like arrangements (7).

Therefore, at a molecular level, cross-linked HA isn’t representative of the structure or characteristics of natural HA.

And only certain soluble parts of cross-linked HA have been shown to interact with the CD44 receptors (8).

The CD44 receptor itself is like a docking station found on the surface of many cells in the body, including our joints.

It plays a crucial role in guiding cellular movements and tissue repair processes.

For this reason, cross-linked HA isn’t as bio-compatible as linear, non-cross-linked HA.

Remember:

The more bio-compatible a substance is (in our case HA), the better it works with the body’s joints and surrounding tissues without causing harm or unwanted reactions.

Nonetheless, it’s fair to mention why manufacturers choose to include cross-linked HA in their formulations.

As we said above, It’s more durable and lasts longer, because it degrades at a slower rate. Therefore, the patient doesn’t have to repeat the injections as often.

For this reason, you should carefully consider the type of hyaluronic acid prior to getting any injections. Make sure to discuss it with your health practitioner and mention these nuances in the clinical literature.

How Long Does Synvisc Take To Work?

Both Synvisc and Synvisc-One usually begin working within a few days to a week after the initial injection.

But since they differ in terms of dosage and injection regimen, as we outlined above, understanding their typical timelines can help you set realistic expectations.

For Synvisc (three injections): We observed in a study by Day et al. (9) that some patients reported improvement in pain and function as early as one week after the first injection. However, the full benefits typically become more apparent after completing the three-injection series, which takes about three weeks.

For Synvisc-One (single injection): In a controlled trial by Chevalier et al. (10) some patients experienced significant relief within the first week after the injection. Since you get a bolus dose of hyaluronic acid with Synvisc-One, this is probably why the onset of action is quicker for most people.

Either way, for both formulations, the maximum benefit is typically achieved around 8-12 weeks post-treatment (11), although this varies between individuals.

And in theory, if you’re tolerating Synvisc or Synvisc-One well, you can get injections every 6-12 months, in perpetuity. As long as your healthcare provider considers this a prudent course of action.

Just remember, like any medical treatment, the success rate is never 100%. There are statistical outliers.

The same applies to Synvisc and Synvisc-One. And you should keep that in consideration when evaluating your best treatment options.

There are other similar brands which offer hyaluronic acid injections. And some offer different versions of HA which may be more befitting for your particular condition.

To learn more about these different options, check our Alternatives section by (clicking here).

Synvisc Injections – Price

In the UK, Synvisc injection prices can range from £250 – £450+ per 6 mL of Hylan G-F 20.

• 6 mL Hylan G-F 20 = 3 Synvisc injections

• 6 mL Hylan G-F 20 = 1 Synvisc-One injection

Synvisc-One is simply 3 regular Synvisc injections, combined into one.

So the Synvisc (3 injections) cost should equal the Synvisc-One (1 injection) cost. Because they both offer the same total amount of Hylan G-F 20.

It mainly depends on the clinic and the injection specialist.

It’s always advisable to choose a clinic or a specialist who has a lot of experience in intra-articular injections, i.e. joint injections.

Preferably someone who does Ultrasound-guided Synvisc injections, which ensures accuracy in delivering the hyaluronic acid directly into the affected joint space.

And are Synvisc Injections available on the NHS?

Unfortunately, rarely.

As per the NHS commissioning decision:

“Hyaluronic Acid injections (Synvisc and others included) are considered a low priority for funding and will only be considered in exceptional circumstances. Funding approval must be sought from the local integrated care board (ICB) via the Individual Funding Request process prior to treatment.” (NHS Decision)

This specific statement is taken from an NHS Gloucestershire document but is effectively the same for the entirety of the UK.

If you fall within these “exceptional circumstances” and manage to get Synvisc via the NHS, great.

But if you wish not to waste time, it’s best to seek private treatment.

Synvisc Injections – Patient Reviews

What do people who’ve had Synvisc say?

Let’s break down the patient data into two groups – empirical (scientific) and anecdotal (word of mouth).

Empirical:

We reviewed multiple empirical studies on Synvisc regarding its efficacy and patient outcomes.

In study (12) 199 patients with osteoarthritic knee pain were injected with Synvisc (Hylan G-F 20) and 193 with pure Sodium Hyaluronate.

At 6 months, both groups had a reduction in knee pain, but the Synvisc results were statistically superior (2.5 mm, p = 0.02).

In study (13) Synvisc was compared with a lower molecular weight hyaluronic acid. At the final evaluation, yet again, the Synvisc patient group had better outcomes.

However, in both of these studies, patients were allowed to use other medications such as acetaminophen (Paracetamol). And neither study had a placebo control group, which limits our ability to definitively attribute the observed improvements solely to Synvisc. For this reason, you should take these results with a grain of salt.

A long-term study (14) found that repeated courses of Synvisc injections over several years maintained its effectiveness, suggesting potential long-term clinical merit.

While a meta-analysis by Bellamy et al. (15) examined multiple Synvisc research papers, and while most showed pain reduction and joint function improvement, the magnitude of these effects varied. Also, most studies had noteworthy limitations, as we pointed out above.

So the heterogeneity (discrepancy) in patient results could be due to differences in study design, patient populations, and concomitant treatments.

Anecdotal:

As for anecdotal (word of mouth) patient reviews, there are quite a few online.

According to (Patient Reviews) sorted by ‘most helpful’, you can see for yourself that the opinions are mixed.

This seems to be the case for every hyaluronic acid injection brand that we’ve reviewed on our website.

Some patients have had tremendous pain relief from Synvisc injections, while others haven’t had much improvement.

Individual responses can vary significantly due to differences in joint morphology, genetic predispositions, the stage and severity of osteoarthritis, as well as overlapping effects of previous treatments.

So our consensus is that Synvisc injections are beneficial or net-neutral for most people.

The success rate is similar to the other top hyaluronic acid injection treatments. However, unlike the other brands we’ve reviewed, Synvisc has a slightly higher probability of side effects due to its avian origin. Specifically for people sensitive to avian (bird) products or with such allergies.

Also, just like any other HA injection, Synvisc should be administered by an experienced injection specialist with ultrasound guidance.

Otherwise, complications may occur or Synvisc might not work as intended.

For these reasons, you must ensure to only work with qualified professionals who have sufficient experience with intra-articular (joint) injections.

What to Expect During The Procedure?

The Synvisc injection procedure is quite straightforward and minimally invasive.

In most cases, the doctor or injection specialist will first apply a local anaesthetic to completely numb the area.

Then they will use ultrasound to accurately guide and inject Synvisc into the affected joint.

This ensures the hyaluronic acid goes exactly where it’s needed most.

Most patients typically experience minimal or no discomfort at all, during the procedure.

After the injection, some may notice immediate relief, while for others, the reduction in pain and improvement in joint function may develop over the following weeks.

In general, resting is recommended for at least 24-48 hours after the injection. And it’s best to avoid strenuous exercise or heavy lifting for about a week.

But these are just general guidelines for all hyaluronic acid treatments. You should always follow your healthcare provider’s personalised instructions for post-injection care.

What Are The Side Effects of Synvisc?

Synvisc created by Sanofi Genzyme, was first approved in August 1997 for the treatment of knee osteoarthritis.

It’s one of the very first hyaluronic acid injection brands to market.

And since 1997, it it has accumulated a lot of empirical and anecdotal data.

Thousands of people have had Synvisc injected in joints commonly affected by osteoarthritis.

And most haven’t had any serious adverse side effects.

However, like any other medical procedure, there are potential side effects and risks.

We’ll list the side effects below. And in the next section, we’ll discuss how to minimise or eliminate them entirely.

These side effects can happen with any hyaluronic acid injection, not just Synvisc. That’s because all HA injections have the same mechanism of action and similar excipients. Therefore similar side effect profiles can be expected. Most of these adverse reactions depend primarily on the skillfulness and care of the injection specialist or doctor.

But there is one subtle difference which makes Synvisc slightly more prone to creating adverse reactions, and that will be explained below.

Common MILD side effects (10-20% of patients):

• Pain at the injection site: Some patients may experience temporary discomfort or mild pain where the injection was administered. This shouldn’t last more than 1 week.
• Swelling and redness: Minor swelling or erythema (redness) around the injection area can occur. This typically resolves on its own within a week.
• Joint and muscle stiffness: A temporary increase in stiffness at the target joint, or the muscles around it. You might notice this immediately after the procedure but it should subside within 1-2 weeks.

Rare SEVERE side effects (≤1% of patients):

• Allergic reaction: In very rare cases, patients may have an allergic reaction to the components of the HA injection. This can involve symptoms such as swelling, redness, and itching at the injection site.
• Pseudosepsis: Which combines “Pseudo” + “sepsis” = it mimics the symptoms of sepsis. Such as fever, increased heart rate, and increased white blood cell count, but does not involve a bacterial infection or actual sepsis.

Both allergic reactions and pseudosepsis are very uncommon.

Hyaluronic acid is naturally found in our joints, skin, eyes and connective tissue. It has high bio-compatibility. Therefore, when injected into the problem area, the body easily recognises and accepts it.

Extremely Rare SEVERE side effects (≤0.1% of patients):

• Infection: Like with any other injection, a needle must penetrate the skin to deliver the active ingredients. And this always carries a tiny risk of an infection. If you notice severe swelling, pain, intense warmth arising from the joint and/or fever, contact your doctor immediately.

Infections are extremely uncommon. They are more dependent on the doctor’s clinical expertise and sanitary practices than anything else.

Therefore Synvisc is considered generally very safe.

Also, it’s important to note, that just like many other HA injection brands, Synvisc shouldn’t be used in pregnant and lactating women as it’s not been evaluated in these cases.

Synvisc-specific side effects:

As we explained above, Synvisc is derived from avian sources, specifically chicken combs (the fleshy crest on top of chickens’ heads).

For some patients, this may potentially cause more side effects than non-avian-derived hyaluronic acid injections. Primarily due to the risk of allergic reactions to avian proteins.

We found in a study by Reichenbach et al. (16) that patients receiving avian-derived hyaluronic acid injections, such as Synvisc, had a higher incidence of local adverse events compared to those receiving non-avian injections.

The hypothesis is that for some patients, these residual avian proteins in Synvisc might trigger an immune response, which can lead to inflammation or hypersensitivity reactions.

Also, as mentioned above, Synvisc contains Hylan G-F 20 which is cross-linked. While cross-linking hyaluronic acid is beneficial for its longevity in the joint, it may also contribute to a higher risk of adverse reactions.

Study (17) discovered that, for some patients, the larger molecular size and increased residence time of cross-linked hyaluronic acid products could potentially lead to more pronounced local reactions.

It’s important to note, however, that while these risks exist, many patients tolerate Synvisc well.

So you have to speak with your healthcare provider and carefully consider whether to use Synvisc or a non-avian alternative, taking into account your individual preferences and medical history.

How to Prevent Side Effects?

To prevent or minimise the risk of side effects from Synvisc or any other hyaluronic acid injection, consider the following:

• Ultrasound Guidance: Ensure your doctor is using ultrasound to guide the injection. As this study demonstrated (18) patients receiving ultrasound-guided knee hyaluronic acid injections were significantly less likely to undergo subsequent knee complications than patients receiving landmark-guided (physical touch, no imaging) hyaluronic acid injections.
• Combined Therapy: Theoretically, combining Hyaluronic Acid with a Corticosteroid (such as Cortisone) may reduce the risk of an acute inflammatory reaction or pseudosepsis. Corticosteroids block pro-inflammatory mediators, suppress the production of cytokines, and prevent factor NF-κB from activating, all of which decrease inflammatory gene expression (19). Therefore, in theory, corticosteroids can reduce the risk of acute inflammation or pseudosepsis. And even augment the positive effects of HA. However, corticosteroids themselves can have side effects. This includes potentially impacting blood sugar levels and the tissues around the injection site. So you and your doctor should carefully consider the pros and cons of combined HA + Corticosteroid therapy.
• Treatment Quality: Ensure the Hyaluronic Acid brand your doctor uses is of high quality and sourced from reputable manufacturers. Be aware of the product’s composition, as certain additives or preservatives (excipients) might increase the risk of an adverse reaction. And in the case of Synvisc, be mindful of its avian origin.

The full ingredients list of Synvisc and Synvisc-One is:

• Hylan G-F 20 (a mixture of Hylan A and Hylan B derived from chicken combs)
• Sodium Chloride
• Potassium Chloride
• Disodium Hydrogen Phosphate
• Sodium Dihydrogen Phosphate Monohydrate
• Water for injection

The Hylan G-F 20 is the active ingredient, it replenishes the joint’s synovial fluid.

Whereas the remaining excipients collectively adjust the osmolarity, maintain the pH balance, protect against degradation, and keep the injection sterile.

Even though they are generally considered safe, individual sensitivities or allergies can exist. This caution is especially relevant for patients with a history of allergies to pharmaceutical excipients.

Always ask the clinic or doctor who’ll be administering any type of HA injection about the inactive ingredients. What are they? Do they pose a risk of an allergic reaction or other adverse complications?

Are There Better Alternatives to Synvisc?

In terms of other brands which offer Hyaluronic Acid injections, there are quite a few.

And we have reviewed the top ones:

• Ostenil
• Durolane
• Cingal
• Monovisc

You can view each one to learn more.

Some of these other brands might be more befitting to your needs.

So it’s difficult to say whether they are “better” than Synvisc because that depends on multiple factors.

Not to mention, there are numerous other regenerative treatments which have been proven to be efficacious in the treatment of osteoarthritis and other musculoskeletal problems, such as PRP, enriched PRP, nStride, Stem Cells, Arthrosamid, Goldic, Corticosteroids and more.

We have reviewed all of them meticulously. To learn more check out our Research page.

And if you’re feeling overwhelmed with all the possible treatment options, don’t be.

We can help you pick the best one for your particular condition and circumstances.

Scroll to the bottom of this article, to get bespoke guidance.

The Verdict – Is Synvisc an Effective Treatment?

Synvisc injections are similar to the other Hyaluronic Acid injection brands we’ve discussed on our website in depth.

In terms of composition, Synvisc is available in two formulations: a three-injection series (Synvisc) or a single injection (Synvisc-One), containing high-molecular-weight, cross-linked, avian-derived Hyaluronic Acid (Hylan G-F 20).

In terms of pharmacodynamics (its effect), Synvisc supplements the joint’s synovial fluid. It lubricates and provides ‘cushioning’, thereby reducing pain and stiffness and enhancing mobility.

Based on the empirical evidence and patient data shown in this article, Synvisc injections have demonstrated sufficient clinical efficacy.

However, some studies we reviewed found Synvisc to have a higher incidence of local adverse events compared to non-avian-derived products.

Also, the Hyaluronic Acid in Synvisc is cross-linked and avian-derived, which has lower bio-compatibility and potential for allergic reactions.

So the effectiveness of Synvisc can vary among individuals and like any medical treatment, the outcomes can depend on several factors including:

• The severity of osteoarthritis.
• The specific joint(s) affected.
• The doctor’s level of injection proficiency and overall care.
• Is the doctor using ultrasound or landmark guidance? Preferably ultrasound.

Overall, Synvisc is a good choice. But if you are allergic to avian products, then it’s best to look for an alternative. We’ve reviewed all major hyaluronic acid injection brands, just check the alternatives section of this article by (clicking here).