The Health Benefits of N-Acetylglucosamine

A dietary form of glucosamine that may increase joint lubrication

Glucosamine supplement

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N-acetylglucosamine (also known as N-acetyl glucosamine) is a simple sugar derived from the outer shell of crustaceans. Chemically similar to glucosamine (a natural substance found in cartilage), N-acetylglucosamine is thought to alleviate joint stiffness and pain, protect the lining of the stomach and intestines, and reduce dark spots on the skin caused by sun exposure and aging.

Available in capsule, tablet, powder, cream, and serum formulations. N-acetylglucosamine is one of three supplemental forms of glucosamine alongside glucosamine sulfate and glucosamine hydrochloride. Despite their similarities, the supplements are not considered interchangeable and have different mechanisms of action in the body.

Health Benefits

Glucosamine has long been embraced by consumers as an over-the-counter remedy for osteoarthritis (also known as "wear-and-tear arthritis"). It can be taken alone or used in tandem with chondroitin to restore joint cartilage and reduce joint pain.

Of the three forms of glucosamine on market shelves, N-acetylglucosamine is believed to stimulate the production of hyaluronic acid (a lubricating joint fluid) more effectively than the other two.

N-acetylglucosamine is also believed to benefit other organ systems, preventing or treating such diseases as stroke, inflammatory bowel disease (IBD), multiple sclerosis, and heart disease. In addition, N-acetylglucosamine is purported to have a lightening effect when applied to the skin.

Some of these health claims are better supported by research than others. Here is just some of what the current research says:

Osteoarthritis

Unlike many dietary supplements that lack clinical evaluation, glucosamine's effect on osteoarthritis has been studied extensively by researchers.

One of the largest research efforts, called the Glucosamine/Chondroitin Arthritis Intervention Trial (GAIT), involved nearly 1,600 patients with painful knee osteoarthritis. After 24 weeks of daily supplementation, glucosamine was reported to decreased knee pain in people with moderate to severe osteoarthritis by 65.7%—more or less the same level as a daily dose of Celebrex (celecoxib).

By contrast, glucosamine offered no benefit to people with mild knee osteoarthritis compared to a placebo.

With respect to N-acetylglucosamine specifically, the supplement has both its benefits and drawbacks. While N-acetylglucosamine stimulates the production of hyaluronic acid (a lubricating fluid in joints), is it poorly absorbed by cartilage cells when compared to glucosamine sulfate (meaning that it has less impact in rebuilding cartilage).

In order to achieve comparable permeability, inordinately high doses of N-acetylglucosamine would be needed. As such, N-acetylglucosamine may be more effective in improving joint function than preventing cartilage loss.

Inflammatory Bowel Disease

N-acetylglucosamine may help reduce the severity and recurrence inflammatory bowel disease (IBD), suggests a 2018 study published in the journal PNAS.

For this study, intestinal tissues taken from people with ulcerative colitis (a typically more serious form of IBD) were exposed to N-acetylglucosamine in the test tube. Doing so inhibited molecules on the surface of intestinal cells, called T-cell receptors, that instigate inflammation.

This suggests that N-acetylglucosamine may aid in the treatment of IBD by tempering the often-unrelenting inflammation that characterizes the disease. Further research is needed.

Multiple Sclerosis

A 2011 study in the Journal of Biological Chemistry suggested that N-acetylglucosamine can help suppress the excessive immune response associated with multiple sclerosis (MS). As an autoimmune disease, MS is characterized by the progressive destruction of the outer membrane of nerve cells (called the myelin sheath). It has been proposed that, by reducing the persistent autoimmune inflammation, many of the characteristic symptoms of MS can be delayed.

For this study, mice with chemically-induced MS were treated with oral N-acetylglucosamine supplement. Compared to untreated mice, those provided N-acetylglucosamine had fewer clinical signs of myelin destruction. The effect was attributed in part to the inhibition of T-cell receptors, also seen with IBD.

Skin Lightening

N-acetylglucosamine has long been touted for its skin-lightening properties by many cosmetic and skin care manufacturers.

According to a 2007 study in the Journal of Cosmetic Dermatology, adults with facial hyperpigmentation were treated with an ointment comprised of 2% N-acetylglucosamine and 4% nicotinamide on one side of the face and a placebo ointment on the other side. After eight weeks, the side treated with N-acetylglucosamine and nicotinamide was visibly lighter among all participants.

A 2010 study in the British Journal of Dermatology further reported that the same combination of N-acetylglucosamine and nicotinamide exerted a protective benefit against sun damage comparable to a 15 SPF sunscreen.

Despite the positive findings, it is unclear what effect N-acetylglucosamine had compared to nicotinamide. It is also unclear if the cream is able to reduce dark spots (such as solar keratosis) or simply provides a general lightening of the skin.

Possible Side Effects

Although little is known about the long-term safety of N-acetylglucosamine supplements, they are generally regarded as safe (GRAS) by the U.S. Food and Drug Administration (FDA). Side effects tend to be mild and may include:

  • Bloating
  • Constipation
  • Diarrhea
  • Flatulence
  • Heartburn
  • Indigestion
  • Nausea
  • Stomach upset

People allergic to shellfish may also experience an allergic reaction to N-acetylglucosamine, causing itching, sneezing, rash, diarrhea, or shortness of breath. People with a history of anaphylaxis to shellfish should avoid N-acetylglucosamine without exception.

N-acetylglucosamine may also aggravate symptoms of asthma in some people. With that said, the risk is considered low and is mainly evidenced by a solitary case report published in 2002.

As a simple sugar, N-acetylglucosamine may affect blood glucose levels but generally not enough to require intervention. However, you should stop taking N-acetylglucosamine at least two weeks before a scheduled surgery to reduce the risk of high blood sugar and blood clots.

The safety of N-acetylglucosamine during pregnancy is unknown. To be safe, avoid using N-acetylglucosamine while pregnant or breastfeeding.

Interactions

N-acetylglucosamine may slow blood clotting and enhances the effects of anticoagulants ("blood thinners") like Coumadin (warfarin) and Plavix (clopidogrel). Taking N-acetylglucosamine with either of these drugs can increase the risk of easy bleeding and bruising.

For this same reason, you should stop taking N-acetylglucosamine two weeks before scheduled surgery to prevent excessive bleeding.

Dosage and Preparation

Widely available for purchase online, N-acetylglucosamine supplements are also sold in many natural foods stores, drugstores, and shop specializing in dietary supplements.

Tablet and capsule formulations are the easiest to use because the dose is consistent. By contrast, N-acetylglucosamine powder (which can be mixed into coffee or tea as a sweetener) requires precise measurement with a proper measuring spoon.

There are no guidelines for the appropriate use of N-acetylglucosamine supplements. Dosages of up to 1,000 milligrams (mg) per day have been used safely in adults for 16 weeks. Similarly, a 2% N-acetylglucosamine ointment has been applied safely to the skin for up to 10 weeks.

Some manufacturers endorse dosages of up to 1,500 mg daily, taken in either a single or split dose. However, there is no clear evidence that higher doses confer to better results in all people. As a rule of thumb, start with the lowest possible dose and increase gradually as tolerated.

Most importantly, never switch from one form of glucosamine to another thinking that they are the same thing. Each has distinctive mechanisms of action and specific dosing instructions.

Always follow the prescribing information on the product label, and never exceed the recommended dose.

What to Look For

Unlike prescription drugs, dietary supplements are not strictly regulated in the United States. To ensure quality and safety, only buy brands that have been voluntarily submitted for testing by an independent certifying body like the U.S. Pharmacopeia (USP), ConsumerLab, or NSF International.

N-acetylglucosamine can be safely stored at room temperature. Avoid excessive heat or moisture exposure, and never use a supplement past its expiration date.

Common Questions

Which form of glucosamine is best?

Each form of glucosamine has its pros and cons. As mentioned, N-acetylglucosamine can increase the production of hyaluronic acid in the joint space but has low permeability in the cartilage itself. By contrast, glucosamine sulfate has high permeability but no tangible effect on hyaluronic acid levels.

Dose size is also a differentiating factor. For example, you need to take almost twice as much glucosamine chloride to achieve the same blood concentration as glucosamine hydrochloride. With that said, the concentration of glucosamine in cartilage and joint fluid is far greater than glucosamine hydrochloride and persist for hours longer.

When evaluating which form of glucosamine is "best," most health experts consider glucosamine sulfate superior because it contains sulfate, a mineral that the body needs to produce cartilage. The other two do not.

According to a 2016 review of studies in Seminars in Arthritis and Rheumatism, glucosamine sulfate demonstrated clear superiority over N-acetylglucosamine and glucosamine hydrochloride based on the reduced need for painkillers and nonsteroidal anti-inflammatory drugs (NSAIDs) as well as a reduced incidence of total knee replacement surgery.

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Article Sources

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  2. Sawitzke AD, Shi H, Finco MF, et al. Clinical efficacy and safety of glucosamine, chondroitin sulphate, their combination, celecoxib or placebo taken to treat osteoarthritis of the knee: 2-year results from GAIT. Annal Rheum Dis. 2010;69:1459-64 doi:10.1136/ard.2009.120469


  3. Kubomura D, Ueno T, Yamada M, et al. Effect of N-acetylglucosamine administration on cartilage metabolism and safety in healthy subjects without symptoms of arthritis: A case report. Exp Ther Med. 2017 Apr;13(4):1614-21. doi:10.3892/etm.2017.4140


  4. Meulyzer M, Vachon P, Beaudry P, et al. Comparison of pharmacokinetics of glucosamine and synovial fluid levels following administration of glucosamine sulphate or glucosamine hydrochloride 1. Osteoarthritis Cartilage. 2008 Sept;16(9):973-9. doi:10.1016/j.joca.2008.01.006


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