What do lobsters, fungi, and your connective tissue have in common? They all rely on N-acetylglucosamine for structure and elasticity. NAG supports the joints, gut, nerves, and skin, but it’s still in the investigational phase. Read on to learn everything about NAG and see if its potential benefits outweigh the risks.
What is N-Acetylglucosamine?
N-acetyl-D-glucosamine (NAG or GlcNAc) is an amino sugar derived from glucosamine. They both build chitin, the skeleton of shellfish (lobsters, shrimp, crabs) [1].
N-acetyl-glucosamine is a part of complex glycosaminoglycans, found in the cell walls of fungi and bacteria. They impregnate our skin, joints, gut lining, and connective tissue. A popular member of this family of compounds is hyaluronic acid [1].
Snapshot
Proponents:
- Repairs the joints
- Relieves gut inflammation
- May help with multiple sclerosis
- Rejuvenates the skin
Skeptics:
- Limited clinical evidence
- May worsen diabetes and glaucoma
- May interact with blood thinners
- Not suitable for people with shellfish allergies
N-Acetyl-Glucosamine vs. Glucosamine
Add acetic acid to glucosamine, and you get N-acetylglucosamine (NAG). Both glucosamine and NAG are commercially made by breaking down and modifying chitin [1].
Although both have similar structures and build the same long chains of molecules, NAG has some unique functions in the human body and potential health benefits we’ll discuss in this article.
According to one cell-based study, NAG is more efficient at building hyaluronic acid and thus potentially better for the skin, joints, and other elastic tissues. On the other hand, glucosamine is well researched and has a known safety profile [2].
Uses & Benefits of N-Acetylglucosamine
Preliminary research on NAG is promising, but the available clinical evidence is limited. The following studies should encourage further investigation before we make any definite conclusions and recommendations. Remember to speak with a doctor before taking NAG supplements. They can not replace medical treatment for any health condition.
How It Works
Glucosamine and N-acetylglucosamine (NAG) act as the building blocks of large elastic molecules that support connective tissues [3, 1].
As mentioned, they build glycosaminoglycans such as hyaluronic acid, giving strength and elasticity to our skin, joints, nerves, and gut surface [4, 5, 6].
NAG polymers (long chains) suppress inflammation in the body. In theory, this effect could help with autoimmune and inflammatory diseases [7, 8, 9].
N-acetylglucosamine may prevent the burst of free radicals from the immune cells and thus protect against oxidative stress [10].
Possibly Effective:
The benefits in this section stem from smaller clinical trials, animal, and cell-based studies. They are not researched well enough to recommend grape seed extract for any of the below conditions.
1) May Help With Joint Disorders
Glucosamine and N-acetylglucosamine (NAG) build complex elastic molecules in the cartilage that lubricate the joints and enable smooth movement. These nutrients may enhance cartilage recovery and repair the joints [3, 1].
Although the majority of research in this field has focused on glucosamine, NAG has also shown potential benefits for different joint disorders.
Osteoarthritis
In osteoarthritis, cartilage thinning in large joints causes pain and restricts movement. Painkillers can ease the symptoms, but they don’t impact disease progression [11].
A combination of N-acetylglucosamine and chondroitin reduced pain and enhanced knee function in 50 people with knee osteoarthritis (12+ weeks of treatment) [12].
In rabbits with knee osteoarthritis, joint injections of N-acetyl-glucosamine (NAG) [13, 14]:
- Stopped cartilage destruction
- Boosted collagen production
- Relieved joint inflammation
NAG showed better results than hyaluronic acid.
Joint Recovery
In a study on 68 volunteers, N-acetylglucosamine (500-1000 mg daily for 4 months) strengthened the cartilage by inhibiting collagen degradation [15].
Joint injections with NAG and hyaluronic acid improved tendon and bone healing in rabbits with knee injuries. NAG extracted from algae showed similar effects in rats when applied directly to their injured tendons [16, 17].
Rheumatoid Arthritis
Rheumatoid arthritis is an autoimmune disease in which joint inflammation causes pain and stiffness [18].
In mice with rheumatoid arthritis, both glucosamine and N-acetylglucosamine relieved inflammation and improved joint function [19].
Summary
Although N-acetylglucosamine may help recover the joints, we should wait for well-designed clinical trials to confirm these effects and establish optimal dosage.
Insufficient Evidence:
No valid clinical evidence supports the use of NAG for any of the conditions in this section. Below is a summary of up-to-date animal studies, cell-based research, or low-quality clinical trials, which should spark further investigation. However, you shouldn’t interpret them as supportive of any health benefit.
2) Inflammatory Bowel Disease
In a clinical trial with 34 IBD patients, N-acetylglucosamine (6 g daily for 4 weeks) improved symptoms such as pain, diarrhea, and bleeding in most cases (88%) [20].
N-acetylglucosamine showed promising effects in children with severe drug-resistant IBD.
In one study, 8 out of 12 children with IBD who received NAG orally (3-6 g a day) experienced notable improvement. Rectal application of NAG relieved the symptoms in 5 out of 9 children while all of them showed the signs of gut healing [21].
The above IBD clinical trials had small samples and lacked placebo controls. They indicate positive clinical experience with NAG but don’t allow for definite conclusions.
A study on gut tissue of IBD patients showed that NAG builds the layer of mucus in the bowels and combats inflammation. The gut of IBD patients failed to transform glucosamine into NAG and thus lacked this protective effect [22].
This may explain why NAG was able to silence the autoimmune response in the gut samples of IBD patients [23].
Animal studies voice these potential benefits. In mice with IBD, N-acetylglucosamine prevented disease progression and reduced gut inflammation [23].
3) Multiple Sclerosis
In multiple sclerosis (MS), progressive nerve damage causes an array of physical and cognitive impairments. Once again, we have autoimmune inflammation lurking as one of the culprits [24].
N-acetylglucosamine (NAG) suppressed the Th1 and Th17 autoimmune responses in mice with MS. It worked by blocking nerve inflammation (lowering IFN-gamma, TNF-alpha, IL-17, IL-22) and autoimmune nerve destruction [25].
Another study on mice confirmed that the lack of NAG polymers might strip the nerve-protecting sheath, myelin, and trigger multiple sclerosis [26].
In test tubes, glucosamine and N-acetylglucosamine protected brain cells against oxidative damage and death, which may be useful in nerve-damaging diseases such as MS [27].
4) Bleeding Control and Wound Healing
Polymers of N-acetylglucosamine (NAG) stimulate blood clotting, and they are being researched for different wound-healing patches and bandages [28, 29].
In a clinical trial of 20 patients, NAG nanofibers significantly improved wound healing when added to standard treatment [30].
Units of glucosamine and NAG build chitosan, a material with potent wound-healing properties. NAG polymers have shown even better results in test tubes [31, 32, 33].
In mice, NAG nano-fibers promoted wound healing and lowered the risk of infections and bleeding complications. They were particularly effective against diabetic wounds [34, 35, 36].
Hemophilia is a genetic disorder in which a person lacks specific proteins that enable blood clotting. Scientists are developing cures to prevent severe bleeding in hemophilia patients [37].
In the blood samples of dogs with hemophilia, NAG polymers enhanced blood clotting in combination with standard treatment [38].
Benefits of N-Acetyl-Glucosamine for the Skin
Hyaluronic acid is all the rage in skincare, and for a good reason: it’s responsible for keeping your skin soft and rejuvenated. Since N-acetylglucosamine (NAG) builds hyaluronic acid and other elastic polymers, it may [3, 1]:
- Reduce wrinkles and other signs of aging
- Hydrate the skin
- Speed-up wound healing
NAG also inhibits the production of the skin pigment melanin and aids in skin lightening.
5) Removes Skin Spots
A cream with 2% N-acetylglucosamine (NAG) removed dark face spots in 2 clinical trials (200+ people). A combination of NAG and niacinamide showed even better results [39, 40].
6) Anti-Age
In 42 older women, a neck and decolletage cream with N-acetylglucosamine (NAG) rejuvenated the skin and removed aging spots. Women who used the cream noticed a significant improvement in skin complexion [41].
Another clinical trial found that NAG may moisturize the skin [42].
Limitations and Caveats
We don’t have enough data to draw reliable conclusions from the research on N-acetylglucosamine (NAG). Most potential benefits are still limited to animal and cell studies.
Clinical trials with NAG are scarce and come with notable limitations, such as [12, 15, 21]:
- Lack of placebo control
- Small sample size
- Involvement of other substances
That said, N-acetylglucosamine did show encouraging health effects, and it’s worth further investigation.
N-Acetylglucosamine Side Effects
Keep in mind that the safety profile of NAG is relatively unknown, given the lack of well-designed clinical studies. The list of side effects below is not a definite one, and you should consult your doctor about other potential side effects, based on your health condition and other factors.
In the US, you may report drug or supplement side effects to the FDA at 1-800-FDA-1088 or at www.fda.gov/medwatch. In Canada, you may report side effects to Health Canada at 1-866-234-2345.
Clinical trials with N-acetyl-glucosamine (NAG) reported only minor digestive side effects, such as [12, 15, 21]:
- Bloating
- Constipation
- Heartburn
- Diarrhea
The following side effects were observed for glucosamine supplements. They may not refer to N-acetyl-glucosamine, but caution is warranted.
Glucosamine and NAG are derived from glucose and may interfere with its metabolism, but clinical studies haven’t found adverse effects of glucosamine in people with controlled diabetes [43, 44, 45, 46].
Glucosamine may raise blood glucose levels in cases of uncontrolled diabetes or insulin resistance [47, 48].
It may also increase eye pressure in the elderly and thus raise the risk of glaucoma [49, 50, 51].
Doctors reported one case of worsened asthma symptoms, probably caused by a supplement with glucosamine and chondroitin, but no other studies confirmed this effect [52].
Most supplement manufacturers derive NAG from shellfish and warrant caution for people with shellfish/seafood allergy.
There’s not enough evidence to proclaim NAG safe for pregnant women, while children should take it only under strict medical supervision.
NAG Drug Interactions
Supplement-drug interactions can be dangerous and, in rare cases, even life-threatening. Always consult your doctor before supplementing and let them know about all drugs and supplements you are using or considering.
Glucosamine interacts with blood thinners such as warfarin (Coumadin). Their combination may extend bleeding time and increase the risk of bruising [53].
Due to its potential effect on blood glucose, glucosamine may reduce the effectiveness of anti-diabetic medications.
Again, this doesn’t mean that N-acetylglucosamine would act the same way, but their similar structures imply this possibility.
To stay on the safe side, stop taking NAG at least two weeks prior to a scheduled surgery.
NAG Supplements
Despite the promising clinical and preclinical research, NAG supplements have not been approved by the FDA for medical use. In general, regulatory bodies aren’t assuring the quality, safety, and efficacy of supplements. Speak with your doctor before supplementing.
Most supplements on the market contain caps with 500-1000 mg of N-acetylglucosamine.
Watch out! Some products claim to have vegetarian/vegan caps, but they source NAG from shellfish. If you have a shellfish/seafood allergy or avoid animal products, look for products with NAG from vegan sources.
Bulk powders with 750 mg of NAG per serving are also available.
Dosage
The below doses used in clinical trials may not apply to you personally. If your doctor suggests using a NAG supplement, work with them to find the optimal dosage according to your health condition and other factors.
The following doses of N-acetyl-glucosamine (NAG, GlcNAc) were effective in clinical trials:
- Osteoarthritis: 100 mg/day for 12+ weeks (with chondroitin) [12]
- Joint recovery: 500-1000 mg/day for 16 weeks [15]
- IBD (children): 3-6 g/day [21]
A cream with 2% NAG (+4% niacinamide) successfully removed skin spots after 8 weeks [39, 40].
Reviews & User Experiences
The opinions expressed in this section are solely from the users who may or may not have medical background. Their reviews do not represent the opinions of SelfHacked. SelfHacked does not endorse any specific product, service, or treatment.
Do not consider user experiences as medical advice. Never delay or disregard seeking professional medical advice from your doctor or another qualified healthcare provider because of something you have read on SelfHacked.
Users take N-acetylglucosamine (NAG) for joint pain, IBD, and skincare, and most of them are satisfied with the result. Interestingly enough, some users reported the benefits of N-acetylglucosamine for anxiety and multiple sclerosis.
There are people with osteoarthritis and gut inflammation who experienced no improvement from NAG supplements. Some of them even complained about digestive side effects and worsened asthma.
Takeaway
N-acetylglucosamine (NAG or GlcNAc) builds large elastic molecules that support your joints, skin, and connective tissue. According to limited clinical research, NAG supplements may enhance joint recovery.
Despite some promising results, there’s insufficient evidence for IBD, wound healing, and multiple sclerosis. Cosmetics with NAG may help rejuvenate the skin and remove aging spots, especially in combination with niacinamide.
NAG may not be suitable for people with diabetes and glaucoma, pregnant women, and people on blood thinners. Those with shellfish/seafood allergy should look for NAG from vegan sources. Always consult your doctor before supplementing.