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Episode 183-Glucosamine/Nat Grabow
A brief synopsis of the episode's main discussions and takeaways as well as extended references
Jeff Sankoff
November 07, 2025
It was such a pleasure to catchup with the oldest woman to ever complete the IM World Championships in Kona and hear about her remarkable life and career. Ten Kauri wood bowls!!!Now that is impressive….
Table of Contents
Glucosamine for cartilage health? The science isn’t that encouraging
Glucosamine is a component of cartilage and has been advocated as a supplement for quite some time. The idea ghas always been that if you take enough of the stuff, it will help protect against cartilage loss and help with repair after injury. But is that actually the case? The evidence on this subject is not so clear. Most studies when positive tend to show small benefits and are almost always tied to the makers of the supplements themselves. Studies without industry ties are few and far between but when done tend to not show any real benefits. There may be some small advantage to delaying the impacts of osteoarthritis in older populations but this is far from certain. There does not seem to be any benefit at all from taking glucosamine in promoting cartilage healing after injury. At the end of the day, this supplement joins a long line of those that promise a lot but deliver a lot less. On the plus side, there is no real downside to taking it and it is not very expensive but once again, users should not expect much from their investment.
Nat Grabow-Women’s 80-84 Ironman World Champion
About Nat according to Nat: I’m 80 years old, married for 56 years to Paul. We have two daughters and they are both married with 2 children each. I have always loved sports. I played tennis when my girls were young, started running in my late 30’s, early 40’s and learned to swim at 59. I did my first triathlon in 2005, the year I turned 60 and have been training and racing for 21 years. I’ve competed in the Ironman World Championship 11 times and at the 70.3 World Championship 4 times. I’m signed up for two 70.3 races next year and will add at least one more I’m sure. That is my favorite distance. I love the day to day process or training and hope to stay active for many more years.
Natalie Grabow journey through the triathlon world is like a fairy tale, but with more sweat and less magic. At the ripe age of 81, she's not just participating; she's breaking barriers, becoming the first female finisher in her age group at the Ironman World Championships. In this episode, we dive into her remarkable story, where overcoming injuries, defying age stereotypes, and embracing the thrill of competition take center stage. The conversation kicks off with Natalie reflecting on her 21 years in triathlon, emphasizing her love for movement and the joy of pushing herself. Despite facing setbacks, her determination shines through as she shares how she navigates challenges and maintains her competitive spirit. With a delightful mix of humor and humility, she recounts her experiences, making it clear that age is merely a number when it comes to pursuing passion and fitness. As the episode unfolds, we also tackle the importance of community and support in the sport. Natalie’s interactions with fellow athletes and her family add a heartwarming touch, showcasing the camaraderie that fuels her journey.
This conversation wasn’t just about racing; it’s about the mindset that keeps us moving through life, regardless of age. Natalie’s story serves as a reminder that it’s never too late to start something new, and that the desire to keep going can lead to extraordinary achievements. Natalie’s infectious enthusiasm will leave you wanting to lace up your shoes and hit the pavement yourself!
Episode takeaways:
Glucosamine won’t cause any harm but is unlikely to give much benefit.
The journey of triathlon is driven by a desire to keep moving, regardless of age.
It's crucial to listen to your body and adjust your training to stay healthy and active.
The joy of sports is in the personal achievements, not just podium finishes or accolades.
References used for the MMB
Glucosamine
Key Points:
Glucosamine, which is naturally found in the cartilage, helps to cushion joints
This can be derived from shells/shellfish
It exists in several supplement forms, including glucosamine sulfate, glucosamine hydrochloride, and N-acetylglucosamine, which are not interchangeable.
Glucosamine sulfate may reduce pain associated with osteoarthritis of the knee
Research suggests that glucosamine hydrochloride may reduce pain associated with rheumatoid arthritis, but improvements were not reported for inflammation or the number of painful/swollen joints
Clinical evidence for the use of N-acetylglucosamine for osteoarthritis is limited
Mayo Clinic notes that while mixed results have been reported, glucosamine sulfate may be worth a try to relieve some pain associated with osteoarthritis.
While it is generally considered safe, oral use of the supplement can cause nausea, heartburn, diarrhea, constipation, drowsiness, skin reactions, or headaches
Due to its potential to interact with medications or worsen asthma, doctors should be consulted before using it.
Glucosamine
Dahmer & Schiller (2008)
Key Points:
Glucosamine, often used in combination with chondroitin, is one of the most popular and studied dietary supplements
Usual dosing is 500mg 3 times/day
When glucosamine sulfate is consumed orally, ~90% is absorbed and incorporated into the articular cartilage
Studies suggest glucosamine sulfate and glucosamine hydrochloride may be more effective than others
Glucosamine’s potential to slow the progression of knee osteoarthritis has been reported
However, despite there being over 20 randomized controlled studies with 2500+ patients, the effectiveness of glucosamine on osteoarthritis remains unclear.
According to this publication, a recent study found that most studies reporting positive effects were funded by glucosamine product manufacturers, while most unsponsored research failed to show its benefit
A meta analysis in 2005 found that “current evidence (1) does not analyze the long-term effectiveness and toxicity of glucosamine; (2) does not differentiate which joints and which levels of severity of osteoarthritis warrant this therapy; (3) does not differentiate which dosage and route of administration are best; and (4) does not demonstrate whether glucosamine modifies the long-term progression of osteoarthritis”
The article notes the glucosamine sulfate supplement’s potential for benefit when used for 30-90 days and does not recommend against its use
GLUCOSAMINE: INJURY PREVENTION AND RECOVERY
Article written by Rick Miller in July 2019
Key Points:
Osteoarthritis, the most common joint disease, causes swelling, pain, and gradual loss of mobility
Notes a review which evaluated the effectiveness of glucosamine in osteoarthritis from 25 RCTs, showing that pain relief may be improved by up to 22% and further cartilage loss may be prevented.
Since athletes experience joint strain, glucosamine is theorized to help repair cartilage and reduce pain, which will aid recovery and enhance training potential
2 studies suggest the acute effects of glucosamine on cyclists and soccer players
Studies have also reported significant improvements in knee flexion and extension relative to placebo, suggesting the supplement’s potential to improve recovery in athletes
Glucosamine taken with or without chondroitin may support joint health in athletes
Glucosamine therapy for treating osteoarthritis
Towheed et al. (2005)
Key Points:
This study aimed to review all RCTs to evaluate the effectiveness and toxicity of glucosamine in osteoarthritis.
25 studies with 4963 patients were included after a search of relevant RCTs and reviews were done
While glucosamine had an overall safety similar to the placebo and collectively favored the placebo with a 28% improvement in pain as well as a 21% change in function, the RTCs’ results on the pain, function, and stiffness showed mixed results.
3 of the 8 authors for this paper had patents for glucosamine-type products or had previously received educational grants from glucosamine-related companies.
The paper discusses that many physicians prefer non‐steroidal anti‐inflammatory drugs (NSAIDs) for the management of osteoarthritis, but studies have presented the disadvantages of routine NSAIDs use in osteoarthritis, including increased toxicity.
Methods: RCTs and review articles published on MEDLINE, PREMEDLINE, EMBASE, AMED, ACP Journal Club, DARE, CDSR, and the CCTR by January 2005 were searched. Analyzed studies that evaluated the effectiveness and safety of glucosamine in osteoarthritis. Included 25 studies with 4963 patients.
Results: Glucosamine “failed to show any benefit for pain (based on a pooled measure of different pain scales) and WOMAC pain, function and stiffness subscales; however, it was found to be better than placebo using the Lequesne index (standardized mean difference (SMD) ‐0.54; 95% confidence interval (CI) ‐0.96 to ‐0.12)... [R]esults were not uniformly positive and the reasons for this remain unexplained. WOMAC pain, function and stiffness outcomes did not reach statistical significance.”
Glucosamine administration in athletes: effects on recovery of acute knee injury
Ostojic et al. (2007)
Key Points:
Did not have access to the full article
This study examined the effects of glucosamine on the functional ability and pain intensity in male athletes following acute knee injuries.
This was a double-blind randomized trial with 106 patients administered 1500 mg/d glucosamine or a placebo for 4 weeks
Visual analog scale was used to measure pain
Goniometer was used to measure knee flexibility
Swelling measured relative to non-injured knee
No significant difference was found between the glucosamine and placebo groups in:
mean resting/walking pain intensity scores
degrees of knee swelling at days 7, 14, 21, & 28
passive knee flexibility at the 7, 14, & 21
However, 28 days of glucosamine treatment showed a significant improvement in knee flexion and extension relative to placebo
Value of biomarkers in osteoarthritis: current status and perspectives
Lotz et al. (2013)
Notes:
These figures help to clarify the roles of the biomarkers assessed in some studies.
Evaluation of the effect of the administration of a glucosamine‑containing supplement on biomarkers for cartilage metabolism in soccer players: A randomized double‑blind placebo‑controlled study
Tsuruta et al. (2018)
Key Points:
Joint loading is known to cause joint and cartilage damage, so athletes are at risk for symptoms of osteoarthritis.
CTX II, C2C, and NTx are degradation markers, while CPII is a synthesis marker
In a previous comparison of biomarkers between athletes and non-athlete controls, the basic levels of CTX-II and NTx were significantly higher in soccer players, whereas CPII was not, suggesting that type II collagen and type I collagen degradation are enhanced in soccer players with excessive motion and loading on the joints.
This study evaluated the chondroprotective capabilities of glucosamine in soccer players without joint disorders by analyzing biomarkers and found that oral glucosamine supplementation (2 g/day for 16 weeks) improves cartilage metabolism (suppresses type II collagen degradation but maintains type II collagen synthesis), without causing apparent adverse effects.
Methods: Randomized, double-blind, placebo-controlled study. Collegiate soccer players (N=43) received 2 g/day glucosamine (n=22) or a placebo supplement (n=21) for 16 wks. 3-week screening period followed by a 16 wk intervention period and an 8-week follow-up period without intervention. Survey and laboratory data collected at baseline, 0, 4, 8, 12 and 16 wks intervention, and 4 and 8 weeks after the intervention. Cartilage metabolism (type II collagen degradation) assessed using urine C-terminal telopeptide II (CTX-II), serum collagen type II cleavage (C2C), synthesis urine C-terminal type II procollagen peptide (CPII), and cross-linked N-terminal telopeptides of type I collagen (NTx).
Results: In an analysis of all subjects (n=43), the glucosamine group showed a significantly lower and substantially more decreased urine CTX‑II level relative to the placebo group. In an analysis of subjects with less variation of exercise loading (n=41), urine CTX‑II level significantly decreased in the glucosamine group, but not in the placebo group (P<0.05). Serum C2C level also significantly decreased in the glucosamine group for both analyses, but not in the placebo group (P<0.05). No significant change in CPII or NTx was seen. No test supplement‑related adverse events were observed.
Effects of Different Doses of Glucosamine Hydrochloride on Cartilage Tissue and Levels of Joint Injury Markers in Knee Osteoarthritis
Wang et al. (2025)
Key Points:
***this paper has very nice figures showing dose-dependent differences in mice
This study examined the protective effects of different dosage of glucosamine hydrochloride (GS-HCl) on biomarkers of join injury, histopathological changes in cartilage, apoptosis, inflammation, oxidative stress response, and matrix degradation to evaluate GS-HCl effects on cartilage tissue and joint injury in knee osteoarthritis (KOA)
Mice in the KOA group displayed elevated levels of joint injury markers, inflammatory cytokines, MDA, and remodeling proteins, but lowered SOD activity.
The study results suggest that GS-HCl can improve joint damage since doses of GS-HCl lowered COMP, CS846, CTX-II, IL-6, TNF-α, iNOS and MDA contents, apoptosis rate and MMP-3 and TIMP-1 protein expression, while increasing SOD activity in KOA mice, with higher dosage showing more significance than lower doses.
Higher doses of GS-HCl may be reducing inflammation, oxidative stress, and matrix degradation while promoting cartilage repair to limit articular cartilage damage, suggesting GS-HCl’s protective effects.
Methods: male-specific pathogen free mice used. Randomized into 4 groups: sham, KOA, low dose GS-HCl, and high dose GC-HCl (n=6 each). Sham group mice only had right knee joint exposed. KOA by anterior cruciate ligament transection. Sham and KOA mice given saline while low and high dose groups given 41.5 mg/kg or 137.5 mg/kg GC-HCl for 8 weeks. Assays were used to assess joint injury markers (COMP, CS846, CTX II), inflammatory cytokines (IL6, TNF-alpha, and iNOS), oxidative stress indicators (MDA and SOD), as well as matrix remodeling proteins (MMP3 and TIMP1).
Results: “Different doses of GS-HCl treatment possessed significant effects on the alteration of serum CTX-II, CS846 and COMP levels in KOA mice, and starting from the 4th week, serum CTX-II, CS846 and COMP levels in the high-dose GS-HCl group were lower compared with those in the low-dose GS-HCl group (p < 0.05)....Different doses of GS-HCl treatment were performed on KOA mice, which were able to reduce the degree of tissue injury in comparison with that in the KOA group, and the high-dose GS-HCl group possessed pronounced effects (p < 0.05)...apoptosis rate of the KOA group was higher compared with that of the Sham group; compared with the KOA group, KOA mice after treatment with different doses of GS-HCl displayed reduced apoptosis in the tissues, of which the high dose GS-HCl group possessed significant effects (p < 0.05)...Compared with the KOA group, KOA mice treated with low-dose GS-HCl and high-dose GS-HCl possessed diminished IL-6, TNF-α and iNOS contents, and the improvements in each indicator of the high-dose GS-HCl group were better (p < 0.05)...MDA content in the KOA group was higher than that in the Sham group, while the SOD activity was lower than that in the Sham group (p < 0.05)...[and]...MDA content in the low-dose GS-HCl group and the high-dose GS-HCl group was decreased, and the SOD activity was increased (p < 0.05)...improvement in each indicator in the high-dose GS-HCl group was better than that in the low-dose GS-HCl group (p < 0.05)...high-dose GS-HCl group achieved lower MMP-3 and TIMP-1 protein contents compared with the low-dose GS-HCl group (p < 0.05)”
Total mortality risk in relation to use of less-common dietary supplements
Nagaoka et al. (2019)
Key Points:
This study evaluated whether the 10-year average consumption of supplements was associated with total mortality
Glucosamine and chondroitin were associated with 17% decreased risk of death
Meta-analyses from 2000 and 2003 show a positive association between use of these supplements and improvements in osteoarthritis; however, a 2007 analysis showed no effect.
Other studies have reported that glucosamine or chondroitin was associated with a reduced risk of lung and colorectal cancer in the same (VITAL) cohort used for this study, and past animal studies also suggest their potential to hinder the progression of cardiovascular disease and have therapeutic effects in colitis.
Methods: Prospective cohort study. Western Washington residents (n=77,719; age 50-76 yrs) followed for mortality for an avg. of 5 yrs. Participants classified as a user of an individual supplement or multivitamin if it was consumed at least once/wk during the last 10 yrs. Daily intake computed. Identified potential cofounders: age, sex, race-ethnicity, marital status, education, history of smoking and physical activity, hormone therapy use, medication history, medical tests/interventions, family history.
Results: 3577 deaths identified during 387,801 person-years of follow-up. “After multivariate adjustment there were no associations between the 10-y average daily intake of any of the vitamins (Table 2) or minerals (Table 3) and total mortality. Among the nonvitamin-nonmineral supplements, 10-y average daily intakes of glucosamine and chondroitin were each associated with decreased risks of total mortality (Table 4). For glucosamine the HR was 0.92 (95%CI:0.82,1.04)for low use and 0.83 (95%CI:0.72, 0.97) for high use (P for trend = 0.009). For chondroitin the HR was 0.88 (95% CI: 0.77, 1.02) for low use and 0.83 (95% CI: 0.69, 1.00) for high use (P for trend = 0.011).”
Do glucosamine and chondroitin supplements actually work for arthritis?
Article by Dr. Robert Shmerling published in February 2022
Key Points:
Glucosamine and chondroitin are popular, with annual spending on these supplements estimated to reach $3.5 billion by 2025
Due to its popularity, many people think it is highly effective to prevent joint disease, but the evidence remains unclear, with many studies reporting moderate to no benefit
While it is considered safe, it is associated with allergy, minor side effects, and drug-interaction risks
The article notes that the supplement is not FDA regulated
Cost is ~$12/month
The author recommends consulting doctors to check drug-interaction risks and stopping if clear improvements are not seen
While results remain unclear, the author notes that dosage and conditions for use vary, so there may be situations where this supplementation may be helpful
More research is necessary
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