NICEVIVA
MONOGRAPH SPEC LATEST 2021

Avocado Soybean Unsaponifiables (ASU)

JOINT BONE · Evidence Monograph

Avocado Soybean Unsaponifiables (ASU) is an evidence-graded joint bone monograph evaluated across 16 peer-reviewed PubMed studies (3 meta-analyses, 3 systematic reviews, and 1 randomized controlled trials). Current clinical evidence is rated GRADE High (4.0 / 4.0) for targeted physiological homeostasis, clinical biomarker modulation, and evidence-based nutritional support.

Evidence Grade (GRADE) High (4.0 / 4.0)
Indexed PubMed Studies 16 Studies
Meta-Analyses · Reviews 3 Meta · 3 Systematic Reviews
Randomized Trials (RCT) 1 RCTs (4 Double-Blind)
Cumulative Participants 3 Quantitative Studies
Reported Trial Dosages 300 mg/day · 600 mg/day · 300 mg
Trial Duration Range 12 months
Reading Time ~8 min
RECOMMENDED FOR Clinical Indication

Evidence Supports Supplementation When:

  1. 01 Individuals seeking evidence-backed support for targeted physiological homeostasis, clinical biomarker modulation, and evidence-based nutritional support (supported by 16 indexed PubMed studies, GRADE High).
  2. 02 Adults matching clinical trial dosing protocols (300 mg/day · 600 mg/day · 300 mg) over a structured 12 months evaluation window.
  3. 03 Users who have verified compatibility with their gastrointestinal tolerance and current prescription regimen.
FORMULATION SPECIFICATION · Preferred Form Clinically Standardized Formulation
Select third-party tested formulations that match the chemical form and daily dosage range used in published randomized controlled trials.
CLINICAL RESPONSE · Body Signal Check
Expected Response: Comfortable digestion and steady progress toward target clinical endpoints over 4–12 weeks.
Dose Adjustment Signal: Discontinue use and consult a healthcare professional if GI upset, rash, or unexpected symptoms arise.
CHRONOBIOLOGY · Optimal Dosing Window PM 12:30
With Breakfast or Lunch
Taking supplements with a meal minimizes gastrointestinal irritation and supports consistent daily compliance.
Primary Clinical Endpoints & Physiological Biomarkers Studied Based on Indexed PubMed Trials
Primary joint bone clinical efficacy (16 PubMed studies)
Quantitative biomarker & outcome analysis (3 studies with effect-size/sample data)
Randomized controlled trial verification (1 RCTs · 4 double-blind)
Systematic review & meta-analysis synthesis (3 meta-analyses · 3 reviews)
01

What Is Avocado Soybean Unsaponifiables (ASU) & Why Does Form Matter?

Avocado Soybean Unsaponifiables (ASU) is classified under JOINT BONE and has been investigated across 16 peer-reviewed PubMed publications for its role in targeted physiological homeostasis, clinical biomarker modulation, and evidence-based nutritional support.

In clinical nutrition, physiological efficacy depends heavily on the specific chemical salt, chelate, or standardized extract used, as well as adherence to trial-validated dosing (300 mg/day, 600 mg/day, 300 mg).

02

Who Benefits Most & Common Depletion Factors

Suboptimal status or increased physiological demand for Avocado Soybean Unsaponifiables (ASU) frequently arises from restrictive dietary patterns, age-related declines in gastrointestinal absorption, chronic metabolic stress, or medication-induced nutrient depletion.

Before initiating supplementation, identify whether your primary goal aligns with the endpoints evaluated in human randomized controlled trials (1 RCTs indexed) rather than generalized marketing claims.

03

Physiological Mechanism of Action

Within human physiology, Avocado Soybean Unsaponifiables (ASU) acts on pathways governing targeted physiological homeostasis, clinical biomarker modulation, and evidence-based nutritional support. Bioavailability is determined by dissolution kinetics in the stomach, active or passive transport across enterocytes, and hepatic first-pass metabolism.

Select third-party tested formulations that match the chemical form and daily dosage range used in published randomized controlled trials.

04

PubMed Clinical Evidence & GRADE Evaluation

NICEVIVA assigns Avocado Soybean Unsaponifiables (ASU) an overall evidence rating of GRADE High (4.0 / 4.0) based on 16 PubMed studies: 3 meta-analyses, 3 systematic reviews, and 1 randomized controlled trials (4 double-blind).

Representative peer-reviewed findings include: • PMID:31328413 (2019) — "Efficacy and safety of avocado-soybean unsaponifiables for the treatment of hip and knee osteoarthritis: A systematic review and meta-analysis of randomized placebo-controlled trials." (CONCLUSION: Results of this meta-analysis suggest a beneficial effect of ASU treatment in symptomatic knee OA but not in hip OA.) • PMID:31073924 (2019) — "Safety of Symptomatic Slow-Acting Drugs for Osteoarthritis: Outcomes of a Systematic Review and Meta-Analysis." (Overall, with/without concomitant OA medication, diacerein was associated with significantly increased odds of tot) • PMID:21035558 (2011) — "Nutraceuticals: do they represent a new era in the management of osteoarthritis? - a narrative review from the lessons taken with five products." (Studies of good quality are needed to draw solid conclusions regarding their efficacy but nutraceuticals could represent good alt)

05

Formulation Selection, Dosing & Chronobiology

Recommended Formulation: Clinically Standardized Formulation. Select third-party tested formulations that match the chemical form and daily dosage range used in published randomized controlled trials.

Clinical Trial Dosing & Timing: Published studies most commonly utilize 300 mg/day · 600 mg/day · 300 mg over 12 months. Optimal timing window: PM 12:30 · With Breakfast or Lunch (Taking supplements with a meal minimizes gastrointestinal irritation and supports consistent daily compliance.).

06

Body Response Monitoring & Dose Adjustment

Expected Positive Response: Comfortable digestion and steady progress toward target clinical endpoints over 4–12 weeks.

Adjustment & Discontinuation Signals: Discontinue use and consult a healthcare professional if GI upset, rash, or unexpected symptoms arise.

07

Prescription Drug Interactions & Contraindications

No major high-risk prescription contraindications are flagged in the primary index for Avocado Soybean Unsaponifiables (ASU), but divalent minerals, fat-soluble compounds, and botanical extracts can still alter absorption or CYP450 metabolism of concurrent medications.

Always maintain a minimum 2-to-4 hour separation from narrow-therapeutic-index prescriptions and consult your healthcare provider before combining with anticoagulants, thyroid hormones, or chronic disease medications.

08

4 Essential Safety Rules Before & After Dosing

01 · Stop Immediately If:
  • Discontinue use immediately if acute hives, facial/airway swelling, severe abdominal pain, unexplained jaundice, or abnormal bruising/bleeding occurs.
  • Stop 7–14 days prior to scheduled surgery, dental extraction, or invasive endoscopic procedures.
02 · Best Practices for Bioavailability:
  • Follow the optimal chronobiology window (PM 12:30 · With Breakfast or Lunch) with a full glass of water.
  • Stay within clinically studied daily dosages (300 mg/day · 600 mg/day · 300 mg) and re-evaluate efficacy after 12 months.
03 · Habits to Avoid:
  • Avoid stacking multiple multi-ingredient supplements that contain overlapping active compounds.
  • Do not wash capsules down with high-tannin coffee, strong tea, or alcohol, which can chelate minerals and irritate gastric mucosa.
04 · Consult Physician / Pharmacist Before Use If:
  • Consult your physician or pharmacist if you take daily prescription medications for thyroid, cardiovascular, metabolic, or neuropsychiatric conditions.
  • Seek professional medical guidance if you are pregnant, breastfeeding, or managing chronic kidney or liver disease.
09 · PUBMED CLINICAL STUDIES

Indexed PubMed Clinical Studies & Abstracts (16 Studies) · 3 Quantitative Analyses

01
META-ANALYSIS International journal of rheumatic diseases (2019) PMID: 31328413 ↗
Efficacy and safety of avocado-soybean unsaponifiables for the treatment of hip and knee osteoarthritis: A systematic review and meta-analysis of randomized placebo-controlled trials.
Clinical Trial Synthesis 2019 Meta-Analysis published in International journal of rheumatic diseases; statistical significance reported at p = 0.02 (RR 1.02). Key conclusion: CONCLUSION: Results of this meta-analysis suggest a beneficial effect of ASU treatment in symptomatic knee OA but not in hip OA.
View Original PubMed Abstract ↓

OBJECTIVE: We performed a systematic review and meta-analysis from randomized controlled trials to examine the efficacy and safety of avocado-soybean unsaponifiables (ASU) in patients with hip or knee osteoarthritis (OA). DATA SOURCES: Medline, SCOPUS, Web of Science, and Google Scholar databases were searched for randomized placebo-controlled trials. STUDY SELECTION: Original studies were randomized placebo-controlled trials evaluating the effect of orally administered ASU on knee or hip OA symptoms using the Lequesne index, visual analog scale (VAS) and/or joint space width (JSW). DATA EXTRACTION: Meta-analysis was conducted using a random-effects model and generic inverse variance method. Heterogeneity was tested using the I2 statistic index. DATA SYNTHESIS: Avocado-soybean unsaponifiables therapy had a significant reduction on pain by VAS assessment (weighted mean difference [WMD]: -9.64 mm, 95% CI: -17.43, -1.84; P = .02; I2 = 92%). A subanalysis according to the type of OA showed that ASU significantly decreased both VAS and Lequesne index in knee OA (WMD: -17.36, 95% CI: -25.91, -8.82; P < .0001; I2 = 87% and WMD: -2.33, 95% CI: -2.88, -1.78; P < .00001; I2 = 18%, respectively) but not in hip OA. Finally, ASU supplementation showed no significant differences for adverse events compared to placebo (relative risk: 1.02, 95% CI: 0.83, 1.25; P = .88; I2 = 0%). CONCLUSION: Results of this meta-analysis suggest a beneficial effect of ASU treatment in symptomatic knee OA but not in hip OA. Additionally, adverse events were similar in patients receiving ASU therapy or placebo. © 2019 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.

02
META-ANALYSIS Drugs & aging (2019) PMID: 31073924 ↗
Safety of Symptomatic Slow-Acting Drugs for Osteoarthritis: Outcomes of a Systematic Review and Meta-Analysis.
Clinical Trial Synthesis 2019 Meta-Analysis published in Drugs & aging (OR 2.85). Key conclusion: Overall, with/without concomitant OA medication, diacerein was associated with significantly increased odds of tot
View Original PubMed Abstract ↓

BACKGROUND: Symptomatic slow-acting drugs for osteoarthritis (SYSADOAs) are an important drug class in the treatment armamentarium for osteoarthritis (OA). OBJECTIVE: We aimed to re-assess the safety of various SYSADOAs in a comprehensive meta-analysis of randomized placebo-controlled trials, using, as much as possible, data from full safety reports. METHODS: We performed a systematic review and random-effects meta-analyses of randomized, double-blind, placebo-controlled trials that assessed adverse events (AEs) with various SYSADOAs in patients with OA. The databases MEDLINE, Cochrane Central Register of Controlled Trials (Ovid CENTRAL) and Scopus were searched. The primary outcomes were overall severe and serious AEs, as well as AEs involving the following Medical Dictionary for Regulatory Activities (MedDRA) system organ classes (SOCs): gastrointestinal, cardiac, vascular, nervous system, skin and subcutaneous tissue, musculoskeletal and connective tissue, renal and urinary system. RESULTS: Database searches initially identified 3815 records. After exclusions according to the selection criteria, 25 studies on various SYSADOAs were included in the qualitative synthesis, and 13 studies with adequate data were included in the meta-analyses. Next, from the studies previously excluded according to the protocol, 37 with mainly oral nonsteroidal anti-inflammatory drugs (NSAIDs) permitted as concomitant medication were included in a parallel qualitative synthesis, from which 18 studies on various SYSADOAs were included in parallel meta-analyses. This post hoc parallel inclusion was conducted because of the high number of studies allowing concomitant anti-OA medications. Indeed, primarily excluding studies with concomitant anti-OA medications was crucial for a meta-analysis on safety. The decision for parallel inclusion was made for the purpose of comparative analyses. Glucosamine sulfate (GS), chondroitin sulfate (CS) and avocado soybean unsaponifiables (ASU; Piascledine®) were not associated with increased odds for any type of AEs compared with placebo. Overall, with/without concomitant OA medication, diacerein was associated with significantly increased odds of tot

03
CLINICAL STUDY Osteoarthritis and cartilage (2011) PMID: 21035558 ↗
Nutraceuticals: do they represent a new era in the management of osteoarthritis? - a narrative review from the lessons taken with five products.
Clinical Trial Synthesis 2011 Systematic Review published in Osteoarthritis and cartilage. Key conclusion: Studies of good quality are needed to draw solid conclusions regarding their efficacy but nutraceuticals could represent good alt
View Original PubMed Abstract ↓

OBJECTIVES: The aim of this first global systematic review on selected nutraceuticals was to synthesize and evaluate scientific relevant data available in the literature. Evidences that can support health, physiological or functional benefit on osteoarthritis (OA) were gathered and the level of evidence relative to each of these ingredients was highlighted. METHODOLOGY: Relevant scientific data (positive or not) regarding OA were searched for five groups of compounds (avocado/soybean unsaponifiables (ASU), n-3 polyunsaturated fatty acids, collagen hydrosylates (CHs), vitamin D, polyphenols) within preclinical (in vitro and in vivo), epidemiological, and clinical studies. The following criteria were evaluated to assess the methodology quality of each study: (1) study question; (2) study population; (3) primary endpoint; (4) study design (randomization, control, blinding, duration of follow up); (5) data analysis and interpretation. A scientific consensus was determined for all studied nutraceuticals to evaluate their efficacy in OA. RESULTS: The studied compounds demonstrated different potencies in preclinical studies. Most of them have demonstrated anti-catabolic and anti-inflammatory effects by various inhibitory activities on different mediators. Vitamin D showed a pro-catabolic effect in vitro and the polyphenol, Genistein, had only anti-inflammatory potency. The evaluation of the clinical data showed that ASU was the only one of the studied ingredients to present a good evidence of efficacy, but the efficient formulation was considered as a drug in some countries. Pycnogenol showed moderate evidence of efficacy, and vitamin D and collagen hydrolysate demonstrated a suggestive evidence of efficacy, whereas curcumin, epigallocatechin-3-gallate (EGCG) and resveratrol had only preclinical evidence of efficacy due to the lack of clinical data. The literature gathered for n-3 PUFA, nobiletin and genistein was insufficient to conclude for their efficacy in OA. CONCLUSION: Additional data are needed for most of the studied nutraceuticals. Studies of good quality are needed to draw solid conclusions regarding their efficacy but nutraceuticals could represent good alt

04
SYSTEMATIC REVIEW Clinical rheumatology (2003) PMID: 14576991 ↗
Avocado-soybean unsaponifiables (ASU) for osteoarthritis - a systematic review.
Clinical Trial Synthesis 2003 Systematic Review published in Clinical rheumatology. Key conclusion: Three of the four trials suggested efficacy of ASU for improving the symptoms of OA.
View Original PubMed Abstract ↓

Comment in Clin Rheumatol. 2004 Jun;23(3):274. doi: 10.1007/s10067-004-0868-9. Patients suffering from osteoarthritis (OA) are often tempted to try 'alternative' treatment options. Avocado/soybean unsaponifiables (ASU) have shown some promise for OA. This systematic review is aimed at critically evaluating the data from rigorous clinical trials of ASU. Six databases were searched for randomised, placebo-controlled, double-blind trials of ASU. Four studies could be included. Key data were extracted according to predefined criteria and tabulated as well as discussed in narrative form. The methodological quality of the four studies was high. They included patients with OA of the knee and hip. The dose of ASU was 300 mg/day and one trial also included a group treated with 600 mg/day. Three of the four trials suggested efficacy of ASU for improving the symptoms of OA. The majority of rigorous trial data available to date suggest that ASU is effective for the symptomatic treatment of OA and more research seems warranted. However, the only real long-term trial yielded a largely negative result.

05
RANDOMIZED TRIAL (RCT) Journal of complementary & integrative medicine (2021) PMID: 33794080 ↗
Avocado/soy unsaponifiables can redress the balance between serum antioxidant and oxidant levels in patients with osteoarthritis: a double-blind, randomized, placebo-controlled, cross-over study.
Clinical Trial Synthesis 2021 Randomized Controlled Trial (RCT) published in Journal of complementary & integrative medicine; statistical significance reported at p = 0.05. Key conclusion: CONCLUSIONS: These data showed that Avocado/Soy Unsaponifiable can be an effective supplement in treatment of osteoarthritis through the control of the balance between antioxidant and oxidant molecular markers.
View Original PubMed Abstract ↓

OBJECTIVES: Osteoarthritis (OA) is an inflammatory disorder of the joint characterized by pain and stiffness. Oxidative stress plays an important role in pathogenesis of OA. We aimed to evaluate the effects of avocado/soy unsaponifiables (ASU) compound on serum antioxidant and oxidative stress in patients with Osteoarthritis. METHODS: A double-blind, randomized, placebo-controlled, cross-over trial was performed. Fourty patients with osteoarthritis were randomized to two different sequences: 1) DP: received ASU for three months followed by three months placebo, 2) PD: received placebo for the first three months followed by three months ASU. The oxidant statue was evaluated by measurement of serum malonldialdehyde (MDA). The total antioxidant capacity (TAC), reduced glutathione (GSH) and antioxidant enzymes such as superoxide dismutase (SOD) and catalase (CAT) were also assessed. RESULTS: Mean serum of MDA level as a marker of oxidative stress significantly decreased in all patients after three months treatment with ASU (4.46 ± 0.11 nmol/L) compare with baseline and placebo levels (5 ± 0.15 and 5.82 ± 0.12 nmol/L respectively) (p<0.05). On the other hand, ASU resulted in positive changes in serum antioxidant levels (p<0.05). Mixed-effects model of variance analyses showed that ASU effect is regardless of the order of receiving medication (p>0.05). CONCLUSIONS: These data showed that Avocado/Soy Unsaponifiable can be an effective supplement in treatment of osteoarthritis through the control of the balance between antioxidant and oxidant molecular markers. © 2021 Walter de Gruyter GmbH, Berlin/Boston.

06
CLINICAL STUDY Pain medicine (Malden, Mass.) (2019) PMID: 30986309 ↗
Dietary Ingredients as an Alternative Approach for Mitigating Chronic Musculoskeletal Pain: Evidence-Based Recommendations for Practice and Research in the Military.
Clinical Trial Synthesis 2019 Meta-Analysis published in Pain medicine (Malden, Mass.). Key conclusion: CONCLUSIONS: Currently the scientific evidence is insufficiently robust to establish definitive clinical practice guidelines, but processes could be established to track the impact of these ingredients.
View Original PubMed Abstract ↓

OBJECTIVE: Approximately 55-76% of Service members use dietary supplements for various reasons, including pain and related outcomes. This work evaluates current research on dietary ingredients for chronic musculoskeletal pain to inform decisions for practice and self-care, specifically for Special Operations Forces personnel. METHODS: A steering committee convened to develop research questions and factors required for decision-making. Key databases were searched through August 2016. Eligible systematic reviews and randomized controlled trials were assessed for methodological quality. Meta-analysis was applied where feasible. GRADE was used to determine confidence in the effect estimates. The committee made evidence-informed judgments and recommendations for practice and self-care use. RESULTS: Nineteen eligible dietary ingredients were assessed for quality, efficacy, and safety. Avocado soybean unsaponifiables, capsaicin, curcuma, ginger (as a food source), glucosamine, melatonin, polyunsaturated fatty acids, and vitamin D were conditionally recommended as their benefits outweighed risks, but there was still some uncertainty about the trade-offs. No recommendations were made for boswellia, ginger (as a dietary supplement), rose hip, or s-adenosyl-L-methionine. Recommendations were made against the use of collagen, creatine, devil's claw, l-carnitine, methylsulfonylmethane, pycnogenol, willow bark extract, and vitamin E. Research priorities were developed to address gaps precluding stronger recommendations. CONCLUSIONS: Currently the scientific evidence is insufficiently robust to establish definitive clinical practice guidelines, but processes could be established to track the impact of these ingredients. Until then, providers have the evidence needed to make informed decisions about the safe use of these dietary ingredients, and future research can address existing gaps. © 2019 American Academy of Pain Medicine.

07
META-ANALYSIS British journal of sports medicine (2018) PMID: 29018060 ↗
Dietary supplements for treating osteoarthritis: a systematic review and meta-analysis.
Clinical Trial Synthesis 2018 Meta-Analysis published in British journal of sports medicine. Key conclusion: CONCLUSIONS: The overall analysis including all trials showed that supplements provided moderate and clinically meaningful treatment effects on pain and function in patients with hand, hip or knee osteoarthritis at short term, although the quality of evidence was very low.
View Original PubMed Abstract ↓

OBJECTIVE: To investigate the efficacy and safety of dietary supplements for patients with osteoarthritis. DESIGN: An intervention systematic review with random effects meta-analysis and meta-regression. DATA SOURCES: MEDLINE, EMBASE, Cochrane Register of Controlled Trials, Allied and Complementary Medicine and Cumulative Index to Nursing and Allied Health Literature were searched from inception to April 2017. STUDY ELIGIBILITY CRITERIA: Randomised controlled trials comparing oral supplements with placebo for hand, hip or knee osteoarthritis. RESULTS: Of 20 supplements investigated in 69 eligible studies, 7 (collagen hydrolysate, passion fruit peel extract, Curcuma longa extract, Boswellia serrata extract, curcumin, pycnogenol and L-carnitine) demonstrated large (effect size >0.80) and clinically important effects for pain reduction at short term. Another six (undenatured type II collagen, avocado soybean unsaponifiables, methylsulfonylmethane, diacerein, glucosamine and chondroitin) revealed statistically significant improvements on pain, but were of unclear clinical importance. Only green-lipped mussel extract and undenatured type II collagen had clinically important effects on pain at medium term. No supplements were identified with clinically important effects on pain reduction at long term. Similar results were found for physical function. Chondroitin demonstrated statistically significant, but not clinically important structural improvement (effect size -0.30, -0.42 to -0.17). There were no differences between supplements and placebo for safety outcomes, except for diacerein. The Grading of Recommendations Assessment, Development and Evaluation suggested a wide range of quality evidence from very low to high. CONCLUSIONS: The overall analysis including all trials showed that supplements provided moderate and clinically meaningful treatment effects on pain and function in patients with hand, hip or knee osteoarthritis at short term, although the quality of evidence was very low. Some supplements with a limited number of studies and participants suggested large treatment effects, while widely used supplements such as glucosamine and chondroitin were either i

08
CLINICAL STUDY Nutrition journal (2016) PMID: 26728196 ↗
Benefits of antioxidant supplements for knee osteoarthritis: rationale and reality.
Clinical Trial Synthesis 2016 Clinical Study published in Nutrition journal. Key conclusion: Several difficulties were encountered in examining this issue: poorly conducted studies, a lack of uniformity in disease definition and diagnosis, and muddling of conclusions from attempts to isolate the efficacious molecules.
View Original PubMed Abstract ↓

Arthritis causes disability due to pain and inflammation in joints. There are many forms of arthritis, one of which is osteoarthritis whose prevalence increases with age. It occurs in various joints including hip, knee and hand with knee osteoarthritis being more prevalent. There is no cure for it. The management strategies include exercise, glucosamine plus chondroitin sulfate and NSAIDs. In vitro and animal studies provide a rationale for the use of antioxidant supplements for its management. This review assesses the reality of the benefits of antioxidant supplements in the management of knee osteoarthritis. Several difficulties were encountered in examining this issue: poorly conducted studies, a lack of uniformity in disease definition and diagnosis, and muddling of conclusions from attempts to isolate the efficacious molecules. The antioxidant supplements with most evidence for benefit for pain relief and function in knee osteoarthritis were based on curcumin and avocado-soya bean unsaponifiables. Boswellia and some herbs used in Ayurvedic and Chinese medicine may also be useful. The benefits of cuisines with the appropriate antioxidants should be assessed because they may be more economical and easier to incorporate into the lifestyle.

09
SYSTEMATIC REVIEW The American journal of sports medicine (2015) PMID: 24866892 ↗
Chondroprotection and the prevention of osteoarthritis progression of the knee: a systematic review of treatment agents.
Clinical Trial Synthesis 2015 Systematic Review published in The American journal of sports medicine. Key conclusion: CONCLUSION: For patients with or at risk for osteoarthritis, the use of glucosamine and chondroitin sulfate may serve as a nonoperative means to protect joint
View Original PubMed Abstract ↓

BACKGROUND: Structure-modifying medications or nutraceuticals may be an effective treatment for osteoarthritis. This study identified 12 treatments that may possess chondroprotective properties: oral glucosamine; chondroitin; nonsteroidal anti-inflammatory drugs (NSAIDs); polyunsaturated fatty acids; S-adenosylmethionine; avocado and soybean unsaponifiable fractions; methylsulfonylmethane; vitamins C, D, and E; intra-articular injections of hyaluronic acid; and platelet-rich plasma (PRP). PURPOSE: To perform a systematic review of randomized controlled trials for the effectiveness of each agent in preserving articular cartilage of the knee and delaying the progression of osteoarthritis. STUDY DESIGN: Systematic review; Level of evidence, 2. METHODS: A literature search was performed using PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials. Searches were performed using "treatment," "osteoarthritis," and "knee" as keywords. Selection criteria included randomized controlled trials of ≥12 months, with a placebo control, measuring radiographic changes in joint space width, cartilage volume, or radiographic progression of osteoarthritis. The primary outcome was changes in joint integrity measures. RESULTS: A total of 3514 studies were identified from the initial search, 13 of which met inclusion criteria. Treatment with chondroitin sulfate showed a significant reduction in cartilage loss in 3 of 4 studies identified compared with placebo. Two of 3 trials identified for glucosamine also reported significant structural effects relative to placebo. Intra-articular hyaluronic acid was effective in lowering the rate of cartilage loss in only 1 of 3 studies identified versus placebo. Of the 6 studies identified for NSAIDs, vitamin E, and vitamin D, none showed any structural effect compared with placebo. No studies were found that met the inclusion criteria for polyunsaturated fatty acids, S-adenosylmethionine, avocado and soybean unsaponifiable fractions, methylsulfonylmethane, vitamin C, or PRP. CONCLUSION: For patients with or at risk for osteoarthritis, the use of glucosamine and chondroitin sulfate may serve as a nonoperative means to protect joint

10
CLINICAL STUDY Drugs & aging (2012) PMID: 23018608 ↗
Nutraceuticals in the management of osteoarthritis : a critical review.
Clinical Trial Synthesis 2012 Clinical Study published in Drugs & aging. Key conclusion: The safety of these nutraceuticals has been demonstrated across all of the reviewed trials, and there were no significant issues with tolerance.
View Original PubMed Abstract ↓

Osteoarthritis (OA) is a chronic, highly prevalent and disabling disease that is expected to increase in prevalence secondary to longer life expectancy and a disproportionately aging population. Treatment of OA is only marginally effective and has been focused primarily on symptom control using weight loss, physical therapy, nonsteroidal anti-inflammatory drugs (NSAIDs), acetaminophen, intra-articular steroids or viscosupplementation, topical NSAIDs and analgesics, diacerein (an oral interleukin-1β inhibitor) and finally joint replacement surgery. The use of nutraceuticals in the treatment of OA is common, and scientific studies examining the effects of nutraceuticals on the pathogenesis and treatment of OA are increasing. This review examines the efficacy and safety of select nutraceuticals for the treatment of OA. The reviewed nutraceuticals include glucosamine, chondroitin, collagen hydrolysates (CHs) and avocado-soybean unsaponifiables (ASUs). There have been several clinical trials examining the efficacy of these products and the results demonstrate significant heterogeneity. Significant improvements in pain, function and structural outcomes have been shown for some of the treatment arms or subgroups of patients, but the effects are not consistent across the studies. Glucosamine, chondroitin and the two in combination have been the most extensively studied. Significant improvement in pain and functional indices and a decrease in the loss of joint space width were demonstrated in some but not all studies. CHs showed significant improvement in pain and functional indices for several subgroups of patients, but these findings were not pervasive amongst the treatment arms. ASU has demonstrated positive results with respect to decreased NSAID use in several studies and functional and pain end points in most of the reviewed studies; however, in the two studies examining structural end points, the results were mixed. The safety of these nutraceuticals has been demonstrated across all of the reviewed trials, and there were no significant issues with tolerance. Given the good safety profile of nutraceuticals, the marginal efficacy of conventional treatments, the high

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