Table 2.
Details of the studies examining exposure to dietary supplements (n = 14).
| Study | Design | Aim | Population | Nutritional exposure | Concurrent exposure | Comparator | Outcome measure(s) | Results | Conclusion |
|---|---|---|---|---|---|---|---|---|---|
| Arquer et al. (2014) [44] | Non-comparative intervention study | To evaluate the efficacy and safety of a nutritional supplement on the clinical and structural evolution of AT, PT and LET tendinopathies | 98 tendinopathy patients, AT (n = 32): 49.2 ±3.64 y; PT (n = 32): 47.7 ±1.69 y; LET (n = 34): 39.0 ±2.44 y, both sexes | 3 capsules Tendoactive (mucopolysaccharides (435 mg), type I collagen (75 mg), vitamin C (60 mg)) per day for 90 consecutive days | None | Pre-measurements | Pain intensity at rest and when active (VAS); joint function (VISA-A/VISA-P/PRTEE); tendon cross-sectional thickness (USI) | After 90 days: Pain at rest decreased by 80% (AT), 71% (PT) and 91% (LET) (p <0.001). Pain when active decreased by 82% (AT), 73% (PT) and 81% (LET) (p <0.001). Functional scores improved by 38% (AT), 46% (PT) and 77% (LET) (p <0.001). Thickness reduced by 12% (AT), 10% (PT) and 20% (LET) (p <0.05). | Administration of Tendoactive is effective for improving the clinical symptoms and structural evolution of tendinopathies |
| Balius et al. (2016) [36] | RCT | To determine the additional benefit of mucopolysaccharides, collagen and vitamin C (MCVC) to a physical therapy program in patients with AT tendinopathy | 58 reactive or degenerative AT tendinopathy patients (18-70 y, both sexes) | 3 capsules MCVC (mucopolysaccharides (435 mg), type I collagen (75 mg), vitamin C (60 mg)) per day for 3 months | Eccentric training (EC+MCVC) or passive stretching (PS+MCVC) | Eccentric training only (EC) | VISA-A; pain at rest and during activity (VAS); tendon bilateral thickness (USI) | After 12 weeks: Statistically and clinically significant improvement in VISA-A scores in all groups without between-group effect (p >0.1). VAS scores decreased in all groups with a difference for pain at rest between PS+MCVC (−3.7(0.8) and EC (−2.7(1.3), p <0.05). Bilateral thickness remained constant in EC and EC+MCVC, and reduced in PS+MCVC (−0.63(0.3) mm, p <0.05). | MCVC seems to be therapeutically useful for the management of tendinopathies |
| Praet et al. (2019) [39] | RCT (cross-over) | To investigate whether oral supplementation of specific collagen peptides improves symptoms and tendon vascularization in patients with chronic mid-portion AT tendinopathy in combination with structured exercise | 20 mid-portion AT tendinopathy patients (44 ±8 y, 65% male) | Two daily sachets Tendoforte (2.5 g hydrolyzed specific collagen peptides) for 3 months | Eccentric and running exercises for 6 months | Placebo + eccentric and running exercises for 6 months | Pain and functional limitations (VISA-A); vascularization (USI) | The group receiving the supplement in the first 3 months improved by 12.6 (9.7-15.5) in the supplemental phase and 5.9 (2.8-9.0) in the placebo phase. The other group improved by 5.3 (2.3-8.3) and 17.7 (14.6-20.7). There was a difference between groups in evolution of the VISA-A scores over time (p <0.0001). No difference in vascularization between groups. | Supplementation of specific collagen peptides may accelerate the clinical benefits of exercise program in AT patients. |
| Vitali (2019) [43] | Non-randomized controlled study | To determine the efficacy of Extracorporeal Shock Wave Therapy (ESWT) in combination with the dietary supplement Tendisulfur Forte in the treatment of shoulder, LET and AT tendinopathies | 90 AT, shoulder or LET tendinopathies (39-69 y, 50% male) | Tendisulfur Forte (containing methyl-sulfonyl-methane (MSM), hydrolyzed swine collagen (Type I and Type II), L-arginine and L-lysine, vitamin C, chondroitin sulfate, glucosamine, Curcuma longa extracted to obtain curcuminoids, dry Boswellia serrata extracted to obtain acetyl-11-keto-b-boswellic acid (AKBA), and myrrh) 2x day for 1 month, 1x day for 1 month | ESWT | ESWT | Pain (VAS); clinical functional evaluation (VISA-A, UCLA shoulder score, MEPS) | After 60 days: UCLA scores were higher in TG [27] compared to CG (23, p = 0.0002). MEPS was higher in TG compared to CG (p <0.00001). VISA-A scores improved more in TG (+27, +39%) compared to CG (+7, 17%). VAS scores were lower in TG compared to CG for all tendinopathy types (p <0.0001). | Combined treatment of ESWT and oral supplementation leads to a faster recovery and better outcomes of AT, shoulder and LET tendinopathy. |
| Merolla et al. (2015) [35] | RCT | To assess the analgesic effect of a dietary supplement containing Boswellia serrata and Curcuma longa in a population of subjects with full-thickness SSP tendon tear treated arthroscopically | 100 patients who underwent surgical SSP tendon repair (TG: 53.3 ±7.6 y, 54% male; CG: 55.4 ±9.4 y, 56% male) | Two daily sachets for 15 days, 1 sachet Tendisulfur (methyl-sulfonyl-methane, type I and II collagen, glycosaminoglycans, L-arginine, L-lysine, Boswellia serrata dry extract titrated to 30% inacetyl-1 1-keto-B-boswellic acid, Curcuma longa dry extract titrated to 95% curcuminoids) for 45 days | Conventional analgesic therapy | Placebo + conventional analgesic therapy | Overall pain, and pain at night, during activity and at rest (VAS); CMS; shoulder function (SST) | Lower overall and night pain scores in TG compared to CG at week 1 (p = 0.0477, p = 0.0113), but not for other pain scores or subsequent time points (p >0.05). CMS in TG (60.3 ±8.6) was not different from CG (59.3 ±8.8, p = 0.884) after 12 weeks or 24 weeks (71.6 ±8.1 vs. 69.9 ±7.2, p = 0.352). SST in TG (7.7 ±1.8) was not different from CG (6.9 ±2.7, p = 0.523) after 12 weeks or after 24 weeks (8.2 ±1.7 vs. 8.1 ±0.9, p = 0.292) | Tendisulfur alleviated short and partially mid-term pain after SSP tendon repair, while long-term pain was unchanged. |
| Gumina et al. (2012) [34] | RCT | To determine whether the intake of an oral integrator might mitigate shoulder pain and improve repair integrity of RC shoulder tear after arthroscopic repair | 87 RC patients who underwent surgical repair (47-69 y, 48% male) | Two daily sachets Tenosan (arginine-L-alpha-ketoglutarate, methyl-sulfonyl-methane, hydrolyzed type I collagen and bromelain) for 3 months starting from postoperative day 1 | Motion and strengthening exercises | Motion and strengthening exercises | Shoulder pain (VAS); CMS; shoulder function (SST); maximum strength; repair integrity according to Sugaya’s classification (MRI) | After 6 months: Pain decreased more in TG (−6.7) compared to CG (−5.0, p <0.001). After 12 months: no differences between groups in CMS (TG: 21.3 ±4.6, CG: 22.6 ±6.6, p = 0.329) and SST (TG: 6.9 ±1.4, CG: 7.0 ±1.9, p = 0.072). The groups were different in terms of repair type (I, II, III) (p = 0.045). | Use of the supplement for 3 months after RC repair decreases postoperative shoulder pain and leads to slight improvement in repair integrity. |
| Notarnicola et al. (2012) [38] | RCT | To assess the clinical efficacy and perfusion effects of oral dietary supplements in association with ESWT for insertional AT tendinopathy | 64 insertional AT tendinopathy patients (55.8 ±13.2 y, 53% male) | Two daily sachets Tenosan (500 mg arginine-L-alpha-ketoglutarate, 550 mg methyl-sulfonyl-methane, 300 mg hydrolyzed collagen type I, 125 mg Vinitrox, 50 mg bromelain, 60 mg vitamin C) for 60 days | ESWT | Placebo + ESWT | Pain (VAS); subjective scores of pain and function and objective scores of physical examination (Ankle-Hindfoot Scale); pain and limitations of activity (Roles and Maudsley score) | VAS scores were lower in TG compared to CG after 2 months (3.9 ±3.2 vs. 5.1 ±2.7, p = 0.07) and 6 months (2.9 ±2.3 vs. 2.0 ±1.8, p = 0.04). Values for the Ankle-Hindfoot Scale were higher in TG compared to CG after 2 months (85 ±12.4 vs. 72.1 ±23.1, p = 0.0035) and 6 months (92.4 ±8.5 vs. 76.5 ±21.6, p = 0.0002). Roles and Maudsley scores were lower in TG compared to CG after 2 months (1.7 ±0.9 vs. 2.8 ±0.4, p <0.0001) and 6 months (1.5 ±0.6 vs. 2.3 ± 0.8, p <0.0001). | Dietary supplement plus ESWT can induce better clinical and functional outcome in AT patients. |
| Baar (2019) [45] | Case study | To determine whether a targeted loading and nutritional program could enhance the outcomes of a PT tendinopathy rehabilitation program | 1 professional basketball player (21 y, male) with PT tendinopathy | 15 g gelatine + 225 mg vitamin C twice a week for 18 months (one hour before every PT targeted training session) | Strength-based rehabilitation program | Pre-measurements | Maximal single-leg isometric hamstring strength; isometric leg extension strength; leg press strength; tendon thickness (MRI) | After 18 months: Increased hamstring (196%), leg extension (156%) and leg press (187%) strength. Thickness of proximal end of the tendon decreased by 25%. Thickness at tendon midpoint increased by 10%. | A nutritional intervention combined with a rehabilitation program can improve clinical outcomes in elite athletes |
| Mavrogenis et al. (2004) [37] | RCT | To evaluate the effect of essential fatty acids, antioxidants and physiotherapy on chronic tendon disorder | 31 active recreational athletes with chronic tendon disorder (TG: 31 y, 76% male; CG: 32 y, 86% male) | 8 capsules/day 376 mg eicosapentaenoic acid (EPA), 264 mg docosahexaenoic acid (DHA) and 672 mg gamma-linolenic acid (GLA) + 1 antioxidant-complex tablet 100 µg selenium, 15 mg zinc, 1 mg vitamin A, 2.2 mg vitamin B6, 90 mg vitamin C and 15 mg vitamin E for 32 days | Physiotherapy (therapeutic ultrasound), 16 sessions x 5 min | Placebo + physiotherapy (as TG) | Pain during sporting activity and after an isometric test (VAS); quantification of sports activity | After 32 days: Pain during sporting activity and after an isometric test decreased more in TG (99%, 99%) compared to CG (31%, 37%, p <0.001). Sports activity increased by 53% in TG and 11% in CG. | Essential fatty acids and antioxidants in combination with physiotherapy have beneficial effects in treating chronic tendon disorders. |
| Sandford et al. (2018) [41] | RCT | To compare the effectiveness of long chain omega-3 polyunsaturated fatty acids (PUFAs) as part of the management for people diagnosed with RC-related shoulder pain | 73 patients with RC-related shoulder pain (TG: 52.2 ±12.0 y, 45% male; CG: 52.0 ±16.2 y, 57% male) | 9 daily capsules MaxEPA (170 mg eicosapentaenoic acid, 115 mg docosahexaenoic acid, 2 units/g tocopherols acetate (vitamin E)) for 2 months | Weekly exercise and education groups for 8 weeks | Placebo (with same amount of vitamin E + antioxidants as TG) + weekly exercise and education groups for 8 weeks | Disability (OSS, SPADI); Pain (NRS, SF-36 bodily pain domain); Quality of life (SF-36, Euro QoL 5D-3 L); Function (PSFS); global perception of change; impairment measures (shoulder range of motion, strength). | Improved OSS scores of 25% in both groups, without differences between groups at 2 (−0.1, p = 0.95) and 12 months (−0.3, p = 0.82). SPADI scores differed only at 3 months between TG (25.3 ±21.1) and CG (13.9 ±18.1). Other outcomes improved in both groups without statistically significant differences between groups. | Omega-3 PUFA supplementation may have a modest effect on disability and pain outcomes in patients with RC-related shoulder pain at 3 months, but not over the course of one year. |
| Farup et al. (2014) [42] | Non-randomized controlled study | To investigate the effect of 12 weeks of either maximal eccentric or concentric resistance training combined with either a high-leucine whey protein hydrolyzate + carbohydrate supplement or placebo, on quadriceps muscle and PT hypertrophy | 22 healthy young recreationally active men (23.9 ±0.8 y) | A drink containing 19.5 g high-leucine (14.2%) whey protein hydrolyzate + 19.5 g carbohydrate (glucose) on all training days (33x in 12 weeks) | Eccentric training with one leg, concentric training with the other leg | Placebo (isoenergetic carbohydrate (glucose)) + training (as TG) | PT CSA (MRI); isometric strength (MVC, RFD) | After 12 weeks: Greater increase in PT CSA at proximal level in TG (14.9 ±3.1%) compared to CG (8.1 ±3.2%, p = 0.054). MVC and RFD increased by 15.6 ±3.5% (p <0.001) and 12-63% (p <0.05) without group effects. | Training-induced hypertrophy of the PT was augmented with a high-leucine whey protein hydrolyzate supplement. |
| Saggini et al. (2010) [40] | RCT (two-arm) | To evaluate the efficacy of a specific rehabilitative, therapeutic protocol integrated with administration of a supplement in both conservative rehabilitation treatment and post-surgery, in patients with RC lesions | Arm A: 30 RC lesion patients, treated conservatively (45 ±10 y, 37% male). Arm B: 50 RC lesion patients, treated conservatively (59.5 (30-80) y (female), 58.4 (28-78) y (male), 48% male) | 1 sachet/day 3.5 g Amedial BF (glucosamine sulfate, chondroitin sulfate, hydrolyzed type II collagen, hydrolyzed hyaluronic acid, L-carnitine fumarate) for 1 month (Arm A) for 60 days (Arm B) | Arm A: 3 shock waves + 9 sittings Multi Joint System; Arm B: rehabilitation treatment | Arm A: 3 shock waves + 9 sittings Multi Joint System (CG1) or 3 shock waves (CG2); Arm B: rehabilitation treatment | Arm A: ROM; pain (VAS); Arm B: UCLA (pain, functionality, active frontal flexion, strength in frontal flexion, satisfaction) | Arm A, after 1 month: VAS scores reduced by 45% in TG, 22% in CG1 and 45% in CG2. Flexion, extension, abduction and external rotation increased by 38%, 57%, 47% and 52% in TG, 28%, 40%, 42% and 40% in CG1 and 26%, 23%, 36% and 25% in CG2. Arm B, after 60 days: Higher improvement in TG compared to CG for pain (73% vs. 70%), function (49% vs. 36%), flexion (41% vs. 29%) and strength (39% vs. 30%) scores. Satisfaction was higher in TG (92%) than in CG (84%). | Supplementation of natural substances is a conservative treatment for RC lesions to consider. Quicker functional recovery with post-surgical supplementation. |
| Schneider et al. (2009) [46] | Case series | To identify characteristics associated with bilateral ruptures of the distal biceps tendons | 10 patients with sustained non-simultaneous bilateral distal biceps brachii tendon ruptures, surgically repaired (49.5 (27.7-76.2) y, male) | Nutritional supplements (multivitamins and omega 3 oils) | NA | NA | Disability (DASH) | DASH scores were not significantly related to using nutritional supplements at the time of injury (p = .145) | No correlation found between outcome following surgical treatment and use of nutritional supplements. |
| Szczurko et al. (2009) [28] | RCT | To evaluate the potential for the combined efficacy of a naturopathic approach including acupuncture, dietary advice and hydrolytic enzymes in the treatment of RC tendinitis | 85 Canadian postal employees with RC tendinitis (TG: 50.7 ±8.16 y, 42% male; CG: 50.9 ±7.86 y, 40% male) | 6 tablets/day of Phlogenzym (90 mg bromelain, 48 mg trypsin, 100 mg rutin) + patient-customized dietary counseling, with special emphasis on reducing alcohol consumption and increasing consumption of fish, berries, fruits, vegetables, nuts, and whole grains for 12 weeks | Acupuncture | Placebo + physical exercise | Disability (SPADI); health-related QoL (SF-36); pain over the last week (VAS); patient experiences (MYMOP); flexion, extension, abduction, adduction, internal rotation and external rotation of affected shoulder | After 12 weeks: SPADI scores improved more in TG (54.5%) compared to CG (18%, p <0.0001). TG also showed superiority in SF-36, VAS, MYMOP scores and range of motion. | Naturopathic treatments including dietary changes, acupuncture and Phlogenzym have a significant effect on decreasing RC tendinitis symptoms. |
AT, Achilles tendon; CG, control group; CMS, Constant-Murley score; CSA, cross-sectional area; DASH, Disabilities of Arm, Shoulder, and Hand; ESWT, Extracorporeal Shock Wave Therapy; LET, lateral epicondyle tendon; MEPS, Mayo Elbow Performance Score; MMYOP, Measure Yourself Medical Outcomes Profile; MRI, magnetic resonance imaging; MVC, maximal voluntary contraction; NRS, Numerical Rating Scale; OSS, Oxford Shoulder Score; PRTEE, Patient-rated Tennis Elbow Evaluation; PSFS, Patient-Specific Functional Scale; PT, patellar tendon; RC, rotator cuff; RCT, randomized controlled trial; RFD, rate of force development; SF-36, Short-Form Health Survey; SPADI, Shoulder Pain and Disability Index; SSP, supraspinatus; SST, Simple Shoulder Test; TG, treatment group; RC, rotator cuff; VAS, Visual Analogue Scale; VISA-A, Victorian Institute of Sports Assessment – Achilles questionnaire; VISA-P, Victorian Institute of Sports Assessment – Patellar questionnaire; USI, ultrasound imaging.