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. 2021 Oct 20;12:20406223211047026. doi: 10.1177/20406223211047026

Table 2.

Complete list of human studies involving vitamin C and osteoarthritis used for analysis and commentary.

Human studies
Title of study Study type Patient population Significant findings Citation
Effect of antioxidants on knee cartilage and bone in healthy, middle-aged subjects: a cross-sectional study Prospective cohort 297 Australians, 99% of which were aged 40–69 years Tibial bone plateau area was smaller, fewer bone marrow lesions when supplementing AA Wang et al. 50
The effects of vitamin C supplementation on incident and progressive knee osteoarthritis: a longitudinal study Longitudinal study 1023 males and females aged 40 + years 11% less likely to develop OA when taking vitamin C supplement compared to control
-No effect on pre-existing OA progression
Peregoy and Wilder 40
High plasma levels of vitamin C and E are associated with incident radiographic knee OA Nested case-control 3026 males and females aged 50–79 years or at high risk of knee OA Taking higher amounts than the RDA of both vitamin C and E may be associated with more OA changes Chaganti et al. 53
Do antioxidant micronutrients protect against the development and progression of knee OA Retrospective cohort 640 males and females High dietary intake of AA was associated with reduced structural progression of OA. No effect on incidence McAlindon et al. 54
Associations between dietary antioxidants intake and radiographic knee OA Cross sectional study 4685 subjects over 40 years & undergoing weight bearing bilateral AP radiography of knee More radiological evidence of knee OA in those supplementing with vitamin C Li et al. 55
Synergistic chondroprotective effect of alpha-tocopherol, ascorbic acid, and
Selenium . . .
In vitro analysis Human chondrosarcoma cell lines (SW1353) induced into an inflammatory state Adding additional antioxidant augments vitamin C’s ability to slow progression of OA in an vitro analysis. Graeser et al. 56
Ascorbic acid provides protection for
human chondrocytes against oxidative stress.
In vitro analysis Human C28/I2 chondrocyte cell line treated with H2O2 AA reduced activity of pro-inflammatory markers, decreased apoptosis, and stimulated production of collagen and proteoglycan Chang et al. 57
Comparative effects of vitamin C on the effects of local anesthetics ropivacaine, bupivacaine, and lidocaine on human chondrocytes. In vitro analysis Human chondrocytes isolated and exposed to local anesthetics Adding vitamin C to intra-articular injections of local anesthetic reduces the chondrotoxicity seen with using the anesthetic injection alone Tian and Li 58
Relationship of sociodemographic and anthropometric characteristics and nutrient and food intakes with osteoarthritis prevalence in elderly subjects with controlled dyslipidemia: a cross-sectional study Cross-sectional study 314 subjects aged ⩾ 65 years old who were diagnosed with dyslipidemia Average vitamin C intake was positively correlated with risk of developing osteoarthritis Jeong et al. 51
Ascorbic acid attenuates Senescence of Human osteoarthritic osteoblasts Control trial Bone chips from sclerotic and non-sclerotic regions of subchondral bone of human OA joints Bone fragments grown in AA showed a negative correlation with senescent cells and a decreased expression of ROS. Supplementation with AA was found to help expand subchondral bone osteoblast in-vitro Burger et al. 59
Dietary antioxidants, non-enzymatic antioxidant capacity and the risk of osteoarthritis in the Swedish National march Cohort Prospective cohort study 29,406 males and females ⩾ 40 years old were included No association between vitamin C intake and risk of developing OA was noted Veen et al. 60
Associations Between Vitamins C and D Intake and Cartilage Composition and Knee Joint Morphology Over 4 Years: Data From the Osteoarthritis Initiative Longitudinal Study 1785 male and females ⩾ 45 years old with Kellgren/Lawrence knee grades 0–3 The cross-sectional analysis found a beneficial effect of vitamin C on joint degeneration (having inverse associations with cartilage T2 values and WORMS scores), while the longitudinal results showed no significant associations. Joseph et al. 52

AA, Ascorbic Acid; AP, Anteroposterior; OA, osteoarthritis; RDA, Recommended Dietary Allowance; ROS, reactive oxygen species; WORMS, Whole-organ magnetic resonance imaging score.