In this meta-analysis, we investigated the association between β-carotene intake and the risk of fractures. A total of 9 studies with 190,545 men and women were included. We found that β-carotene was associated with a 12% reduction in the risk of fracture. There also, a higher intake of β-carotene was associated with a lower risk of hip fracture. The findings of our meta-analysis suggested that higher dietary intake of β-carotene may have a favorable role in the protection of fracture risk.
To our knowledge, this is the first meta-analysis that synthesized the relationship between beta-carotene intakes from only dietary sources with the risk of fracture. Our findings were consistent with the results of a previous meta-analysis published by Xu et al. 11, who found that a high intake of dietary β-carotene was significantly decreased the risk of hip fracture by 28% (OR 0.72; 95% CI: 0.54–0.95). However, our findings were contradicted with recent meta-analysis 38, which revealed that higher β-carotene intake was weakly associated with the increased risk of total fracture (RR 1.07; 95% CI: 0.97, 1.17). The difference can be explained by a limited number of studies included for both total fracture and hip fracture risk by Zhang et al.38, in their studies all sources of beta-carotene such as serum, plasma, and dietary intake were analyzed together.
In the current meta-analysis, we also found that an inverse association between beta-carotene intake and risk of fracture in cohort and case-control study; this may strength the robustness of our results. Regarding gender, we found that a lower risk of fracture for males compared to females among high (vs low) beta-carotene intakes. This may be a plausible result because due to hormone differences across gender, while this extends the results of the previous two meta-analyses 11,38 that reported a null association between beta-carotene intakes and fracture risk in females rather than in males. In a meta-analysis, the individual studies were performed in different geographical regions and the population also shared different genetic backgrounds, different dietary habits, and lifestyles, thus why it is no surprise to found inconsistent results across the continents.
The underlying mechanism for the association between beta-carotene intakes with lower incidence of fracture risk remains unclear. However, some probable biological mechanisms have been proposed: a sufficient intake of vitamin A including beta-carotene is essential for normal physiological activities 39 by affecting the growth hormone axis 40,41. Although, some evidence from animal studies suggest that antioxidant β-carotene contributes as a body’s defense against reactive oxygen species 42. Thus, oxidative stress is thought to play an important role in the development of several chronic diseases including osteoporotic fracture. Therefore, antioxidant beta-carotene may have a beneficial effect against oxidative stress related to chronic diseases or osteoporosis. Indeed, β-carotene antioxidant seems a reactive oxygen species that enhance osteoclastogenesis and reduce osteoblast apoptosis by stabilizing the β-catenin signaling pathway, this leads to a decrease in bone resorption 43−45. In addition, carotenoids may interfere with growth factor receptor signaling by regulating IGF-1/IGFBP3, which are associated with cognitive function 46, and impaired cognitive function is a known risk factor for falls and hip fracture 47.
There are some limitations in our meta-analysis. First, the beta-carotene intake consumption level is not consistent in most of the individual studies. In addition, the fruit and vegetable consumption patterns among countries are quite different; this might influence the reliability of our results. Second, the methods of beta-carotene intake assessment across studies are quite different, some of them used the standard form of food frequency questionnaire and the other not, and this also plays a great role in diverging our results. Third, the extracted relative risk was adjusted for multiple variables, and all included studies made an attempt to control for the confounding variables. However, some of the potential confounding factors (i.e., age, physical activity, supplementary carotenoid intake, smoking, and vitamins) have not been taken into account, which contributes to heterogeneity and sparse finding within individual’s studies. Lastly, our analysis was based on observational studies, in which randomized control trials might be needed to confirm our findings.