Evidence regarding the associations of pyridoxal 5'-phosphate level in plasma and dietary intake of vitamin B6 with depression risk is scarce. Accordingly, we investigated the aforementioned associations in US adults. This is a cross-sectional study that included data from two independent samples of 12,716 and 11,967 individuals (aged ≥20years) participating in the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2010. The associations of the pyridoxal 5'-phosphate level in plasma and dietary intake of vitamin B6 with depression risk were examined through multivariable logistic regression. In addition, we determined dose-response associations by fitting restricted cubic splines to the data. In the multivariable model, the highest quarter of dietary intake of vitamin B6 was associated with a significantly lower risk of depression compared to the lowest quarter (OR=0.63, 95% CI: 0.50, 0.79, p< 0.001). Similarly, the highest quartile of plasma PLP levels was linked to a reduced risk of depression compared to the lowest quartile (OR=0.76, 95% CI: 0.62, 0.93, p<0.01). With increasing quartiles of dietary intake of vitamin B6 and plasma PLP levels, the risk of depression also decreased accordingly (all p for trend < 0.01). Furthermore, the correlation analysis revealed that for every 1-SD increase in the level of plasma lutein+zeaxanthin and dietary intake of vitamin B6, the risk of depression showed a decreasing trend (all p<0.01). The interaction test results indicated that the dietary consumption of vitamin B6 did not significantly interact with any of the stratification factors (all p for interaction >0.05). Moreover, no significant interaction was found between the amount of plasma PLP and any hierarchical factors (all p for interaction >0.05), except for gender-based subgroup analysis (p for interaction >0.05). The dose-response relationship results showed a linear decrease trend in the relationship between dietary vitamin B6 intake and plasma pyridoxal 5'-phosphate with the risk of depression. Plasma PLP levels and dietary vitamin B6 intake in the highest quartiles are associated with a lower risk of depression. These findings support the promotion of a balanced diet rich in vitamin B6. However, future randomized controlled trials are necessary to confirm the effects of vitamin B6 supplementation on depression risk. We should aim for a healthy and balanced diet in terms of nutritional supplementation.
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