The Putative Role of 1,25(OH)2D3 in the Association of Milk Consumption and Parkinson's Disease.

The consumption of dairy products, particularly of low fat milk, has been shown to be associated with the occurrence of Parkinson's disease. This association does not necessarily reflect a pathophysiological role of milk intake in the development of Parkinson's disease. Nevertheless, the present review discusses a potential mechanism possibly mediating an effect of milk consumption on Parkinson's disease. The case is made that milk is tailored in part to support bone mineralization of the suckling offspring and is thus rich in calcium and phosphate. Milk intake is thus expected to enhance intestinal calcium phosphate uptake. As binding to fatty acids impedes Ca²⁺ absorption, low fat milk is particularly effective. Calcium and phosphate uptake inhibit the formation of 1,25(OH)₂D₃ (1,25-dihydroxy-vitamin D3 = calcitriol), the active form of vitamin D. Calcium inhibits 1,25(OH)₂D₃ production in part by suppressing the release of parathyroid hormone, a powerful stimulator of 1,25(OH)₂D₃ formation. Phosphate excess stimulates the release of fibroblast growth factor FGF23, which suppresses 1,25(OH)₂D₃ formation, an effect requiring Klotho. 1,25(OH)₂D₃ is a main regulator of mineral metabolism, but has powerful effects apparently unrelated to mineral metabolism, including suppression of inflammation and influence of multiple brain functions. In mice, lack of 1,25(OH)₂D₃ and excessive 1,25(OH)₂D₃ formation have profound effects on several types of behavior, such as explorative behavior, anxiety, grooming and social behavior. 1,25(OH)₂D₃ is produced in human brain and influences the function of various structures including substantia nigra. In neurons 1,25(OH)₂D₃ suppresses oxidative stress, inhibits inflammation and stimulates neurotrophin formation thus providing neuroprotection. As a result, 1,25(OH)₂D₃ is considered to favorably influence the clinical course of Parkinson's disease. In conclusion, consumption of milk could in theory accelerate the downhill course of neuronal function in Parkinson's disease. However, substantial additional experimentation is required to define the putative causal role of 1,25(OH)₂D₃ in the pathophysiology of Parkinson's disease and its sensitivity to milk consumption.