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

Abstract

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.

• Authors: Florian Lang, Ke Ma, Christina B Leibrock, Madhuri S Salker, Yogesh Singh
• Journal: Neuro-Signals (Neurosignals) Vol. 28 Issue 1 Pg. 14-24 (12 31 2020) ISSN: 1424-8638 [Electronic] Switzerland
• PMID: 33382545 (Publication Type: Journal Article, Review)
• Copyright: © Copyright by the Author(s). Published by Cell Physiol Biochem Press.

Chemical References

• FGF23 protein, human
• Fgf23 protein, mouse
• Neuroprotective Agents
• dihydroxy-vitamin D3
• Vitamin D
• Fibroblast Growth Factor-23
• Calcium

Topics

• Animals
• Brain (drug effects, metabolism)
• Calcium (administration & dosage)
• Fibroblast Growth Factor-23
• Humans
• Inflammation (metabolism, pathology, prevention & control)
• Milk
• Neuroprotective Agents (administration & dosage)
• Parkinson Disease (epidemiology, metabolism, pathology, prevention & control)
• Vitamin D (administration & dosage, analogs & derivatives)