Department of Physiology, Eberhard-Karls-University of Tübingen, Tübingen, Germany,
Department of Physiology, Eberhard-Karls-University of Tübingen, Tübingen, Germany.
Neurosignals. 2020 Dec 31;28(1):14-24. doi: 10.33594/000000321.
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 Ca absorption, low fat milk is particularly effective. Calcium and phosphate uptake inhibit the formation of 1,25(OH)D (1,25-dihydroxy-vitamin D3 = calcitriol), the active form of vitamin D. Calcium inhibits 1,25(OH)D production in part by suppressing the release of parathyroid hormone, a powerful stimulator of 1,25(OH)D formation. Phosphate excess stimulates the release of fibroblast growth factor FGF23, which suppresses 1,25(OH)D formation, an effect requiring Klotho. 1,25(OH)D 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)D and excessive 1,25(OH)D formation have profound effects on several types of behavior, such as explorative behavior, anxiety, grooming and social behavior. 1,25(OH)D is produced in human brain and influences the function of various structures including substantia nigra. In neurons 1,25(OH)D suppresses oxidative stress, inhibits inflammation and stimulates neurotrophin formation thus providing neuroprotection. As a result, 1,25(OH)D 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)D in the pathophysiology of Parkinson's disease and its sensitivity to milk consumption.
乳制品的消费，特别是低脂牛奶的消费，已被证明与帕金森病的发生有关。这种关联并不一定反映了牛奶摄入在帕金森病发展中的病理生理作用。然而，本综述讨论了一种可能的机制，该机制可能介导了牛奶消费对帕金森病的影响。有人认为，牛奶在一定程度上是为了支持哺乳期后代的骨骼矿化而定制的，因此富含钙和磷酸盐。因此，牛奶的摄入有望增强肠道钙磷的吸收。由于与脂肪酸结合会阻碍钙的吸收，低脂牛奶尤其有效。钙和磷酸盐的吸收会抑制 1,25(OH)D（1,25-二羟基维生素 D3=骨化三醇）的形成，维生素 D 的活性形式。钙通过抑制甲状旁腺激素的释放部分抑制 1,25(OH)D 的产生，甲状旁腺激素是 1,25(OH)D 形成的有力刺激物。磷酸盐过多会刺激成纤维细胞生长因子 FGF23 的释放，FGF23 会抑制 1,25(OH)D 的形成，这种作用需要 Klotho。1,25(OH)D 是矿物质代谢的主要调节剂，但具有明显与矿物质代谢无关的强大作用，包括抑制炎症和影响多种脑功能。在小鼠中，缺乏 1,25(OH)D 和过多的 1,25(OH)D 形成对几种类型的行为有深远影响，如探索行为、焦虑、梳理和社交行为。1,25(OH)D 在人脑内产生，并影响包括黑质在内的各种结构的功能。在神经元中，1,25(OH)D 抑制氧化应激、抑制炎症并刺激神经营养因子的形成，从而提供神经保护。因此，1,25(OH)D 被认为有利于影响帕金森病的临床病程。总之，从理论上讲，牛奶的消耗可能会加速帕金森病神经元功能的下降。然而，需要进行大量额外的实验来确定 1,25(OH)D 在帕金森病的病理生理学及其对牛奶消耗的敏感性中的潜在因果作用。
