PD.JPGGood for PD: Vitamin A, Carotenoid

Carotenoids (alpha- and beta-carotene) are precursors of vitamin A in human. Egg yolks, organ meats, and milk are rich sources of vitamin A, while carotenoid rich diet includes carrots, sweet potatoes, and peaches, as well as other fruits and vegetables. Previously, vitamin A and beta-carotene were shown to inhibit alpha-synuclein fibril formation and destabilize formed fibrils in dose-dependent manner in vitro [6]. While several human studies did not identify a link with vitamin A and PD [7–10], Miyake et al. found a protective effect of beta-carotene in PD (Parkinson’s Disease) in a Japanese population

Good for PD: Vitamin B

Vitamin B complexes are found in meat, fish, cereal, dairy products, and some vegetables (i.e., potato) and fruits (i.e., banana). Although there are several types of vitamin B, the focus of this discussion is on vitamin B2 (riboflavin), B6 (pyridoxine), B9 (folate), and B12 (cobalamin).

Homocysteine is a metabolite of methionine that is essential for the DNA synthesis and has been shown to exert adverse effects of mitochondrial alterations. Vitamins B6, B9, and B12 indirectly regulate level of homocysteine [13, 14]. Folate-deficient diets result in increases in homocysteine [15]. High homocysteine level damages DNA and depletes energy reserves, subsequently inducing neuron apoptosis [16, 17].

In one study on the effects of folate deficiency, two-month-old C57B1/6 mice were subjected to a diet lacking folate or control diet containing 2 mg folate/kg of food for two months followed by intraperitoneal (ip) MPTP injection at subtoxic doses or saline [15]. Mice fed with control diet did not exhibit differences in motor activity between MPTP or saline groups. Similarly, motor activity in folate-deficient mice was not significantly different from mice with control diet. However, MPTP-induced motor activity impairment and loss of nigral dopaminergic neurons were exacerbated in folate-deficient mice. Further, vitamin B2 deficiency in rodents was shown to decrease circulating iron levels and increase iron turnover, resulting in disturbance of iron metabolism, which is one of the well-established hypotheses in PD [18, 19]. Therefore, in animal models, vitamin B deficiency appears to exacerbate neurotoxicant-induced motor deficits and pathology.

Epidemiological studies presented variable findings. Higher intake of vitamins B6, B9, and B12, but not B2, was associated with lower risk of PD in a German populatio

Good for PD: Saltwater fish, Vit D

Major vitamin D rich foods are fortified milk, liver, and saltwater fish [28]. Vitamin D is metabolized into its active form, 1,25-dihydroxyvitamin D (1,25-(OH)2 Vit D or calcitriol) in the cytoplasm of neurons and glial cells [29, 30]. The vitamin D receptor (VDR) is activated by binding to calcitriol which increases calcium uptake in bones.

Although a protective role of vitamin D against PD is not well established, there are number of laboratory studies suggesting that exogenous administration may be protective: MPP+ toxicity in primary mesencephalic dopaminergic neurons was decreased by low doses of vitamin D (1–100 nM) in vitro [31]. Pretreatment of rats with calcitriol prior to 6-hydroxydopamine (6-OHDA) administration attenuated neuronal toxicity in vivo [32]. It is worth noting that significantly lower bone mass index and vitamin D deficiency were detected in PD patients

Good for PD: Vit E in nuts and vegetable oils

Vitamin E is found at high levels in vegetable oils, nuts, and whole-grain products. It has strong antioxidant capacity. Pretreatment of neurons with vitamin E alleviated MPTP-induced dopaminergic neuron toxicity in vitro [42]. Further, vitamin E-deficient mice exhibit heightened sensitivity to MPTP

Good for PD: Berries and citrus fruits

Flavonoids are the most common groups of polyphenols in human diet [52]. Many plant-based foods and beverages are rich in flavonoids, such as berry fruits and citrus fruits [53]. Flavonoids have high antioxidant capacity [54]; they have been shown to modulate oxidative-related enzymes and regulate mitochondrial function in neurons [52, 55]. These findings point to a potential protective role of flavonoids in PD.

Nobiletin, a flavonoid that is found in citrus fruit peel, was found to improve MPTP-induced motor and cognitive deficits in mice [56]. Although nobiletin administration (50 mg/kg) via ip injections for 2 weeks did not prevent loss of dopaminergic neurons in the midbrain of MPTP-induced PD model mice, motor deficits were alleviated significantly compared to mice that did not receive the injections.

A potential neuroprotective role of flavonoids in PD was recently examined using anthocyanins and proanthocyanidins. Strathearn et al. reported that the treatment of primary midbrain cultures with blueberry, grape seed, hibiscus, blackburrant, or Chinese mulberry extracts rescued rotenone-induced loss of dopaminergic neurons [57]. Here, blueberry and grape seed extracts were shown to rescue disruption of mitochondrial respiration, suggesting that the protective effect might be mediated via enhancement of mitochondrial function.

Good for PD: Beer

A meta-analysis was performed recently to investigate association of alcohol consumption with PD risk [178]. Meta-analysis of 32 studies including 9,994 cases among 677,550 subjects found a significant association of beer with decreased risk of PD (RR 0.59, 95% CI 0.39–0.90), but not with wine and liquor.

Good PD, good fat: MUFA and PUFA

Dairy products and meat are rich in saturated acids. Monounsaturated fatty acids (MUFAs) are found in sunflower oil, peanut oil, and olive oil, which are commonly used in Mediterranean diet. There are different types of polyunsaturated fatty acid (PUFA): vegetable oils that contain omega-6 and omega-3 is abundant in fish and marine products.  MUFAs and PUFAs have been shown to have anti-inflammatory and neuroprotective properties, by reducing the oxidative stress and inhibiting neuronal apoptosis [105–110]. PUFAs help regulation of dopamine activity in basal ganglia, controlling movement [111, 112]. Omega-3 fatty acid is crucial for neurogenesis in olfactory bulb and myelination by oligodendrocytes, which has been shown to be significantly affected in PD [113]. Moreover, omega-3 deficiency causes alteration of the dopamine mesocorticolimbic pathway, which is anatomically relevant to PD [114, 115]. Zimmer et al. reported that dopamine levels in cerebral areas and D2 receptor mRNA expression in frontal cortex were lower in rat fed with omega-3 deficient rats.

Good for PD: Dietary restriction

Dietary restriction has been repeatedly shown to prolong lifespan and decrease age-related diseases [61–63]. Low calorie intake attenuated age-related decline in dopamine signaling and increased resistance of nigral neurons to excitotoxic or oxidative stress [64, 65]. Dietary restriction in mice enhanced expression of neurotrophic factor, especially brain-derived neurotrophic factor (BDNF), in hippocampus, resulting in an excitoprotective effect, preventing excitotoxicity which is caused by neurotransmitters such as glutamate [66–68]. Protein chaperones, such as hsp70, that help cells to resist various stressors, were also induced in vivo

Good for PD: Magnesium

Dopaminergic neurodegeneration in the substantia nigra was more evident in magnesium-deficient rats than calcium and magnesium deficient rats. The same study also suggested that magnesium deficiency is toxic to the dopaminergic system only if occurring in fetal and newborn periods of life, suggesting the importance of magnesium in early development of dopaminergic neurons. The synergistic effect of calcium and magnesium was confirmed in a mouse model as well. Mice fed with low calcium/magnesium-deficient diet displayed cataleptic behavior, which was inhibited by treatment with L-DOPA in a dose-dependent manner, and these mice had significantly lower TH activity in substantia nigra [169]. Since magnesium was found to decrease NMDA activity [170], hypofunction of dopamine might be due to supersensitivity of NMDA receptors enhanced by lack of magnesium.

In humans, magnesium showed a protective effect against PD in a Japanese population (OR 0.33, 95% CI 0.17–0.73 for highest quartile >312.9 mg/day; P = 0.002) [11]. A relatively small-sized case control study in Sweden reported that lower dietary magnesium intake was associated with lower brief smell identification test score (P = 0.012), which is an olfactory function test in which PD patients generally perform less efficiently than healthy controls.

60% Calcium, 40% Magnesium, Vit C and D

Good for PD: Women and Caffeine (with no estrogen therapy):

The relation between caffeine intake, estrogen use, and PD is difficult to explain and requires more careful consideration of case-control study design with discrepancies among hormone usage when dealing with female populations.

Toxic: Manganese, iron, toxins

Occupational manganese exposure at chronic and high levels in welders, miners, and smelters was associated with increased incidence of Parkinsonian-like symptoms.

The iron hypothesis in PD suggests that Fenton’s reaction induces production of hydroxyl radical and higher oxidation states of iron [138–140]. Hydroxyl radicals are toxic to neurons by inducing lipid peroxidation and subsequent cell death. Lewy bodies in PD brains are iron-positive and iron has been shown to induce alpha-synuclein accumulation [141, 142]. Reactive microglia, a common pathological finding in PD brains, contain high levels of iron

Toxic: metals

Epidemiologic studies have found increased risk of PD associated with exposure to environmental toxicants such as pesticides, solvents, metals, and other pollutants, and many of these compounds recapitulate PD pathology in animal models.