2.1. Fat and Obesity

Obesity continues to increase rapidly in the United States [1] and it is well established that obesity can increase the risk of Parkinson’s disease and decrease life expectancy. A study has proved that high skinfold thickness in midlife was associated with Parkinson’s disease [2]. And another study found that obesity in middle age increases the risk of future dementia independently of comorbid conditions. Perhaps adiposity works together with other risk factors to increase neurodegenerative disease [3]. In addition, some evidence shows that body mass index is associated with a risk of Parkinson’s disease and the effect is graded and independent of other risk factors [4].

In an animal model of Parkinson’s disease, high fat diet may lower the threshold for developing Parkinson’s disease through affecting glucose transport and decreasing phosphorylation of HSP27 and degradation of IκBα in the nigrostriatal system, at least following dopamine-specific toxin exposure [5, 6]. Moreover, increasing inflammatory signaling, adipokine levels, oxidative or nitrosative stress, mitochondrial dysfunction, and lipid metabolism have all been shown to occur with high fat feeding [7–9].

2.2. Glucose, Hyperglycemia, Insulin Resistance, and Diabetes

High glucose induced cell death is sustained by oxidative, nitrosative stress and mitochondrial superoxide generation through cleavage of the caspase 3 to regulate the apoptotic pathway [10–14]. In aging, hyperglycemia is also associated with Parkinson’s disease through damage in central nervous system, a consequence of long-term exposure to glucose [15, 16]. Indeed, epidemiologic studies have implicated that prior type 2 diabetes is also the risk factor of developing Parkinson’s disease [17]. Although, in different regions, the Parkinson’s disease patients’ brain exhibits similar cellular and functional changes with signs of increased oxidative stress, reduced mitochondrial function, reduced glucose uptake, and increased peroxidation of cellular membranes [18].

2.3. Hypertension

Many studies have been carried out on this topic: whether hypertension is the risk factor for Parkinson’s disease. Much work, both theoretical and practical, has been reported recently in this field that hypertension is less frequent in Parkinson’s disease patient than general population and others show that there is no difference between Parkinson’s disease patients and healthy people [19, 20]. Nonetheless, a large prospective study suggested that Parkinson’s disease risk is not significantly related to history of hypertension (RR = 0.96; 95% CI = 0.80 to 1.15) [21]. Although a lot of effort is being spent on proving the relation between Parkinson’s disease and hypertension, the surely inerrable conclusion has yet to be reached.

2.4. Hyperhomocysteinemia and Endothelial Dysfunction

Hyperhomocysteinemia, a risk factor for endothelial dysfunction [22], has been involved in the pathophysiology of neurodegenerative disorders such as Alzheimer disease and Parkinson disease [23]. And homocysteine leads to endothelial dysfunction that hydrogen peroxide plays a critical role in mediating cell injury in vitro [24]. Large increases in cellular oxidative stress and inflammations occurred in response to high homocysteine that induced toxicity by decreased NAD+ [25–29]. In comparison, recent studies have also demonstrated that homocysteine is largely involved in antioxidant and reductive cellular biochemistry [30].

3.1. Plant Extract

Previous works, such as Bournival et al. [41, 47], Bureau et al. [48], and Ge´linas and Martinoli [49], reported that several plant extracts are powerful in neuroprotective activity of dopaminergic neurons against the oxidative burden provoked by administration of the potent parkinsonian toxin MPP+ in vitro or 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in vivo. The plant extract, which contains resveratrol and quercetin and sesamin [41, 47, 48], fermented papaya preparation [50], cinnamon polyphenols [51], and estradiol and phytoestrogens [49], was inhibited by oxidative stress that damages the normal physiological function of cellular organelle by regulating caspase 3, DNA fragment, estrogen receptors, cytokines, Akt, p38, MAPK, and ERK pathway.

An additional research which focuses on the extremely important antioxidant properties of cannabinoids, extract of hemp plant, may contribute to the neuroprotective effect in Parkinson’s disease through banding the canonical cannabinoid CB1 and CB2 receptors [52–55].

3.2. Uric Acid

A large community-based survey indicated that the associated higher serum uric acid was able to decrease the prevalence of Parkinson’s disease [56]. Similarly, it has been observed that UA levels in the serum of patients with Parkinson’s disease are lower than in controls and that increased levels of UA are associated with a lower risk of Parkinson’s disease [56–59]. Evidence was also proved that physiological concentration of uric acid would exert antioxidant effects, attenuating neuronal lesions caused by oxygen radicals, generated during an acute ischemic stroke and in cases of Parkinson’s disease [60]. It had been established that the protective mechanisms of uric acid may be through regulating the DNA damage pathway [60–62]. The recent study from Massachusetts General Hospital found that the urate’s ability to protect neurons requires the presence of astrocytes in Parkinson’s disease unexpectedly [63].

3.3. Molecular Hydrogen

Hydrogen has great potential for improving oxidative stress-related diseases by inhaling H2 gas, injecting saline with dissolved H2, or drinking water with dissolved H2 [64]. Recent basic and clinical research has revealed that hydrogen is an important physiological regulatory factor with antioxidant, anti-inflammatory, and antiapoptotic protective effects on cells and organs [65]. Meanwhile, a large number of studies report that molecular hydrogen acts as a novel antioxidant and prevents or ameliorates diseases associated with oxidative stress in animal experiments [66–77] and clinical tests [78–81]. Molecular hydrogen improves obesity and diabetes by inducing hepatic FGF21 and stimulating fatty acid and glucose expenditure in mice [64]. Another research reported that molecular hydrogen is protective against 6-hydroxydopamine-induced nigrostriatal degeneration in a rat model of Parkinson’s disease [75]. However, little is known about the mechanism that H2 acts on to prevent oxidative stress in Parkinson’s disease.

3.4. Coffee and Caffeine Intake

Higher coffee and caffeine intake is associated with a significantly lower incidence of Parkinson’s disease as discussed by Ross et al. [82]. Caffeine, a well-known central nervous system stimulant, inhibits the dopamine neurotransmission through adenosine receptor antagonism and mobilizes of intracellular calcium [83–85]. In addition, caffeine was regarded as an antioxidant against all the three reactive oxygen species, hydroxyl radical, peroxyl radical, and singlet oxygen [86].

3.5. Vitamin D and Vitamin E

Individuals with higher serum vitamin D concentrations showed a reduced risk of Parkinson disease. The relative risk between the highest and lowest quartiles was 0.33 (95% confidence interval, 0.14–0.80) [87]. Even so, the exact mechanisms by which vitamin D may protect against Parkinson disease are not fully understood [87]. High vitamin D status, however, has been shown to exhibit neuroprotective effects through antioxidative mechanisms, neuronal calcium regulation, immunomodulation, enhanced nerve conduction, and detoxification mechanisms [88–90]. Furthermore, the central issue in all these studies is to declare that high intake of dietary vitamin E [91, 92] may protect against the occurrence of PD, but vitamin C or β carotene does not [92]. And the protective influence for Parkinson’s disease was seen with both moderate intake (relative risk: 0.81; 95% CI: 0.67–0.98) and high intake (0.78, 0.57–1.06) of vitamin E [92, 93].

This study was supported by NSFC (nos. 31071208 and 31371384).