Dietary Amino Acids Impact LRRK2-Induced Neurodegeneration in Parkinson's Disease Models.

The G2019S mutation in leucine-rich repeat kinase 2 (LRRK2) is a common cause of Parkinson's disease (PD) and results in age-related dopamine neuron loss and locomotor dysfunction in Drosophila melanogaster through an aberrant increase in bulk neuronal protein synthesis. Under nonpathologic conditions, protein synthesis is tightly controlled by metabolic regulation. Whether nutritional and metabolic influences on protein synthesis can modulate the pathogenic effect of LRRK2 on protein synthesis and thereby impact neuronal loss is a key unresolved question. Here, we show that LRRK2 G2019S-induced neurodegeneration is critically dependent on dietary amino acid content in Drosophila studies with both sexes. Low dietary amino acid concentration prevents aberrant protein synthesis and blocks LRRK2 G2019S-mediated neurodegeneration in Drosophila and rat primary neurons. Unexpectedly, a moderately high-amino acid diet also blocks dopamine neuron loss and motor deficits in Drosophila through a separate mechanism involving stress-responsive activation of 5'-AMP-activated protein kinase (AMPK) and neuroprotective induction of autophagy, implicating the importance of protein homeostasis to neuronal viability. At the highest amino acid diet of the range tested, PD-related neurodegeneration occurs in an age-related manner, but is also observed in control strains, suggesting that it is independent of mutant LRRK2 expression. We propose that dietary influences on protein synthesis and autophagy are critical determinants of LRRK2 neurodegeneration, opening up possibilities for future therapeutic intervention.SIGNIFICANCE STATEMENT Parkinson's disease (PD) prevalence is projected to rise as populations continue to age, yet there are no current therapeutic approaches that delay or stop disease progression. A broad role for leucine-rich repeat kinase 2 (LRRK2) mutations in familial and idiopathic PD has emerged. Here, we show that dietary amino acids are important determinants of neurodegeneration in a Drosophila model of LRRK2 PD. Restricting all amino acids effectively suppresses dopaminergic neuron loss and locomotor deficits and is associated with reduced protein synthesis, while moderately high amino acids similarly attenuate these PD-related phenotypes through a stress-responsive induction of 5'-AMP-activated protein kinase and autophagy. These studies suggest that diet plays an important role in the development of PD-related phenotypes linked to LRRK2.

Healthy Effects of Plant Polyphenols: Molecular Mechanisms.

The increasing extension in life expectancy of human beings in developed countries is accompanied by a progressively greater rate of degenerative diseases associated with lifestyle and aging, most of which are still waiting for effective, not merely symptomatic, therapies. Accordingly, at present, the recommendations aimed at reducing the prevalence of these conditions in the population are limited to a safer lifestyle including physical/mental exercise, a reduced caloric intake, and a proper diet in a convivial environment. The claimed health benefits of the Mediterranean and Asian diets have been confirmed in many clinical trials and epidemiological surveys. These diets are characterized by several features, including low meat consumption, the intake of oils instead of fats as lipid sources, moderate amounts of red wine, and significant amounts of fresh fruit and vegetables. In particular, the latter have attracted popular and scientific attention for their content, though in reduced amounts, of a number of molecules increasingly investigated for their healthy properties. Among the latter, plant polyphenols have raised remarkable interest in the scientific community; in fact, several clinical trials have confirmed that many health benefits of the Mediterranean/Asian diets can be traced back to the presence of significant amounts of these molecules, even though, in some cases, contradictory results have been reported, which highlights the need for further investigation. In light of the results of these trials, recent research has sought to provide information on the biochemical, molecular, epigenetic, and cell biology modifications by plant polyphenols in cell, organismal, animal, and human models of cancer, metabolic, and neurodegenerative pathologies, notably Alzheimer's and Parkinson disease. The findings reported in the last decade are starting to help to decipher the complex relations between plant polyphenols and cell homeostatic systems including metabolic and redox equilibrium, proteostasis, and the inflammatory response, establishing an increasingly solid molecular basis for the healthy effects of these molecules. Taken together, the data currently available, though still incomplete, are providing a rationale for the possible use of natural polyphenols, or their molecular scaffolds, as nutraceuticals to contrast aging and to combat many associated pathologies.

Healthspan Enhancement by Olive Polyphenols in C. elegans Wild Type and Parkinson's Models.

Parkinson's disease (PD) is the second most prevalent late-age onset neurodegenerative disorder, affecting 1% of the population after the age of about 60 years old and 4% of those over 80 years old, causing motor impairments and cognitive dysfunction. Increasing evidence indicates that Mediterranean diet (MD) exerts beneficial effects in maintaining health, especially during ageing and by the prevention of neurodegenerative disorders. In this regard, olive oil and its biophenolic constituents like hydroxytyrosol (HT) have received growing attention in the past years. Thus, in the current study we test the health-promoting effects of two hydroxytyrosol preparations, pure HT and Hidrox® (HD), which is hydroxytyrosol in its "natural" environment, in the established invertebrate model organism Caenorhabditis elegans. HD exposure led to much stronger beneficial locomotion effects in wild type worms compared to HT in the same concentration. Consistent to this finding, in OW13 worms, a PD-model characterized by α-synuclein expression in muscles, HD exhibited a significant higher effect on α-synuclein accumulation and swim performance than HT, an effect partly confirmed also in swim assays with the UA44 strain, which features α-synuclein expression in DA-neurons. Interestingly, beneficial effects of HD and HT treatment with similar strength were detected in the lifespan and autofluorescence of wild-type nematodes, in the neuronal health of UA44 worms as well as in the locomotion of rotenone-induced PD-model. Thus, the hypothesis that HD features higher healthspan-promoting abilities than HT was at least partly confirmed. Our study demonstrates that HD polyphenolic extract treatment has the potential to partly prevent or even treat ageing-related neurodegenerative diseases and ageing itself. Future investigations including mammalian models and human clinical trials are needed to uncover the full potential of these olive compounds.

Effects of Ketone Bodies on Brain Metabolism and Function in Neurodegenerative Diseases.

Under normal physiological conditions the brain primarily utilizes glucose for ATP generation. However, in situations where glucose is sparse, e.g., during prolonged fasting, ketone bodies become an important energy source for the brain. The brain's utilization of ketones seems to depend mainly on the concentration in the blood, thus many dietary approaches such as ketogenic diets, ingestion of ketogenic medium-chain fatty acids or exogenous ketones, facilitate significant changes in the brain's metabolism. Therefore, these approaches may ameliorate the energy crisis in neurodegenerative diseases, which are characterized by a deterioration of the brain's glucose metabolism, providing a therapeutic advantage in these diseases. Most clinical studies examining the neuroprotective role of ketone bodies have been conducted in patients with Alzheimer's disease, where brain imaging studies support the notion of enhancing brain energy metabolism with ketones. Likewise, a few studies show modest functional improvements in patients with Parkinson's disease and cognitive benefits in patients with-or at risk of-Alzheimer's disease after ketogenic interventions. Here, we summarize current knowledge on how ketogenic interventions support brain metabolism and discuss the therapeutic role of ketones in neurodegenerative disease, emphasizing clinical data.

The Pathology of Parkinson's Disease and Potential Benefit of Dietary Polyphenols.

Parkinson's disease (PD) is a progressive neurodegenerative disorder that is characterized by a loss of dopaminergic neurons, leading to bradykinesia, rigidity, tremor at rest, and postural instability, as well as non-motor symptoms such as olfactory impairment, pain, autonomic dysfunction, impaired sleep, fatigue, and behavioral changes. The pathogenesis of PD is believed to involve oxidative stress, disruption to mitochondria, alterations to the protein α-synuclein, and neuroinflammatory processes. There is currently no cure for the disease. Polyphenols are secondary metabolites of plants, which have shown benefit in several experimental models of PD. Intake of polyphenols through diet is also associated with lower PD risk in humans. In this review, we provide an overview of the pathology of PD and the data supporting the potential neuroprotective capacity of increased polyphenols in the diet. Evidence suggests that the intake of dietary polyphenols may inhibit neurodegeneration and the progression of PD. Polyphenols appear to have a positive effect on the gut microbiome, which may decrease inflammation that contributes to the disease. Therefore, a diet rich in polyphenols may decrease the symptoms and increase quality of life in PD patients.

Role of green tea catechins in prevention of age-related cognitive decline: Pharmacological targets and clinical perspective.

Over the past decade, a wide range of scientific investigations have been performed to reveal neuropathological aspects of cognitive disorders; however, only limited therapeutic approaches currently exist. The failures of conventional therapeutic options as well as the predicted dramatic rise in the prevalence of cognitive decline in the coming future show the necessity for novel therapeutic agents. Recently, a wide range of research has focused on pharmacological activities of green tea catechins worldwide. Current investigations have clarified mechanistic effects of the catechins in inflammatory cascades, oxidative damages, different cellular transcription as well as transduction pathway in various body systems. It has been demonstrated that green tea polyphenols prevent age-related neurodegeneration through improvement of endogenous antioxidant defense mechanisms, modulation of neural growth factors, attenuation of neuroinflammatory pathway, and regulation of apoptosis. The catechins exhibited beneficial effects in cellular and animal models of neurodegenerative diseases including Alzheimer's disease, MS, and Parkinson's disease. The present review discusses the current pharmacological targets, which can be involved in the treatment of cognitive decline and addresses the action of catechin derivatives elicited from green tea on the multiple neural targets.

Lessons learned from recent clinical trials of ketogenic diet therapies in adults.

PURPOSE OF REVIEW: Although ketogenic diet therapies (KDTs) were first developed as a treatment for patients with epilepsy, their potential efficacy for a broader number of neurologic and nonneurologic disorders and conditions has been explored over the last 10-20 years. The most recent clinical trials of KDTs in adults have highlighted common methodological aspects that can either facilitate or thwart appropriate risk/benefit analyses, comparisons across studies, and reproducibility of findings in future studies. RECENT FINDINGS: Recent evidence suggests that KDTs not only improve seizure control, but also improve other neurologic conditions, including nonmotor Parkinson's disease symptoms. Therapies targeting nutritional ketosis without comprehensive diet modification improve cognition and cerebral blood flow in Alzheimer's disease patients. KDTs lower hemoglobin A1c levels and diabetes medication use in patients with Type 2 diabetes and mixed results have been observed when used for performance enhancement in athletes and healthy volunteers. SUMMARY: Clinical studies of KDTs show promise for a variety of clinical indications. Future studies should factor in high potential participant attrition rates and utilize consistent and standard reporting of diet type(s), compliance measures, and side-effects to enable the reproducibility and generalizability of study outcomes.

Dietary Macronutrient Management to Treat Mitochondrial Dysfunction in Parkinson's Disease.

Mitochondrial dysfunction has been demonstrated to play an important role in the pathogenesis of Parkinson's disease (PD). The products of several PD-associated genes, including alpha-synuclein, parkin, pink1, protein deglycase DJ-1, and leucine rich repeat kinase 2, have important roles in mitochondrial biology. Thus, modifying mitochondrial function could be a potential therapeutic strategy for PD. Dietary management can alter mitochondrial function as shifts in dietary macronutrients and their ratios in food can alter mitochondrial energy metabolism, morphology and dynamics. Our studies have established that a low protein to carbohydrate (P:C) ratio can increase lifespan, motor ability and mitochondrial function in a parkin mutant Drosophila model of PD. In this review, we describe mitochondrial dysfunction in PD patients and models, and dietary macronutrient management strategies to reverse it. We focus on the effects of protein, carbohydrate, fatty acids, and their dietary ratios. In addition, we propose potential mechanisms that can improve mitochondrial function and thus reverse or delay the onset of PD.

Probiotics for Parkinson's Disease.

Parkinson's disease (PD) is a complex neurological disorder classically characterized by impairments in motor system function associated with loss of dopaminergic neurons in the substantia nigra. After almost 200 years since the first description of PD by James Parkinson, unraveling the complexity of PD continues to evolve. It is now recognized that an interplay between genetic and environmental factors influences a diverse range of cellular processes, reflecting on other clinical features including non-motor symptoms. This has consequently highlighted the extensive value of early clinical diagnosis to reduce difficulties of later stage management of PD. Advancement in understanding of PD has made remarkable progress in introducing new tools and strategies such as stem cell therapy and deep brain stimulation. A link between alterations in gut microbiota and PD has also opened a new line. Evidence exists of a bidirectional pathway between the gastrointestinal tract and the central nervous system. Probiotics, prebiotics and synbiotics are being examined that might influence gut-brain axis by altering gut microbiota composition, enteric nervous system, and CNS. This review provides status on use of probiotics for PD. Limitations and future directions will also be addressed to promote further research considering use of probiotics for PD.

Dietary Polyphenols: A Multifactorial Strategy to Target Alzheimer's Disease.

Ageing is an inevitable fundamental process for people and is their greatest risk factor for neurodegenerative disease. The ageing processes bring changes in cells that can drive the organisms to experience loss of nutrient sensing, disrupted cellular functions, increased oxidative stress, loss of cellular homeostasis, genomic instability, accumulation of misfolded protein, impaired cellular defenses and telomere shortening. Perturbation of these vital cellular processes in neuronal cells can lead to life threatening neurological disorders like Alzheimer's Disease, Parkinson's Disease, Huntington's Disease, Lewy body dementia, etc. Alzheimer's Disease is the most frequent cause of deaths in the elderly population. Various therapeutic molecules have been designed to overcome the social, economic and health care burden caused by Alzheimer's Disease. Almost all the chemical compounds in clinical practice have been found to treat symptoms only limiting them to palliative care. The reason behind such imperfect drugs may result from the inefficiencies of the current drugs to target the cause of the disease. Here, we review the potential role of antioxidant polyphenolic compounds that could possibly be the most effective preventative strategy against Alzheimer's Disease.

Low-fat versus ketogenic diet in Parkinson's disease: A pilot randomized controlled trial.

BACKGROUND: Preliminary evidence suggests that diet manipulation may influence motor and nonmotor symptoms in PD, but conflict exists regarding the ideal fat to carbohydrate ratio. OBJECTIVES: We designed a pilot randomized, controlled trial to compare the plausibility, safety, and efficacy of a low-fat, high-carbohydrate diet versus a ketogenic diet in a hospital clinic of PD patients. METHODS: We developed a protocol to support PD patients in a diet study and randomly assigned patients to a low-fat or ketogenic diet. Primary outcomes were within- and between-group changes in MDS-UPDRS Parts 1 to 4 over 8 weeks. RESULTS: We randomized 47 patients, of which 44 commenced the diets and 38 completed the study (86% completion rate for patients commencing the diets). The ketogenic diet group maintained physiological ketosis. Both groups significantly decreased their MDS-UPDRS scores, but the ketogenic group decreased more in Part 1 (-4.58 ± 2.17 points, representing a 41% improvement in baseline Part 1 scores) compared to the low-fat group (-0.99 ± 3.63 points, representing an 11% improvement) (P < 0.001), with the largest between-group decreases observed for urinary problems, pain and other sensations, fatigue, daytime sleepiness, and cognitive impairment. There were no between-group differences in the magnitude of decrease for Parts 2 to 4. The most common adverse effects were excessive hunger in the low-fat group and intermittent exacerbation of the PD tremor and/or rigidity in the ketogenic group. CONCLUSIONS: It is plausible and safe for PD patients to maintain a low-fat or ketogenic diet for 8 weeks. Both diet groups significantly improved in motor and nonmotor symptoms; however, the ketogenic group showed greater improvements in nonmotor symptoms. © 2018 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

Biochemical Properties and Neuroprotective Effects of Compounds in Various Species of Berries.

Several species of berries, such as blueberries (Vaccinium angustifolium) and lingonberries (Vaccinium vitis-idaea L.), have attracted much scientific attention in recent years, especially due to their reported antioxidant and anti-inflammatory properties. Berries, as with other types of plants, have developed metabolic mechanisms to survive various environmental stresses, some of which involve reactive oxygen species. In addition, the fruits and leaves of berries have high amounts of polyphenols, such as flavonoids, which act as potent antioxidants. These compounds could potentially be beneficial for brain aging and neurodegenerative disorders. There are now several studies documenting the beneficial effects of various berries in cell models of neurotoxicity as well as in vivo models of neurodegenerative disease. In the current review, we discuss the metabolic strategies that plants and animals have developed in order to combat reactive oxygen species. We then discuss issues of bioavailability of various compounds in mammals and provide a synopsis of studies demonstrating the neuroprotective ability of berries and polyphenols. We also summarize findings from our own research group. For example, we have detected various polyphenols in samples of blueberries and lingonberries and have found that the leaves have a much higher antioxidant capacity than the fruits. Extracts from these species have also demonstrated neuroprotective effects in cellular models of toxicity and inflammation, which are being further pursued in animal models.

The Ketogenic Diet: Making a Comeback.

Americans have embraced a large number of diets in an attempt to manage obesity, improve quality of life, and address specific health problems. Among diets developed to address health problems, the ketogenic diet has had a long and variable history. Developed in the 1920s by a faith healer to help children with epilepsy, this diet induces a state that mimics carbohydrate starvation. As medications became available and effectively addressed seizures, the diet fell out of favor. During the last few decades, researchers and clinicians have learned that it can be useful in children and adults with refractory epilepsy and a variety of other conditions. Once again, pharmacists may encounter patients who are employing dietary management of serious health problems. This very high-fat diet almost eliminates carbohydrates from the patient's food selection. The result is the substitution of ketone bodies as a source of energy. Today's ketogenic diet has been modified with scientifically proven adjustments to increase palatability and help with adherence. Effective for some forms of epilepsy, the ketogenic diet also seems to have some utility in Alzheimer's disease, Parkinson's disease, and glaucoma, and many Americans are using it to lose weight. Consultant pharmacists may field questions about this diet, its potential to correct or alleviate health conditions, and its limitations. The article discusses the ketogenic diet's strengths, limitations, potential mechanisms, and use in a number of conditions with an emphasis on the elderly.

Weight stability in Parkinson's disease.

OBJECTIVES: Parkinson's disease (PD) has traditionally been associated with weight loss. However, recent studies have not found any evidence of underweight in PD. Nevertheless, few studies have addressed nutritional status changes over time in relation to other clinical PD features. Here, we explore changes in nutritional status and motor and non-motor PD features (including dopaminergic drug therapy) in PD patients after 1 year. METHODS: Motor and non-motor PD features, dopaminergic drug therapy, under-nutrition and malnutrition risk, and anthropometric measures (BMI, handgrip strength, triceps skin-fold, mid-arm circumference, and mid-upper arm muscle circumference) were assessed at baseline and 1 year later among 65 people with PD. RESULTS: Disability, PD motor symptoms, dysautonomia, and dopaminergic drug therapy increased. Underweight was uncommon both at baseline (n = 3) and follow-up (n = 2); malnutrition risk was common but stable (88 and 92%), whereas triceps skin-fold increased (P = 0.030); mid-upper arm muscle circumference decreased (P = 0.002); and the proportion of people with low handgrip strength (P = 0.012) increased. Correlations between nutritional variables and motor and non-motor PD features were absent to modest. Multiple linear regression analysis showed that baseline pupillomotor functioning was associated with decreased weight and BMI, and sleep with increased weight and BMI. In addition, increases in anxiety were associated with decreased weight, BMI, and triceps skin-fold. DISCUSSION: During the PD course, there seems to be redistribution in body composition from muscle to fat. Studies are needed to identify possible explanations for the findings. This implies that malnutrition should be regularly screened to identify those at risk of developing reduced muscle mass and increased morbidity.

Neuroprotective effects of the cultivated Chondrus crispus in a C. elegans model of Parkinson's disease.

Parkinson's disease (PD) is the second most common neurodegenerative disorder in the elderly people, currently with no cure. Its mechanisms are not well understood, thus studies targeting cause-directed therapy or prevention are needed. This study uses the transgenic Caenorhabditis elegans PD model. We demonstrated that dietary supplementation of the worms with an extract from the cultivated red seaweed Chondrus crispus decreased the accumulation of α-synulein and protected the worms from the neuronal toxin-, 6-OHDA, induced dopaminergic neurodegeneration. These effects were associated with a corrected slowness of movement. We also showed that the enhancement of oxidative stress tolerance and an up-regulation of the stress response genes, sod-3 and skn-1, may have served as the molecular mechanism for the C. crispus-extract-mediated protection against PD pathology. Altogether, apart from its potential as a functional food, the tested red seaweed, C. crispus, might find promising pharmaceutical applications for the development of potential novel anti-neurodegenerative drugs for humans.

Ketone body therapy: from the ketogenic diet to the oral administration of ketone ester.

Ketone bodies (KBs), acetoacetate and ß-hydroxybutyrate (ßHB), were considered harmful metabolic by-products when discovered in the mid-19th century in the urine of patients with diabetic ketoacidosis. It took physicians many years to realize that KBs are normal metabolites synthesized by the liver and exported into the systemic circulation to serve as an energy source for most extrahepatic tissues. Studies have shown that the brain (which normally uses glucose for energy) can readily utilize KBs as an alternative fuel. Even when there is diminished glucose utilization in cognition-critical brain areas, as may occur early in Alzheimer's disease (AD), there is preliminary evidence that these same areas remain capable of metabolizing KBs. Because the ketogenic diet (KD) is difficult to prepare and follow, and effectiveness of KB treatment in certain patients may be enhanced by raising plasma KB levels to ≥2 mM, KB esters, such as 1,3-butanediol monoester of ßHB and glyceryl-tris-3-hydroxybutyrate, have been devised. When administered orally in controlled dosages, these esters can produce plasma KB levels comparable to those achieved by the most rigorous KD, thus providing a safe, convenient, and versatile new approach to the study and potential treatment of a variety of diseases, including epilepsy, AD, and Parkinson's disease.

Improved nutritional status is related to improved quality of life in Parkinson's disease.

BACKGROUND: Quality of life is poorer in Parkinson's disease than in other conditions and in the general population without Parkinson's disease. Malnutrition also results in poorer quality of life. This study aimed at determining the relationship between quality of life and nutritional status. METHODS: Community-dwelling people with Parkinson's disease >18 years old were recruited. The Patient-Generated Subjective Global Assessment (PG-SGA) assessed nutritional status. The Parkinson's Disease Questionnaire 39 (PDQ-39) measured quality of life. Phase I was cross-sectional. The malnourished in Phase I were eligible for a nutrition intervention phase, randomised into 2 groups: standard care (SC) with provision of nutrition education materials only and intervention (INT) with individualised dietetic advice and regular weekly follow-up. Data were collected at baseline, 6 weeks, and 12 weeks. RESULTS: Phase I consisted of 120 people who completed the PDQ-39. Phase II consisted of 9 in the SC group and 10 in the INT group. In Phase I, quality of life was poorer in the malnourished, particularly for mobility and activities of daily living domains. There was a significant correlation between PG-SGA and PDQ-39 scores (Phase I, rs = 0.445, p = .000; Phase II, rs = .426, p = .002). In Phase II, no significant difference in the PDQ-39 total or sub-scores was observed between the INT and SC groups; however, there was significant improvement in the emotional well-being domain for the entire group, X2(2) = 8.84, p = .012. CONCLUSIONS: Malnourished people with Parkinson's disease had poorer quality of life than the well-nourished, and improvements in nutritional status resulted in quality of life improvements. Attention to nutritional status is an important component of quality of life and therefore the total care of people with Parkinson's disease. TRIAL REGISTRATION: ACTRN12610000819022.

Ischemic heart disease and the Mediterranean diet.

Lifestyle modification is primary in cardiovascular (CV) disease prevention. A major contribution is the Mediterranean diet (MedDiet), defined by two of seven components. Italian investigators determined a significant decrease in peripheral arterial disease of 56 % for a high score. Multiple specific CV risk factors are also favorably modified by the MedDiet. This includes beneficial effect on inflammation, vascular endothelium, and insulin resistance. There is also evidence that coronary heart disease, diabetes mellitus, and metabolic syndrome are decreased. Benefit appears to extend to new migrants in France. The economics of dietary adherence are favorable with decreased total lifetime health costs. Although mixed nuts appear to be a major factor in the MedDiet, special emphasis goes to extra virgin olive oil. Benefit also extends to other noncommunicable diseases with a decrease in cancer, Parkinson's disease, and Alzheimer's disease. Further quantitation of benefit and understanding of mechanisms involved in dietary benefit is essential.

A randomised clinical trial to evaluate the effects of Plantago ovata husk in Parkinson patients: changes in levodopa pharmacokinetics and biochemical parameters.

BACKGROUND: Plantago ovata husk therapy could be used in patients with Parkinson disease to reduce the symptoms of gastrointestinal disorders, but it is important to know whether this compound modifies levodopa pharmacokinetics. The maintenance of constant plasma concentrations of levodopa abolishes the clinical fluctuations in parkinsonian patients. The aim of this randomised clinical trial was to establish the influence of the fiber Plantago ovata husk in the pharmacokinetics of levodopa when administered to Parkinson patients well controlled by their oral medication. METHODS: To evaluate the effects of this fiber on several biochemical parameters. 18 volunteers participated in the study and received alternatively two treatments (Plantago ovata husk or placebo) with their usual levodopa/carbidopa oral dose. On days 0 (initial situation), 14 and 35 of the study, blood samples were taken to assess levodopa pharmacokinetics and to determine biochemical parameters. RESULTS: Levodopa Cmax was very similar in the initial situation (603.2 ng/ml) and after placebo administration (612.0 ng/ml), being slightly lower (547.8 ng/ml) when Plantago ovata husk was given. AUC was very similar in the three groups: initial situation.- 62.87 µg.min/ml, fiber treatment.- 64.47 µg.min/ml and placebo treatment.- 65.10 µg.min/ml. Fiber reduced significantly the number of peaks observed in the levodopa concentrations, maintaining concentrations more stable. No significant differences were found in total cholesterol, LDL-cholesterol and triglycerides with the administration of Plantago ovata husk. CONCLUSIONS: Plantago ovata husk administration caused a smoothing and homogenization of levodopa absorption, providing more stable concentrations and final higher levels, resulting in a great benefit for patients. TRIAL REGISTRATION: EudraCT2006-000491-33.

Dietary Interventions in Parkinson's Disease.

Several dietary patterns and nutritional supplements have been linked to the development, progression, and symptomatic treatment of Parkinson's disease (PD). Most of the evidence, at this point, is preliminary and based largely on observational studies. Interventional studies are scarce, so the evidence on effectiveness remains inconclusive. Dietary interventions could, analogous to exercise, potentially have a beneficial effect on disease symptoms as well as on the progression of the disease and should therefore be researched in high quality studies. Further work is also needed to study whether dietary interventions, when applied to an at-risk population, have any potential to postpone the onset of manifest PD. In this paper, we summarize all ongoing clinical trials on dietary interventions in PD. We found 10 ongoing studies, all aimed at a different intervention. These studies are mostly exploratory in nature or represent phase I or phase II trials focusing on safety, biological responses, and symptomatic effects. Taken together, we conclude that research on dietary interventions in persons with PD is still in its early days. The results of the various ongoing trials are expected to generate new hypotheses and will help to shape the agenda for future research on this important topic.