Fig 1 - uploaded by Joanne Donoghue
Content may be subject to copyright.
![Homocysteine metabolism. Vitamin B 12 is needed for methyltetrahydrofuran to homocysteine. Levodopa undergoes Omethylation which requires S-adenosylmethionine (SAM) as a methyl donor and produces S-adenosylhomocysteine (SAH) causing increased homocysteine. Vitamin B 6 serves as a cofactor for cystathionine -synthase (CBS) and then -glutamylcysteine synthetase (GCS) to convert homocysteine to cystathionine and then to cysteine which synthesizes GSH. This figure has been modified from Morris [37]. DMG = Dimethylglycine; BHMT = betaine homocysteine methyltransferase.](profile/Joanne-Donoghue/publication/221763005/figure/fig1/AS:1107920506880000@1641160241310/Homocysteine-metabolism-Vitamin-B-12-is-needed-for-methyltetrahydrofuran-to.png)
Homocysteine metabolism. Vitamin B 12 is needed for methyltetrahydrofuran to homocysteine. Levodopa undergoes Omethylation which requires S-adenosylmethionine (SAM) as a methyl donor and produces S-adenosylhomocysteine (SAH) causing increased homocysteine. Vitamin B 6 serves as a cofactor for cystathionine -synthase (CBS) and then -glutamylcysteine synthetase (GCS) to convert homocysteine to cystathionine and then to cysteine which synthesizes GSH. This figure has been modified from Morris [37]. DMG = Dimethylglycine; BHMT = betaine homocysteine methyltransferase.
Source publication
Individuals with Parkinson's disease (PD) have decreased glutathione levels and elevated homocysteine levels. These substances are considered markers of health, and an inverse relationship has been suggested through the transsulfuration pathway. This experiment tested the effects of exercise and B vitamin supplementation on homocysteine and glutath...
Citations
... Twenty trials (29 pairwise comparisons) involving 1225 participants compared exercise with a control group (ie, no intervention or sham exercise). [6][7][8]27,28,[35][36][37][38]43,[46][47][48]53,56,60,63,64,66,68,71,73,74,77 Twenty-four trials (31 comparisons) involving 1044 participants compared 2 different exercise groups. 6,27,33,34,41,42,44,45,[49][50][51][52]54,55,[57][58][59]61,62,65,67,[69][70][71][72][75][76][77][78] Exercise was categorized according to the primary nature of the intervention: aerobic, 6,7,27,28,33,42,48,52,53,55,58,63,65,67,69,70,72,77,78 strength, 35,38,44,62,71 balance, 43,56,59,60,73,74,77 dance, 46,66 aquatic, 51,76 or multimodal, 6,8,34,[36][37][38]41,42,44,45,47,49,50,54,55,57,59,61,62,64,68,71,72,75 the latter including a combination of aerobic, strength, balance, flexibility, and/or functional exercises where no single component was ≥50% of the entire intervention. ...
... [6][7][8]27,28,[35][36][37][38]43,[46][47][48]53,56,60,63,64,66,68,71,73,74,77 Twenty-four trials (31 comparisons) involving 1044 participants compared 2 different exercise groups. 6,27,33,34,41,42,44,45,[49][50][51][52]54,55,[57][58][59]61,62,65,67,[69][70][71][72][75][76][77][78] Exercise was categorized according to the primary nature of the intervention: aerobic, 6,7,27,28,33,42,48,52,53,55,58,63,65,67,69,70,72,77,78 strength, 35,38,44,62,71 balance, 43,56,59,60,73,74,77 dance, 46,66 aquatic, 51,76 or multimodal, 6,8,34,[36][37][38]41,42,44,45,47,49,50,54,55,57,59,61,62,64,68,71,72,75 the latter including a combination of aerobic, strength, balance, flexibility, and/or functional exercises where no single component was ≥50% of the entire intervention. The dosage of exercise varied among the 60 pairwise comparisons: session duration ranged from 30 55,63,72 to 165 41 minutes, frequency ranged from 2 35,[43][44][45][46]51,56,59,60,[62][63][64]66,71,76,77 to 15 8 times per week and total program duration ranged from 4 8,57,58,76 to 104 44,62,66 weeks, with the majority of trials (n = 38, 78%) reporting intervention durations no longer than 12 weeks. ...
... 6,27,33,34,41,42,44,45,[49][50][51][52]54,55,[57][58][59]61,62,65,67,[69][70][71][72][75][76][77][78] Exercise was categorized according to the primary nature of the intervention: aerobic, 6,7,27,28,33,42,48,52,53,55,58,63,65,67,69,70,72,77,78 strength, 35,38,44,62,71 balance, 43,56,59,60,73,74,77 dance, 46,66 aquatic, 51,76 or multimodal, 6,8,34,[36][37][38]41,42,44,45,47,49,50,54,55,57,59,61,62,64,68,71,72,75 the latter including a combination of aerobic, strength, balance, flexibility, and/or functional exercises where no single component was ≥50% of the entire intervention. The dosage of exercise varied among the 60 pairwise comparisons: session duration ranged from 30 55,63,72 to 165 41 minutes, frequency ranged from 2 35,[43][44][45][46]51,56,59,60,[62][63][64]66,71,76,77 to 15 8 times per week and total program duration ranged from 4 8,57,58,76 to 104 44,62,66 weeks, with the majority of trials (n = 38, 78%) reporting intervention durations no longer than 12 weeks. Participants completed between 8 76 and 286 55 exercise sessions throughout the intervention period. ...
Introduction:
Exercise has many benefits for people with Parkinson's disease (PD) and has been suggested to modify PD progression, but robust evidence supporting this is lacking.
Objective:
This systematic review (PROSPERO registration: CRD42020169999) investigated whether exercise may have neuroplastic effects indicative of attenuating PD progression.
Methods:
Six databases were searched for randomized controlled trials (RCTs) that compared the effect of exercise to control (no or sham exercise) or to another form of exercise, on indicators of PD progression (eg, brain-derived neurotrophic factor [BDNF], brain activation, "off" Unified Parkinson's Disease Rating Scale [UPDRS] scores). Trial quality was assessed using the Physiotherapy Evidence Database Scale. Random-effects meta-analyses were performed where at least 3 comparable trials reported the same outcome; remaining results were synthesized narratively.
Results:
Forty-nine exercise trials involving 2104 PD participants were included. Compared to control, exercise improved "off" UPDRS motor scores (Hedge's g -0.39, 95% CI: -0.65 to -0.13, P = .003) and BDNF concentration (Hedge's g 0.54, 95% CI: 0.10-0.98, P = .02), with low to very low certainty of evidence, respectively. Narrative synthesis for the remaining outcomes suggested that compared to control, exercise may have neuroplastic effects. The exercise versus exercise comparisons were too heterogenous to enable pooling of results.
Discussion:
This review provides limited evidence that exercise may have an attenuating effect on potential markers of PD progression. Further large RCTs are warranted to explore differential effects by exercise type, dose and PD stage, and should report on a core set of outcomes indicative of PD progression.
... DiFrancisco-Donoghue et al. (2012) studied the benefit of co-supplementation with vitamins B6, B9 and B12, combined or not with physical activity, in homocysteine and glutathione levels, two markers associated with PD [88]. This open-label clinical trial was conducted for 6 weeks with 40 participants that were randomly divided into four groups. ...
Neurodegenerative diseases are caused by the gradual loss of neurons’ function. These neurological illnesses remain incurable, and current medicines only alleviate the symptoms. Given the social and economic burden caused by the rising frequency of neurodegenerative diseases, there is an urgent need for the development of appropriate therapeutics. Natural compounds are gaining popularity as alternatives to synthetic drugs due to their neuroprotective properties and higher biocompatibility. While natural compounds’ therapeutic effects for neurodegenerative disease treatment have been investigated in numerous in vitro and in vivo studies, only few have moved to clinical trials. This article provides the first systematic review of the clinical trials evaluating natural compounds’ safety and efficacy for the treatment of the five most prevalent neurodegenerative disorders: Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, amyotrophic lateral sclerosis, and Huntington’s disease.
... In the literature, the effects of resistance training in subjects with Parkinson's disease have been evaluated in many studies [58][59][60][61][62][63][64]. More specifically, some of these evaluate the effect of this training on respiratory capacity [65][66][67][68][69], on the risk of falls and balance camp [70][71][72][73][74][75][76][77], and on the quality of life and depression camp [78][79][80]. ...
Parkinson’s disease (PD) is a neurodegenerative disorder characterized by motor impairments and it is correlated with loss of bone mineral density. This study aimed to analyze the effects of resistance training on bone metabolism, systemic homeostasis, body composition, and physical performance in people with PD. Thirteen subjects (age 64.83 ± 5.70) with PD diagnosis were recruited. Participants performed neuromuscular tests, body composition assessment, and blood sample analysis at baseline, and after an 11 weeks-training period. Each training session lasted 90 min, three times a week. The participants had significant improvements in the timed up and go (p < 0.01), sit to stand (p < 0.01), dominant peg-board (p < 0.05), dominant foot-reaction time (p < 0.01), and functional reach tests (p < 0.05). They showed better pressure foot distributions in the left forefoot (p < 0.05) and hindfoot (p < 0.05) and increased cervical right lateral bending angle (p < 0.05). The protocol affects bone metabolism markers osteocalcin (p < 0.05), calcium (p < 0.01), PTH (p < 0.01), the C-terminal telopeptide (CTX) (p < 0.01), and vitamin D (p < 0.05). Eleven weeks of resistance training improved manual dexterity, static and dynamic balance, reaction time, cervical ROM, and reduced bone loss in people with PD.
... Deficiencies of these vitamins cause HHcy [91]. However, vitamin supplementation can significantly reduce peripheral Hcyconcentrations [92]. Some authors have speculated that proper vitamin B6, B12, and folate intake can help to maintain low Hcy concentrations and support the increased demand on metabolism during high-intensity exercise [93][94][95][96]. ...
Elevated peripheral expression of homocysteine (Hcy) is associated with an increased risk of coronary heart disease and stroke, diabetes, and cancer. It is also associated with cognitive impairment as it has been reported that high levels of Hcy cause cognitive dysfunction and memory deficit. Among several etiological factors that contribute to the pathogenesis of neurodegenerative diseases, including Alzheimer’s disease (AD), Hcy seems to directly contribute to the generation of neurotoxicity factors. This study aims to hypothesize the molecular mechanism by which exercise can reduce the risk of neurological complications promoted by hyperhomocysteinemia (HHcy), and discuss how exercise could reduce the risk of developing AD by using bioinformatics network models. According to the genes network, there are connections between proteins and amino acids associated with Hcy, exercise, and AD. Studies have evidenced that exercise may be one of several processes by which nitric acid availability can be maximized in the human body, which is particularly important in reducing cell loss and tau pathology , thereby reducing in the risk of complications associated with HHcy and AD.
... In contrast to KYN, KYNA is unable to cross the blood-brain barrier (BBB). [120,138,140,146,147,[151][152][153] the selected factors may influence on neuroprotection or neuroinflammation in reducing or worsening Parkinson`s decrease. (A) The proper diet combined with regular physical activity can lead to neuroprotection and consequently lowering the markers of inflammation and free radicals damage of macromolecules, improving the function of mitochondria as well as reducing the risk of osteoporosis, which is associated with decreasing risk of falls. ...
From year to year, we know more about neurodegeneration and Parkinson's disease (PD). A positive influence of various types of physical activity is more often described in the context of neuroprotection and prevention as well as the form of rehabilitation in Parkinson's patients. Moreover, when we look at supplementation, clinical nutrition and dietetics, we will see that balancing consumed products and supplementing the vitamins or minerals is necessary. Considering the biochemical pathways in skeletal muscle, we may see that many researchers desire to identify molecular mediators that have an impact through exercise and balanced diet on human health or development of the neurodegenerative disease. Therefore, it is mandatory to study the potential mechanism(s) related to diet and factors resulted from physical activity as molecular mediators, which play a therapeutic role in PD. This review summarizes the available literature on mechanisms and specific pathways involved in diet-exercise relationship and discusses how therapy, including appropriate exercises and diet that influence molecular mediators, may significantly slow down the progress of neurodegenerative processes. We suggest that a proper diet combined with physical activity will be a good solution for psycho-muscle BALANCE not only in PD but also in other neurodegenerative diseases.
... Aeróbne cvičenie priaznivo ovplyvnilo aktivitu procesov oxidatívnej fosforylácie v mitochondriách spojených s tvorbou ATP v neurónoch modelu myší s PCh [26]. Fyzicky aktívni jedinci majú oproti sedavým kontrolám porovnateľného veku, pohlavia a BMI vyššie cirkulujúce hladiny glutatiónu, jedného z kľúčových antioxidantov [75] a fyzická aktivita dokáže významne potlačiť prejavy chronického subklinického zápalu, a to nielen na periférii, ale aj v mozgu. Vieme napr., že aeróbny trén ing výrazne znižuje expresiu prozápalových cytokínov IL-1 a TNF-α v hipokampe myší [76]. ...
... The impact of vitamin B 6 supplementation with other vitamins has been also evaluated [140,141]. Combined vitamin B 6 (200 mg/day) and folic acid (15 mg/day) supplementation for 1 month increased RBC and whole blood GSH levels in both hemodialysis patients and healthy patients [141]. Similarly, Parkinson's disease patients supplemented with folic acid and vitamins B 12 and B 6 had improved GSH status [140]. ...
... Combined vitamin B 6 (200 mg/day) and folic acid (15 mg/day) supplementation for 1 month increased RBC and whole blood GSH levels in both hemodialysis patients and healthy patients [141]. Similarly, Parkinson's disease patients supplemented with folic acid and vitamins B 12 and B 6 had improved GSH status [140]. ...
Glutathione (GSH) is a critical endogenous antioxidant found in all eukaryotic cells. Higher GSH concentrations protect against cellular damage, tissue degeneration, and disease progression in various models, so there is considerable interest in developing interventions that augment GSH biosynthesis. Oral GSH supplementation is not the most efficient option due to the enzymatic degradation of ingested GSH within the intestine by γ-glutamyltransferase, but supplementation of its component amino acids—cysteine, glycine, and glutamate—enhances tissue GSH synthesis. Furthermore, supplementation with some non-precursor amino acids and micronutrients appears to influence the redox status of GSH and related antioxidants, such as vitamins C and E, lowering systemic oxidative stress and slowing the rate of tissue deterioration. In this review, the effects of oral supplementation of amino acids and micronutrients on GSH metabolism are evaluated. And since specific dietary patterns and diets are being prescribed as first-line therapeutics for conditions such as hypertension and diabetes, the impact of overall diets on GSH homeostasis is also assessed.
... This is similar to the results of the current study and, therefore; further supports the methioninehomocysteine-hypothesis. B6, B12 and folic acid supplementation has been showed to lower the serum homocysteine level (DiFrancisco-Donoghue et al. 2012;Zappacosta et al. 2013). It is, therefore; probable that increased serum methionine level is itself capable of lowering NOS activity, but this requires further studies. ...
Introduction. Various protein-based supplements are at least periodically consumed by 30-40% of sportspeople. The current study compares cardiovascular effects of diet supplementation with two different protein-rich products – bee pollen and whey proteins. Material and methods. 30 Wistar rats were divided into two parts, one subjected to daily moderate physical activity and one not. Each part consisted of three groups: one control group, one whey-protein-supplemented and one bee-pollen-supplemented. After eight weeks rats were decapitated and proximal parts of thoracic aortas were collected, and embed in paraffin blocks. Histological slides were stained according to standard H&E, Masson’s trichrome and Verhoeff-Van Gieson stainings. Special immunohistochemical stains against nNOS, eNOS and α-SMA were also prepared. Results. Histological evaluation has revealed noticeable changes in all supplemented groups – disturbances in elastic laminae, slight increase in collagen deposition and significantly lowered nNOS and eNOS expression. The prevalence of micro atherosclerotic plaques has been the highest in not-running supplemented groups, while in running supplemented groups it has resembled the prevalence in control groups. Both running groups have had also thinner tunica media than control. Conclusions. Both supplements exerts visible effects on aortic structure, but the difference between them is far less evident. In some aspects, however; the bee pollen seems to be even slightly more harmful which may be probably related to various possible contaminants like mycotoxins or pesticides.
... 55,56 Consistent exercise can even increase serum levels of glutathione in humans. 57 This is especially important because in human studies, people with PD have decreased baseline levels of antioxidants, such as glutathione and urate, compared with people without PD, providing support for recent clinical trials. [58][59][60][61] Physical activity and exercise disrupt the molecular mechanisms underlying PD pathogenesis in numerous ways. ...
The incidence of Parkinson's disease (PD) is expected to increase as our population ages and will likely strain the projected capacity of our health care system. Despite being the most common movement disorder, there have been few noninvasive therapeutic advances for people with PD since the first levodopa clinical trial in 1961. The study of PD pathogenesis, combined with an appreciation for the biochemical mechanisms by which physical activity and exercise may impact physiology, has resulted in emerging hypotheses for new modifiable risk factors for PD. Physical activity and exercise as a means of preventing PD, or maintaining the functionality of people with PD, are a promising area of investigation. Conversely, physical inactivity is implicated in many disease states, some of which are also correlated with the development of PD, such as metabolic syndrome. The primary relationship between these diseases is likely rooted in heightened inflammation and oxidative stress at the cellular level. Physical activity and exercise as a means of attenuating inflammation have led to increased interest in related potential therapeutic targets for PD. Ultimately, these findings may translate into low-cost, universally available therapies for PD disease modification or prevention. © 2016 International Parkinson and Movement Disorder Society.
... After including five reports found from the reference lists of identified review articles, 224 records were screened on the basis of their titles and abstracts. Of these records, full texts of 58 reports were screened more thoroughly, and 12 were considered relevant for qualitative analysis [11][12][13][14][15][16][17][18][19][20][21][22] (details in figure 1). Similarity of outcome measures, needed for meta-analysis, was found among five different reports. ...
... Of 12 studies, 10 reported a positive effect of intervention. Six studies compared progressive resistance training with weakly defined 'usual activities', 11-13 16-18 four with different low-intensity strengthening, endurance or balance exercises, 14 15 19 20 one with the use of vitamins, 17 and one with treadmill training. 22 It is selfevident that most of the patients with PD have more than one treatment. ...
Objectives To investigate if there is evidence on effectiveness of progressive resistance training in rehabilitation of Parkinson disease.
Design Systematic review and meta-analysis. Data sources: Central, Medline, Embase, Cinahl, Web of Science, Pedro until May 2014. Randomised controlled or controlled clinical trials. The methodological quality of studies was assessed according to the Cochrane Collaboration's domain-based evaluation framework. Data synthesis: random effects meta-analysis with test for heterogeneity using the I² and pooled estimate as the raw mean difference.
Participants Adults with primary/idiopathic Parkinson's disease of any severity, excluding other concurrent neurological condition.
Interventions Progressive resistance training defined as training consisting of a small number of repetitions until fatigue, allowing sufficient rest between exercises for recovery, and increasing the resistance as the ability to generate force improves.
Comparison Progressive resistance training versus no treatment, placebo or other treatment in randomised controlled or controlled clinical trials.
Primary and secondary outcome measures Any outcome.
Results Of 516 records, 12 were considered relevant. Nine of them had low risk of bias. All studies were randomised controlled trials conducted on small samples with none or 1 month follow-up after the end of intervention. Of them, six were included in quantitative analysis. Pooled effect sizes of meta-analyses on fast and comfortable walking speed, the 6 min walking test, Timed Up and Go test and maximal oxygen consumption were below the level of minimal clinical significance.
Conclusions There is so far no evidence on the superiority of progressive resistance training compared with other physical training to support the use of this technique in rehabilitation of Parkinson's disease.
Systematic review registration number PROSPERO 2014:CRD42014009844.
