Highlights
- •This is the first, placebo-controlled study to investigate biochemical and clinical effects of Whey protein in PD patients.
- •Whey supplementation at 20 g/day for 6 m significantly increases plasma reduced glutathione, and decreases homocysteine level.
- •No significant improvement in clinical outcomes was demonstrated with Whey supplementation in this study.
- •Further studies are needed to evaluate of clinical effects of Whey protein involving larger number of patients.
Abstract
Background
Parkinson's disease (PD) is an oxidative stress-mediated degenerative disorder. Elevated
plasma homocysteine (Hcy) is frequently found in the levodopa-treated PD patients,
is associated with disease progression and is a marker of oxidative stress. Whey protein
is a rich source of cysteine, and branched-chain amino acids (BCAA). It has been shown
that supplementation with Whey protein increases glutathione synthesis and muscle
strength.
Objectives and methods
In this study, we conducted a placebo-controlled, double-blind study (NCT01662414)
to investigate the effects of undenatured Whey protein isolate supplementation for
6 months on plasma glutathione, plasma amino acids, and plasma Hcy in PD patients. Clinical
outcome assessments included the unified Parkinson's disease rating scale (UPDRS)
and striatal L-3,4-dihydroxy-6-(18)F-fluorophenylalanine (FDOPA) uptake were determined
before and after supplementation. 15 patients received Whey protein, and 17 received
Soy protein, served as a control group.
Results
Significant increases in plasma concentration of reduced glutathione and the ratio
of reduced to oxidized glutathione were found in the Whey-supplemented patients but
not in a control group. This was associated with a significant decrease of plasma
levels of Hcy. The plasma levels of total glutathione were not significantly changed
in either group. Plasma BCAA and essential amino acids (EAA) were significantly increased
in the Whey-supplemented group only. The UPDRS and striatal FDOPA uptake in PD patients
were not significantly ameliorated in either group. However, significant negative
correlation was observed between the UPDRS and plasma BCAA and EAA in the pre-supplemented
PD patients.
Conclusion
This study is the first to report that Whey protein supplementation significantly
increases plasma reduced glutathione, the reduced to oxidized glutathione ratio, BCAAs
and EAAs in patients with PD, together with a concomitant significant reduction of
plasma Hcy. However, there were no significant changes in clinical outcomes. Long-term,
large randomized clinical studies are needed to explore the benefits of Whey protein
supplementation in the management of PD patients.
Keywords
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References
- Parkinson's disease. First of two parts.N. Engl. J. Med. 1998; 339: 1044-1053
- The fate of striatal dopaminergic neurons in Parkinson's disease and Huntington's chorea.Brain. 2007; 130: 222-232
- Oxidative stress in Parkinson's disease.Ann. Neurol. 2003; 53 (discussion S-8): S26-S36
- Glutathione metabolism and Parkinson's disease.Free Radic. Biol. Med. 2013; 62: 13-25
- Alterations in the distribution of glutathione in the substantia nigra in Parkinson's disease.J. Neural Transm. 1997; 104: 661-677
- Redox imbalance in Parkinson's disease.Biochim. Biophys. Acta. 1780; 2008: 1362-1367
- Glutathione–a review on its role and significance in Parkinson's disease.FASEB J. 2009; 23: 3263-3272
- Glutathione redox imbalance in brain disorders.Curr. Opin. Clin. Nutr. Metab. Care. 2015; 18: 89-95
- Randomized, double-blind, pilot evaluation of intravenous glutathione in Parkinson's disease.Mov. Disord. 2009; 24: 979-983
- Therapeutic applications of Whey protein.Altern. Med. Rev. 2004; 9: 136-156
- Whey proteins influence hepatic glutathione after CCl4 intoxication.Toxicol. Ind. Health. 2009; 25: 325-328
- Protective effect of Whey proteins against nonalcoholic fatty liver in rats.Lipids Health Dis. 2011; 10: 57
- Oral supplementation with Whey proteins increases plasma glutathione levels of HIV-infected patients.Eur. J. Clin. Investig. 2001; 31: 171-178
- The biological activity of undenatured dietary Whey proteins: role of glutathione.Clin. Invest. Med. 1991; 14: 296-309
- Open-labeled pilot study of cysteine-rich Whey protein isolate supplementation for nonalcoholic steatohepatitis patients.J. Gastroenterol. Hepatol. 2009; 24: 1045-1050
- The Unified Parkinson's Disease Rating Scale (UPDRS): status and recommendations.Mov. Disord. 2003; 18: 738-750
- Nitric oxide and peroxynitrite serum levels in Parkinson's disease: correlation of oxidative stress and the severity of the disease.Eur. Rev. Med. Pharmacol. Sci. 2013; 17: 964-970
- Evaluation of striatal oxidative stress in patients with Parkinson's disease using [62Cu]ATSM PET.Nucl. Med. Biol. 2011; 38: 945-951
- Elevated homocysteine levels in levodopa-treated idiopathic Parkinson's disease: a meta-analysis.Acta Neurol. Scand. 2013; 128: 73-82
- Hyperhomocysteinemia in levodopa-treated patients with Parkinson's disease dementia.Mov. Disord. 2009; 24: 1028-1033
- Immunocal(R) and preservation of glutathione as a novel neuroprotective strategy for degenerative disorders of the nervous system.Recent Pat. CNS Drug Discov. 2012; 7: 230-235
- Preventive effects of genistein on motor dysfunction following 6-hydroxydopamine injection in ovariectomized rats.Neurosci. Lett. 2008; 448: 10-14
- Effect of supplementation with a cysteine donor on muscular performance.J. Appl. Physiol. 1999; 87: 1381-1385
- Parkinsonism: onset, progression and mortality.Neurology. 1967; 17: 427-442
- Clinical Global Impression. ECDEU Assessment Manual for Psychopharmacology-revised.National Institute of Mental Health, Rockville, MD.1976
- The Parkinson's Disease Questionnaire.Health Services Research Unit, Univerisity of Oxford, Oxford2012
- Age-specific CT and MRI templates for spatial normalization.NeuroImage. 2012; 61: 957-965
- Graphical evaluation of blood-to-brain transfer constants from multiple-time uptake data. Generalizations.J. Cereb. Blood Flow Metab. 1985; 5: 584-590
- Whey proteins in cancer prevention.Cancer Lett. 1991; 57: 91-94
- An open-label dose-response study of lymphocyte glutathione levels in healthy men and women receiving pressurized Whey protein isolate supplements.Int. J. Food Sci. Nutr. 2007; 58: 429-436
- Symposium on branched-chain amino acids: conference summary.J. Nutr. 2006; 136: 333S-336S
- Leucine regulates translation initiation of protein synthesis in skeletal muscle after exercise.J. Nutr. 2006; 136: 533S-537S
- Branched-chain amino acids, mitochondrial biogenesis, and healthspan: an evolutionary perspective.Aging (Albany NY). 2011; 3: 464-478
- Nonessential amino acids are not necessary to stimulate net muscle protein synthesis in healthy volunteers.J. Nutr. Biochem. 1999; 10: 89-95
- Oral branched-chain amino acids have a beneficial effect on manifestations of hepatic encephalopathy in a systematic review with meta-analyses of randomized controlled trials.J. Nutr. 2013; 143: 1263-1268
- Branched-chain amino acids as pharmacological nutrients in chronic liver disease.Hepatology. 2011; 54: 1063-1070
- Effect of Whey protein on plasma amino acids in diabetic mice.Exp. Ther. Med. 2013; 6: 1449-1454
- Ingestion of Whey hydrolysate, casein, or soy protein isolate: effects on mixed muscle protein synthesis at rest and following resistance exercise in young men.J. Appl. Physiol. (1985). 2009; 107: 987-992
- Whey protein stimulates postprandial muscle protein accretion more effectively than do casein and casein hydrolysate in older men.Am. J. Clin. Nutr. 2011; 93: 997-1005
- Muscle protein synthesis in cancer patients can be stimulated with a specially formulated medical food.Clin. Nutr. 2011; 30: 759-768
- Major nutritional issues in the management of Parkinson's disease.Mov. Disord. 2009; 24: 1881-1892
- Malnutrition in a sample of community-dwelling people with Parkinson's disease.PLoS One. 2013; 8e53290
- Prevalence of malnutrition in Parkinson's disease: a systematic review.Nutr. Rev. 2011; 69: 520-532
- Is there muscular weakness in Parkinson's disease?.Am. J. Phys. Med. Rehabil. 2010; 89: 70-76
- Parkinson's disease and resistive exercise: rationale, review, and recommendations.Mov. Disord. 2008; 23: 1-11
- Homocysteine is not associated with global motor or cognitive measures in nondemented older Parkinson's disease patients.Mov. Disord. 2009; 24: 176-182
- Role of hyperhomocysteinemia in endothelial dysfunction and atherothrombotic disease.Cell Death Differ. 2004; 11: S56-S64
- Effects of levodopa and COMT inhibitors on plasma homocysteine in Parkinson's disease patients.Mov. Disord. 2005; 20: 69-72
- The emerging role of nutrition in Parkinson's disease.Front. Aging Neurosci. 2014; 6: 36
- Peripheral markers for oxidative stress in Parkinson's disease patients of Eastern India.Neurochem. J. 2011; 5: 146-149
- Folate and homocysteine metabolism in neural plasticity and neurodegenerative disorders.Trends Neurosci. 2003; 26: 137-146
- Hyperhomocysteinemia and neurologic disorders: a review.J. Clin. Neurol. 2014; 10: 281-288
- The combination of homocysteine and C-reactive protein predicts the outcomes of Chinese patients with Parkinson's disease and vascular parkinsonism.PLoS One. 2011; 6e19333
Article info
Publication history
Published online: May 31, 2016
Accepted:
May 30,
2016
Received in revised form:
May 20,
2016
Received:
November 26,
2015
Identification
Copyright
© 2016 Elsevier B.V. All rights reserved.
