Elsevier

Neurochemistry International

Volume 108, September 2017, Pages 183-189
Neurochemistry International

The effects of omega-3 fatty acids and vitamin E co-supplementation on clinical and metabolic status in patients with Parkinson's disease: A randomized, double-blind, placebo-controlled trial

https://doi.org/10.1016/j.neuint.2017.03.014Get rights and content

Highlights

  • The effects of omega-3 plus vitamin E in Parkinson's disease were evaluated.

  • Co-supplementation in PD improved UPDRS.

  • Co-supplementation in PD improved some metabolic profiles.

Abstract

The current research was performed to evaluate the effects of omega-3 fatty acids and vitamin E co-supplementation on clinical signs and metabolic status in people with Parkinson's disease (PD). This randomized double-blind placebo-controlled clinical trial was conducted in 60 patients with PD. Participants were randomly assigned into two groups to receive either 1000 mg omega-3 fatty acids from flaxseed oil plus 400 IU vitamin E supplements (n = 30) or placebo (n = 30) for 12 weeks. Unified Parkinson's disease rating stage (UPDRS) were recorded at baseline and the after 3-month intervention. After 12 weeks' intervention, compared with the placebo, omega-3 fatty acids and vitamin E co-supplementation led to a significant improve in UPDRS (−3.3 ± 10.0 vs. +4.4 ± 14.9, P = 0.02). Furthermore, co-supplementation decreased high-sensitivity C-reactive protein (hs-CRP) (−0.3 ± 0.6 vs. +0.3 ± 0.3 μg/mL, P < 0.001), and increased total antioxidant capacity (TAC) (+65.2 ± 68.7 vs. +16 ± 52.4 μmol/L, P = 0.003) and glutathione (GSH) concentrations (+41.4 ± 80.6 vs. −19.6 ± 55.9 μmol/L, P = 0.001) compared with the placebo. Additionally, co-supplementation meaningfully decreased insulin (−2.1 ± 4.9 vs. +1.4 ± 6.2 μIU/mL, P = 0.01), homeostasis model of assessment-estimated insulin resistance (−0.7 ± 1.8 vs.+0.3 ± 1.6, P = 0.02) and Beta cell function (−5.9 ± 13.9 vs. +5.7 ± 25.5, P = 0.03), and increased quantitative insulin sensitivity check index (+0.009 ± 0.02 vs. −0.006 ± 0.03, P = 0.03) compared with the placebo. Overall, our study demonstrated that omega-3 fatty acids and vitamin E co-supplementation in people with PD had favorable effects on UPDRS, hs-CRP, TAC, GSH and markers of insulin metabolism.

Introduction

Parkinson's disease (PD) is a progressive disorder influencing more than 3% of subjects with age over 75 years (de Lau and Breteler, 2006). Prior studies have demonstrated that the pathological marking of PD is the intraneuronal reposition of uncommon filamentous inclusions containing phosphorylated α-synuclein (phosαSYN) (Jellinger, 2003, Braak and Del Tredici, 2008). In addition, increased oxidative stress involves early events associated with dopaminergic neuronal degeneration in PD (Lv et al., 2015). Neuroendocrine abnormalities including glucose intolerance, insulin resistance and bone metabolism, and body weight changes are also common in PD (De Pablo-Fernandez et al., 2017).

Previous reports have indicated that omega-3 fatty acids deficiency can reduce the nigrostriatal system's ability to maintain homeostasis under oxidative conditions, which may increase the risk of PD (Fabelo et al., 2011, Cardoso et al., 2014). Furthermore, few researchers have exhibited that concentrations of vitamin E were lower in PD patients than healthy subjects (Paraskevas et al., 2003, Fukushima et al., 2011). Our previous study among gestational diabetes (GDM) have demonstrated that co-supplementation with 1000 mg omega-3 fatty acids and 400 IU vitamin E daily for 6 weeks increased total antioxidant capacity (TAC) and nitric oxide (NO), and decreased malondialdehyde (MDA) values, but unaltered glutathione (GSH) and high-sensitivity C-reactive protein (hs-CRP) levels (Jamilian et al., 2016). However, no significant effect in indices of oxidative stress and/or inflammation was seen following supplementation with omega-3 fatty acids in healthy adults for 4 weeks (Cunnane et al., 1995) and vitamin E in hemodialysis (HD) people for 8 weeks (Ahmadi et al., 2013).

Omega-3 and vitamin E may result in improved clinical signs, indices of inflammation and oxidative stress, and metabolic status through their effects on modifications in the dopamine metabolism (Cardoso et al., 2014), decreased inflammatory markers (Zhuang et al., 2013), reducing production of reactive oxygen species (ROS) in the mitochondria (Capo et al., 2015) and improved antioxidant defense (Gupta et al., 2011). However, whether omega-3 and vitamin E co-supplementation have direct benefits on clinical signs, biomarkers of inflammation and oxidative stress, and metabolic parameters in people with PD has to date not been evaluated. This intervention was, therefore, performed to determine the effects of omega-3 and vitamin E co-supplementation on clinical signs, indices of inflammation and oxidative stress, and metabolic parameters in people with PD.

Section snippets

Participants

This treatment, registered in the Iranian website for registration of clinical trials (http://www.irct.ir: IRCT201604035623N73), was a randomized, double-blind, placebo-controlled clinical trial that was done among people with PD aged 50–80 years old diagnosed according to clinical diagnostic criteria of the UK PD Society Brain Bank (Hughes et al., 1992) referred to the Shahid Beheshti Clinic in Kashan, Iran, between March 2016 and June 2016. The diagnosis of PD was confirmed by 2 neurologists.

Results

Among subjects in the supplements and placebo groups, 3 people [withdrawn (n = 3)] were excluded (Fig. 1). In the end, 54 subjects [omega-3 and vitamin E (n = 27) and placebo (n = 27)] completed the trial. However, as the analysis was based on the ITT principle, all 60 people (30 in each group) were included in the final analysis.

Distribution of gender, disease severity, mean age, height, weight and BMI as well as METs at week 0 and week 12 were not different between the two groups (Table 1).

Discussion

In this research, we evaluated the effects of omega-3 and vitamin E co-supplementation on clinical signs and metabolic indices in people with PD. We found that omega-3 fatty acids and vitamin E co-supplementation for 12 weeks in patients with PD had favorable effects on UPDRS, serum hs-CRP, plasma TAC, GSH and markers of insulin metabolism, but did not affect other indices of inflammation and oxidative stress, and lipid profiles. To our knowledge, this trial is the first to have assessed the

Conclusions

Overall, our study demonstrated that omega-3 fatty acids and vitamin E co-supplementation in people with PD had favorable effects on UPDRS, hs-CRP, TAC, GSH and markers of insulin metabolism, whereas it did not affect other biomarkers of inflammation and oxidative stress, and lipid profiles.

Conflicts of interest

No conflicts are declared.

Author contributions

ZA and MT contributed in conception, design, statistical analysis and drafting of the manuscript. O-RT, ED, RD-K, FB, JA, M-HA, EK and M-RM. contributed in conception, data collection and manuscript drafting. The final version was confirmed by all authors for submission.

Clinical registration

http://www.irct.ir: IRCT201604035623N73.

Acknowledgements

The present study was supported by a grant from the Vice-chancellor for Research, KUMS, and Iran (94141).

References (59)

  • P.G. Khatami et al.

    The effects of high-dose vitamin E supplementation on biomarkers of kidney injury, inflammation, and oxidative stress in patients with diabetic nephropathy: a randomized, double-blind, placebo-controlled trial

    J. Clin. Lipidol.

    (2016)
  • H. Li et al.

    EPA and DHA reduce LPS-induced inflammation responses in HK-2 cells: evidence for a PPAR-gamma-dependent mechanism

    Kidney Int.

    (2005)
  • G. Martinovits et al.

    Systemic administration of antioxidants does not protect mice against the dopaminergic neurotoxicity of 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP)

    Neurosci. Lett.

    (1986)
  • S. Moylan et al.

    Oxidative & nitrosative stress in depression: why so much stress?

    Neurosci. Biobehav Rev.

    (2014)
  • I.N. Odunze et al.

    MPTP toxicity in the mouse brain and vitamin E

    Neurosci. Lett.

    (1990)
  • G.P. Paraskevas et al.

    Plasma levels of antioxidant vitamins C and E are decreased in vascular parkinsonism

    J. Neurol. Sci.

    (2003)
  • S. Phani et al.

    Neurodegeneration and inflammation in Parkinson's disease

    Park. Relat. Disord.

    (2012)
  • M. Taghizadeh et al.

    A randomized-controlled clinical trial investigating the effect of omega-3 fatty acids and vitamin E co-supplementation on markers of insulin metabolism and lipid profiles in gestational diabetes

    J. Clin. Lipidol.

    (2016)
  • E. Tatsch et al.

    A simple and inexpensive automated technique for measurement of serum nitrite/nitrate

    Clin. Biochem.

    (2011)
  • A. Vines et al.

    The role of 5-HT(1)A receptors in fish oil-mediated increased BDNF expression in the rat hippocampus and cortex: a possible antidepressant mechanism

    Neuropharmacology

    (2012)
  • A. Wypijewska et al.

    Iron and reactive oxygen species activity in parkinsonian substantia nigra

    Park. Relat. Disord.

    (2010)
  • A. Ahmadi et al.

    Effect of alpha-lipoic acid and vitamin E supplementation on oxidative stress, inflammation, and malnutrition in hemodialysis patients

    Iran. J. Kidney Dis.

    (2013)
  • M. Akbar et al.

    Docosahexaenoic acid: a positive modulator of Akt signaling in neuronal survival

    Proc. Natl. Acad. Sci. U. S. A.

    (2005)
  • D. Altavilla et al.

    IRFI 042, a novel dual vitamin E-like antioxidant, inhibits activation of nuclear factor-kappaB and reduces the inflammatory response in myocardial ischemia-reperfusion injury

    Cardiovasc Res.

    (2000)
  • Z. Asemi et al.

    Effects of omega-3 fatty acid plus alpha-tocopherol supplementation on malnutrition-inflammation score, biomarkers of inflammation and oxidative stress in chronic hemodialysis patients

    Int. Urol. Nephrol.

    (2016)
  • A. Baillet et al.

    The role of oxidative stress in amyotrophic lateral sclerosis and Parkinson's disease

    Neurochem. Res.

    (2010)
  • E. Beutler et al.

    Plasma glutathione in health and in patients with malignant disease

    J. Lab. Clin. Med.

    (1985)
  • M.C. Borges et al.

    Omega-3 fatty acids, inflammatory status and biochemical markers of patients with systemic lupus erythematosus: a pilot study

    Rev. Bras. Reumatol.

    (2016)
  • H. Braak et al.

    Invited Article: nervous system pathology in sporadic Parkinson disease

    Neurology

    (2008)
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