Access the full text.
Sign up today, get DeepDyve free for 14 days.
References for this paper are not available at this time. We will be adding them shortly, thank you for your patience.
Hindawi Journal of Aging Research Volume 2018, Article ID 5302105, 5 pages https://doi.org/10.1155/2018/5302105 Clinical Study Feasibility and Safety of Perilla Seed Oil as an Additional Antioxidative Therapy in Patients with Mild to Moderate Dementia 1 1 2 Chuntida Kamalashiran, Junya Pattaraarchachai, and Sombat Muengtaweepongsa Chulabhron International College of Medicine, ammasat University, Pathum ani, ailand Faculty of Medicine, ammasat University, Pathum ani, ailand Correspondence should be addressed to Sombat Muengtaweepongsa; sombatm@hotmail.com Received 28 February 2018; Revised 25 April 2018; Accepted 3 May 2018; Published 4 June 2018 Academic Editor: Antonello Lorenzini Copyright © 2018 Chuntida Kamalashiran et al. *is is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Dementia is a broad-spectrum terminology for a degenerate in cognitive function severe enough to intervene in activities of daily living. Oxidative stress plays a major role in the neurodegenerative cascade, leading to the irreversible mechanism in dementia. Perilla seed oil is extracted from its seeds and contains a high source of antioxidative substances such as omega-3 fatty acid. With its prominent antioxidative property, perilla seed oil demonstrates neuroprotective effects against dementia in preclinical studies. We aim to prove the feasibility and safety of perilla seed oil as an additional antioxidative therapy in patients with dementia. *is single-centered, double-blinded, placebo-controlled trial randomized 239 patients with clinical diagnosis of mild to moderate dementia according to the *ai Mini-Mental State Examination (TMSE) score of 10 to 23 or the *ai Montreal Cognitive Assessment score of 12 to 25. Either two capsules containing 500 milligrams of perilla seed oil or similarly appearing two capsules containing 500 milligrams of olive oil (placebo) four times daily was added to conventional standard treatment of dementia for six months. Clinical side effects and routine laboratory results at baseline and after treatment were compared between both groups. Nausea and vomiting were the most common clinical side effects (3%) found equally in both groups. *ree patients in the placebo group prematurely discontinued the medication, while only one patient in the treatment group quit the medication early. However, about 5% of patients in both groups could not comply with the regimen of the treatment. *e routine laboratory results, including complete blood counts, kidney function tests, and liver function panels, at baseline and after treatment, were not significantly different in both groups. In conclusion, perilla seed oil was feasible and safe to add on with standard treatment in patients with mild to moderate dementia. Further study is needed to confirm its benefit to use as additional antioxidative therapy in patients with dementia. was 5% in people aged between 71 and 79, but it raised to 1. Introduction 37.4% in people older than 90 [6]. According to a cross- Dementia is a broad-spectrum terminology for a degenerate sectional national survey in 2001, the prevalence of dementia in cognitive function severe enough to intervene in activities among the *ai population increased from 1% of elderly of daily living [1]. *e most common subtypes of dementia aged 60–64 to 31.3% of elderly aged 90 or older [7]. include Alzheimer disease, vascular dementia, fronto- Dementia is a degenerative and irreversible brain disease temporal dementia, dementia with Lewy body, and dementia [8]. Oxidative stress plays a major role in the neurode- in Parkinson’s disease [2]. Prevalence of dementia increases generative cascade, leading to the irreversible mechanism in with age [3]. *e age-specific prevalence of dementia is dementia [9, 10]. Oxidative stress leads to beta-amyloid duplicated with every five-year increase in individuals aged deposit in the brain tissue and cerebral vessels [11]. Pe- 65 [4, 5]. In the United States, the prevalence of dementia rilla oil is extracted from its seeds and contains a high source 2 Journal of Aging Research Table 1: Inclusion and exclusion criteria. 69.87 % Inclusion criteria 1. Age> 50–90 years 2. Screening cognitive function by the *ai Mental State Examination (TMSE) between 10 and 23 and/or MoCA between 7 and 20 3. Diagnosing mild to moderate dementia by following the 14.64 % 12.13 % Diagnosis and Statistical Manual of Mental Disorder, Fourth 3.34 % Edition (DSM-IV) 4. Can recognize and communicate No education Primary school High school ≥BCS 5. Do not have severe complications that influence patient ≥BCS = bachelor degree or above cooperation with this study 6. Willing to participate in this study and conducts oneself follow Figure 1: Education level. by suggestion duration in this study 7. Volunteer or proxy is able to provide the consent Exclusion criteria 1. Serum creatinine higher than 2 mg/dL Table 2: Demographic data (n � 239). 2. Serum alanine aminotransferase (ALT), aspartate Age, mean (years-old) 76.2 aminotransferase (AST), total bilirubin, or alkaline phosphatase Gender higher than 2.5 times of the upper normal range Male (%) 118 (49) 3. Vitamin B12 deficiency Female (%) 121 (51) 4. Hypothyroidism Educational level 5. Syphilis No education (%) 8 (3.34) 6. Bleeding disorder or taking warfarin Primary school (%) 167 (69.87) 7. Major depressive disorder Secondary school (%) 35 (14.64) 8. History of medicinal and herbal hypersensitivities Bachelor degree or above (%) 29 (12.13) 9. Having severe illness history Comorbid conditions 10. Intake of other supplements Hypertension (%) 129 (53.97) Diabetes (%) 51 (21.33) Hyperlipidemia (%) 32 (13.38) of antioxidative substances such as omega-3 fatty acid [12]. Heart disease (%) 2 (0.83) With its prominent antioxidative property, perilla seed oil Smoking (%) 37 (15.48) demonstrates neuroprotective effects against dementia in Alcohol drinking (%) 38 (15.89) preclinical studies [13]. Learning ability and memory im- History of head injury (%) 15 (6.27) proved in rats fed with perilla seed oil diet [14]. We aim to Family history of dementia (%) 37 (15.48) prove the feasibility and safety of perilla seed oil as an additional antioxidative therapy in patients with dementia. features were reported. *e study was registered under the *ai Clinical Trials Registry: register number 142/2556. 2. Materials and Methods *is is a single-centered, double-blinded, placebo-controlled 3. Results trail. Patients with mild to moderate dementia who visited dementia clinic at *ammasat University Hospital from A total of 239 patients with mild to moderate dementia were January 2014 to December 2016 were enrolled in the study. enrolled in the study. Proportion of either gender was almost Routine clinical examination, laboratory results, and neuro- equal. Mean age was 76 years old. Most of the patients had imaging per protocol for diagnosis of dementia were per- completed primary school. *e education level of partici- formed. *e *ai Mini-Mental State Examination (TMSE) pants is shown in Figure 1. *e most common preexisting score [15] and/or the *ai Montreal Cognitive Assessment disease was hypertension. Demographic data are shown in (MoCA) score [16] were completed. Patients with treatable Table 2. etiologies, such as hypothyroidism, vitamin B12 deficiency, *e most common subtype of dementia was Alzheimer and normal pressure hydrocephalus, were excluded. Mild to disease, and the second most common subtype was vascular moderate dementia is defined by the *ai Mini-Mental State dementia. *e subtypes of dementia are shown in Figure 2. Examination (TMSE) score of less than 20 or the *ai Fifty-seven patients could not complete the study as they Montreal Cognitive Assessment (MoCA) score of less than 23. were not able to comply with the regimen of the treatment. Inclusion and exclusion criteria are shown in Table 1. *e most common reasons for noncompliance were unable Dementia subtypes were diagnosed based on clinical to follow the regimen three times daily. *is was accounted features, laboratory results, and imaging findings [17, 18]. *e for almost 25% of all participants. *e remaining, 182 pa- patients were 1 :1 randomized and divided into 2 groups. tients, were able to complete the study. *e subtypes of Perilla seed oil or placebo (olive oil), taking 2 capsules three dementia in 182 patients enrolled to the study and in 57 times after meal, was added to conventional standard treat- patients dropped out from the study are shown in Table 3. ment of dementia for six months. Adverse effect and clinical *ere was no statistical significance between Alzheimer and Journal of Aging Research 3 Dementia subtypes (N = 239) Mixed dementia Parkinson’s disease 2% with dementia Others 10% 5% Alzheimer disease 47% Vascular dementia 36% Figure 2: Dementia subtypes. Table 3: Patients enrolled to the study and dropped out from the study divided by subtypes of dementia. Alzheimer’s Vascular Parkinson’s disease Mixed Other Volunteers according to the type N � 182 disease dementia with dementia dementia dementia of dementia enrolled (N � 86) (N � 68) (N � 18) (N � 3) (N � 7) Perilla seed oil 94 (51.65) 49 (56.98) 32 (47.06) 8 (44.44) 2 (66.66) 3 (42.86) Placebo 88 (48.35) 37 (43.02) 36 (52.94) 10 (55.55) 1 (33.33) 4 (57.14) Volunteers according to the type Alzheimer’s Vascular Parkinson’s disease Mixed Other N � 57 of dementia drop-out disease dementia with dementia dementia dementia Perilla seed oil 27 (47.37) 15 (55.55) 6 (22.22) 3 (11.11) 1 (3.70) 2 (7.41) Placebo 30 (52.60) 12 (40.00) 11 (36.66) 3 (10.00) 0 (0.00) 4 (13.33) Table 4: Comparison between Alzheimer and non-Alzheimer non-Alzheimer subgroups in both the enrolled and drop-out subtypes in enrolled and drop-out groups. groups (Table 4). Nausea and vomiting were the most common clinical Volunteers according to Non- Alzheimer’s P side effects (3%) found equally in both groups. *ree patients the type of dementia Alzheimer’s disease value in the placebo group prematurely discontinued the medi- enrolled (N � 182) disease cation, while only one patient in the treatment group quit the Perilla seed oil 49 (52.17%) 45 (47.87%) 0.173 medication early. However, about 5% of patients in both Placebo 37 (42.04%) 5 (58%) Volunteers according to the groups could not comply with the regimen of the treatment. type of dementia drop-out *e routine laboratory results, including complete blood (N � 57) counts, kidney function tests, and liver function panels, at Perilla seed oil 15 (55.5%) 12 (44.4%) baseline and after treatment, were not significantly different 0.24 Placebo 12 (40%) 18 (60%) in both groups. Perilla seed oil contains remarkable amount of omega-3 fatty 4. Discussion acid [12]. Interaction between omega-3 fatty acid and Perilla seed oil appears to be safe to add on with the con- warfarin is still controversial [22, 23]. Patients who currently ventional treatment in patients with mild to moderate de- take vitamin K antagonist were initially excluded from the mentia. Natural ingredients of perilla seed oil seem to be study due to potential interaction between perilla seed oil nontoxic [19]. However, as many as 57 patients or almost one- and warfarin. However, the interaction between perilla seed fourth of participants did not comply with the high frequency oil and warfarin needs to be confirmed by both in vitro and in vivo studies. of medical ingestion with 2 capsules three times daily. *is may imply that three times daily dosage is not appropriate to *e most common subtypes of dementia in our study be applied in patients with dementia. Enteric coating for- were Alzheimer disease and vascular dementia. *is prev- mulation should help improve bioavailability and reduce alence of dementia subtype is correlated with a previous frequency of administration of perilla seed oil treatment [20]. clinicopathological study from a developing country [24]. Perilla seed oil in a soft gelatin capsule can be taken in twice *e proportion of vascular dementia in developing countries daily regimen and is now available in the market [12]. including in our study is higher than that in developed Interaction between perilla seed oil and conventional countries, while there is no difference in the proportion of medications for patients with dementia is unlikely [21]. Alzheimer disease in either population [24, 25]. *is finding 4 Journal of Aging Research [5] M. Prince, R. Bryce, E. Albanese, A. Wimo, W. Ribeiro, and may represent the poor control of vascular risk factors in C. P. Ferri, “*e global prevalence of dementia: a systematic developing countries. review and metaanalysis,” Alzheimer’s and Dementia, vol. 9, Relationship between education level and dementia is no. 1, pp. 63–75, 2013. controversial. Many studies demonstrated that lesser edu- [6] B. Plassman, K. Langa, G. Fisher et al., “Prevalence of de- cational accomplishment was related to higher occurrence of mentia in the United States: the aging, demographics, and dementia [26]. Patients with low education level begin with memory study,” Neuroepidemiology, vol. 29, no. 1-2, lesser cognitive reserve and then end up with lower ability to pp. 125–132, 2007. deal with dementia [27]. In contrast, higher education may [7] S. Jitapunkul, C. Kunanusont, W. Phoolcharoen, and lead to faster cognitive decline in patients with Alzheimer P. Suriyawongpaisal, “Prevalence estimation of dementia disease and vascular dementia [28, 29]. among *ai elderly: a national survey,” Journal of the Medical *e neuroprotective therapy is a kind of disease modi- Association of ailand, vol. 84, no. 4, pp. 461–467, 2001. fication treatment which is helpful for outcomes improvement [8] T. K. Khan, “An algorithm for preclinical diagnosis of Alz- heimer’s disease,” Frontiers in Neuroscience, vol. 12, p. 275, [30]. *e preclinical study demonstrated neuroprotective effects of perilla seed oil in the guinea pig [31]. *e neuro- [9] E. Rojas-Gutierrez, G. Muñoz-Arenas, S. Treviño et al., protective therapy is lacking in the present formula of con- “Alzheimer’s disease and metabolic syndrome: a link from ventional treatment for patients with mild to moderate oxidative stress and inflammation to neurodegeneration,” dementia [32]. *erefore, add-on treatment with neuro- Synapse, vol. 71, no. 10, p. e21990, 2017. protective therapy should provide some benefits. However, [10] C. Schoneich, A. Hewarathna, R. Pal, L. Jiang, and a clinical study is needed to demonstrate the exact benefits E. Michaelis, “Oxidative stress markers of Alzheimer’s disease in human. in peripheral cell mitochondria,” Free Radical Biology and Medicine, vol. 108, p. S100, 2017. 5. Conclusions [11] A. Muche, T. Arendt, and R. Schliebs, “Oxidative stress affects processing of amyloid precursor protein in vascular endo- Perilla seed oil was feasible and safe to add on with standard thelial cells,” PLoS One, vol. 12, no. 6, article e0178127, 2017. treatment in patients with mild to moderate dementia. [12] M. Asif, “Health effects of omega-3,6,9 fatty acids: Perilla Further study is needed to confirm its benefit to use as frutescens is a good example of plant oils,” Oriental Pharmacy and Experimental Medicine, vol. 11, no. 1, pp. 51–59, 2011. additional antioxidative therapy in patients with mild to [13] R. Crupi, A. Marino, and S. Cuzzocrea, “n-3 fatty acids: role in moderate dementia. neurogenesis and neuroplasticity,” Current Medicinal Chemistry, vol. 20, no. 24, pp. 2953–2963, 2013. Data Availability [14] J. Lee, S. Park, J.-Y. Lee, Y. K. Yeo, J. S. Kim, and J. Lim, “Improved spatial learning and memory by perilla diet is *e data used to support the findings of this study are correlated with immunoreactivities to neurofilament and available from the corresponding author upon request. α-synuclein in hilus of dentate gyrus,” Proteome Science, vol. 10, no. 1, p. 72, 2012. Conflicts of Interest [15] Committee TtBF, ai Mental State Examination (TMSE), Committee TtBF, *ailand, 1993. *e authors declare that there are no conflicts of interests [16] S. Tangwongchai, M. Phanasathit, T. Charernboon et al., “*e regarding the publication of this paper. validity of *ai version of the Montreal cognitive assessment (MoCA-T),” Dementia e Neuropsychologia, vol. 3, no. 2, Acknowledgments p. 172, 2009. [17] A. Robillard, “Clinical diagnosis of dementia,” Alzheimer’s *is study was supported by the Agriculture Research De- and Dementia, vol. 3, no. 4, pp. 292–298, 2007. velopment Agency (Public Organization), ARDA (Funding [18] G. M. McKhann, D. S. Knopman, H. Chertkow et al., “*e no. CRP5705020540) and the Center of Excellence Stroke diagnosis of dementia due to Alzheimer’s disease: recom- mendations from the National Institute on Aging-Alzheimer’s from *ammasat University Hospital, *ammasat University. Association workgroups on diagnostic guidelines for Alz- heimer’s disease,” Alzheimer’s and Dementia, vol. 7, no. 3, References pp. 263–269, 2011. [19] T. Longvah, Y. G. Deosthale, and P. Uday Kumar, “Nutri- [1] J. C. S. Breitner, “Dementia—epidemiological considerations, tional and short term toxicological evaluation of perilla seed nomenclature, and a tacit consensus definition,” Journal of oil,” Food Chemistry, vol. 70, no. 1, pp. 13–16, 2000. Geriatric Psychiatry and Neurology, vol. 19, no. 3, pp. 129–136, [20] E. M. Kurowska, G. K. Dresser, L. Deutsch, D. Vachon, and [2] F. M. Elahi and B. L. Miller, “A clinicopathological approach W. Khalil, “Bioavailability of omega-3 essential fatty acids from perilla seed oil,” Prostaglandins, Leukotrienes, and Es- to the diagnosis of dementia,” Nature Reviews Neurology, vol. 13, no. 8, pp. 457–476, 2017. sential Fatty Acids, vol. 68, no. 3, pp. 207–212, 2003. [21] R. Tisserand and R. Young, Essential Oil Safety-e-Book: A [3] W. A. Kukull and M. Ganguli, “Epidemiology of dementia,” Neurologic Clinics, vol. 18, no. 4, pp. 923–949, 2000. Guide for Health Care Professionals, Elsevier Health Sciences, New York, NY, USA, 2013. [4] K. Y. Chan, W. Wang, J. J. Wu et al., “Epidemiology of Alzheimer’s disease and other forms of dementia in China, [22] M. S. Buckley, A. D. Goff, and W. E. Knapp, “Fish oil in- teraction with warfarin,” Annals of Pharmacotherapy, vol. 38, 1990-2010: a systematic review and analysis,” e Lancet, vol. 381, no. 9882, pp. 2016–2023, 2013. no. 1, pp. 50–52, 2004. Journal of Aging Research 5 [23] R. Pryce, N. Bernaitis, A. K. Davey, T. Badrick, and S. Anoopkumar-Dukie, “*e use of fish oil with warfarin does not significantly affect either the international normalised ratio or incidence of adverse events in patients with atrial fibrillation and deep vein thrombosis: a retrospective study,” Nutrients, vol. 8, no. 9, p. 578, 2016. [24] L. T. Grinberg, R. Nitrini, C. K. Suemoto et al., “Prevalence of dementia subtypes in a developing country: a clinicopatho- logical study,” Clinics, vol. 68, no. 8, pp. 1140–1145, 2013. [25] R. A. Goodman, K. A. Lochner, M. *ambisetty, T. S. Wingo, S. F. Posner, and S. M. Ling, “Prevalence of dementia subtypes in United States Medicare fee-for-service beneficiaries, 2011- 2013,” Alzheimer’s and Dementia, vol. 13, no. 1, pp. 28–37, [26] E. S. Sharp and M. Gatz, “*e relationship between education and dementia an updated systematic review,” Alzheimer Disease and Associated Disorders, vol. 25, no. 4, pp. 289–304, [27] C. M. Roe, C. Xiong, J. P. Miller, and J. C. Morris, “Education and Alzheimer disease without dementia: support for the cognitive reserve hypothesis,” Neurology, vol. 68, no. 3, pp. 223–228, 2007. [28] A. Bruandet, F. Richard, S. Bombois et al., “Cognitive decline and survival in Alzheimer’s disease according to education level,” Dementia and Geriatric Cognitive Disorders, vol. 25, no. 1, pp. 74–80, 2008. [29] M. L. Chaves, A. L. Camozzato, C. Kohler, and J. Kaye, “Predictors of the progression of dementia severity in Bra- zilian patients with Alzheimer’s disease and vascular de- mentia,” International Journal of Alzheimer’s Disease, vol. 2010, Article ID 673581, 7 pages, 2010. [30] J. Cummings, “Disease modification and neuroprotection in neurodegenerative disorders,” Translational Neurodegenera- tion, vol. 6, p. 25, 2017. [31] G. P. Eckert, C. Franke, M. Noldner et al., “Plant derived omega-3-fatty acids protect mitochondrial function in the brain,” Pharmacological Research, vol. 61, no. 3, pp. 234–241, [32] M. Ayaz, A. Sadiq, M. Junaid, F. Ullah, F. Subhan, and J. Ahmed, “Neuroprotective and anti-aging potentials of es- sential oils from aromatic and medicinal plants,” Frontiers in Aging Neuroscience, vol. 9, p. 168, 2017. MEDIATORS of INFLAMMATION The Scientific Gastroenterology Journal of World Journal Research and Practice Diabetes Research Disease Markers Hindawi Hindawi Publishing Corporation Hindawi Hindawi Hindawi Hindawi www.hindawi.com Volume 2018 http://www www.hindawi.com .hindawi.com V Volume 2018 olume 2013 www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 International Journal of Journal of Immunology Research Endocrinology Hindawi Hindawi www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 Submit your manuscripts at www.hindawi.com BioMed PPAR Research Research International Hindawi Hindawi www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 Journal of Obesity Evidence-Based Journal of Journal of Stem Cells Complementary and Ophthalmology International Alternative Medicine Oncology Hindawi Hindawi Hindawi Hindawi Hindawi www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 www.hindawi.com Volume 2013 Parkinson’s Disease Computational and Behavioural Mathematical Methods AIDS Oxidative Medicine and in Medicine Neurology Research and Treatment Cellular Longevity Hindawi Hindawi Hindawi Hindawi Hindawi www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 www.hindawi.com Volume 2018 www.hindawi.com Volume 2018
Journal of Aging Research – Hindawi Publishing Corporation
Published: Jun 4, 2018
You can share this free article with as many people as you like with the url below! We hope you enjoy this feature!
Read and print from thousands of top scholarly journals.
Already have an account? Log in
Bookmark this article. You can see your Bookmarks on your DeepDyve Library.
To save an article, log in first, or sign up for a DeepDyve account if you don’t already have one.
Copy and paste the desired citation format or use the link below to download a file formatted for EndNote
Access the full text.
Sign up today, get DeepDyve free for 14 days.
All DeepDyve websites use cookies to improve your online experience. They were placed on your computer when you launched this website. You can change your cookie settings through your browser.