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Fulltext The Efficacy of Squalene in Cardiovascular Disease Risk-A Systematic Review

Ibrahim N', Fairus S, Zulfarina MS, Naina Mohamed I

Nutrients, 2020 Feb 05;12(2).
PMID: 32033387 DOI: 10.3390/nu12020414

INTRODUCTION: Cardiovascular disease (CVD) is the leading cause of death worldwide. Squalene (SQ), an intermediate for the cholesterol biosynthesis, has been proposed to act similarly to statins via inhibition of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase in the liver.
PURPOSE: This paper explores the effects of SQ in CVD.
METHODS: A systematic review of the literature was performed to identify relevant studies about SQ and CVD. A comprehensive search in Medline and Scopus for relevant studies published between the years 1946 and 2019 was performed. The main inclusion criteria were that the study was published in English; that the study reported association or effect of SQ and CVD; and that CVD should be related to lifestyle variables, aging, or experimentally induced conditions.
RESULTS: The literature searches identified 5562 potentially relevant articles, whereby 21 studies met the inclusion criteria. There were three human studies and 18 animal experimental studies included in this paper. Only one human study reported positive outcome of SQ in CVD. The remaining two studies reported inconsistent and/or no effect. For animal studies, 15 studies reported positive effect while the remaining reported negative and/or no effect of SQ on various related parameters.
CONCLUSIONS: This evidence-based review emphasizes the potential of SQ being used for cardiovascular-related diseases. The effect of SQ, especially of plant-based warrants further exploration. Controlled human observational studies should be performed to provide comprehensive evidence.
Fulltext The Pharmacological Potential of Oil Palm Phenolics (OPP) Individual Components

Syarifah-Noratiqah SB, Zulfarina MS, Ahmad SU, Fairus S, Naina-Mohamed I

Int J Med Sci, 2019;16(5):711-719.
PMID: 31217739 DOI: 10.7150/ijms.29934

The oil palm tree (Elaeis guineensis) from the family Arecaceae is a high oil-producing agricultural crop. A significant amount of vegetation liquor is discarded during the palm oil milling process amounting to 90 million tons per year around the world. This water-soluble extract is rich in phenolic compounds known as Oil Palm Phenolics (OPP). Several phenolic acids including the three isomers of caffeoylshikimic acid (CFA), p-hydroxybenzoic acid (PHBA), protocatechuic acid (PCA) and hydroxytyrosol are among the primary active ingredients in the OPP. Previous investigations have reported several positive pharmacological potentials by OPP such as neuroprotective and atheroprotective effects, anti-tumor and reduction in Aβ deposition in Alzheimer's disease model. In the current review, the pharmacological potential for CFA, PHBA, PCA and hydroxytyrosol is carefully reviewed and evaluated.
The Effects of Palm Oil on Plasma and Serum Lipid Parameters: A Systematic Review on Animal Intervention Studies

Syarifah-Noratiqah SB, Fairus S, Zulfarina MS, Nasrullah Z, Qodriyah HMS, Naina-Mohamed I

Front Vet Sci, 2020;7:303.
PMID: 32775343 DOI: 10.3389/fvets.2020.00303

Background: Accumulative evidences on the beneficial effects of palm oil are progressively reported; however, there are still several controversies related to their effects on the risks of cardiovascular disease (CVD). This review explores the effects of palm oil and its liquid fraction namely palm olein, which is commonly used as cooking oil on four lipid parameters; total cholesterol (TC), triglyceride (TG), high-density lipoprotein-cholesterol (HDL-C) and low-density lipoprotein-cholesterol (LDL-C), which play an important role as CVD-related biomarkers. A systematic review of the literature was conducted to identify the relevant studies on palm oil and the lipid parameters specifically focusing on the in-vivo animal model. Methods: A comprehensive search was conducted in Medline via EBSCOhost, Medline via OVID and Scopus. Studies were limited to the English language published between the years of 2000 and 2019. The main inclusion criteria were as follows: (1) Study with in-vivo animal experiments [the animal should be limited to mammals] (2) Study should have evaluated the effects of palm oil or palm olein on plasma or serum lipid parameter (3) Study should have used palm oil or palm olein in the form of pure or refined oil (4) The treatment of palm oil or palm olein was assessed using the following outcomes: plasma or serum TC, TG, HDL-C, and LDL-C concentration (5) Study should have control group and (6) studies on specific fatty acid, fraction enriched tocotrienol and tocopherol, crude palm oil, kernel oil, red palm oil, thermally oxidized palm oil, hydrogenated palm oil, and palm oil or palm olein based products namely margarine, palm milk, butter and cream were excluded. The quality and the risk of bias on the selected studies were assessed using the ARRIVE Guideline and SYRCLE's Risk of Bias tools, respectively. Results: The literature search successfully identified 17 potentially relevant articles, whereby nine of them met the inclusion criteria. All research articles included in this review were in vivo studies comprising seven rats, one hamster and one mice model. Conclusion: Significant positive outcomes were observed in several lipid parameters such as TC and LDL-C. The evidence from this review supported that palm oil and palm olein possess high potential as lipid-lowering agents.
Natural Polyphenols in the Treatment of Alzheimer's Disease

Syarifah-Noratiqah SB, Naina-Mohamed I, Zulfarina MS, Qodriyah HMS

Curr Drug Targets, 2018;19(8):927-937.
PMID: 28356027 DOI: 10.2174/1389450118666170328122527

Neurodegenerative disease is an incurable disease which involves the degeneration or death of the nerve cells. Alzheimer's Disease (AD) is a neurodegenerative disease discovered in 1906 by Alois Alzheimer, a German clinical psychiatrist and neuroanatomist. The main pathological hallmarks of this disease are the formation of extracellular amyloid β (Aβ) plaques and intracellular neurofibrillary tangle (NFT). The accumulation of the amyloid protein aggregates in the brain of AD patients leads to oxidative stress and inflammation. Other postulated reasons for the development of this disease are cholinergic depletion and excessive glutamatergic neurotransmission. The current drugs approved and marketed for the treatment of AD are cholinesterase inhibitors (ChEIs) and N-methyl-Daspartate (NMDA) receptor antagonists. The function of ChEIs is to avoid cholinergic depletion; whereas the function of NMDA receptor antagonist is to block excessive glutamatergic neurotransmission. Unfortunately, the current drugs prescribed for AD show only modest improvement in terms of symptomatic relief and delay the progression of the disease. This review will discuss about several polyphenolic compounds as potential natural treatment options for AD. Three compounds are highlighted in this review - Curcumin (Cur), Resveratrol (Rsv) and Epigallocatechin-3- gallate (EGCG). These compounds have huge potential for AD treatment, especially due to their low frequency of adverse events. However, the current conventional pharmaceutical drugs remain as the mainstay of treatment for AD.
Fulltext Pharmacological Therapy in Panic Disorder: Current Guidelines and Novel Drugs Discovery for Treatment-resistant Patient

Zulfarina MS, Syarifah-Noratiqah SB, Nazrun SA, Sharif R, Naina-Mohamed I

Clin Psychopharmacol Neurosci, 2019 May 31;17(2):145-154.
PMID: 30905115 DOI: 10.9758/cpn.2019.17.2.145

Panic disorder (PD) being one of the most intensively investigated anxiety disorders is considered a heterogeneous psychiatric disease which has difficulties with early diagnosis. The disorder is recurrent and usually associated with low remission rates and high rates of relapse which may exacerbated social and quality of life, causes unnecessary cost and increased risk for complication and suicide. Current pharmacotherapy for PD are available but these drugs have slow therapeutic onset, several side effects and most patients do not fully respond to these standard pharmacological treatments. Ongoing investigations indicate the need for new and promising agents for the treatment of PD. This article will cover the importance of immediate and proper treatment, the gap in the current management of PD with special emphasis on pharmacotherapy, and evidence regarding the novel anti-panic drugs including the drugs in developments such as metabotropic glutamate (mGlu 2/3) agonist and levetiracetam. Preliminary results suggest the anti-panic properties and the efficacy of duloxetine, reboxetine, mirtazapine, nefazodone, risperidone and inositol as a monotherapy drug. Apart for their effectiveness, the aforementioned compounds were generally well tolerated compared to the standard available pharmacotherapy drugs, indicating their potential therapeutic usefulness for ambivalent and hypervigilance patient. Further strong clinical trials will provide an ample support to these novel compounds as an alternative monotherapy for PD treatment-resistant patient.
Fulltext Lifestyle indices of body composition and obesity risk and prevalence among multi-ethnic adolescents in Malaysia

Zulfarina MS, Sharif R, Mokhtar SA, Shuid AN, Naina-Mohamed I

Front Pediatr, 2022;10:899014.
PMID: 36389377 DOI: 10.3389/fped.2022.899014

The prevalence of childhood obesity in Malaysia has doubled in less than a decade. Moreover, being overweight and obese have been associated with immediate and later comorbidities, thus emphasizing the need to prevent obesity from an early age. This cross-sectional study involved 923 multi-ethnic Malaysian adolescents aged between 15 and 17 years old. Body composition was estimated using bioelectrical impedance analysis. Body mass index (BMI) classification was based on the World Health Organization (WHO) growth reference and the International Obesity Task Force (IOTF) cut-off. Meanwhile, the Child Growth Foundation (CGF) body fat reference was used to classify adolescents' adiposity. Lifestyle indices including physical activity, sedentary behavior, supplement intake, smoking and alcohol status were assessed via questionnaires. A high prevalence of overweight/obesity among the adolescents was observed according to the CGF (26%), followed by that of the WHO (24%) and then the IOTF (23%) cut-off, with high concordance values between each pair. After adjustment, a significant association was found between physical activity (PAQ score) and lean mass (p = 0.027). No lifestyle determinant was found to be a significant predictor of fat percentage. A high sedentary level increased the likelihood of obesity (OR 3.0, p
Quality of energy intake in Malaysian adolescents: prevalence, characteristics, determinants and impact of implausible reporters

Zulfarina MS, Sharif R, Sharkawi AM, Mokhtar SA, Shuid AN, Naina-Mohamed I

Public Health Nutr, 2023 Jan;26(1):122-131.
PMID: 35321764 DOI: 10.1017/S1368980022000726

OBJECTIVE: Misreporting of energy intake (EI) in nutritional epidemiology is common and even severe among adolescents. Thus, the current study aims to examine the presence, bias and impact introduced by implausible reporters.
DESIGN: Cross-sectional.
SETTING: Central and eastern regions of Peninsular Malaysia.
PARTICIPANTS: A stratified random sampling was employed to select 917 secondary school-going adolescents (aged 15-17 years).
RESULTS: The prevalence of under-reporters was 17·4 %, while no over-reporters were identified. Under-reporters had higher body composition and lower dietary intakes (except for vitamin C, Cr and Fl) compared with plausible reporters (P < 0·05). Adolescents with overweight and obesity had a higher odds of under-reporting compared with under-/normal weight adolescents (P < 0·001). In model 3, the highest regression coefficient (R2 = 0·404, P < 0·001) was obtained after adjusting for reporting status.
CONCLUSIONS: Overweight and obese adolescents were more likely to under-report their food intake and consequently affect nutrient intakes estimates. Future analyses that include nutrient intake data should adjust for reporting status so that the impact of misreporting on study outcomes can be conceded and consequently improve the accuracy of dietary-related results.
Influence of Adolescents' Physical Activity on Bone Mineral Acquisition: A Systematic Review Article

Zulfarina MS, Sharkawi AM, Aqilah-S N ZS, Mokhtar SA, Nazrun SA, Naina-Mohamed I

Iran J Public Health, 2016 Dec;45(12):1545-1557.
PMID: 28053920

BACKGROUND: This study conducted to examine and to provide a systematic literature over the influence of adolescents' physical activity (PA) in maximizing`s peak bone mass (PBM). PBM or the 'bone bank' is an important determinant in achieving healthy bone. PA is one of the bone's lifestyle contributors and high PBM is one of the major strategies for preventing osteoporosis.
METHODS: A computerized literature search using Medline (Ovid) and Scopus were conducted to identify relevant observational studies on the influence of different level of PA on bone acquisition among the healthy adolescent population. All articles included, were limited to original articles and English language.
RESULTS: Nine studies met the inclusion criteria. Reported bone outcomes were of bone mass, bone structure and bone strength. Eight studies showed positive association between adolescents' PA and high bone variables. The influence of PA may differ according to sex, skeletal sites and bone outcomes.
CONCLUSION: This study supported the importance of increase adolescents' regular PA in optimizing PBM thus preventing osteoporosis at later life.
Fulltext Activities of Daily Living and Determinant Factors among Older Adult Subjects with Lower Body Fracture after Discharge from Hospital: A Prospective Study

Ibrahim NI, Ahmad MS, Zulfarina MS, Zaris SNASM, Mohamed IN, Mohamed N, et al.

Int J Environ Res Public Health, 2018 05 16;15(5).
PMID: 29772744 DOI: 10.3390/ijerph15051002

Fracture is a type of musculoskeletal injury that contributes to an inability to perform daily activities. The objective of this study was to evaluate activities of daily living (ADL) of older adult patients with lower body fracture and to determine factors influencing ADL. Patient's ADL was assessed at pre-fracture, ward admission and post-discharge phases using the Katz ADL questionnaire. There were 129 subjects at pre-fracture and ward phases and 89 subjects at discharge phase. There were four independent variables; age, gender, type of fracture and ability to walk before fracture. Logistic regression models showed that 'age' and 'ability to walk before fracture' were the determinant factors of dependent for 'bathing', 'dressing' and 'toileting'. The 'ability to walk before fracture' was the determinant factor of dependent for 'transferring'. 'Age' and 'gender' were the determinant factors of dependent for 'continence', while 'age' was the determinant factor of dependent for 'feeding'. The ADL score changes were significant across the phases with a reduction in ADL score in the ward admission phase and partial increment during the post-discharge phase. There were improvements in the health outcomes of subjects aged more than 50 years old after 3 months of being discharged from the hospital. In conclusion, age, being female, having a hip fracture and using a walking aid before fracture were the determinants identified in this study.
Fulltext Modifiable factors associated with bone health in Malaysian adolescents utilising calcaneus quantitative ultrasound

Zulfarina MS, Sharif R, Syarifah-Noratiqah SB, Sharkawi AM, Aqilah-Sm ZS, Mokhtar SA, et al.

PLoS One, 2018;13(8):e0202321.
PMID: 30106982 DOI: 10.1371/journal.pone.0202321

Maximizing bone mineral accrual to attain an optimal peak bone mass (PBM), particularly during adolescence, appears to be an effective protective strategy in the prevention of osteoporosis. This study aimed to evaluate the influence of physical activity (PA), fat mass (FM), lean mass (LM), body mass index (BMI), calcium, or combination of vitamin D supplement intake, smoking and alcohol drinking status on bone health assessed by calcaneus quantitative ultrasound (QUS) in a healthy adolescent population. The participants comprised of 920 male and female secondary school adolescents aged 15-17 years old. Quantitative ultrasound measurements of the left heel were performed using Lunar Achilles EX II, which included results of broadband ultrasound attenuation (BUA), speed of sound (SOS), and a calculated stiffness index (SI). Multivariable linear regression analyses revealed that-PA was positively associated with all three QUS indices in both genders; BMI was positively associated with SI and SOS in females; LM was positively associated with BUA in both genders; and FM was negatively associated with SI in females. These variables accounted for 32.1%, 21.2% and 29.4% of females' SOS, BUA and SI variances (p<0.001), respectively and 23.6%, 15.4% and 17.2% of males' SOS, BUA and SI variances (p<0.001), respectively. Promoting health benefits from physical activity could influence bone status and consequently improve PBM, which is a potent protective determinant against osteoporosis in adulthood.
Fulltext Physical function assessment of older adults with lower body fractures at 3 months post-discharge from hospital

Ibrahim N', Sharkawi Ahmad M, Zulfarina MS, Zaris SNASM, Nor Azlin ZA, Naina Mohamed I, et al.

Ther Clin Risk Manag, 2019;15:201-210.
PMID: 30774356 DOI: 10.2147/TCRM.S189748

Background and purpose: Physical function assessment can be performed to assess functional mobility among older adults, especially after a traumatic incident such as lower body fracture (LBF). The objective of this study was to evaluate physical function of older patients with LBF after 3 months of discharge from the hospital.
Patients and methods: A total of 89 patients were followed up at the discharge phase. Four independent variables were tested: age, sex, type of fracture, and use of a walking aid before fracture. Mobility and strength were assessed with the Timed Up and Go (TUG) test and hand-grip strength (HGS) test, respectively.
Results: The majority of the patients were ≥65 years old (64%), female (61.8%), of Chinese ethnicity (50.6%), and had a hip fracture (51.7%). The mean time for TUG test was 26.11 seconds, while mean HGS was 19.02 kg. We found significant differences in TUG test scores with respect to all independent variables tested: age (P=0.026), sex (P=0.011), fracture type (P<0.001), and use of a walking aid before fracture (P=0.004). Significant differences were also detected in HGS test scores with respect to all independent variables tested: age (P<0.001), sex (P<0.001), fracture type (P<0.001), and use of a walking aid before fracture (P=0.035).
Conclusion: Increasing age, female sex, having a hip fracture, and use of a walking aid before fracture predicted reduction in the physical function and strength among older adults with LBF.
Fulltext Safety and efficacy of oil palm phenolic supplementation in improving lipid profile among hyperlipidemic adults: a phase 2, randomized, double-blind, placebo-controlled clinical trial

Muhammad Ismail Tadj NB, Ibrahim NI, Tg Abu Bakar Sidik TMI, Zulfarina MS, Haji Mohd Saad Q, Leow SS, et al.

Front Pharmacol, 2023;14:1190663.
PMID: 37484009 DOI: 10.3389/fphar.2023.1190663

Introduction: Oil palm phenolic (OPP) is an antioxidant aqueous palm oil by-product and contains a high amount of phenolics. OPP has been proven to have many therapeutical benefits, and one of them is as an antihyperlipidemic agent. The previous phase 1 clinical trial proved OPP was safe to be orally consumed by healthy volunteers and yielded a good lipid profile. Thus, this phase 2 clinical trial was conducted to determine the effectiveness of OPP in improving the lipid profile among hyperlipidemic subjects. Methods: A parallel, placebo-controlled, randomized, double-blinded clinical trial was conducted for 2 months on 50 hyperlipidemic subjects aged 20-50 years old. The subjects were randomly distributed to two treatment arms with 25 participants each: control/placebo (11 males and 14 females) and 250 mg of OPP (10 males and 15 females). The subjects were required to consume one capsule per day for 60 days. Fasting blood sampling for routine blood profile (hematology, liver function, renal function, and lipid) analysis and a medical examination were conducted at baseline, day 30, and day 60. t-test analysis was used to compare the difference between two test groups. Results: The baseline lipid profile between control group (TC, 5.78 ± 0.52 mmol/L; LDL, 3.88 ± 0.51 mmol/L; HDL, 1.30 ± 0.25; TG, 1.30 ± 0.82), and 250 mg OPP (TC, 5.76 ± 0.54 mmol/L; LDL, 3.82 ± 0.59 mmol/L; HDL, 1.37 ± 0.34; TG, 1.25 ± 0.54) is insignificant. No serious adverse events (SAEs) were reported. No abnormality in fasting blood parameters in all groups was found. Compared to the control group among male participants, the 250 mg OPP group showed an improved serum triglyceride level. There were no statistically significant changes in all blood parameters from day 1 to day 60 with the exception of triglyceride level. Conclusion: The absence of SAEs reported and no abnormal findings in biochemistry and hematology results suggested that the 250 mg OPP was safe to be taken by hyperlipidemic patients with a high probability of reducing triglyceride level in hyperlipidemic male patients The outcomes from this phase II trial suggest that by incorporating OPP supplements into the diet may be a promising strategy for individuals with hyperlipidemia to improve their lipid profiles and reduce cardiovascular risk. However, more research is needed to fully understand the mechanisms of action and establish the long-term efficacy and safety of OPP supplementation in larger scale. Limitation: Small samples size hence lack of diversity (25 subjects per groups) and early sharing of treatment-response results. Clinical Trial Registration: clinicaltrials.gov, identifier NCT04573218.

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