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Tocotrienols are needed for normal bone calcification in growing female rats

Norazlina M, Ima-Nirwana S, Abul Gapor MT, Abdul Kadir Khalid B

Asia Pac J Clin Nutr, 2002;11(3):194-9.
PMID: 12230232

In this study the effects of vitamin E deficiency and supplementation on bone calcification were determined using 4-month-old female Sprague-Dawley rats. The rats weighed between 180 and 200 g. The study was divided in three parts. In experiment I the rats were given normal rat chow (RC, control group), a vitamin E deficient (VED) diet or a 50% vitamin E deficient (50%VED) diet. In experiment 2 the rats were given VED supplemented with 30 mg/kg palm vitamin E (PVE30), 60 mg/kg palm vitamin E (PVE60) or 30 mg/kg pure alpha-tocopherol (ATF). In experiment 3 the rats were fed RC and given the same supplements as in experiment 2. The treatment lasted 8 months. Vitamin E derived from palm oil contained a mixture of ATF and tocotrienols. Rats on the VED and 50%VED diets had lower bone calcium content in the left femur compared to the RC group (91.6 +/- 13.3 mg and 118.3 +/- 26.0 mg cf 165.7 +/- 15.2 mg; P < 0.05) and L5 vertebra (28.3 +/- 4.0 mg and 39.5 +/- 6.2 mg compared with 51.4 +/- 5.8 mg; P < 0.05). Supplementing the VED group with PVE60 improved bone calcification in the left femur (133.6 +/- 5.0 mg compared with 91.6 +/- 13.3 mg; P < 0.05) and L5 vertebra (41.3 +/- 3.3 mg compared with 28.3 +/- 4.0 mg; P < 0.05) while supplementation with PVE30 improved bone calcium content in the L5 vertebra (35.6 +/- 3.1 mg compared with 28.3 +/- 4.0 mg; P < 0.05). However, supplementation with ATF did not change the lumbar and femoral bone calcium content compared to the VED group. Supplementing the RC group with PVE30, PVE60 or ATF did not cause any significant changes in bone calcium content. In conclusion, vitamin E deficiency impaired bone calcification. Supplementation with the higher dose of palm vitamin E improved bone calcium content, but supplementation with pure ATF alone did not. This effect may be attributed to the tocotrienol content of palm vitamin E. Therefore, tocotrienols play an important role in bone calcification.
Fulltext Vitamin A and Bone Health: A Review on Current Evidence

Yee MMF, Chin KY, Ima-Nirwana S, Wong SK

Molecules, 2021 Mar 21;26(6).
PMID: 33801011 DOI: 10.3390/molecules26061757

Vitamin A is a fat-soluble micronutrient essential for growth, immunity, and good vision. The preformed retinol is commonly found in food of animal origin whereas provitamin A is derived from food of plant origin. This review summarises the current evidence from animal, human and cell-culture studies on the effects of vitamin A towards bone health. Animal studies showed that the negative effects of retinol on the skeleton were observed at higher concentrations, especially on the cortical bone. In humans, the direct relationship between vitamin A and poor bone health was more pronounced in individuals with obesity or vitamin D deficiency. Mechanistically, vitamin A differentially influenced the stages of osteogenesis by enhancing early osteoblastic differentiation and inhibiting bone mineralisation via retinoic acid receptor (RAR) signalling and modulation of osteocyte/osteoblast-related bone peptides. However, adequate vitamin A intake through food or supplements was shown to maintain healthy bones. Meanwhile, provitamin A (carotene and β-cryptoxanthin) may also protect bone. In vitro evidence showed that carotene and β-cryptoxanthin may serve as precursors for retinoids, specifically all-trans-retinoic acid, which serve as ligand for RARs to promote osteogenesis and suppressed nuclear factor-kappa B activation to inhibit the differentiation and maturation of osteoclasts. In conclusion, we suggest that both vitamin A and provitamin A may be potential bone-protecting agents, and more studies are warranted to support this hypothesis.
Fulltext A Review on the Enhancement of Calcium Phosphate Cement with Biological Materials in Bone Defect Healing

Wong SK, Wong YH, Chin KY, Ima-Nirwana S

Polymers (Basel), 2021 Sep 12;13(18).
PMID: 34577976 DOI: 10.3390/polym13183075

Calcium phosphate cement (CPC) is a promising material used in the treatment of bone defects due to its profitable features of self-setting capability, osteoconductivity, injectability, mouldability, and biocompatibility. However, the major limitations of CPC, such as the brittleness, lack of osteogenic property, and poor washout resistance, remain to be resolved. Thus, significant research effort has been committed to modify and reinforce CPC. The mixture of CPC with various biological materials, defined as the materials produced by living organisms, have been fabricated by researchers and their characteristics have been investigated in vitro and in vivo. This present review aimed to provide a comprehensive overview enabling the readers to compare the physical, mechanical, and biological properties of CPC upon the incorporation of different biological materials. By mixing the bone-related transcription factors, proteins, and/or polysaccharides with CPC, researchers have demonstrated that these combinations not only resolved the lack of mechanical strength and osteogenic effects of CPC but also further improve its own functional properties. However, exceptions were seen in CPC incorporated with certain proteins (such as elastin-like polypeptide and calcitonin gene-related peptide) as well as blood components. In conclusion, the addition of biological materials potentially improves CPC features, which vary depending on the types of materials embedded into it. The significant enhancement of CPC seen in vitro and in vivo requires further verification in human trials for its clinical application.
Fulltext Effects of age, sex, and ethnicity on bone health status of the elderly in Kuala Lumpur, Malaysia

Chin KY, Kamaruddin AA, Low NY, Ima-Nirwana S

Clin Interv Aging, 2016;11:767-73.
PMID: 27358558 DOI: 10.2147/CIA.S108772

Osteoporosis is a significant health problem in the developing countries and its prevalence data are important for the estimation of health care burden and policy making. This study aimed to determine the age-related changes in bone health and the prevalence of osteoporosis in males and females aged 50 years or above living in Kuala Lumpur, Malaysia.
Fulltext A review of knowledge, belief and practice regarding osteoporosis among adolescents and young adults

Chan CY, Mohamed N, Ima-Nirwana S, Chin KY

Int J Environ Res Public Health, 2018 08 12;15(8).
PMID: 30103534 DOI: 10.3390/ijerph15081727

Osteoporosis is a major public health problem affecting millions of people worldwide. Increasing knowledge, correcting health belief and promoting osteoprotective practices are effective measures for building and maintaining strong bone throughout ones' life-span. This review aims to summarize the contemporary evidence on the knowledge, beliefs and practice of adolescents and young adults on bone health. We performed literature searches using the PubMed and Scopus databases to identify original studies from 2008 to May 2018 using the search terms "(knowledge OR beliefs OR attitude OR practice OR behaviours OR physical activity OR exercise OR diet OR nutrition) AND (young OR youth OR adolescents OR children OR young adults OR students OR teenager) AND (osteoporosis OR bone health)". Of the 3206 articles found, 34 met the inclusion criteria. Studies showed that most adolescents and young adults had poor knowledge and expressed disinterest in osteoporosis. They believed that other diseases were more serious than osteoporosis, contributing to low perceived susceptibility and seriousness towards this disease. Popular media emerged as a platform to obtain information regarding osteoporosis. The lack of knowledge and misconceptions about osteoporosis led to poor osteoprotective practices. As a conclusion, the current evidence revealed a lack of awareness about osteoporosis among adolescents and young adults. Educational interventions may be useful to improve the awareness of osteoporosis among this population.
Fulltext Proton Pump Inhibitors and Fracture Risk: A Review of Current Evidence and Mechanisms Involved

Thong BKS, Ima-Nirwana S, Chin KY

Int J Environ Res Public Health, 2019 May 05;16(9).
PMID: 31060319 DOI: 10.3390/ijerph16091571

The number of patients with gastroesophageal problems taking proton pump inhibitors (PPIs) is increasing. Several studies suggested a possible association between PPIs and fracture risk, especially hip fractures, but the relationship remains contentious. This review aimed to investigate the longitudinal studies published in the last five years on the relationship between PPIs and fracture risk. The mechanism underlying this relationship was also explored. Overall, PPIs were positively associated with elevated fracture risk in multiple studies (n = 14), although some studies reported no significant relationship (n = 4). Increased gastrin production and hypochlorhydria are the two main mechanisms that affect bone remodeling, mineral absorption, and muscle strength, contributing to increased fracture risk among PPI users. As a conclusion, there is a potential relationship between PPIs and fracture risks. Therefore, patients on long-term PPI treatment should pay attention to bone health status and consider prophylaxis to decrease fracture risk.
Biochemical and histopathological assessment of liver in a rat model of metabolic syndrome induced by high-carbohydrate high-fat diet

Wong SK, Chin KY, Ahmad F, Ima-Nirwana S

J Food Biochem, 2020 Aug 03.
PMID: 32744348 DOI: 10.1111/jfbc.13371

This study aimed to evaluate the oxidative stress status, antioxidants capacity, and presence of nonalcoholic fatty liver disease (NAFLD) in an animal model of MetS induced by high-carbohydrate high-fat (HCHF) diet. Male Wistar rats were randomized into two groups, assigned for two different types of diet (standard rat pellet or HCHF diet) for 20 weeks. Liver was excised, weighed, and subjected to lipid peroxidation, nitric oxide (NO·) production, antioxidants activity, and histological assessment. The HCHF rats had higher lipid peroxidation and NO· level but lower enzymatic and nonenzymatic antioxidant levels than the normal animals. Histological evaluation revealed higher lobular inflammation, hepatocellular ballooning, NAFLD activity score, and lipid accumulation in the liver of HCHF group. In conclusion, the HCHF diet causes an increase in oxidative stress, depletion of antioxidants capacity, NAFLD, and liver injury. The induction of oxidative stress may be partially responsible for the development of NAFLD in MetS. PRACTICAL APPLICATIONS: The prevalence of MetS is estimated to increase rapidly with the escalating levels of obesity, diabetes, hypertension, and dyslipidemia. A suitable animal model of MetS that best mimicked the human disease state with known underlying mechanisms responsible for the pathogenesis of MetS is indispensable to search for potential adjunct therapies and drug targets. Thus, our current study elucidated the involvement of oxidative stress in linking MetS and NAFLD which might resemble the pathogenesis of MetS among Southeast Asian population.
Fulltext The relationships between thyroid hormones and thyroid-stimulating hormone with lipid profile in euthyroid men

Chin KY, Ima-Nirwana S, Mohamed IN, Aminuddin A, Johari MH, Ngah WZ

Int J Med Sci, 2014;11(4):349-55.
PMID: 24578612 DOI: 10.7150/ijms.7104

Alteration in lipid profile is a common observation in patients with thyroid dysfunction, but the current knowledge on the relationship between lipids and thyroid hormone levels in euthyroid state is insufficient. The current study aimed to determine the association between thyroid hormones and thyroid-stimulating hormone (TSH) with lipid profile in a euthyroid male population.
Fulltext Serum osteocalcin is significantly related to indices of obesity and lipid profile in Malaysian men

Chin KY, Ima-Nirwana S, Mohamed IN, Ahmad F, Ramli ES, Aminuddin A, et al.

Int J Med Sci, 2014;11(2):151-7.
PMID: 24465160 DOI: 10.7150/ijms.7152

Recent studies revealed a possible reciprocal relationship between the skeletal system and obesity and lipid metabolism, mediated by osteocalcin, an osteoblast-specific protein. This study aimed to validate the relationship between serum osteocalcin and indices of obesity and lipid parameters in a group of Malaysian men.
Piper sarmentosum: a new hope for the treatment of osteoporosis

Mohd Ramli ES, Suhaimi F, Ahmad F, Shuid AN, Mohamad N, Ima-Nirwana S

Curr Drug Targets, 2013 Dec;14(14):1675-82.
PMID: 24107234

Osteoporosis is a major global health problem. Osteoporosis is characterized by the loss of bone mass and strength which leads to an increased risk of fracture. Glucocorticoid treatment is the leading cause of secondary osteoporosis. Glucocorticoid action in bone depends upon the expression of 11beta-hydroxysteroid dehydrogenase type 1 enzyme (11β-HSD1). The oestrogen deficient state causes osteoporosis due to enhancement of osteoclastogenesis by oxidative stress which leads to increased bone resorption. Piper sarmentosum (Daun Kaduk) is commonly used in the local cuisine of South East Asia. It is also traditionally used to treat many diseases such as inflammation, dermatitis and joint pain. Studies have revealed antioxidant properties through its flavonoids compound naringenin which acts as a superoxide scavenger that may help in the endogenous antioxidant defence system to protect bone against osteoporosis. Recent studies found that Ps extract has the ability to inhibit the expression and activity of 11β-HSD1 in adipose tissue and bone which restored bone structure and strength. It also accelerates fracture healing in the oestrogen deficient state through its antioxidant properties. The cost of conventional treatment is high and together with the adverse effects it leads to noncompliance. Treatment modalities with herbal medicine, less side effects and is cheaper need to be explored.This review focused on the therapeutic effect of Ps extract on fracture healing in ovariectomized rats and its protective effects against glucocorticoid induced osteoporotic rats.
Fulltext Thyroid-stimulating hormone is significantly associated with bone health status in men

Chin KY, Ima-Nirwana S, Mohamed IN, Aminuddin A, Johari MH, Ngah WZ

Int J Med Sci, 2013;10(7):857-63.
PMID: 23781131 DOI: 10.7150/ijms.5870

Recent studies revealed a novel association between thyroid-stimulating hormone (TSH) and bone health status in healthy male populations. The present study aimed to validate this association and provide new information on the relationship between TSH levels and calcaneal speed of sound (SOS) in men.
Fulltext Vitamin E reversed nicotine-induced toxic effects on bone biochemical markers in male rats

Norazlina M, Hermizi H, Faizah O, Nazrun AS, Norliza M, Ima-Nirwana S

Arch Med Sci, 2010 Aug 30;6(4):505-12.
PMID: 22371792 DOI: 10.5114/aoms.2010.14460

Vitamin E is beneficial in restoring bone histomorphometric parameters in nicotine-treated rats. This study determined the effectiveness of 3 forms of vitamin E in restoring bone metabolism in nicotine-treated rats.
Fulltext The relationship between metabolic syndrome and osteoporosis: a review

Wong SK, Chin KY, Suhaimi FH, Ahmad F, Ima-Nirwana S

Nutrients, 2016 Jun 07;8(6).
PMID: 27338453 DOI: 10.3390/nu8060347

Metabolic syndrome (MetS) and osteoporosis are two major healthcare problems worldwide. Metabolic syndrome is a constellation of medical conditions consisting of central obesity, hyperglycemia, hypertension, and dyslipidemia, in which each acts on bone tissue in different ways. The growing prevalence of MetS and osteoporosis in the population along with the controversial findings on the relationship between both conditions suggest the importance for further investigation and discussion on this topic. This review aims to assess the available evidence on the effects of each component of MetS on bone metabolism from the conventional to the contemporary. Previous studies suggested that the two conditions shared some common underlying pathways, which include regulation of calcium homeostasis, receptor activator of NF-κB ligand (RANKL)/receptor activator of the NF-κB (RANK)/osteoprotegerin (OPG) and Wnt-β-catenin signaling pathways. In conclusion, we suggest that MetS may have a potential role in developing osteoporosis and more studies are necessary to further prove this hypothesis.
The association between backpack use and low back pain among pre-university students: A pilot study

Amyra Natasha A, Ahmad Syukri A, Siti Nor Diana MK, Ima-Nirwana S, Chin KY

J Taibah Univ Med Sci, 2018 Apr;13(2):205-209.
PMID: 31435325 DOI: 10.1016/j.jtumed.2017.06.005

Background: Individuals aged 30-60 years have a high possibility of experiencing low back pain. However, children and adolescents are not exempted from this problem. This study aimed to determine the relationship between backpack usage and the frequency of low back pain in pre-university students.
Methods: A total of 101 currently enrolled pre-university students were recruited for this cross-sectional study. They answered a questionnaire about their demographic details and their frequency of backpack usage. Their backpacks were weighed for four consecutive school days. The Roland-Morris Disability Questionnaire and Body Discomfort Chart were used to rate discomfort levels.
Results: The use and weight of a backpack were not significantly associated with low back pain, as indicated by the Roland-Morris Disability Questionnaire and Body Discomfort Chart (p > 0.05).
Conclusion: This study did not find an association between the use of a backpack and low back pain in Malaysian pre-university students.
Osteoporosis knowledge and practice among Malaysian university students

Chan CY, Subramaniam S, Ravintharan K, Ima-Nirwana S, Chin KY

J Pak Med Assoc, 2021 Feb;71(Suppl 2)(2):S30-S36.
PMID: 33785938

OBJECTIVE: This study aimed to investigate osteoporosis knowledge and bone health practices among students of a Malaysian public university.
Methods: A cross-sectional study was conducted amongst university students from a Malaysian's public university. A total of 228 students responded to a self-administered questionnaire consisting of items evaluating knowledge and practices of osteoporosis.
RESULTS: The students showed a moderate level of osteoporosis awareness with a score of 63.3%. Male subjects had higher awareness scores of osteoporosis complications compared to female subjects (p= 0.010). Malay (p= 0.002) and Chinese (p= 0.005) had higher levels of osteoporosis awareness compared to Indian students. Coffee and alcohol intakes were significantly different between the sexes (p= 0.013) and the ethnic groups (p= 0.029). Most of the subjects in our study were minimally active (43.9%).
CONCLUSIONS: The students had a reasonable levels of knowledge about osteoporosis, but their health activities to avoid osteoporosis were insufficient. This illustrates the need for educational programmes to improve students' knowledge and awareness for successful osteoporosis prevention.
Effect of vitamin E on periodontitis: Evidence and proposed mechanisms of action

Shadisvaaran S, Chin KY, Shahida MS, Ima-Nirwana S, Leong XF

J Oral Biosci, 2021 06;63(2):97-103.
PMID: 33864905 DOI: 10.1016/j.job.2021.04.001

BACKGROUND: Periodontitis is a noncommunicable inflammatory disease of the soft tissue and bone surrounding the teeth in the jaw, which affects susceptible individuals with poor oral hygiene. A growing interest has been seen in the use of dietary supplements and natural products for the treatment and prevention of periodontitis. Vitamin E consists of two major groups, namely tocopherols and tocotrienols, which are botanical lipophilic compounds with excellent anti-inflammatory and antioxidant properties.
HIGHLIGHT: This review aimed to summarize the preclinical and clinical findings on the effects of vitamin E on periodontitis. The current literature suggests that vitamin E could improve the periodontal status by correcting redox status imbalance, reducing inflammatory responses, and promoting wound healing, thus highlighting the potential of vitamin E in the management of periodontitis.
CONCLUSION: Direct evidence for the use of vitamin E supplementation or treatment of periodontitis in humans is still limited. More well-designed and controlled studies are required to ascertain its effectiveness.
Fulltext Animal models of metabolic syndrome: a review

Wong SK, Chin KY, Suhaimi FH, Fairus A, Ima-Nirwana S

Nutr Metab (Lond), 2016;13:65.
PMID: 27708685 DOI: 10.1186/s12986-016-0123-9

Metabolic syndrome (MetS) consists of several medical conditions that collectively predict the risk for cardiovascular disease better than the sum of individual conditions. The risk of developing MetS in human depends on synergy of both genetic and environmental factors. Being a multifactorial condition with alarming rate of prevalence nowadays, establishment of appropriate experimental animal models mimicking the disease state in humans is crucial in order to solve the difficulties in evaluating the pathophysiology of MetS in human. This review aims to summarize the underlying mechanisms involved in the pathophysiology of dietary, genetic, and pharmacological models of MetS. Furthermore, we will discuss the usefulness, suitability, pros and cons of these animal models. Even though numerous animal models of MetS have been established, further investigations on the invention of new animal model and clarification of plausible mechanisms are still necessary to confer a better understanding to researchers on the selection of animal models for their studies.
Exploring the potential of tocotrienol from Bixa orellana as a single agent targeting metabolic syndrome and bone loss

Wong SK, Chin KY, Suhaimi FH, Ahmad F, Ima-Nirwana S

Bone, 2018 11;116:8-21.
PMID: 29990585 DOI: 10.1016/j.bone.2018.07.003

Metabolic syndrome (MetS) is associated with osteoporosis due to the underlying inflammatory and hormonal changes. Annatto tocotrienol has been shown to improve medical complications associated with MetS or bone loss in animal studies. This study aimed to investigate the effects of annatto tocotrienol as a single treatment for MetS and osteoporosis in high-carbohydrate high-fat (HCHF) diet-induced MetS animals. Three-month-old male Wistar rats were randomly divided into five groups. The baseline group was euthanized at the onset of the study. The normal group received standard rat chow and tap water. The remaining groups received HCHF diet and treated with three different regimens orally daily: (a) tocopherol-stripped corn oil (the vehicle of tocotrienol), (b) 60 mg/kg annatto tocotrienol, and (c) 100 mg/kg annatto tocotrienol. At the end of the study, measurements of MetS parameters, body compositions, and bone mineral density were performed in animals before sacrifice. Upon euthanasia, blood and femur of the rats were harvested for the evaluations of bone microstructure, biomechanical strength, remodelling activities, hormonal changes, and inflammatory response. Treatment with annatto tocotrienol improved all MetS parameters (except abdominal obesity), trabecular bone microstructure, bone strength, increased osteoclast number, normalized hormonal changes and inflammatory response in the HCHF animals. In conclusion, annatto tocotrienol is a potential agent for managing MetS and osteoporosis concurrently. The beneficial effects of annatto tocotrienol may be attributed to its ability to prevent the hormonal changes and pro-inflammatory state in animals with MetS.
Fulltext The Effects of Vitamin E from Elaeis guineensis (Oil Palm) in a Rat Model of Bone Loss Due to Metabolic Syndrome

Wong SK, Chin KY, Suhaimi FH, Ahmad F, Ima-Nirwana S

Int J Environ Res Public Health, 2018 08 24;15(9).
PMID: 30149518 DOI: 10.3390/ijerph15091828

The beneficial effects of vitamin E in improving components of MetS or bone loss have been established. This study aimed to investigate the potential of palm vitamin E (PVE) as a single agent, targeting MetS and bone loss concurrently, using a MetS animal model. Twelve-week-old male Wistar rats were divided into five groups. The baseline group was sacrificed upon arrival. The normal group was given standard rat chow. The remaining three groups were fed with high-carbohydrate high-fat (HCHF) diet and treated with tocopherol-stripped corn oil (vehicle), 60 mg/kg or 100 mg/kg PVE. At the end of the study, the rats were evaluated for MetS parameters and bone density. After euthanasia, blood and femurs were harvested for the evaluation of lipid profile, bone histomorphometric analysis, and remodeling markers. PVE improved blood pressure, glycemic status, and lipid profile; increased osteoblast surface, osteoid surface, bone volume, and trabecular thickness, as well as decreased eroded surface and single-labeled surface. Administration of PVE also significantly reduced leptin level in the HCHF rats. PVE is a potential agent in concurrently preventing MetS and protecting bone loss. This may be, in part, achieved by reducing the leptin level and modulating the bone remodeling activity in male rats.
Fulltext Wound Healing Properties of Selected Natural Products

Ibrahim N', Wong SK, Mohamed IN, Mohamed N, Chin KY, Ima-Nirwana S, et al.

Int J Environ Res Public Health, 2018 10 25;15(11).
PMID: 30366427 DOI: 10.3390/ijerph15112360

Wound healing is a complex process of recovering the forms and functions of injured tissues. The process is tightly regulated by multiple growth factors and cytokines released at the wound site. Any alterations that disrupt the healing processes would worsen the tissue damage and prolong repair process. Various conditions may contribute to impaired wound healing, including infections, underlying diseases and medications. Numerous studies on the potential of natural products with anti-inflammatory, antioxidant, antibacterial and pro-collagen synthesis properties as wound healing agents have been performed. Their medicinal properties can be contributed by the content of bioactive phytochemical constituents such as alkaloids, essential oils, flavonoids, tannins, saponins, and phenolic compounds in the natural products. This review highlights the in vitro, in vivo and clinical studies on wound healing promotions by the selected natural products and the mechanisms involved.

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