Mohd Shara

The Safety of Citrus aurantium (Bitter Orange) and its Primary Protoalkaloid p-Synephrine

Citrus aurantium (bitter orange) extract and its principal protoalkaloidal constituent p‐synephrine are widely used in weight loss and weight management as well as in sports performance products. However, questions are raised frequently regarding the safety of these ingredients. The potential inherent dangers associated with the use of products containing C. aurantium extract are frequently touted, while conversely, millions of doses of dietary supplements have been consumed by possibly millions of individuals in recent years. Furthermore, millions of people consume on a daily basis various juices and food products from Citrus species that contain p‐synephrine. This review summarizes current information regarding the safety of C. aurantium (bitter orange) extract and p‐synephrine based on human, animal and in vitro assessments as well as receptor binding and mechanistic studies. The data indicate that based on current knowledge, the use of bitter orange extract and p‐synephrine appears to be exceedingly safe with no serious adverse effects being directly attributable to these ingredients. Copyright

A Review of the Human Clinical Studies Involving Citrus aurantium (Bitter Orange) Extract and its Primary Protoalkaloid p-Synephrine

This review summarizes the published as well as unpublished human studies involving Citrus aurantium (bitter orange) extract and its primary protoalkaloid p-synephrine, providing information and an assessment of the safety and efficacy of these widely used products. The results of over 20 studies involving a total of approximately 360 subjects that consumed p-synephrine alone or in combination with other ingredients are reviewed and critiqued. Over 50 % of the subjects involved in these studies were overweight/obese, and approximately two-thirds of these overweight/obese subjects consumed caffeine (132-528 mg/day) in conjunction with p-synephrine (10-53 mg/day). Bitter orange/p-synephrine containing products were consumed for up to 12 weeks. Approximately 44 % of the subjects consumed a bitter orange/p-synephrine only product, while the remainder consumed a complex product that contained multiple ingredients in addition to p-synephrine. In general, bitter orange extract alone (p-synephrine) or in combination with other herbal ingredients did not produce significant adverse events as an increase in heart rate or blood pressure, or alter electrocardiographic data, serum chemistry, blood cell counts or urinalysis. p-Synephrine alone as well as in combination products were shown to increase resting metabolic rate and energy expenditure, and modest increases in weight loss were observed with bitter orange extract/p-synephrine-containing products when given for six to 12 weeks. Longer term studies are needed to further assess the efficacy of these products and affirm their safety under these conditions.

A Review of the Receptor-Binding Properties of p-Synephrine as Related to Its Pharmacological Effects

Bitter orange (Citrus aurantium) extract and its primary protoalkaloid p-synephrine are used widely in weight loss/weight management and sports performance products. Because of structural similarities, the pharmacological effects of p-synephrine are widely assumed to be similar to those of ephedrine, m-synephrine (phenylephrine), and endogenous amine neurotransmitters as norepinephrine and epinephrine. However, small structural changes result in the receptor binding characteristics of these amines that are markedly different, providing a plausible explanation for the paucity of adverse effects associated with the wide-spread consumption of p-synephrine in the form of dietary supplements as well as in various Citrus foods and juices. This paper summarizes the adrenoreceptor binding characteristics of p-synephrine relative to m-synephrine, norepinephrine, and other amines as related to the observed pharmacological effects.

Public knowledge and awareness of cardiovascular disease and its risk factors: a cross-sectional study of 1000 Jordanians

Objective  To assess the level of the current knowledge and understanding of cardiovascular disease (CVD) among Jordans general public, their behaviour towards CVD and the factors associated with different CVD knowledge levels.

Efficacy and Safety of White Willow Bark (Salix alba) Extracts

Willow bark extract has been used for thousands of years as an anti‐inflammatory, antipyretic, and analgesic. In spite of its long history of use, relatively few human and animal studies have been published that confirm anecdotal observations. A small number of clinical studies have been conducted that support the use of willow bark extracts in chronic lower back and joint pain and osteoarthritis. Willow bark extracts also are widely used in sports performance and weight loss products presumably because of anti‐inflammatory and analgesic activities, although no human studies have been published that specifically and directly document beneficial effects. In recent years, various in vitro and animal studies have demonstrated that the anti‐inflammatory activity of willow bark extract is associated with down regulation of the inflammatory mediators tumor necrosis factor‐α and nuclear factor‐kappa B. Although willow bark extracts are generally standardized to salicin, other ingredients in the extracts including other salicylates as well as polyphenols, and flavonoids may also play prominent roles in the therapeutic actions. Adverse effects appear to be minimal as compared to non‐steroidal anti‐inflammatory drugs including aspirin. The primary cause for concern may relate to allergic reactions in salicylate‐sensitive individuals. Copyright

Cardiovascular Safety of Oral p-Synephrine (Bitter Orange) in Healthy Subjects: A Randomized Placebo-Controlled Cross-Over Clinical Trial

Bitter orange (Citrus aurantium) extract and its primary protoalkaloid p‐synephrine are widely consumed in combination with multiple herbal ingredients for weight management and sports performance. p‐Synephrine is also present in juices and foods derived from a variety of Citrus species. Questions exist regarding the safety of p‐synephrine because of structural similarities with other biogenic amines. This study assessed the cardiovascular (stimulatory) effects of bitter orange extract (49‐mg p‐synephrine) given to 18 healthy subjects (nine men and nine women) in a double‐blinded, placebo‐controlled cross‐over study. Heart rates, blood pressures, and electrocardiograms were determined at baseline, 30, 60, 90 min, 2, 4 , 6, and 8 h. Blood samples were drawn at baseline, 2 h and 8 h for serum chemistries, blood cell counts, and p‐synephrine and caffeine levels. No significant changes occurred in electrocardiograms, heart rates, systolic blood pressure, blood chemistries, or blood cell counts at any time point in either control or p‐synephrine treated group. A small (4.5 mmHg) decrease in diastolic blood pressure occurred in the p‐synephrine treated group at 60 min. No adverse effects were reported. Caffeine ingestion varied markedly among the participants. p‐Synephrine does not act as a stimulant at the dose used. Copyright

Implementation of clinical pharmacy services at a university hospital in Jordan

Clinical pharmacy services are still in the early stages of implementation in the Middle East. This study assessed the implementation of clinical pharmacy services at a major university hospital.

Safety evaluation of p-synephrine following 15 days of oral administration to healthy subjects: A clinical study

Extracts of bitter orange (BOE, Citrus aurantium L.) and its primary protoalkaloid p‐synephrine are extensively consumed as dietary supplements. p‐Synephrine is also present in foods and juices prepared from various Citrus species. The safety of p‐synephrine has been questioned as a result of structural similarities with ephedrine. This study assessed the cardiovascular (stimulant) and hemodynamic effects of BOE (49 mg p‐synephrine) daily given to 16 healthy subjects for 15 days in a placebo‐controlled, cross‐over, double‐blinded study. A physical evaluation by a cardiologist, as well as heart rates, blood pressures, and electrocardiograms were determined, and blood samples were drawn at baseline, and Days 5, 10, and 15. Serum levels for caffeine and p‐synephrine were measured at 1 and 2 weeks. Subjects completed a 10‐item health and metabolic questionnaire at baseline and on Day 15. No significant changes occurred in heart rate, electrocardiograms, systolic blood or diastolic pressures, blood cell counts, or blood chemistries in either the control or p‐synephrine treated groups at any time point. No adverse effects were reported in response to the bitter orange (p‐synephrine). Caffeine consumed by the participants varied markedly. Under these experimental conditions, BOE and p‐synephrine were without stimulant (cardiovascular) and adverse effects.

Prevalence of non-adherence among psychiatric patients in Jordan, a cross sectional study

It has been estimated that up to 50% of any patient population is at least partially non‐adherent to their prescribed treatment. Identifying barriers to adherence is required to develop effective interventions for psychiatric patients.

Sources of information used when prescribing for children, a survey of hospital based pediatricians.

BACKGROUND Due to the lack of properly tested medicines for children, there is little available information with regards to indications and dosing of medications in children. AIM To collect data on sources where hospital based pediatricians obtain prescribing information when treating children and the extent of collaboration with the hospital pharmacist. METHOD Two hundred and fifty pediatricians in different hospitals within different cities in Jordan were asked to fill in a structured questionnaire regarding information sources used when prescribing for children. RESULTS Questionnaires were collected from 162 (64.8%) hospital based pediatricians, who have completed the questionnaire by the designated date. Most (75.5%) reported that the Lexi Comps Drug Information Handbook was the source that they most frequently used for drug information when prescribing for in children. The BNF and the BNFc (British National Formulary for children) were found to be the most sources that contain sufficient information that aids pediatricians when prescribing for children. A minority (22%) claimed to consult with the hospital pharmacist when they face difficulties when prescribing for children. CONCLUSIONS Pediatricians rely on different information sources when they prescribe for children. Those sources vary in their reliability in aiding pediatrician when prescribing. Further work should be done in the provision of useful information on pediatric drug therapy to pediatricians. More steps should be taking place to activate collaboration and interaction between pediatricians and pharmacists as well.