Fenugreek final

According to the Natural Standard Research Collaboration, diabetic patients taking 25 grams of powdered Fenugreek seeds reported no renal or clinical hepatic toxicity. However, the sample of the study was too small to generalize a conclusion. According to Opdyke, the rats showed acute oral LD50 to be greater than 5 g/kg and acute dermal LD50 to be greater than 2 g/kg in rabbits. 8 After evaluating the reverse mutation assay, mouse lymphoma forward mutation assay, and mouse micronucleus assay Flammang concluded that 4-Hydroxyisoleucine (4-OH-Ile) causes no genotoxicity. In addition, it was found that the addition of Fenugreek seed extract to food was expected to be safe for patients due to the wide margin of safety. 9 ,[object Object],The hypoglycemic effects and the antihyperglycemic effects of Fenugreek seeds are thought to be from several mechanisms: stimulation of pancreatic beta cells, phosphorylation of a number of proteins, and promotion of glucose uptake by peripheral cells. (CITE) 4-Hydroxyisoleucine, an amino acid that can be extracted from the seeds, seems to promote insulin secretion. This activity is from the direct effect of the amino acid on pancreatic B cells in rats and humans. It is believed that its major isomer is responsible for this action. The effect is glucose-dependent occurring only at certain glucose concentrations as seen in human and rat pancreatic cells. 4 Additionally, Fenugreek seeds are a source of dietary fiber. Fenugreek seeds contain mucilaginous fiber and total fiber to the extent of 20% and 50%, respectively. Fiber has been shown to reduce plasma glucose in diabetic human subjects. With high fiber foods, there is a delay in glucose absorption, which contributes the most to reducing after-meal blood glucose. The lowering of blood glucose comes from decreasing the absorption of glucose after its consumption. 5 Other pathways, including the inhibition of certain enzymes involved in glucose metabolism, the effect of fiber on plasma glucose, alterations in hepatic glucose production, and the peripheral glucose utilization, are currently being investigated. 5,6 In 2007 7.8% of the US population had Diabetes Mellitus, and there are over 1.6 million new diagnosed cases every year 1 . When these statistics are combined with a health care system that is complicated, expensive, and cumbersome to navigate, it creates a market for self treatment. It is believed that at least one-third of the United States uses herbal medicines on a regular basis for a variety of illnesses and medical conditions. It is extremely important that pharmacists have a working knowledge of these herbals medications because whether they work or not, pharmacists need to be able to educate the portion of the population that chooses to use them. Fenugreek is one of the oldest cultivated medicinal plants in the world. There is evidence that these seeds were used for medicinal purposes in Chinese, Greek, Arabian and Indian cultures for thousands of years. 2 This presentation will focus on the anti-diabetic effects that Fenugreek seeds are marketed to have by exploring the pharmacology, safety and efficacy of the Fenugreek seed. Fenugreek for Diabetics: The Hypoglycemic Effect Merid Belayneh , Julie Kaplan, Thomas Lu, Jonathan Mendonsa , Stephaine Moore, Rachel S. Seidman and Tosha Wyatt. VCU Pharmacy School ( 410 North 12th Street , Richmond, Virginia 23298-058) Side Effects Toxicity We would like to thank Dr. Y. Zhang for guidance and Mrs. Veronica P. Shuford for providing the poster template. Pharmacology Safety Resources Active Ingredients The major components of Fenugreek seeds are mucilaginous fiber, protein, saponins, lipids, and unavailable carbohydrates. The seeds also contain the major alkaloid Trigonelline, and flavonoids, carotenoids, and coumarins 2 Fenugreek plants are annuals and therefore must be replanted each year. They have grey-green, tripartite, toothed leaves and grow to approximately 30 to 60 cm tall. In the summer, white or pale yellow flowers appear and eventually develop into long, slender, sword-shaped seed pods with a curved, beak-like tip. 3 Latin Name: Trigonella foenum-graecum Synonyms: Kasoori Methi, Bird’s Foot, Greek Hay Seed 2 Several small scale human studies have found Fenugreek to lower blood glucose levels. Ulbricht et al. conducted a systematic review on the efficacy of Fenugreek in lowering glucose levels in diabetic patients (Table 1). All studies showed some form of hypoglycemic effect in diabetic patients, as depicted on Table 2, but there are concerns about the limitations in sample size and study conditions. 2 Lu et al. conducted a randomized, double-blind, placebo-paralleled trial on 64 Type 2 diabetic patients that had poor control glucose levels while on sulfonylurea medications (ie. glipizide, glyburide, and glimipride) (Table 3,4). 7 Figure 4: Serum glucose concentrations. Control group received a placebo capsule, dietary control, and exercise. Changes in fasting glucose (FG) and mean glucose tolerance (MGT) tests after two months are similar in both groups. Gupta et al. suggest that Fenugreek may be as effective as exercise and healthy diet. 2 Figure 5 : Serum clearance rate. The study reported that the control group had a serum clearance rate of 153 ± 11.92 mg/mL/min, while the Fenugreek group had a serum clearance rate of 136.4 ± 6.36 mg/mL/min. 2 Although blood glucose was not reported, this data implies that it is increased. 2 The active ingredient attributed to have hypoglycemic activity is 4-Hydroxyisoleucine (an amino acid) 2 Fenugreek’s (Trigonella foennum graecum) use can be traced back to Ayurevedic and Chinese medicine as a remedy for inflammation, high cholesterol, and diabetes. This research is set forth to determine if Fenugreek seeds can be used to lower blood glucose as a possible treatment for diabetes. The proposed mechanisms of action are that 4-Hydroxyisoleucine (a component of Fenugreek) acts directly on the pancreatic B cells in inducing insulin secretion or that Fenugreek acts as a fiber to reduce sugar absorption in the GI tract. Toxicity and side effects for Fenugreek are hardly found in literature. Small scale human studies have found that Fenugreek lowers blood glucose levels, but research conditions were less than ideal to make further inferences. A study conducted in China found that Fenugreek may be beneficial in conjunction with sulfonylurea (a hypoglycemic medication) . If a patient chooses to use Fenugreek, monitoring of blood glucose levels by a health care professional is highly recommended. Figure 1 : Fenugreek leaves and seeds 3 Figure 2: Chemical Structure of 4-Hydroxyisoleucine 4 Table 1: Study conditions for the efficacy of Fenugreek in Diabetic Patients. 2 Table 2: The efficacy of Fenugreek in Diabetic Patients. 2 Figure 3: Minor side effects of Fenugreek 10 Table 3: Effect of Fenugreek/ Sulfonylurea co-administration on monitoring parameters. 7 Table 4: Effect of Fenugreek/ Sulfonylurea co-administration on the Liver and Kidney 7 Efficacy ,[object Object],[object Object],[object Object],[object Object],[object Object],A summary of the studies condition included in the systematic review. A summary of the study results included in the systematic review. Gupta et al and Raghuram et al are illustrated on figures 4 and 5, respectfully. The Lu et al. study (2010) gives a possible insight into the future clinical application of Fenugreek. For patients that don’t have their blood glucose adequately controlled with sulfonylurea medications these results could be important. The study showed improvement in the core three parameters that diabetic patients need to monitor: free glucose, two hour post-prandial blood glucose and HbA1c. It also demonstrated that Fenugreek had no negative effects on the liver and kidney (Table 2). Furthermore, the study provided novel evidence that Fenugreek might alleviate symptoms of diabetics (Table 2). All these findings show that further research is warranted. 7

Fenugreek final

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