WO1999025370A1

WO1999025370A1 - Methods for reducing the intestinal absorption of a caloric of compound in diabetics

Info

Publication number: WO1999025370A1
Application number: PCT/US1998/024507
Authority: WO
Inventors: Michael E. Osband
Original assignee: Nutricept, Inc.
Priority date: 1997-11-18
Filing date: 1998-11-17
Publication date: 1999-05-27

Abstract

A method for administering fenugreek to a diabetic subject is disclosed herein. The diabetic ingests fenugreek between 20 and 90 minutes prior to a meal in order to produce a maximal hypoglycemic response. Kits are also provided.

Description

METHODS FOR REDUCING THE INTESTINAL ABSORPTION

OF A CALORIC OF COMPOUND IN DIABETICS

Background of the Invention

Fenugreek, (trigonella foenum-graecum), an aromatic plant from the family of leguminosae found predominantly in Mediterranean countries and in Asia, has been important for many centuries as a food, as spice for flavoring of food products, and in traditional herbal medicines.

The seeds of the fenugreek plant, which have a very strong odor and taste, have been used as a flavoring agent in a variety of food products. For instance, ground fenugreek seeds are commonly found in Indian curry spices. In various other cultures ground fenugreek seeds have been used to make tea or mixed with water and other substances to form a thick dip called hilba. More recently, various extracts of fenugreek seeds have been used as seasonings in coffee, vanilla extracts, chutney, tobacco flavorings, and artificial maple syrup.

For centuries, extracts of fenugreek seeds also have been used in herbal medicines for the treatment of a variety of disorders. For example, it is believed that fenugreek seeds are useful for treating the symptoms of menopause and as a gelatinous soother for irritated tissues to help relieve sore throat pain, cough, and minor indigestion. (The Complete Book of Natural and Medicinal Cures, Prevention Magazine, p. 325-327.) More recently, studies aimed at identifying the medicinal properties of fenugreek seeds have revealed that fenugreek seeds are useful for regulating glucose levels in diabetics and for reducing cholesterol levels in patients with high cholesterol.

Diabetes mellitus, which encompasses both Type I (i.e., Insulin Dependent Diabetes Mellitus (IDDM)) and Type II (i.e., Non-Insulin Dependent Diabetes Mellitus (NIDDM)), is .known to affect more than one hundred million individuals worldwide. Although the exact cause of diabetes is unclear it is believed that diabetes may arise from any of a variety of physiological conditions such as genetic syndromes, viral infections, age related deterioration of structures responsible for maintaining the glycemic response, pancreatic disease, hormonal abnormalities, certain drugs or chemicals, insulin receptor abnormalities, etc.

Approximately five percent of the United States population is believed to be inflicted with diabetes. One fourth of these diabetics have insulin dependent disease, while three fourths have non-insulin dependent disease. The symptoms associated with IDDM result from the destruction of beta cells in the pancreas, generally by an autoimmune reaction. Patients with Type II non-insulin dependent diabetes exhibit abnoimal insulin secretion and resistance to insulin action in target tissues.

Although the underlying mechanisms associated with IDDM and NIDDM are different, both diseases result in the same diabetic complications. Complications associated with diabetes include circulatory abnormalities including coronary artery disease and stroke, retinopathy, nephropathy, neuropathy, foot ulcer, blindness, amputations, and kidney failure.

In order to prevent the complications associated with diabetes, the levels of glucose and insulin in diabetics must be carefully monitored and regulated. Diabetics may be prescribed a restricted diet by a physician. Generally carbohydrates are recommended as forty to sixty percent of the total energy intake. Consumption of sucrose is usually forbidden. In addition to diet restrictions, dietary fiber has been demonstrated to slow the absorption of sugar from the intestine, preventing the rise in blood glucose that ordinary follows the ingestion of carbohydrates.

Additionally, oral pharmaceutical agents are used to control glucose levels in patients with type II diabetes. Such agents include sulfonylureas, which stimulate the pancreas to secrete more insulin, metformin, which enhances the action of insulin on the liver and muscles, and acarbose, which interferes with the intestinal digestion of carbohydrates.

Some NIDDM diabetics may be treated to maintain glucose levels through regulation of diet without the administration of insulin. Diabetics with more severe cases of NIDDM and those unable to follow a strict diet may be administered insulin in combination with a regulated diet. If the diet of these patients is carefully regulated, insulin administration may be reduced but not eliminated.

All patients with IDDM must be administered insulin daily, either by oral agents, periodic injections or infusion pumps. In conventional insulin therapy, one or two doses of modified insulin, sometimes containing small amounts of regular insulin, are injected. Multiple subcutaneous insulin injection involves the administration of a long acting insulin as a single dose in the evening with the administration of regular insulin prior to each meal. Continuous subcutaneous insulin infusion involves the delivery of insulin subcutaneously into the abdominal wall by a battery driven pump. In normal nondiabetic subjects, the plasma glucose concentration is maintained within a normal range despite large variations in food intake. This is the result of a rapid release of insulin after a meal which immediately transports the carbohydrate to the liver and other tissues. Only enough insulin is released to maintain a normal postprandial glucose level. As the level of plasma glucose decreases, the release of insulin is inhibited. When a diabetic subject is administered insulin, the insulin is often not capable of maintaining the plasma glucose concentration within the same narrow range as would be found in a normal subject. If not enough insulin is administered, a hyperglycemic effect is seen. If an appropriate amount of insulin is given to maintain a noimal postprandial glucose level, often too much insulin is then present during the post-absorptive phase and hypoglycemia results.

Fenugreek seeds have been found to have a hypoglycemic effect in diabetic subjects. Sharma, R.D., Nutrition Research, v. 6, p. 1353-1364 (1986). When ground fenugreek seeds are mixed with food or administered concurrently with food to diabetic animals, postprandial glucose levels are reduced. Madar, Nwtr. Rep. Inter., v. 29, p. 1267-1273 (1984); Ribes et al., Ann. Nutr. Metab., v. 28, p. 37-43 (1984). Additional studies have revealed that fenugreek is useful for reducing plasma post-prandial glucose in ΝIDDM. Arad, Y. et al., Clinical Nutrition, 23, p. 121-125). These studies have important implications for the treatment of diabetes because they suggest that fenugreek may allow a diabetic to consume a less restricted diet without increasing the amount of insulin required. Although several research studies have suggested that fenugreek be administered to diabetics because of the hypoglycemic effect of the seeds, fenugreek is not routinely administered.

Fenugreek has also been demonstrated to reduce cholesterol levels in hypercholesteremic patients. High levels of blood cholesterol have been causally linked with atherosclerosis due to an accumulation of cholesterol on blood vessel walls resulting in plaque formation. Several research studies have indicated that in addition to the fiber, the cholesterol lowering effect of fenugreek is due to the saponin fraction of the seed. It has been hypothesized that saponins and cholesterol form insoluble complexes which prevent or reduce cholesterol absorption in the intestine. Alternatively the saponin may increase the conversion of cholesterol to bile acids in the liver, thus reducing the plasma cholesterol level. Sauvaire et al., Lipids, v. 26, n. 3, p. 191- 197 (1991). Saponins from a variety of plant sources have been demonstrated to be useful for removing cholesterol from food products in vitro. See e.g., U.S. Patent No. 5,370,890.

Many researchers have attempted to identify the active components of fenugreek which are responsible for the anti-diabetic and hypocholesteremic effects. The studies have involved the preparation of various types of extracts of fenugreek followed by assays for the biological activity. The studies have produced variable results. Some investigators have attributed the beneficial biological effects of fenugreek to the galactomannans, whereas, others have attributed these effects to either saponins or the proteins.

Groups such as Ribes et al., Sharma, Sauvaire et al., and Garti et al. produced fenugreek extracts which maintain the anti-diabetic activity of intact fenugreek but with the removal of several other components of fenugreek.

Ribes et al. produced an extract of fenugreek by grinding mature fenugreek seeds into a powder. The powder was then mixed into a solution containing trifluorotrichloroethane and hexane which promotes the separation of the different histological parts of the seed based on density. Two fractions were separated and defatted with hexane using a soxhlet apparatus and their anti-diabetic activity was measured. Ribes et al. concluded that the fraction containing the testa and endosperm of the seeds were responsible for the anti-diabetic action of fenugreek. Ribes et al., P. Soc. Exper. Biol. Med, v. 182, p. 159-166 (1986).

Sharma prepared an extract of fenugreek seeds to determine which components within the seeds were capable of eliciting the hypoglycemic effect. The fenugreek seeds were cleaned and ground in a cyclone mill to produce a 40 mesh powder. The powder was then extracted with ether in a soxhlet extractor for 16 hours, followed by an alcohol extraction for 24 hours. The extracted powder was then air dried on a filter paper for 4-5 days at room temperature. Sharma noted that the defatted extract was not bitter to taste and was free of lipids and saponins. When the hypoglycemic activity of the fenugreek extracts were compared with that of the fenugreek seeds in human subjects, the fenugreek extract exhibited a significant response. Sharma concluded that the lipids and saponins are not critical to the hypoglycemic effect and that the hypoglycemic activity of fenugreek is due to the gum fiber found in the fenugreek extract. Sharma, Nutrition Research, v. 6, p. 1353-1364 (1986).

In an attempt to isolate the hypoglycemic activity of fenugreek from fenugreek seeds, Sauvaire et al. prepared ground fenugreek seeds and extracted the lipid with hexane at room temperature to produce a delipidized cake. The delipidized cake was then subjected to a series of successive 70% ethanol extractions at room temperature. The extract was then concentrated and passed over a cation exchange column. The concentrated product was eluted from the column with 2N ammonia and then further concentrated, mixed with ethanol and subject to adsorption chromatography to separate the 4-hydroxyisoleucine. Sauvaire then demonstrated that the 4- hydroxyisoleucine product maintained the anti-diabetic activity of fenugreek. U.S. Patent No. 5,470,879. Garti, in published PCT patent application WO95/21199 disclosed that the galactomannan component of fenugreek is responsible for the anti-diabetic activity and disclosed several methods for preparing isolated galactomannan from fenugreek seeds. Each extraction procedure produced a product having less than 20% protein, less than 5% saponin, and less than 1% lipid. In preferred embodiments, the extract had less than 15% protein, less than 2% saponin, and less than 0.1% lipid. The first method disclosed involved the grinding of dry fenugreek seeds to a fine powder. Lipid was then extracted from the powder utilizing hexane in a soxhlet apparatus. The remaining solid fraction was then further extracted with methanol, followed by ethanol. The remaining product was vacuum dried and then dissolved in water to foπri a viscous aqueous solution of crude fenugreek gums. After repeating the extraction procedure several times, the water soluble fractions were combined and the gum was precipitated out using ethanol. The gum was dried and ground into a powder. The gum powder was used in biological activity assays or was optionally percolated through a florusil column to eliminate more protein. A second method for producing the galactomannan gum involved grinding fenugreek seeds to a fine powder, which was then combined with water and heated. A liquid was separated from the solid phase by centrifugation and combined with ethanol to precipitate out galactomannan gum. Again, the gum material was dried and ground to foirn a powder. In a third method, the fenugreek seeds were crushed and introduced into a solvent having a specific gravity range of between 1.25 and 1.35, and selected from CH₂, Cl₂, CHC1₃, and CC1₄. The gummed components of the outer coating of the seeds were allowed to settle to the bottom in the solvent and were isolated. This material was then ground to a fine powder combined with water and heated. A liquid was separated from a solid phase by centrifugation and combined with ethanol to precipitate out the gum.

Several researchers have also attempted to identify the active hypocholesteremic components of fenugreek. Petite et al. identified the steroid saponins as being the active hypocholesteremic component of fenugreek. Petite et al. prepared a purified steroid saponin extract from fenugreek seeds by grinding fenugreek seeds in a mag grinder to produce a powder that could pass through a 0.8 mm mesh sieve. The powder was then extracted with ethanol/water (25:75, v/v) at room temperature for tliree hours, and then centrifuged to form a pellet. The extraction step was repeated three times on the pellet. Each of the supematants was combined and concentrated under vacuum at a temperature below 50 °C and defatted with hexane. The extract was then dried and solubilized with a mixture of water and ethanol. The material was precipitated with alcohol to remove the gum component and the hydroalcoholic extract was passed over an ion exchange column to produce a steroid saponin extract having at least 90% purity. Petite et al. demonstrated that the pure steroid saponin extract caused a significant decrease in plasma cholesterol in both normal and diabetic rats. The extract, however, did not modify plasma insulin or blood glucose levels in rats, suggesting that the hypoglycemia or hyperinsulinemia previously observed by fenugreek seed administration was not due to saponin. Petite et al., Steroids, v. 60, p. 674-680 (1995).

Procedures for extracting various components of fenugreek seeds have been performed for a variety of other reasons. For example, Raymond et al. disclosed in U.S. Patent No. 5,301,694, a method for preparing plant extracts which have the flavor of tobacco but without the nicotine. A variety of plants may be used in the preparation of such an extract, including fenugreek. The process for preparing plant extracts which are useful as flavoring agents involves a solvent extraction of the plant material in water, ethanol or mixtures thereof at a temperature of between 30°C and 60°C. The solvent is then removed by evaporation and the solid is subjected to a size exclusion process to produce the plant extract flavoring agent.

The volatile constituents of fenugreek seeds were characterized and tested for activity by Girardon et al. Girardon et al., Planta Medica, p. 533-534 (1985). Three fenugreek extracts were prepared. The first extract was produced by head space vacuum entrainment of the seed. It was found that several carbonyl compounds of high aroma value were lost during head space vacuum entrainment. Two other extracts were prepared by steam distillation of the seeds at atmospheric pressure. Four monoterpenoids, usually found in essential oils, were detected in one of the steamed distillation extracts. Fifty-one constituents were detected in the three extracts. Although the authors hypothesized that several of these components may contribute to the characteristic odor of fenugreek, the theory was not tested. Furthermore it is unclear from the study whether all of the components contributing to the odor and taste of the fenugreek were removed from the extracts or whether the extracts retained any of the biological activity of intact fenugreek.

Summary of the Invention Fenugreek seeds have traditionally been used in food preparation and as herbal medicinals. Several research studies have also suggested that fenugreek seeds should be used for regulating glucose levels in diabetics because of the hypocholesteremic properties of fenugreek. Yet fenugreek seeds are not ordinarily prescribed by physicians for the treatment of diabetes. The invention provides an improved method for treating diabetics by administering fenugreek to the diabetic. The fenugreek has the effect of reducing the intestinal absorption of a caloric compound from a comestible product which is consumed by the diabetic. The method is an improvement over prior art methods of treating diabetics with fenugreek because the fenugreek is administered to the diabetic within a specific time frame prior to the administration of the caloric containing comestible product. The improved method is based on the surprising finding that the ability of fenugreek to reduce the intestinal absorption of a caloric compound from a comestible is maximal during a specific window of time. Prior to the present invention it was believed that fenugreek should be administered concurrently with or just prior to a comestible product in order to exhibit its biological effects. Surprisingly it was found according to the invention that when fenugreek is administered concurrently with a comestible product to both a normal subject and a diabetic subject that the hypoglycemic effect of the fenugreek is less in the diabetic subject than the normal subject. It was additionally found that if the fenugreek is administered to a diabetic subject during a specific window of time (between 20 and 90 minutes) prior to administering the comestible product that the hypoglycemic effect of the fenugreek was greatly improved.

In one aspect the invention is a method for reducing the intestinal absorption of a caloric compound from a comestible product in a diabetic human. The method involves the step of orally administering fenugreek and a comestible product to a diabetic human, wherein the fenugreek is administered between 20 and 90 minutes before the comestible product, and wherein the step of oral administration includes self administration.

According to an embodiment of the invention the fenugreek is formulated as a gel dosage having a fenugreek concentration of 0.05-0.2 grams/milliliter and containing between 5 and 15 grams of a fenugreek powder. Preferably the gel is administered between 30 and 60 minutes before the comestible product.

In another embodiment the fenugreek is a liquid dosage having a fenugreek concentration of more than 0.002 and less than 0.05 grams/milliliter and containing between 5 and 15 grams of a fenugreek powder. Preferably the liquid is administered between 30 and 60 minutes before the comestible product. According to yet another embodiment the fenugreek is a fenugreek powder. Preferably the powder is administered between 30 and 60 minutes before the comestible product.

In one embodiment the fenugreek is a fenugreek seed material having at least 50% of the protein components present in fenugreek seeds, at least 80% of the carbohydrate components present in fenugreek seeds, at least 50% of the ash components present in fenugreek seeds, and less than 20% of the fat components present in fenugreek seeds. The fenugreek seed material has substantially reduced taste and odor versus flaked or ground fenugreek seeds. In another embodiment the fenugreek is a fenugreek seed material. The fenugreek seed material is a flaked or ground fenugreek seed material having an OD 390 value of 80% less than native fenugreek when mixed for 3 hours in ethanol and the supernatant is measured in a spectrometer. In a preferred embodiment the fenugreek seed material has an OD 390 value of 85% less than native fenugreek. In a more preferred embodiment the fenugreek seed material has an OD 390 value of 90% less than native fenugreek. According to one embodiment the fenugreek seed material has an OD 390 value of 88% less than native fenugreek when dissolved in ethanol for three hours and measured in a spectrometer.

According to another aspect of the invention a kit is provided. The kit includes a container containing fenugreek and instructions for consumption by a diabetic human which include the step of consuming the fenugreek between 20 and 90 minutes before eating a meal. In one embodiment the container is a capsule and the fenugreek is formulated as a fenugreek powder. In another embodiment the fenugreek powder is a fenugreek seed material having at least 50% of the protein components present in fenugreek seeds, at least 80% of the carbohydrate components present in fenugreek seeds, at least 50% of the ash components present in fenugreek seeds, and less than 20% of the fat components present in fenugreek seeds and wherein the fenugreek seed material has substantially reduced taste and odor versus flaked or ground fenugreek seeds. In another embodiment the fenugreek powder is a flaked or ground fenugreek extract having an OD 390 value of 80% less than native fenugreek when mixed for three hours in ethanol and the supernatant is measured in a spectrometer. In a preferred embodiment the fenugreek seed material has an OD 390 value of 85% less than native fenugreek. In a more preferred embodiment the fenugreek seed material has an OD 390 value of 90% less than native fenugreek. According to one embodiment the fenugreek seed material has an OD 390 value of 88% less than native fenugreek when dissolved in ethanol for three hours and measured in a spectrometer. According to one embodiment the fenugreek seed material is foimulated as a fenugreek liquid having a fenugreek concentration of more than 0.002 and less than 0.05 grams/milliliter of an aqueous solution and wherein the instructions for consumption include the step of consuming the liquid between 30 and 60 minutes before eating a meal. In another embodiment the fenugreek liquid is in a unit dose which contains between 5 and 15 grams of a fenugreek powder. In one embodiment the fenugreek liquid is formulated from a fenugreek seed material having at least 50%) of the protein components present in fenugreek seeds, at least 80% of the carbohydrate components present in fenugreek seeds, at least 50% of the ash components present in fenugreek seeds, and less than 20% of the fat components present in fenugreek seeds and wherein the fenugreek seed material has substantially reduced taste and odor versus flaked or ground fenugreek seeds. In another embodiment the fenugreek liquid is a flaked or ground fenugreek extract having an OD 390 value of 80% less than native fenugreek when mixed for three hours in ethanol and the supernatant is measured in a spectrometer. In a preferred embodiment the fenugreek seed material has an OD 390 value of 85% less than native fenugreek. In a more prefeired embodiment the fenugreek seed material has an OD 390 value of 90% less than native fenugreek. According to one embodiment the fenugreek seed material has an OD 390 value of 88% less than native fenugreek when dissolved in ethanol for three hours and measured in a spectrometer.

According to another embodiment the fenugreek seed material is formulated as a fenugreek gel wherein the fenugreek gel has a fenugreek concentration of between 0.05 and 0.2 grams/milliliter of an aqueous solution and wherein the instructions for consumption include the step of consuming the gel between 30 and 60 minutes before eating a meal. In another embodiment the fenugreek gel is in a unit dose which contains between 5 and 15 grams of a fenugreek powder. The fenugreek gel is formulated from a fenugreek seed material having at least 50%) of the protein components present in fenugreek seeds, at least 80% of the carbohydrate components present in fenugreek seeds, at least 50% of the ash components present in fenugreek seeds, and less than 20% of the fat components present in fenugreek seeds and wherein the fenugreek seed material has substantially reduced taste and odor versus flaked or ground fenugreek seeds in yet another embodiment. In another embodiment the fenugreek gel is a flaked or ground fenugreek extract having an OD 390 value of 80% less than native fenugreek when mixed for three hours in ethanol and the supernatant is measured in a spectrometer. In a preferred embodiment the fenugreek seed material has an OD 390 value of 85% less than native fenugreek. In a more preferred embodiment the fenugreek seed material has an OD 390 value of 90%) less than native fenugreek. According to one embodiment the fenugreek seed material has an OD 390 value of 88% less than native fenugreek when dissolved in ethanol for tliree hours and measured in a spectrometer.

Detailed Description Of The Invention

Fenugreek seeds have several well established biological activities, useful in therapeutic treatments. For many years, fenugreek seeds have been used in food products and herbal medicinals. Due to the strong odor and taste of fenugreek, however, its use in the preparation of modern medicines and other therapeutic modalities has been limited although many researchers have attempted to isolate the active components of fenugreek in order to prepare such compositions. None of these attempts, however, has accomplished the preparation of a fenugreek seed material having substantially reduced taste and odor versus intact fenugreek seeds, but which also maintains a significant proportion of the carbohydrate, protein, and saponin material. For a variety of reasons fenugreek is not routinely used for modern therapeutic purposes.

Prior to the present invention it was not .known that timing of administration of fenugreek was an important parameter for maximizing the hypoglycemic effect of fenugreek seeds in diabetics. When fenugreek is administered to normal subjects with or immediately before a comestible product the extract has a hypoglycemic effect, causing a reduction in the intestinal absorption of a caloric compound within that product. This was also believed to be true in diabetics. Surprisingly it was found according to the invention that when fenugreek is administered concurrently with a comestible product to both a normal subject and a diabetic subject, the hypoglycemic effect of the fenugreek is less in the diabetic subject than the normal subject. It was additionally found that if the fenugreek is administered to a diabetic subject during a specific window of time (between 20 and 90 minutes) prior to administering the comestible product that the hypoglycemic effect of the fenugreek was greatly improved.

When the fenugreek is administered to a diabetic by the method of the invention the intestinal absorption of caloric compounds including glucose consumed by the diabetic is reduced. Although Applicants do not wish to limit the scope of the invention to a particular mechanism, it is believed that the fenugreek forms a viscous mass with the comestible product, slowing down the release of the comestible product from the stomach and the movement of the comestible product through the intestinal tract. The rate at which partially digested food leaves the stomach is inversely proportional to the viscosity of the food. Ordinarily when a comestible product is ingested it is released from the stomach within a narrow time period. As the food travels through the intestinal tract it is broken down and absorbed through the intestinal wall causing a rapid rise in blood glucose. The body responds to the rise in blood glucose by secreting insulin which aids in the conversion of glucose into energy. If more glucose is absorbed from the intestine than the insulin can process then the excess glucose is converted to fat and stored in the body rather than being used for energy. By slowing down the transportation of the comestible product from the stomach and through the intestine the fenugreek of the invention causes a slower glucose absorption rate resulting in a consistent low level of glucose in the blood rather than a rapid rise in glucose level. Because the glucose level is lower, all of the glucose is processed by the insulin rather than being stored as fat.

It is also believed that the fenugreek functions as a surfactant, preventing the absorption of the caloric compound. When the fenugreek of the invention is ingested within a particular window of time prior to the caloric containing comestible product the fenugreek coats the stomach and intestinal lining and thus blocks the absorption of some of the caloric compounds. A "diabetic human" as used herein is a human having either Type I or Type II diabetes mellitus. Type I diabetes, also known as Insulin Dependent Diabetes Mellitus (IDDM), is believed to be caused by a destruction of beta cells in the pancreas. Type I diabetics require daily insulin administration which may be reduced but not altogether eliminated by careful restriction of diet. Type II diabetes, also known as Non- Insulin Dependent Diabetes Mellitus (NIDDM), is caused by abnormal insulin secretion and/or resistance to insulin action in target tissues. Although Type II diabetes may be treated with insulin the need for insulin may be altogether eliminated in many cases by careful restriction of the diet. The fenugreek can be used to treat both Type I and Type II diabetics. When the fenugreek is administered to diabetics in combination with a restricted diet insulin administration may be reduced.

The fenugreek is delivered to a diabetic prior to a caloric containing comestible product. A comestible as used herein is any type of edible food or drink containing at least one caloric compound and/or a cholesterol compound. For example, comestible products include dairy products such as milk and ice cream, baked goods such as cookies and cakes, gelled desserts, puddings, salad dressings, etc.

The fenugreek is orally administered to a diabetic human within a specific window of time. The step of administration may be performed by anyone. For instance the fenugreek may be administered to the diabetic by a physician or may be self administered by the diabetic as long as it is administered within the appropriate time period. The appropriate time period is between about 20 and 90 minutes prior to the ingestion of the comestible product to the subject. When the fenugreek is ingested by the subject between 20 and 90 minutes before the comestible product the hypoglycemic effect of the fenugreek is maximized. Preferably the extract is administered between 30 and 60 minutes before the comestible product.

The fenugreek is any formulation of fenugreek which retains the hypoglycemic activity of native fenugreek. For instance the fenugreek may be native fenugreek seeds, a partial extract of fenugreek in which one or several components have been removed but that maintains the hypoglycemic activity such as that described in Ribes, described supra, or a fenugreek seed material having reduced taste and odor versus native fenugreek.

Native fenugreek is a composition made up of non-extracted fenugreek seeds. The composition may be prepared in any way. For instance the fenugreek seeds may be ground, chopped or diced to form the composition or the composition may simply be made up of intact fenugreek seeds. Fenugreek seeds are produced by the leguminous herb of the family papilionaceae trifolieae, and genus trigonella which is grown predominantly in Northern Africa, the Middle East, and Asia. Fenugreek seeds are readily available from a wide variety of commercial sources, such as Morris J. Golombeck (Brooklyn, NY) or Dirigo Spices (Boston MA). Fenugreek seeds useful for preparing the fenugreek seed material of the invention may be obtained from any source.

A "partial extract of fenugreek" as used herein is an extract of fenugreek in which at least one component has been removed. For instance Ribes et al prepared an extract of fenugreek seeds which contained the testa and endosperm of the seeds and which maintained the hypoglycemic activity of fenugreek. Ribes et al., supra (1986). An extract of fenugreek seeds consisting of gum fiber which maintained the hypoglycemic activity of native fenugreek was also disclosed in Sharma. Sharma, supra (1986). Garti, also disclosed a fenugreek extract consisting of the gum fiber galactomannan which according to Garti was responsible for the anti-diabetic activity of fenugreek seeds. PCT patent application WO95/21199. Additionally, Sauvaire et al. prepared ground fenugreek seeds and extracted the 4-hydroxyisoleucine which according to Sauvaire demonstrated the anti-diabetic activity of fenugreek. U.S. Patent No. 5,470,879.

A "fenugreek seed material" as used herein is an extract of fenugreek seeds having the hypoglycemic activity of native fenugreek but having substantially reduced taste and odor versus native fenugreek seeds. (Described in co-pending US Patent Application by the same inventors and filed herewith, which is hereby incorporated by reference). Native fenugreek seeds are ordinarily composed of approximately 50-70% carbohydrate, 1-5 % ash, 15-30 % protein, 1-10% fat, and 1-10% moisture. The fenugreek seed material having reduced odor and/or taste has altered concentrations of fenugreek components than native fenugreek but retains enough of the components to retains the hypoglycemic activity of native fenugreek. For instance, in one embodiment, the fenugreek seed material includes at least 50% of the protein components present in fenugreek seeds, at least 80% of the carbohydrate components present in fenugreek seeds, at least 50% of the ash components present in fenugreek seeds but has less than 20% of the fat components present in native fenugreek seeds. In another embodiment the fenugreek seed material is formulated as a fenugreek powder and includes at least 80% of the active components found in unmodified fenugreek. The active components are protein, saponins (including a carbohydrate and lipid portion), and carbohydrates including fiber. In another embodiment the fenugreek seed material is an alcohol-extracted fenugreek seed material containing at least eighty percent of the carbohydrate components present in fenugreek seeds and less than twenty percent of the fat components present in fenugreek seeds. Preferably the flaked or ground alcohol extracted fenugreek seed material is composed of 20-40% protein, 40-70% carbohydrate, 2-5% ash, less than 1% fat, and 1-10% moisture. Saponins are included within the carbohydrate or lipid portion of the fenugreek seed material depending on assaying technique. Carbohydrate as used herein includes both soluble and insoluble crude fibers as well as other types of carbohydrates ordinarily found in fenugreek seeds.

A fenugreek seed material which has substantially reduced taste and odor is one having 10% or less of the odor and/or taste of native fenugreek based on the average organoleptic taste and/or odor detection thresholds for the fenugreek seed material and native fenugreek. Preferably the fenugreek seed material has 5% or less of the odor and/or taste of native fenugreek based on the average organoleptic taste and/or odor detection thresholds. Most preferably it has 2% or less of the odor and/or taste of native fenugreek based on the average organoleptic taste and/or odor detection thresholds.

The following organoleptic evaluation methods for quantitatively or qualitatively measuring odor and taste are useful for determining whether a fenugreek seed material has substantially reduced odor and taste according to the invention.

Rapid Organoleptic Ethanol Extraction Test: An equal volume of the test sample fenugreek seed material and control ground fenugreek seeds are each added to a solution of ethanol at approximately 10% w/v. The solutions are incubated at room temperature with intermittent vortexing for several hours. The solutions are then centrifuged to pellet the solid material. A one milliliter extract of each solution is removed and analyzed in a spectrometer at OD 390. The absorbance reading for the native fenugreek seed typically is over 0.400 OD Units, and the absorbance reading of material prepared according to the methods described below is typically between 0.030 - 0.080 OD Units. In one aspect of the invention the fenugreek seed material is a fenugreek seed material, flaked or ground, having an OD 390 value of 80% less than native fenugreek when mixed for tliree hours in ethanol and the supernatant is measured in a spectrometer. In a preferred embodiment the fenugreek seed material has an OD 390 value of 85% less than native fenugreek. In a more preferred embodiment the fenugreek seed material has an OD 390 value of 90% less than native fenugreek. According to one embodiment the fenugreek seed material has an OD 390 value of 88%> less than native fenugreek when dissolved in ethanol for three hours and measured in a spectrometer.

Average Organoleptic Taste and/or Odor Detection Threshold Evaluation Method: As used herein, the "average organoleptic taste and/or odor detection threshold evaluation" is a measure for assessing the relative amount of taste and/or odor which has been removed from a fenugreek material. The relative amount of taste and/or odor removed is quantified as a threshold concentration required for an average group of persons to taste and/or smell a test fenugreek material as compared to that amount required to taste and/or smell the same concentration of native fenugreek. Briefly, various quantities of the fenugreek seed material or native fenugreek are added to

50 ml of deionized water in plastic tubes. Prior to each testing, the tubes are shaken for a few seconds by hand and a cotton swab is dipped into the various solutions. The subject to be tested is then given the swab to taste to determine if any taste is detected. The solutions are tested in increasing concentration of fenugreek beginning with a control tube containing deionized water only. The order of testing between fenugreek seed material and native fenugreek is randomized between subjects. All testing is conducted by a single tester. A threshold concentration at which a subject can detect a taste is established for each subject.

Quantitative Organoleptic Evaluation Method: The organoleptic evaluation method described in US Patent No. 4,356,190, which is hereby incorporated by reference, provides a method for quantitatively evaluating the odor intensity of a sample as an absolute value. This provides a quantitative description of the odor intensities between different samples. The method may also be used to evaluate the taste of a fenugreek sample. Although the organoleptic evaluation method described in 4,356J 90 does not specifically contemplate a comparison of the odor and taste of fenugreek samples, the method is described briefly below with reference to analysis of a fenugreek sample.

Initially, the threshold concentration of a sample odor is established by the method described in Steiger, F.H., Chemical Technology, VJ . P.225 (1971). Briefly, a panel of subjects is presented with a series of samples containing native ground fenugreek seeds in water in increasing concentrations. The panelists are presented the fenugreek samples in ajar in order of increasing concentration with the first sample at zero concentration (water only). They are then asked to identify the first sample having a detectable odor. The accumulated data is plotted as described in the Steiger article in order to determine the concentration level of which an arbitrary percentage of the panelists can detect the odor. The concentration at 50% is taken as the threshold concentration.

A master fenugreek curve is prepared by presenting a panel of subjects a series of fenugreek samples prepared at concentrations which are various multiples of the threshold concentration (and referred to as odor units). The fenugreek samples are prepared by mixing various quantities of ground fenugreek in 3 ml of water and incubating for one hour. Each panelist is asked to evaluate the set of samples assigning each sample a value between 0 and 20 correlating to the odor intensity of the sample. The data is then organized with each sample corresponding to a specific multiple of the threshold concentration such that the sample twenty times the threshold concentration is assigned a value of one hundred and the threshold sample is assigned a value of zero. The data is obtained as a series of ratio values corresponding to each sample. The mean of the ratio values for each sample (based on multiple subjects) is calculated and is taken as the ratio value for that multiple of threshold concentration. The log of the ratio value is plotted, as the ordinate, against the log of the multiple of threshold concentration for the fenugreek samples and a straight line is fitted to the data points between three and twenty times threshold concentration to produce the master fenugreek curve.

The master fenugreek curve can be used to evaluate the odor intensity of any fenugreek seed test sample to determine whether the preparation has a substantially reduced odor intensity. In order to accomplish this, a panel is presented with a series of samples, one of which is a standard native ground fenugreek sample consisting of a known concentration of fenugreek being tested in an environment identical to that used in producing the master curve. Preferably the standard sample is twenty times the threshold concentration so that it has a ratio value of one hundred on the master curve. Alternatively three standard samples are used having three, ten and twenty times the threshold concentration and thus having a ratio value of fifteen, fifty, and one hundred on the master curve. Panelists are asked to evaluate the series of fenugreek seed test samples at various concentrations at the same time as evaluating the standard native ground fenugreek samples and to assign an odor intensity value to each sample (test samples and standard samples) based on the scale. The mean of the values assigned by the panelists can then be assigned an odor intensity by matching the mean ratio value to the master curve. A fenugreek seed material having substantially reduced odor according to the invention is one having a ratio value of less than or equal to 50 when evaluated by the modified ratio scale organoleptic evaluation method and the sample is prepared at a concentration equivalent to the fenugreek concentration which is twenty times the threshold concentration. This sample is said to have at least 50%) less odor intensity than native fenugreek. Preferably the fenugreek seed material of the invention has a ratio value of less than or equal to 25 when evaluated by the modified ratio scale organoleptic evaluation method and the sample is prepared at a concentration equivalent to the fenugreek concentration which is twenty times the threshold concentration. This sample is said to have at least 75% less odor intensity than native fenugreek. Most preferably the ratio value is less than or equal to 10. This sample is said to have at least 90% less odor intensity than native fenugreek.

The above described assays are provided for exemplary purposes only. Any assay ordinarily used in the art may be sufficient to determine whether the fenugreek seed material has substantially reduced odor and taste compared to fenugreek. Other assays for measuring and comparing the odor and taste of different compounds which are useful for determining whether the fenugreek seed material has a substantially reduced taste with respect to fenugreek are disclosed in US Patent Nos. 4,381,402, 4,180,589, 5,482,855 and 5,571,519, each of which is hereby incorporated by reference.

In one aspect the fenugreek seed material is an alcohol-extracted fenugreek seed material. The alcohol extracted fenugreek seed material is produced by the steps of flaking a fenugreek seed to form a fenugreek preparation, extracting soluble components from the fenugreek preparation by extraction of the fenugreek preparation with an alcohol solvent at a cool extraction temperature to produce a fenugreek solid, treating a fenugreek solid to remove the alcohol solvent to produce a dry solid, and grinding the dry solid into a powder to produce the fenugreek seed material. The fenugreek seed material may be prepared by an alcohol extraction of fenugreek seeds, to produce the fenugreek seed material having substantially reduced taste and odor versus native fenugreek. For example, native fenugreek seeds may be flaked or ground and extracted with methanol to produce a fenugreek solid which can be ground into a powder to produce the fenugreek seed material. Other straight chain lower alcohols may be used in place of methanol (e.g., ethanol). As will be understood by one of ordinary skill in the art, multiple alcohol extractions may be performed to further refine the fenugreek material. One of skill in the art can easily determine whether the fenugreek seed material has been sufficiently extracted by the Rapid Organoleptic Ethanol Extraction Test discussed above. Briefly, an equal volume of ground fenugreek seed test sample are added to a solution of ethanol at approximately 10% w/v. For comparison purposes native ground fenugreek seeds are added to a solution of ethanol at approximately 10% w/v. The solutions are incubated at room temperature with intermittent vortexing for three hours. The solutions are then centrifuged to pellet the solid material. A one milliliter extract of each solution is removed and analyzed in a spectrometer at OD 390. The absorbance reading for the native fenugreek seed typically is over 0.400 OD Units. ./\n absorbance reading for the fenugreek seed test sample of approximately 80% less than that for native fenugreek indicates that the extraction is sufficient and that the fenugreek seed test sample is the fenugreek seed material of the invention.

Indeed, as will be understood by one of ordinary skill in the art, the fenugreek seed material produced by the alcohol extraction method may be further purified and refined by a variety of fractionation and separation techniques (e.g., chromatography, dialysis, filtration, electrophoresis) as long as the biological activity of the fenugreek seed material is not altered by the purification steps. After such fractionation or separation steps, one may, without undue experimentation, perform the assays described herein to determine whether the preparation maintains the biological activity of native fenugreek. Any such preparation constitutes a "fenugreek seed material" as used herein and in the appended claims.

The following example of a procedure for preparing the fenugreek seed material of the invention is provided for illustrative purposes only. Native fenugreek seeds are flaked to form a fenugreek preparation. The seed is flaked in order to expose a larger surface area for the subsequent solvent extraction step. The step of flaking which is commonly used in the preparation of grain for animal feeds is preferably accomplished using a commercially available flaking mill. For example, the flaking mill produced by the Simon-Day (Sandvik Process System, Canada) is useful according to the invention. Other flaking mills have been described extensively in the prior art (e.g., U.S. Patent Nos. 5,386,946; 3,881,663, etc.).

Soluble components are extracted from the flaked fenugreek preparation with an alcohol solvent at a cool extraction temperature to produce a fenugreek solid. Although various extraction methods are feasible, a continuous countercurrent extraction procedure is preferred. Countercurrent extractors are commonly used in the food processing industry for the continuous extraction of liquids, solubles, and fine particulate matter from solid material. Typically in a countercurrent extractor, material to be processed is fed into the lower end of a housing and carried upwards, while an extracting liquid which is fed into the top of the housing flows downward under gravity. The material to be processed is generally carried upwards within the extractor by a screw rotation. More advanced types of continuous countercurrent extractors, such as the Crown model II continuous loop, shallow bed extractor (Crown Works Company, Minneapolis, Minnesota) produce highly efficient extraction steps. In an advanced extractor such as the Crown model, the fenugreek preparation is fed onto a conveyor chain in the extractor which carries the preparation around a vertical loop. An alcohol solvent is fed into the loop in a direction opposite of the fenugreek preparation. The speed at which the fenugreek preparation is moved through the extractor loop is controlled electronically to conform to the input of raw material in order to maintain a uniform density and depth relative to the preparation.

The solvent suitable for use in the extraction procedure is an alcohol solvent. As used herein, "an alcohol solvent" is any solvent which is made up of a single straight chain alcohol or combination of more than one type of alcohol. Preferred alcohol solvents of the invention are methanol, ethanol, or a combination of ethanol and methanol. Solvents traditionally used for extraction procedures, such as hexane and isopropanol, are not useful in the method of the present invention. The amount of solvent useful in the extraction procedure is any amount which results in the extraction of soluble components of the fenugreek solid. Preferably the amount of solvent used is sufficient to extract the maximum amount of soluble components. A weight ratio of alcohol solvent to fenugreek solid which is sufficient to extract a maximum amount of soluble components is 10(alcohol):l (fenugreek) - 3 (alcohol) :1 (fenugreek). In one embodiment the weight ratio is 5 (alcohol): 1 (fenugreek).

The extraction steps can also be accomplished in more than one extraction, i.e., the fenugreek preparation can undergo several extractions with fresh solvent in order to insure more complete removal of the soluble components. For example, a first extraction may leave significant amount of the soluble components in the fenugreek preparation. More of the soluble components can be extracted by at least one additional extraction with fresh solvents.

The extraction procedure is performed at a cool extraction temperature. A "cool extraction temperature" as used herein is a temperature between 30 °C and 60 °C. Ordinarily, extraction temperatures are greater than 80 °C. In a prefeired embodiment, the cool extraction temperature is less than 55 °C. In a particularly prefeired embodiment, the cool extraction temperature is 52 °C. The cool extraction temperature is believed to prevent the reintroduction of the bitter flavor into the fenugreek material. The fenugreek solid which remains after the extraction step is treated to remove the alcohol solvent to produce a dry, solid material. The treatment of the fenugreek solid includes the steps of desolventizing, solvent wash, and drying.

The step of desolventization involves a combination of heat and vacuum to evaporate the extraction solvent. Methods for desolventizing seed material are well .known in the art (e.g., U.S. Patent No. 4,376,073 and U.S. Patent No. 4,622,760). Preferably the desolventization step is performed in a desolventizer toaster, such as the one manufactured by Crown Iron Works (Minneapolis, Minnesota). Alternatively, a sparse steaming desolventization step may be performed.

A "solvent wash" as used herein is a series of solubilization washes to solubilize and remove the alcohol solvent. When the alcohol solvent is methanol, the first of the series of solvent washes is preferably 100% ethanol. The subsequent washes are preferably 50% ethanol and 50% water. Any apparatus commonly used for solvent washing may be used for the solvent wash step. A decanter centrifuge may be used to recover the ethanol and the ethanol may be recycled. In an other embodiment, the solvent wash solution is added at a ratio of 3 : 1 solvent to fenugreek solid (w/w).

The desolventized fenugreek material is tumble dried. "Tumble dried" as used herein refers to a process involving vacuum, heat, and movement of the fenugreek material to ensure an even and thorough drying of the material. Movement of the fenugreek material is important. Stationary dryers, such as a fluid bed dryer and a desolventizer toaster, are not well suited to achieve a complete removal of the alcohol solvent without burning the fenugreek material. Tumble dryers are commercially available by various suppliers such as Patterson Ind. Canada, Ltd. Once the fenugreek solid has been treated to produce a dry solid, the material may be ground into a powder to produce the finished fenugreek seed material product.

The fenugreek used according to the methods of the invention may be formulated by any manner known in the art. For instance, the fenugreek may be formulated as a powder. As used herein a "fenugreek powder" is a ground composition of the fenugreek of the invention. Preferably the material is ground to an intermediate-course size. Surprisingly, a fenugreek powder having a particle distribution mesh size of -80 was found to produce an optimal fenugreek material. Ordinarily it is believed that a finer grind material will have greater binding capacity than a course grind because of its greater surface area. It was discovered according to the invention that fenugreek material that is ground to an intermediate-course size has better cholesterol binding capacity and reduces post prandial glucose more effectively than the same material ground to a fine powder or ground to a course material. Several commercial companies, including PowderSize (Quaker Town PA), which are licensed by the FDA can prepare food grade powder to made-to-order particle size specifications. Generally the fenugreek material is introduced with high pressure air into a spiral air jet mill (PowderSize, Quaker Town PA) to produce a ground fenugreek powder. The powdered material in the form of micronized particles is then separated from the air in a separator.

The powder may be stored in any type of container. For example the powder may be stored in plastic or glass bottles or jars, vials, bags, boxes, or capsules.

The fenugreek may also be formulated as a solid material. A fenugreek solid material is a composition of the fenugreek of the invention which may or may not be ground. The fenugreek solid material may be consumed as a solid material by a human subject or may be ground to produce a fenugreek powder. For example, the fenugreek solid material may be formulated into tablets.

Alternatively, the fenugreek may be foimulated as a fenugreek gel. A "fenugreek gel" as used herein is a viscous aqueous solution or suspension of the fenugreek of the invention having a concentration of between 0.05 and 0.2 gram fenugreek/ml aqueous solution. The gel may also be used in the preparation of a food or drink product which may be stored prior to consumption. For example the fenugreek gel may be immersed in a carrageenan based gelatin to form a gelatinous product which can be consumed prior to a meal. The fenugreek gel may be dispersed throughout the gelatin to produce a substantially homogenous substance or may be stirred into the gelatin to produce a gelatinous substance having clumps of fenugreek throughout the gelatin. The gel may be stored in any type of container. The fenugreek may also be formulated as a fenugreek liquid. The fenugreek liquid is prepared by dissolving fenugreek in an aqueous solution. A "fenugreek liquid" as used herein is an aqueous solution having a concentration of more than 0.002 and less than 0.05 grams of fenugreelc/ml of aqueous solution. The fenugreek liquid may be stored in any type of container. The fenugreek liquid and the fenugreek gel are foimulated such that they are compatible with a physiological environment. Formulations which are compatible with a physiological environment are well .known in the art. In a prefeired embodiment the fenugreek gel and the fenugreek liquid have a pH of between 3.5 and 7.

In a preferred embodiment the fenugreek gel and the fenugreek liquid useful according to the invention have a salt concentration of less than 0.01 %.

The fenugreek may be administered alone or in conjunction with other medicinal therapies. For example the patient may also be administered insulin or oral hypoglycemic agents.

The invention also encompasses kits for administering the fenugreek according to the methods of the invention. The kits include a container containing fenugreek and instructions for consumption by a diabetic human which include the step of consuming the fenugreek between 20 and 90 minutes before eating a meal.

The container containing the fenugreek may be any type of container known to those of skill in the art to store food or medicament material. The container includes but is not limited to a bag, a vial, ajar, a box, a foil or paper wrap, or a bottle.

The fenugreek in the kit may be foimulated in any manner disclosed above. The following examples are provided to illustrate the methods and products of the present invention. As described above, many variations on these particular examples are possible and, therefore, the examples are merely illustrative and not limiting of the present invention. Examples

Example I: Administration of fenugreek to diabetic and normal subjects at varying time intervals.

10 diabetic experimental and 10 normal experimental subjects were fed a standardized 500 kcal metabolic meal. Each experimental subject was administered a 120ml serving of a fenugreek gel (LIMITROL-DM™) at a specific time point relative to the meal. Control subjects were not given any fenugreek but measurements were made at the same time points as the experimental subjects. The serving of LIMITROL-DM™ was administered either concurrently with the meal or 15, 30, 45, or 60 minutes before the meal. Glucose levels were measured in each subject before the meal and at 30, 60, and 90 minutes after the meal. The percent reduction in maximal glucose levels achieved were calculated as a function of the time of administration of the LIMITROL-DM™. The percent reduction for normal subjects was determined by calculating the increase in glucose levels from a premeal baseline level in normal control subjects and in normal experimental subjects that were administered LIMITROL-DM™ at a specific time point. The percent reduction for the specific time point is the delta or the difference seen between the control subject and the experimental subject. The percent reduction for diabetic subjects is calculated in the same manner using the data obtained from the diabetic subjects. The results are shown in Table 1 below.

As demonstrated in Table 1 the time of administration of the fenugreek is important for the hypoglycemic results seen. Maximal hypoglycemic results are seen in diabetic patients when the fenugreek is administered prior to 20 minutes before the meal. Maximal hypoglycemic results are seen in normal subjects, however, occur when the fenugreek is administered concurrently with the meal or within 20 minutes of the meal.

Each of the foregoing patents, patent applications and references is herein incorporated by reference in its entirety. Having described the presently preferred embodiments in accordance with the present invention, it is believed that other modifications, variations and changes will be suggested to those sldlled in the art in view of the teachings set forth herein. It is, therefore, to be understood that all such variations, modifications, and changes are believed to fall within the scope of the present invention as defined by the appended claims.

What we claim is:

Claims

1. A method for reducing the intestinal absorption of a caloric compound from a comestible product in a diabetic human, comprising the step of: orally administering fenugreek and a comestible product to a diabetic human, wherein the fenugreek is administered between 20 and 90 minutes before the comestible product, and wherein the step of oral administration includes self administration.

2. The method of claim 1 , wherein the fenugreek is a gel dosage having a fenugreek concentration of 0.05-0.2 grams/milliliter and containing between 5 and 15 grams of a fenugreek powder.

3. The method of claim 2, wherein the gel is administered between 30 and 60 minutes before the comestible product.

4. The method of claim 1 , wherein the fenugreek is a liquid dosage having a fenugreek concentration of more than 0.002 and less than 0.05 grams/milliliter and containing between 5 and 15 grams of a fenugreek powder.

5. The method of claim 4, wherein the liquid is administered between 30 and 60 minutes before the comestible product.

6. The method of claim 1 , wherein the fenugreek is a fenugreek powder.

7. The method of claim 6, wherein the powder is administered between 30 and 60 minutes before the comestible product.

8. The method of claim 1 , wherein the fenugreek is a fenugreek seed material having at least 50% of the protein components present in fenugreek seeds, at least 80% of the carbohydrate components present in fenugreek seeds, at least 50% of the ash components present in fenugreek seeds, and less than 20% of the fat components present in fenugreek seeds and wherein the fenugreek seed material has substantially reduced taste and odor versus flaked or ground fenugreek seeds.

9. A kit, comprising: a container containing fenugreek; and, instructions for consumption by a diabetic human which include the step of consuming the fenugreek between 20 and 90 minutes before eating a meal.

10. The kit of claim 9, wherein the container is a capsule and the fenugreek is formulated as a fenugreek powder.

11. The kit of claim 10, wherein the fenugreek powder is a fenugreek seed material having at least 50%) of the protein components present in fenugreek seeds, at least 80% of the carbohydrate components present in fenugreek seeds, at least 50% of the ash components present in fenugreek seeds, and less than 20% of the fat components present in fenugreek seeds and wherein the fenugreek seed material has substantially reduced taste and odor versus flaked or ground fenugreek seeds.

12. The kit of claim 9, wherein the fenugreek seed material is formulated as a fenugreek liquid having a fenugreek concentration of more than 0.002 and less than 0.05 grams/milliliter of an aqueous solution and wherein the instructions for consumption include the step of consuming the liquid between 30 and 60 minutes before eating a meal.

13. The kit of claim 12, wherein the fenugreek liquid contains between 5 and 15 grams of a fenugreek powder.

14. The kit of claim 12, wherein the fenugreek liquid is formulated from a fenugreek seed material having at least 50% of the protein components present in fenugreek seeds, at least 80% of the carbohydrate components present in fenugreek seeds, at least 50% of the ash components present in fenugreek seeds, and less than 20% of the fat components present in fenugreek seeds and wherein the fenugreek seed material has substantially reduced taste and odor versus flaked or ground fenugreek seeds.

15. The kit of claim 9, wherein the fenugreek seed material is foimulated as a fenugreek gel wherein the fenugreek gel has a fenugreek concentration of between 0.05 and 0.2 grams/milliliter of an aqueous solution and wherein the instructions for consumption include the step of consuming the gel between 30 and 60 minutes before eating a meal.

16. The kit of claim 15, wherein the fenugreek gel contains between 5 and 15 grams of a fenugreek powder.

17. The kit of claim 15, wherein the fenugreek gel is formulated from a fenugreek seed material having at least 50% of the protein components present in fenugreek seeds, at least 80% of the carbohydrate components present in fenugreek seeds, at least 50% of the ash components present in fenugreek seeds, and less than 20% of the fat components present in fenugreek seeds and wherein the fenugreek seed material has substantially reduced taste and odor versus flaked or ground fenugreek seeds.