1. Field of the Invention
The present invention relates to a dietary supplement and method for use as a probiotic(immuno-stimulant) and for alleviating the symptoms associated with irritable bowel syndrome.
2. Description of Related Art
The use of dietary supplements for alleviating specific symptoms associated with particular human health problems is well known. Going back to ancient times, references are made to various dietary foods, herbs, and other naturally produced substances that are associated with improving the human health condition.
Many times, a person has poor health conditions based on dietary deficiencies, such as vitamins, minerals, and other natural elements that are essential for good human health. Many times, the dietary supplements available can supply missing dietary minerals and vitamins that are essential for proper metabolism and function of the human body. Therefore, it is well known that improvements to human health and well-being can be achieved using dietary supplements, especially if they provide for deficiencies in a person's diet. The use of daily or weekly supplements supplying missing natural dietary elements such as vitamins and minerals can alleviate symptoms for improvement related to specific maladies of human health.
The human condition known as irritable bowel syndrome can best be defined as a chronic disorder of the bowels, resulting in variable abdominal discomfort or pain, constipation, diarrhea, cramps, nausea, belching, excess flatus, spasm, abdominal distention, tired and weak feeling, and mechanical irritation of the bowel. Medical treatment has traditionally entailed bland diet, mild sedatives, hydrophilic colloid laxatives, anti-cholinergics, and anti-diarrhea agents and are often associated with numerous side effects such as drowsiness, dry mouth, visual disturbances, and food intolerances.
Aloe is a tropical or subtropical plant with thick lance-shaped leaves with jagged edges and has been known for centuries for its medicinal and therapeutic properties useful in treating many different human conditions.
The aloe plant and extracts from aloe, aloe vera, and various specific aloe extracts from the natural plant can alleviate symptoms related to irritable bowel syndrome as shown in the following literature.
Title or Subject Authors Date Reference "The Small Intestines Chikalo, I. & Sept. Quoted in "The Function Affected by Bolovyeve, V. 1966 Aloes of Aloe Extract" Ukraine Tropical Africa and Madagascar" by Reynolds, G. W. "Aloe Vera Gel in Blitz, J., 1963 J. Amer. Peptic Ulcer Therapy; Smith, J., & Osteopathic Preliminary Report" Gerard, J. Assoc. 62 731- 735 Aloenin and Aloe-Ulcin Yamamoto, I. 1970 J. Med. Soc. From A arborescens Toho Jpn. 17 Inhibit Gastric 361 Secretion Aloe-Ulcin Equals Mg Hirata, T. & 1977 Naturforsch 32c Lactate Suga, T. 731 Aloenin and Aloe-Ulcin Hirata, T. & 1978 Bull. Chem. From A arborescens Suga, T. Soc. Jpan. 51 Inhibit Gastric 842 Secretion "Effect of Orally Bland, J. 1985 Preventive Consumed Aloe Vera Medicine, Juice on March/April Gastrointestinal Function in Normal Humans" "Effects of Aloe Salto, H., 1989 Jpn. Yakugaku Extracts Aloctin A on Imanishi, K., Zasshi 109 (5) Gastric Secretion and Okabe, S. 335-339 on Experimental Gastric Lesions in Rats" "A Double-Blind Trial Odes, H. S. & 1991 Digestion -49 of a Celandin, Aloe Madar, Z. (2) 65-71 Vera and Psyllium Laxative Preparation in Adult Patients with Constipation"
Freeze-dried aloe and extract from the natural aloe plant have been determined to have a positive influence as a dietary supplement and probiotic to improve the overall health and condition of a person. Specifically, freeze dried aloe and aloe extracts have been found to have antibacterial and antiviral properties.
The following information is from UK Patent No. GB 2245143B, describing a freeze-dried aloe process that could be used to prepare aloe for use in the present invention. Aloe has been extensively used as medicine. In U.S. Pat. No. 5,455,033 to Silverman, the soothing action of aloe vera extract was disclosed and utilized in an topical anti-inflammatory composition. In addition, the Silverman patent reported inulin, an ingredient in Applicant's present invention, as being an activator in the immune system and the root extract demonstrating anti-viral activity against influenza, herpes and vesicular stomatis viruses. Reference to aloe powders is also made in the Japanese Pharmacopeia. Certain low, medium, and high molecular weight compounds have been separated from aloe. For example, it is known that aloe arborescens var. natalensis (referred to hereinafter as "Kidacki aloe") contains polysaccharides such as aloetin, alcenin, aloeursin or D-mannose, aloemannan or aloe albonacite; that aloe vera contains polysaccharides; and that Cape aloe contains anthraquinonic ingredients such as aloin or aloe-emodin. Bioactive factors were separated from freeze dried aloe in U.S. Pat. No. 5,902,796 to Shand. Mixtures of these active chemical substances identified, isolated, and stabilized from aloe vera leaves have been described in U.S. Pat. Nos. 4,735,935; 4,851,224; 4,917,890; 4,957,907; 4,959, 241; and 4,966,892. One group of these active chemical substances has been referred to as aloe vera mucilaginous polysaccharides, which are comprised of oligomers and polymers of carbohydrates. The pharmaceutical application of these mucilaginous polysaccharides and uses of aloe products have been described in U.S. Pat. Nos. 5,106,616; 5,118,673; 5,308,838; 5,441,943; and 5,443,830.
Intensive attempts have been made to process aloe into medicines. Presently, as an officially allowed health food, food products prepared from Kidachi aloe have been extensively commercialized in Japan. Most of these products, however, are prepared by drying aloe leaves under the sun or by hot air and, at the time of tableting, up to about 10% of an additive such as Avicel.RTM. microcrystalline cellulose or cornstarch, is added as a binder to facilitate tableting.
It is noted that most ingredients isolated and purified from the aloe and found to be medically efficacious to animals by animal experiments, are polysaccharides, glycoproteins, or enzymes, all of which may exhibit activity in a stable condition through purification at lower temperatures. For this reason, it is generally thought to be desirable to apply as little heat as possible for the preparation of a health food or medicine from aloe.
However, since the products now available on the market are prepared by drying aloe leaves under the sun or by circulation of hot air, the polysaccharides, glycoproteins, and enzymes in them will have been thermally degraded or oxidized in the course of drying.
Furthermore, the additives for facilitating tableting, such as Avicel.RTM. or cornstarch, are added in an amount of several to tens of percents in the conventional aloe tablet products. Since a small amount of water is added under heating to knead the additives with the dried aloe mass, the resulting product undergoes further thermal degradation by such heating.
Soluble fiber in the diet is well known for its salutary effects on gastrointestinal health and for being a very good fermentation substrate for intestinal flora. Such salutary effects include providing bulk to the stool, decreasing the pH of the gastrointestinal tract, producing volatile fatty acids, decreasing intestinal transit time, and beneficially influencing various blood parameters. Dietary fiber has also been shown to have a beneficial effect on cholesterol and lipid metabolism that results in decreased serum cholesterol, triglycerides, and phospholipids and an improved (increased) HDL to LKL ratio. A study on laboratory animals showed that adding fiber to the diet decreases the incidence of bacterial translocation, i.e. corrsing the intestinal barrier and entering systemic circulation. C. Palacio et al., Dietary Fiber: Physiologic Effects and Potential Applications to Enteral Nutrition, in Clinical Nutrition: Enteral and Tube Feeding (2d. ed., 1990). Nutritional and epidemiological studies have indicated that a general increase in the consumption of dietary fiber may play a role in preventing deleterious effects of oxygen free radicals that have been involved in such processes as aging, inflammation, and some disease processes. R. Kohen et al., Prevention of Oxidative Damage in the Rat Jejunal Mucosa by Pectin, 69 Br. J. Nutrition 789 (1993).
Inulin is a naturally occurring soluble fiber, a fructo-oligo saccharide composed of a mixture of oligomers of varying degrees of polymerization or molecular weights that occurs in numerous plants, including the dahlia tuber. It is not digested in the small intestine, but is fermented in the colon. The main effects of inulin on the digestive system are a decrease in the duration of the intestinal transit, a decrease in the level of glycemia, a decrease in the lipid content in the blood, a decrease in the pH in the colon, a decrease in the constipation phenomenon and a bifidogenic effect, for example. Thus, inulin can be fermented by bifidobacteria, which has the consequence of increasing the concentration of these bacteria at the level of the intestinal flora and of decreasing the concentration of enterobacteria, in particular Clostridiae, at the level of the intestinal flora.
While prior art formulas as dietary supplements containing soluble fiber or aloe extracts are known and are generally suitable for their limited purposes, they possess certain inherent deficiencies that detract from their overall utility in restoring and maintaining gastrointestinal health. For example, a dietary supplement containing soluble dietary fiber without aloe extracts lacks antibacterial and antiviral activity. Similarly, a dietary supplement containing aloe without soluble dietary fiber lacks means for providing bulk to the stool, decreasing the pH of the gastrointestinal tract, producing volatile fatty acids, decreasing intestinal transit time, beneficially influencing various blood parameters, beneficially influencing cholesterol and lipid metabolism, decreasing the incidence of bacterial translocation, preventing deleterious effects of oxygen free radicals, and favoring the growth of beneficial bacteria in the gastrointestinal tract. Further, such prior art formulas fail to provide living intestinal bacteria that are beneficial for gastrointestinal health by providing an inhibitory effect on the growth of pathogenic bacteria, reducing the levels of toxic amines, and lowering the pH of the gastrointestinal tract.
In the prior art the production of inulin from plant materials such as Jerusalem artichoke, dahlia and chicory tubers is normally accomplished by using the following general procedure:
1. Washing the tubers; PA1 2. Chopping, grinding or slicing the tubers; PA1 3. Extracting the inulin from the tubers with water; PA1 4. Treatment with Lime and Carbon Dioxide; PA1 5. Filtering; and PA1 6. Recovering the inulin by evaporation or precipitation.
The inulin may be subjected to heat and/or pH adjustment at some stage in the process to denature inulinase.
The biology, chemistry and analysis of inulin and related substances is reviewed in "Science and Technology of Fructans", M.Suzuki and N. J. Chatterton, Eds., CRC Press, Boca Raton, Fla. 1993. A review of technology relating to inulin is found in "Inulin and Inulin-containing Crops", S. Fuchs, Ed., Elsevier Science Publishers B. V., Amsterdam, 1993. In particular, see Vogel, "A PROCESS FOR THE PRODUCTION OF INULIN AND ITS HYDROLYSIS PRODUCTS FROM PLANT MATERIAL", pp. 65-75.
It is also known that the maintenance of a balance between the various bacteria that constitute the enterobacterial flora is closely related to man's health and, when pathogenic bacteria which are usually in the minority in the intestines become predominant, the systems of a disease develop. A typical example is diarrhea which occurs as a result of the disappearance of Bifidobacterium bifidum or the action of Escherichia coli or Staphylococcus. Bifidobacterium bifidum is also closely related to infant health. More specifically, Bifidobacterium bifidum is predominant in the enterobacterial flora of healthy infants. It is known that the feces of a dysenteric infant have a markedly lowered Bifidobacterium bifidum content and the relative proportions of the various bacteria in the enterobacterial flora is considerably out of balance.
On the basis of these various known facts, a typical well-balanced enterobacterial flora is now considered to be such that Bifidobacterium bifidum, which has excellent staying and proliferation potencies in the intestines, is most predominant at all times.
In view of the useful activities of Bifidobacterium bifidum, various kinds of Bifidobacterium bifidum-containing preparations and dairy products have recently been developed for the purpose of increasing the amount of Bifidobacterium bifidum in the intestines.
It is considered that the most essential factor for the proliferation of Bifidobacterium in the intestines is saccharides.
Recent, studies found that fructooligosaccharides are effective in promoting the proliferation of Bifidobacterium bifidum. Fructooligosaccharides (FOS) are natural substances composed primarily of fructose molecules. They belong to a group of carbohydrates that occur in many different plants. FOS are indigestible oligosaccharides that are members of the inulin subclass of fructosans, polymers composed of fructose residues. Specifically, inulins are glucofructosans, carbohydrate polymers consisting of a chain of fructose resides linked by glycosidic bonds. FOS are not hydrolyzed in the small intestine and pass through without being digested, reaching the large intestine where intact they are selectively fermented and utilized many intestinal microorganisms. FOS can be utilized efficiently by lactobacilli and bifidobacteria, species of bacteria that are beneficial for human health (Hidaka et al. "Fructooligosaccharides: Enzymatic Preparation and Biofunctions", Journal of Carbohydrate Chemistry 10(4): 509-522, 1991). Selective fermentation of FOS by Bifidobacterium leads to an increase in the presence of these bacteria and to the production of acetic acid and lactic acid as fermentation endproducts, resulting in a lower pH in the digestive tract and providing a means to prevent the overgrowth harmful bacteria like Escherichia coli, Clostridium perfringens and Clostridium difficile. (Hidaka et al., supra.) Hikada et al., also state that fermentation of FOS can also lead to an increase in the presence of short chain fatty acids and the suppression of undesirable microorganisms such as Clostridium perfringens, C. difficile, or E. coli and the toxins they produce. FOS can be utilized most efficiently by bifidobacteria, which are believed to be highly beneficial organisms (Hidaka, et al.), but cannot be utilized by certain undesirable as E. coli and putrefactive bacteria such as Clostridium perfringens or Clostridium difficile. It has also been shown, H. Hidaka et al., Effects of Fructooligosaccharides on Intestinal Flora and Human Health, 5 Bifidobacteria Microflora 37-50 (1986), that administration of fructo-oligosaccharides (FOS) enhances growth of the bifidobacteria population in the intestine, suppresses production of putrefactive factors, improves blood lipid levels in hyperlipidemia patients and provides relief from constipation.
Fructooligosaccharides (FOS) can be produced enzymatically through chemical techniques or by extraction from natural substances. FOS occur in nature in many kinds of plants, including onions, dahlias, garlic, shallots, artichokes, wheat, rye, bananas, asparagus and tomatoes, that are commonly part of a human diet (Speights et al., "Fructooligosaccharides-A Low Caloric Bulking Agent And More From Sucrose", Carbohydrates in Industrial Synthesis, ed. M. A. Clarke, Proceedings of the Symposium of the Division of Carbohydrate Chemistry of the American Chemical Society, 1992).
It has been shown, A. Hata, The Influence of Neosugar on the Lipid Metabolism of Experimental Animals, Proc. 1.sup.st Neosugar Res. Conference, Tokyo (1982), that fructo-oligosaccharides (FOS) in the diet of experimental animals cause reduction of blood sugar, serum cholesterol, triglycerides, phospholipids; significant improvement in the HDL/LDL ratio; an increase in free fatty acids; and significant decreases in total cholesterol in lipidemia cases.
Animal toxicology studies have shown no evidence of toxicity, mutagenicity, or carginogenic effects due to FOS (Clevenger et al., "Toxicological evaluation of neosugar: genotoxicity, carcinogenicity, and chronic toxicity", Journal of the American College of Toxicology 7:643-622, 1988). Indigestible oligosaccharides such as FOS can be added to a nutritional product to create an environment in the gastrointestinal tract that is not conducive to the growth of microbial pathogens. Such a nutritional product can also be useful in the prevention of diarrhea caused by these pathogens. FOS is used in Japan in many food products and has been added to infant formula (Fructooligosaccharide Information Package, Coors Bio Tech, Inc. May 1990).
Certain bacteria have also been shown to be beneficial to human gastrointestinal health. The intestinal flora of the human gut contains some 100.times.10.sup.9 viable bacteria, representing 100 or more different species. The major bacteria of the intestine can be roughly divided into three groups: (a) lactic acid bacteria, including lactobacilli, bifidobacteria, and streptococci; (b) anaerobic bacteria; and (c) aerobic bacteria.
Bacteria of the genus Lactobacillus have been used for several hundred years for treating various illnesses. Lactobacilli found in the human intestinal tract include L. acidophilus, L. casei, L. fermentum, L. salivaroes, L. brevis, L. leichmannii, L. plantarum, and L. cellobiosus. In recent years, L. acidophilus has been shown to be exceptionally useful in treating conditions such as antibiotic-induced imbalances in the gastrointestinal microflora, hypercholesterolemia, vaginal infections, E.coli infection, oral contraceptive failure, depressed immunity, cancerous tumors, chronic granulomatous disease, and lactose indigestion. A. G. Shauss, Method of Action, Clinical Application, and Toxicity Data, 3 J. Advancement Med. 163 (1990). In vitro studies have shown L. acidophilus to have an inhibitory effect on the growth of pathogenic bacteria such as Campylobacterpylori, Staphylococcus aureus, Pseudomonas aeruginosa, and Sarcina lutea. K. M. Shahani et al., Natural Antibiotic Activity of Lactobacillus Acidophilus and Bulgaricus, 11 Cultured Dairy Products J. 14 (1976).
The beneficial effect of L. acidophilus is further illustrated by preliminary evidence that L. acidophilus inhibits the toxic activities of bacteria in patients with chronic kidney failure. M. L. Simenhoff et al., Biomodulation of Uremic Pathophysiology in Man, abstract presented at Am. Soc. Of Nephrology Meeting, Baltimore, 1992. Such patients often have toxic levels of amines in their blood due to bacterial overgrowth in the small bowel. Consumption of high levels of freeze dried bacteria drastically reduces levels of these toxic amines. These results demonstrate the ability of L. acidophilus to exert a positive effect on the microflora of the intestines.
Bifidobacteria are also known to exert a beneficial influence on human health. These bacteria exert antimicrobial activity in the human intestine by producing lactic acid and acetic acid as a result of carbohydrate metabolism. These acids lower the intestinal pH, thereby inhibiting overgrowth of gastrointestinal pathogens. Therapeutic applications of bifidobacteria are indicated for the management of diarrhea and constipation, and the management of hepatic encephalopathy with hyperammonemia. Additional benefits include the production of B vitamins and breakdown of carginogenic N-nitrosamines.
Bifidobacteria can be significantly reduced in elderly ispeople due to a reduction of secreted gastric juices. The bifidobacteria population in adults is much more stable, however, changes in the diet, administration of antibiotics, exposure to gamma radiation or x-rays, disease, stress and other disturbances can result in overgrowth of potentially pathogenic bacteria, decrease in beneficial bacteria (lactobacilli and bifidobacteria), and in the gut is associated with various forms of diarrhea, susceptibility to systemic infections, constipation, vague and acute abdominal symptoms, fatigue, dyspepsia, and presence of carcinogenic metabolites. Reestablishment of a normal balance of gastrointestinal flora can be accelerated, and such normal balance maintained, with dietary administration of lactobacilli and/or bifidobacteria such as in the present invention. Even when the Bifidobacteria have become temporarily predominant in intestines, its influence may readily change. Thus, it is preferred to promote the growth of not only Bifidobacteria but also other useful bacteria such as lactic acid bacteria in order to stably obtain the effect of improving intestinal floras. In other words, the influence of lactic acid bacteria and so forth may also be increased together with that of Bifidobacteria.
Lactobacilli and bifidobacteria produce organic acids that reduce intestinal pH and thereby inhibit the growth of acid-sensitive undesirable bacteria. Lactobacilli produce lactic acid, hyrdrogen peroxide, and possibly acetic and benzoic acids. Bifidobacteria produce short chain fatty acids (SCFA) such as acetic, propionic, and butyric acids, as well as lactic and formic acids. The most plentiful short chain fatty acid produced by bifidobacteria is acetic acid, which has a wide range of antimicrobial activities against yeasts, molds and other bacteria. Additionally, short chain fatty acids support normal gastrointestinal function by increasing colonic blood flow, stimulating pancreatic enzyme secretion, promoting sodium and water absorption, and potentiating intestinal mucosal growth. Bifidobacteria are also known to deconjugate bile salts to free bile acids, which are more inhibitory to susceptible bacteria than are the conjugated forms. Further, lactobacilli and bifidobacteria are able to produce other antimicrobial substances, such as bacteriocins, that inhibit the growth and proliferation of harmful bacteria in the gut.
In view of the foregoing, it will be appreciated that a composition for alleviating irritable bowel symptoms and for improving and maintaining gastrointestinal health comprising aloe, that has antibacterial and antiviral activity, and soluble dietary fibers such as fructo-oligosaccharides and inulin, that provide the typical advantages of dietary fiber and additionally are low in calories, does not affect blood glucose or insulin levels, further including beneficial/friendly bacteria which favor the growth of other beneficial bacteria in the gastrointestinal tract while at the same time inhibiting the growth of potentially pathogenic or harmful microorganisms would be a significant advancement in the art.