Methods of reversing oxidative stress with lactulose and other prebiotic compounds

Abstract

A composition for reversing oxidative stress including a gut flora maintaining agent. A food product for reversing oxidative stress including a gut flora maintaining agent. A method of reversing oxidative stress, by administering the gut flora maintaining agent to an individual, inducing the individual's microbiome to generate systemic hydrogen, and reversing oxidative stress.

Description

METHODS OF REVERSING OXIDATIVE STRESS WITH LACTULOSE AND OTHER PREBIOTIC COMPOUNDSBACKGROUND OF THE INVENTION1. TECHNICAL FIELD

[0001] The present invention relates to compositions and methods of reversing oxidative stress in the body. More specifically, the present invention relates to compositions and methods for using prebiotics in general and more specifically lactulose to reverse oxidative stress.2. BACKGROUND ART

[0002] Oxidative stress in an individual occurs when there is a disturbance in the balance between the production of reactive oxygen species (ROS - such as free radicals or peroxides) and the body’s antioxidant defenses. Normally, the body can produce enough antioxidants to reduce any ROS. However, when the body is unable to keep the ROS under control, a wide range of diseases can develop such as neurodegenerative diseases (Lou Gehrig’s disease, Alzheimer’s disease, Huntington’s disease, depression, or multiple sclerosis), cardiovascular diseases, and cancer, as well as general aging of the body. ROS are constantly formed and subsequently reduced in the body; however, a number of events can cause a harmful imbalance of ROS to develop, including hard exercise, smoking, exposure to environmental pollutants, stress, and exposure to ultraviolet rays.

[0003] Supplements of antioxidants (vitamins A C, E, folic acid, beta carotene, polyphenols, etc.) are sometimes used to counteract oxidative stress, but they can also cause harm to high risk groups of individuals because they actually interfere with essential defense mechanisms in the body. Beta carotene has been shown to increase cancer risk in smokers instead of decrease the risk. Vitamin E also is shown to reduce heart disease risk if it is found in food, but actual supplements increase risk of heart disease. Alternative treatments for oxidative stress are needed.

[0004] Ohta (Curr Pharm Des. 2011 Jul; 17(22): 2241-2252.) describes that molecular hydrogen gas (H2) can be used as an antioxidant. H2 has several very important advantages over other antioxidants. First, since H2 is the smallest known molecule, it rapidly diffuses into tissues and cells and can penetrate biomembranes and diffuse through barriers into cellular components. Second, H2 is uniquely selective as an antioxidant in the body in that it will target harmful ROS, but yet is mild enough neither to disturb metabolic redox reactions nor to affect ROS that function in cell signaling. A third important benefit of H2 relative to other antioxidants currently used in supplements is that high concentrations do not cause cytotoxicity. It was found that H2 scavenges OH, but not O2_, H2O2 and NO in cultured cells. Therefore, the adverse effectsof H2 are minimal compared to other antioxidants.

[0005] Aoki, et al. describe that short intervals of intense exercise causes oxidative stress and can lead to increased fatigue, muscle microinjury, or inflammation. Soccer players were given hydrogen-rich water or placebo water during exercise. Oral intake of the hydrogen water prevented an elevation of blood lactate during heavy exercise, and exercise-induced decline of muscle function was improved.

[0006] In recent years, the therapeutic antioxidant benefits of H2 have been recognized and multiple delivery systems have been developed and utilized in the fields of medicine, supplements, and food and beverage. Presently, there are three different delivery systems utilized - inhalation of H2 gas, oral ingestion of H2 in water solutions, and H2 in water solutions delivered intravenously. All of these methods present significant challenges to delivering the benefits of H2 to a larger portion of the population in a safe, efficacious, convenient and cost- effective way. Hydrogen gas (H2) is highly flammable and explosive, so any system in which it is consumed through inhalation presents substantial safety risks. H2 can be delivered in conventional high-pressure tank systems, which are large, heavy, and very inconvenient to use, or through expensive hydrogen-generation machines. H2 in water solutions (for oral ingestion or IV) can be administered immediately after the H2 in water solution is formed, most commonly via electrolysis, but this method still involves expensive equipment, and is highly inconvenient given the fact that the H2 water must be consumed quickly before the H2 diffuses out of the water (and container). More recently, there has been a number of “Hydrogen Water” products developed that are geared towards expanding the therapeutic use of hydrogen to a mass market. Not only is the manufacture of such products very expensive relative to regular, non-hydrogen containing food and beverage counterparts, but the high diffusivity of H2 creates serious shelf-life issues since maintaining meaningful levels of the gas inside the product is difficult to impossible using current food, beverage, or supplement packaging technology.

[0007] Therefore, there remains a need for a delivery system that can effectively reduce and reverse oxidative stress in the body in a safe, cost-effective, efficacious, convenient and cost- effective way.SUMMARY OF THE INVENTION

[0008] The present invention provides for a composition for reversing oxidative stress including a gut flora maintaining agent that induces gut flora to generate hydrogen.

[0009] The present invention provides for a food, beverage, or supplement product for reversing oxidative stress including a gut flora maintaining agent that induces gut flora to generate hydrogen.

[0010] The present invention also provides for a method of reversing oxidative stress, by administering the gut flora maintaining agent to an individual, inducing the individual’s microbiome to generate systemic hydrogen, and reversing oxidative stress.DETAILED DESCRIPTION OF THE INVENTION

[0011] The present invention generally provides for compositions and methods of reversing oxidative stress using a gut flora maintaining agent. The gut flora maintaining agent also provides beneficial therapeutic properties to an individual, such as decreasing inflammation, positively effecting fat metabolism, and increasing antibody half-life.

[0012] “Hydrogen” as used herein, refers to the composition H2(also written herein as “H2”), but can also include molecular hydrogen (H) and any composition capable of releasing hydrogen.

[0013] “Nutraceutical” as used herein, refers to a food (or part of a food) that provides medical or health benefits, including the prevention and / or treatment of a disease. A nutraceutical can include dietary supplements and processed foods such as cereals, soups, and beverages. A nutraceutical can also include feed for animals or pets.

[0014] “Individual” as used herein, can refer to humans or animals, and most preferably mammals.

[0015] The gut flora maintaining agent is preferably one of a non-absorbable or non- digestible polysaccharide, sugar, or other prebiotic. It should be understood that the gut flora maintaining agent can have one of these properties or both, depending upon the specific compound. Preferably, the gut flora maintaining agent also has the ability to reduce and / or eliminate inflammation.

[0016] The gut flora maintaining agent is preferably lactulose, or homologues thereof. Lactulose has all of the properties described above (i.e. it is a non-absorbable sugar, a compound that is able to convert NH3 to NH4+ in the body, a prebiotic, a hydrogen-generating compound, and reduces / eliminates inflammation). Lactulose is a synthetic sugar that is a disaccharide of a molecule of fructose and a molecule of galactose. It is currently indicated for constipation treatment or for hepatic encephalopathy in removing ammonia from blood. Lactulose is nonabsorbable and fermented by intestinal bacteria, resulting in the production of hydrogen. A lactulose hydrogen breath test has previously been used to detect irritable bowel syndrome by detecting an abnormal amount of hydrogen in the breath. However, the creation of hydrogen in the present invention is a positive effect of the compound so that inflammation can be reduced. Any suitable amount of lactulose (or the gut flora maintaining agent in general) can be used. Most preferably, less than 10 g per day are consumed by a person ingesting any food products madewith lactulose.

[0017] When the gut flora maintaining agent is a non-absorbable or non-digestible sugar, it can also be any other monosaccharide, polysaccharide, or other non-saccharide sweetener, such as, but not limited to, mannitol, inulin, sucralose, aspartame, dextrose, maltodextrin, homologues, or combinations thereof. Inulin in particular is composed of a heterogeneous collection of fructose polymers, is not absorbed in the blood, and elevates the amount of H2 in mice with oral administration. The non-absorbable sugar can be administered in amounts similar to lactulose.

[0018] The gut flora maintaining agent can also be any suitable prebiotic, including, but not limited to, lactulose (and other disaccharides), inulin, fructooligosaccharides (FOS) (produced by a degradation of inulin), xylooligosaccharides (XOS), polydextrose, oligofructose-enriched inulin, resistant starch, galactooligosaccharides (GOS), transgalactooligosaccharide, mannooligosaccharides, or tagatose (and other monosaccharides). The prebiotics can be shortchain (containing 2-8 links per saccharide molecule and typically fermenting more quickly in the right side of the colon), long-chain (containing 9-64 links per saccharide molecule and fermenting slower in the left side of the colon), or full-spectrum (containing 2-64 links per saccharide molecule and fermenting through the whole colon). The prebiotics can stimulate the growth of many types of bacterial, but especially beneficial bifidobacteria and lactic acid species in the gut. Prebiotics are generally dosed at 4-15 g but lower doses can be used when used as additives in food.

[0019] The prebiotics can work synergistically with any suitable probiotic as well. Lactulose is also advantageous in that it can provide a much better probiotic action than Lactobacillus (yogurt bacteria) and changes the bacterial flora in the gut from bad to good. Probiotics are microorganisms that are introduced into the body due to their beneficial qualities. Examples of probiotics are bacteria and yeast in supplements and food. Probiotics are meant to maintain the health of the digestive system and lining of the intestines and aid the immune system. The natural balance of bacteria can become disturbed after an infection or the use of antibiotics, and it can be helpful to take probiotics to repopulate the digestive system with beneficial bacteria. The lactulose of the present invention is a true probiotic, i.e. a substance that has a beneficial effect on the intestinal microbial balance of the individual taking the composition. The composition that generates increased hydrogen in the body, preferably lactulose, can induce the growth of beneficial bacterial flora in the gut and that induces the flora to generate systemic hydrogen, which, in turn, positively affects the redox value systemically of the person and reduces inflammation, so it is a true probiotic unlike most substances that claim to be probiotic that really just provide dead culture to the body. The composition actually, in essence, feeds and inducesthe flora in the gut to grow, which, in turn, induces generation of hydrogen by the flora and the bacteria in the gut, which positively affects the redox value of the body (it raises the levels of antioxidant hydrogen in the body). Reducing the number of free radicals (and thus the redox value) to reduce oxidative stress is the goal of taking antioxidants (Lobo, et al., Pharmacogn Rev. 2010 Jul-Dec; 4(8): 118-126). By ingesting the composition of the present invention over time, there is a cumulative probiotic effect.

[0020] It should be understood that the mechanism of action of the gut flora maintaining agent can be through the generation of hydrogen.

[0021] The gut flora maintaining agent can be formulated as a nutraceutical or easily included as an additive in efficacious levels in virtually any food, beverage, or supplement product such as, but not limited to, sports drinks, bottled water, juices, coffees, teas, soft drinks, cookies, cakes, granola bars, cereal bars, meal replacement bars, candy, fruit chews, breads, crackers, cereal, soup, stews, sauces, pasta dishes, frozen dinners, chips, pastries, meat products, yogurts, ice cream, dairy products, non-dairy alternative milks, prepackaged cheese, tablets, baby food, powdered beverages, tablets, capsules, confections, or any other suitable product. The gut flora maintaining agent can also be included as an additive in animal feed or pet feed, and designed for animals such as, but not limited to, cattle, sheep, llamas, alpacas, bison, chickens, geese, ducks, turkeys, pigs, dogs, cats, rabbits, birds, reptiles, fish, mice, rats, hamsters, and guinea pigs. The present invention provides for a food product including the gut flora maintaining agent. The present invention also provides for an animal feed product including the gut flora maintaining agent. The food, beverage, or supplement product and the animal feed product can also be formulated for intravenous delivery.

[0022] As a result of their physical and chemical properties, most of the above mentioned gut flora maintaining agents can be added to virtually all food and beverage products in an easy and cost-effective way. Numerous non-absorbable polysaccharides named above possess solubility, stability, taste and bulking properties similar to sugar (sucrose), one of the most common food additives present in most food and beverage product forms currently on the market. Lactulose, in particular, is an excellent ingredient to include in products for the purpose of increasing H2 production in the gut since it is approximately 60% as sweet as sugar, is slightly more soluble, and has similar taste and bulking properties. It can therefore be substituted for sugar on an almost 1 :1 basis with little impact to any food or beverage product.

[0023] The above-described delivery system of H2 in which a gut flora maintaining agent is added to a food, beverage, or supplement product in order to induce H2 production inside the body presents significant benefits over the current inhalation, oral, or IV ingestion methods. Usingfood, beverage, or supplement products in which a gut flora maintaining agent is added completely eliminates the safety issues associated with H2 inhalation or the production of H2 in water solutions. These products are also substantially less expensive to produce since efficacious doses of the gut flora maintaining agents can easily be incorporated into the formulations without the need to add expensive H2-generating equipment. These products also completely eliminate the shelf-life issues associated with hydrogen-containing products due to the extremely high diffusivity of H2. Finally, since the gut flora maintaining agents described above can so easily be incorporated into virtually any food or beverage product, this delivery system represents the safest, most convenient, and cost-effective method possible of enabling large numbers of patients and consumers to realize the tremendous health benefits of H2. Exercise is known to cause oxidative stress as higher levels of ROS are detected after exercise. This can lead to muscle damage. Lactulose is particularly useful in reducing and reversing oxidative stress by generating systemic hydrogen in the body that can counteract ROS.

[0024] Lactulose's ability to mitigate oxidative stress does not impede the production of lnterleukin-6 (IL-6), a multifunctional cytokine with various roles in the immune system, inflammation, and tissue repair. IL-6 is known to be produced in response to exercise and can play a crucial role in muscle adaptation and repair. Unlike some interventions, such as antiinflammatories, that suppress IL-6 production while reducing inflammation, lactulose administration does not hinder the beneficial effects of IL-6, allowing for optimal muscle recovery, buildup, and strengthening following exercise while providing an anti-inflammatory effect.. This dual action of lactulose in reducing oxidative stress and producing an anti-inflammatory effect while preserving IL-6-related benefits underscores its potential as a valuable tool in enhancing the post-exercise recovery process and overall muscle health. In other words, post workout pain and inflammation can be reduced while still allowing for buildup of muscle mass.

[0025] The present invention also provides generally for a method of reversing oxidative stress, by administering the gut flora maintaining agent to an individual, inducing the individual’s microbiome to generate systemic hydrogen, and reversing oxidative stress. The gut flora maintaining agent can be any described above, and is preferably a prebiotic, and more preferably lactulose. By systemically producing hydrogen in the body, the ROS can be countered and inflammation can be reduced caused by any ROS. For example, the gut flora maintaining agent is able to reduce levels of the pain markers NGF (nerve growth factor) and Substance P and the levels of IL-10 in the body (U.S. Patent No. 9,545,415). The gut flora maintaining agent can be administered at any suitable time, such as after exposure to ROS, after hard exercise to aid in recovery, or on a daily basis to prevent excessive ROS from accumulating in the body. The gutflora maintaining agent also does not have the negative side effects of depleting ROS that are necessary in cell signaling.

[0026] The gut flora maintaining agent can further provide other benefits to individuals using it. The gut flora maintaining agent also has lipid-metabolism altering properties and generally lowers high cholesterol levels, as described in U.S. Patent Application No. 14 / 758,903. For example, it has been shown that Ox-LDL cholesterol is lowered and atherosclerotic plaque reduced with lactulose, and fatty liver development is prevented.

[0027] The gut flora maintaining agent can also extend the half-life of an antibody that the individual is taking, such as, but not limited to a lipid-lowering antibody (monoclonal antibody (MAb) anti-PCSK9). In other words, the gut flora maintaining agent can work synergistically with any antibody that the individual is taking to extend its half-life. This allows for lower dosing of antibodies.

[0028] The invention is further described in detail by reference to the following experimental examples. These examples are provided for the purpose of illustration only, and are not intended to be limiting unless otherwise specified. Thus, the present invention should in no way be construed as being limited to the following examples, but rather, be construed to encompass any and all variations which become evident as a result of the teaching provided herein.

[0029] EXAMPLE 1 : Lactulose Water

[0030] A ready-to-drink water beverage including lactulose or another previously mentioned gut flora maintaining agent can be created according to the formula below and shown in TABLE 1 . The manufacturing procedure is as follows:

[0031] 1 ) Add water to a vessel and begin agitation.

[0032] 2) Ingredients should be added to the batch one at a time in the order listed in the formula from top to bottom. Sufficient time under agitation should be allowed to ensure each ingredient is completely dissolved before adding the next ingredient.

[0033] 3) This formula can be made shelf-stable through either the addition of chemical preservatives or via common beverage thermal processing methods if chemical preservatives are not desired.

[0034] a) If chemical preservatives are used, the product can be filled into bottles without any heat applied in the bottling process.

[0035] b) If a non-chemically preserved product is desired, the product can be thermally processed at a temperature of 195 - 205 for 30 seconds and then filled into bottles at 175F - 183F. Bottles should be inverted for 3-6 seconds (to ensure the cap is heat treated) and thencooled quickly to ambient temperatures.TABLE 1

[0036] EXAMPLE 2: Energy Drink

[0037] A ready-to-drink energy drink including lactulose or another previously mentioned gut flora maintaining agent can be created according to the formula below and shown in TABLE 2. The manufacturing procedure is as follows:

[0038] 1 ) Add the desired amount of water to the vessel and start agitation.

[0039] 2) Gradually introduce lactulose while continuing agitation to ensure proper dissolution.

[0040] 3) Sequentially add electrolytes (sodium, potassium, magnesium) in the order specified below. Allow each electrolyte to dissolve fully before adding the next one: Sodium, Potassium, Magnesium

[0041] 4) Incorporate natural flavorings, adjusting the quantity based on taste preferences. Continue to agitate the mixture.

[0042] 5) Add citric acid to provide desired acidity and flavor enhancement. Stir well.

[0043] 6) Include vitamins like B vitamins to enhance the drink's nutritional profile. Mix thoroughly.

[0044] 7) Incorporate natural colorings to achieve the desired visual appeal. Mix until the color is evenly distributed.

[0045] 8) Sufficient time under agitation should be allowed to ensure each ingredient is completely dissolved before adding the next ingredient.

[0046] 9) This formula can be made shelf-stable through either the addition of chemical preservatives or via common beverage thermal processing methods if chemical preservatives are not desired.

[0047] a) If chemical preservatives are used, the product can be filled into bottles withoutany heat applied in the bottling process.

[0048] b) If a non-chemically preserved product is desired, the product can be thermally processed at a temperature of 195 - 205 for 30 seconds and then filled into bottles at 175F - 183F. Bottles should be inverted for 3-6 seconds (to ensure the cap is heat treated) and then cooled quickly to ambient temperatures.TABLE 2

[0049] EXAMPLE 3: Protein Shake

[0050] A ready-to-drink protein nutrition shake including lactulose or another previously mentioned gut flora maintaining agent can be produced according to the formula below. The manufacturing procedure is as follows:

[0051] 1 ) Add water to a vessel and begin agitation.

[0052] 2) Add Protein Stabilizer Blend and allow 20 - 30 minutes for proper mixing and hydration.

[0053] 3) Slowly add Milk Protein Isolate (or other desired protein source) under constant agitation. High shear mixing is preferred to ensure proper mixing and hydration. Once all of the protein is added, the resulting blend should be allowed to mix for 20 - 30 minutes to ensure proper protein hydration and interaction with the Protein Stabilizer Blend.

[0054] 4) Add remaining ingredients to the batch in the order listed in the formula below in TABLE 3

[0055] 5) Once batching is completed, the product should be thermally processed and filled in accordance with low-acid canned food regulations. The product can be filled aseptically in cartons or bottles using UHT thermal processing (either direct steam or indirect heat) at a temperature of 285295F for 3-6 seconds.TABLE 3

[0056] EXAMPLE 4: Protein Powder

[0057] A ready-to-mix Protein Powder product including lactulose or another gut flora maintaining agent mentioned above can be produced according to the formula below. Such a product can be added to water, milk or any other food or beverage desired by the end consumer. To manufacture this product, all ingredients should be added to a powder blender in the order listed in the formula in TABLE 4. The resultant blend should then be agitated until a homogeneous blend is achieved.TABLE 4

[0058] EXAMPLE 5: Nutrition Bar

[0059] A nutrition bar containing lactulose or another previously mentioned gut flora maintaining agent can be created according to the formula in TABLES 5-8 and process below:

[0060] 1 ) A Granola Blend should be created by adding the ingredients to a blending vessel in the amounts below in TABLE 5:TABLE 5

[0061] 2) A Coating Syrup should be created by adding the ingredients and amounts below in TABLE 6 to a heated kettle under gentle agitation. The temperature should be maintained at 80 - 84C and the mixture should be blended until it is homogeneous.TABLE 6

[0062] 3) The Granola Blend should be added to a tumbling enrober at a rotation speed that yields a gentle tumbling action. The Coating Syrup, still at roughly 80 - 84C should be slowly poured over the Granola Blend until the resultant blend is homogeneous.

[0063] 4) The Coating Syrup I Granola Blend product should be laid out on a flat surface at roughly 1 - 2” thickness and dried in an oven to a moisture content of 2.8 - 3.2% by mass. The oven temperature should not exceed 290F to ensure the cereal base is not degraded. The resultant intermediate product from this process is a Granola Cereal.

[0064] 5) A Binding Syrup should be prepared in a separate mixing vessel in which the ingredients are added in the amounts and order listed below in TABLE 7 under constant agitation. Mixing should continue until a homogeneous blend is achieved.TABLE 7

[0065] 6) The Binding Syrup should be added to the Granola Cereal product in a HobartMixer along with Crisp Rice in the amount listed below in TABLE 8.TABLE 8

[0066] 7) The resultant product should be laid out on a flat surface at the desiredthickness and cut into individual bars in the desired dimensions.

[0067] Throughout this application, various publications, including United States patents, are referenced by author and year and patents by number. Full citations for the publications are listed below. The disclosures of these publications and patents in their entireties are hereby incorporated by reference into this application in order to more fully describe the state of the art to which this invention pertains.

[0068] The invention has been described in an illustrative manner, and it is to be understood that the terminology which has been used is intended to be in the nature of words of description rather than of limitation.

[0069] Obviously, many modifications and variations of the present invention are possible in light of the above teachings. It is, therefore, to be understood that within the scope of the appended claims, the invention can be practiced otherwise than as specifically described.

Claims

CLAIMSWhat is claimed is:

1. A composition for reversing oxidative stress, comprising a gut flora maintaining agent.

2. The composition of claim 1 , wherein said gut flora maintaining agent is chosen from the group consisting of a non-absorbable or non-digestible polysaccharide, sugar, or other prebiotic.

3. The composition of claim 2, wherein said non-absorbable or non-digestible sugar is chosen from the group consisting of lactulose, mannitol, inulin, sucralose, aspartame, maltodextrin, homologues, and combinations thereof.

4. The composition of claim 2, wherein said prebiotic is chosen from the group consisting of lactulose, disaccharides, inulin, fructooligosaccharides (FOS), xylooligosaccharides (XOS), polydextrose, oligofructose-enriched inulin, resistant starch, galactooligosaccharides (GOS), transgalactooligosaccharide, mannooligosaccharides, tagatose, and monosaccharides.

5. A food, beverage, or supplement product for reversing oxidative stress comprising a gut flora maintaining agent.

6. The food, beverage, or supplement product of claim 5, wherein said food product is chosen from the group consisting of sports drinks, bottled water, juices, coffees, teas, soft drinks, cookies, cakes, granola bars, cereal bars, meal replacement bars, candy, fruit chews, breads, crackers, cereal, soup, stews, sauces, pasta dishes, frozen dinners, chips, pastries, meat products, yogurts, ice cream, dairy products, non-dairy alternative milks, prepackaged cheese, tablets, baby food, powdered beverages, tablets, capsules, and confections.

7. The food, beverage, or supplement product of claim 5, wherein said gut flora maintaining agent is chosen from the group consisting of a non-absorbable or non-digestible polysaccharide, sugar, or other prebiotic.

8. The food, beverage, or supplement product of claim 7, wherein said non-absorbable or non-digestible sugar is chosen from the group consisting of lactulose, mannitol, inulin, sucralose, aspartame, maltodextrin, homologues, and combinations thereof.

9. The food, beverage, or supplement product of claim 7, wherein said prebiotic is chosen from the group consisting of lactulose, disaccharides, inulin, fructooligosaccharides (FOS), xylooligosaccharides (XOS), polydextrose, oligofructose-enriched inulin, resistant starch, galactooligosaccharides (GOS), transgalactooligosaccharide, mannooligosaccharides, tagatose, and monosaccharides.

10. An animal feed product for reversing oxidative stress comprising a gut flora maintaining agent.11 . The animal feed product of claim 10, wherein said animal feed product is designed for an animal chosen from the group consisting of cattle, sheep, llamas, alpacas, bison, chickens, geese, ducks, turkeys, pigs, dogs, cats, rabbits, birds, reptiles, fish, mice, rats, hamsters, and guinea pigs.

12. The animal feed product of claim 10, wherein said gut flora maintaining agent is chosen from the group consisting of non-absorbable or non-digestible polysaccharide, sugar, or other prebiotic.

13. The animal feed product of claim 12, wherein said non-absorbable or non-digestible sugar is chosen from the group consisting of lactulose, mannitol, inulin, sucralose, aspartame, dextrose, maltodextrin, homologues, and combinations thereof.

14. The animal feed product of claim 12, wherein said prebiotic is chosen from the group consisting of lactulose, disaccharides, inulin, fructooligosaccharides (FOS), xylooligosaccharides (XOS), polydextrose, oligofructose-enriched inulin, resistant starch, galactooligosaccharides (GOS), transgalactooligosaccharide, mannooligosaccharides, tagatose, and monosaccharides.

15. A method of reversing oxidative stress, including the steps of: administering the gut flora maintaining agent to an individual; inducing the individual’s microbiome to generate systemic hydrogen; and reversing oxidative stress.

16. The method of claim 15, wherein the gut flora maintaining agent is chosen from the group consisting of a non-absorbable or non-digestible polysaccharide, sugar, or other prebiotic.

17. The method of claim 15, wherein the gut flora maintaining agent is lactulose.

18. The method of claim 15, further including the step of reducing inflammation in the individual.

19. The method of claim 15, wherein said administering step is further defined as administering the gut flora maintaining agent after hard exercise.

20. The method of claim 15, further including a step chosen from the group consisting of lowering high cholesterol levels in the individual and extending the half-life of an antibody that the individual is taking.

21. The method of claim 15, wherein the gut flora maintaining agent is a food, beverage, or supplement product.

22. The method of claim 21 , wherein the food, beverage, or supplement product is chosen from the group consisting of sports drinks, bottled water, juices, coffees, teas, soft drinks, cookies, cakes, granola bars, cereal bars, meal replacement bars, candy, fruit chews, breads, crackers, cereal, soup, stews, sauces, pasta dishes, frozen dinners, chips, pastries, meat products, yogurts, ice cream, dairy products, non-dairy alternative milks, prepackaged cheese, tablets, baby food, powdered beverages, tablets, capsules, and confections23. The method of claim 15, wherein the gut flora maintaining agent is an animal feed product.

24. The method of claim 23, wherein the animal feed product is designed for an animal chosen from the group consisting of cattle, sheep, llamas, alpacas, bison, chickens, geese, ducks, turkeys, pigs, dogs, cats, rabbits, birds, reptiles, fish, mice, rats, hamsters, and guinea pigs.

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