Compositions of nitrates and methods of use thereof

Abstract

Disclosed is a method of preventing hypoglycemia and/or hyperglycemia in a human subject, the method comprising administering inorganic nitrate (NO3−) to the human subject. Also disclosed is a method of improving blood glucose homeostasis in a human subject, the method comprising administering inorganic nitrate (NO3−) to the human subject.

We claim: 
     
         1 . A method of improving blood glucose homeostasis in a human subject, the method comprising administering inorganic nitrate (NO 3   − ) to the human subject. 
     
     
         2 . The method of  claim 1 , wherein the inorganic nitrate is administered in a composition comprising the inorganic nitrate and at least one other ingredient selected from a polyphenol and a carbohydrate. 
     
     
         3 . The method of  claim 2 , wherein the polyphenol provided is from at least one natural source selected from the group consisting of: apple, pear, grapes, lemon, orange, lime, peach, pomegranate, grapefruit, kiwi, ginger, pineapple, blackberries, black raspberries, blueberries, cranberries, red raspberries, cherries, bog wortleberry, lingonberries, black elderberry, black chokeberry, black currant, cloudberries, strawberries, carrots, chili, rhubarb, onions, cacao products, green tea, black tea, nuts, Yerba mate, and coffee. 
     
     
         4 . The method of  claim 3 , wherein the amount of the inorganic nitrate in the composition is at least 50%. 
     
     
         5 . The method of  claim 2 , wherein the composition comprises the carbohydrate, the human subject is administered 50 kcal, 100 kcal, or 200 kcal carbohydrate. 
     
     
         6 . The method of  claim 5 , wherein the human subject is administered the inorganic nitrate before the human subject undergoes surgery. 
     
     
         7 . The method of  claim 1 , wherein the human subject is administered the inorganic nitrate after the human subject undergoes surgery. 
     
     
         8 . The method of  claim 1 , wherein the administration of inorganic nitrate (NO 3   − ) prevents insulin resistance. 
     
     
         9 . The method of  claim 1 , wherein the administration of inorganic nitrate (NO 3   − ) prevents hyperglycemia. 
     
     
         10 . The method of  claim 1 , wherein the subject has disturbed glucose homeostasis, the administration of inorganic nitrate (NO 3   − ) ameliorates disturbed glucose homeostasis. 
     
     
         11 . The method of  claim 10 , wherein the subject is diagnosed with a condition selected from the group consisting of: diabetes, prediabetes, metabolic syndrome, and obesity. 
     
     
         12 . The method of  claim 10 , wherein the subject is a patient in intensive care unit, has burn injury, or is under metabolic stress. 
     
     
         13 . The method of  claim 10 , wherein the subject is hypoglycemic. 
     
     
         14 . The method of  claim 1 , wherein the human subject administered the inorganic nitrate once a day. 
     
     
         15 . The method of  claim 1 , wherein the human subject is administered the inorganic nitrate for at least two days. 
     
     
         16 . The method of  claim 14 , wherein the human subject is administered the inorganic nitrate daily for three days. 
     
     
         17 . The method of  claim 1 , wherein the inorganic nitrate is administered in a composition consisting of the inorganic nitrate and at least one additive. 
     
     
         18 . The method of  claim 16 , wherein the source of the inorganic nitrate is in the form of a nitrate salt. 
     
     
         19 . The method of  claim 17 , wherein the nitrate salt is selected from the group consisting of:
 sodium nitrate, potassium nitrate, calcium nitrate, zinc nitrate, and ammonium nitrate.   
     
     
         20 . The method of  claim 17 , wherein the nitrate salt is arginine nitrate. 
     
     
         21 . The method of  claim 1 , wherein the inorganic nitrate is provided from a natural nitrate source. 
     
     
         22 . The method of  claim 21 , wherein the natural nitrate source is juice or dried concentrate from at least one of spinach, lettuce, fennel, cabbage, Chinese cabbage, and beetroot. 
     
     
         23 . The method of  claim 1 , wherein between 0.01 to about 100 mmol inorganic nitrate is administered per kg body weight of the human subject. 
     
     
         24 . The method of  claim 1 , wherein between 0.01 mmol and 10 mmol inorganic nitrate is administered per kg body weight of the human subject. 
     
     
         25 . The method of  claim 1 , wherein between 0.1 mmol and 1 mmol inorganic nitrate is administered per kg body weight of the subject. 
     
     
         26 . The method of  claim 1 , wherein 0.1 mmol inorganic nitrate is administered per kg body weight of the subject. 
     
     
         27 . The method of  claim 1 , wherein the inorganic nitrate is administered orally. 
     
     
         28 . The method of  claim 1 , wherein the inorganic nitrate is administered in a composition in the form of a liquid, a paste, a gel, a bar, a cake, a powder, a granulate, an effervescent tablet, a chewing gum, a tablet, a capsule, a lozenge, a fast melting tablet or wafer, a sublingual tablet, or a spray. 
     
     
         29 . The method of  claim 17 , wherein the additive is selected from the group comprising: natural flavor, artificial flavor, sweetener, flavor enhancer, color additive, emulsifier, stabilizer, fat, and preservative. 
     
     
         30 . A method of preventing hypoglycemia and/or hyperglycemia in a human subject, the method comprising administering inorganic nitrate (NO 3   − ) to the human subject. 
     
     
         31 . The method of  claim 30 , wherein the inorganic nitrate is administered in a composition comprising the inorganic nitrate and a polyphenol. 
     
     
         32 . The method of  claim 31 , wherein the polyphenol provided is from at least one natural source selected from the group consisting of: apple, pear, grapes, lemon, orange, lime, peach, pomegranate, grapefruit, kiwi, ginger, pineapple, blackberries, black raspberries, blueberries, cranberries, red raspberries, cherries, bog wortleberry, lingonberries, black elderberry, black chokeberry, black currant, cloudberries, strawberries, carrots, chili, rhubarb, onions, cacao products, green tea, black tea, nuts, Yerba mate, and coffee. 
     
     
         33 . The method of  claim 32 , wherein the amount of the inorganic nitrate in the composition is at least 50%. 
     
     
         34 . The method of  claim 30 , wherein the administration of inorganic nitrate (NO 3   − ) prevents insulin resistance. 
     
     
         35 . The method of  claim 30 , wherein the subject has disturbed glucose homeostasis. 
     
     
         36 . The method of  claim 35 , wherein the subject is diagnosed with a condition selected from the group consisting of: diabetes, prediabetes, metabolic syndrome, and obesity. 
     
     
         37 . The method of  claim 30 , wherein the human subject administered the inorganic nitrate once a day. 
     
     
         38 . The method of  claim 30 , wherein the human subject is administered the inorganic nitrate for at least two days. 
     
     
         39 . The method of  claim 38 , wherein the human subject is administered the inorganic nitrate daily for three days. 
     
     
         40 . The method of  claim 30 , wherein the inorganic nitrate is administered in a composition consisting of the inorganic nitrate and at least one additive. 
     
     
         41 . The method of  claim 40 , wherein the additive is selected from the group comprising:
 natural flavor, artificial flavor, sweetener, flavor enhancer, color additive, emulsifier, stabilizer, fat, and preservative.   
     
     
         42 . The method of  claim 40 , wherein the source of the inorganic nitrate is in the form of a nitrate salt. 
     
     
         43 . The method of  claim 42 , wherein the nitrate salt is selected from the group consisting of: sodium nitrate, potassium nitrate, calcium nitrate, zinc nitrate, and ammonium nitrate. 
     
     
         44 . The method of  claim 42 , wherein the nitrate salt is arginine nitrate. 
     
     
         45 . The method of  claim 30 , wherein the inorganic nitrate is provided from a natural nitrate source. 
     
     
         46 . The method of  claim 45 , wherein the natural nitrate source is juice or dried concentrate from at least one of spinach, lettuce, fennel, cabbage, Chinese cabbage, and beetroot. 
     
     
         47 . The method of  claim 30 , wherein between 0.01 to about 100 mmol inorganic nitrate is administered per kg body weight of the human subject. 
     
     
         48 . The method of  claim 30 , wherein between 0.01 mmol and 10 mmol inorganic nitrate is administered per kg body weight of the human subject. 
     
     
         49 . The method of  claim 30 , wherein between 0.1 mmol and 1 mmol inorganic nitrate is administered per kg body weight of the subject. 
     
     
         50 . The method of  claim 30 , wherein 0.1 mmol inorganic nitrate is administered per kg body weight of the subject. 
     
     
         51 . The method of  claim 30 , wherein the inorganic nitrate is administered orally. 
     
     
         52 . The method of  claim 30 , wherein the inorganic nitrate is administered in a composition in the form of a liquid, a paste, a gel, a bar, a cake, a powder, a granulate, an effervescent tablet, a chewing gum, a tablet, a capsule, a lozenge, a fast melting tablet or wafer, a sublingual tablet, or a spray.