Compositions of nitrates and methods of use thereof

Abstract

Inorganic anions nitrate and nitrite influence metabolic rate and glucose homeostasis. Infusion of nitrite iv caused an acute drop in resting energy expenditure (oxygen consumption) and nitrate, when given perorally, caused a reduction in oxygen consumption during exercise and a depression of the increase in blood glucose observed after an oral glucose tolerance test. The doses of nitrate and nitrite did not cause any detectable change in methemoglobin levels of blood. Also, nitrate and nitrite did not alter lactate levels in blood. This discovery provides useful treatments to regulate the energy expenditure and glucose homeostasis of a mammal by administration of inorganic nitrite and/or nitrate.

We claim: 
     
         1 . A method of reducing blood pressure in a human comprising orally administering to the human a composition comprising an inorganic nitrite (NO 2   − ) and an acid. 
     
     
         2 . The method of  claim 1 , wherein the administration of the composition reduces systolic blood pressure and/or diastolic blood pressure of the human. 
     
     
         3 . The method of  claim 1 , wherein the acid is administered in the form of juice or dried concentrate of a lemon, juice or dried concentrate of a lime, ascorbic acid, acetic acid, or vinegar. 
     
     
         4 . The method of  claim 1 , wherein the composition is a nutritional supplement and further comprises at least one additive. 
     
     
         5 . The method of  claim 4 , wherein the at least one additive is selected from the group consisting of: natural flavor, artificial flavor, sweetener, flavor enhancer, color additive, emulsifier, stabilizer, fat, and preservative. 
     
     
         6 . The method of  claim 1 , wherein the inorganic nitrite (NO 2   − ) is provided from a natural source. 
     
     
         7 . The method of  claim 6 , wherein the natural source of the inorganic nitrite (NO 2   − ) is juice or dried concentrate from at least one of spinach, lettuce, fennel, cabbage, Chinese cabbage, and beetroot. 
     
     
         8 . The method of  claim 7 , wherein the natural source of the inorganic nitrite (NO 2   − ) is juice or dried concentrate from beetroot. 
     
     
         9 . The method of  claim 1 , wherein the source of the inorganic nitrite (NO 2   − ) is in the form of a nitrite salt. 
     
     
         10 . The method of  claim 9 , wherein the nitrite salt is selected from the group consisting of:
 sodium nitrite, potassium nitrite, calcium nitrite, zinc nitrite, ammonium nitrite, and arginine nitrite.   
     
     
         11 . The method of  claim 1 , wherein 0.1-100 umol inorganic nitrite (NO 2   − ) is administered per kg body weight of the human. 
     
     
         12 . The method of  claim 1 , wherein the composition is 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. 
     
     
         13 . The method of  claim 12 , wherein the administered composition is in the form of a liquid with a pH of 5 or below. 
     
     
         14 . The method of  claim 13 , wherein the liquid has a pH of between 4-5. 
     
     
         15 . The method of  claim 12 , wherein the composition is a functional food. 
     
     
         16 . The method of  claim 1 , wherein the composition further comprises a polyphenol. 
     
     
         17 . The method of  claim 16 , 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. 
     
     
         18 . The method of  claim 1 , wherein the amount of the inorganic nitrite (NO 2   − ) is at least about 10% by weight or by volume of the composition. 
     
     
         19 . A method of decreasing systolic blood pressure comprising orally administering to an adult human subject a composition comprising inorganic nitrite (NO 2   − ) and an acid. 
     
     
         20 . The method of  claim 19 , wherein administration of the composition also reduces diastolic blood pressure of the adult human subject. 
     
     
         21 . The method of  claim 19 , wherein the composition is 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. 
     
     
         22 . The method of  claim 21 , wherein the composition is a functional food 
     
     
         23 . The method of  claim 19 , wherein 0.1-100 umol inorganic nitrite (NO 2   − ) is administered per kg body weight of the adult human subject. 
     
     
         24 . The method of  claim 19 , wherein the composition is a nutritional supplement and further comprises at least one additive. 
     
     
         25 . The method of  claim 19 , wherein the inorganic nitrite (NO 2   − ) is provided from a natural source. 
     
     
         26 . The method of  claim 25 , wherein the natural source of the inorganic nitrite (NO 2   − ) is juice or dried concentrate from beetroot. 
     
     
         27 . The method of  claim 19 , wherein the inorganic nitrite (NO 2   − ) is a nitrite salt. 
     
     
         28 . The method of  claim 19 , wherein the composition further comprises a polyphenol. 
     
     
         29 . The method of  claim 28 , 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. 
     
     
         30 . The method of  claim 19 , wherein the amount of the inorganic nitrite (NO 2   − ) is at least 50% by weight or by volume of the composition.