Dietary supplements for treating cancer

Abstract

Methods and compositions for treating cancer and other disorders associated with undesired cellular proliferation are provided comprising administering to a subject in need thereof an amino acid mixture, wherein the amino acid mixture comprises glycine, optionally comprising at least a 2:1 molar ratio of glycine to serine.

What is claimed: 
     
         1 . A nutritional supplement comprising an amino acid mixture, wherein the amino acid mixture comprises at least a 2:1 molar ratio of glycine to serine. 
     
     
         2 . The nutritional supplement of  claim 1 , wherein the molar ratio of glycine to serine in the supplement is about 3:1, 4:1, 5:1, 6:1, 7:1, 8:1, 9:1, 10:1, 20:1, 30:1, 40:1, 50:1, 60:1, 70:1, 80:1, 90:1, or 100:1. 
     
     
         3 . The nutritional supplement of  claim 1 , wherein the supplement is substantially devoid of serine. 
     
     
         4 . The nutritional supplement of  claim 1 , wherein the amino acid mixture comprises amino acids in free form, in prodrug form, salts, or amino acid esters. 
     
     
         5 . The nutritional supplement of  claim 1 , further comprising recombinantly synthesized protein deficient in serine. 
     
     
         6 . A nutritional supplement that is high in serine and low in glycine, wherein high serine is at least 2, 3, 4, 5 or 6 times the average daily intake of serine based on average daily total protein consumption. 
     
     
         7 . The nutritional supplement of  claim 6  wherein the molar ratio of serine to glycine is about 3:1, 4:1, 5:1, 6:1, 7:1, 8:1, 9:1, 10:1, 20:1, 30:1, 40:1, 50:1, 60:1, 70:1, 80:1, 90:1, or 100:1. 
     
     
         8 . A nutritional supplement that is high in glycine and low in serine, wherein high glycine is at least 2, 3, 4, 5 or 6 times the average daily intake of glycine based on average daily total protein consumption. 
     
     
         9 . A pharmaceutical composition comprising high glycine, optionally comprising low serine, and a pharmaceutically acceptable carrier, wherein high glycine is at least 2, 3, 4, 5 or 6 times the average daily intake of glycine based on average daily total protein consumption. 
     
     
         10 . The pharmaceutical composition of  claim 9  wherein the molar ratio of glycine to serine in the composition is about 3:1, 4:1, 5:1, 6:1, 7:1, 8:1, 9:1, 10:1, 20:1, 30:1, 40:1, 50:1, 60:1, 70:1, 80:1, 90:1, or 100:1. 
     
     
         11 . The pharmaceutical composition of  claim 9  that is substantially devoid of serine. 
     
     
         12 . A method of treating cancer comprising administering to a subject in need thereof a diet comprising the nutritional supplement of any one of  claims 1 - 8  or a pharmaceutical composition of any one of  claims 9 - 11 . 
     
     
         13 . A method of treating cancer comprising administering to a subject in need thereof one or more pharmacological inhibitors of cancer cell growth and instructing the subject to consume a diet comprising the nutritional supplement of any one of  claims 1 - 8 . 
     
     
         14 . The method of  claim 13 , wherein the subject is further instructed to consume a diet low in serine, methionine, choline, or a combination thereof. 
     
     
         15 . The method of  claim 13 , wherein the subject is additionally instructed to consume a supplement comprising homocysteine. 
     
     
         16 . The method of  claim 13 , wherein the pharmacological inhibitor is an inhibitor of folate metabolism. 
     
     
         17 . The method of  claim 16 , wherein the inhibitor of folate metabolism is methotrexate or pemetrexed. 
     
     
         18 . The method of  claim 13 , wherein the pharmacological inhibitor is an inhibitor of DNA methylation. 
     
     
         19 . The method of  claim 18 , wherein the inhibitor of DNA methylation is azacytidine. 
     
     
         20 . A method of treating cancer comprising administering to a subject in need thereof a nutritional supplement of pharmaceutical composition comprising at least a 2:1 molar ratio of glycine to serine 
     
     
         21 . The method of  claim 20  wherein the treatment is administered over a time period of at least 2 weeks. 
     
     
         22 . The method of  claim 21  wherein the treatment is administered over a time period of 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 9 weeks, 10 weeks, 11 weeks, 12 weeks, 13 weeks, 14 weeks, 15 weeks, 16 weeks, 17 weeks, 18 weeks, 19 weeks, 20 weeks, 21 weeks, 22 weeks, 23 weeks, 24 weeks, 25 weeks, 26 weeks, or until a therapeutic endpoint is observed. 
     
     
         23 . A method of treating cancer in a subject comprising administering a chemotherapeutic agent and a pharmaceutical composition or nutritional supplement comprising high glycine, wherein the subject is administered about 4-8 g, 6-10 g, or 4-12 g of glycine daily. 
     
     
         24 . The method of  claim 23  wherein the glycine is administered 1, 2, 3 or 4 times daily to achieve the total daily dose of glycine. 
     
     
         25 . The method of  claim 23  wherein the chemotherapeutic agent is an antifolate. 
     
     
         26 . A method of treating cancer in a subject comprising administering a chemotherapeutic agent and a pharmaceutical composition or nutritional supplement comprising high serine, wherein the subject is administered about 4-8 g, 6-10 g, or 4-12 g of serine daily. 
     
     
         27 . The method of  claim 26  wherein the chemotherapeutic is an antifolate.