Phosphatidylinositol increases HDL-C levels in humans

Studies have shown that phosphatidylinositol (PI) can stimulate reverse cholesterol transport by enhancing the flux of cholesterol into HDL and by promoting the transport of high density lipoprotein-cholesterol (HDL-C) to the liver and bile. The goal of this study was to determine the safety and therapeutic value of PI after oral administration to normolipidemic human subjects. We performed a randomized 2 week study in 16 normolipidemic subjects. Subjects received either 2.8 or 5.6 g of PI, with or without food. PI was well tolerated by all subjects. PI significantly affected the levels of HDL-C and triglyceride in the plasma of subjects receiving PI with food. The lower dose showed a 13% increase in HDL-C, whereas the high dose showed an increase of 18% over the 2 week period. Both low- and high-dose groups showed significant increases in plasma apolipoprotein A-I. The high dose of PI also decreased plasma triglycerides by 36% in the fed subjects.These data suggest that after only 2 weeks, PI may have a comparable therapeutic value to niacin, with negligible side effects. Studies have shown that phosphatidylinositol (PI) can stimulate reverse cholesterol transport by enhancing the flux of cholesterol into HDL and by promoting the transport of high density lipoprotein-cholesterol (HDL-C) to the liver and bile. The goal of this study was to determine the safety and therapeutic value of PI after oral administration to normolipidemic human subjects. We performed a randomized 2 week study in 16 normolipidemic subjects. Subjects received either 2.8 or 5.6 g of PI, with or without food. PI was well tolerated by all subjects. PI significantly affected the levels of HDL-C and triglyceride in the plasma of subjects receiving PI with food. The lower dose showed a 13% increase in HDL-C, whereas the high dose showed an increase of 18% over the 2 week period. Both low- and high-dose groups showed significant increases in plasma apolipoprotein A-I. The high dose of PI also decreased plasma triglycerides by 36% in the fed subjects. These data suggest that after only 2 weeks, PI may have a comparable therapeutic value to niacin, with negligible side effects. Epidemiological studies have established an inverse association between high density lipoprotein-cholesterol (HDL-C) and coronary artery disease (CAD) (1Gordon D.J. Rifkind B.M. High-density lipoprotein. The clinical implications of recent studies.N. Engl. J. Med. 1989; 321: 1311-1316Crossref PubMed Scopus (1402) Google Scholar). Controlled intervention trials suggest that a 1% increase in HDL-C will correspond to a 3% reduction in CAD event rate (2Manninen V. Elo M.O. Frick M.H. Haapa K. Heinonen O.P. Heinsalmi P. Helo P. Huttunen J.K. Kaitaniemi P. Koskinen P. Lipid alterations and decline in the incidence of coronary heart disease in the Helsinki Heart Study.J. Am. Med. Assoc. 1988; 260: 641-651Crossref PubMed Scopus (849) Google Scholar). Conservative treatment measures (e.g., dietary modification, smoking cessation, aerobic exercise) only increase HDL-C modestly (3Grundy S.M. Goodman D.W. Rifkind B.M. Cleeman J.I. The place of HDL in cholesterol management. A perspective from the National Cholesterol Educational Program.Arch. Intern. Med. 1989; 149: 505-510Crossref PubMed Google Scholar), and available agents for increasing HDL-C are currently limited to niacin and the fibrates (4King J.M. Crouse J.R. Terry J.G. Morgan T.M. Spray B.J. Miller N.E. Evaluation of effects of unmodified niacin on fasting and postprandial plasma lipids in normolipidemic men with hypoalphalipoproteinemia.Am. J. Med. 1994; 97: 323-331Abstract Full Text PDF PubMed Scopus (51) Google Scholar, 5Miller M. of in men with a J. Med. Full Text PDF PubMed Scopus Google Scholar). have available for limited by the side effects with therapeutic HDL therapeutic are and recent suggest that the and may for increasing HDL-C levels and CAD T.M. in of an study of PubMed Scopus Google Scholar, J. and safety of a in a randomized PubMed Scopus Google Scholar). HDL levels by of HDL or apolipoprotein also to have effects on in P. M. of on coronary in with coronary a randomized Am. Med. Assoc. PubMed Scopus Google Scholar). with studies are to to increase HDL levels may the and of over the have that may also plasma HDL oral administration of from to g have in significant in cholesterol and triglyceride levels J.G. M. plasma triglyceride levels and and Med. PubMed Scopus Google Scholar, of of on lipids in J. Full Text PDF PubMed Scopus Google and HDL-C levels J.G. M. plasma triglyceride levels and and Med. PubMed Scopus Google Scholar). a of and administration of shown to significantly density lipoprotein-cholesterol and triglycerides K. K. the in J. 1994; Google Scholar, K. of with in J. 1989; Google to have on HDL-C K. of with in J. 1989; Google Scholar, M. P. The of administration on and in with Google Scholar, of and and in with and Med. Google Scholar). The of the of have that PI the reverse cholesterol transport PI of cholesterol from to HDL and an transport and of cholesterol the and cholesterol transport in Lipid Full Text Full Text PDF PubMed Google Scholar, J. P. cholesterol transport and Lipid Full Text Full Text PDF PubMed Scopus Google Scholar). a study was to the effects of PI on HDL-C and in normolipidemic PI well tolerated and to plasma HDL and triglyceride levels with study was by the of the of Heart and by The of the study are shown in The of men and between and of The HDL-C and to and of or in the the was to to The subjects to dietary and the study g without 2 g with g without g with high density density in a from after an Subjects randomized to of and 2 2.8 and 5.6 g of PI, with and without the subjects to have a a or with and 2.8 and 5.6 g of PI, with a from all subjects and that the PI administration without and or with and was for 2 the administration performed after an and the administration of for this study was from by and The was to a by on with of and and that also from PI, after of the PI was into for oral a was and to the of and the for and The a and also for and HDL-C, and HDL-C, and plasma triglycerides a levels and by the J. Lipid of between and to for all of the These for and the of shown in was to the between and for of the significant between randomized an was for a a for was lipids and after of treatment with 2 2 g with 2.8 g without 2 2 g with 2.8 g without g with 5.6 g without food. are and the of to between and was by between and significantly between randomized groups by 2.8 g with 2.8 g without 5.6 g with 2.8 g without 5.6 g with 5.6 g without food. in a subjects randomized to the with and high with and without food. or the treatment of the clinical for all and for all subjects the 2 and and levels for subjects in the treatment of PI without a negligible on HDL-C levels with the lower dose HDL-C by with the high dose with PI showed an increase in plasma HDL-C from to showed the fed to significantly from of the groups that received the without Subjects receiving the 2.8 g dose with a increase in plasma HDL-C of and administration of 5.6 g of PI with was with an 18% increase in plasma HDL-C HDL-C for after the treatment was and after the the HDL-C levels by and to the of high-dose all subjects receiving PI with showed plasma levels from to The increase of for low- and high-dose groups a significant increase in in plasma apolipoprotein in receiving oral PI fed Subjects received either 2.8 g or 5.6 g of PI with a for to with in plasma triglycerides PI was without whereas significant PI was with a Subjects received PI with all decreased from to lower receiving the 5.6 g dose showed a significant in plasma triglycerides of 36% was also a in plasma triglycerides in the fed this was in plasma triglycerides in receiving oral PI with a in triglyceride levels and on are shown for subjects received 2.8 g or 5.6 g of PI with a levels in subjects receiving PI with or without that of subjects in the high-dose fed showed in from to lower in plasma density lipoprotein-cholesterol in receiving oral PI with a in levels and on are shown for subjects received 2.8 g or 5.6 g of PI with a that HDL-C can an of CAD density a coronary heart The J. Med. Full Text PDF PubMed Scopus Google Scholar). Subjects with HDL (e.g., and density and by and PubMed Scopus Google Scholar, and plasma a study in Full Text PDF PubMed Scopus Google are of whereas HDL-C a by an of CAD M. an for coronary heart Heart J. PubMed Google Scholar). also well that in J. apolipoprotein after in 1994; PubMed Scopus Google Scholar, J.M. P. of in human apolipoprotein PubMed Scopus Google Scholar). therapeutic to increase HDL-C levels have for with and side effects have limited the of the currently available HDL-C levels are with fibrates and currently the increases in HDL of after of The and are also for increasing HDL-C levels and may have value with the T.M. in of an study of PubMed Scopus Google Scholar, J. and safety of a in a randomized PubMed Scopus Google Scholar). HDL levels to have the for A of shown to the of in P. M. of on coronary in with coronary a randomized Am. Med. Assoc. PubMed Scopus Google study shown that PI well tolerated and will in significant increases in HDL-C and and in plasma triglycerides 5.6 in plasma levels after only a of treatment and a by 2 The significant effects PI was with food. The increase in HDL-C in fed high-dose 18% after only 2 of niacin can in HDL-C 2 weeks, this that PI or the of niacin in fed subjects an increase in HDL-C HDL-C in subjects received PI without also significantly with the high dose with the dose of fed subjects showed in whereas subjects receiving PI without triglyceride These suggest that of PI may to or with the of to increase HDL-C levels by a flux of cholesterol to HDL and transport and in PI and increases of cholesterol to and increases transport of HDL-C to the and cholesterol transport in Lipid Full Text Full Text PDF PubMed Google Scholar, J. P. cholesterol transport and Lipid Full Text Full Text PDF PubMed Scopus Google Scholar). PI may to the and of cholesterol in the and to stimulate reverse cholesterol that of PI the in and the high dose in this study a plasma PI that to that in studies cholesterol transport in Lipid Full Text Full Text PDF PubMed Google Scholar, J. P. cholesterol transport and Lipid Full Text Full Text PDF PubMed Scopus Google Scholar). These effects to PI a in the J. P. cholesterol transport and Lipid Full Text Full Text PDF PubMed Scopus Google Scholar). this significant in the that PI in The effects of this may also to a of PI significant effects in a of cholesterol transport in Lipid Full Text Full Text PDF PubMed Google and may the of cholesterol and PI a of of human plasma PubMed Scopus Google Scholar, of in with apolipoprotein Lipid Full Text Full Text PDF PubMed Google Scholar), studies suggest that PI may a of and an of on of phosphatidylinositol with PubMed Scopus Google Scholar, B.J. and of and PubMed Google the of of PI and from that of the may have and PI may have value an in on PI may also have value in CAD with HDL-C cholesterol in the of M. with plasma cholesterol levels and coronary artery J. Full Text PDF PubMed Scopus Google Scholar, M. of with coronary artery disease and levels of plasma PubMed Scopus Google Scholar). studies are to the effects of PI in with HDL-C Epidemiological studies have established an inverse association between high density lipoprotein-cholesterol (HDL-C) and coronary artery disease (CAD) (1Gordon D.J. Rifkind B.M. High-density lipoprotein. The clinical implications of recent studies.N. Engl. J. Med. 1989; 321: 1311-1316Crossref PubMed Scopus (1402) Google Scholar). Controlled intervention trials suggest that a 1% increase in HDL-C will correspond to a 3% reduction in CAD event rate (2Manninen V. Elo M.O. Frick M.H. Haapa K. Heinonen O.P. Heinsalmi P. Helo P. Huttunen J.K. Kaitaniemi P. Koskinen P. Lipid alterations and decline in the incidence of coronary heart disease in the Helsinki Heart Study.J. Am. Med. Assoc. 1988; 260: 641-651Crossref PubMed Scopus (849) Google Scholar). Conservative treatment measures (e.g., dietary modification, smoking cessation, aerobic exercise) only increase HDL-C modestly (3Grundy S.M. Goodman D.W. Rifkind B.M. Cleeman J.I. The place of HDL in cholesterol management. A perspective from the National Cholesterol Educational Program.Arch. Intern. Med. 1989; 149: 505-510Crossref PubMed Google Scholar), and available agents for increasing HDL-C are currently limited to niacin and the fibrates (4King J.M. Crouse J.R. Terry J.G. Morgan T.M. Spray B.J. Miller N.E. Evaluation of effects of unmodified niacin on fasting and postprandial plasma lipids in normolipidemic men with hypoalphalipoproteinemia.Am. J. Med. 1994; 97: 323-331Abstract Full Text PDF PubMed Scopus (51) Google Scholar, 5Miller M. of in men with a J. Med. Full Text PDF PubMed Scopus Google Scholar). have available for limited by the side effects with therapeutic HDL therapeutic are and recent suggest that the and may for increasing HDL-C levels and CAD T.M. in of an study of PubMed Scopus Google Scholar, J. and safety of a in a randomized PubMed Scopus Google Scholar). HDL levels by of HDL or apolipoprotein also to have effects on in P. M. of on coronary in with coronary a randomized Am. Med. Assoc. PubMed Scopus Google Scholar). with studies are to to increase HDL levels may the and of Studies over the have that may also plasma HDL oral administration of from to g have in significant in cholesterol and triglyceride levels J.G. M. plasma triglyceride levels and and Med. PubMed Scopus Google Scholar, of of on lipids in J. Full Text PDF PubMed Scopus Google and HDL-C levels J.G. M. plasma triglyceride levels and and Med. PubMed Scopus Google Scholar). a of and administration of shown to significantly density lipoprotein-cholesterol and triglycerides K. K. the in J. 1994; Google Scholar, K. of with in J. 1989; Google to have on HDL-C K. of with in J. 1989; Google Scholar, M. P. The of administration on and in with Google Scholar, of and and in with and Med. Google Scholar). The of the of We have that PI the reverse cholesterol transport PI of cholesterol from to HDL and an transport and of cholesterol the and cholesterol transport in Lipid Full Text Full Text PDF PubMed Google Scholar, J. P. cholesterol transport and Lipid Full Text Full Text PDF PubMed Scopus Google Scholar). a study was to the effects of PI on HDL-C and in normolipidemic PI well tolerated and to plasma HDL and triglyceride levels with food. study was by the of the of Heart and by The of the study are shown in The of men and between and of The HDL-C and to and of or in the the was to to The subjects to dietary and the study g without 2 g with g without g with high density density in a from after an Subjects randomized to of and 2 2.8 and 5.6 g of PI, with and without the subjects to have a a or with and 2.8 and 5.6 g of PI, with a from all subjects and that the PI administration without and or with and was for 2 the administration performed after an and the administration of for this study was from by and The was to a by on with of and and that also from PI, after of the PI was into for oral a was and to the of and the for and The a and also for and HDL-C, and HDL-C, and plasma triglycerides a levels and by the J. Lipid of between and to for all of the These for and the of shown in was to the between and for of the significant between randomized an was for a a for was lipids and after of treatment with 2 2 g with 2.8 g without 2 2 g with 2.8 g without g with 5.6 g without food. are and the of to between and was by between and significantly between randomized groups by 2.8 g with 2.8 g without 5.6 g with 2.8 g without 5.6 g with 5.6 g without food. in a study was by the of the of Heart and by The of the study are shown in The of men and between and of The HDL-C and to and of or in the the was to to The subjects to dietary and the study g without 2 g with g without g with high density density in a The study was by the of the of Heart and by The of the study are shown in The of men and between and of The HDL-C and to and of or in the the was to to The subjects to dietary and the HDL-C, high density density from after an Subjects randomized to of and 2 2.8 and 5.6 g of PI, with and without the subjects to have a a or with and 2.8 and 5.6 g of PI, with a from all subjects and that the PI administration without and or with and was for 2 the administration performed after an and the administration of for this study was from by and The was to a by on with of and and that also from PI, after of the PI was into for oral from after an Subjects randomized to of and 2 2.8 and 5.6 g of PI, with and without the subjects to have a a or with and 2.8 and 5.6 g of PI, with a from all subjects and that the PI administration without and or with and was for 2 the administration performed after an and the administration of PI for this study was from by and The was to a by on with of and and that also from PI, after of the PI was into for oral a was and to the of and the for and The a and also for and HDL-C, and HDL-C, and plasma triglycerides a levels and by the J. Lipid of a was and to the of and the for and The a and also for and HDL-C, and HDL-C, and plasma triglycerides a levels and by the J. Lipid of between and to for all of the These for and the of shown in was to the between and for of the significant between randomized an was for a a for was lipids and after of treatment with 2 2 g with 2.8 g without 2 2 g with 2.8 g without g with 5.6 g without food. are and the of to between and was by between and significantly between randomized groups by 2.8 g with 2.8 g without 5.6 g with 2.8 g without 5.6 g with 5.6 g without food. in a The between and to for all of the These for and the of shown in was to the between and for of the significant between randomized an was for a a for was are and the of to between and was by between and significantly between randomized groups by subjects randomized to the with and high with and without food. or the treatment of the clinical for all and for all subjects the 2 and and levels for subjects in the treatment of PI without a negligible on HDL-C levels with the lower dose HDL-C by with the high dose with PI showed an increase in plasma HDL-C from to showed the fed to significantly from of the groups that received the without Subjects receiving the 2.8 g dose with a increase in plasma HDL-C of and administration of 5.6 g of PI with was with an 18% increase in plasma HDL-C HDL-C for after the treatment was and after the the HDL-C levels by and to the of high-dose all subjects receiving PI with showed plasma levels from to The increase of for low- and high-dose groups a significant increase in to with in plasma triglycerides PI was without whereas significant PI was with a Subjects received PI with all decreased from to lower receiving the 5.6 g dose showed a significant in plasma triglycerides of 36% was also a in plasma triglycerides in the fed this was in plasma triglycerides in receiving oral PI with a in triglyceride levels and on are shown for subjects received 2.8 g or 5.6 g of PI with a levels in subjects receiving PI with or without that of subjects in the high-dose fed showed in from to lower in plasma density lipoprotein-cholesterol in receiving oral PI with a in levels and on are shown for subjects received 2.8 g or 5.6 g of PI with a subjects randomized to the with and high with and without food. or the treatment of the clinical for all and for all subjects the 2 and and levels for subjects in the treatment of PI without a negligible on HDL-C levels with the lower dose HDL-C by with the high dose with PI showed an increase in plasma HDL-C from to showed the fed to significantly from of the groups that received the without Subjects receiving the 2.8 g dose with a increase in plasma HDL-C of and administration of 5.6 g of PI with was with an 18% increase in plasma HDL-C HDL-C for after the treatment was and after the the HDL-C levels by and to the of high-dose all subjects receiving PI with showed plasma levels from to The increase of for low- and high-dose groups a significant increase in to with in plasma triglycerides PI was without whereas significant PI was with a Subjects received PI with all decreased from to lower receiving the 5.6 g dose showed a significant in plasma triglycerides of 36% was also a in plasma triglycerides in the fed this was levels in subjects receiving PI with or without that of subjects in the high-dose fed showed in from to lower that HDL-C can an of CAD density a coronary heart The J. Med. Full Text PDF PubMed Scopus Google Scholar). Subjects with HDL (e.g., and density and by and PubMed Scopus Google Scholar, and plasma a study in Full Text PDF PubMed Scopus Google are of whereas HDL-C a by an of CAD M. an for coronary heart Heart J. PubMed Google Scholar). also well that in J. apolipoprotein after in 1994; PubMed Scopus Google Scholar, J.M. P. of in human apolipoprotein PubMed Scopus Google Scholar). therapeutic to increase HDL-C levels have for with and side effects have limited the of the currently available HDL-C levels are with fibrates and currently the increases in HDL of after of The and are also for increasing HDL-C levels and may have value with the T.M. in of an study of PubMed Scopus Google Scholar, J. and safety of a in a randomized PubMed Scopus Google Scholar). HDL levels to have the for A of shown to the of in P. M. of on coronary in with coronary a randomized Am. Med. Assoc. PubMed Scopus Google study shown that PI well tolerated and will in significant increases in HDL-C and and in plasma triglycerides 5.6 in plasma levels after only a of treatment and a by 2 The significant effects PI was with food. The increase in HDL-C in fed high-dose 18% after only 2 of niacin can in HDL-C 2 weeks, this that PI or the of niacin in fed subjects an increase in HDL-C HDL-C in subjects received PI without also significantly with the high dose with the dose of fed subjects showed in whereas subjects receiving PI without triglyceride These suggest that of PI may to or with the of to increase HDL-C levels by a flux of cholesterol to HDL and transport and in PI and increases of cholesterol to and increases transport of HDL-C to the and cholesterol transport in Lipid Full Text Full Text PDF PubMed Google Scholar, J. P. cholesterol transport and Lipid Full Text Full Text PDF PubMed Scopus Google Scholar). PI may to the and of cholesterol in the and to stimulate reverse cholesterol that of PI the in and the high dose in this study a plasma PI that to that in studies cholesterol transport in Lipid Full Text Full Text PDF PubMed Google Scholar, J. P. cholesterol transport and Lipid Full Text Full Text PDF PubMed Scopus Google Scholar). These effects to PI a in the J. P. cholesterol transport and Lipid Full Text Full Text PDF PubMed Scopus Google Scholar). this significant in the that PI in The effects of this may also to a of PI significant effects in a of cholesterol transport in Lipid Full Text Full Text PDF PubMed Google and may the of cholesterol and PI a of of human plasma PubMed Scopus Google Scholar, of in with apolipoprotein Lipid Full Text Full Text PDF PubMed Google Scholar), studies suggest that PI may a of and an of on of phosphatidylinositol with PubMed Scopus Google Scholar, B.J. and of and PubMed Google the of of PI and from that of the may have and PI may have value an in on PI may also have value in CAD with HDL-C cholesterol in the of M. with plasma cholesterol levels and coronary artery J. Full Text PDF PubMed Scopus Google Scholar, M. of with coronary artery disease and levels of plasma PubMed Scopus Google Scholar). studies are to the effects of PI in with HDL-C that HDL-C can an of CAD density a coronary heart The J. Med. Full Text PDF PubMed Scopus Google Scholar). Subjects with HDL (e.g., and density and by and PubMed Scopus Google Scholar, and plasma a study in Full Text PDF PubMed Scopus Google are of whereas HDL-C a by an of CAD M. an for coronary heart Heart J. PubMed Google Scholar). also well that in J. apolipoprotein after in 1994; PubMed Scopus Google Scholar, J.M. P. of in human apolipoprotein PubMed Scopus Google Scholar). therapeutic to increase HDL-C levels have for with and side effects have limited the of the currently available HDL-C levels are with fibrates and currently the increases in HDL of after of The and are also for increasing HDL-C levels and may have value with the T.M. in of an study of PubMed Scopus Google Scholar, J. and safety of a in a randomized PubMed Scopus Google Scholar). HDL levels to have the for A of shown to the of in P. M. of on coronary in with coronary a randomized Am. Med. Assoc. PubMed Scopus Google Scholar). study shown that PI well tolerated and will in significant increases in HDL-C and and in plasma triglycerides 5.6 in plasma levels after only a of treatment and a by 2 The significant effects PI was with food. The increase in HDL-C in fed high-dose 18% after only 2 of niacin can in HDL-C 2 weeks, this that PI or the of niacin in fed subjects an increase in HDL-C HDL-C in subjects received PI without also significantly with the high dose with the dose of fed subjects showed in whereas subjects receiving PI without triglyceride These suggest that of PI may to or with the of food. PI to increase HDL-C levels by a flux of cholesterol to HDL and transport and in PI and increases of cholesterol to and increases transport of HDL-C to the and cholesterol transport in Lipid Full Text Full Text PDF PubMed Google Scholar, J. P. cholesterol transport and Lipid Full Text Full Text PDF PubMed Scopus Google Scholar). PI may to the and of cholesterol in the and to stimulate reverse cholesterol that of PI the in and the high dose in this study a plasma PI that to that in studies cholesterol transport in Lipid Full Text Full Text PDF PubMed Google Scholar, J. P. cholesterol transport and Lipid Full Text Full Text PDF PubMed Scopus Google Scholar). These effects to PI a in the J. P. cholesterol transport and Lipid Full Text Full Text PDF PubMed Scopus Google Scholar). this significant in the that PI in The effects of this may also to a of PI significant effects in a of cholesterol transport in Lipid Full Text Full Text PDF PubMed Google and may the of cholesterol and PI a of of human plasma PubMed Scopus Google Scholar, of in with apolipoprotein Lipid Full Text Full Text PDF PubMed Google Scholar), studies suggest that PI may a of and an of on of phosphatidylinositol with PubMed Scopus Google Scholar, B.J. and of and PubMed Google Scholar). the of of PI and from that of the may have and PI may have value an in on PI may also have value in CAD with HDL-C cholesterol in the of M. with plasma cholesterol levels and coronary artery J. Full Text PDF PubMed Scopus Google Scholar, M. of with coronary artery disease and levels of plasma PubMed Scopus Google Scholar). studies are to the effects of PI in with HDL-C

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