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Atherogenicity of animal and vegetable protein
429
Atherosclerosis, 41 (1982) 429-431 @ Elsevier/North-Holland Scientific
Publishers,
Ltd.
Letter to the Editors ATHEROGENICITY OF ANIMAL AND VEGETABLE PRGTEIN Influence of the Lysine to Arginine Ratio Sir
Protein of animal origin (casein or beef) is more cholesterolemic and atherogenic than plant protein (soy) [l-4]. Weigensberg et al. [ 51 suggested that the lysine content of a protein may be a determinant of its atherogenicity. In a retrospective analysis of diets of men who had died of coronary disease, Moore et al. [6] found a significant correlation between the lysine content of the diet and the trend towards increased severity of coronary disease. We have hypothesized that the lysine/arginine ratio of a protein may be an important determinant of its atherogenic potential [ 781. The addition of lysine to soy protein, sufficient to change its normal lysine/arginine ratio [l.O] to that of casein (2.0), significantly increases its atherogenicity. Addition of arginine to casein to lower its lysine/arginine ratio to that of soy protein decreases its atherogenicity [ 8,9]. We have compared the atherogenicity of 3 proteins whose lysine levels are virtually the same but whose lysine/arginine ratios are quite different. The proteins used were fish protein (lysine, 6.81; arginine, 4.74; lysine/ arginine, 1.44); casein (lysine, 6.91; arginine, 3.65; lysine/arginine, 1.89); and whole milk protein (lysine, 6.61; arginine, 2.71; lysine/arginine, 2.44). The pro-
TABLE
1
INFLUENCE
OF
SCLEROSIS Rabbits
FISH,
CASEIN
OR
WHOLE
MILK
PROTEIN
ON
LIPID
LEVELS
AND
ATHERO-
IN RABBITS
were
fed
are significantly
semipurified
different
diets
containing
(P < 0.05)
by
25%
protein
for
8 months.
Values
bearing
the
same
letter
t-test.
Protein Fish Serum
lipids
*
238
cholesterol
Triglycerides Serum
*
*
f 40
15.7 122
protein (g/dl) atherosclerosis
f
ab
Arch
1.55
f
0.23
Thoracic
0.95
*
0.17
(P < 0.05)
by analysis
0021-9150/82/0000-0000/$02.75@1982
C 76 a
11.8
+ 20 f
* Significant
530
l.$C
4.00
Aortic
Whole
milk
(mg/dl)
Cholesterol % HDL
Casein
177
0.14
+
462
1.1’
f 47 4.05
+
e
2.05
f
f
1.10
f
~62~
11.9 251
0.18
+
1.5
-f 56
d
4.14
f
0.21
0.25
2.61
+
0.16
e
0.25
1.56
c
0.19
f
of variance.
Elsevier/North-Holland
Scientific
Publishers,
Ltd.
430
/
??
? ? ??
FISH CASEIN PROTEIN
MILK PROTEIN
LYSINE ARGININE Fig. 1. Average atherosclerosis levels in rabbits P < 0.05). ratio of those proteins (r = 0.9979,
fed 3 different
proteins
plotted
against
lysinglarginine
teins were fed to female New Zealand white rabbits as 25% of a semipurified diet containing 40% sucrose, 14% coconut oil, 15% cellulose, 5% salt mix and 1% vitamin mix. This diet has been shown to be hypercholesterolemic, hyperbetalipoproteinemic and atherogenic for rabbits [2,3,10]. After 8 months the rabbits were killed, serum lipids determined [ 11-131 and aortic atherosclerosis assessed by visual grading on a O-4 scale [ 14,151. The data are summarized in Table 1 and Fig. 1. Plotting the lysine/arginine ratio against average atherosclerosis (arch plus thoracic divided by 2) gives a statistically significant, positive regression coefficient (r = 0.9979, P < 0.05). Serum cholesterol, triglyceride and HDL cholesterol levels were significantly different in the three groups. Serum protein levels [ 161 were not affected. The mechanism underlying this phenomenon is still unclear. It may involve inhibition by lysine of liver arginase [17] which would make more arginine available for synthesis of the arginine-rich lipoprotein, which is associated with enhanced atherosclerosis in rabbits [18]. Addition of lysine to soy protein or arginine to casein affects the lipoprotein spectrum [ 8,191. Another possibility is that increased levels of serum arginine may exert glucagon-like activity [20].
431
The influence tigation.
of other proteins
of differing
lysine/arginine
ratios is under inves-
References 1 Meeker, D.R. and Kesten, H.D., Effect of high protein diets on experimental atherosclerosis in rabbits. Arch. Path., 31 (1941) 147. 2 Kritchevsky. D.. Tepper, S.A., Williams, D.E. and Story, J.A.. Experimental atherosclerosis in rabbits fed cholesterol-free diets, Part 7 (Interaction of animal or vegetable protein with fiber), Atherosclerosis. 26 (1977) 397. 3 Kritchevsky. D., Tepper. S.A., Czamecki, S.K., Klurfield, D.M. and Story, J.A., Experimental atherosclerosis in rabbits fed cholesterol-free diets, Part 9 (Beef protein and textured vegetable protein), Atherosclerosis, 39 (1981) 169. 4 Carroll, K.K. and Hamilton, R.M.G., Effects of dietary protein and carbohydrate on plasma cholesterol levels in relation to atherosclerosis, J. Food Sci., 40 (1975) 18. 5 Weigensberg. B.I.. Stary, H.C. and McMillan, G.C., Effect of lysine deficiency on cholesterol atherosclerosis in rabbits, Exp. Mol. Path., 3 (1964) 444. 6 Moore, M.C.. Guzman, M.A.. Schilling, P.E. and Strong. J.P., Dietary-atherosclerosis study on deceased persons. J. Amer. Dietetic Ass.. 70 (1977) 602. I Kritchevsky. D., Tepper, S.A. and Story, J.A., Influence of soy protein and casein on atherosclerosis in rabbits, Fed. Proc., 37 (1978) 747. 8 Czarnecki, S.K. and Kritchevsky, D., The effect of dietary proteins on lipoprotein metabolism and atherosclerosis in rabbits. J. Amer. Oil Chem. Sot., 56 (1979) 388A. 9 Kritchevsky, D., Vegetable protein and atherosclerosis, J. Amer. Oil Chem. Sot., 56 (1979) 135. 10 Kritchevsky. D. and Tepper, S.A., Experimental atherosclerosis in rabbits fed cholesterol-free diets Influence of chow components, J. Atheroscler. Res., 8 (1968) 357. 11 Rudel. L.L. and Morris, M.D., Determination of cholesterol using o-phthalaldehyde, J. Lipid Res.. I4 (1973) 364. 12 Manual of Laboratory Operation, Lipid Research Clinics Program. Vol. 1 (Lipid and Lipoprotein Analysis) (DHWW Publication No. (NIH) 75-625). 1974. P. 56. 13 Levy, A.L. and Keyloun, C., Measurements of triglycerides using nonane extraction and’colorimetry. In: Advances in Automated Analysis, Vol. 1, Thurman Ass., Miami, FL, 1972. PP. 487-502. 14 Duff, G.L. and McMillan. G.C., The effect of alloxan diabetes on experimental atherosclerosis in the rabbit, J. Exp. Med., 89 (1949) 611. 15 Kritchevsky, D., Tepper. S.A. and Story, J.A., Cholesterol vehicle in experimental atherosclerosis, Part 16 (Effects of peanut oil on we-established lesions), Atherosclerosis, 31 (1978) 365. 16 Lowry, O.H.. Rosebrough, N.J., Farr, A.L. and Randall, R.J., Protein measurement with the Folin phenol reagent, J. Biol. Chem.. 193 (1951) 265. 17 Cittadini, D., Pietropaolo, C., DeCristofaro. D. and D’Ayjello-Caracciolo, M.. In viva effect of Glysine on rat liver arginase, Nature (Land.), 203 (1964) 643. 18 Shore. B.. Shore. V., S&l, A.. Mason, D. and Zelis. R., An apolipoprotein preferentially enriched in cholesterol ester-rich very low density lipoproteins, Biochem. Biophys. Res. Comm., 58 (1974) 1. 19 Kritchevsky, D., Dietary protein in atherosclerosis. In: G. Noseda, B. Lewis and R. Paoletti (Eds.), Diet and Drugs in Atherosclerosis, Raven Press, New York, NY, 1980. pp. 9-14. 20 Noseda, G. and Fragiacomo, C., Effects of soybean protein diet on serum lipids, plasma glucagon and insulin. In: G. Noseda. B. Lewis and R. Paoletti (Eds.). Raven Press, New York, NY, 1980. pp. 61-65.
The Wistar Institute of Anatomy 36th Street at Spruce, Philadelphia, PA 19104 (U.S.A.)
and Biology,
DAVID KRITCHEVSKY * SHIRLEY A. TEPPER SUSANNE K. CZARNECKI DAVID M. KLURFELD
(Received 24 July, 1981) (Revised, received 8 September, 1981) (Accepted 10 September, 1981)
* Supported.
in part, by grants (HL-03299 and CA-09171) and a Research Career Award (HL-00734) from the National Institutes of Health, by the United States Department of Agriculture-SGA, Grant 59-24264-l-4794 and by the Mobil Foundation, Inc.
Atherosclerosis, 41 (1982) 429-431 @ Elsevier/North-Holland Scientific
Publishers,
Ltd.
Letter to the Editors ATHEROGENICITY OF ANIMAL AND VEGETABLE PRGTEIN Influence of the Lysine to Arginine Ratio Sir
Protein of animal origin (casein or beef) is more cholesterolemic and atherogenic than plant protein (soy) [l-4]. Weigensberg et al. [ 51 suggested that the lysine content of a protein may be a determinant of its atherogenicity. In a retrospective analysis of diets of men who had died of coronary disease, Moore et al. [6] found a significant correlation between the lysine content of the diet and the trend towards increased severity of coronary disease. We have hypothesized that the lysine/arginine ratio of a protein may be an important determinant of its atherogenic potential [ 781. The addition of lysine to soy protein, sufficient to change its normal lysine/arginine ratio [l.O] to that of casein (2.0), significantly increases its atherogenicity. Addition of arginine to casein to lower its lysine/arginine ratio to that of soy protein decreases its atherogenicity [ 8,9]. We have compared the atherogenicity of 3 proteins whose lysine levels are virtually the same but whose lysine/arginine ratios are quite different. The proteins used were fish protein (lysine, 6.81; arginine, 4.74; lysine/ arginine, 1.44); casein (lysine, 6.91; arginine, 3.65; lysine/arginine, 1.89); and whole milk protein (lysine, 6.61; arginine, 2.71; lysine/arginine, 2.44). The pro-
TABLE
1
INFLUENCE
OF
SCLEROSIS Rabbits
FISH,
CASEIN
OR
WHOLE
MILK
PROTEIN
ON
LIPID
LEVELS
AND
ATHERO-
IN RABBITS
were
fed
are significantly
semipurified
different
diets
containing
(P < 0.05)
by
25%
protein
for
8 months.
Values
bearing
the
same
letter
t-test.
Protein Fish Serum
lipids
*
238
cholesterol
Triglycerides Serum
*
*
f 40
15.7 122
protein (g/dl) atherosclerosis
f
ab
Arch
1.55
f
0.23
Thoracic
0.95
*
0.17
(P < 0.05)
by analysis
0021-9150/82/0000-0000/$02.75@1982
C 76 a
11.8
+ 20 f
* Significant
530
l.$C
4.00
Aortic
Whole
milk
(mg/dl)
Cholesterol % HDL
Casein
177
0.14
+
462
1.1’
f 47 4.05
+
e
2.05
f
f
1.10
f
~62~
11.9 251
0.18
+
1.5
-f 56
d
4.14
f
0.21
0.25
2.61
+
0.16
e
0.25
1.56
c
0.19
f
of variance.
Elsevier/North-Holland
Scientific
Publishers,
Ltd.
430
/
??
? ? ??
FISH CASEIN PROTEIN
MILK PROTEIN
LYSINE ARGININE Fig. 1. Average atherosclerosis levels in rabbits P < 0.05). ratio of those proteins (r = 0.9979,
fed 3 different
proteins
plotted
against
lysinglarginine
teins were fed to female New Zealand white rabbits as 25% of a semipurified diet containing 40% sucrose, 14% coconut oil, 15% cellulose, 5% salt mix and 1% vitamin mix. This diet has been shown to be hypercholesterolemic, hyperbetalipoproteinemic and atherogenic for rabbits [2,3,10]. After 8 months the rabbits were killed, serum lipids determined [ 11-131 and aortic atherosclerosis assessed by visual grading on a O-4 scale [ 14,151. The data are summarized in Table 1 and Fig. 1. Plotting the lysine/arginine ratio against average atherosclerosis (arch plus thoracic divided by 2) gives a statistically significant, positive regression coefficient (r = 0.9979, P < 0.05). Serum cholesterol, triglyceride and HDL cholesterol levels were significantly different in the three groups. Serum protein levels [ 161 were not affected. The mechanism underlying this phenomenon is still unclear. It may involve inhibition by lysine of liver arginase [17] which would make more arginine available for synthesis of the arginine-rich lipoprotein, which is associated with enhanced atherosclerosis in rabbits [18]. Addition of lysine to soy protein or arginine to casein affects the lipoprotein spectrum [ 8,191. Another possibility is that increased levels of serum arginine may exert glucagon-like activity [20].
431
The influence tigation.
of other proteins
of differing
lysine/arginine
ratios is under inves-
References 1 Meeker, D.R. and Kesten, H.D., Effect of high protein diets on experimental atherosclerosis in rabbits. Arch. Path., 31 (1941) 147. 2 Kritchevsky. D.. Tepper, S.A., Williams, D.E. and Story, J.A.. Experimental atherosclerosis in rabbits fed cholesterol-free diets, Part 7 (Interaction of animal or vegetable protein with fiber), Atherosclerosis. 26 (1977) 397. 3 Kritchevsky. D., Tepper. S.A., Czamecki, S.K., Klurfield, D.M. and Story, J.A., Experimental atherosclerosis in rabbits fed cholesterol-free diets, Part 9 (Beef protein and textured vegetable protein), Atherosclerosis, 39 (1981) 169. 4 Carroll, K.K. and Hamilton, R.M.G., Effects of dietary protein and carbohydrate on plasma cholesterol levels in relation to atherosclerosis, J. Food Sci., 40 (1975) 18. 5 Weigensberg. B.I.. Stary, H.C. and McMillan, G.C., Effect of lysine deficiency on cholesterol atherosclerosis in rabbits, Exp. Mol. Path., 3 (1964) 444. 6 Moore, M.C.. Guzman, M.A.. Schilling, P.E. and Strong. J.P., Dietary-atherosclerosis study on deceased persons. J. Amer. Dietetic Ass.. 70 (1977) 602. I Kritchevsky. D., Tepper, S.A. and Story, J.A., Influence of soy protein and casein on atherosclerosis in rabbits, Fed. Proc., 37 (1978) 747. 8 Czarnecki, S.K. and Kritchevsky, D., The effect of dietary proteins on lipoprotein metabolism and atherosclerosis in rabbits. J. Amer. Oil Chem. Sot., 56 (1979) 388A. 9 Kritchevsky, D., Vegetable protein and atherosclerosis, J. Amer. Oil Chem. Sot., 56 (1979) 135. 10 Kritchevsky. D. and Tepper, S.A., Experimental atherosclerosis in rabbits fed cholesterol-free diets Influence of chow components, J. Atheroscler. Res., 8 (1968) 357. 11 Rudel. L.L. and Morris, M.D., Determination of cholesterol using o-phthalaldehyde, J. Lipid Res.. I4 (1973) 364. 12 Manual of Laboratory Operation, Lipid Research Clinics Program. Vol. 1 (Lipid and Lipoprotein Analysis) (DHWW Publication No. (NIH) 75-625). 1974. P. 56. 13 Levy, A.L. and Keyloun, C., Measurements of triglycerides using nonane extraction and’colorimetry. In: Advances in Automated Analysis, Vol. 1, Thurman Ass., Miami, FL, 1972. PP. 487-502. 14 Duff, G.L. and McMillan. G.C., The effect of alloxan diabetes on experimental atherosclerosis in the rabbit, J. Exp. Med., 89 (1949) 611. 15 Kritchevsky, D., Tepper. S.A. and Story, J.A., Cholesterol vehicle in experimental atherosclerosis, Part 16 (Effects of peanut oil on we-established lesions), Atherosclerosis, 31 (1978) 365. 16 Lowry, O.H.. Rosebrough, N.J., Farr, A.L. and Randall, R.J., Protein measurement with the Folin phenol reagent, J. Biol. Chem.. 193 (1951) 265. 17 Cittadini, D., Pietropaolo, C., DeCristofaro. D. and D’Ayjello-Caracciolo, M.. In viva effect of Glysine on rat liver arginase, Nature (Land.), 203 (1964) 643. 18 Shore. B.. Shore. V., S&l, A.. Mason, D. and Zelis. R., An apolipoprotein preferentially enriched in cholesterol ester-rich very low density lipoproteins, Biochem. Biophys. Res. Comm., 58 (1974) 1. 19 Kritchevsky, D., Dietary protein in atherosclerosis. In: G. Noseda, B. Lewis and R. Paoletti (Eds.), Diet and Drugs in Atherosclerosis, Raven Press, New York, NY, 1980. pp. 9-14. 20 Noseda, G. and Fragiacomo, C., Effects of soybean protein diet on serum lipids, plasma glucagon and insulin. In: G. Noseda. B. Lewis and R. Paoletti (Eds.). Raven Press, New York, NY, 1980. pp. 61-65.
The Wistar Institute of Anatomy 36th Street at Spruce, Philadelphia, PA 19104 (U.S.A.)
and Biology,
DAVID KRITCHEVSKY * SHIRLEY A. TEPPER SUSANNE K. CZARNECKI DAVID M. KLURFELD
(Received 24 July, 1981) (Revised, received 8 September, 1981) (Accepted 10 September, 1981)
* Supported.
in part, by grants (HL-03299 and CA-09171) and a Research Career Award (HL-00734) from the National Institutes of Health, by the United States Department of Agriculture-SGA, Grant 59-24264-l-4794 and by the Mobil Foundation, Inc.