Detary
fiber
and other
dietary
factors
in
David
Kritchevsky
The current interest in the role of fiber in human disease can be attributed largely to the observations of Burkitt (1) and Trowell (2) who found that certain diseases which are common in western countries are virtually unknown in the developing countries of Africa (3). They concluded that the differences in disease spectra could be related to the decreased consumption of fiber by the developed countries. Their findings must be viewed as correlative associations and they do not prove cause and effect For example, colon cancer is considered by Burkitt to be one of the conditions related to low fiber intake A high fiber diet, it is argued, by decreasing intestinal transit time reduces the colonic residence time of potential carcinogenic agents. Hill (4, 5) on the other hand, presents a good case for considering the differences in disease spectra to be rebated to the action of different intestinal microflora (due to diet?) with their specific metabolic effects. There is no standard definition of fiber. Crude fiber is material remaining after rigorous treatment of food with acid and alkali. The residue contains the cellulose hemicelbubose and lignin that were present in the original sample Dietary fiber can be viewed as material that is impervious to the degradative enzymes of our own digestive tract or to those of our microflora. Dietary fiber is comprised of cellulose, hemicellulose, bignm, gums, and pectins. Spiller and Amen (6) have proposed a revised terminology for fiber. Nonpurified plant fiber would be the designation for fibrous material in its natural state; purified plant fiber would be the sum of polymeric fibrous components and substances such as cellophane would be called nonnutritive synthetic fiber. Recognition of the intricacies of plant fiber structure (7) has bed to advances in fractionation and analysis (8 9). These will help to systema.
.
,
,
,
.
,
The
American
Journal
ofClinicoi
Nutrition
30: JUNE
1977,
tize fiber analysis and this, in turn should provide more accurate nomenclature. The idea of a possible deleterious effect of a purified (or fiber free) diet is not new. Cleave (1 0) wrote a book in which he described the wages of the metabolic sins attributabbe to an overpurified diet as “The Saccharine Disease Spiller and Amen (11) quote authors of the 1 6th century who recognized the laxative effects of high fiber diets. Cowgill (1 2 1 3) studied the laxative effect of bran. Williams and Olmstead (14) attempted to correlate the cathartic effects of a number of foods with their composition They fed a series of ten bulking agents and found increments in stool weights ranging from over 600 to under 1 00 gm (Table 1) However, stool weights were not correbated with estimated laxative effect which, in turn, could not be easily related to the content of cellulose hemicellubose or bignin (Table 2). Since fiber appears to increase fecab bulk ,
.“
,
.
.
,
(14) (15),
and
to decrease
intestinal
transit
time
it is logical to investigate its effects on lipid excretion. Portman and Murphy (16) found that, when rats were fed a semipurifled, fiber-free diet containing starch, they excreted 72% less cholic acid and 36% less neutral steroid than when fed laboratory ration Chobic acid half-time in these animals was increased by 62% Substitution of sucrose for starch caused further declines in excretion of cholic acid and neutral steroids and a further rise in chobic acid half-time. .
.
I From the Wistar Institute of Anatomy and Biology, 36th Street at Spruce, Philadelphia, Pennsylvania 19104. 2 Supported, in part, by United States Public Health Service Research Grant HL-03299 and HL-05209 and a Research Career Award HL-0734 from the National Heart, Lung and Blood Institute and by grants-in-aid from the National Dairy Council, the International Sugar Research Foundation and the National Live Stock and Meat Board.
pp.
979-984.
Printed
in U.S.A.
979
Downloaded from https://academic.oup.com/ajcn/article-abstract/30/6/979/4650301 by University of Rhode Island user on 30 November 2018
2
980
KRITCHEVSKY
TABLE 1 Influence of various patients)
Wt.
fed
(average
(A)
of 3
B/A g
Agar
agar
Cabbage Carrots Sugar beet pulp Corn germ meal Wheat bran Alfalfa leaf Canned peas Celluflour Cottonseed hull a After Williams TABLE Laxative
2 effect Material
a
666 625 541 401 578 475 240 167 93 97 (14).
8.30 6.15 5.06 4.29 3.74 3.25 3.04 2.24 1.34 0.91
and composition” Major
residu&
C
H
.
Estimated
.
Agar agar Cabbage Carrots Sugar beet pulp Corn germ meal Wheat bran Alfalfa leaf Canned peas Celluflour Cottonseed hull lose;
80.2 101.5 106.8 93.4 154.4 146.0 79.5 74.5 71.7 105.9 and Olmstead
L
#{247} +
+
+
+
+ + +
+
After Williams and Olmstead H, hemicellulose; L, lignin.
(1-10)
6 10 9 7 8 5
+
+ + +
laxative
effect
1 4 2
,
TABLE 3 Effect of fiber source on absorption of [4-’4C] cholesterol in rats fed isocaloric, isogravic diets” Radioactivity Major (50%)
source
of caloriesb
Fiber
Simm liver
dpm 10’
3
+
(14).
b
C, cellu-
Leveible and Sauberlich (1 7) tested the effects of pectin in cholesterol-fed rats and found relatively few differences in serum and liver lipids, but observed a significant increase in excretion of bile acids. We (18-20) had observed that protein, carbohydrate or fat elicited different effects when fed to rats as 50% of the calories of an isocaloric isogravic diet and that these effects varied with the fiber. When the fiber in that diet was changed from cellulose to alfalfa, serum and liver lipids weren’t affected but steroid excretion was. Table 3 shows that when the rats were fed a single dose of [4-14 C] cholesterol 3 days before termination of the experiment the animals fed ceblulose excreted considerably less neutral steroid than did those fed alfalfa. The major source of calories did not affect this increase The increase in neutral steroid excretion was 81 % when 50% of the calories
Dextrose
Corn
Oil
Casein a After components
recovered Feces
(dpm
10’)
Neutral
Acidic
2.01 3.64 2.50 4.17 2.05 3.74 1 .45 2.49
0.76 0.65 0.44 0.83 0.58 0.78 0.66 1.37
Kritchevsky et al. (20). 1) Two each present as 25% of calories.
TABLE 4 Influence of dietary rats” (8 rats/group:
x
x
3.39 2.02 2.58 2.10 2.83 1.21 4.1 1 3.31
Cellulose Alfalfa Cellulose Alfalfa Cellulose Alfalfa Cellulose Alfalfa
Sucrose
plus
additions on cholesterol fed 28 days)
minor
levels in
,
.
Cholesterol
Galls
Wt.
Diet
g
BasaV’ (B) B plus 1% cholesterol (BC) BC plus: 10% pectin 10%guargum 10%locustbeangum 10% carrageenan After Ershoff crose, 24% casein, a
Plasma
Liver
mg/dl
‘ng/g
153 157
85 106
2.9 16.2
138 134 136 147
96 91 101 89
4.1 6.1 7.6 5.5
and Wells (21, 22). b 61% su10% cottonseed oil, 5% salt mix.
Downloaded from https://academic.oup.com/ajcn/article-abstract/30/6/979/4650301 by University of Rhode Island user on 30 November 2018
Material
were derived from dextrose 67 % when the calories were from sucrose, 83 % from corn oil and 72 % from casein. The alfalfa-fed rats excreted 34 to 1 08 % more acidic steroid except in the dextrose groups where they excreted 14% less. Ershoff and Wells (21 22) have found that when rats are fed a fiber-free diet contaming 1 % cholesterol, they show a slight increase in serum cholesterol but a massive increase in liver cholesterol. Addition of 10% fiber to the diet markedly reduces their liver cholesterol bevels (Table 4). Riccardi and Fahrenbach (23) have observed similar effects. Vijayagopaban and Kurup (24) have cobbated their experiments on the effects of dietary carbohydrate on serum, liver, and aorta cholesterol in rats. Cholesterol accumulated as the fiber content of the starch fell (Table 5). ,
foods on fecal bulk’s
DIETARY TABLE Influence
5 of starches
on cholesterol
FIBER
levels
Fiber
Corn
Bojia Jowar
Tapioca Ragi
Black grain Sucrose a After hydrate; terol.
%
mg/dl
0.10 0.12 0.28 0.44 0.85 1.25 2.16 7.10
348 358 233 226 142 205 93 75 372
Vijayagopalan et al. (24). 15% hydrogenated peanut
Liver
Aorta
mg/g
31 41 27 25 20 24 16 5 48 b
oil;
14 16 12 11 8 8 5 3 18
56% carbo2% choles-
taming saturated fat but no cholesterol and had observed atherosclerotic lesions. Collation of the existing data (30) showed that a similar level of saturated fat added to laboratory ration was neither hyperchobesteremic nor atherogenic (Table 6) Our conclusion was that the type of fiber in the diet might be the determining factor (30). Our experiments (3 1 32) showed that addition of saturated fat to the delipidized residue of rabbit ration or to the ration itself had little effect on serum lipids or atherosclerosis. Moore (33) carried out a similar experiment in which he fed rabbits a semipurified diet containing 20% butter oil and roughage in the form of cellophane cellulose wheat straw or celbophane:peat, 14:5 The cellophane-containing diet was the most cholesteremic and atherogenic followed (in de.
,
,
,
.
In man, similar effects can be deduced. Grande (25) has summarized the results of a number of experiments in which sucrose was exchanged for starch in diets of normolipemic patients In all, 1 2 experiments using an average of 1 5 patients and in which an average of 23 % of calories were exchanged for 23 days were described. Serum cholesterob levels fell in all 1 2 experiments and the results were significant in seven. The sources of starch were fruit, cereal, begumes, and vegetablesall of which contain some fiber. Mathur et ab. (26) placed 20 patients on a high fat diet for 10 weeks. In that period their serum cholesterol rose from 123 ± 23 to 260 ± 20 mg/dl. Fecal steroid excretion rose from 436 mg/24 hr .
(38%
chobic
and
deoxycholic
acids)
to 692
mg/24 hr (3 1 % cholic and deoxycholic acids). When fed for 55 weeks on the high fat diet to which bengal gram (chick peas) had been added, cholesterol bevels dropped to 1 60 ± 24 mg/db and fecab steroid excretion was 776 mg/24 hr (39% cholic and deoxychobic acids). Obviously, certain types of fiber affect lipid metabolism in man and in experimentab animals Bran however, does not appear to lower serum lipids in man. Truswell and Kay (27) have summarized all the published data (10 experiments) relating to bran administration and no effect is seen. Pectin, however, does seem to have a hypocholesteremic effect in man (28). In 1958 Lambert et al. (29) reported that they had fed rabbits a semipurified diet con.
,
creasing
order)
by
cellulose,
wheat
straw
and celbophane:peat. Although the chobesteremic effect of semipurified diet has been well documented, there are few data as to their mechanism of action We fed semipurified diets containing casein, coconut oil, cellulose, and different carbohydrates to baboons for 1 year (34). All the test diets were hyperlipemic and sudanophibic Analysis of the bile lipids fobbowing the administration of radioactive mevabonic acid revealed that the ratio of specific activities of primary to secondary bile acids was much lower in the baboons .
.
fed
the
semipurified
diet
(Table
We hypothesized that diet there was reduced acids,
possibly
because
7).
with the synthesis they
purified of bile
were
not
being
excreted. In other words, the high fiber, natural diet fed to the control baboons led to increased excretion of bile acids, possibly through some binding mechanism Kyd and Bouchier (35) working with rabbits fed a .
TABLE 6 Summary of effects of saturated and commercial ration”
fat in semipurifled
(SP)
Fat Diet
No.
Atheromata
Type
Stock SP
5 5 10 7
a Summarized
20 21 16 16
Saturated Unsaturated Saturated Unsaturated
from
% (range)
Kritchevsky
(9-50) (9-28) (8-24) (8-20)
(30).
0.02 0.02 1.62 0.02
Downloaded from https://academic.oup.com/ajcn/article-abstract/30/6/979/4650301 by University of Rhode Island user on 30 November 2018
Rice
Wheat
levels
conten
Serum
981
HYPERCHOLESTEREMIA
in rats”
Ch olesterol Starch’
IN
982
KRITCHEVSKY
TABLE
7 of semipurifled
Influence
diets
on lipid
metabolism
Serum
lipi da (mg/dI)
in baboons”
for
1 yr)
sudanophi.
Triglycerides
P/SC
activity’
S
‘
Bile
Cholesterol
salts
%
Fructose Sucrose Starch
162 ± 10 152 ± 9 156±8 151 ± 11 113±3
Glucose
Control
129 ± 11 116 ± 8 108±5 107 ± 7 78±4
11.2 6.7 9.3 6.2 0.02
0.56 0.61 1.33 0.81 1.67
3 3 2 2 15
a After Kritchevsky et al. (34). 40% carbohydrate; 25% casein; 15% cellulose; coconut oil; 5% salt mix; 1% vitamin mix. C (cholic and chenodeoxycholic)/secondary and lithocholic). d dpm/mg x 10’ in bile lipids of baboons given [5-3H] mevalonic acid.
TABLE Binding
8 of bile acids and salts by different types of fiber” Bile
acid
or salt’
Cholic Taurocholic
Glycocholic Chenodeoxycholic Taurochenodeoxy-
Alfalfa
Bran
19.9
10.2
6.9
1.4
Cellulose
Lignin
1 1 .5 24.8 15.1
3.8 18.2 9.8
3.0 1.0 1 .2 1 .9 0.0
43.7 22.1 22.5 23.3 25.4
14.9
21.4
0.2
25.2
10.4 1 1 .4 27.8
5 .4
0.2 0.7 4.7
17.4 30.9 52.6
cholic Glycochenodeoxy-
cholic Deoxycholic Taurodeoxycholic Glycodeoxycholic
hydrogenated (deoxycholic
14%
acids and their taurine and glycine conjugates. Table 8 shows that each binding substance exhibits specific binding affinities. In studying dietary effects one must be aware of the interactions among all dietary components. There are a number of papers in the literature which show that casein is more cholesteremic and/or atherogenic than soya protein for rabbits (41 42) or chickens (43). Carroll and Hamilton (44) confirmed these findings and showed that, in general, animal protein was more cholesteremic than vegetable protein. When fed as part of a diet containing defatted protein and dextrose, casein resulted in cholesterol levels of 208 mg/dl and soya protein of 70 mg/dl. When the carbohydrate was potato starch, cholesterol levels of rabbits fed either casein or soya protein were normal (50 ± 5 mg/dl). We have carried out an experiment (45) in which rabbits were fed a semipurified diet ,
3 .4 7.8
C After Story and Kritchevsky (39, 40). b50mg binder, 50 .tmoles bile acid or salt in 5 ml phosphate buffer (pH 7.0); incubated at 37 C for 2 hr. Values represent average of three experiments.
lithogenic diet reached a similar conclusion regarding hypercholesteremia caused by a semipurified diet. We have found (36) that rabbits fed a semipurified diet exhibited a lower cholic/deoxycholic acid ratio than did controls. Eastwood and Hamilton (37) studied the adsorption of bile acids and bile salts to various grains and found that the lignin component bound the test materials most avidly. Balmer and Zibversmit (38) studied the binding of sodium taurocholate to ground wheat, corn and oats as well as to other grains and found that the extent of binding was characteristic of the grain used. We (39, 40) have tested alfalfa, bran, cellulose and bignin for their ability to bind chobic, chenodeoxycholic, and deoxycholic ,
88 30 47 47 59
TABLE
9
Fiber-protein interactions fed semipurifled diets”
in rabbits
Protein5 Caaein
Fiber Serum
cholesterol
Soya Athero. matac
mg/dJ
Cellulose Wheat straw Alfalfa
402 ± 40 375 ± 42 193 ± 34
Serum
protein
cholesterol
Atheromats
ng/dI
1 .50 1 .03 0.63
248 ± 44 254 ± 35 159 ± 20
1.25
0.91 0.73
a After Story et al. (45). Diets contained 40% sucrose, 25% protein, 15% fiber, 14% hydrogenated coconut oil, 5 % salt mix, 1 % vitamin mix. (Arch plus thoracic)/2.
Downloaded from https://academic.oup.com/ajcn/article-abstract/30/6/979/4650301 by University of Rhode Island user on 30 November 2018
Cholesterol
fed
Bile Aortic
Diet’
(6 per group:
DIETARY
FIBER
IN
,
.
.
References
2.
3.
D . P . Some diseases characteristic of modern Western civilization . Brit . Med . M . 1: 274, 1973. TROWELL, H. C. Ischemic heart disease and dietary fiber. Am. J. Chin. Nutr. 25: 926, 1972. BURKZTI, D. P., A. R. P. WALKER AND N . S. BURKITr,
PAINTER.
Dietary
fiber
and
disease.
J.
Am.
Med.
Assoc. 229: 1068, 1974. 4 . HILL, M . J . Bacteria and the etiology of colonic cancer. Cancer 34: 815, 1974. 5. HILL. M. J. Colon cancer: a disease of fiber depletion or of dietary excess? Digestion 1 1 : 289, 1974. 6. SPILLER, G. A. , AND R. J. AMEN. Plant fibers in nutrition: need for better nomenclature. Am. J. Clin. Nutr. 28: 675, 1975. 7 . VAN S0E5T, P. J. Development of a comprehensive system of feed analyses and its application to forages. J. Animal Sci. 26: 119, 1967. 8. VAN SoEsr, P. J., AND R. W. MtQUEEN. The chemistry and estimation of fibre. Proc. Nutr. Soc. 32: 123, 1973. 9. SoumGAm, D. A. T. Fibre and other unavailable carbohydrates and their effects on the energy value ofthe diet. Proc. Nutr. Soc. 32: 131, 1973. 10. CAvn, T. L. The Saccharine Disease. Bristol: John Wright and Sons, Ltd., 1974. 1 1 . SPILLER, G. A. , AND R. J. AMEN. Dietary fiber in human nutrition. Food Sci. Nutr. 7: 39, 1975. 12. COWGILL, G. R., AND W. E. ANDERSON. Laxative effect of wheat bran and washed bran in healthy man. J. Am. Med. Assoc. 98: 1886, 1932. 13. COWGILL, G. R., AND A. J. SULLIVAN. Further studies on the use of wheat bran as a laxative . J. Am. Med. Assoc. 100: 795, 1933. 14. WILLIAMS, R. D., AND W. H. OLMSTED. The manner in which food controls the bulk of the feces. Ann. Int. Med. 10: 717, 1936. 15 . BURKITr, D. P., A. R. P. WALKER AND N. S. PMwraR. Effect of dietary fibre on stools and transit times, and its role in the causation of disease. Lancet 2: 1408, 1972. 16. PORTMAN, 0. W., AND P. Mup.pHY. Excretion of bile acids and ,8-hydroxysterols by rats. Arch. Biochem. Biophys. 76: 367, 1958.
17.
LEVEILLE, G. A., AND H. E. SAUBERLICH. Mechanism of the cholesterol-depressing effect of pectin in the cholesterol-fed rat. J. Nutr. 88: 209, 1966. 18. KRITCHEvSKY, D., AND S. A. TEPPER. Influence of isocaloric, isogravic diets on serum and liver lipids in rats. Nutr. Rep. Internat. 3: 283, 1971. 19. KRITCHEVSKY, D., R. P. CASEY AND S. A. Tm’PER. Isocaloric, isogravic diets in rats. II. Effect on cholesterol absorption and excretion. Nutr. Rep. Internat. 7: 61, 1973. 20. KRiTCHEvSKY, D. , S. A. TEPPER AND J. A. STORY. Isocaloric, isogravic diets in rats. III. Effect on non-nutritive fiber (alfalfa or cellulose) on cholesterol metabolism. Nutr. Rep. Internat. 9: 301, 1974. 21 . ERSHOFF, B. H. AND A. F. WELLS. Effects of gum guar, locust bean gum and carrageenan on liver cholesterol of cholesterol-fed rats . Proc . Soc. Exptl. Biol. Med. 1 10: 580, 1962. 22. ERSHOFF, B. F., AND A. F. WELLS. Effects of methoxyl content on anticholesterol activity of pectic substances in the rat. Exptl. Med. Surg. 20: 272, 1962. 23. RICCARDI, B. A., AND M. J. FARRENBACH. Effect of guar gum and pectin N.F. on serum and liver lipids of cholesterol fed rats. Proc. Soc. Exptl. Biol. Med. 124: 749, 1967. 24. VUAYAGOPALAN, P. , K. S. DEW AND P. A. KuRUP. Fibre content of different dietary starches and their effect on lipid levels in high fat-high
cholesterol
fed
rats.
Atherosclerosis
1 7:
156,
1973. 25
F. Sugars in cardiovascular disease . In: Sugars in Nutrition, edited by H. L. Sipple, K. W. McNutt. New York: Academic Press, Inc. , 1974, pp. 401. 26. MAmuR, K. S., M. A. KHANAND R. D. SHARMA. Hypocholesterolaemic effect of Bengal gram: A long-term study in man. Brit. Med. J. 1: 30, 1968. 27. TRUSWELL, A. S., AND R. M. KAY. Bran and blood-lipids. Lancet 1 : 367, 1976. 28. JENKINS, D. J. A., A. R. LEEDS, C. NEWTON AND J. H. CUMMINGS. Effect of pectin, guar gum, and wheat fibre on serum cholesterol. Lancet 1 : 1116, 1975. 29. LAMBERT, G. F., J. P. MILLER, R. T. OLSEN AND D. V. FROST. Hypercholesteremia and atherosclerosis induced in rabbits by purified high fat rations devoid of cholesterol. Proc. Soc. Exptl. Biol. Med. 97: 544, 1958. 30. KRITCHEvSKY, D. Experimental atherosclerosis in rabbits fed cholesterol-free diets. J. Atheroscier. Res. 4: 103, 1964. 31. KIUTCHEvSKY, D., AND S. A. TEPPER. Factors affecting atherosclerosis in rabbits fed cholesterolfree diets. Life Sci. 4: 1467, 1965. 32. Karrcssevsicy, D. AND S. A. TEPPER. Experimental atherosclerosis in rabbits fed cholesterol-free diets: influence of chow components. J. Atheroscler. Res. 8: 357, 1968. 33. Mooiu, J. H. The effectofthe type ofroughage in the diet on plasma cholesterol levels and aortic atherosis in rabbits. Brit. J. Nutr. 21: 207, 1967. 34. KarrcHEvsxy, D., L. M. DAVIDSON, I. L. Sisplao, H. K. Kus, M. KrFAGAWA, S. MALHOTRA, P. P. N, T. B. CLARICSON, I. BERSOHN AND P. A. .
GRANDE,
Downloaded from https://academic.oup.com/ajcn/article-abstract/30/6/979/4650301 by University of Rhode Island user on 30 November 2018
in which the protein was casein or soya protein and the fiber cellulose wheat straw, or alfalfa Within each protein group cellulose was the most cholesteremic and atherogenic fiber and alfalfa the least When the proteins were compared, soya-cellulose and soya-wheat straw were less chobesteremic and atherogenic than their casein counterparts. When the diets contained alfalfa, the two proteins were roughly equivalent (Table 9). The data presented here indicate that dietary fiber may play an important role in lipid metabolism and that we must be cognizant of the complex interactions of all cornponents of the diet.
1.
983
HYPERCHOLESTEREMIA
984
KRITCHEVSKY 40.
STORY,
the
41
42.
43.
44.
45.
.
J. A.,
binding
D. Kntchevsky. Comparison of bile acids and bile salts in types offiber. J. Nutr. 106: 1292,
AND
of various
vitro by several 1976. NEWBURGH, L. H., AND T. L. SQUIER. High protein diets and arteriosclerosis in rabbits: a preliminary report. Arch. Internat. Med. 26: 38, 1920. MEEKER, D. R., AND H. D. KESTEN. Experimental atherosclerosis and high protein diets . Proc. Soc. Exptl. Biol. Med. 45: 543, 1940. KRITCHEVSKY, D. , R. R. KOLMAN, R. M. GuuMACHER AND M. Foaar.s. Influence of dietary carbohydrate and protein on serum and liver cholesterol in germ-free chickens. Arch. Biochem. Binphys. 85: 444, 1959. CARROLL, K. K., AND R. M. G. HAMiLTON. Effects of dietary protein and carbohydrate on plasma cholesterol levels in relation to atherosclerosis.J. Food Sci. 40: 18, 1975. STORY, J. A., S. A. TEPPER AND D. KRJTCHEVSKY. Atherosclerosis in rabbits fed cholesterol-free diets: effect of protein and fiber. Federation Proc. 35: 294, 1976. (abstr.).
Downloaded from https://academic.oup.com/ajcn/article-abstract/30/6/979/4650301 by University of Rhode Island user on 30 November 2018
D. WINTER. Lipid metabolism and experimental atherosclerosis in baboons: influence of cholesterol-free, semi-synthetic diets. Am. J. Clin. Nutr. 27: 29, 1974. 35. Kyti, P. A., AND I. A. D. BOUCHIER. Cholesterol metabolism in rabbits with oleic acid-induced cholelithiasis. Proc. Soc. Exptl. Biol. Med. 141 : 846, 1972. 36. KarrcHEvsKY, D., S. A. TEPPER, H. K. Kn.i, D. E. MOSES AND J. A. SToRY. Experimental atherosclerosis in rabbits fed cholesterol-free diets . 4. Investigation into the source of cholesteremia. Exptl. Mol. Pathol. 22: 11, 1975. 37. EASTWOOD, M. A. , AND D. HAMILTON. Studies on the adsorption of bile salts to non-absorbed components of diet. Biochim. Biophys. Acta 152: 165, 1968. 38. BALMER, J. , AND D. B. ZILVERSMIT. Effects of dietary roughage on cholesterol absorption, cholesterol turnover and steroid excretion in the rat. J. Nutr. 104: 1319, 1974. 39 . KRJTCHEVSKY, D . , AND J. A . STORY. Binding of bile salts in vitro by non-nutritive fiber. J. Nutr. 104: 458, 1975.
fiber
and other
dietary
factors
in
David
Kritchevsky
The current interest in the role of fiber in human disease can be attributed largely to the observations of Burkitt (1) and Trowell (2) who found that certain diseases which are common in western countries are virtually unknown in the developing countries of Africa (3). They concluded that the differences in disease spectra could be related to the decreased consumption of fiber by the developed countries. Their findings must be viewed as correlative associations and they do not prove cause and effect For example, colon cancer is considered by Burkitt to be one of the conditions related to low fiber intake A high fiber diet, it is argued, by decreasing intestinal transit time reduces the colonic residence time of potential carcinogenic agents. Hill (4, 5) on the other hand, presents a good case for considering the differences in disease spectra to be rebated to the action of different intestinal microflora (due to diet?) with their specific metabolic effects. There is no standard definition of fiber. Crude fiber is material remaining after rigorous treatment of food with acid and alkali. The residue contains the cellulose hemicelbubose and lignin that were present in the original sample Dietary fiber can be viewed as material that is impervious to the degradative enzymes of our own digestive tract or to those of our microflora. Dietary fiber is comprised of cellulose, hemicellulose, bignm, gums, and pectins. Spiller and Amen (6) have proposed a revised terminology for fiber. Nonpurified plant fiber would be the designation for fibrous material in its natural state; purified plant fiber would be the sum of polymeric fibrous components and substances such as cellophane would be called nonnutritive synthetic fiber. Recognition of the intricacies of plant fiber structure (7) has bed to advances in fractionation and analysis (8 9). These will help to systema.
.
,
,
,
.
,
The
American
Journal
ofClinicoi
Nutrition
30: JUNE
1977,
tize fiber analysis and this, in turn should provide more accurate nomenclature. The idea of a possible deleterious effect of a purified (or fiber free) diet is not new. Cleave (1 0) wrote a book in which he described the wages of the metabolic sins attributabbe to an overpurified diet as “The Saccharine Disease Spiller and Amen (11) quote authors of the 1 6th century who recognized the laxative effects of high fiber diets. Cowgill (1 2 1 3) studied the laxative effect of bran. Williams and Olmstead (14) attempted to correlate the cathartic effects of a number of foods with their composition They fed a series of ten bulking agents and found increments in stool weights ranging from over 600 to under 1 00 gm (Table 1) However, stool weights were not correbated with estimated laxative effect which, in turn, could not be easily related to the content of cellulose hemicellubose or bignin (Table 2). Since fiber appears to increase fecab bulk ,
.“
,
.
.
,
(14) (15),
and
to decrease
intestinal
transit
time
it is logical to investigate its effects on lipid excretion. Portman and Murphy (16) found that, when rats were fed a semipurifled, fiber-free diet containing starch, they excreted 72% less cholic acid and 36% less neutral steroid than when fed laboratory ration Chobic acid half-time in these animals was increased by 62% Substitution of sucrose for starch caused further declines in excretion of cholic acid and neutral steroids and a further rise in chobic acid half-time. .
.
I From the Wistar Institute of Anatomy and Biology, 36th Street at Spruce, Philadelphia, Pennsylvania 19104. 2 Supported, in part, by United States Public Health Service Research Grant HL-03299 and HL-05209 and a Research Career Award HL-0734 from the National Heart, Lung and Blood Institute and by grants-in-aid from the National Dairy Council, the International Sugar Research Foundation and the National Live Stock and Meat Board.
pp.
979-984.
Printed
in U.S.A.
979
Downloaded from https://academic.oup.com/ajcn/article-abstract/30/6/979/4650301 by University of Rhode Island user on 30 November 2018
2
980
KRITCHEVSKY
TABLE 1 Influence of various patients)
Wt.
fed
(average
(A)
of 3
B/A g
Agar
agar
Cabbage Carrots Sugar beet pulp Corn germ meal Wheat bran Alfalfa leaf Canned peas Celluflour Cottonseed hull a After Williams TABLE Laxative
2 effect Material
a
666 625 541 401 578 475 240 167 93 97 (14).
8.30 6.15 5.06 4.29 3.74 3.25 3.04 2.24 1.34 0.91
and composition” Major
residu&
C
H
.
Estimated
.
Agar agar Cabbage Carrots Sugar beet pulp Corn germ meal Wheat bran Alfalfa leaf Canned peas Celluflour Cottonseed hull lose;
80.2 101.5 106.8 93.4 154.4 146.0 79.5 74.5 71.7 105.9 and Olmstead
L
#{247} +
+
+
+
+ + +
+
After Williams and Olmstead H, hemicellulose; L, lignin.
(1-10)
6 10 9 7 8 5
+
+ + +
laxative
effect
1 4 2
,
TABLE 3 Effect of fiber source on absorption of [4-’4C] cholesterol in rats fed isocaloric, isogravic diets” Radioactivity Major (50%)
source
of caloriesb
Fiber
Simm liver
dpm 10’
3
+
(14).
b
C, cellu-
Leveible and Sauberlich (1 7) tested the effects of pectin in cholesterol-fed rats and found relatively few differences in serum and liver lipids, but observed a significant increase in excretion of bile acids. We (18-20) had observed that protein, carbohydrate or fat elicited different effects when fed to rats as 50% of the calories of an isocaloric isogravic diet and that these effects varied with the fiber. When the fiber in that diet was changed from cellulose to alfalfa, serum and liver lipids weren’t affected but steroid excretion was. Table 3 shows that when the rats were fed a single dose of [4-14 C] cholesterol 3 days before termination of the experiment the animals fed ceblulose excreted considerably less neutral steroid than did those fed alfalfa. The major source of calories did not affect this increase The increase in neutral steroid excretion was 81 % when 50% of the calories
Dextrose
Corn
Oil
Casein a After components
recovered Feces
(dpm
10’)
Neutral
Acidic
2.01 3.64 2.50 4.17 2.05 3.74 1 .45 2.49
0.76 0.65 0.44 0.83 0.58 0.78 0.66 1.37
Kritchevsky et al. (20). 1) Two each present as 25% of calories.
TABLE 4 Influence of dietary rats” (8 rats/group:
x
x
3.39 2.02 2.58 2.10 2.83 1.21 4.1 1 3.31
Cellulose Alfalfa Cellulose Alfalfa Cellulose Alfalfa Cellulose Alfalfa
Sucrose
plus
additions on cholesterol fed 28 days)
minor
levels in
,
.
Cholesterol
Galls
Wt.
Diet
g
BasaV’ (B) B plus 1% cholesterol (BC) BC plus: 10% pectin 10%guargum 10%locustbeangum 10% carrageenan After Ershoff crose, 24% casein, a
Plasma
Liver
mg/dl
‘ng/g
153 157
85 106
2.9 16.2
138 134 136 147
96 91 101 89
4.1 6.1 7.6 5.5
and Wells (21, 22). b 61% su10% cottonseed oil, 5% salt mix.
Downloaded from https://academic.oup.com/ajcn/article-abstract/30/6/979/4650301 by University of Rhode Island user on 30 November 2018
Material
were derived from dextrose 67 % when the calories were from sucrose, 83 % from corn oil and 72 % from casein. The alfalfa-fed rats excreted 34 to 1 08 % more acidic steroid except in the dextrose groups where they excreted 14% less. Ershoff and Wells (21 22) have found that when rats are fed a fiber-free diet contaming 1 % cholesterol, they show a slight increase in serum cholesterol but a massive increase in liver cholesterol. Addition of 10% fiber to the diet markedly reduces their liver cholesterol bevels (Table 4). Riccardi and Fahrenbach (23) have observed similar effects. Vijayagopaban and Kurup (24) have cobbated their experiments on the effects of dietary carbohydrate on serum, liver, and aorta cholesterol in rats. Cholesterol accumulated as the fiber content of the starch fell (Table 5). ,
foods on fecal bulk’s
DIETARY TABLE Influence
5 of starches
on cholesterol
FIBER
levels
Fiber
Corn
Bojia Jowar
Tapioca Ragi
Black grain Sucrose a After hydrate; terol.
%
mg/dl
0.10 0.12 0.28 0.44 0.85 1.25 2.16 7.10
348 358 233 226 142 205 93 75 372
Vijayagopalan et al. (24). 15% hydrogenated peanut
Liver
Aorta
mg/g
31 41 27 25 20 24 16 5 48 b
oil;
14 16 12 11 8 8 5 3 18
56% carbo2% choles-
taming saturated fat but no cholesterol and had observed atherosclerotic lesions. Collation of the existing data (30) showed that a similar level of saturated fat added to laboratory ration was neither hyperchobesteremic nor atherogenic (Table 6) Our conclusion was that the type of fiber in the diet might be the determining factor (30). Our experiments (3 1 32) showed that addition of saturated fat to the delipidized residue of rabbit ration or to the ration itself had little effect on serum lipids or atherosclerosis. Moore (33) carried out a similar experiment in which he fed rabbits a semipurified diet containing 20% butter oil and roughage in the form of cellophane cellulose wheat straw or celbophane:peat, 14:5 The cellophane-containing diet was the most cholesteremic and atherogenic followed (in de.
,
,
,
.
In man, similar effects can be deduced. Grande (25) has summarized the results of a number of experiments in which sucrose was exchanged for starch in diets of normolipemic patients In all, 1 2 experiments using an average of 1 5 patients and in which an average of 23 % of calories were exchanged for 23 days were described. Serum cholesterob levels fell in all 1 2 experiments and the results were significant in seven. The sources of starch were fruit, cereal, begumes, and vegetablesall of which contain some fiber. Mathur et ab. (26) placed 20 patients on a high fat diet for 10 weeks. In that period their serum cholesterol rose from 123 ± 23 to 260 ± 20 mg/dl. Fecal steroid excretion rose from 436 mg/24 hr .
(38%
chobic
and
deoxycholic
acids)
to 692
mg/24 hr (3 1 % cholic and deoxycholic acids). When fed for 55 weeks on the high fat diet to which bengal gram (chick peas) had been added, cholesterol bevels dropped to 1 60 ± 24 mg/db and fecab steroid excretion was 776 mg/24 hr (39% cholic and deoxychobic acids). Obviously, certain types of fiber affect lipid metabolism in man and in experimentab animals Bran however, does not appear to lower serum lipids in man. Truswell and Kay (27) have summarized all the published data (10 experiments) relating to bran administration and no effect is seen. Pectin, however, does seem to have a hypocholesteremic effect in man (28). In 1958 Lambert et al. (29) reported that they had fed rabbits a semipurified diet con.
,
creasing
order)
by
cellulose,
wheat
straw
and celbophane:peat. Although the chobesteremic effect of semipurified diet has been well documented, there are few data as to their mechanism of action We fed semipurified diets containing casein, coconut oil, cellulose, and different carbohydrates to baboons for 1 year (34). All the test diets were hyperlipemic and sudanophibic Analysis of the bile lipids fobbowing the administration of radioactive mevabonic acid revealed that the ratio of specific activities of primary to secondary bile acids was much lower in the baboons .
.
fed
the
semipurified
diet
(Table
We hypothesized that diet there was reduced acids,
possibly
because
7).
with the synthesis they
purified of bile
were
not
being
excreted. In other words, the high fiber, natural diet fed to the control baboons led to increased excretion of bile acids, possibly through some binding mechanism Kyd and Bouchier (35) working with rabbits fed a .
TABLE 6 Summary of effects of saturated and commercial ration”
fat in semipurifled
(SP)
Fat Diet
No.
Atheromata
Type
Stock SP
5 5 10 7
a Summarized
20 21 16 16
Saturated Unsaturated Saturated Unsaturated
from
% (range)
Kritchevsky
(9-50) (9-28) (8-24) (8-20)
(30).
0.02 0.02 1.62 0.02
Downloaded from https://academic.oup.com/ajcn/article-abstract/30/6/979/4650301 by University of Rhode Island user on 30 November 2018
Rice
Wheat
levels
conten
Serum
981
HYPERCHOLESTEREMIA
in rats”
Ch olesterol Starch’
IN
982
KRITCHEVSKY
TABLE
7 of semipurifled
Influence
diets
on lipid
metabolism
Serum
lipi da (mg/dI)
in baboons”
for
1 yr)
sudanophi.
Triglycerides
P/SC
activity’
S
‘
Bile
Cholesterol
salts
%
Fructose Sucrose Starch
162 ± 10 152 ± 9 156±8 151 ± 11 113±3
Glucose
Control
129 ± 11 116 ± 8 108±5 107 ± 7 78±4
11.2 6.7 9.3 6.2 0.02
0.56 0.61 1.33 0.81 1.67
3 3 2 2 15
a After Kritchevsky et al. (34). 40% carbohydrate; 25% casein; 15% cellulose; coconut oil; 5% salt mix; 1% vitamin mix. C (cholic and chenodeoxycholic)/secondary and lithocholic). d dpm/mg x 10’ in bile lipids of baboons given [5-3H] mevalonic acid.
TABLE Binding
8 of bile acids and salts by different types of fiber” Bile
acid
or salt’
Cholic Taurocholic
Glycocholic Chenodeoxycholic Taurochenodeoxy-
Alfalfa
Bran
19.9
10.2
6.9
1.4
Cellulose
Lignin
1 1 .5 24.8 15.1
3.8 18.2 9.8
3.0 1.0 1 .2 1 .9 0.0
43.7 22.1 22.5 23.3 25.4
14.9
21.4
0.2
25.2
10.4 1 1 .4 27.8
5 .4
0.2 0.7 4.7
17.4 30.9 52.6
cholic Glycochenodeoxy-
cholic Deoxycholic Taurodeoxycholic Glycodeoxycholic
hydrogenated (deoxycholic
14%
acids and their taurine and glycine conjugates. Table 8 shows that each binding substance exhibits specific binding affinities. In studying dietary effects one must be aware of the interactions among all dietary components. There are a number of papers in the literature which show that casein is more cholesteremic and/or atherogenic than soya protein for rabbits (41 42) or chickens (43). Carroll and Hamilton (44) confirmed these findings and showed that, in general, animal protein was more cholesteremic than vegetable protein. When fed as part of a diet containing defatted protein and dextrose, casein resulted in cholesterol levels of 208 mg/dl and soya protein of 70 mg/dl. When the carbohydrate was potato starch, cholesterol levels of rabbits fed either casein or soya protein were normal (50 ± 5 mg/dl). We have carried out an experiment (45) in which rabbits were fed a semipurified diet ,
3 .4 7.8
C After Story and Kritchevsky (39, 40). b50mg binder, 50 .tmoles bile acid or salt in 5 ml phosphate buffer (pH 7.0); incubated at 37 C for 2 hr. Values represent average of three experiments.
lithogenic diet reached a similar conclusion regarding hypercholesteremia caused by a semipurified diet. We have found (36) that rabbits fed a semipurified diet exhibited a lower cholic/deoxycholic acid ratio than did controls. Eastwood and Hamilton (37) studied the adsorption of bile acids and bile salts to various grains and found that the lignin component bound the test materials most avidly. Balmer and Zibversmit (38) studied the binding of sodium taurocholate to ground wheat, corn and oats as well as to other grains and found that the extent of binding was characteristic of the grain used. We (39, 40) have tested alfalfa, bran, cellulose and bignin for their ability to bind chobic, chenodeoxycholic, and deoxycholic ,
88 30 47 47 59
TABLE
9
Fiber-protein interactions fed semipurifled diets”
in rabbits
Protein5 Caaein
Fiber Serum
cholesterol
Soya Athero. matac
mg/dJ
Cellulose Wheat straw Alfalfa
402 ± 40 375 ± 42 193 ± 34
Serum
protein
cholesterol
Atheromats
ng/dI
1 .50 1 .03 0.63
248 ± 44 254 ± 35 159 ± 20
1.25
0.91 0.73
a After Story et al. (45). Diets contained 40% sucrose, 25% protein, 15% fiber, 14% hydrogenated coconut oil, 5 % salt mix, 1 % vitamin mix. (Arch plus thoracic)/2.
Downloaded from https://academic.oup.com/ajcn/article-abstract/30/6/979/4650301 by University of Rhode Island user on 30 November 2018
Cholesterol
fed
Bile Aortic
Diet’
(6 per group:
DIETARY
FIBER
IN
,
.
.
References
2.
3.
D . P . Some diseases characteristic of modern Western civilization . Brit . Med . M . 1: 274, 1973. TROWELL, H. C. Ischemic heart disease and dietary fiber. Am. J. Chin. Nutr. 25: 926, 1972. BURKZTI, D. P., A. R. P. WALKER AND N . S. BURKITr,
PAINTER.
Dietary
fiber
and
disease.
J.
Am.
Med.
Assoc. 229: 1068, 1974. 4 . HILL, M . J . Bacteria and the etiology of colonic cancer. Cancer 34: 815, 1974. 5. HILL. M. J. Colon cancer: a disease of fiber depletion or of dietary excess? Digestion 1 1 : 289, 1974. 6. SPILLER, G. A. , AND R. J. AMEN. Plant fibers in nutrition: need for better nomenclature. Am. J. Clin. Nutr. 28: 675, 1975. 7 . VAN S0E5T, P. J. Development of a comprehensive system of feed analyses and its application to forages. J. Animal Sci. 26: 119, 1967. 8. VAN SoEsr, P. J., AND R. W. MtQUEEN. The chemistry and estimation of fibre. Proc. Nutr. Soc. 32: 123, 1973. 9. SoumGAm, D. A. T. Fibre and other unavailable carbohydrates and their effects on the energy value ofthe diet. Proc. Nutr. Soc. 32: 131, 1973. 10. CAvn, T. L. The Saccharine Disease. Bristol: John Wright and Sons, Ltd., 1974. 1 1 . SPILLER, G. A. , AND R. J. AMEN. Dietary fiber in human nutrition. Food Sci. Nutr. 7: 39, 1975. 12. COWGILL, G. R., AND W. E. ANDERSON. Laxative effect of wheat bran and washed bran in healthy man. J. Am. Med. Assoc. 98: 1886, 1932. 13. COWGILL, G. R., AND A. J. SULLIVAN. Further studies on the use of wheat bran as a laxative . J. Am. Med. Assoc. 100: 795, 1933. 14. WILLIAMS, R. D., AND W. H. OLMSTED. The manner in which food controls the bulk of the feces. Ann. Int. Med. 10: 717, 1936. 15 . BURKITr, D. P., A. R. P. WALKER AND N. S. PMwraR. Effect of dietary fibre on stools and transit times, and its role in the causation of disease. Lancet 2: 1408, 1972. 16. PORTMAN, 0. W., AND P. Mup.pHY. Excretion of bile acids and ,8-hydroxysterols by rats. Arch. Biochem. Biophys. 76: 367, 1958.
17.
LEVEILLE, G. A., AND H. E. SAUBERLICH. Mechanism of the cholesterol-depressing effect of pectin in the cholesterol-fed rat. J. Nutr. 88: 209, 1966. 18. KRITCHEvSKY, D., AND S. A. TEPPER. Influence of isocaloric, isogravic diets on serum and liver lipids in rats. Nutr. Rep. Internat. 3: 283, 1971. 19. KRITCHEVSKY, D., R. P. CASEY AND S. A. Tm’PER. Isocaloric, isogravic diets in rats. II. Effect on cholesterol absorption and excretion. Nutr. Rep. Internat. 7: 61, 1973. 20. KRiTCHEvSKY, D. , S. A. TEPPER AND J. A. STORY. Isocaloric, isogravic diets in rats. III. Effect on non-nutritive fiber (alfalfa or cellulose) on cholesterol metabolism. Nutr. Rep. Internat. 9: 301, 1974. 21 . ERSHOFF, B. H. AND A. F. WELLS. Effects of gum guar, locust bean gum and carrageenan on liver cholesterol of cholesterol-fed rats . Proc . Soc. Exptl. Biol. Med. 1 10: 580, 1962. 22. ERSHOFF, B. F., AND A. F. WELLS. Effects of methoxyl content on anticholesterol activity of pectic substances in the rat. Exptl. Med. Surg. 20: 272, 1962. 23. RICCARDI, B. A., AND M. J. FARRENBACH. Effect of guar gum and pectin N.F. on serum and liver lipids of cholesterol fed rats. Proc. Soc. Exptl. Biol. Med. 124: 749, 1967. 24. VUAYAGOPALAN, P. , K. S. DEW AND P. A. KuRUP. Fibre content of different dietary starches and their effect on lipid levels in high fat-high
cholesterol
fed
rats.
Atherosclerosis
1 7:
156,
1973. 25
F. Sugars in cardiovascular disease . In: Sugars in Nutrition, edited by H. L. Sipple, K. W. McNutt. New York: Academic Press, Inc. , 1974, pp. 401. 26. MAmuR, K. S., M. A. KHANAND R. D. SHARMA. Hypocholesterolaemic effect of Bengal gram: A long-term study in man. Brit. Med. J. 1: 30, 1968. 27. TRUSWELL, A. S., AND R. M. KAY. Bran and blood-lipids. Lancet 1 : 367, 1976. 28. JENKINS, D. J. A., A. R. LEEDS, C. NEWTON AND J. H. CUMMINGS. Effect of pectin, guar gum, and wheat fibre on serum cholesterol. Lancet 1 : 1116, 1975. 29. LAMBERT, G. F., J. P. MILLER, R. T. OLSEN AND D. V. FROST. Hypercholesteremia and atherosclerosis induced in rabbits by purified high fat rations devoid of cholesterol. Proc. Soc. Exptl. Biol. Med. 97: 544, 1958. 30. KRITCHEvSKY, D. Experimental atherosclerosis in rabbits fed cholesterol-free diets. J. Atheroscier. Res. 4: 103, 1964. 31. KIUTCHEvSKY, D., AND S. A. TEPPER. Factors affecting atherosclerosis in rabbits fed cholesterolfree diets. Life Sci. 4: 1467, 1965. 32. Karrcssevsicy, D. AND S. A. TEPPER. Experimental atherosclerosis in rabbits fed cholesterol-free diets: influence of chow components. J. Atheroscler. Res. 8: 357, 1968. 33. Mooiu, J. H. The effectofthe type ofroughage in the diet on plasma cholesterol levels and aortic atherosis in rabbits. Brit. J. Nutr. 21: 207, 1967. 34. KarrcHEvsxy, D., L. M. DAVIDSON, I. L. Sisplao, H. K. Kus, M. KrFAGAWA, S. MALHOTRA, P. P. N, T. B. CLARICSON, I. BERSOHN AND P. A. .
GRANDE,
Downloaded from https://academic.oup.com/ajcn/article-abstract/30/6/979/4650301 by University of Rhode Island user on 30 November 2018
in which the protein was casein or soya protein and the fiber cellulose wheat straw, or alfalfa Within each protein group cellulose was the most cholesteremic and atherogenic fiber and alfalfa the least When the proteins were compared, soya-cellulose and soya-wheat straw were less chobesteremic and atherogenic than their casein counterparts. When the diets contained alfalfa, the two proteins were roughly equivalent (Table 9). The data presented here indicate that dietary fiber may play an important role in lipid metabolism and that we must be cognizant of the complex interactions of all cornponents of the diet.
1.
983
HYPERCHOLESTEREMIA
984
KRITCHEVSKY 40.
STORY,
the
41
42.
43.
44.
45.
.
J. A.,
binding
D. Kntchevsky. Comparison of bile acids and bile salts in types offiber. J. Nutr. 106: 1292,
AND
of various
vitro by several 1976. NEWBURGH, L. H., AND T. L. SQUIER. High protein diets and arteriosclerosis in rabbits: a preliminary report. Arch. Internat. Med. 26: 38, 1920. MEEKER, D. R., AND H. D. KESTEN. Experimental atherosclerosis and high protein diets . Proc. Soc. Exptl. Biol. Med. 45: 543, 1940. KRITCHEVSKY, D. , R. R. KOLMAN, R. M. GuuMACHER AND M. Foaar.s. Influence of dietary carbohydrate and protein on serum and liver cholesterol in germ-free chickens. Arch. Biochem. Binphys. 85: 444, 1959. CARROLL, K. K., AND R. M. G. HAMiLTON. Effects of dietary protein and carbohydrate on plasma cholesterol levels in relation to atherosclerosis.J. Food Sci. 40: 18, 1975. STORY, J. A., S. A. TEPPER AND D. KRJTCHEVSKY. Atherosclerosis in rabbits fed cholesterol-free diets: effect of protein and fiber. Federation Proc. 35: 294, 1976. (abstr.).
Downloaded from https://academic.oup.com/ajcn/article-abstract/30/6/979/4650301 by University of Rhode Island user on 30 November 2018
D. WINTER. Lipid metabolism and experimental atherosclerosis in baboons: influence of cholesterol-free, semi-synthetic diets. Am. J. Clin. Nutr. 27: 29, 1974. 35. Kyti, P. A., AND I. A. D. BOUCHIER. Cholesterol metabolism in rabbits with oleic acid-induced cholelithiasis. Proc. Soc. Exptl. Biol. Med. 141 : 846, 1972. 36. KarrcHEvsKY, D., S. A. TEPPER, H. K. Kn.i, D. E. MOSES AND J. A. SToRY. Experimental atherosclerosis in rabbits fed cholesterol-free diets . 4. Investigation into the source of cholesteremia. Exptl. Mol. Pathol. 22: 11, 1975. 37. EASTWOOD, M. A. , AND D. HAMILTON. Studies on the adsorption of bile salts to non-absorbed components of diet. Biochim. Biophys. Acta 152: 165, 1968. 38. BALMER, J. , AND D. B. ZILVERSMIT. Effects of dietary roughage on cholesterol absorption, cholesterol turnover and steroid excretion in the rat. J. Nutr. 104: 1319, 1974. 39 . KRJTCHEVSKY, D . , AND J. A . STORY. Binding of bile salts in vitro by non-nutritive fiber. J. Nutr. 104: 458, 1975.
