43
Atherosclerosis, 29 (1978) 43-51 @ Elsevier/North-Holland Scientific Publishers, Ltd.
LOW-FAT DIET VERSUS LOW-CARBOHYDRATE DIET IN THE TREATMENT OF TYPE IV HYPERLIPOPROTEINAEMIA
D. SOMMARIVA, L. SCOTT1 and A. FASOLI Cattedra di Terapia Medica Sistematica, Milan-Vialba (Italy)
University
of Milan, “L. Sacco” Hospital,
(Received 13 June, 1977) (Revised, received 13 September, 1977) (Accepted 14 September, 1977)
Summary
The response to dietary management was studied in 24 hypertriglyceridaemic out-patients. Fourteen patients were kept on a diet low in fat and cholesterol and high in polyunsaturated fatty acids; 10 of these patients subsequently followed a period of low-carbohydrate diet. At the end of the first period a significant decrease of serum triglyceride, cholesterol and &lipoproteins was observed; after the second feeding period no substantial change of serum lipoprotein pattern occurred. Ten patients were given a low-carbohydrate diet that produced a significant fall of the levels of triglycerides and pre-fl-lipoproteins. Six of these subjects continued the experiment with the low-fat diet; during this period a further trend toward reduction of serum triglyceride, cholesterol and /3-lipoproteins was observed which, however, was not statistically significant. We conclude that serum triglyceride levels can be lowered both by a lowcarbohydrate diet and by a low-fat diet, but the latter has the advantage of also producing a significant fall of serum cholesterol and P-lipoproteins.
Key words:
Low-carbohydrate pro teinaemia
diet -
Low-fat
diet -
Triglyceride
-
Type IV hyperlipo-
Introduction Cmrmal &lrliPC r1-1.51 m&lnnre nf %a“YA”“b rtvnna nncitivn onrrnla_ irr.rr“YUU1U” LA A.“, haxm 1AU.U n*nrentcarl “L u y”“‘ “‘.” .,VAIUIU yLY0”‘vu.A V.IxAYllru tion between plasma triglyceride and atherosclerosis. These reports raise the possibility that hypertriglyceridaemia may be a risk factor for the development of atherosclerotic lesions as important as hypercholesterolaemia. In the
44
primary prevention of atherosclerosis it is then necessary to control, as strictly as possible, the serum triglyceride levels with an appropriate dietary and, perhaps, drug therapy. In endogenous hypertriglyceridaemia the reduction of dietary carbohydrate intake is followed by a significant decrease of serum triglyceride; such effect is also evident after a marked reduction of total caloric intake, probably because hypocaloric diets are low both in carbohydrate and in fat. In 1974 Chait et al. [16] proposed a new approach to dietary management of type IV hyperlipidaemia based on a diet with a high ratio of polyunsaturated to saturated fatty acids. This diet is commonly used in the management of hyper-fi-lipoproteinaemia. The effectiveness of the diet in lowering serum triglyceride levels would make it useful in the treatment of all the commonest forms of hyperlipidaemia. To test the effectiveness of this approach, we compared the results obtained in a series of patients with hyperpre-fl-lipoproteinaemia by a low-carbohydrate diet or by a low-fat diet rich in polyunsaturated fatty acids. Material and Methods Twenty-four out-patients were studied; all had fasting blood levels of triglycerides higher than 170 mg/lOO ml while on a regular diet, serum cholesterol was in the normal range (lower than 250 mg/lOO ml) in 23 patients and higher than normal in 1 patient (298 mg/lOO ml). The range of age of the patients was 27-66 years, with a mean of 45.6; 20 patients were males, 4 were females. None of the patients had overt diabetes; 4 of them displayed a reduced tolerance to oral glucose loading and were, at the same time, slightly to moderately over-weight (lo-20% above ideal body weight), 4 other patients, who, too, were moderately over-weight (lo-20% above i.b.w.) had a normal glucose tolerance. In all patients, serum cholesterol [ 171 and triglyceride [ 181 were determined. Serum lipoprotein analysis was performed by electrophoresis on agarose gel [ 191 at the beginning and at the end of each dietary period. The lipoproteins were quantitatively determined according to the method of Hatch et al. 1201, the internal standardization procedure being followed against the harmonic mean of serum cholesterol and serum triglyceride factors. For the purpose of this study, hyperlipoproteinaemia was classified as type IV if, before treatment, the pre-fl fraction was higher than 150 mg/lOO ml and the 0 fraction lower than 700 mg/lOO ml. According to these criteria 1 patient (cholesterol 298 mg/lOO ml) was borderline between types IV and IIb. In 7 patients the hyperlipoproteinaemia had a familial character (2 kinships); in the other 17 patients hyperlipoproteinaemia was of the non-familial idiopathic type. In 12 patients the period of dietary management was preceded by a period of study of 20-30 days while they were on normal diet. Two types of diet were. compared. In the first, carbohydrate provided 43% (15% of total carbohydrates were mono- and disaccharides, 6% fructose), fat 38% and protein 19% of total calories. The other had a low cholesterol (less than 300 mg/day) and relatively high polyunsaturated fatty acid content (P/S = 1.2): carbohydrate accounted for 59% (19% of total carbohydrates were
45
mono- and disaccharides, 10% fructose), fat 23% and protein 18% of total calories. The diet prescribed to each patient had about the same caloric content as his usual diet (30 Cal/kg b.w., on the average). Ten patients were kept on the low-fat diet for the first month, then on the low-carbohydrate diet for the second month. Six patients followed a reversed sequence with the low-carbohydrate diet preceding the low-fat diet. Four patients followed a low-carbohydrate diet for 1 month and 4 a low-fat diet for 1 month. The adherence of the patients to the assigned diet was investigated in 10 cases by asking the participants to write down a detailed history throughout the period of study. Statistical analysis was performed by Student’s “t” test and correlation analysis (Pearson’s “r”).
TABLE 1 CHANGE DIET
OF LIPOPROTEIN
PATTERN
IN 12 CASES DURING THE FIRST PERIOD WITH “USUAL”
Values are expressed in mg/lOO ml of serum.
Triglycerides a
SD’-
Cholesterol a SD P-Lipoproteins a SD Pre-p-Lipoproteins a SD a-Lipoproteins a SD
Before
After
96 change
P
t
316.92 110.42 236.33 36.89 539.50 166.99 366.67 120.44 287.83 70.24
269.42 16.83 241.08 33.76 593.17 130.18 301.58 135.55 330.50 128.03
-15.0
N.S.
1.302
+4.5
N.S.
-0.715
+10.0
N.S.
-0.864
-17.7
N.S.
0.992
+14.a
N.S.
1.371
a Meanfasting values. b Standard deviation.
TABLE 2 RESULTS
OBTAINED
IN 14 PATIENTS DURING THEnFIRST PERIOD OF LOW-FAT
DIET
Values are expressed in mg/lOO ml of serum.
Triglycerides a
SD” Cholesterol a SD P-Lipoproteins a SD PreQ-Lipoproteins a SD a-Lipoproteins SD a Mean fasting values. b Standard deviation.
Before
After
% change
P
t
307.00 136.11 237.64 39.16 588.00 135.05 285.70 122.30 334.77 153.46
190.14 117.06 206.57 44.40 430.85 103.62 205.70 118.95 271.17 93.22
-38.1
P > 0.05 N.S. N.S.
-11.7 -24.8 -19.2 -15.9
1Pl’E
‘S’N
P9L.O
ZO’O>
961’8
‘S’N
L&6.1
‘S’N
9LO’O
I’L-
6’6E-
CO-
8’6
0’9Z-
09’9ZE
Ot’EOE
LL’ZG
TE’TL
OI’OEP
O&‘PSZ
99’291
lP’T61
OO’EPP
09.6&P
Z9’6ET
87’861
01’LGZ
OE’E&Z
96’82
PS’VP
OZ’PEE
OT’SPZ
6P”GOI
6I’TOT
‘UIIIIOS
JO urn
OO~/%LLI
“!
passardxa
are san@~ 3NIa33d
3.LVXaAHOB?3V3-M0?
A0
aOIZI3d
.LSXIId
3H.L
ZI3LrIV
SJN3ILVd
01
NI
a3NIVLL80
SATflS32I
ayl uo squayd ay7 30 spjdg UIIU~S30 sanieA a%laAv ayl sazuwuurns p alqB& *(g alqeJ,) asaa.wu! pn?~o$ pual$ I? paMoys su!ac)ordodg-n, aqq q%Ioy?le ‘pant-w0 Sp!dg wnctas 30 saryea a&aAe ayl u! aihya ~uE~~~J!u~~!s ou qq~ Suy;mp $a!p a$r?lprlyoqnX+Mol 30 poilad B paMoIIo3 6Iluanbasqns squayd asay? 30 uaA ‘(z alql?&) ~~~_ITxH~uS!Slou qnq ‘a%raAv ay? uo paDnpa1 os~t? alaM su!alold -odg-x, pue su!a$ordodg-d_ard tsu!alordod!l-g’ pun IoraqsaIoya ‘sap~~a~b~f3~q u.nUas 30 asI?araap I)UX?XJ~L@S I.?paMoys !Jayp ~E?~-MOI ay? uaA@ s$uayd pi ayJ, ‘pahxasqo alah sp!diI tunas 30 suoyn~an~ ‘po!lad ~uaur~ear~a~d ay? %.+na *uoy?sn@A--lapun ~y5_ua@s B 03 sn paI uoy@$saAuI hwa!p ayl bq pau!e?qo BJt2p ayq uo sa!JoIw ayq 30 uoy2InaIw aqq qt?y? $no paInr aq !jouut?~ 71 ‘&3AaMOH‘+oIwodLy 61$$h$ fIIsnsn SBM paurns -uo3 QaAya33a qa!p ayq qt2yq urJ!3uoD ol pauraas y@aM 6poq aq3 30 pualq ayq ‘plauail UI *paI.@ssB CJI?~?uey? JaMoI SI?M‘guayd auo u! IdaDxa ‘ay’e!)u! +IOIT?:, ~09 ay& +(&?p rad ~oqocyt? 30 1u1 001 qnoqe) au!~ 30 sJunoure ~aS.niy ‘u?y.j no3 AI ad& ITXJLLIE~yg!~ ‘y.Iayd It?nsn SBM SE ‘pamnsuo3 ‘t?!urasu!aloldod!Inad6y au0 t(bt?p rad 1oyo31~ ~$01 30 1~ op ucy? ssal) aura 30 squnoure ~~EXXIS ‘bpn)s 30 pollad ay$ %u!mp ‘paurnsuo3 pey s$ua!qt?d uaAas *paq!rDsand uey? (aSIaAt? ayq uo oj()~) Jaq$Lj SI?Mqa!p a~eJp~yoqrt?3-Mo~ 30 poilad ayq %uynp pasnpor$u! aprpbyoqni9 30 a8quawad ay? aI!yM ‘6173gs arour paMoIIo3 uaaq pey la!p qJ-Mo1 aycj y2yl pa?lnsal7! ‘poo3 30 puiy aqq 0) &uprow~ aye+Il ~!ro1~3 ay? 30 sysS@uv aycj urol3 :qInsal Bu!~o1103 ayl aAe%!ja!p ayq oq aauaraypv ay? Zlu!yaay9 103 uogt@~saAu! kela!p aqt~ ‘6pnqs ayq u! papnlw! s?uayEd ayq 30 01 UI ‘sp!d!I tunas 30 saik?ya ayl y$+ paqyalroa 6~y.n2~~3~uEZ~s lou seM ssol c@$aM ayl ssaIayl.raAaN ‘(*S*N =: a) laip y23-~01 ayq laq3t2 2 00~~ pw (g)‘() > a) av2rpdyoqJw u! MO1 polnad Ila’ya!p ayl 30 pua aycj JE a%raAe ayq uo B 09~ :paurwo SSOIc@!aM y.@gs B bpnqs ayl 30 poyad ayy Su!rna
LP
LIPIDS
a Mean
values.
deviation.
fasting
b Standard
99.81
312.16
a
ol-Lipoproteins
SD
174.80
SD
401.00
a
596.50
Pm-~-Lipoproteins
a
23.32
264.83
97.90
322.33
138.17
a
a
Before
SD
@-Lipoproteins
SD
Cholesterol
SD b
Triglycerides
AFTER
THE
85.82
323.33
132.83
291.83
145.04
599.33
50.59
250.17
81.19
257.67
After
diet
ml of serum.
Low-carbohydrate
in mg/lOO
IN 6 PATIENTS
are expressed
SERUM
Values
5
TABLE
+3.6
-27.2
+0.5
-5.5
-20.1
% change
FIRST
N.S.
0.1
N.S.
N.S.
0.1
P
PERIOD
> P
> P
OF
> 0.05
> 0.05
-0.320
2.395
-0.034
0.888
2.447
t
LOW-CARBOHYDRATE
85.82
323.33
132.83
291.83
145.04
599.33
50.59
250.17
81.19
257.67
Before
Low-fat
AND
diet
THE
96.91
325.00
168.60
288.00
197.96
449.33
59.88
218.67
103.68
226.83
After
SECOND
OF
+0.5
-1.3
-25.0
-12.6
-12.0
% change
PERIOD
N.S.
N.S.
0.1
N.S.
N.S.
P
LOW-FAT
> P
> 0.05
DIET
4.038
0.065
2.256
1.215
0.741
t
49
low-carbohydrate diet; the levels of triglycerides and of pre-P-lipoproteins fell significantly, while the other lipid fractions remained practically unchanged. Six of these subjects continued the experiment with the low-fat diet: during this period we observed a further, but not statistically significant, reduction of serum levels of triglycerides, cholesterol and P-lipoproteins (Table 5). Discussion A number of primary and secondary prevention trials have presented evidence that lowering serum lipids by diet or drugs may reduce the incidence of, and the mortality from, atherosclerotic disease [ 21-281. Serum triglycerides, which are considered to be an independent risk factor for the development of atherosclerosis, can be decreased by a diet low in carbohydrate content [29331. A triglyceride-lowering effect of a diet with a high ratio of polyunsaturated to saturated fatty acids (P/S) has also been documented [ 34-391. In a long-term study on a group of hyperlipidaemic patients and non-obese normal men, Wilson et al. [40], using a high P/S diet, found the fall in serum triglyceride to be 11.7% after 6 months. However, the decrease of serum triglyceride was more marked in those patients who had reduced their carbohydrate intake and their total caloric intake. Hall et al. [ 411 showed that serum triglyceride levels in hypertriglyceridaemic patients were significantly reduced after 1 year of management with a lowfat diet containing highly polyunsaturated fats. Chait et al. [ 161, using lo-day feeding periods and maintaining constant the total carbohydrate and lipid content of the diet, showed that the mean serum level of triglycerides was 35% lower during consumption of a high P/S diet than during a diet rich in saturated fatty acids. The magnitude of the decrease of triglycerides was strongly correlated with the levels of triglycerides during the period when the saturated-fat diet was given. Different results were reported by Hodges et al. [ 421, who made a study on 24 young couples sub-divided into 4 groups given a diet high in saturated fat or a diet high in polyunsaturated fat for 20 weeks. They did not observe any significant difference in the levels of serum triglycerides, probably because of the wide fluctuations of the values in each group, although serum cholesterol was reduced after the diet rich in polyunsaturated fat. Moreover, they did not find any relation between the serum triglyceride levels and the gain or loss of weight. The results of the present study show that both a diet low in carbohydrate and a diet low in lipid content produced a significant decrease of serum triglyceride levels and that this effect was independent of weight changes. As expected, a diet with a low content of fat and cholesterol and a relatively high content of polyunsaturated fatty acids also caused a significant decrease of serum cholesterol and /3-lipoproteins; this effect was not present after treatment with the low-carbohydrate diet. When the experiment with the low-carbohydrate feeding was followed by a period of low-fat diet, no substantial change of the serum lipoprotein pattern was observed, though there was a trend to a further reduction of triglycerides, cholesterol and P-lipoproteins.
50
When an isocaloric diet low in carbohydrate was given to patients previously treated with a low-fat diet, the average values of serum lipids remained unmodified as compared with the values observed at the end of the first dietary period. We may conclude that the dietary management of type IV hyperlipoproteinaemia by a low-carbohydrate diet or by a low-fat diet is effective in decreasing the serum levels of triglycerides in out-patients living in their usual environment. On the whole, the diet low in fat content showed a greater hypolipidaemic effect and had the further advantage of producing a significant fall of serum cholesterol and P-lipoproteins; this effect is of particular relevance for the prevention of atherosclerosis. Therefore the diet with a low content of fat, that also appeared to be more agreeable to our patients, seems to be an effective means in the treatment of the commonest forms of hyperlipoproteinaemia. It must be pointed out that appreciable results have been obtained in our patients with a diet having a lower ratio of polyunsaturated to saturated fatty acids than suggested by other authors. References 1 Albrink, 2 3 4 5
6 7 8 9
10 11
12 13
M.J. and Man, E.B., Serum lipids, hypertension
and coronary
artery disease, Am. J. Med., 31
(1961) 4. Hayes, D. and Neill, D.W., Serum cholesterol and triglycerides in ischemic heart disease, Clin. Sci.. 26 (1964) 185. Fasoli, A.. Ischaemic heart disease and peripheral arterial pathology, G. Arterioscl.. 4 (1966) 177. Fasoli, A., Lipoprotei’nes du s&urn. ath&osclCrose et thrombose, Arch. Mal. Coeur. 3 (1967) 23. Blankenhom. D.H., Chin, H.P. and Lau, F.Y.K.. Ischemic heart disease in young adults. Metabolic and angiographic diagnosis and the prevalence of type IV hyperlipoproteinemia, Ann. Intern. Med., 69 (1968) 21. Heinle, R.A.. Levy. R.I. and Fredrickson, D.S., Lipid and carbohydrate abnormalities in patients with angiographically demonstrated coronary artery disease. Am. J. Cardiol., 24 (1969) 178. Kannel, W.B., Castelli, W.P., Gordon, T. and McNamara, P., Serum cholesterol, lipoproteins and the risk of coronary heart disease (the Framingham study), Ann. Intern. Med.. 74 (1971) 1. Patterson, D. and Slack, J., Lipid abnormalities in male and female survivors of myocardial infarction and their first-degree relatives, Lancet, i (1972) 393. Fasoli. A., Gandini, R., Costantino, D., Sommariva, D., Cremonesi. G. and Adelasco. L.. Lipoproteine ed aterosclerosi: la relazione tra lipoproteine sieriche ed evoluzione clinica di pazienti con manifestazione di arteriopatia aterosclerotica. In: Atti de1 1” Simposio di Fisiopatologia della Nutrizione e Dietetica Clinica. R. Patron, Bologna, 1972. P. 147. Gertler, M.M., Leetma. H.E.. Saluste. E., Rosenberger, J.L. and Guthrie. R.G.. Ischemic heart disease: insulin, carbohydrate and lipid interrelationship. Circulation, 46 (1972) 103. Gustafson. A., Elmfeldt. D., Wilhelmsen. L. and Tibblin. G., Serum lipids and lipoproteins in men after myocardial infarction compared with representative population sample, Circulation. 46 (1972) 709. Carlson. L.A. and Bottiger, L.E.. Ischemic heart disease glyceride and cholesterol, Lancet, i (1972) 865. Ballantyne, D. and Lawrle, T.D.V., Hyperlipoproteinemia
in relation
to fasting values of plasma tri-
and peripheral
vascular disease, Clin. Chim.
Acta, 47 (1973) 269. 14 Goldstein, J.L., Hazzard, W.R., Schrott. H.G.. Bierman, E.L. and Motulsky. A.G., Hyperlipidemia in coronary artery disease. Lipid levels in 500 survivors of myocardial infarction, J. Clin. Invest.. 52 (1973) 1533. 15 Block, A., Dinsmore. R.E. and Lees, R.S., Coronary arteriographic findings in type II and type IV hyperlipoproteinemia, Lancet, i (1976) 928. 16 Chait, A., Onitiri. A.. Nicoll. A., Rabaya. E.. Davies, J. and Lewis, B.. Reduction of serum triglyceride levels by polyunsaturated fat. Studies on the mode of action and on very low density lipoprotein composition, Atherosclerosis, 20 (1974) 347. 17 Babson, A.L., Shapiro, P.O. and Phillips, G.E.. A new assay for cholesterol and cholesterol esters which is not affected by bilirubin. Clin. Chim. Acta. 7 (1962) 800.
51 18
Eggstein,
19
(1966) Noble,
20
21 22
23 24
25 26
27 28 29 30
31 32
M., Eine
267. R.P..
n&e
Electrophoretic
Bestimmung separation
der Neutralfette of plasma
in Blutserum
lipoproteins
und Gewebe.
in agarose
Klin. Wschr.,
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gel. J. Lipid Res., 9 (1968)
693. Hatch, F.T., Lindgren. F.T., Adamson, C.L., Jensen, L.C., Won& A.W. and Levy, R.I.. Quantitative agarose gel electrophoresis of plasma lipoproteins; a simple technique and two methods for standardization, J. Lab. Clin. Med., 81 (1973) 946. Leren, P., The effect of plasma cholesterol-lowering diet in male survivors of myocardial infarction, Acta Med. &and.. Suppl. 466 (1966) 1. Christakis, G., Rinzler. S.H.. Archer, M., Winslow, G.. Jampel. S., Stephenson, J., Friedman, G., Fein, H., Krauss, A. and James, G.,Theanticoronary club. A dietary approach to the prevention of coronary heart disease -A seven year report, Am. J. Publ. Hlth, 56 (1966) 299. Rinzler, S.H., Primary prevention of coronary heart disease by diet, Bull. N.Y. Acad. Med., 44 (1968) 936. Turpeinen, 0.. Miettinen, M., Karvonen. M.J.. Roine, P. Pekkarinen. M.. Lehtsuo, E.J. and Allvirta. P.. Dietary prevention of coronary heart disease: long-term experiment, Am. J. Clin. Nutr.. 21 (1968) 255. The National Diet Heart Study Research Group with the Executive Committee on Diet and Heart Disease, The national-diet heart study final report, Circulation. 37. Suppl. 1 (1968) 1. Dayton, S., Pearce, M.L.. Hashimoto. S., Dixon, W.J. and Tomiyasu, U., A controlled clinical trial of a diet high in unsaturated fat in preventing complications of atherosclerosis, Circulation, 40, Suppl. 2 (1969) 1. Miettinen. M.. Turpeinen, O., Karvonen, M.J., Elosuo, R. and Paavilainen, E., Effect of cholesterol lowering diet on mortality from coronary heart disease and other causes, Lance& ii (1972) 835. Leren, P., The Oslo diet heart study - 2 year report, Circulation, 42 (1972) 935. Jepson, E.M., Fabmy. M.F.I., Torrens. P.E., Billiioria, J.D. and McLagan, N.F.. Treatment of essential hyperlipidaemia, Lancet, ii (1969) 1315. Fredrickson, D.S. and Levy, R.I., Familial hyperlipoproteinemias. In: J.B. Stanbury. J.B. Wyngaarden and D.S. Fredrickson (Eds.). The Metabolic Basis of Inherited Diseases, 3rd ed.. McGraw-Hill, New York, 1972, p. 545. Murphy, B.F.. Management of hyperlipidemias. J. Am. Med. Assoc., 230 (1974) 1683. Smith, L.K., Luepker, R.V.. Rothchild, S.S., Gillis, A., Kochman, L. and Warbasse. J.R.. Management of type IV hyperlipoproteinemia. Evaluation of practical clinical approaches, Ann. Intern. Med., 84
(1976) 22. Rouffy, J.. Dreux. C.. Dakkak, R. and Loeper, J., Les hypertriglyceriddmies essentielles et leur traitement, Rev. M6d., 9 (1976) 523. 34 Kinsell. L.W., Partridge, J., Baling, L., Margen. S. and Michaelis. G., Dietary modification of serum 33
cholesterol and phospholipid levels, J. Clin. Endocr., 12 (1952) 909. Ahrens, Jr., E.H.. Hirsh, J., Insull. Jr., W.. Tsaltas. T.T., Blomstrand. R. and Peterson. T.L., The influence of dietary fats on serum lipid levels in man. Lancet, i (1957) 943. 36 .Kinsell. L.W., Michaelis, G.. Walker, G., Wheeler, P., Splitter, S. and Flynn, P.. Dietary linoleic acid and linoleate. Effects in diabetic and in non-diabetic subjects with and without vascular disease, 35
Diabetes, 8 (1959) 179. Antonis. A. and Bersohn, I.. The influence of diet on serum triglyceride in South African white and Be&u prisoners, Lance& i (1961) 3. 38 Beveridge, J.M.R., Jagannathan, S.N. and Cannel, W.F., The effect of the type and amount of dietary fat on the level of plasma triglyceride in human subjects and in the postabsorptive state. Can. J. Biothem. Physiol.. 42 (1964) 999. 39 Bagdade. J.D., Hazzard. W.R. and Carl@ J., Effect of unsaturated dietary fat on plasma lipoprotein lipase activity in normal and hyperlipidemic states, Metabolism, 19 (1970) 1020. 40 Wilson, W.S., Hulley. S.B., Burrows, M.I. and Nichaman. M.E., Serum lipid and lipoprotein response to the American Heart Association fat-controlled diet, Am. J. Med., 51 (1971) 491. 41 Hall, T., Stamler, J., Cohen, D.B.. Moionnier, L., Epstein, M.B.. Be&son, D.M.. Whipple, I.T. and Catching, S.. Effectiveness of a low saturated fat, low cholesterol, weight reducing diet for the control of hypertriglyceridaemia. Atherosclerosis. 16 (1972) 389. 42 Hodges. E.S., Salel. A.F., Dunkley. W.L., Zelis. R.. McDonagh, P.F., Clifford. C., Hobbs, R.K., Smith, L.M., Fan, A., Mason, D.T. and Lykke. C.. Plasma lipid changes in young adult couples consuming polyunsaturated meats and dairy products, Am. J. Clin. Nutr.. 28 (1975) 1126. 37
Atherosclerosis, 29 (1978) 43-51 @ Elsevier/North-Holland Scientific Publishers, Ltd.
LOW-FAT DIET VERSUS LOW-CARBOHYDRATE DIET IN THE TREATMENT OF TYPE IV HYPERLIPOPROTEINAEMIA
D. SOMMARIVA, L. SCOTT1 and A. FASOLI Cattedra di Terapia Medica Sistematica, Milan-Vialba (Italy)
University
of Milan, “L. Sacco” Hospital,
(Received 13 June, 1977) (Revised, received 13 September, 1977) (Accepted 14 September, 1977)
Summary
The response to dietary management was studied in 24 hypertriglyceridaemic out-patients. Fourteen patients were kept on a diet low in fat and cholesterol and high in polyunsaturated fatty acids; 10 of these patients subsequently followed a period of low-carbohydrate diet. At the end of the first period a significant decrease of serum triglyceride, cholesterol and &lipoproteins was observed; after the second feeding period no substantial change of serum lipoprotein pattern occurred. Ten patients were given a low-carbohydrate diet that produced a significant fall of the levels of triglycerides and pre-fl-lipoproteins. Six of these subjects continued the experiment with the low-fat diet; during this period a further trend toward reduction of serum triglyceride, cholesterol and /3-lipoproteins was observed which, however, was not statistically significant. We conclude that serum triglyceride levels can be lowered both by a lowcarbohydrate diet and by a low-fat diet, but the latter has the advantage of also producing a significant fall of serum cholesterol and P-lipoproteins.
Key words:
Low-carbohydrate pro teinaemia
diet -
Low-fat
diet -
Triglyceride
-
Type IV hyperlipo-
Introduction Cmrmal &lrliPC r1-1.51 m&lnnre nf %a“YA”“b rtvnna nncitivn onrrnla_ irr.rr“YUU1U” LA A.“, haxm 1AU.U n*nrentcarl “L u y”“‘ “‘.” .,VAIUIU yLY0”‘vu.A V.IxAYllru tion between plasma triglyceride and atherosclerosis. These reports raise the possibility that hypertriglyceridaemia may be a risk factor for the development of atherosclerotic lesions as important as hypercholesterolaemia. In the
44
primary prevention of atherosclerosis it is then necessary to control, as strictly as possible, the serum triglyceride levels with an appropriate dietary and, perhaps, drug therapy. In endogenous hypertriglyceridaemia the reduction of dietary carbohydrate intake is followed by a significant decrease of serum triglyceride; such effect is also evident after a marked reduction of total caloric intake, probably because hypocaloric diets are low both in carbohydrate and in fat. In 1974 Chait et al. [16] proposed a new approach to dietary management of type IV hyperlipidaemia based on a diet with a high ratio of polyunsaturated to saturated fatty acids. This diet is commonly used in the management of hyper-fi-lipoproteinaemia. The effectiveness of the diet in lowering serum triglyceride levels would make it useful in the treatment of all the commonest forms of hyperlipidaemia. To test the effectiveness of this approach, we compared the results obtained in a series of patients with hyperpre-fl-lipoproteinaemia by a low-carbohydrate diet or by a low-fat diet rich in polyunsaturated fatty acids. Material and Methods Twenty-four out-patients were studied; all had fasting blood levels of triglycerides higher than 170 mg/lOO ml while on a regular diet, serum cholesterol was in the normal range (lower than 250 mg/lOO ml) in 23 patients and higher than normal in 1 patient (298 mg/lOO ml). The range of age of the patients was 27-66 years, with a mean of 45.6; 20 patients were males, 4 were females. None of the patients had overt diabetes; 4 of them displayed a reduced tolerance to oral glucose loading and were, at the same time, slightly to moderately over-weight (lo-20% above ideal body weight), 4 other patients, who, too, were moderately over-weight (lo-20% above i.b.w.) had a normal glucose tolerance. In all patients, serum cholesterol [ 171 and triglyceride [ 181 were determined. Serum lipoprotein analysis was performed by electrophoresis on agarose gel [ 191 at the beginning and at the end of each dietary period. The lipoproteins were quantitatively determined according to the method of Hatch et al. 1201, the internal standardization procedure being followed against the harmonic mean of serum cholesterol and serum triglyceride factors. For the purpose of this study, hyperlipoproteinaemia was classified as type IV if, before treatment, the pre-fl fraction was higher than 150 mg/lOO ml and the 0 fraction lower than 700 mg/lOO ml. According to these criteria 1 patient (cholesterol 298 mg/lOO ml) was borderline between types IV and IIb. In 7 patients the hyperlipoproteinaemia had a familial character (2 kinships); in the other 17 patients hyperlipoproteinaemia was of the non-familial idiopathic type. In 12 patients the period of dietary management was preceded by a period of study of 20-30 days while they were on normal diet. Two types of diet were. compared. In the first, carbohydrate provided 43% (15% of total carbohydrates were mono- and disaccharides, 6% fructose), fat 38% and protein 19% of total calories. The other had a low cholesterol (less than 300 mg/day) and relatively high polyunsaturated fatty acid content (P/S = 1.2): carbohydrate accounted for 59% (19% of total carbohydrates were
45
mono- and disaccharides, 10% fructose), fat 23% and protein 18% of total calories. The diet prescribed to each patient had about the same caloric content as his usual diet (30 Cal/kg b.w., on the average). Ten patients were kept on the low-fat diet for the first month, then on the low-carbohydrate diet for the second month. Six patients followed a reversed sequence with the low-carbohydrate diet preceding the low-fat diet. Four patients followed a low-carbohydrate diet for 1 month and 4 a low-fat diet for 1 month. The adherence of the patients to the assigned diet was investigated in 10 cases by asking the participants to write down a detailed history throughout the period of study. Statistical analysis was performed by Student’s “t” test and correlation analysis (Pearson’s “r”).
TABLE 1 CHANGE DIET
OF LIPOPROTEIN
PATTERN
IN 12 CASES DURING THE FIRST PERIOD WITH “USUAL”
Values are expressed in mg/lOO ml of serum.
Triglycerides a
SD’-
Cholesterol a SD P-Lipoproteins a SD Pre-p-Lipoproteins a SD a-Lipoproteins a SD
Before
After
96 change
P
t
316.92 110.42 236.33 36.89 539.50 166.99 366.67 120.44 287.83 70.24
269.42 16.83 241.08 33.76 593.17 130.18 301.58 135.55 330.50 128.03
-15.0
N.S.
1.302
+4.5
N.S.
-0.715
+10.0
N.S.
-0.864
-17.7
N.S.
0.992
+14.a
N.S.
1.371
a Meanfasting values. b Standard deviation.
TABLE 2 RESULTS
OBTAINED
IN 14 PATIENTS DURING THEnFIRST PERIOD OF LOW-FAT
DIET
Values are expressed in mg/lOO ml of serum.
Triglycerides a
SD” Cholesterol a SD P-Lipoproteins a SD PreQ-Lipoproteins a SD a-Lipoproteins SD a Mean fasting values. b Standard deviation.
Before
After
% change
P
t
307.00 136.11 237.64 39.16 588.00 135.05 285.70 122.30 334.77 153.46
190.14 117.06 206.57 44.40 430.85 103.62 205.70 118.95 271.17 93.22
-38.1
P > 0.05 N.S. N.S.
-11.7 -24.8 -19.2 -15.9
1Pl’E
‘S’N
P9L.O
ZO’O>
961’8
‘S’N
L&6.1
‘S’N
9LO’O
I’L-
6’6E-
CO-
8’6
0’9Z-
09’9ZE
Ot’EOE
LL’ZG
TE’TL
OI’OEP
O&‘PSZ
99’291
lP’T61
OO’EPP
09.6&P
Z9’6ET
87’861
01’LGZ
OE’E&Z
96’82
PS’VP
OZ’PEE
OT’SPZ
6P”GOI
6I’TOT
‘UIIIIOS
JO urn
OO~/%LLI
“!
passardxa
are san@~ 3NIa33d
3.LVXaAHOB?3V3-M0?
A0
aOIZI3d
.LSXIId
3H.L
ZI3LrIV
SJN3ILVd
01
NI
a3NIVLL80
SATflS32I
ayl uo squayd ay7 30 spjdg UIIU~S30 sanieA a%laAv ayl sazuwuurns p alqB& *(g alqeJ,) asaa.wu! pn?~o$ pual$ I? paMoys su!ac)ordodg-n, aqq q%Ioy?le ‘pant-w0 Sp!dg wnctas 30 saryea a&aAe ayl u! aihya ~uE~~~J!u~~!s ou qq~ Suy;mp $a!p a$r?lprlyoqnX+Mol 30 poilad B paMoIIo3 6Iluanbasqns squayd asay? 30 uaA ‘(z alql?&) ~~~_ITxH~uS!Slou qnq ‘a%raAv ay? uo paDnpa1 os~t? alaM su!alold -odg-x, pue su!a$ordodg-d_ard tsu!alordod!l-g’ pun IoraqsaIoya ‘sap~~a~b~f3~q u.nUas 30 asI?araap I)UX?XJ~L@S I.?paMoys !Jayp ~E?~-MOI ay? uaA@ s$uayd pi ayJ, ‘pahxasqo alah sp!diI tunas 30 suoyn~an~ ‘po!lad ~uaur~ear~a~d ay? %.+na *uoy?sn@A--lapun ~y5_ua@s B 03 sn paI uoy@$saAuI hwa!p ayl bq pau!e?qo BJt2p ayq uo sa!JoIw ayq 30 uoy2InaIw aqq qt?y? $no paInr aq !jouut?~ 71 ‘&3AaMOH‘+oIwodLy 61$$h$ fIIsnsn SBM paurns -uo3 QaAya33a qa!p ayq qt2yq urJ!3uoD ol pauraas y@aM 6poq aq3 30 pualq ayq ‘plauail UI *paI.@ssB CJI?~?uey? JaMoI SI?M‘guayd auo u! IdaDxa ‘ay’e!)u! +IOIT?:, ~09 ay& +(&?p rad ~oqocyt? 30 1u1 001 qnoqe) au!~ 30 sJunoure ~aS.niy ‘u?y.j no3 AI ad& ITXJLLIE~yg!~ ‘y.Iayd It?nsn SBM SE ‘pamnsuo3 ‘t?!urasu!aloldod!Inad6y au0 t(bt?p rad 1oyo31~ ~$01 30 1~ op ucy? ssal) aura 30 squnoure ~~EXXIS ‘bpn)s 30 pollad ay$ %u!mp ‘paurnsuo3 pey s$ua!qt?d uaAas *paq!rDsand uey? (aSIaAt? ayq uo oj()~) Jaq$Lj SI?Mqa!p a~eJp~yoqrt?3-Mo~ 30 poilad ayq %uynp pasnpor$u! aprpbyoqni9 30 a8quawad ay? aI!yM ‘6173gs arour paMoIIo3 uaaq pey la!p qJ-Mo1 aycj y2yl pa?lnsal7! ‘poo3 30 puiy aqq 0) &uprow~ aye+Il ~!ro1~3 ay? 30 sysS@uv aycj urol3 :qInsal Bu!~o1103 ayl aAe%!ja!p ayq oq aauaraypv ay? Zlu!yaay9 103 uogt@~saAu! kela!p aqt~ ‘6pnqs ayq u! papnlw! s?uayEd ayq 30 01 UI ‘sp!d!I tunas 30 saik?ya ayl y$+ paqyalroa 6~y.n2~~3~uEZ~s lou seM ssol c@$aM ayl ssaIayl.raAaN ‘(*S*N =: a) laip y23-~01 ayq laq3t2 2 00~~ pw (g)‘() > a) av2rpdyoqJw u! MO1 polnad Ila’ya!p ayl 30 pua aycj JE a%raAe ayq uo B 09~ :paurwo SSOIc@!aM y.@gs B bpnqs ayl 30 poyad ayy Su!rna
LP
LIPIDS
a Mean
values.
deviation.
fasting
b Standard
99.81
312.16
a
ol-Lipoproteins
SD
174.80
SD
401.00
a
596.50
Pm-~-Lipoproteins
a
23.32
264.83
97.90
322.33
138.17
a
a
Before
SD
@-Lipoproteins
SD
Cholesterol
SD b
Triglycerides
AFTER
THE
85.82
323.33
132.83
291.83
145.04
599.33
50.59
250.17
81.19
257.67
After
diet
ml of serum.
Low-carbohydrate
in mg/lOO
IN 6 PATIENTS
are expressed
SERUM
Values
5
TABLE
+3.6
-27.2
+0.5
-5.5
-20.1
% change
FIRST
N.S.
0.1
N.S.
N.S.
0.1
P
PERIOD
> P
> P
OF
> 0.05
> 0.05
-0.320
2.395
-0.034
0.888
2.447
t
LOW-CARBOHYDRATE
85.82
323.33
132.83
291.83
145.04
599.33
50.59
250.17
81.19
257.67
Before
Low-fat
AND
diet
THE
96.91
325.00
168.60
288.00
197.96
449.33
59.88
218.67
103.68
226.83
After
SECOND
OF
+0.5
-1.3
-25.0
-12.6
-12.0
% change
PERIOD
N.S.
N.S.
0.1
N.S.
N.S.
P
LOW-FAT
> P
> 0.05
DIET
4.038
0.065
2.256
1.215
0.741
t
49
low-carbohydrate diet; the levels of triglycerides and of pre-P-lipoproteins fell significantly, while the other lipid fractions remained practically unchanged. Six of these subjects continued the experiment with the low-fat diet: during this period we observed a further, but not statistically significant, reduction of serum levels of triglycerides, cholesterol and P-lipoproteins (Table 5). Discussion A number of primary and secondary prevention trials have presented evidence that lowering serum lipids by diet or drugs may reduce the incidence of, and the mortality from, atherosclerotic disease [ 21-281. Serum triglycerides, which are considered to be an independent risk factor for the development of atherosclerosis, can be decreased by a diet low in carbohydrate content [29331. A triglyceride-lowering effect of a diet with a high ratio of polyunsaturated to saturated fatty acids (P/S) has also been documented [ 34-391. In a long-term study on a group of hyperlipidaemic patients and non-obese normal men, Wilson et al. [40], using a high P/S diet, found the fall in serum triglyceride to be 11.7% after 6 months. However, the decrease of serum triglyceride was more marked in those patients who had reduced their carbohydrate intake and their total caloric intake. Hall et al. [ 411 showed that serum triglyceride levels in hypertriglyceridaemic patients were significantly reduced after 1 year of management with a lowfat diet containing highly polyunsaturated fats. Chait et al. [ 161, using lo-day feeding periods and maintaining constant the total carbohydrate and lipid content of the diet, showed that the mean serum level of triglycerides was 35% lower during consumption of a high P/S diet than during a diet rich in saturated fatty acids. The magnitude of the decrease of triglycerides was strongly correlated with the levels of triglycerides during the period when the saturated-fat diet was given. Different results were reported by Hodges et al. [ 421, who made a study on 24 young couples sub-divided into 4 groups given a diet high in saturated fat or a diet high in polyunsaturated fat for 20 weeks. They did not observe any significant difference in the levels of serum triglycerides, probably because of the wide fluctuations of the values in each group, although serum cholesterol was reduced after the diet rich in polyunsaturated fat. Moreover, they did not find any relation between the serum triglyceride levels and the gain or loss of weight. The results of the present study show that both a diet low in carbohydrate and a diet low in lipid content produced a significant decrease of serum triglyceride levels and that this effect was independent of weight changes. As expected, a diet with a low content of fat and cholesterol and a relatively high content of polyunsaturated fatty acids also caused a significant decrease of serum cholesterol and /3-lipoproteins; this effect was not present after treatment with the low-carbohydrate diet. When the experiment with the low-carbohydrate feeding was followed by a period of low-fat diet, no substantial change of the serum lipoprotein pattern was observed, though there was a trend to a further reduction of triglycerides, cholesterol and P-lipoproteins.
50
When an isocaloric diet low in carbohydrate was given to patients previously treated with a low-fat diet, the average values of serum lipids remained unmodified as compared with the values observed at the end of the first dietary period. We may conclude that the dietary management of type IV hyperlipoproteinaemia by a low-carbohydrate diet or by a low-fat diet is effective in decreasing the serum levels of triglycerides in out-patients living in their usual environment. On the whole, the diet low in fat content showed a greater hypolipidaemic effect and had the further advantage of producing a significant fall of serum cholesterol and P-lipoproteins; this effect is of particular relevance for the prevention of atherosclerosis. Therefore the diet with a low content of fat, that also appeared to be more agreeable to our patients, seems to be an effective means in the treatment of the commonest forms of hyperlipoproteinaemia. It must be pointed out that appreciable results have been obtained in our patients with a diet having a lower ratio of polyunsaturated to saturated fatty acids than suggested by other authors. References 1 Albrink, 2 3 4 5
6 7 8 9
10 11
12 13
M.J. and Man, E.B., Serum lipids, hypertension
and coronary
artery disease, Am. J. Med., 31
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cholesterol and phospholipid levels, J. Clin. Endocr., 12 (1952) 909. Ahrens, Jr., E.H.. Hirsh, J., Insull. Jr., W.. Tsaltas. T.T., Blomstrand. R. and Peterson. T.L., The influence of dietary fats on serum lipid levels in man. Lancet, i (1957) 943. 36 .Kinsell. L.W., Michaelis, G.. Walker, G., Wheeler, P., Splitter, S. and Flynn, P.. Dietary linoleic acid and linoleate. Effects in diabetic and in non-diabetic subjects with and without vascular disease, 35
Diabetes, 8 (1959) 179. Antonis. A. and Bersohn, I.. The influence of diet on serum triglyceride in South African white and Be&u prisoners, Lance& i (1961) 3. 38 Beveridge, J.M.R., Jagannathan, S.N. and Cannel, W.F., The effect of the type and amount of dietary fat on the level of plasma triglyceride in human subjects and in the postabsorptive state. Can. J. Biothem. Physiol.. 42 (1964) 999. 39 Bagdade. J.D., Hazzard. W.R. and Carl@ J., Effect of unsaturated dietary fat on plasma lipoprotein lipase activity in normal and hyperlipidemic states, Metabolism, 19 (1970) 1020. 40 Wilson, W.S., Hulley. S.B., Burrows, M.I. and Nichaman. M.E., Serum lipid and lipoprotein response to the American Heart Association fat-controlled diet, Am. J. Med., 51 (1971) 491. 41 Hall, T., Stamler, J., Cohen, D.B.. Moionnier, L., Epstein, M.B.. Be&son, D.M.. Whipple, I.T. and Catching, S.. Effectiveness of a low saturated fat, low cholesterol, weight reducing diet for the control of hypertriglyceridaemia. Atherosclerosis. 16 (1972) 389. 42 Hodges. E.S., Salel. A.F., Dunkley. W.L., Zelis. R.. McDonagh, P.F., Clifford. C., Hobbs, R.K., Smith, L.M., Fan, A., Mason, D.T. and Lykke. C.. Plasma lipid changes in young adult couples consuming polyunsaturated meats and dairy products, Am. J. Clin. Nutr.. 28 (1975) 1126. 37
