Randomized trials substituting polyunsaturated fat for saturated fat and their effect on coronary heart disease (CHD). A closer look.
Results from randomized trials are often used to prove a causal relation between consumption of saturated fat and CHD. But can results from these
trials be attributed to the changes in saturated fat intake, or could other dietary and non-dietary changes have contributed to these results?
Also, changes in serum cholesterol levels are often considered to be a reliable marker for subsequent changes in CHD risk. But can changes in serum cholesterol -
which are caused by changes in consumption of dietary fat - predict subsequent changes in CHD in a reliable way?
Until now, no review tried to answer these questions.
I used articles about the randomized trials included by the systematic reviews from Mozaffarian D (2010) Ramsden CE (2010) and Skeaff CM (2009)
[references 10-12, respectively] and collected data about changes in cholesterol caused by the interventions and looked for correlations with changes in CHD risk.
Also, I summarized both the dietary, and non-dietary changes which occured during these trials and evaluated whether or not effects on CHD risk can be
attributed to changes in saturated fat consumption in a reliable way. As always, more details about the data extracted from the original articles can be found in
the extended tables on the bottom of this page.
It should be noted that there were possibly more publications presenting additive details about these trials, so the findings in the tables should be considered
a starting point, and not as detailed findings from a systematic literature review.
Substitution of polyunsaturated fat for saturated fat and the predictive effect of serum cholesterol on coronary heart disease (CHD).
The dietary changes decreased levels of serum cholesterol in all 8 trials. The percentage change in cholesterol correlated fairly well with the predicted
decrease in CHD risk in 6 trials (2-5, 7-8), though the predicted effect size on CHD was smaller in one trial (3), and larger in another one (8). In 2 trials, the
decrease in serum cholesterol was followed by an increase in CHD rates (1, 6).
Some information should be taken into account when this data is interpreted:
- 2) The LA Veterans Study Changes in cholesterol levels among the experimental subjects proved to be poorly correlated with adherence to the diet. The greatest difference between incidence rates of control and experimental subjects occured in the stratum with lowest adherence to the study diet. Also, within the experimental diet group alone, incidence rates were highest in the stratum with highest adherence to the study diet.
- 5) The Oslo Diet-Heart Study The overall reduction in cholesterol levels correlated well with the overall reduction in CHD. But among subjects who died at age < 60, cholesterol levels were significantly higher among subjects who died from CHD, than among the survivors, while no significant differences in CHD mortality rates were found between these groups (36.5%, and 40.7% for the experimental and control group, respectively). Also, among subjects who died at age > 60, cholesterol levels did not differ significantly between subjects who died from CHD and the survivors, while significantly less subjects in the experimental group died from CHD (41.7%, and 53.0% for the experimental and control group, respectively).
- 7) The DART Study The small significant decrease in serum cholesterol correlated with the small nonsignificant decrease in CHD risk. But the trial included 2 other dietary interventions. Increased fiber consumption was not related to serum cholesterol, while a nonsignificantly increased risk of CHD was found (RR = 1.23; 95% CI = 0.97-1.57). And increased fish consumption was related to a small significant increase of serum cholesterol, while a nonsignificant protective effect against CHD risk was found (RR = 0.84; 95% CI = 0.67-1.07).
- 8) The STARS Included subjects in the trial only when their cholesterol levels decreased in response to use of the drug cholestyramine. In addition, further dietetic counseling, and if requested, suitable foodstuffs, were given to participants in the exerpimental group who did not achieve or maintain a cholesterol reduction of 15%.
Conclusion: Randomized studies consistently showed that dietary changes aimed at substitution of polyunsaturated fat for saturated fat decreased serum cholesterol levels. A global look at the subsequent effect on CHD suggests that these decreased levels of serum cholesterol, often correspond fairly well with the predicted decrease in CHD rates. But when more detailed findings are taken into account, little evidence remains that changes in serum cholesterol created by changes in dietary fat intake are predictive of CHD rates.
| Author | Cohort name | Decrease of serum cholesterol in relation to dietary change (difference between experimental group and control group) | Effect dietary change on CHD risk |
|---|---|---|---|
| 8) Watts GF (1992) | The STARS | -12.2% | RR = 0.41 (0.09-1.96) ** |
| 7) Burr ML (1989) | The DART | -3.5% | RR = 0.91 (0.72-1.16) |
| 6) Frantz ID Jr (1989) | The Minnesota Coronary Survey | -13.8% | RR = 1.08 (0.84-1.37) ** |
| 5) Leren P (1970) | The Oslo Diet-Heart Study | -13.9% | RR = 0.75 (0.57-0.99) ** |
| 4) Turpeinen O (1979) Miettinen M (1983) | The Finnish Mental Hospital Study | Women: -12.8% Men: -15.5% | Women: RR = 0.64 (0.41-1.00) ** Men: RR = 0.55 (0.34-0.88) ** |
| 3) Report of a Research Committee (1968) | MRC Soybean Oil | - 13.5% * | RR = 0.86 (0.61-1.22) ** |
| 2) Dayton S (1969) | LA Veterans | -12.7% | RR = 0.74 (0.53-1.03) ** |
| 1) Rose GA (1965) | Rose Corn Oil Trial | -8.8% * | RR = 1.86 (0.63-5.44) *** |
** = RR from Mozaffarian D. 2010 [10].
*** = RR from Ramsden CE. 2010 [11].
Can effects from randomized trials aimed at reducing intake of saturated fat solely be attributed to changes in intake of saturated fat?
No randomized trials exist where the only dietary difference existed of a reduction of saturated fat. Instead all randomized trials aimed at replacing saturated
fats by polyunsaturated fats.
If effects from saturated fats on serum cholesterol and CHD do exist, these effects may be counterbalanced by the content - and possibly even the composition
(e.g., amino acid profile of the protein) - of other nutrients in whole foods. Both diets rich in saturated fat and diets rich in polyunsaturated fats
correlate with specific nutrient profiles. Therefore, substitution of polyunsaturated fats for saturated fats will also change the nutrient profile of the entire
diet.
Until now, no review was created where both the dietary goals, and the actual dietary changes occuring during the trials were described.
An attempt was made to summarize both the dietary, and non-dietary changes which occured during these trials. They are presented in the following tables.
Dietary differences: Table 2 describes dietary differences - other than the decreased intake of saturated fat- occuring during the trial period between
the experimental groups and the control groups. Detailed differences occurring during the trial period were provided by different reports about only two trials (4, 8),
and to a lesser extend about two other trials (2, 3). Little to no data was provided about the other trials.
Results show that most diets from the experimental groups were higher in polyunsaturated fat intake and lower in dietary cholesterol intake. Also, results clearly
show that the dietary changes in fat intake correlated to lots of other changes in dietary intakes of both foods and nutrients.
Nondietary differences: Table 3 describes nondietary changes occuring during the trial period between the experimental groups and the control groups.
Detailed findings were provided about two trials only (4, 8).
Both trials were seriously contaminated:
-In the Finnish Mental Hospital Study (4), two psychotropic drugs were used more abundantly in the control group. And during the first half of the follow-up
period, the more chronic cases were transferred from the hospital of the control group to another hospital. Ramsden CE (11) pointed out that one of these
drugs 'thioridazine' is significantly associated with risk of sudden death (OR = 5.3; 95% CI = 1.7-16.2; P = 0.004). Also, this drug causes T-wave distortions,
QRS changes, ST elevations and other electrocardiogram changes and clinical presentations both with therapeutic administration and overdoses. These
electrocardiogram changes and clinical presentations overlap with those seen in MI and sudden death and may have been counted as CHD events. Furthermore, the drug
may also induce weight gain.
-In the STARS Study (8), overweight patients in the experimental group only, were put on a co-intervention aimed at losing weight. And patients in the control
group who died had severe CHD at entry.
Results from which trials can not only be attributed to the effect of subtituting polyunsaturated fats for saturated fats?
- 8) The STARS Study In addition to the two nondietary effects mentioned above, the experimental group consumed several foods/nutrients which could have favourably influenced the effect on CHD (13): more fruits, vegetables, and EPA/DHA.
- 5) The Oslo Diet-Heart Study All control groups consumed trans fats, usually varying from 1.3-2.4 g/day. But in this control group trans fat consumption was exceptionally high: Ramsden CE (11) pointed out that subjects in the control group consumed 65 g/d of partially hydrogenated fish and vegetable oil margarine, delivering 9.6 g trans fat/day. While these foods were restricted to the experimental group. In addition, the experimental group consumed several foods/nutrients which could have favourably influenced the effect on CHD (13): more vegetables, fruits, nuts, fish, and whole grains
- 4) The Finnish Mental Hospital Study In addition to the two nondietary effects mentioned above, diets from the experimental group and the control group differed not mildly, but distinctly for a large amount of dietary items during the first half of the follow-up period (Turpeinen O. 1968). But the most important reason for exclusion would be, that the study was not randomized!
- 2) The LA Veterans Study The control group was distinctly deficient in vitamin E. Dietary vitamin E has been linked to CHD (13)
The remaining four trials (1, 3, 6, 7) were most likely to isolate the effect of replacing saturated fats by polyunsaturated fats. The RR was < 1 in two
trials (3, 7), and RR's were > 1 in the other two trials (1, 6). Of these four trials, one aimed at reducing dietary cholesterol (6), and a reduction
in dietary cholesterol intake during the trial period was found in two other cohorts (3, 7). Though dietary cholesterol was not mentioned in the fourth cohort (1),
the dietary goals will most likely have led to a reduction in intake. Polyunsaturated fat intake increased in all 8 trial included in this analysis.
Ramsden CE (11) extensively examined data about specific dietary fats and contacted authors to obtain additional information. He found that non-hydrogeneted
study oils were substituted for trans fatty acids-containing fats, oils and foods (e.g., common hard margarines, shortenings, pastries, fried foods in all eight
trials in this analysis.
Conclusion: Various confounders were able to influence the effect of replacing saturated fats by polyunsaturated fats. Sometimes, experimental groups were randomized
to a complete mediterranean diet, including increased consumption of vegetables and fruits. The effect of reduced trans fat
intake in the experimental groups, is likely to have attributed to the protective effects against coronary heart disease in all 8 trials. Saturated fat was
replaced by polyunsaturated fat in all trials, and dietary cholesterol intake correlated strongly to saturated fat intake. Subsequently, none of the trials
involved in the analysis was able to isolate the effect from saturated fats on CHD.
| Author | Cohort name | Dietary changes other than a decrease in saturated fat |
|---|---|---|
| 8) Watts GF (1992/1996) | The STARS | Dietary intervention: -Reduced intakes of animal protein, meat, cheese, fish, margarine, oils, cookies, pastry, and cakes. -Increased intakes of bread, potatoes, pasta, vegetables, fruits, legumes, and oats. -Limit intake of alcohol. Dietary changes during trial: -Reduced intakes of energy, total fat, monounsaturated fat, trans fat, alpha-linolenic acid, and dietary cholesterol. -Increased intakes of linoleic acid, EPA, DHA, carbohydrate, and fiber. |
| 7) Burr ML (1989) | The DART | Dietary intervention: -Reduced intake of total fat. -Increased intake of polyunsaturated fat. Dietary changes during trial: -Reduced intakes of total fat, trans fat*, and dietary cholesterol. -Increased polyunsaturated fat:saturated fat ratio. |
| 6) Frantz ID Jr (1989) | The Minnesota Coronary Survey | Dietary intervention: -Reduced intake of dietary cholesterol. -Increased intake of polyunsaturated fat, liquid corn oil*, corn oil polyunsaturated margarine*, and possibly safflower oil*. Dietary changes during trial: -Reduced intake of trans fat*. |
| 5) Leren P (1968/1970) | The Oslo Diet-Heart Study | Dietary intervention: -Reduced intake of dietary cholesterol, refined grains*, and sugar*. -Increased intakes of polyunsaturated fat, soya bean oil, cod liver oil*, fish*, shellfish*, nuts*, fruits*, vegetables*, and whole grains*. Dietary changes during trial: -Reduced intake of trans fat*. -Increased intake of linoleic acid*, linolenic acid*, EPA/DHA*, and vitamin D*. |
| 4) Turpeinen O (1979) Miettinen M (1983) | The Finnish Mental Hospital Study | Dietary intervention: -Reduced intakes of dairy fat, butter, ordinary margarine. -Increased intakes of soybean oil, soft margarine, polyunsaturated fat. Dietary changes during trial: -Reduced intakes of potatoes, cream, butter, common margarine, meat (products), eggs, trans fat*, dietary cholesterol and sucrose. -Increased intakes of root vegetables, buttermilk, monounsaturated fat, total polyunsaturated fat, linolenic acid, and linolenic acid. |
| 3) Report of a Research Committee (1968) | MRC Soybean Oil | Dietary intervention: -Reduced intakes of butter, other margarines, cooking-fat, other oils, fat meat, whole milk, cheese, egg yolk, and most biscuits and cakes. -Increased intake of soya bean oil and fruit juice Dietary changes during trial: -Reduced intakes of trans fat*, dietary cholesterol, calcium, and vitamin A. |
| 2) Dayton S (1969) | LA Veterans | Dietary intervention: -Reduced intakes of butterfat and meat fat. -Increased intakes of corn oil, soybean oil, safflower oil, cottonseed oil, and unsaturated margarine Dietary changes during trial: -Reduced intakes of total fat, trans fat*, and dietary cholesterol . -Increased intakes of linoleic acid, alpha-linolenic acid, and plant sterols. Note: The control group was distinctly deficient in vitamin E. |
| 1) Rose GA (1965) | Rose Corn Oil Trial | Dietary intervention: -Reduced intakes of fried foods, fatty meat, sausages, pastry, ice-cream, cheese, cakes, milk, eggs, and butter. -Increased intake of corn oil. Dietary changes during trial: -Reduced intake of trans fat*. -Increased intake of corn oil. |
| Author | Cohort name | Non-dietary changes differing between the experimental group and the control group |
|---|---|---|
| 8) Watts GF (1992) | The STARS | -Overweight patients in the experimental group, but not control group, were described a diet that contained 1,000-1,200 kcal/day. -No significant differences in the demographic and clinical characteristics were found, but subjects in the control group tended to be older, drink more alcohol, and were more likely to have angina. On the other hand subjects in the control group were less likely to have previous MI. -The patients in the control group who died had severe CHD at entry. |
| 7) Burr ML (1989) | The DART | No differences were found. |
| 6) Frantz ID Jr (1989) | The Minnesota Coronary Survey | No data was provided. |
| 5) Leren P (1970) | The Oslo Diet-Heart Study | No differences were found. |
| 4) Miettinen M (1972) Turpeinen O (1979) | The Finnish Mental Hospital Study | -Two psychotropic drugs were used somewhat less abundantly in the experimental group: 0.63 vs 0.97 dosis/day for thioridazine, and 1.61 vs 1.92 dosis/day for total phenothiazines. -During the first half of the follow-up period, the more chronic cases were transferred from the hospital of the control group to another hospital. |
| 3) Report of a Research Committee (1968) | MRC Soybean Oil | No differences were found. |
| 2) Dayton S (1969) | LA Veterans | Body weight declined in the control group, while it rose in the experimental group. |
| 1) Rose GA (1965) | Rose Corn Oil Trial | No data was provided. |
References.
1) Rose GA. Corn oil in treatment of ischaemic heart disease. Br Med J. 1965 Jun 12;1(5449):1531-3.
Full text
2) Dayton S. Composition of lipids in human serum and adipose tissue during prolonged feeding of a diet high in unsaturated fat. J Lipid Res. 1966 Jan;7(1):103-11.
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+ Dayton S. Controlled trial of a diet high in unsaturated fat for prevention of atherosclerotic complications. Lancet. 1968 Nov 16;2(7577):1060-2.
Abstract
+ Dayton S. Diet high in unsaturated fat. A controlled clinical trial. Minn Med. 1969 Aug;52(8):1237-42.
Abstract
+ Dayton S. A controlled clinical trial of a diet high in unsaturated fat in preventing complications of atherosclerosis. Circulation. 1969;40(suppl 2):1-63.
Abstract
+ Dayton S. Diet and atherosclerosis. Lancet. 1970 Feb 28;1(7644):473-4.
Abstract
3) Report of a research committee to the medical research council. Controlled trial of soya-bean oil in myocardial infarction. Lancet. 1968 Sep 28;2(7570):693-9.
Abstract
4) Turpeinen O. Dietary prevention of coronary heart disease: long-term experiment. I. Observations on male subjects. Am J Clin Nutr. 1968 Apr;21(4):255-76.
Full text
+ Miettinen M. Effect of cholesterol-lowering diet on mortality from coronary heart-disease and other causes. A twelve-year clinical trial in men and women. Lancet. 1972 Oct 21;2(7782):835-8.
Abstract
+ Turpeinen O. Dietary prevention of coronary heart disease: the Finnish Mental Hospital Study. Int J Epidemiol. 1979 Jun;8(2):99-118.
Abstract
+ Miettinen M. Dietary prevention of coronary heart disease in women: the Finnish mental hospital study. Int J Epidemiol. 1983 Mar;12(1):17-25.
Abstract
5) Leren P. The effect of plasma-cholesterol-lowering diet in male survivors of myocardial infarction. A controlled clinical trial. Bull N Y Acad Med. 1968 Aug;44(8):1012-20.
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+ Leren P. The Oslo diet-heart study. Eleven-year report. Circulation. 1970 Nov;42(5):935-42.
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6) Frantz ID Jr. Test of effect of lipid lowering by diet on cardiovascular risk. The Minnesota Coronary Survey. Arteriosclerosis. 1989 Jan-Feb;9(1):129-35.
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7) Burr ML. Diet and reinfarction trial (DART): design, recruitment, and compliance. Eur Heart J. 1989 Jun;10(6):558-67.
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+ Burr ML. Effects of changes in fat, fish, and fibre intakes on death and myocardial reinfarction: diet and reinfarction trial (DART). Lancet. 1989 Sep 30;2(8666):757-61.
Abstract
+ Ness AR. The long-term effect of dietary advice in men with coronary disease: follow-up of the Diet and Reinfarction trial (DART). Eur J Clin Nutr. 2002 Jun;56(6):512-8.
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8) Watts GF. Effects on coronary artery disease of lipid-lowering diet, or diet plus cholestyramine, in the St Thomas' Atherosclerosis Regression Study (STARS). Lancet. 1992 Mar 7;339(8793):563-9.
Abstract
+ Watts GF. Dietary fatty acids and progression of coronary artery disease in men. Am J Clin Nutr. 1996 Aug;64(2):202-9.
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9) Ravnskov U. Cholesterol lowering trials in coronary heart disease: frequency of citation and outcome. BMJ. 1992 Jul 4;305(6844):15-9.
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10) Mozaffarian D. Effects on coronary heart disease of increasing polyunsaturated fat in place of saturated fat: a systematic review and meta-analysis of randomized controlled trials. PLoS Med. 2010 Mar 23;7(3):e1000252.
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11) Ramsden CE. n-6 fatty acid-specific and mixed polyunsaturate dietary interventions have different effects on CHD risk: a meta-analysis of randomised controlled trials.
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| Author | Cohort name | Subjects | Years of follow-up | Cases | End point | Consumption of | Relative Risk (RR) | Adjustments | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 8) Watts GF (1996) | The St Thomas' Atherosclerosis Regression Study (STARS) | 50 middle-aged men refered for coronary angiography because of aninga pectoris or myocardial infarction, who did not require revascularization, and who had fasting plasma cholesterol concentrations in the range of 6.1-10.0 mmol/L (236-387 mg/dL). (Randomized trial) | - | - | - | Experimental group 1: (dietary guidelines to strictly limit their intake of animal protein [e.g., meat, cheese, fish], margarine and oils. To avoid processed foods [e.g., cookies, pastry, cakes], and to consume relatively large quantities of starchy, low-fat foods [e.g., bread, potatoes, pasta] as well as fruits and vegetables [particularly legumes and oats]. And to limit intake of alcohol to no more than three standard drinks [30 g alcohol]). Experimental group 2: (diet plus cholestyramine). Control group: (usual care. Broad qualitative dietary recommendations given by a physician). |
Study design: Both patients following the diet and the usual-care group were advised to lose weight if their BMI was > 25. Dietary differences: -Men in the experimental group consumed significantly less energy (8,610 vs 9,135 kJ), fat (61.5 vs 90.2 g), saturated fat (20.8 vs 42.1 g), monounsaturated fat (21.3 vs 41.5 g), and cholesterol (215.0 vs 341.5 mg). -Men in the experimental group consumed nonsignificantly more polyunsaturated fat (16.9 vs 11.7 g), carbohydrate (267.1 vs 234.2 g), fiber (27.9 vs 18.2 g), and alcohol (15.1 vs 13.8 g). Both groups consumed the same amount of protein. -Men in the experimental group consumed nonsignificantly less of the saturated fatty acid behenic acid, and significantly less of all other saturated fatty acids (butyric, caproic, caprylic capric, lauric, myristic, palmitic, stearic, and arachidic acid; P = ≤ 0,008 for all fatty acids). -Men in the experimental group consumed significantly less of all monounsaturated fatty acids (palmitoleic, oleic, t-18:1, 20:1n-9, and erucic acid; P = ≤ 0,028 for all fatty acids). -Men in the experimental group consumed significantly less trans-unsaturated fatty acids (total, and total-t-18:1 [vaccenic, and elaidic acid]; P = < 0.001). -Men in the experimental group consumed nonsignificantly more of the polyunsaturated fatty acids linoleic, EPA, and DHA, nonsignificantly less GLA, and significantly less alpha-linolenic acid (P = 0.05), and arachidonic acid (P = < 0.001). Nondietary differences: -Men in the experimental group lost weight (-2.9 kg) compared with the control group (0.3; P = 0.001). -During the trial, plasma lipids fell significantly with diet (-14.0%), but not with usual care. | - | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 8) Watts GF (1992) | The St Thomas' Atherosclerosis Regression Study (STARS) | 90 men aged < 66 with plasma cholesterol concentrations above 6.0 mmol/l, and referred for coronary angiography to investigate angina pectoris or other findings suggestive of CHD. Cholesterol levels of the men had to respond to use of the drug cholestyramine. Grounds for exclusion were fasting plasma trygliceride concentrations above 4.0 mmol/l or remnant hyperlipidaemia, fasting glucose above 7 mmol/l, cardiac failure, myocardial infarction in the previous 8 weeks, malignancy, other major organ disease, accelerated hypertension, and previous - or planned - artery revascularisation. (Randomized controlled end-point-blinded trial) | 1982- | See variables | CHD & Stroke | Experimental group D (26 men): (A lipid-lowering diet. Total fat intake was reduced to 27% of dietary energy, saturated fat to 8-10%, and dietary cholesterol to 100 mg/1000 kcal; omega-6 and omega-3 polyunsaturated fatty acids were increased to 8% of dietary energy, and plant-derived soluble fibre [chiefly pectin] was increased to the equivalent of 3.6 g polygalacturonate/1000 kcal. Intake of alcohol was permitted at the patient's habitual level.). Experimental group DC (24 men): (Diet plus cholestyramine [8 g twice daily with meals]). Control group (U) (24 men): (Usual care only) |
Study design: -For patients with a BMI below < 25 an isocaloric diet was prescribed. Overweight patients were described a diet that contained 1000-1200 kcal daily to achieve a BMI of 25. -Further dietetic counseling and, if requested, suitable foodstuffs, were given to participants in the diet or diet plus cholestyramine groups who did not achieve or maintain serum cholesterol reductions of 15% or 25%, respectively. -74 men completed the study. Dietary differences: Not defined. Non-dietary differences: -All groups received counselling against smoking, antihypertensive treatment if appropriate, and the advice for a suitable level of daily exercise. -Patients in the control group with a BMI > 25 were advised to lose weight but did not receive formal dietary counseling. -There were no statistically significant differences in the demographic and clinical characteristics of the patients between the treatment groups. But the control group tended to be older (U = 53.9. vs D = 48.9, and DC = 49.6). The control group contained more current smokers (U = 29.2%. vs D = 26.9%, and DC = 20.8%). And the control group drank more alcohol (U = 15 units/week. vs D = 10, and DC = 12). Full details of the differences can be seen in the table below. -In the control group, total cholesterol (7.07 to 6.93 mmol/l; P = 0.15), LDL-, and HDL-cholesterol, and triglycerides did not significantly change during the trial period. -In the diet only group, total cholesterol (7.19 to 6.17 mmol/l; P = < 0.001; 14.2%), LDL-cholesterol (5.00 to 4.19; P = < 0.001; 16.2%), and triglycerides (2.31 to 1.85; P = 0.005; 20%) decreased, but HDL-cholesterol remained unchanged (1.14 to 1.14; P = 0.82). -In the diet + cholestyramine group, total cholesterol (7.44 to 5.56 mmol/l; P = < 0.001; 25.3%) and LDL-cholesterol (5.26 to 3.37; P = < 0.001; 35.7%) decreased, but HDL-cholesterol (1.24 to 1.19; P = 0.29), and triglycerides (2.20 to 2.21; P = 0.97) remained unchanged. -Total numbers of occluded segments, patients with occlusions, and mean ejection fractions were similar between groups. -The 3 patients in group U who died had severe CHD at entry. -All angiographic criteria consistently worsened in the control group and consistently improved in both experimental groups. -the STARS trial used as an end-point arteriographic assessment of the arterial lumen, which may not necessarily equate with progression and regression of atherosclerosis. -Angina symptoms were not significantly changed among controls, whereas both intervention groups showed significant improvements (p = < 0.01) in severity of angina and CHA functional score. -10 controls (42%) required increased anti-anginal treatment compared with 5 (19%) in group D and 6 (25%) in group DC. Results (based on 28 men in group U, 27 men in group D, and 26 men in group DC):
Unadjusted. |
7) Ness AR (2002) | The Diet and Reinfarction Trial (DART) | 2,033 men aged < 70 who had survived a MI, and were rectruited from hospitals in England. | (Randomized trial) 1983-87 to 2000 | 738 CHD | 52 stroke CHD mortality | & Stroke mortality Experimental group: (Fat advice. The advice aimed to achieve a reduction in total fat intake and increase in the (polyunsaturated fat=saturated fat) P=S ratio.). | Control group: (No fat advice)
Dietary differences: | At 2 y the percentage of energy from fat was around 35% in those not given fat advice and just over 32% in those given fat advice. The P=S ratio was around 0.4 in those not given fat advice compared to just under 0.8 in the fat advice group. CHD: HR = 0.91 (0.79-1.05). Hazard by follow-up period in years: 0-2: HR = 0.98 (0.74-1.30). 2-5: HR = 1.02 (0.75-1.40). 5-10: HR = 0.89 (0.68-1.16). 10+: HR = 0.76 (0.57-1.03). Stroke: HR = 2.03 (1.14-3.63). Hazard by follow-up period in years: 0-2: HR = -. 2-5: HR = -. 5-10: HR = 1.69 (0.67-4.29). 10+: HR = 2.97 (1.18-7.48). Unadjusted. |
Adjustment for history of MI, angina, hypertension at baseline; X-ray evidence of cardiomegaly, pulmonary congestion or pulmonary oedema at baseline; and treatment (at entry) with b-blockers, other anti-hypertensives, digoxin/anti-arrhythmics, or anticoagulants did not change the HRs. 7) Burr ML (1989) | The Diet And Reinfarction Trial (DART) | 2,033 men aged < 70, admitted to 21 hospitals, and who had recovered from acute MI (excluding diabetic patients). | (Randomised controlled trial). 2 | See variables | CHD | Experimental group: fat advice (not defined, but designed to reduce fat intake to 30% of total energy, and to increase the polyunsaturated/saturated ratio to 1-0). | Control group: No fat advice.
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-Men were allocated to receive or not to receive advice on each of 3 dietary factors: (1) fat advice, (2) fish advice, and (3) fibre advice, thus creating 8 possible combinations. -At 6 months and 2 years, the subjects was administered a detailed dietary questionnaire. -The % of fat energy at 6 months and 2 years were 32.1/32.3 for the fat advice group, and 35.3/35.0 for no fat advice. -The P/S ratios at 6 months and 2 years were 0.78/0.78 for the fat advice group, and 0.40/0.44 for no fat advice. -Fat advice dropped cholesterol levels, whereas no fat advice showed a rise of cholesterol levels. The difference between these 2 groups was significant (3.6 % at 6 months; P = < 0.001). This difference remained after 2 years (3.5 % difference; P = < 0.01). -HDL cholesterol rose equally in both groups during the first 6 months and thereafter remained constant. -In 111 men given fat advice the mean percentage of linoleic acid was 28-1% (95% CI = 26.9-29.2%) compared with 25-0% (24.0-26.0%) in 92 men not given fat advice (p = < 0.001). -On average the weights of the subjects did not change much during the trial: the overall mean weight rose by 0-6 kg. Unadjusted. |
7) Burr ML (1989) | The Diet And Reinfarction Trial (DART) | 2,033 men from 21 hospitals, aged < 70 and who survived myocardial infarction, but without a history of diabetes or other serious illness (e.g., malignant disease, renal failure). | (randomized controlled trial) Not defined | Not defined | Not defined | Experimental groups: | -Fat advice = a reduction in saturated fat intake and an increase in the intake of polyunsaturated fat, such that the total fat intake provided 30% of the energy and the polyunsaturated:saturated ratio was 1:0. -Fish advice = An increased intake of fatty fish (mackerel, herring, kipper, pilchard, sardine, salmon and trout) to at least two portions weekly (200-400 g). Men allocated to the fish diet who could not tolerate fatty fish were supplied with 'Maxepa' capsules and asked to take three daily, so as to supply 0.5 g of EPA daily, approximately equivalent to 63 g fatty fish. -Fibre advice = An increased intake of cereal fibre, to 18 g daily, with a total fibre intake of 30 g daily. Control group: No advice (no specific dietary advice, but being told to take a 'balanced diet').
Study design: | Men were randomly allocated to receive advice on each of three dietary factors, the allocation with regard to each factor being independent of the allocation regarding the others. Dietary differences 'fat advice': -74% of the men in the 'fat advice' group had a P:S ratio of ≥ 0.6, while 23% had a ratio of ≥ 1.0. Mean P:S ratios were 0.78 in the 'fat advice' group, and 0.40 in the group of men not given 'fat advice'. -The mean % of energy from fat were 32.1 in the 'fat advice' group, and 35.3 in the control group. -The mean cholesterol intake was 219 mg/day for the 'fat advice' group and 277 mg/day for the 'no fat advice' group. Dietary differences 'fish advice': -14% of the subjects in the 'fish advice' group took 'Maxepa' capsules as a partial or total substitute for fatty fish. -The mean weekly intake of EPA was 2.3 g for the 'fish advice' group, and 0.7 in the control group, corresponding approximately to 290 and 80 g respectively of fatty fish. Dietary differences 'fibre advice': -53% of the 'fibre advice' group ate ≥ 18 g/day, compared with 7% of the other subjects. Mean daily intakes of cereal fibre were 19 g and 9 g in the 'fibre advice' and 'no fibre advice' groups respectively. The total fibre intakes being 30 g and 20 g respectively. Non-dietary differences: -Men in the 'fish advice' group were somewhat more likely to have had an anterior infarct (48.3% vs 43.0%) and cardiomegaly (19.5% vs 14.7%) (both adverse risk factors) than the non-fish group. -A smaller % of men in the 'fish advice' group took beta blockers (26.2 vs 32.6%). Not defined. |
6) Frantz ID Jr (1989) | The Minnesota Coronary Survey | (an outgrowth of The National Diet-Heart Feasibility Study) 4,393 institutionalized men and 4,664 Institutionalized women from six mental hospitals and one nursing home. | (Double-blind randomized clinical trial) 4.5 | See variables | CHD | Experimental group [n = 2,197 men, and 2,344 women]: a 38% fat treatment diet (9% saturated fat, 15% polyunsaturated fat, 14% monounsaturated fat, 166 mg dietary cholesterol per day. Products particularly useful were filled milk and ice cream, a whole egg substitute, soft margarine, whipped topping, filled cheese, low fat ground beef with added vegetable oil, and filled sausage products). | Control group [2,196 men, and 2,320 women]: a 39% fat diet (18% saturated fat, 5% polyunsaturated fat, 16% monounsaturated fat, 446 mg dietary cholesterol per day).
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-Serum cholesterol fell by 14.5% in the experimental group, and by 0.7% in the control group. Unadjusted. |
5) Leren P (1970) | The Oslo diet-heart study | 412 men aged 30-64 in the period 1-2 years after a first myocardial infarction. | (Randomized trial) 11 | 190 | Total cardiovascular mortality (including MI, heart failure, sudden death, cerebral vascular death, ruptured aortic aneurysm, atherosclerotic occlusions of aorta, and pulmonary emboli) | Experimental group (206 men): (a diet low in saturated fats and cholesterol, and high in polyunsaturated fats was recommended). | Control group (206 men): (not defined)
Study design: | The men were allocated at random to the experimental diet group and to the control group for a period of 5 years. Diet, clinical, and laboratory examinations were discontinued after 5 years. At the end of this 5-year period the surviving dieters were adviced to adhere to the cholesterol lowering diet in the future. The surviving controls were informed that a reducted fat intake possibly might be beneficial, but they received no detailed dietary instructions. Dietary differences: -The experimental diet contained 269 g carbohydrates/day (45.5 % of calories), 51 g sugar, 92 g protein (15.0 %), 104 g total fat (39.0 %), 22 g saturated fat (8.5 %), 27 g monounsaturated fat (10.1 %), 55 g polyunsaturated fat (20.7 %), and 264 mg dietary cholesterol. -No data was provided about the diet of the control group. Other differences: -Mean cholesterol reduction in the diet group was 17.6% (296 to 244 mg/100 ml) vs 3.7% (296 to 285 mg/100 ml) in the control group. -At the age < 60 men who died had a higher mean cholesterol value than the survivors (P = 0.01). At the age > 60 there is no such difference. -The mean blood pressure, as well as the relative distribution of normotensives and hypertensives in the two groups remained almost unchanged. -The mean body weight in the control group remained almost unchanged. The dieters however, had an average weight loss of 2 kg as compared to the controls. -Smoking habits were about the same in the two groups. Results: CVD: There were 88 cardiovascular deaths in the experimental group, and 102 in the control group; P = 0.13.
Cerebral vascular death: There were 7 cerebral vascular deaths in the experimental group, and 5 in the control group. Unadjusted. |
5) Leren P (1968) | Cohort name not defined | 412 men aged 30-64 discharged from medical departments in Oslo, and diagnosed with a first myocardial infarction. | (Randomized trial) 5 | See variables | CHD | Experimental group (206 men): (A diet low in animal fats and in dietary cholesterol, and rich in vegetable oil.). | Control group (206 men): (not defined)
Dietary differences: | -Mean daily intake in the experimental group was 92 g protein, 104 g fat (39% of energy), 269 g carbohydrates, 264 mg cholesterol, 2,387 calories. -Sources of fat in the experimental group were soy bean oil (72%), fish fat (11.6%), animal fat (8.8%), cereal fat (5.0%), and fat from other sources (2.6%). -Mean dietary fats in the experimental group were 21.6% saturated fat, 25.7% monounsaturated fat, and 52.7% polyunsaturated fat. Nondietary differences: -The comparability of the groups was thoroughly studied, and it was found that they were strictly comparable. -Blood pressure was higher in the diet group. -Mean cholesterol reduction in the diet group was 17.6% (296 to 244 mg/100 ml) vs 3.7% (296 to 285 mg/100 ml) in the control group. -Among men aged < 60, serum cholesterol was higher in the patients with CHD relapses than in those without. Among men aged ≥ 60 no difference in serum cholesterol was found between those with and without relapses. Results:
Effect modification: -The difference in the CHD relapse rate was statistically significant only in patients below the age of 60. -The effect of cholesterol reduction was most pronounced in those who were without angina pectoris at the start of the trial. The difference in the CHD relapse rate between these dieters and controls was highly significant (P = 0.002). In those with angina pectoris at the start of the trial the difference in CHD relapse rate between dieters and controls was not statistically significant. -Significantly reduced relapse rate in the dieters as compared with the controls was found only in those with a normal relative heart volume at the time of the primary infarction. Unadjusted. |
4) Miettinen M (1983) | The Finnish Mental Hospital Study | hospitalized women aged 44-64 without evidence of CHD. | (controlled intervention trial) 12 | (1959-71) See variables | CHD | Experimental group: (ordinary milk was replaced by an emulsion of soybean oil in skim milk ['filled milk'], and by replacing butter and ordinary margarine by a 'soft margarine' with a high content of polyunsaturated fatty acids. The quantity of fats was not appreciably changed, but the proportion of dairy fats wass radically reduced [to 4% of total fats]). | Control group: (normal diet containing 34% food energy as fat, over half [51%] of which were dairy fats)
Study design: | -The intervention consisted of 2 time periods: from 1959-1965 all women in hospital N were put in the experimental group, while hospital K served as the control group. From 1965-1971 all women in hospital K were put in the experimental group, while hospital N served as the control group. -At the reversal of the diets in 1965, the patients populations were rejuvenated by discardig the six oldest annual cohorts, and by admitting 6 new annual cohorts at the younger end of the age range. -Just over 20% of all women remained in one of the hospitals during both 2 time periods. Dietary differences: -The diets of the female patients were identical to those served to men. -Both diets contained approximatly the same amount of total fats (110 vs 107 g/day), and monoethenoid fat (36.8 vs 33.3 g/day, for the experimental and control groups, respectively). -The experimental diet contained less saturated fat (27.3 vs 54.7 g/day), and cholesterol (282 vs 480 mg/day), but more polyethenoid fat (40.5 vs 13.6 g/day). Other differences: -Serum cholesterol was lower in the experimantal group (239.7 mg/dl), than in the control group (274.8 mg/dl; P = < 0.001). Results:
Unadjusted. |
4) Turpeinen O (1979) | The Finnish Mental Hospital Study | 676 hospitalized men aged 34-64, and without evidence of CVD from 2 mental hospitals near Helsinki. | (controlled intervention trial) 12 | (1959-71) See variables | CHD | Experimental group: (ordinary milk was replaced by an emulsion of soybean oil in skim milk ['filled milk'] and by replacing butter and ordinary margarine by a 'soft margarine' with a high content of polyunsaturated fatty acids). Both the filled milk and soft margarine were fortified with vitamins A and D. | Control group: (normal diet containing moderate amounts of fat [31-33% of total food energy] over half [54%] of which were dairy fats, mainly from milk and butter).
Study design: | -From 1959-1965 the diet in one of the hospitals (N) was changed, whereas the other hospital (K) served as the control. -From 1965-1971 hospital N returned to the normal diet, and hospital K was placed on the diet. -At the reversal of the diets in 1965 the patient populations were rejuvenated by discarding the 6 oldest annual cohorts and by admitting 6 new annual cohorts at the younger end of the age range. -About 45% of the men remained in the study through the whole on one 6-year period, and about 36% of the men was present during both time periods. Dietary differences (food items): -The experimental group consumed more root vegetables (89 vs 79 g/day for the experimental and control group, respectively), filled milk (706 vs 0), buttermilk (116 vs 97), soft margarine (36 vs 0), and vegetable oils (17 vs 10). -The experimental group consumed less potatoes (398 vs 420 g/day for the experimental and control group, respectively), sugar (74 vs 83), whole milk (0 vs 500), skim milk (84 vs 250), cream (3 vs 12), butter (0 vs 33), common margarine (1 vs 12), meat and meat products (147 vs 169), and eggs (23 vs 30). -Both groups consumed approximatly the same amount of cereals (202 vs 202 g/day for the experimental and control group, respectively), dried peas (5 vs 4), other vegetables (108 vs 103), berries and fruits (110 vs 118), cheese (18 vs 17), and fish (58 vs 59). Dietary differences (nutrients): -The experimental group consumed more oleic acid (33.2 vs 28.1 g/day for the experimental and control group, respectively), total monoethenoid acid (36.8 vs 33.3 g), linoleic acid (34.3 vs 10.7 g), linolenic acid (5.6 vs 1.9 g), and total polyethenoid acid (40.5 vs 13.6 g). -The experimental group consumed less sucrose (77.6 vs 90.2 g/day for the experimental and control group, respectively), cholesterol (282 vs 480 mg), myristic acid (1.5 vs 7.6 g), palmitic acid (16.3 vs 25.7 g), stearic acid (6.8 vs 8.9 g), other saturated fatty acids (2.7 vs 12.5 g), total saturated fat (27.3 vs 54.7 g), palmitoleic acid (1.9 vs 2.8 g), monoethenoid acid other than palimtoleic and oleic acid (1.7 vs 2.4 g), and polyethenoid acid other than linoleic and lininolenic acid (0.6 vs 1.0 g). -Both groups consumed approximatly the same amount of energy (11.8 vs 11.8 MJ/day for the experimental and control group, respectively), proteins (96.4 vs 97.5 g), fats (110 vs 107 g), carbohydrates (372 vs 379 g), calcium (1.47 vs 1.42 g), iron (15.7 vs 16.0 mg), vitamin A (4340 vs 4420 IU), thiamine (1.70 vs 1.76 mg), riboflavin (2.86 vs 2.80 mg), nicotinamide (17.4 vs 18.2 mg), and ascorbic acid (125 vs 126 mg). Other differences: -Mean serum cholesterol levels over the 12 year period were lower in the experimental group (226.2 mg/dl) compared to the control group (267.6 mg/dl). Difference is - 41.4 mg/dl (15%; P = < 0.001). -Two psychotropic drugs were used somewhat less abundantly in the experimental group: 0.63 vs 0.97 dosis/day for thioridazine, and 1.61 vs 1.92 dosis/day for total phenothiazines. Results:
Unadjusted. |
4) Miettinen M (1972) | No cohort name defined: | Finnish Mental Hospital Middle-aged (> 15 y) male & female subjects with or without pre-existing disease from two mental hospitals in Helsinki, Finland. | (Controlled preventive trial with a cross-over design) 12 | (1959-1971) See variables | Death from diseases of the circulatory system | Experimental diet (2,276 men, and 3,598 women) (Ordinary milk was replaced by an emulsion of soybean oil in skim milk [filled milk]. And butter and ordinary margarine were replaced by a "soft" margarine with a high content of polyunsaturated fatty acids). | Normal diet (1,902 men, and 2,836 women) (not defined)
The data in are not suitable for making comparisons because there are notable differences between the two hospitals and between the two study periods. One of these
differences concerns the period of hospital admission (personyears per patient), which on average is considerably shorter in hospital K than in hospital N, and in
hospital K is shorter during the second than during the first period. Another difference exists in the age distribution (and the median age) of the patients the patients
are generally older in hospital N, during the second period, and in the female sex. |
-The polyunsaturated/saturated fatty-acid ratio was 0.22-0.29 in the normal diet and 1.42-1.78 in the experimental diet. -Serum cholesterol was reduced by 12-18% in the experimental diets in both hospitals and in both sexes. -Among the female patients of hospital K the mortality figures in general seem to have been exceptionally low during the first period. This may be because between 1959 and 1965 many of the more chronic cases were transferred to another hospital. These patients may have been at a higher than average risk of death and hence their absence may have reduced the mortality for this period. Age. |
4) Turpeinen O (1968) | No cohort name defined: | Finnish Mental Hospital Men aged 34-64 from 2 mental hospitals in Helsinki. | 1959-1965 | See variables | CHD | Experimental diet (327 men) (In hospital N, the diet was changed: 1) whole milk was replaced by an emulsion of soybean oil in skim milk ["filled milk"], with a mean fat content of 3.9%. 2) butter and margarine were replaced by a brand of margarine especially prepared for this experiment and considerably more unsaturated than any of the brands marketed in Finland ("soft margarine"). The margarine as well as the filled milk were fortified with vitamins A and D. 3) The use of fat meats was discouraged. 4) Generous use of vegetable oils in cooking was recommended.). | Normal diet (254 men): (In hospital K, the diet was kept without any intentional change)
Follow-up period: | -In early 1965, when the experimental diet had been in use in hospital N a little over 6 years, the roles of the hospitals in the experimental design were reversed. -A considerable number of subjects (35% in hospital N and 44% in hospital K) remained in the study for the whole period of over 6 years. Population differences: -The mean age was almost identical. But in hospital N, a relatively smaller proportion of the total period of observation was contributed by subjects of the intermediate age classes and a relatively larger proportion by old subjects than in hospital K. -Diastolic hypertension was found to be present in 60 out of 225 patients (26.7%) in hospital N and in 64 out of 198 patients (32.3%) in hospital K. The difference was hardly of consequence. Dietary differences (food items): -During the follow-up period in hospital N the consumption was higher in the following food groups: cereals (average consumption over the 6 different years of follow-up = 230 vs 189 g/day), dried peas (7 vs 3), potatoes (512 vs 328), root vegetables (102 vs 76), filled milk (765 vs 0), buttermilk (122 vs 54), and soft margarine (29 vs 0). -During the follow-up period in hospital N the consumption was lower in the following food groups: berries and fruits (74 vs 140 g/day), sugar (62 vs 102), whole milk (0 vs 500), skim milk (2 vs 321), cream (2 vs 21), butter (0 vs 36), common margarine (2 vs 18), meat (131 vs 166), and eggs (13 vs 32). -During the follow-up period in hospital N the consumption was similar in the following food groups: other vegetables (91 vs 95), cheese (16 vs 15), and fish (61 vs 59). -The consumption of food energy was somewhat higher in hospital K during the earlier years of the experiment. Dietary differences (nutrients): -The amount of fat intake was consistently higher in hospital K by an amount of 9-28 g/day. -Carbohydrates in hospital K consisted of simple sugars to a larger extent than in hospital N. This was evident from the higher consumption of sugar and of berries and fruits including preserves. -The diet of hospital K contained considerably more cholesterol than that of hospital N. This difference was mainly due to the markedly higher consumption of eggs in the former hospital, and a nearly total removal of milk fat from the diet in hospital N. -Intakes of iron, thiamine, nicotinamide, and ascorbic acid showed small differences in favor of hospital N and that of vitamin A in favor of hospital K. -The dietary change in hospital N increased the quantity of polyunsaturated fatty acids more than threefold and decreased that of saturated fatty acids by one-half. 85% of the polyunsaturated fatty acids was made up by linoleic acid, and the rest consisted of linolenic acid. -The fatty acid composition of the diets differed considerably. Hospital N consumed less of the saturated fatty acids (lauric [ratio of N to K: 0.44], myristic [0.27], palmitic [0.62], and stearic [0.69]), and monounsaturated fatty acid (myristoleic [0.25]). But more of the polyunsaturated fatty acids (linoleic [2.61], linolenic [3.00]), and the monounsaturated fatty acid (eicosenoic [4.00]). Consumption of two other monounsaturated fatty acids was similar (palmitoleic [1.00], oleic [1.05]). Differences in cholesterol: -Serum cholesterol dropped in hospital N (235.8 → 214.6; P = < 0.001), but increased somewhat in hospital K (252.6 → 259.2; P = < 0.2) over the period 6 weeks after the dietary change. Results:
Coronary death: death ratios (observed/expected) for hospital N = 1.01, and for hospital K = 1.82 (P = ≥ 0.05), based on 17 deaths. Unadjusted. |
3) Report of a research committee to the medical research council (1968) | No cohort name defined | 393 men aged < 60, recently recovered from a first MI and discharched from 4 hospitals in London. | (Randomized allocation to experimental or control group) trial period: 2-7 | (1960-1967) See variables | Coronary heart disease | Experimental group: (a serum-cholesterol-lowering diet [diet low in saturated fats and containing 85 g of soya-bean oil - often drunk with fruit juice - daily]. The diet included 14 g moderately unsaturated 'blue band' margarine/day. Foods allowed included lean meat, any fish, skimmed milk, and clear soups. Foods forbidden included butter, other margarines, cooking-fat, other oils, fat meat, whole milk, cheese, egg yolk, and most biscuits and cakes). | Control group: (ordinary diet)
Differences in diet/nutrients between the experimental and control group: | -73 men in the experimental group, and 90 men in the control group were put on a reduced carbohydrate diet because of persistent weight gain. -No difference was found between intakes of total carbohydrates (243 g/d for the experimental, and 228 g/d for the control group, respectively), and sucrose (66 g/d for the experimental, and 60 g/d for the control group, respectively), but more controls were on the reduced carbohydrate diet. -There was some evidence that the control patients were eating less fried food than they did before their infarcts. -The experimental diet consumed less cholesterol (258 mg/d), than the control group (588 mg/d). -Calcium intake was consistently lower in the experimental group (808 mg/d), compared to the control group (930 mg/d), mainly because most cheeses were forbidden in the test diet. -Vitamin A intake was 1000 I.U. lower in the men on the test diet. Non-dietary difference: -A high degree of cooperation was achieved. -Subjects in the control group were significantly shorter. -Neither one of the diets influenced blood pressure, or average weight. -The experimental diet significantly decreased serum cholesterol. Results: CVD: There were 27 deaths from CVD (13.6 %) in the experimental group, and 25 (12.9 %) in the control group. CHD: There were 62 first relapses (31.2 %) in the experimental group, and 74 first relapses (38.1 % in the control group; P = NS).
Stroke: There were 2 stroke deaths (0.01 %) in the experimental group, and 0 (0 %) in the control group. Unadjusted. |
2) Dayton S (1970) | No cohort name defined | 846 men | Not defined | Not defined | Atherosclerotic disease (sudden death, definite overs/silent myocardial infarction, definite cerebral infarction, amputation of an extremity due to ischaemic gangrene, ruptured aneurysm, or intestinal infarction) | Not defined |
In incidences per 100 man-years. | Co = control group. Ex = experimental group.
Unadjusted. |
2) Dayton S (1969) | No cohort name defined | 846 (mostly Caucasian) male veterans aged 50-89 from the LA 'Domicile' (center), who did not use therapeutic diets, and did not have a known disease likely to result in death within 5 years. | (Randomized double blind trial of primary and secondary prevention) 8 | (1959-67 to 1967-68) See variables | Cardiovascular events (sudden death, definite/probable/possible MI, definite/possible cerebral infarction, definite/possible cerebral ischemia, [ruptured] aneurysm, intermittend claudication, peripheral occlusion, and angina pectoris) | Experimental diet (424 men) (Involving substitution of vegetable oils for about two thirds of the animal fat. Multiple vegetable oils were used, including corn, soybean, safflower, and cottonseed. Vegetable oils were incorporated into the experimental diet in the form of filled milk [butterfat has been removed and replaced by soybean or safflower oil], imitation ice cream, "unsaturated" margarine, special sausage products, and filled cheeses. Vegetable oils were used liberally in cooking and baking. Meat fat was minimized by the use of specially trimmed lean cuts. Egg yolks were restricted to 7 per week. Total fat was kept at around 40%.). | Normal diet (422 men) (conventional diet containing 40% fat calories, mostly of animal origin).
Mode of food service: Most persons ate in a single large facility with one kitchen and two dining rooms. The food was served ad libitum, cafetaria style, with the two groups of subjects separated physically from each other and from men not in the study. | Dietary differences: -The experimental diet contained less fat in grams (107.9 vs 111.2 g/d; P = < 0.001), and % calories (38.9 vs 40.1%; P = < 0.001). -The experimental diet contained more linoleic acid (almost 4 times as high), and alpha-linolenic acid, but less saturated fatty acids (myristic acid, palmitic acid, stearic acid). -The experimental diet contained less cholesterol (365 vs 653 mg/d; P = < 0.01). -The experimental diet contained more beta-sitosterol (a plant sterol) (215 vs < 50 mg/d; P = < 0.01). -No differences were found between diets in the amounts of calories, protein, or sucrose. -Experimental subjects had a much higher intake of alpha-tocopherol than the controls. Still, the experimental diet appeared slightly deficient and the control diet distinctly deficient in vitamin E. Changes in cholesterol: -Serum cholesterol in the control subjects showed a small rise over the first 20 months, then a progressive decline for the next 6 years. In the experimental subjects there was an immediate drop in serum cholesterol, amounting to 11%, followed by a slow decline paralleling that in the control group. The mean difference in cholesterol between diets amounted to 12.7%. -The change in serum cholesterol concentration among the experimental subjects proved to be poorly correlated with adherence to the diet (correlation coefficient = 0.13), indicating that a single follow-up blood cholesterol value is a poor index of adherence to diet during the 1 to 12 preceding weeks. Other differences: -There were more withdrawals in the experimental group (117 vs 58). -No effects were found on body weight. Weights from both diets remained within 2% of the starting level. -Among subjects from whom arteries were obtained for analysis, no differences were found between the two groups in lipid concentrations of the aorta, circle of Willis, coronary atheroma, or uncomplicated aortic atheroma. But the concentration of complicated aortic atheroma was higher in the experimental subjects than among the controls (P = 0.05). -The greatest difference between incidence rates of control and experimental subjects occured in the stratum with lowest adherence to the study diet. Also, within the experimental diet group alone, incidence rates were highest in the stratum with highest adherence to the study diet. Results:
Unadjusted. |
2) Dayton S (1969) | No cohort name defined: | LA Veterans 846 men aged ≥ 54 from the Domicilliary Unit in the LA Veterans Administration Center. | (randomized double-blind trial) 8 | (1959-1968) See variables | CHD | & Stroke Experimental group (n = 424): (a diet low in saturated fat and supplemented with unsaturated fat). | Control group (n = 422): (received a conventional American diet of typical composition)
Meals were served ad libitum, cafetaria style, from service lines which were separated physically. | Dietary differences: -Both diets were comparable with respect to caloric content, protein, and the quantity of fat. -The experimental diet contained almost 4 times as much linoleic acid as the control diet and correspondingly less saturated fat. The experimental diet contained less cholesterol (365 vs 655 mg/day). Other differences: -Mean weight in both groups remained within 2% of the starting levels. -Serum cholesterol levels dropped in both groups, but were lower in the experimental group (mean difference = 12.7% over the 8 year period). -Both groups were comparable at the start with regard to a large amount of variables, including age, weight, blood pressure, diabetes, serum cholesterol, serum total lipids, and previous CVD. -A larger amount of men in the experimental group withdrew from the study (117 vs 58), mainly due to dissatisfaction with filled milk. Results (number of men with CVD events in the control group vs the experimental group):
Some subjects had multiple events! Unadjusted. |
2) Dayton S (1968) | No cohort name defined | 846 male veterans aged 54-88 living in the domiciliary unit of the Los Angeles Veterans Administration Center. | (Randomized clinical trial) Not defined | See variables | CHD | & Stroke Experimental group (424 men): (a diet low in saturated fat and cholesterol, and high in unsaturated fat of vegetable origin). | Control group (422 men): (conventional diet)
Study design: | Food was served ad libitum, cafetaria style. Dietary differences: -The experimental group consumed a slightly smaller % of energy from fat (38.9 vs 40.1%). -The experimental group consumed more linoleic acid (38.4 vs 10.0% of total fatty acids), beta-sitosterol (215.0 vs 3.3 mg/day), and other sterols (48.4 vs 3.3 mg/day). -The experimental group consumed less cholesterol (365.4 vs 652.7 mg/day). -Adherence over the entire period of the trial amounted to 56% of total possible meals for the control subjects and 49% for the experimental group. Nondietary differences: -Mean differences in serum cholesterol between the experimental group and the control group amounted to 12.7% of the starting level. Results:
-The pooled data for definite myocardial infarction, sudden death, and definite cerebral infarction showed that a protective effect was found in the experimental group (P = 0.04). This effect was found among subjects younger than 65.5 years (P = 0.06), but not among subjects aged > 65 (P = 0.21). -The incidence of fatal atherosclerotic events was lower in the experimental group than among the controls, but the P was 0.26 Unadjusted. |
2) Dayton S (1966) | No cohort name defined | 782 institutionalized men aged ≥ 55 in a Veterans Administration Domiciliary unit. | (Randomized trial) 5 | (1959-1965) - | - | Experimental group (393 men): (a diet containing 40% of its calories as fab, but in which vegetable oil was subsituted for most of the saturated fats provided by the natural foods). | Control group (389 men): (a diet containing 40% of its calories as fat).
Dietary differences: | -Both groups consumed the same amount of calories (2,425 vs 2,400 for the experimental group and the control group, respectively), protein (95 vs 94 g), and fat (106 vs 108 g). -The experimental group consumed less dietary cholesterol in 1960-61 (365 vs 721 mg/day for the experimental group and the control group, respectively), and in 1964-65 (289 vs 675 mg/day). -The experimental group consumed more sterols (33 vs 0 mg/day alpha-sitosterol, 187 vs 16 mg/day beta-sitosterol, 269 vs 93 mg/day sitosterol, and 115 vs 41 mg/day campesterol/stigmasterol for the experimental group and the control group, respectively). -The experimental group consumed less of the fatty acids (lauric acid, myristic acid, pentadecylic acid, palmitic acid, 16:1, and stearic acid). -The experimental group consumed more of the fatty acids linoleic acid, and alpha-linolenic acid. -Both groups consumed the approximately the same amount of oleic acid. Nondietary differences: -Mean body weight of the control subjects underwent a small decline, while there was a rise of similar magnitude in weight of the experimental group. The reasons for these changes are not clear. -The major trends in serum cholesterol are not due to changes in composition of the study population. -The over-all mean difference in serum cholesterol = 14%. The over-all mean difference in the serum total lipid is half that of serum cholesterol (6.8%). - |
1) Rose GA (1965) | No cohort name defined | 51* subjects aged < 70, and with a history of infarction or angina (without valvular disease, anaemia, or syphilis), but without heart failure, or any non-cardiac disease likely to threaten life within 2 years. | (Randomized trial) 2 | See variables | Major cardiac events (sudden death, fatal infarction, and non-fatal infarction) | Experimental group [n = 25]: instructions were given to avoid fried foods, fatty meat, sausages, pastry, ice-cream, cheese, cakes (except plain sponge), etc. Milk, eggs, and butter were restricted. A corn oil supplement of 80 g./day was prescribed. | Control group [n = 26]: No advice on dietary fat was given.
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* = 3 subjects (2 control/1 experimental) were lost to follow-up, and 2 subjects (experimental) were removed from trial because of complications, leaving 51 subjects. -An attempt was made to assess how much oil each patient actually took, based on maximum estimates. For corn oil this was 64 g/day. -Patients in both groups tended on average to lose a little weight as time went on. This loss was greatest in the corn-oil group. -Mean calorie intakes were similar in both groups. -Corn oil decreased absolute levels of serum cholesterol, but no change was found in the control group. Unadjusted. |
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