High protein diet complements resin therapy of familial hypercholesterolemia. Randomised controlled trial of use by hypercholesterolaemic patients of a vegetable oil sterol-enriched fat spread. Comparison of the effects of dietary plant sterol and stanol esters on lipid metabolism. Dietary management of patients with familial hypercholesterolaemia treated with simvastatin. A randomized controlled trial of a public health nurse directed treatment program for rural patients with high blood cholesterol. Effects on coronary artery disease of lipid-lowering diet, or diet plus cholestyramine, in the St Thomas' Atherosclerosis Regression Study (STARS) The effect of soy protein with or without isoflavones relative to milk protein on plasma lipids in hypercholesterolemic postmenopausal women. Plant sterol ester-enriched spread lowers plasma total and LDL cholesterol in children with familial hypercholesterolemia. Cholesterol-lowering effect of the Food for Heart Nutrition Education Program.
The intermediate-term effects on plasma lipoprotein lipids of substituting meat and dairy protein for carbohydrate in the diets of five subjects (three women, two men) with familial hypercholesterolemia receiving cholestyramine (mean dose, 18 g/d) were studied. Subjects were randomly allocated to either the high or low protein diets (mean 27 versus 10% of energy as protein, 25% as fat, and 48 versus 65% as carbohydrate) for 4 to 5 weeks and then switched to the other diet for another 4 to 5 weeks. Mean fasting plasma HDL cholesterol rose significantly by 17 +/- 3% (1.11 +/- 0.12 vs 0.95 +/- 0.11 mmol/L, p less than 0.005, n = 5), whereas total triglycerides fell by 23 +/- 2% (1.7 +/- 0.3 vs 2.2 +/- 0.3 mmol/L, p less than 0.005, n = 5), VLDL triglycerides fell by 28 +/- 5% (0.88 +/- 0.15 vs 1.18 +/- 0.19 mmol/L, p less than 0.02, n = 5), VLDL cholesterol fell by 32 +/- 7% (0.39 +/- 0.08 vs 0.56 +/- 0.09 mmol/L, p less than 0.01, n = 5), the ratio of LDL cholesterol: HDL cholesterol by 19 +/- 5% (4.7 +/- 0.7 vs 5.7 +/- 0.7, p less than 0.05) and that of total cholesterol: HDL cholesterol by 16 +/- 5% (6.6 +/- 0.5 vs 8.0 +/- 0.7, p less than 0.05) on the high versus low protein diet. Increasing dietary protein intake at the expense of carbohydrate may be useful in treating hypoalphalipoproteinemia and/or hypertriglyceridemia in patients with familial hypercholesterolemia. Plant sterols may be a useful additive therapy in the treatment of hypercholesterolaemic patients. The purpose of this study was to determine the effect of a fat spread enriched with vegetable oil sterols on plasma lipid, lipoprotein and apolipoprotein concentrations. A randomised double blind placebo-controlled crossover trial with two consecutive periods of 8 weeks was conducted. 30 patients with heterozygous familial hypercholesterolaemia treated concurrently with an HMG-CoA reductase inhibitor (statin) and 32 patients with type IIa primary hypercholesterolaemia with a total cholesterol concentration >6.5 mmol/l not taking lipid-lowering drug therapy were recruited from a hospital lipid clinic. The active treatment was a fortified fat spread (25 g/day) providing 2.5 g of plant sterols. The control spread was indistinguishable in taste and appearance. Comparison at the end of the two 8-week trial periods showed a statistically significant reduction in total and LDL-cholesterol with use of the fortified spread but the results were confounded by a carry-over effect, which was partly explained by changes in the background diet. Because a carry-over effect was present, further analyses were restricted to the parallel arms of the first treatment period and were conducted on an intention to treat basis. After 4 weeks, LDL-cholesterol had decreased by 0.04 mmol/l ([0.8%] 95% confidence interval -0.44-0.37 NS) in the placebo group and decreased by -0.76 mmol/l ([15.0%] 95% CI -1.03--0.48, P<0.0001) in the active treatment group. After 8 weeks, the corresponding results were 0.0 mmol/l ([0.0%] 95% CI -0.26-0.24 NS) and -0.51 mmol/l ([10.0%] 95% CI -0.73--0.29 P<0.0001). There were no significant changes in apolipoprotein AI or B concentrations in the placebo group, but there was a small but statistically significant increase in apolipoprotein AI and a decrease in apolipoprotein B in the active treatment group. HDL cholesterol and triglyceride concentrations were unchanged. There was no difference in response between patients with statin-treated familial hypercholesterolaemia and patients with type IIa hyperlipoproteinaemia. We conclude that a fortified fat spread enriched with vegetable oil sterols reduces LDL-cholesterol by 10-15% with no difference in response between hypercholesterolaemic patients prescribed statins and those not taking lipid-lowering drug therapy. To compare the cholesterol-lowering efficacy and other metabolic effects of plant sterol and stanol esters, both of which are commonly used in the dietary management of hypercholesterolaemia.
                The cholesterol-lowering efficacy of equivalent intakes of sterol and stanol esters and of different intakes of stanol esters were compared at 1 and 2 months, both in normal subjects and treated patients with familial hypercholesterolaemia. Systemic effects were assessed by measuring serum levels of plant sterols and of lathosterol and 7alpha-hydroxy-cholestenone, indices of sterol absorption and of cholesterol and bile acid synthesis respectively. There were no significant differences during the study between 1.6g daily of sterol and stanol esters in reducing total cholesterol (by 3-7%) or low density lipoprotein cholesterol (by 4-8%), nor between 1.6 and 2.6 g daily of stanol. However, the cholesterol-lowering effect of plant sterol esters was attenuated between 1 and 2 months. This was accompanied by increased serum plant sterols and decreased levels of 7alpha-hydroxy-cholestenone, especially in statin-treated hypercholesterolaemic patients not taking bile acid sequestrants.
                These findings suggest that absorption of dietary plant sterols suppressed bile acid synthesis, thereby diminishing their cholesterol-lowering efficacy. In contrast, plant stanols reduced plant sterol absorption and maintained their cholesterol-lowering efficacy. The effect of diet on plasma lipids and lipoproteins was examined in 19 patients with familial hypercholesterolaemia treated with the HMGCoA reductase inhibitor, simvastatin. The study was a randomized double-blind cross-over trial of two diets: a low fat diet and a higher fat diet, and was performed to determine whether ongoing attention to diet is necessary for patients receiving this drug for the treatment of familial hypercholesterolaemia. Plasma cholesterol concentration was 6.5 per cent lower on the low fat diet than on the high fat diet. The difference was within the range predicted by the Jacobs modification of the Keys formula from the reported intake on the two diets. The fall on the low fat diet was principally accounted for by a reduction in low density lipoprotein cholesterol, although high density lipoprotein cholesterol and apolipoprotein A1 also fell. Patients taking HMGCoA reductase inhibitors for the treatment of familial hypercholesterolaemia respond to changes in dietary fat intake. They are thus likely to achieve further reduction in their coronary heart disease risk, and should remain on a low saturated fat low cholesterol diet even when taking these powerful lipid lowering drugs. Many rural residents do not have access to high-quality nutrition counseling for high blood cholesterol. The objective of this study was to assess the effectiveness of an intervention program designed to facilitate dietary counseling for hypercholesterolemia by rural public health nurses.
                Eight health departments (216 participants) were randomized to give the special intervention (SI) and nine (252 participants) to give the minimal intervention (MI). The SI consisted of three individual diet counseling sessions given by a public health nurse, using a structured dietary intervention (Food for Heart Program), referral to a nutritionist if lipid goals were not achieved at 3-month follow-up, and a reinforcement phone call and newsletters. Diet was assessed by the Dietary Risk Assessment (DRA), a validated food frequency questionnaire, at baseline, 3-, and 12-month follow-up; blood lipids and weight were assessed at baseline, 3-, 6-, and 12-month follow-up.
                Participants were largely female (71%), older (mean age 55), and white (80%). At 3-month follow-up, the average reduction (indicating dietary improvement) in total Dietary Risk Assessment score was 3.7 units greater in the SI group (95% confidence interval [CI] 1.9 to 5.5, P = 0.0006), while both groups experienced a similar reduction in blood cholesterol, 14.1 mg/dL (0.37 mmol/L) for SI and 14.5 mg/dL (0.38 mmol/L) for minimal intervention group (difference -0.4 mg/dL [-0.010 mmol/L], 95% CI -12.5 to 11.7 [-0.32 to 0.30], P = 0.9). At 12-month follow-up, the reduction in total Dietary Risk Assessment score was 2.1 units greater in the SI group (95% CI 0.8 to 3.5, P = 0.005), while the reduction in blood cholesterol was similar in both groups, 18.4 mg/dL (0.48 mmol/L) for SI and 15.6 mg/dL (0.40 mmol/L) for minimal intervention group (difference 2.8 mg/dL [0.07 mmol/L], 95% CI -7.5 to 13.1 [-0.19 to 0.34], P = 0.6). During follow-up, weight loss was greater in the SI group; the difference between groups was statistically significant at 3 (1.9 lb [0.86 kg], 95% CI 0.3 to 3.4 [0.14 to 1.55], P = 0.022) and 6 months (2.1 lb [0.95 kg], 95% CI 0.1 to 4.1 [0.04 to 1.86], P = 0.04). At 12 months, the difference was not significant (1.6 lb [0.73 kg], 95% CI -0.05 to 3.7 [-0.02 to 1.68], P = 0.13).
                Improvement in self-reported dietary intake was significantly greater in the SI group, while reduction in blood cholesterol was similar in both groups. To assess the effect of dietary reduction of plasma cholesterol concentrations on coronary atherosclerosis, we set up a randomised, controlled, end-point-blinded trial based on quantitative image analysis of coronary angiograms in patients with angina or past myocardial infarction. Another intervention group received diet and cholestyramine, to determine the effect of a greater reduction in circulating cholesterol concentrations. 90 men with coronary heart disease (CHD), who had a mean (SD) plasma cholesterol of 7.23 (0.77) mmol/l were randomised to receive usual care (U, controls), dietary intervention (D), or diet plus cholestyramine (DC), with angiography at baseline and at 39 (SD 3.5) months. Mean plasma cholesterol during the trial period was 6.93 (U), 6.17 (D), and 5.56 (DC) mmol/l. The proportion of patients who showed overall progression of coronary narrowing was significantly reduced by both interventions (U 46%, D 15%, DC 12%), whereas the proportion who showed an increase in luminal diameter rose significantly (U 4%, D 38%, DC 33%). The mean absolute width of the coronary segments (MAWS) studied decreased by 0.201 mm in controls, increased by 0.003 mm in group D, and increased by 0.103 mm in group DC (p less than 0.05), with improvement also seen in the minimum width of segments, percentage diameter stenosis, and edge-irregularity index in intervention groups. The change in MAWS was independently and significantly correlated with LDL cholesterol concentration and LDL/HDL cholesterol ratio during the trial period. Both interventions significantly reduced the frequency of total cardiovascular events. Dietary change alone retarded overall progression and increased overall regression of coronary artery disease, and diet plus cholestyramine was additionally associated with a net increase in coronary lumen diameter. These findings support the use of a lipid-lowering diet, and if necessary of appropriate drug treatment, in men with CHD who have even mildly raised serum cholesterol concentrations. Clinical trial data and the results of a meta-analysis suggest a hypocholesterolemic effect of soy protein. The effect may be partially attributable to the isoflavones in soy. Few studies have examined the separate effects of soy protein and isoflavones.
                The objective of this study was to determine the effect of soy protein and isoflavones on plasma lipid concentrations in postmenopausal, moderately hypercholesterolemic women.
                This was a randomized, double-blind, placebo-controlled clinical trial with 3 treatment groups. After a 4-wk run-in phase during which the women consumed a milk protein supplement, the subjects were randomly assigned to 12 wk of dietary protein supplementation (42 g/d) with either a milk protein (Milk group) or 1 of 2 soy proteins containing either trace amounts of isoflavones (Soy- group) or 80 mg aglycone isoflavones (Soy+ group).
                LDL-cholesterol concentrations decreased more in the Soy+ group (n = 31) than in the Soy- group (n = 33) (0.38 compared with 0.09 mmol/L; P = 0.005), but neither of these changes was significantly different from the 0.26-mmol/L decrease observed in the Milk group (n = 30). The results for total cholesterol were similar to those for LDL cholesterol. There were no significant differences in HDL-cholesterol or triacylglycerol concentrations between the 3 groups.
                The difference in total- and LDL-cholesterol lowering between the 2 soy-protein supplements suggests an effect attributable to the isoflavone-containing fraction. However, the unexpected LDL-cholesterol lowering observed in the Milk group, and the fact that there was no significant difference between either soy group and the Milk group, suggests that changes may have been due to other factors related to participation in the study. Naturally occurring plant sterol esters (SEs) favorably affect serum cholesterol concentrations in humans and could aid in the treatment of children with familial hypercholesterolemia (FH).
                We studied the effect of SE-enriched spread on serum lipids, lipoproteins, carotenoids, fat-soluble vitamins, and physiologic variables in children with FH aged 7-12 y.
                In a randomized, double-blind crossover study comprising two 8-wk interventions, 38 children with FH consumed 18.2 +/- 1.5 g SE spread/d, corresponding to 1.60 +/- 0.13 g SEs, or a control spread. Blood samples were analyzed at the start and end of each diet period.
                Plasma LDL-cholesterol concentrations decreased by 10.2% (P = 0.003) during the SE period compared with the control period. Total cholesterol and apolipoprotein B concentrations were reduced by 7.4% (P = 0.007 and P = 0.020, respectively) during the SE period. No changes were observed in HDL cholesterol, triacylglycerol, or apolipoprotein A-I. Serum concentration of lipid-adjusted lycopene decreased by 8.1% (P = 0.015) in the SE period, with no changes in the other carotenoids. Lipid-adjusted retinol and alpha-tocopherol concentrations increased by 15.6% (P < 0.001) and 7.1% (P = 0.027), respectively. There was an increase (16.8%, P = 0.04) in alanine transaminase in the SE period, but this was explained by a significantly lower starting concentration in the SE period than in the control period. The children consumed a recommended American Heart Association Step I diet during both intervention periods.
                A daily intake of 1.6 g SEs induces an additional reduction in LDL-cholesterol concentrations in children with FH consuming a recommended diet. The objective of this prospective, randomized controlled trial was to assess the effectiveness of the Food For Heart Program patient nutrition tool in hypercholesterolemic outpatients. The setting for this study was an urban academic primary-care practice; 175 hypercholesterolemic adults not taking cholesterol-lowering medications were enrolled as subjects. The study intervention involved four monthly dietary counseling visits, using the Food For Heart Program, conducted by the study research assistant. The main outcome measures were fasting serum lipids (primary); body weight (secondary); and change in Dietary Risk Assessment score (intervention group only), analyzed using Student's t test. Our results showed that total and low-density lipoprotein cholesterol decreased 0.40+/-0.65 mmol/L and 0.32+/-0.58 mmol/L, respectively, in the intervention group (n=91), compared with 0.06+/-0.57 mmol/L and 0.0088+/-0.56 mmol/L in the control group (n=84) ( P <.001). There was no significant change in high-density lipoprotein cholesterol. Intervention subjects lost a small but statistically significant amount of weight, 2.2+/-7.4 pounds ( P <.01), and decreased their Dietary Risk Assessment score 5.9+/-6.5 points ( P <.001). Based on these findings, we concluded that total and low-density lipoprotein cholesterol, weight, and dietary risk for coronary heart disease decreased significantly in hypercholesterolemic patients counseled using the Food For Heart Program.
No conclusions can be made about the effectiveness of a cholesterol-lowering diet, or any of the other dietary interventions suggested for familial hypercholesterolaemia, due to the lack of adequate data. Large, parallel, randomised controlled trials are needed to investigate the effectiveness of a cholesterol-lowering diet and the addition of omega-3 fatty acids, plant sterols or stanols, soya protein to a cholesterol-lowering diet.