There is very limited evidence of the efficacy of dietary interventions in people with familial hypercholesterolaemia (FH). Recommendations by the National Institute for Health and Clinical Excellence (NICE) for people with FH [NICE, 2008] are extrapolated from three systematic reviews of dietary interventions in the general population [Howell et al, 1997; Hooper et al, 2000; Brunner et al, 2007] which suggest that cholesterol lowering diets can lead to a maximum lipid lowering of 5–10% [National Collaborating Centre for Primary Care, 2008b]. There is also very limited evidence from a systematic review [Moruisi et al, 2006] and one subsequent, small, short-term study [Jakulj et al, 2006] that foods containing plant sterols and stanols can reduce low-density lipoprotein cholesterol (LDL-C) concentrations in people with heterozygous FH.

Dietary interventions in people with FH

• All dietary treatments:
• In a Cochrane review of dietary treatment for FH (most recent search date: 2003), seven small, crossover, randomized controlled trials (RCTs) were included (n = 135) [Poustie and Rutherford, 2001]. The studies were too small, of too short duration (1–3 months), or lacked appropriate analysis for any conclusions to be made about the efficacy of dietary treatments for FH.
• Plant stanols and sterols:
• A systematic review of the efficacy of phytosterols/stanols in lowering total cholesterol and LDL-C concentration in FH subjects reported on the findings of six RCTs (n = 150), four of which were included in the meta-analysis (n = 123), two being excluded because of inappropriately high concentrations of plant sterols used [Moruisi et al, 2006].
• Studies lasted between 4 weeks and 3 months.
• In the meta-analysis of four studies, fat spreads containing phytosterols/stanols reduced total cholesterol and LDL-C by 0.65 mmol/L (95% CI 0.42 to 0.88, p < 0.001) and 0.64 mmol/L (95% CI 0.43 to 0.86, p < 0.001) respectively over an average of 6.5 weeks, compared with control treatment.
• There were either no, or minor, gastrointestinal adverse effects reported.
• The results were statistically homogeneous but no sensitivity analysis was done to assess the effect of excluding the two studies from the meta-analysis.
• A crossover RCT, published subsequently, compared a plant stanol-containing yoghurt with a yoghurt without plant stanol in 41 pre-pubescent children with FH [Jakulj et al, 2006]:
• LDL-C decreased with treatment by a mean of –0.48 mmol/L (9.2%) compared with placebo, but the authors report the 95% CI for the difference as –0.69 to +0.27 and the p-value for the difference as < 0.001; the p-value and 95% CI are inconsistent.

Dietary interventions in the general population

• Three systematic reviews of dietary interventions have been published [Howell et al, 1997; Hooper et al, 2000; Brunner et al, 2007]. Meta-analyses were carried out of trials with mixed populations and diets. Only one review reported clinical outcomes [Hooper et al, 2000]. Based on the findings of the reviews, NICE concluded that cholesterol lowering diets can lead to a maximum lipid lowering of 5–10% [National Collaborating Centre for Primary Care, 2008b].
• In a Cochrane review of primary prevention of cardiovascular disease with reduced or modified dietary fat, 27 trials (30,901 person-years) lasting at least 6 months were included [Hooper et al, 2000]:
• There was no significant effect on total mortality or cardiovascular mortality (relative risk [RR] 0.91, 95% CI 0.77 to 1.07), but a significant reduction in cardiovascular events (RR 0.84, 95% CI 0.72 to 0.99) was found.
• When a large study that included fish oils in the intervention was excluded, statistical significance was lost.
• The average reduction in total serum cholesterol was 0.64 mmol/L (11.1%; confidence interval and p-value not reported).
• In an earlier review of 224 dietary intervention studies, including those of low quality (internal validity), meta-analysis suggested that, in people with baseline LDL-C concentrations greater than 4.14 mmol/L, reductions in intake of saturated and polyunsaturated fatty acids lead to average reductions in LDL-C of 4.5–7.7%, depending on the intensity of the diet [Howell et al, 1997].
• In another Cochrane review of dietary advice for cardiovascular risk, meta-analysis was performed on 38 RCTs in adults (n = 17,871) [Brunner et al, 2007]. Study inclusion criteria were a drop-out rate of less than 20% and a study duration of at least 3 months. Benefits of dietary advice were statistically significant but small: dietary advice reduced total serum cholesterol by 0.16 mmol/L (95% CI 0.06 to 0.25) and reduced LDL-C by 0.18 mmol/L (95% CI 0.1 to 0.27) after 3–24 months.