Cardiovascular Disease/Cholesterol Lowering

Although the IOM AI guidelines were based on an association between high-fiber consumption and a reduced risk of CVD [1], a more recent (2016) comprehensive review found only a weak negative association between total fiber intake and risk of CVD (relative risk 0.92) [4]. Findings were similar for cereal fiber, fruit fiber, and vegetable fiber [4]. The reason for these weak associations may be due to the lack of differentiation between specific fiber characteristics within “dietary fiber” (e.g., insoluble versus soluble, nonviscous versus gel-forming). When specific isolated fibers were assessed for lowering elevated cholesterol, the results were similar to improvement in glycemic control: only gel-forming fibers lowered elevated serum total and low-density lipoprotein (LDL) cholesterol, and the degree of cholesterol lowering was highly correlated with the viscosity of the gel-forming fiber [8]. The viscosity of a gel-forming fiber is actually a better predictor of cholesterol-lowering efficacy than the quantity of fiber consumed [9]. The primary mechanism by which soluble gel-forming fibers lower serum cholesterol is by trapping and eliminating bile acids [3, 5]. These are normally recovered in the distal ileum and recycled, potentially several times within a single meal. When bile acids are trapped in a gel-forming fiber and eliminated via stool, the reduction in the bile acid pool causes hepatocytes to compensate by increasing LDL-cholesterol clearance to synthesize more bile acids (cholesterol is a component of bile) to maintain sufficient bile acids for digestion. This clearance of LDL-cholesterol from the blood lowers serum LDL-cholesterol and total-cholesterol concentrations, without significantly affecting high-density lipoprotein (HDL) cholesterol concentration [3, 5]. Only viscous, gel-forming fibers (e.g., high molecular weight p-glucan, raw guar gum, psyllium), consumed with meals to coincide with bile release, effectively lower elevated serum cholesterol concentrations [3, 5, 7-11].

The importance of viscosity for a gel-forming fiber was demonstrated in a clinical study that compared the cholesterol-lowering effectiveness of several different viscosities of p-glucan (the fiber in oatmeal) [8]. The results showed that cholesterol lowering was highly correlated with the viscosity of the gel-forming fiber: the high-viscosity p-glucan (low heat and pressure processing) exhibited significant LDL-cholesterol lowering (-5.5%; p < 0.05 versus bran placebo), as did the medium- viscosity (-4.7%; p < 0.05), whereas the lower viscosity did not exhibit a significant cholesterollowering effect [8]. This means that it is not only important to recognize which raw fibers provide a specific physiologic effect, but to also consider how processing (e.g., heat/extrusion to create cereal shapes) may affect/eliminate viscosity and efficacy. Note that insoluble fiber (wheat bran) was used as a negative control in the study. Insoluble fibers (e.g., wheat bran, cellulose) and nonviscous soluble fibers (e.g., wheat dextrin, inulin) do not provide viscosity/gel-dependent physiologic effects and can be used as a negative control (placebo) in clinical studies [3]. It should also be noted that viscosity alone is not sufficient to provide gel-dependent cholesterol lowering. In a 2-month clinical study of 163 patients with hyperlipidemia, psyllium, a natural gel-forming fiber, significantly decreased both LDL and total cholesterol versus placebo (insoluble cellulose), while viscous methylcellulose (chemically treated wood pulp) and calcium polycarbophil (synthetic polymer) did not significantly affect cholesterol measures [10].

Psyllium has been well studied for its cholesterol-lowering effects (24 randomized, well-controlled clinical studies, totaling 1568 subjects) and showed reductions of 6-24% for LDL-cholesterol and

2-20% for total cholesterol, versus placebo [11]. Efficacy tends to be greater in studies assessing patients with higher baseline cholesterol concentrations, and studies where diet was not restricted (similar to many patients). Gel-forming fibers are also safe and effective in children. A 2014 study in 51 children and adolescents with hyperlipidemia assessed the effects of psyllium (7 g/day) versus placebo (cellulose) for cholesterol lowering while on a restricted diet [12]. After 2-months of treatment, both total cholesterol and LDL-cholesterol were significantly decreased (8% and 11%, respectively) versus placebo. The authors noted that psyllium therapy was both safe and well tolerated

[12]. There are two fibers approved by the Food and Drug Administration for claims of a reduced risk of CVD by lowering serum cholesterol: p-glucan (oats and barley) and psyllium, both viscous, gelforming fibers [13].

A gel-forming fiber can be an effective lifestyle intervention/co-therapy for statins and bile acid sequestrants, with the potential to lower the required dose and/or side effects of the drugs [3]. In a

3-month study in 68 patients with hyperlipidemia, low-dose simvastatin (10 mg) combined with psyllium (15 g/day, divided doses before meals) was superior to low-dose simvastatin alone [LDL- cholesterol -63 mg/dL (-1.6 mmol/L) versus -55 mg/dL (-1.4 mmol/L), respectively; p = 0.03]

[14]. The combination of psyllium and low-dose simvastatin was equivalent to high-dose (20 mg) simvastatin alone [both -63 mg/dL)(-1.6 mmol/L)] [14]. Similar results were observed for total cholesterol and apolipoprotein B, but there were no significant changes from baseline for triglyceride or HDL-cholesterol concentrations [14]. When combined with colestipol or cholestyramine, psyllium increased cholesterol-lowering efficacy and decreased symptoms associated with seques- trant therapy [3].

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