Using Psyllium to Prevent and Treat Obesity Comorbidities

C H A P T E R

19 Using Psyllium to Prevent and Treat Obesity Comorbidities Sebely Pal, Jenny McKay, Monica Jane, Suleen Ho School of Public Health, Faculty of Health Sciences, Curtin University, Perth, WA, Australia

O U T L I N E Introduction

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Vascular Function

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Psyllium and Health

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Conclusion

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Body Composition and Appetite

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Acknowledgments

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Blood Sugar Levels and Insulin Regulation

References

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Blood Lipids

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INTRODUCTION Overweight and obesity are currently some of the most visible public health problems and have become an escalating global epidemic.1 As of 2014, approximately 1.9 billion individuals 18 years and over were overweight and 600 million were obese.2 In recent years, obesity has superseded malnutrition in becoming the predominant public health issue.3 Being obese significantly increases the risk of developing metabolic syndrome (MS), which is associated with increased cardiovascular morbidity and mortality, and has been implicated in the development of atherosclerosis.4 MS consists of a combination of different abnormalities,5 such as glucose intolerance, insulin resistance, abdominal obesity, atherogenic dyslipidemia, impaired endothelial function, hypertension, and inflammation.6 The prevalence of MS is quoted as 34% according to National Health and Nutrition Examination Survey (NHANES) 2003–2006; however, the

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prevalence of MS is approaching 50% worldwide.7 The risk of having a heart attack or stroke is three times more likely and the risk of developing T2D is five times more likely with MS compared with those without MS.8 Epidemiological and cohort studies have consistently revealed that higher fiber intakes produce health benefits and a consequent risk reduction for MS, cardiovascular disease (CVD), and T2D resulting from a lower body weight, lower body mass index (BMI), lower waist circumference,9,10 improved plasma lipid profiles,11–20 and improved glycemia and insulinemia.21 Current dietary fiber recommendations for adults in Australia, Canada, the United States, and Europe are 25–30 g/day to be achieved by consuming fiber-rich foods such as fruit, vegetables, legumes, and whole grains.22 However, it is estimated that the intake of fiber in the United States and many other developed countries is around 15 g/day,23 only half the amount recommended by the American Heart Association.22 Although the benefits of fiber are well known, most find it difficult to eat the required amounts of fiber by increasing fruit and vegetable intake, as shown by the Continuing Survey of Food Intakes by Individuals 1994–96, 1998.24,25 Therefore, fiber supplements may provide a cost effective and easy alternative for increasing the fiber content of a diet, without the need for other major dietary modifications. Psyllium seed husk is a viscous, water-soluble fiber supplement.26 It is one of the most widely used fiber supplements in the world, because it is reasonably cheap, available in several flavors, and sold as powdered drink mixes, capsules, or wafers. Psyllium is better tolerated than other fiber supplements because it causes less abdominal bloating; thus, it has advantages over other types of soluble fiber.26 Psyllium has been shown to be an effective adjunct to dietary intervention in the control of body weight, body composition, and cholesterol, glucose, insulin, and triglyceride (TG) levels both in animal27–29 and human studies.30–35 Therefore, the aim of this chapter is to review the benefits of psyllium fiber on several components of MS, such as body weight, body composition, satiety, glucose and insulin homeostasis, lipids and lipoproteins, blood pressure, and vascular function.

PSYLLIUM AND HEALTH Dietary fiber is an edible component of all plants that is defined as being resistant to digestion and absorption in the small intestine; it usually undergoes partial or complete fermentation in the large intestine.36,37 Psyllium is a well-established a blood cholesterol-lowering agent and bowel regulator.38,39 These physiological benefits are thought to be due to its composition: it is a soluble gel-forming mucilage from the Plantago ovata plant, the bioactive fraction of which is a fiber composed of highly branched arabinoxylan,26 in which xylose forms the backbone, and arabinose and xylose form the side chains. Psyllium causes less flatulence and abdominal distending because it is less readily fermented than other fiber types.26 Interestingly, a study in rats showed that arabinose undergoes less fermentation in comparison to xylose.40 Arabinose digestibility was also found to be lower than xylose digestibility in human studies of psyllium.41,42 Thus, it seems that the linear chain of psyllium is fermented until an atypical branch point (that is unavailable to microbial activity) is reached41; this explains why it is less completely fermented than other fibers, thus causing less gastrointestinal issues.

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BODY COMPOSITION AND APPETITE Improvements in body weight have been linked to psyllium in animal studies27; however, this issue is still controversial in humans.34,35,43–47 Galisteo et al. observed that Zucker rats (a model for T2D) fed a psyllium-supplemented diet for 25 weeks had a significantly reduced body weight gain compared with those fed a standard diet.27 Results of a parallel-design study by Pal et al. are in agreement with these data.34 Investigators compared the effects of four different diets adults with an average BMI of 34 kg/m2: a control diet (with placebo), a control diet supplemented with 21 g of psyllium (FIB), a healthy diet plus placebo (HLT), and a healthy diet supplemented with 21 g of psyllium (HLT-FIB).34 They found that both diets containing psyllium (FIB and HLT-FIB) significantly reduced body weight (
2.1 kg, p ¼ 0.007 and
2.6 kg, p < 0.001, respectively), and percentage total body fat (
2.3%, p ¼ 0.002 and
2.7%, p < 0.001, respectively) compared with the control diet after 12weeks.34 In contrast, a study of 83 normal-weight participants randomized to receive placebo or 16.5-g Minolest (containing 16% guar gum and 62% psyllium as the principal active ingredients) per day for 3 months found no differences in body weight and BMI between the two treatments.46 More recently, a 6-week crossover intervention study with 47 healthy males 15–16 years of age supplementing 6 g of psyllium/day did not report any significant change in weight, body fat mass, or dietary intake.48 The lack of weight loss in the latter five studies may be related to the fact that the participants were in the healthy weight range or only slightly overweight. However, another study found some improvements in BMI after 6 months of 10.5 g/day of either psyllium or guar fiber supplementation compared with a standard diet in hypertensive, slightly overweight individuals.32 In the psyllium-treated patients, the BMI decrease was statistically significant after 4 months of supplementation (
0.8  0.2), and continued after 6 months (
2.0  0.3).32 In the guar-treated patients, the BMI decrease was already statistically significant after the first 2 months of supplementation (
0.9  0.2) and it progressively continued after 6 months (
1.8  0.3).32 In addition, a randomized crossover design study for 3 weeks separated by a 2-week washout period compared the effects of low-viscosity wheat bran at 10.8 g/day, medium-viscosity psyllium at 9 g/day, and a high-viscosity fiber blend at 5.1 g/day in 23 healthy weight participants with an average BMI of 23.8  4.6 kg/m2.47 This study found no differences among the treatments in the amount of food consumed, total dietary fiber intake, reported physical activity, and body weight.47 A double-blind placebo-controlled study, which included 125 normal weight and overweight patients with T2D, showed no significant changes in body weight in either the low-fat diet plus 15 g/day psyllium or the low-fat diet plus placebo after a 6-week period.45 Another study showed no significant changes in BMI in slightly overweight T2D patients with an average BMI of 26.7 kg/m2 following the consumption for 8 weeks of 10.2 g/day of psyllium compared with placebo.35 Recent research supports these findings. A randomized controlled trial with 40 overweight and obese T2D patients 35 years and over found that adding 10.5 g of psyllium to their habitual diet reduced weight by 2.9 kg (p < 0.001), BMI by 0.9 kg/m2 (p < 0.001), waist circumference by 2.7 cm (p < 0.001), and hip circumference by 2.6 cm (p < 0.001) by the end of the 8-week intervention period.49 Pal et al. conducted a long-term randomized, placebocontrolled trial with overweight and obese adults aged between 19 and 68 years, and involved adding a 5-g psyllium supplement to the usual diet 3 times per day with 500-mL water 10 min

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prior to meals (n ¼ 43).50 By the end of the 52-week intervention, this group showed significantly reduced waist circumference (p < 0.01), body fat mass (p ¼ 0.038), and significantly increased lean mass (p ¼ 0.017) compared with the rice flour control (n ¼ 45).50 In addition, the psyllium group recorded significant weight loss compared with baseline measurements, however there was also a significant decrease in energy intake, which may have been incidental toor as a result of- the 12-month intervention as causation could not be established with the data available.50 The role of psyllium in appetite control has been investigated but the findings are inconsistent.51,52 Dietary protein is thought to be the most satiating macronutrient compared with others such as fat or carbohydrate53–56; however, psyllium fiber may possess similar qualities. Female participants were randomized to one of three treatment groups: psyllium (20 g granules with 200 mL water), placebo (20 g granules with 200 mL water), or plain water (200mL), 3 h before meals and the same dose immediately after meals.52 Psyllium consumption significantly increased fullness (measured using visual analog scales) 1-h post-meal compared with both placebo and water groups (p < 0.05). The authors concluded that psyllium may be a useful supplement in weight control diets because it affects fat intake and may affect subjective feelings of fullness.52 Fiber-enriched meals have also been shown to significantly decrease ghrelin and peptide YY (PYY) appetite hormone responses in healthy participants compared with proteinenriched meals.51 Interestingly, a study showed postprandial ratings of appetite to be similar after meals supplemented with either psyllium fiber or protein.51 Psyllium has been shown to produce a greater suppression of snack intake compared with wheat bran in a study that compared the effects on short-term (24-h) appetite of three isocaloric breakfasts containing high-insoluble fiber cereal (22 g total: 4.4 g psyllium and 17.6 g wheat bran), high-soluble fiber cereal (22 g total: 17.6 g psyllium and 4.4 g wheat bran), or a low-fiber cereal (3 g; 1.5 g of both soluble and insoluble fiber) in healthy, normal-weight males after an overnight fast.57 However, there was no significant effect of break-fast type on total daily energy intake57; although appetite seems to decrease after the consumption of psyllium, this effect does not appear to differ from those of other sources of fiber.52,57 The mechanisms through which dietary fiber, including psyllium, can affect weight loss, appetite, and energy intake include its effects on gastric emptying,58 satiety,59 and gut hormones such as cholecystokinin,60 as well as alterations to glycemic index or insulin response.61 The act of chewing takes longer when consuming fiber-rich foods, which may increase sensory satiety and diminish meal size.62–64 Dietary fiber reduces the energy density of foods, which may directly moderate energy intake and indirectly decrease appetite.65 Another mechanism to explain the satiating power of psyllium includes the role of fiber in decreasing intestinal passage rates, which leads to prolonged nutrient absorption and, consequently, increased satiety.66 Soluble fiber ferments in the large intestine, thus increasing the concentration of short-chain fatty acids that may enhance satiety.67 In addition, fiber has also been suggested to decrease energy absorption by lowering the bioavailability of fatty acids and proteins.68 The effects of fiber-rich diets on appetite control, energy intake, and body weight may be related to the chemical structure of the fiber and its physicochemical properties such as solubility, viscosity, water-holding capacity, and ferment-ability, rather than on the amount of fiber ingested.26,63 While psyllium fiber seems to improve body weight in animals,27 the lack of a significant change in body weight in many of the human studies may be due to the fact that most of the

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participants had a healthy starting weight; however, weight loss has been observed in studies with obese participants. In addition, the controls in many of these studies varied, including a standard or low-fat diet plus placebo, placebo only, or even antidiabetic drugs, thus making it difficult to unravel the true effect of psyllium on body weight alone due to confounding effects of the background diet. In addition, a variety of studies designs have been used. Further, no trials have examined the additional effects of psyllium supplementation and a weight loss diet on body composition. The duration of consumption also varied greatly in the studies described above, from 3 weeks to 6 months,32,35,45–47 which may be related to the differing outcomes. The amount of psyllium supplementation also needs to be considered because many of the highlighted studies report no change in body weight with doses below 15 g/day psyllium supplementation. Therefore, future weight loss studies with psyllium need to consider the starting weight or BMI of individuals because this may be a limiting factor on the magnitude of weight loss. Again, future studies could consider including psyllium supplementation with and without a hypocaloric diet. In addition, doses higher than 15 g/day need to be considered in future trials. Out of all the papers cited in this section, the work published by Pal et al. seems to be the strongest overall in terms of research design, duration, and number of cases, thus strengthening our suggestion that psyllium supplement could improve body composition in overweight and obese people.34

BLOOD SUGAR LEVELS AND INSULIN REGULATION Psyllium intake has been shown to improve glucose and insulin responses in animal27,29 and human studies.34,35,52,69 The effects of psyllium supplementation on peripheral insulin sensitivity and skeletal muscle solute carrier family 2, facilitated glucose transporter member 4 (GLUT4) protein expressions were studied in male, stroke-prone, spontaneously hypertensive rats fed a hypercaloric diet from 5 to 9 weeks of age. An oral glucose tolerance test showed that fasting plasma glucose was significantly reduced in the psyllium-supplemented group compared with the cellulose-supplemented group. The 8-week study with T2D patients previously mentioned also measured glycemic control indicators after a 10.5 g/per day of psyllium was added to a regular diet and found fasting blood glucose, insulin, HbA1c, C-peptide (a measure of insulin sensitivity), and HOMA-IR (homeostatic model assessment of insulin resistance) to be significantly improved in intervention group (n ¼ 20; 43.6 mg/dL, p < 0.001; 8.3 μIU/mL, p < 0.001; 0.9%, p ¼ 0.013; 2 ng/mL, p < 0.001; 5.5 p < 0.001, respectively) compared with the control (n ¼ 20).49 A study in individuals with T2D included three phases: phase 1 (1 week, participants followed a diet designed for diabetes and received the diabetes medication, sulfonylurea); phase 2 (6 weeks, patients continued with both the diet and sulfonylurea and also received 14 g/day psyllium fiber); and phase 3 (4 weeks, participants followed the diet for diabetes and received sulfonylurea).69 A clinical evaluation was performed at the end of each phase after the ingestion of a test breakfast of 436 kcal (1824 kJ). Psyllium supplementation significantly decreased postprandial blood glucose by 12.2% and 11.9% in phase 2, compared with the results at the end of phases 1 and 3, respectively.69 However, this reduction was not associated

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with a change in insulin levels (5%).69 Psyllium supplementation at 10.2 g/day for 8 weeks significantly improved glucose and glycated hemoglobin (HbA1c) in individuals with T2D, compared with a placebo.35 Human studies support the results of animal studies. In one study, 16 healthy participants were randomized to one of the following five isocaloric test meals: (1) low in protein (2.8 g) and fiber (7.6 g); (2) low in protein (2.6 g) and high in soluble fiber (23 g psyllium); (3) high in protein (19.7 g soy) and low in fiber (6.2 g); (4) high in protein (18.4 g) and soluble fiber (23 g psyllium); and (5) white wheat bread.51 Psyllium fiber-enriched meals significantly decreased glucose and insulin compared with non-fiber-enriched meals.51 A study by Pal et al. showed that insulin levels were significantly decreased in a group of overweight participants consuming a healthy diet with a daily addition of 21 g psyllium compared with a control group after 6 and 12 weeks of intervention.34 However, glucose levels were not significantly different between the groups.34 Another study showed that the oral ingestion of 10.5 g/day psyllium or guar gum powder for 6 months significantly improved glucose and insulin concentrations, as well as the HOMA-IR index in hypertensive overweight adults,32 suggesting that longer time frames may be required to see improvements, and/or with a higher daily dosage. The 52-week study with overweight and obese participants by Pal et al. discussed above supports this suggestion.70 This study measured fasting plasma glucose and insulin, as well as HOMA-IR score and by the end of the intervention found significant reductions in insulin by 9.4% (p ¼ 0.029) and HOMA-IR score by 11% (p ¼ 0.011), compared with control group, after adding 15 g of psyllium daily to the habitual diet.70 The glucose-reducing action of psyllium is proposed to result from the formation of a viscous gel in aqueous solution. This gel may hinder the access of glucose to the absorptive epithelium of the small intestine, thereby blunting postprandial glucose peaks.71 In addition, soluble fiber may delay gastric emptying, thus slowing carbohydrate uptake.72 Another mechanism that may contribute to the postprandial effect of psyllium is the sequestration of carbohydrates ingested with the meal, thus retarding their access to digestive enzymes.73 The trials cited above included overweight and obese individuals, participants with hypertension or T2D, and even healthy adults. In addition, many of these studies have used a great variety of control groups, including placebo, placebo in combination with antidiabetic drugs, or a standard diet (not specified).32,34,35,69 The trial periods ranged from 6 weeks to 12 months.32,34,35,69,70 A dose of 10–14 g/day psyllium reduced glucose levels over a period of 6–8 weeks.35,69 Interestingly, reductions in plasma insulin levels seemed to require a greater dose of around 21–23 g/day, as seen in studies with test meals,51 or an intervention of at least 12 weeks at this dose.34 One 6-month study suggested that a longer period of psyllium supplementation may be necessary to improve both glucose and insulin levels at a lower dose of 10 g/day,32 whereas a 12-month intervention with 15 g/day found this to be the case, particularly in relation to fasting insulin.70 Overall, psyllium seems to improve glucose levels and the insulin response in most animal and human studies reported so far. The mechanisms responsible for these effects may be related to the prevention of glucose peaks, delay of gastric emptying, and delayed carbohydrate access to digestive enzymes.

BLOOD LIPIDS Both human and animal models have indicated that psyllium fiber may provide cardiovascular benefits.27,32,34,35,46,57 Increasing dietary fiber intake may elicit favorable changes in III. ROLE OF DIETARY SUPPLEMENTS IN OBESITY

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circulating lipid and lipoprotein levels, including reductions in low-density lipoprotein (LDL), serum TG, and total serum cholesterol levels, as well as an increase in high-density lipoprotein (HDL) concentrations, all of which are independent risk factors for CVD. One animal study showed that a psyllium-supplemented diet for 25 weeks significantly reduced plasma concentrations of TG, total cholesterol, and free fatty acids in Zucker rats compared with those fed the standard diet.27 A meta-analysis conducted to determine the effect of consuming psyllium-enriched cereal products (the amount of psyllium soluble fiber ranged from 3 to 12 g/day) for a period of 14–56 days (mean, 42 days) on lipid and lipoprotein levels in 404 adults with mild-tomoderate hypercholesterolemia, who consumed a low-fat diet included eight published and four unpublished studies conducted in four countries.74 It showed that participants who consumed psyllium cereal had lower total cholesterol and LDL concentrations than did participants who consumed the control cereal; however, LDL concentrations were unaffected.74 The authors concluded that consuming psyllium-enriched cereal as part of a low-fat diet improves the blood lipid profile of hypercholesterolemic adults over that which can be achieved with a low-fat diet alone.74 A study of overweight and obese men evaluated the postprandial effects of consuming a low-fiber meal containing 3 g of psyllium versus a high-fiber meal containing 15 g of psyllium, and observed a significantly lower TG concentration after consumption of the high-fiber meal during a 6-h postprandial period, compared with the low-fiber meal.33 The plasma concentration of apolipoprotein B48 (ApoB48; a marker for TG-rich chylomicrons) was significantly lower after the consumption of a high-fiber meal after the first hour of the postprandial period.33 These authors suggest that a single acute dose of dietary fiber in the form of a psyllium supplement can decrease arterial exposure to TG and modify chylomicron responses in the postprandial period.33 According to the U.S. Food and Drug Administration (FDA), the consumption of a 1.78-g serving of psyllium four times a day can improve lipid levels, thereby reducing cardiovascular risk factors.75 Jenkins et al. assessed the efficacy of this dose of fiber in reducing serum lipid risk factors for CVD in 68 hyperlipidemic adults, who consumed a test diet (four servings of high-fiber foods per day: 1.8–2.5 g psyllium or 0.75 g β-glucan per serving, which delivered 8 g/day more soluble fiber than the control diet) and a control low-fat, low-cholesterol diet for 1 month each in a randomized crossover study.76 Compared with the control diet, the psyllium-enriched diet reduced total cholesterol, total cholesterol:HDL ratio, LDL:HDL ratio, and ApoB:ApoA-I ratio, thus confirming a reduction of cardiovascular risk of 4.2%  1.4% by the Framingham equation.76 The investigators concluded that the reduction in serum lipid risk factors for CVD supports the FDA’s approval of a health claim for a dietary fiber intake of 4 servings/day.76 At the end of a 6-week study, which included the consumption of 14 g/ day of psyllium by individuals with T2D, total cholesterol, and LDL levels significantly decreased (by 7.7% and 9.2%, respectively).69 Another study found that a 10.2-g psyllium treatment over 8 weeks significantly increased HDL levels and decreased the LDL:HDL ratio in individuals with T2D.35 A double-blind, placebo-controlled parallel study of 26 men with mild-to-moderate hypercholesterolemia that involved following their usual diets with 3.4 g of psyllium or cellulose placebo at mealtimes (three times a day) for 8 weeks found that psyllium reduced total serum cholesterol levels by 14.8%, LDL levels by 20.2%, and LDL:HDL ratio by 14.8% relative to baseline values.30 Pal et al. demonstrated that adding psyllium fiber supplementation (21 g/day) to a normal diet was sufficient to see improvements in total cholesterol and LDL cholesterol in overweight and obese individuals, compared with control, III. ROLE OF DIETARY SUPPLEMENTS IN OBESITY

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after 12 weeks.34 Cholesterol levels in the fiber only, healthy diet, and healthy diet plus psyllium groups were lower by 21%, 19%, and 20%, respectively, at week 12 compared with the control group; however, there were no significant differences between groups. The LDL level was lower after the 12-week intervention in the three groups by 29%, 24%, and 28% respectively, compared with the control group. Thus, a high-fiber diet consisting of a psyllium supplement plus the fiber present in a healthy diet provided the greatest improvements in MS risk factors. A randomized, placebo-controlled, double-blind, parallel-group study assessed the effect of Minolest on the lipid profile and obesity46: 83 participants were randomized to receive placebo or 16.5 g/day of Minolest for 3 months. Minolest produced a 3.24% decrease in total cholesterol and a 5.45% decrease in LDL but no significant difference in serum TG compared with the placebo group.46 Psyllium supplementation at 10.5 g/day for 6 months led to a significant improvement in plasma TG concentration (of 13.3%) but not affect LDL levels (compared with guar gum supplementation) in hypertensive overweight adults.32 Another meta-analysis of eight studies looked at the effects of psyllium in an attempt to more precisely define the hypolipidemic effects and safety of psyllium when used as an adjunct to a low-fat diet in men and women with hypercholesterolemia.38 All studies evaluated the hypocholesterolemic effects of 10.2 g/day psyllium as adjunctive to a low-fat diet in individuals with mild-to-moderate hypercholesterolemia for 8 weeks. The meta-analysis found that the consumption of 10.2 g/day of psyllium lowered total serum cholesterol by 4%, LDL by 7%, and the ApoB:ApoA-I ratio by 6% relative to a placebo, but had no effect on serum LDL or TG concentrations.38 Similar results were found in more recent research. An 8-week randomized, double-blind, placebo-controlled trial with dyslipidemic participants aged between 6 and 19 years given 7 g of psyllium/day (n ¼ 26) observed significant reductions in total cholesterol by 7.7% or 20.39 mmol/L (p ¼ 0.003) and LDL cholesterol by 10.7% or 20. 36 mmol/L (p ¼ 0.01) compared with the control group (n ¼ 25).77 Although psyllium supplementation had no significant effect on HDL cholesterol and TG concentrations, or LDL:HDL ratio, normal cholesterol levels (4.4 mmol/L) were attained in six participants in the psyllium group compared with one participant in the control group.77 In the already-mentioned 12-month study by Pal et al., which found promising results at 3 months, such that the psyllium group showed significant reductions in fasting concentrations of total cholesterol 7% and LDL cholesterol of 8.1%, after 15 g psyllium daily.70 In addition, the psyllium group recorded significantly lower TG at 6 months (
12.7%, p ¼ 0.023) compared with baseline; however none of these changes persisted for the remainder of the 52-week intervention period.70 Further studies of long-term psyllium supplementation are required to clarify these results. Three major hypotheses have frequently been postulated to explain the cholesterollowering action of soluble dietary fiber, including psyllium.38,78,79 First, the digestion of macronutrients is delayed by viscous soluble fiber, which slows gastric emptying, thus decreasing the transport and mixing of digestive enzymes, and increasing the resistance of the unstirred water layer lining the mucosa to intestinal absorption.80 This can lead to a reduced glycemic response due to a reduction in glucose absorption81 and a subsequent decrease in postprandial glucose levels, which is accompanied by a reduction in insulin levels.82 Decreased insulin levels can then result in the inhibition of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA reductase) and a subsequent reduction in hepatic cholesterol synthesis.83 Second, the presence of soluble fiber in the small intestine may physically prevent bile salt

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reabsorption into the enterohepatic circulation, resulting in increased fecal bile salt excretion.40,84 This may deplete bile salt in the liver, causing cholesterol to be rapidly catabolized in hepatocytes to replenish the bile salt pool via activation of cholesterol 7-alpha-monooxygenase. In addition, there is increased production of LDL surface membrane receptors, thus enhancing LDL uptake from the bloodstream and consequently lowering cholesterol levels.85 Third, fiber reduces hepatic cholesterol synthesis that is modulated by fermentation products, such as propionate, leading to decreased cholesterol absorption and bile acid reabsorption by physically disrupting the intraluminal formation of micelles.43,86 It is well known that soluble dietary fibers are not digested or absorbed in the small intestine, but instead undergo anaerobic bacterial fermentation in the cecum and colon to produce shortchain fatty acids.87 Short-chain fatty acids, particularly propionate, seem to deplete plasma cholesterol by inhibiting hepatic cholesterol metabolism via mechanisms that include reducing HMG-CoA receptor activity44 and inhibiting of acetyl-CoA reductase, which catalyzes the synthesis of acetyl-CoA from acetate. Overall, psyllium seems to improve the lipid profile of both animals and humans, thereby reducing cardiovascular risk factors. Psyllium seems to improve lipids and lipoproteins at dosages and durations of 10–20 g/day psyllium for 6 weeks to 6 months, although further research is required confirm these benefits in the longer term. Participants in the studies discussed were overweight or obese, or had T2D, hypertension, hypercholesterolemia, or hyperlipidemia. However, these health conditions did not seem to affect the results of the studies. Additionally, although a range of control diets was used, study outcomes consistently showed improved lipid profiles following psyllium consumption. Although the mechanism responsible for effects of fiber on lipids and lipoproteins is still being studied, it seems to be mainly mediated by excess bile salt secretion, which reduces plasma cholesterol.

VASCULAR FUNCTION The augmentation index (AI) is an indicator of arterial stiffness that has been shown to be higher in those with hypercholesterolemia.88 It has been suggested that an increase in arterial stiffness is associated with increased systolic blood pressure (SBP) and diastolic blood pressure (DBP).89–91 Arterial stiffness is one of the major risk factors of CVD,92 presenting an independent risk factor for this condition.92,93 Arterial stiffness is an age-related phenomenon90,94 and its progression is faster in patients exhibiting MS criteria,94–96 luminal enlargement resulting from wall thickening (remodeling), and a loss of flexibility (stiffening) at the level of the large elastic arteries, namely arteriosclerosis.97 Individuals with MS,98 hypertension,99 or diabetes100 exhibit increased carotid wall thickness and stiffness; this “accelerated” arterial aging is a well-established risk factor for CVD.101 An inverse relationship exists between healthy eating and arterial stiffness.100 However, the specific role of dietary fiber in preventing and improving arterial stiffness in both the short and long term has yet to be fully elucidated. Endothelial function has an important role in regulating blood pressure and vascular resistance.101 The hypotensive effect of psyllium has been attributed, at least in part, to its ability to inhibit intestinal sodium absorption and improve endothelial function by improving hyperlipidemia and decreasing

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inflammatory markers.28 Only one study so far, by Pal et al., has measured the effect of psyllium on arterial stiffness.102 In this study, the psyllium-supplemented group did present with a lower AI compared with the control group, but this result did not persist until the end of the study at week 12.102 Mechanisms that involve lipid lowering may explain the effects of fiber on blood pressure and vascular function. Collectively, the studies mentioned above reported no change in blood pressure in hypertensive, nonhypertensive, hyperlipidemic, and hypercholesterolemic adults compared with the control groups. In these studies, the control groups had a standard diet, a low-fat diet, or placebo. The amount of psyllium in these studies ranged from 7 to 21 g/day and interventions were from 8 to 12 weeks. Only one study found a reduction in both SBP and DBP in hypertensive adults after supplementation with 10.5 g/day psyllium. Overall, increasing psyllium intake may promote a reduction in blood pressure and vascular function; however, this is still unconfirmed. The effect of psyllium might depend on the dose and duration of the treatment, as well as the baseline blood pressure of individuals. Therefore, future studies examining the effect of psyllium supplementation on hypertension should use high doses (21 g/day) in hypertensive individuals consuming their usual diet to reduce the confounding effects of background diets. Animal27,28 and human31,32 studies have demonstrated that dietary fiber intake may be inversely related to blood pressure levels and may therefore decrease the risk of hypertension. Accordingly, the World Health Organization has recommended an increase in dietary fiber as a safe and practical approach to CVD risk reduction in the hypertensive population.103 Animal studies suggest that psyllium27,28 and high-fiber diets104 decrease blood pressure in hypertensive and obese rats. Consumption of a fiber-supplemented diet containing 3.5% psyllium for 25 weeks improved SBP and endothelial function in obese Zucker rats.27 Saltaccelerated hypertension was also observed to be significantly attenuated in stroke-prone, spontaneously hypertensive rats supplemented with 3% and 10% psyllium for 30 days.28 In a 6-month study, psyllium fiber supplementation at 10.5 g/day appeared to significantly reduce both SBP and DBP in overweight, hypertensive participants.32 This effect was not observed with guar gum fiber or a standard diet. Another study showed that dietary protein (soy) and soluble fiber (15 g/day psyllium) supplementation for 8 weeks additively lowered blood pressure in hypertensive individuals,31 but there was no difference between the interventions. This result is consistent with another study of hyperlipidemic adults, which observed a slight reduction in both SBP and DBP after high-fiber diet (7.2 g of psyllium and 0.75 g/day of β-glucan) and a control low-fat diet after 1 month. However, the results were not significantly different between groups.76 Interestingly, a randomized parallel-design study by Pal et al. did not find any improvements in blood pressure or vascular function in nonhypertensive overweight and obese individuals with psyllium fiber supplementation of 21 g/day for 12 weeks.102 A randomized placebo-controlled, double-blind, parallel-group study with 83 participants with mild hypercholesterolemia found no significant difference in blood pressure after a 3-month intervention with 16.5 g/day Minolest compared with a placebo group.46 These differing outcomes indicate that further research in hypertensive individuals may be necessary to elucidate whether psyllium supplementation reduces blood pressure and improves vascular function. The precise mechanism by which psyllium consumption may regulate blood pressure is currently unclear. It has been shown that high serum cholesterol impairs endothelium-

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dependent dilation105 via blood pressure regulation.106 Interestingly, many hypertensive patients also appear to have increased serum cholesterol levels.107 However, whether this is only a correlation or whether it represents a pathophysiological link is still under discussion.106 Hypercholesterolemia is associated with a loss of nitric oxide-induced vasodilation108 and a subsequent increase in blood pressure.109 Evidence suggests that cholesterol induces endothelial dysfunction even at normal or high-to-normal ranges by reducing the bioavailability of endothelium-derived nitric oxide.105,108 Higher cholesterol levels may also be associated with increased numbers of atherosclerotic vessels through an increase in intima media thickness, not only in the carotid circulation but also in other arteries.106 In addition, water-soluble fiber seems to reduce insulin resistance,110,111 which is thought to be involved in the development of hypertension.112 Other mechanisms have been hypothesized to account for the effects of dietary fiber intake on blood pressure. Dietary fiber can lower the glycemic index of foods through its effects on the digestion and absorption of foods, thereby altering the insulin response. Insulin plays a role in blood pressure regulation, and dietary fiber can modify insulin levels and vascular endothelial function.113 Insulin resistance and its concomitant compensatory hyperinsulinemia are suggested to be major underlying pathogenic mechanisms for the development of hypertension.114 In this way, the effectiveness of both soluble and insoluble fiber in reducing insulin levels, as well as insulin resistance, in both diabetic and healthy persons115,116 could contribute to the treatment or prevention of hypertension.

CONCLUSION Research to date supports the notion that the consumption of psyllium may provide benefits to many components of MS. Psyllium supplementation improves glucose levels and the insulin response as well as the lipid profile in both animals and humans, thereby reducing metabolic risk factors. Increasing psyllium intake may also promote a reduction in blood pressure and vascular function; however, this could depend on the dose and duration of the treatment as well as the baseline blood pressure of individuals. Appetite has been reported to decrease after the consumption of psyllium but this effect seems to be similar to that of other sources of fiber.51,52,57 Psyllium fiber seems to improve body weight in animals,27 but human studies are still inconsistent on this issue, with most studies showing no improvement in body weight and body composition after psyllium consumption.35,45–47 However, this may be either a dose-related issue or related to the fact that most studies have been conducted in normal-weight or slightly overweight individuals.

Acknowledgments Dr. Pal participated in the conception, design, writing, and critical revision of this chapter. Ms. Jane, Mrs. McKay and Dr. Ho participated in the writing and revision of this chapter.

Conflict of Interest Statement The authors have no conflict of interest to declare in relation to this manuscript.

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