American Journal of Clinical Nutrition. Song M, et al. Fiber intake and survival after colorectal cancer diagnosis. Journal of the American Medical Association: Oncology. Colditz GA. Healthy diet in adults. Dietary reference intakes DRIs : Recommended dietary allowances and adequate intakes, total water and macronutrients.

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But things get sticky when cholesterol begins to build up too much in your bloodstream and starts attaching itself to arteries, potentially causing blockages. According to the Centers for Disease Control and Prevention , over million U. adults have high cholesterol levels, which increases the risks for cardiovascular diseases, the leading cause of death worldwide.

Medication is available to help lower your cholesterol, but the foods you choose can help make a significant difference, too. Our top pick for the No. While there are many types of fiber in plant-based foods like popcorn and nuts that you may eat regularly, two common types are soluble fiber and insoluble fiber.

Soluble fiber slows digestion by absorbing water and turning into a gel-like consistency, allowing it to work its magic on cholesterol. Common food sources of soluble fiber include oats, legumes, berries, vegetables and seeds, and sources of insoluble fiber include whole grains and hearty fruits and vegetables like apples, carrots and potatoes with their skins on.

Insoluble fiber moves more quickly through the digestive tract, adding bulk to stool to help prevent constipation. Eating both types of health-promoting fiber is vital for a healthy eating pattern. Viscous fibers form a gel in your gastrointestinal tract and prevent bad cholesterol from being absorbed.

Science continues to echo the benefits of soluble fiber. Campbell highlights the studies from a review published in Advances in Nutrition. Researchers concluded that 15 grams of soluble fiber daily had the greatest effect on lowering total cholesterol levels.

This process alters the intestinal microbiota, contributing to the cholesterol-lowering effects of soluble fiber. Getting more fiber in your diet can be a cinch. First, start by aiming to have it with every meal if you can. I often recommend adding flax or chia seed with breakfast, high-soluble-fiber fruits like apples or pears with lunch, and including legumes or high-fiber grains with dinner.

Mostek also encourages adding a meatless day into your week. Dining out? You may be surprised at how good vegan food actually can be! Plat J, Bragt MC, Mensink RP: Common sequence variations in ABCG8 are related to plant sterol metabolism in healthy volunteers.

Davis HR, Veltri EP: Zetia: inhibition of Niemann-Pick C1 Like 1 NPC1L1 to reduce intestinal cholesterol absorption and treat hyperlipidemia.

J Atheroscler Thromb. Miettinen TA, Gylling H, Lindbohm N, Miettinen TE, Rajaratnam RA, Relas H, Finnish Treat-to-Target Study Investigators: Serum noncholesterol sterols during inhibition of cholesterol synthesis by statins.

Miettinen TA, Gylling H: Cholesterol synthesis and absorption in coronary patients with lipid triad and isolated high LDL cholesterol in a 4S subgroup. Assmann G, Kannenberg F, Ramey DR, Musliner TA, Gutkin SW, Veltri EP: Effects of ezetimibe, simvastatin, atorvastatin, and ezetimibe-statin therapies on non-cholesterol sterols in patients with primary hypercholesterolemia.

Article Google Scholar. Bingham SA, Gill C, Welch A, Day K, Cassidy A, Khaw KT, Sneyd MJ, Key TJ, Roe L, Day NE: Comparison of dietary assessment methods in nutritional epidemiology: weighed records v.

CAS PubMed Google Scholar. Friedewald WT, Levy RI, Fredrickson DS: Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge.

Clin Chem. Marlett JA, McBurney MI, Slavin JL: Position of the American Dietetic Association: health implications of dietary fiber. J Am Diet Assoc. Article PubMed Google Scholar. Brown L, Rosner B, Willett WW, Sacks FM: Cholesterol-lowering effects of dietary fiber: a meta-analysis.

Anderson JW, Baird P, Davis RH, Ferreri S, Knudtson M, Koraym A, Waters V, Williams CL: Health benefits of dietary fiber. Nutr Rev. Anderson JW: Dietary fiber, lipids and atherosclerosis.

Gylling H, Puska P, Vartiainen E, Miettinen TA: Serum sterols during stanol ester feeding in a mildly hypercholesterolemic population. Ketomaki A, Gylling H, Miettinen TA: Effects of plant stanol and sterol esters on serum phytosterols in a family with familial hypercholesterolemia including a homozygous subject.

Miettinen TA, Gylling H: The effects of statins and sitosterols: benefit or not?. Curr Atheroscler Rep. Davis HR, Altmann SW: Niemann-Pick C1 Like 1 NPC1L1 an intestinal sterol transporter. Biochim Biophys Acta. Salas-Salvado J, Farres X, Luque X, Narejos S, Borrell M, Basora J, Anguera A, Torres F, Bulló M, Balanza R, Fiber in Obesity-Study Group: Effect of two doses of a mixture of soluble fibres on body weight and metabolic variables in overweight or obese patients: a randomised trial.

Tucker LA, Thomas KS: Increasing total fiber intake reduces risk of weight and fat gains in women. J Nutr. Vuksan V, Rogovik AL, Jovanovski E, Jenkins AL: Fiber facts: benefits and recommendations for individuals with type 2 diabetes.

Curr Diab Rep. Panahi S, Ezatagha A, Temelli F, Vasanthan T, Vuksan V: Beta-glucan from two sources of oat concentrates affect postprandial glycemia in relation to the level of viscosity. J Am Coll Nutr. Mello VD, Laaksonen DE: Dietary fibers: current trends and health benefits in the metabolic syndrome and type 2 diabetes.

Arq Bras Endocrinol Metabol. Kim H, Stote KS, Behall KM, Spears K, Vinyard B, Conway JM: Glucose and insulin responses to whole grain breakfasts varying in soluble fiber, beta-glucan: a dose response study in obese women with increased risk for insulin resistance.

Eur J Nutr. Rajpathak SN, Kumbhani DJ, Crandall J, Barzilai N, Alderman M, Ridker PM: Statin therapy and risk of developing type 2 diabetes: a meta-analysis. Diabetes Care. Sattar N, Preiss D, Murray HM, Paul Welsh, Brendan Buckley, Anton de Craen, Sreenivasa Rao Kondapally Seshasai, John McMurray, Dilys Freeman, Wouter Jukema, Peter Macfarlane, Chris Packard, David Stott, Rudi Westendorp, James Shepherd, Barry Davis, Sara Pressel, Roberto Marchioli, Rosa Maria Marfisi, Aldo Maggioni, Luigi Tavazzi, Gianni Tognoni, John Kjekshus, et al: Statins and risk of incident diabetes: a collaborative meta-analysis of randomised statin trials.

Cholesterol Treatment Trialists' CTT Collaboration, Baigent C, Blackwell L, Emberson J, Holland LE, Reith C, Bhala N, Peto R, Barnes EH, Keech A, Simes J, Collins R: Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from , participants in 26 randomised trials.

Download references. MCI has received research grant from FAPESP Foundation for Research of the State of Sao Paulo, Brazil. SCR has received research grant from CNPq National Council for Research and Development, Brazil.

Department of Medicine, Cardiology Division, Federal University of Sao Paulo, Rua Pedro de Toledo, , São Paulo, SP, , Brazil.

Synchrophar, Praça Vinte e Oito de Fevereiro, 55, Paulínia, , SP, Brazil. You can also search for this author in PubMed Google Scholar. Correspondence to Maria C Izar.

Open Access This article is published under license to BioMed Central Ltd. Reprints and permissions. Ramos, S. et al. The role of soluble fiber intake in patients under highly effective lipid-lowering therapy.

Nutr J 10 , 80 Download citation. Received : 08 January Accepted : 02 August Published : 02 August Anyone you share the following link with will be able to read this content:.

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Skip to main content. Search all BMC articles Search. Download PDF. Download ePub. Abstract Background It has been demonstrated that statins can increase intestinal sterol absorption. Objective We examined the role of soluble fiber intake in endogenous cholesterol synthesis and in sterol absorption among subjects under highly effective lipid-lowering therapy.

Conclusion Among subjects treated with highly effective lipid-lowering therapy, the intake of 25 g of fibers added favorable effects, mainly by reducing phytosterolemia. Introduction Dietary fiber is widely prescribed [ 1 ], alone or associated with lipid-lowering therapies, in order to reduce cholesterol levels [ 2 ].

Subjects and methods Design and study population We performed a prospective, randomized, open label study, with parallel arms and blinded endpoints. Table 1 Baseline characteristics of the study population by group Full size table. Results Dietary intake, weight and body mass index The analyses of the dietary recall have shown that the consumption of cholesterol and dietary fiber did not differ between groups; monounsaturated, polyunsaturated, or trans- fatty acids were also similar.

Table 2 Characteristics of the diet consumed at baseline and 12 weeks, by group Full size table. Figure 1. Full size image. Table 3 Anthropometric and laboratory parameters at baseline and 12 weeks, by group Full size table.

Discussion This study examined the role of fiber supplementation in patients under effective therapy with lipid-lowering drugs. Study strenghts and limitations According to a recent meta-analysis of statin trials [ 36 ], lipid-lowering therapy that promotes greater reductions in LDL-cholesterol produces definite further reductions in the incidence of cardiovascular events.

Conclusions Soluble fiber intake in patients receiving effective strategies with lipid-lowering drugs seems important for the achievement of lower phytosterolemia synergistic action with ezetimibe , and is associated with weight loss, and lower levels of plasma glucose. All authors read and approved the final manuscript.

References National Cholesterol Education Program NCEP Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults Adult Treatment Panel III final report. Article CAS PubMed Google Scholar Theuwissen E, Mensink RP: Water-soluble dietary fibers and cardiovascular disease.

It has been demonstrated that statins can increase intestinal sterol absorption. Augments in phytosterolemia seems related to cardiovascular disease. We examined the role of soluble fiber intake in endogenous cholesterol synthesis and in sterol absorption among subjects under highly effective lipid-lowering therapy.

baseline and did not change HDL-cholesterol. other groups. Among subjects treated with highly effective lipid-lowering therapy, the intake of 25 g of fibers added favorable effects, mainly by reducing phytosterolemia.

Additional benefits include improvement in blood glucose and anthropometric parameters. Peer Review reports. Dietary fiber is widely prescribed [ 1 ], alone or associated with lipid-lowering therapies, in order to reduce cholesterol levels [ 2 ]. The exact mechanism by which soluble fibers lower serum LDL-cholesterol levels is not completely understood.

Atherosclerosis has been recognized as a complex disease related in part to lipid disorders. Beyond cholesterol content of lipoproteins, a moderate increase in phytosterolemia seems related to cardiovascular disease [ 4 , 5 ]. Based on clinical trials, high doses of statins have been recommended to achieve lower levels of LDL-cholesterol [ 6 — 8 ].

Nevertheless, the use of high doses of statins is not always well tolerated or effective and the concomitant use of ezetimibe has been proposed. Due to the blockade of the endogenous cholesterol synthesis [ 9 ], statins appear related to increased intestinal absorption of sterols, both cholesterol and plant sterols [ 10 , 11 ].

Ezetimibe has an important synergism with statins in reducing LDL-cholesterol and is able to prevent the increase in intestinal sterols absorption [ 12 , 13 ]. On the other hand, the inhibition of cholesterol absorption increases the endogenous cholesterol synthesis [ 14 — 16 ].

The Framingham Offspring Study showed that cholesterol synthesis markers were associated with reduction in cardiovascular disease risk and, in contrast, absorption markers were associated with an almost two-fold increased risk [ 17 ]. Although changes in lifestyle, including a prudent diet [ 1 ] have been widely recommended for primary or secondary prevention of cardiovascular disease, the usefulness of a soluble fiber-enriched diet, in patients under highly effective lipid-lowering therapy is less reported, not only for the achievement of lipid goals, but particularly to the balance between phytosterolemia and cholesterol synthesis.

Therefore, we hypothesized that soluble fiber intake can reduce plant sterols absorption among subjects receiving highly effective lipid-lowering therapy. The role of fiber intake was tested in two different lipid-lowering strategies, using high-dose statin or the combination of a statin plus a cholesterol absorption inhibitor.

These drugs and dosages were chosen to attain similar changes in lipid profile through distinct mechanisms. We performed a prospective, randomized, open label study, with parallel arms and blinded endpoints.

Patients were recruited from the outpatient unit of dyslipidemias of our university. The trial protocol was conducted in accordance with the ethical standards of the institution on human experimentation and approval was obtained from the local ethics committee.

Informed consent was obtained from all participants prior inclusion. A total of subjects completed the study protocol. Patients with liver, renal or gastrointestinal disease, malignancies, uncontrolled metabolic disorder, that might affect the tolerability or safety of the treatments were excluded.

The major characteristics of the study population are listed in the Table 1. The hour dietary recall [ 18 ] was obtained at the beginning and end of the study. Then, they were randomized to receive or not 44 g of the passion fruit peel flour, to ensure a minimum daily consumption of 6 g of soluble fiber and to achieve the target of 25 g of fiber intake, divided into three daily doses administered before meals.

They were also randomized to rosuvastatin 40 mg or the combination of simvastatin 40 mg plus ezetimibe 10 mg, daily for 12 weeks. The lipid-lowering agents and the fiber were given to the patients every 30 days, with reinforcement of lifestyle changes and to evaluate the adherence to the study protocol.

The passion fruit peel flour was purchased from Tango alimentos Londrina, PR, Brazil. The composition of passion fruit peel flour was analyzed by Centro de Ciências e Qualidade de Alimentos Instituto de Tecnologia de Alimentos, Campinas, SP, Brazil , which revealed that 44 g of flour corresponded to 45 kcal of total energy, being 25 g of total fiber, 6 g of soluble fiber, 5 mg of campesterol, and 35 mg of β-sitosterol.

Biochemical analyses were performed in samples obtained after a hour fasting period at baseline and after 12 weeks of treatment in a central laboratory of our university using automated techniques Advia , Siemens Healthcare Diagnostics, Tokyo, Japan.

Serum cholesterol, HDL-cholesterol, and triglycerides were determined by automated methods Advia , Siemens Healthcare Diagnostics, Tokyo, Japan. LDL-cholesterol was calculated using the Friedewald formula [ 19 ].

Glycated hemoglobin was assayed by high-performance liquid chromatopraphy Tosho G2, Tosho Inc. Brea, CA.

For the quantification of beta-sitosterol and campesterol markers of sterols absorption , as well as for desmosterol precursor of the endogenous cholesterol synthesis we used ultra performance liquid chromatography UPLC and mass spectrometry MS. Briefly, these sterols were quantitated in plasma samples by a method developed and run by Synchrophar, Campinas, SP, Brazil.

The sterols were detected as its free forms, i. The levels of compounds were determined by comparison of peak response against a calibration curve from 0.

Samples presenting higher levels than Results are expressed as mean SEM or percentages unless otherwise specified. Continuous variables were tested for distribution of normality by Kolmogorov-Smirnov test. Comparisons between groups at baseline were made by ANOVA or Pearson's Chi square test. For comparisons between timepoints and groups we used General Linear Model GLM - repeated measures or Kruskal-Wallis test, when data were presented as percentages.

To compare non-fiber supplemented and fiber-supplemented groups, the 2-sided Student's independent or paired t-test or Mann-Whitney test were used. When appropriate, continuous variables were log transformed. All analyses were made using the SPSS The analyses of the dietary recall have shown that the consumption of cholesterol and dietary fiber did not differ between groups; monounsaturated, polyunsaturated, or trans- fatty acids were also similar.

baseline, GLM-repeated measures , with energy from carbohydrates, fatty acids, and proteins being comparable among groups. The estimated daily fiber intakes, obtained from dietary recall were not different along the study, when fiber supplementation with passion fruit peel flour was not counted Table 2.

Box plots of A Weight, B BMI, C Campesterol and D Glucose at baseline white bars and 12 weeks dashed bars. non-fiber supplemented, Student's independent t-test. In Table 3 we present our main laboratory findings. baseline, GLM-repeated measures , without changes in HDL-cholesterol levels.

baseline, GLM-repeated measures , without differences between treatments. Differences on lipids and apolipoproteins according to fiber intake status were not significant data not shown. Desmosterol plasma levels presented interaction between groups.

Sterol intestine absorption markers, campesterol and β-sitosterol, are presented in Table 3. non-fiber supplemented, Student's independent t-test as shown in Figure 1C. Fiber intake status did not affect β-sitosterol plasma levels. Blood glucose and glycated hemoglobin HbA1c did not change along the study between groups Table 3.

However, there were differences in glucose percent change in subjects supplemented with fibers when compared with those not receiving fibers [mean SEM - 2. non-supplemented, Student's independent t-test ; data shown in Figure 1D.

baseline, GLM-repeated measures Table 3. We did not observe differences in highly-sensitive C-reactive protein according to fiber intake status data not shown. This study examined the role of fiber supplementation in patients under effective therapy with lipid-lowering drugs.

It has been reported that consumption of soluble fibers promotes a moderate effect in lowering cholesterol in hypercholesterolemic patients [ 20 , 21 ]. However, the literature is scarce in relation to the benefit of fibers added to therapy in patients taking effective lipid-lowering agents.

Our study has shown that no further reduction was achieved in total cholesterol, LDL-cholesterol, and triglycerides when fibers were added to an effective therapy.

However, fibers seemed to act synergistically with ezetimibe, reducing phytosterolemia, at the recommended dose for total 25 g and soluble fibers 6 g intake [ 1 ]. However, the addition of fibers to the diet, even in patients receiving highly effective therapy can bring important benefits [ 22 , 23 ].

It has been reported that use of statins alone may increase the absorption of sterols by the intestine, causing mild to moderate increase in plasma phytosterols [ 14 ].

This increase appears to be related to statin dose [ 15 , 16 , 24 ]. Furthermore, among patients receiving therapy with simvastatin and ezetimibe, the use of fibers produced significant decrease in phytosterolemia. These findings seem of importance, because they support evidence for supplementation of fibers being a safe strategy when added to the most effective lipid-lowering strategies, reducing the absorption of phytosterols.

Genetic variation in these genes were reported and can increase the absorption of sterols or decrease sterol extrusion to the intestinal lumen, which are associated with increased levels of phytosterolemia [ 27 ].

Other benefits of fiber supplementation observed in our patients were weight loss and the achievement of lower body mass index. The reduction in total energy intake may have contributed to these results, however, differences between groups were only observed in patients receiving fiber supplementation.

Our findings are in agreement with previous studies showing inverse relationship between fiber intake and weight loss [ 28 , 29 ]. Another interesting finding of the study was the mild reduction in blood glucose in subjects receiving fiber supplementation.

Previous studies have demonstrated reduction in fasting glucose, postprandial and glycated hemoglobin levels associated with soluble fiber intake [ 30 — 33 ]. Recently, two meta-analyses have shown a slight increase in the rates of new-onset diabetes mellitus in patients treated with statins [ 34 , 35 ].

Another contribution of fiber intake is the potential benefit for reduction in new cases of diabetes, attributed to statin therapy. According to a recent meta-analysis of statin trials [ 36 ], lipid-lowering therapy that promotes greater reductions in LDL-cholesterol produces definite further reductions in the incidence of cardiovascular events.

Therefore, our study tested the benefit of fiber intake in this scenario. It is possible that the lipid effects of soluble fiber have been masked by the highly effective treatment used in our study.

Soluble fiber intake in patients receiving effective strategies with lipid-lowering drugs seems important for the achievement of lower phytosterolemia synergistic action with ezetimibe , and is associated with weight loss, and lower levels of plasma glucose.

SCR carried out the clinical protocol, performed statistical analysis and drafted the manuscript. FAF conceived of the study, participated in its design and coordination, performed statistical analysis and drafted the manuscript.

SHK carried out the assessment of plasma sterols. FTM carried out the clinical protocol. TH performed statistical analysis; NCB and RAM standardized the assay of plasma sterols. VMR and FCS carried out the assays of plasma sterols.

MCI conceived of the study, participated in its design and coordination, performed statistical analysis and drafted the manuscript. National Cholesterol Education Program NCEP Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults Adult Treatment Panel III final report.

Ortega RM, Palencia A, Lopez-Sobaler AM: Improvement of cholesterol levels and reduction of cardiovascular risk via the consumption of phytosterols.

Br J Nutr. Article CAS PubMed Google Scholar. Theuwissen E, Mensink RP: Water-soluble dietary fibers and cardiovascular disease. Physiol Behav. Assmann G, Cullen P, Erbey J, Ramey DR, Kannenberg F, Schulte H: Plasma sitosterol elevations are associated with an increased incidence of coronary events in men: results of a nested case-control analysis of the Prospective Cardiovascular Munster PROCAM study.

Nutr Metab Cardiovasc Dis. Patel MD, Thompson PD: Phytosterols and vascular disease. Ma Y, Griffith JA, Chasan-Taber L, Olendzki BC, Jackson E, Stanek EJ, Li W, Pagoto SL, Hafner AR, Ockene IS: Association between dietary fiber and serum C-reactive protein.

Am J Clin Nutr. CAS PubMed PubMed Central Google Scholar. Asztalos BF, Le Maulf F, Dallal GE, Stein E, Jones PH, Horvath KV, McTaggart F, Schaefer EJ: Comparison of the effects of high doses of rosuvastatin versus atorvastatin on the subpopulations of high-density lipoproteins.

Am J Cardiol. van Himbergen TM, Matthan NR, Resteghini NA, Otokozawa S, Ai M, Stein EA, Jones PH, Schaefer EJ: Comparison of the effects of maximal dose atorvastatin and rosuvastatin therapy on cholesterol synthesis and absorption markers.

J Lipid Res. Article CAS PubMed PubMed Central Google Scholar. Curr Med Res Opin. Grodos D, Tonglet R: Scandinavian simvastatin study 4S.

Miettinen TA, Gylling H, Lindbohm N, Miettinen TE, Rajaratnam RA, Relas H: Serum noncholesterol sterols during inhibition of cholesterol synthesis by statins. J Lab Clin Med. Plat J, Bragt MC, Mensink RP: Common sequence variations in ABCG8 are related to plant sterol metabolism in healthy volunteers.

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