The effects of dietary fibre on C-reactive protein, an inflammation marker predicting cardiovascular disease

Abstract

Background:

C-reactive protein (CRP), a sensitive marker of inflammation, is an independent predictor of future cardiovascular disease (CVD), which is a major cause of death worldwide. In epidemiological trials, high-fibre intakes have consistently been associated with reduction in CVD risk and CRP levels.

Objective:

The objective of this study was to assess the influence of dietary fibre (DF) on CRP in clinical trials.

Data sources:

Databases were searched from the earliest record to April 2008 and supplemented by crosschecking reference lists of relevant publications.

Study selection:

Human adult intervention trials, at least 2 weeks in duration, with an increased and measurable consumption of DF were included and rated for quality.

Data synthesis:

Seven clinical trials were included, and six of these reported significantly lower CRP concentrations of 25–54% with increased DF consumption with dosages ranging between 3.3–7.8 g/MJ. The seventh trial with psyllium fibre supplementation failed to lower CRP levels significantly in overweight/obese individuals. Weight loss and altered fatty acid intakes were present in most of the studies.

Conclusions:

In the presence of weight loss and modified saturated, monounsaturated and polyunsaturated fat intakes, significantly lower CRP concentrations (↓25–54%) are seen with increased fibre consumption (3.3 g/MJ). Mechanisms are inconclusive but may involve the effect of DF on weight loss, and/or changes in the secretion, turnover or metabolism of insulin, glucose, adiponectin, interleukin-6, free fatty acids and triglycerides. Clinical studies of high- and low-fibre diets are needed to explore the potential favourable effects as observed epidemiologically, and to understand individual susceptibility to its anti-inflammatory effect and long-term cardiovascular reduction.

Introduction

C-reactive protein (CRP), a sensitive marker of inflammation, is an independent predictor of future cardiovascular disease, a major cause of death worldwide (Ridker et al., 1998, 2002; Pearson et al., 2003; Ridker, 2005). In large cohort studies, high fibre intakes have consistently been associated with a reduction in coronary heart disease risk (Pereira et al., 2004; Flight and Clifton, 2006). Cross-sectional (King et al., 2003; Ajani et al., 2004; King, 2005; Bo et al., 2006) and longitudinal (Ma et al., 2006) studies indicate an inverse association between dietary fibre (DF) intake and levels of inflammatory markers. In the prospective study by Ma et al. (2006), multiple dietary and CRP measurements were taken and an inverse association between DF intake in both cross-sectional and longitudinal analyses was found. Compared with subjects in the lower quartile of total fibre intake, participants in the highest quartile had a 63% lower chance of having elevated CRP concentrations in the adjusted (OR 0.37, 95% CI; 0.16, 0.87) and unadjusted models (OR 0.27, 95% CI; 0.12, 0.57). Factors adjusted for included body mass index, age, tobacco use, self-reported infection and season of the year. Furthermore, the risk reduced by 61% (P-value for trend=0.006) for subjects in the highest quartile of water-soluble intake and 75% (P-value for trend <0.01) for insoluble fibre (Ma et al., 2006). However, more recently, Ma et al. (2008) reported no association between DF and CRP among post-menopausal women enrolled in the Women's Health Initiative Observational Study although intakes of DF were inversely associated with other markers of systemic inflammation (interleukin (IL)-6 and tumour necrosis factor-α receptor-2). DF may therefore play an important role in mediating the relation between diet, inflammation and cardiovascular disease (King et al., 2003). Over a period of 2 years, it was shown that a Mediterranean-style diet rich in whole grains, fruits, vegetables, legumes, walnuts and olive oil may be responsible for a cardioprotective effect through the reduction of low-grade inflammation (Esposito et al., 2004). The aim of this systematic review was to assess the influence of DF on CRP in clinical trials.

Materials and methods

Participants

A total of 554 individuals (192 men, 362 women) participated in the studies and are summarized in this systematic review. Participants with metabolic syndrome (n=180) (Esposito et al., 2004), high triglyceride (TG) concentrations (n=25) (Junker et al., 2001), hyperlipidaemia (n=46) (Jenkins et al., 2003) and hypertension (n=17) (King et al., 2007) made up 48% of the study population. The remainder of the participants were healthy and/or overweight/obese (Esposito et al., 2003a; King et al., 2007, 2008).

Inclusion and exclusion criteria

Human adult (men and women) intervention trials with an increased and measurable consumption of DF and a duration of 2 weeks or longer were included. Subjects were excluded if diabetic or suffering from coronary heart disease.

Outcome measures

The primary outcome measures were percentage changes in CRP between intervention and control groups or baseline to end comparisons.

Data sources

To identify potential studies, literature searches were performed in electronic databases. EbscoHost was used as a gateway to the records in MEDLINE (Pubmed), Academic Search Premier, Clinical Pharmacology, Health Source: Nursing/Academic Edition, Health Source: Consumer Edition and Biological and Agricultural Index. In addition, The Cochrane Library, Science Direct, Web of Science and EMBASE databases were also searched. Databases were searched from the earliest record to April 2008. Reference lists of relevant publications were crosschecked manually to ensure that all applicable papers were included. Search terms used included CRP, dietary fibre (fiber), non-digestible carbohydrate(s), lignin(s), non-starch polysaccharide(s), functional fibre (fiber), nutrition and food. Medical subject headings (MeSH), such as ‘fibre’ and ‘fiber,’ were combined with the key search words in the Medline search.

Study selection and data extraction

Two assessors (CJN and CSV) screened the potential studies identified to determine eligibility for inclusion into the review. Using a standardized form, data were extracted to determine the quality of all the identified intervention studies.

Data synthesis

A rating based upon the methodology as it appeared in the publication was given to each of the selected studies. The following criteria for quality assessment of the intervention trials were used (adapted from Verhagen et al. (1998)): (1) the study was controlled; (2) justified sample size (80% power, 5% significance, assuming 1 s.d. change as a clinical significant change); (3) groups were similar at baseline regarding the most important prognostic indicators; (4) compliance was acceptable, based on significant increase in fibre intake as reported by researchers; (5) randomization was performed; and (6) in case of crossover trials, no order of treatment effect. The following quality scores were assigned: 1=if all the criteria were present/if the study was controlled and one criterion was missing; 2=if the study was controlled and two criteria were missing; 3=if the study was not controlled or 3 criteria were missing. Furthermore, the letter a was assigned for controlled feeding trials and b for studies conducted under free-living conditions. No formal statistical analysis was performed due to the large differences in study designs of the clinical trials. This study had no external funding source.

Results

Of the 2123 articles screened (titles, abstracts, original research and review articles), seven original research papers were identified that were suitable for inclusion into this systematic review. Table 1 presents a summary of the baseline characteristics of the studies and participants. The experimental design of these studies was variable, participants’ characteristics differed, as did the amount and type of fibre consumed, duration of the studies, the control diets and the number of subjects.

Table 1 Summary of baseline characteristics of studies and participants

The macronutrient composition and sources of fibre in each study are summarized in Table 2. One study did not report the macronutrient composition of the diet (King et al., 2008). Two studies reported substantial differences in the total fat intake between the control and intervention groups (Jenkins et al., 2003; Koren et al., 2006). In one instance, the authors concluded that plasma CRP concentrations are not affected by isocaloric dietary fat reduction (Koren et al., 2006). In the other, caution should be taken because of the substantial but nonsignificant difference in baseline CRP values between comparative groups (Jenkins et al., 2003). Increases in monounsaturated fatty acids and polyunsaturated fatty acids (PUFAs) and a decrease in saturated fatty acids occurred in some instances in the trials reviewed here. The differences in the consumption of monounsaturated fatty acid, PUFA and saturated fatty acid between the intervention and comparative diets were significant in one instance (Esposito et al., 2004), in saturated fatty acid for another (Esposito et al., 2003a), but not reported for the remainder of the studies (Junker et al., 2001; Jenkins et al., 2003; Koren et al., 2006; King et al., 2007; King et al., 2008).

Table 2 Macronutrient compositions of diets used in intervention trials investigating the effect of dietary fibre on C-reactive protein

The durations of the studies were three (Junker et al., 2001; King et al., 2007), four (Jenkins et al., 2003), 12 (King et al., 2008) and 14 weeks (Koren et al., 2006) and 24 months (Esposito et al., 2003a, 2004), which were sufficient time to achieve stabilization of CRP. CRP is an acute-phase protein with serum concentrations peaking around 48 h after a single stimulus (Pepys and Hirschfield, 2003), and concentrations of pro-inflammatory cytokines and adipokines have been reported to change in response to individual meals (Esposito et al., 2003b). The number of subjects who completed the high fibre interventions ranged between 16 and 90 per treatment group, which have been adequate to detect clinically significant changes in CRP (80% power, 5% significance, assuming 1 s.d. change as a clinically significant change). The characteristics of studies and subjects are shown in Table 3. Also indicated in Table 3 are the quality scores of the publications. Five of the seven studies received a ‘1’ quality score.

Table 3 Characteristics of studies and participants

The results of the studies reviewed are summarized in Table 4. Increased consumption of DF at dosages of 3.3, 3.6, 3.7, 5.0 and 7.8 g/MJ and about 30 g/d significantly lowered CRP concentrations by 25, 34.4, 39.3, 25.9, 54.2, 13.7 (high-fibre Dietary Approaches to Stop Hypertension diet) and 18.1% (fibre-supplemented diet), respectively, comparing baseline with end, which seems to indicate a trend that with higher DF dosages, higher reductions in CRP occurred. However, in the fibre-supplemented diet (psyllium, 7 or 14 g/d) of King et al. (2008), no difference was observed between the high-fibre and low-fibre groups. Furthermore, in the study by King et al. (2007), CRP levels decreased only in the lean, normotensive participants (by 40%), but did not change significantly in obese hypertensives. Concentrations of CRP were significantly reduced when comparing intervention and control groups following two Mediterranean-style diets reporting a difference in CRP of −0.8 (95% CI; −2.0, −0.4; P=0.008) and −1 (95% CI; −1.7, −0.3; P=0.01) (Esposito et al., 2004). Furthermore, a significance of P<0.005 was reached following a vegetarian intervention comparing groups (Jenkins et al., 2003). One study reported that without a concomitant decrease in body weight, a low-carbohydrate (45%) diet (2.1 g fibre/MJ) did not alter CRP concentrations (Koren et al., 2006). However, ad libitum feeding on a high carbohydrate intake (65%) with 3.3 g/MJ DF during the subsequent 3-month phase of the trial resulted in significantly lower CRP levels (Koren et al., 2006). The baseline CRP concentrations in this study were low in the non-obese, healthy subjects. Reductions in body weight were seen in most of the other studies and are specified in Table 4.

Table 4 Increased dietary fibre intake and changes in CRP concentrations (mg/l) in clinical trials

Discussion

The results of this systematic review should be interpreted with care. With the exception of the studies by King et al. (2007, 2008), none of the studies had the primary objective of investigating the independent effects of fibre on CRP. The other studies investigated the effects of different types and amount of fat (Junker et al., 2001; Koren et al., 2006), low-energy Mediterranean diet with an increased physical activity (Esposito et al., 2003a, 2004) or the portfolio diet (plant sterols, soy protein, viscous fibre and almonds; Jenkins et al., 2003). In the study by King et al. (2007), CRP levels decreased in the 18 lean normotensive individuals on either the high-fibre Dietary Approaches to Stop Hypertension diet or the fibre-supplemented diets, but did not change significantly in the obese hypertensive participants. The authors acknowledged that this finding was surprising because ‘many of the proposed mechanisms for how fibre affects CRP levels, such as modulation in abdominal fat (Esposito and Giugliano, 2006), would tend to be more pronounced in the obese participants rather than the lean individuals’. However, psyllium fibre supplementation also failed to significantly reduce CRP levels in overweight and obese individuals in a follow-up study by King et al. (2008), illustrating the complexity of the matter.

Six of the seven clinical trials reviewed report significantly lower CRP concentrations following increased fibre consumption, altered fat intakes and weight loss, whereas in the seventh investigation, psyllium fibre supplementation failed to lower CRP levels significantly in 80 overweight/obese individuals. There were substantial differences between the studies in terms of dietary interventions, study designs and participants. Participants included hyperlipidaemic individuals consuming a vegetarian diet (Jenkins et al., 2003), Mediterranean-style intakes in metabolic syndrome (Esposito et al., 2004) and overweight/obese individuals (Esposito et al., 2003a; King et al., 2007, 2008), as well as hypertriglyceridaemic patients consuming a high-fat/high-fibre diet with resultant decreased CRP concentrations, which remained low after the subsequent low-fat/high-fibre diet (Junker et al., 2001). The majority of these experimental studies strengthen the epidemiological data indicating that DF is inversely associated with CRP concentrations (King et al., 2003; Ajani et al., 2004). According to King et al. (2008), their negative results with psyllium fibre supplementation do not negate the epidemiologic evidence that DF is a factor in reducing inflammation (King et al., 2003) or the risk of cardiovascular disease (Flight and Clifton, 2006), but they do suggest that supplementation with psyllium does not replicate the results seen with a diet naturally high in fibre and that further research with other types of fibre or with combinations of nutrients may be warranted. No weight loss was recorded in the obese/overweight participants in the study of King et al. (2008).

Suggested mechanisms

Weight loss

A positive correlation exists between CRP and body mass index (Ford, 2003). Fogarty et al. (2008) reported a linear association between increase in weight and serum CRP over a period of 9 years, with a 1-kg increment being associated with an increase of 0.09 mg/l in CRP during this time period. Ample clinical evidence indicates that weight loss results in decreased CRP concentrations as reviewed recently (Basu et al., 2006; Selvin et al., 2007), with a 1-kg weight loss being associated with a decrease of −0.13 mg/l in CRP (Selvin et al., 2007). However, some authors found no correlation between the decrease in CRP levels and the decrease in body weight, but a positive correlation with the decrease in waist circumference, suggesting that the decrease in CRP levels depends more on the decrease in abdominal fat than on the weight loss itself (Marfella et al., 2004; Borges et al., 2007). Elevated levels of IL-6 are also reduced in serum and subcutaneous adipose tissue of obese women after weight loss (Bastard et al., 2000). This is to be expected as IL-6 is in part produced by adipose tissue (Fain et al., 2004). Dietary interventions that reduce body weight are thus likely to be effective in lowering inflammatory markers.

The relation between DF and body weight has often been reviewed (Howarth et al., 2001; Pereira and Ludwig, 2001; Slavin, 2005). Mechanisms through which DF can assist in weight loss include, but are not limited to, the effects of DF on gastric emptying (Yao and Roberts, 2001), satiety (Holt et al., 1992), gut hormones such as cholecystokinin (Burton-Freeman et al., 2002) and an altered glycaemic index or insulin response (Anderson et al., 2004). However, in some instances, significance in both weight loss and CRP was not achieved. In hyperlipidaemic subjects, CRP concentrations reduced significantly following a very high fibre vegetarian intake of 7.8 g/MJ DF compared with the control group, with an insignificant weight loss (P=0.06) (Jenkins et al., 2003). Koren et al. (2006) found no effect on CRP following a lower carbohydrate (45%) intake during 2 weeks of isocaloric feeding in overweight subjects. However, CRP lowering was seen with ad libitum feeding on a high-carbohydrate (65%) intake, accompanied by weight loss (significance not reported), during the next phase of the trial (Koren et al., 2006). In another long-term study, the significant favourable results in CRP and IL-6 were adjusted for body weight and the authors attributed the favourable findings to the Mediterranean-style diet and largely independent of the changes in body weight (Esposito et al., 2004).

From the studies included in the review, it seems as if the groups that could have benefited the most from a reduction in CRP (overweight and obese individuals with high baseline CRP levels; King et al., 2007, 2008) were also the groups that did not respond to the increased fibre intake (except for a decrease in fibrinogen level in the high-fibre group; King et al., 2008). These groups also did not lose weight. It is therefore hypothesized that dietary interventions to reduce CRP levels in obese individuals with raised CRP levels may only be effective if the intervention includes weight loss. Taking the suggestion of Borges et al. (2007) into account, namely that a decrease in CRP levels depends more on a decrease in abdominal fat (waist circumference) than on the weight loss itself, this may indicate an association of raised CRP with components of the metabolic syndrome and that waist circumference should be measured in future studies of the effects of DF on inflammatory markers.

Macronutrients

The differences seen between macronutrient intakes in the comparative groups need some consideration (Table 2). Two studies reported substantial differences in the total fat intake between the control and intervention groups (Jenkins et al., 2003; Koren et al., 2006). In one instance, the authors concluded that plasma CRP concentrations are not affected by isocaloric dietary fat reduction (Koren et al., 2006). In the other, caution should be taken because of the substantial but nonsignificant difference in baseline CRP values between comparative groups (Jenkins et al., 2003). Other literature indicate that in young adults (mean age 18 years), saturated fat emerged as the single most important nutrient contributing to increases in CRP levels (Arya et al., 2006), whereas a modest association in adults has been found (King et al., 2003). Other dietary fatty acids that showed a weak inverse relation with CRP include monounsaturated fatty acids, PUFA and omega-3 PUFA in women (Fredrikson et al., 2004). The role of omega-3 PUFA in lowering CRP levels has also been shown in clinical trials (Rallidis et al., 2003; Bemelmans et al., 2004) and cross-sectionally (Lopez-Garcia et al., 2004). The lowering of CRP could thus have in part been attributed to changes in fatty acids intake.

In addition to fat, another major difference in macronutrients occurs in one study in the form of carbohydrates (Koren et al., 2006). Isocaloric substitution of carbohydrates for fat caused no change in CRP in their study. After 12 weeks of ad libitum consumption of a low-fat (15%)/high-carbohydrate (65%) diet, both body weight and CRP reductions reached significance. In the study by O’Brien et al. (2005), CRP concentrations were measured retrospectively in baseline and 3-month samples from obese women completing a randomized trial comparing a low-fat (28%)/high-carbohydrate (54%) diet and a very-low-carbohydrate (15%)/high-fat (57%) diet. Both interventions lead to significantly lower CRP concentrations. These effects were proportional to the amount of weight lost but independent of dietary macronutrient composition (O’Brien et al., 2005). In the context of weight loss, macronutrient composition is probably not important in lowering CRP.

Adiponectin

Adiponectin is an adipocyte-derived hormone with insulin-sensitizing and antiatherogenic properties and may mediate some of its cardioprotective effects through its anti-inflammatory effects (Berg and Scherer, 2005). Reducing adipocyte mass through liposuction does not increase adiponectin or affect CRP (Klein et al., 2004). Havel (2004) hypothesizes that adiponectin is regulated by adipocyte size and that a substantial reduction in adipocyte size is required to increase adiponectin production and circulating levels. Only one study reviewed here measured adiponectin, reporting a significant increase in adiponectin together with the highest mean weight loss (14 kg) compared with the other studies (Table 4) (Esposito et al., 2003a). In this study, the control group also experienced a significant weight loss (3 kg). In fact, the objective of this study was to achieve weight loss and change lifestyle by implementing a multidisciplinary programme. The control group received general information about healthy food choices and exercise. The huge weight loss in the intervention group was probably not the result of the change in DF but rather the change in lifestyle and lower energy intake and the increase in adiponectin, probably the result of weight loss rather than a change in DF intake.

Interleukins

Cytokines, such as the interleukins, are regulatory proteins that are released by cells of the immune system and act as intercellular mediators in the generation of an immune response. The sole determinant of CRP is its synthesis rate (Vigushin et al., 1993), which thus directly reflects the intensity of the pathological processes stimulating CRP production. IL-6 seems to be the chief stimulant to hepatic production of CRP (Castell et al., 1989). Modulation of the fibre content of a meal may influence the cytokine milieu: increasing the fibre content of a meal from 4.5 to 16.8 g was associated with a significant reduction of circulating IL-18 concentrations in healthy and diabetic subjects (Esposito et al., 2003b). IL-18 is a potent pro-inflammatory cytokine that may be important in the process of plaque destabilization and hence in predicting cardiovascular death in patients with acute coronary syndromes (Blankenberg et al., 2002). The intestinal flora, which is dependant on DF (Andoh et al., 1999), may also contribute in preventing inflammation by reducing the production of inflammatory cytokines by altering the intralumen bacterial environment (Kanauchi et al., 2003). With fewer inflammatory cytokines produced in the bowel, the liver may produce less CRP, resulting in lower concentrations of CRP (Rosamond, 2002). In agreement with recent reviews (Bastard et al., 2006; Ma et al., 2008), two studies in this review found simultaneous reductions in CRP and IL-6 (Esposito et al., 2003a, 2004).

Insulin and glucose

Positive correlations exist between CRP/IL-6 and insulin resistance (Chambers et al., 2001), and interventions that alter insulin resistance may also alter CRP concentrations (Clifton, 2003). A significant reduction in insulin and glucose is seen following high fibre intakes (Anderson et al., 1995; Chandalia et al., 2000). Furthermore, the intake of rapidly digested and absorbed carbohydrates with a high dietary glycaemic load is associated with increased CRP concentrations (Liu et al., 2002). Esposito et al. (2002) showed that intravenous glucose administration increases concentrations of the pro-inflammatory markers IL-6 and IL-18 and hypothesize that low-fibre diets can thus contribute to hyperglycaemia with resultant increases in the mentioned cytokines (Esposito et al., 2004). As insulin is known to stimulate IL-6 secretion (Krogh-Madsen et al., 2004), it can be predicted that diets that induce a relatively low post-prandial insulin response will be associated with below-average serum concentrations of IL-6 and CRP. Therefore, it may be possible to moderate CRP concentrations by avoiding high-insulin-response starchy foods (high-glycaemic index foods) and emphasizing whole-grain foods rich in amylose and fibre (Jenkins et al., 2003). The studies reviewed here did not determine the glycaemic indexes or glycaemic loads, and the relevance of this as a potential mechanism in these studies could not be determined. Even in the short term (72 h), insoluble fibre (31.2 g) has been shown to improve whole-body insulin sensitivity in obese and overweight women (Weickert et al., 2006). In a cross-sectional analysis of 780 diabetic men, high glycaemic index and glycaemic load were associated with lower concentrations of plasma adiponectin (Qi et al., 2005) and positive associations between cereal fibre and plasma adiponectin were observed (Esposito et al., 2003b; Richter et al., 2004). In insulin-resistant states, insulin has a pro-inflammatory effect producing more cytokines (Fernandez-Real and Ricart, 2003). McLaughlin et al. (2002) showed that with weight loss, CRP levels are decreased only in insulin-resistant, but not in insulin-sensitive, obese subjects. Insulin and IL-6 were measured in two of the studies being reviewed here, and these reported significant decreases in insulin, IL-6 and body weight (Esposito et al., 2003a, 2004).

Free fatty acids and triglycerides

In a recent clinical trial, the changes in CRP were best described by changes in free fatty acids (FFAs), TG and waist circumference (Dvorakova-Lorenzova et al., 2006). IL-6 (Esposito et al., 2003a) and CRP (Florez et al., 2006) are significantly associated with FFA concentrations in women. Increased IL-6 and decreased adiponectin concentrations from an excess of adipose tissue may have a convergent increased effect on FFA (Esposito et al., 2003a) that affects insulin sensitivity negatively (Trowell, 1975). Soluble fibre is fermented by anaerobic bacteria in the colon to short-chain fatty acids (Cummings and Englyst, 1987) including acetate, which inhibits serum FFA release from adipocytes (Scheppach et al., 1988; Ferchaud-Roucher et al., 2005), resulting in an increased insulin sensitivity (Trowell, 1975). It is possible that the resultant lower insulin levels can reduce the amount of IL-6 produced as shown in vitro (Vicennati et al., 2002) and in vivo (Krogh-Madsen et al., 2004) and thus subsequently CRP. Furthermore, adiponectin may lower circulating FFA concentrations by increasing fatty acid oxidation by skeletal muscle (Yamauchi et al., 2001) and by increasing hepatic FFA extraction directly (Tschritter et al., 2003). Cereal fibre may affect adiponectin by reducing the FFA available for storage in adipose tissue by promoting the clearance of lipids (Jenkins et al., 2001). FFA acts as a ligand for the upstream regulation of adiponectin expression (Iwaki et al., 2003). Lower adiponectin concentrations following high-carbohydrate, low-fibre meals were found in diabetic patients (Esposito et al., 2003b). Altogether, this information warrants more research to investigate the effect of DF on adiponectin and FFA.

A positive correlation between CRP/IL-6 and TG concentrations exists (Fredrikson et al., 2004). Dietary carbohydrates stimulate TG production in the liver and may cause secondary hepatic inflammation with associated higher CRP concentrations (Kerner et al., 2005). This increase in TG seems to be intermittent and the concentrations decrease again over time indicating that DF might counteract the hypertriglyceridaemic effect of carbohydrates (Rivellese et al., 1994). An association observed between high adiponectin and low TG concentrations was independent of insulin sensitivity (Taskinen, 1990). There is also evidence that adiponectin lowers circulating FFA concentrations by decreasing TG content in the muscle and liver (Yamauchi et al., 2001). TG decreased significantly in all (Junker et al., 2001; Esposito et al., 2003a, 2002) but one (Jenkins et al., 2003) of the studies reviewed here that measured TG. In the latter study, the short duration of the intervention could explain the lack of significance. In another study that was short in duration, the subjects had very high baseline TG levels (Junker et al., 2001) and thus likely to have had higher responsiveness during interventions. However, this information is insufficient to advocate a satisfactory mechanism for the link between TG and CRP.

To integrate the possible mechanisms through which DF may affect CRP through its effects on weight loss, secretion, turnover and/or metabolism of insulin, glucose, FFA, TG, adiponectin and/ or IL-6, a schematic representation is shown in Figure 1 that clearly illustrates the complexity and, also at the same time, the interrelationships between DF effects.

Figure 1
figure1

Schematic representation of the mechanisms through which dietary fibre may influence CRP. SCFAs, short-chain fatty acids; FFAs, free fatty acids; TGs, triglycerides, IL-6, interleukin-6; CRP, C-reactive protein.

Type of fibre

A recent prospective study differentiated between the association of CRP and that of total fibre intake and, as far as we know, for the first time, between soluble and insoluble fibre (Ma et al., 2006). The studies included in this review could not make a distinction between types of fibre, as they were part of the same foods and included fruits, vegetables, oats, barley, psyllium, nuts, muesli, whole-grain bread and cereal. Psyllium supplements, used in the studies of King et al. (2007, 2008), suggested that fibre supplementation with psyllium does not replicate the results seen with a diet naturally high in fibre (King et al., 2008). Ma et al. (2006) observed an inverse association between the intake of total DF (separately for soluble and insoluble fibre) and CRP concentrations in both cross-sectional and longitudinal analyses but could not tease apart their effects because they are part of the same foods. Epidemiological (Salmeron et al., 1997; Schulze et al., 2004b) and experimental (Qi et al., 2005, 2006) studies indicate a stronger inverse association of cereal fibre with type 2 diabetes, coronary heart disease and lower CRP concentrations than other types of fibre; however, the mechanisms are not clear.

Future studies and limitations

There is a pressing need to determine if DF can affect CRP as existing epidemiological (King et al., 2003; Ajani et al., 2004) and clinical data (Junker et al., 2001) are promising, but lack appropriate study designs that prevent conclusions. Weight loss and simultaneous changes in the fatty acid intakes and other diet components were prominent confounders in the studies reviewed here. Well-controlled isocaloric trials (preferably controlled feeding) with DF as the only variable, such as in supplemental studies, are recommended to explore the relation between CRP and DF and identify physiological mechanisms. Differentiation between the effects of the different types of DF will be valuable. For future studies, it is important to realize that the CRP response is triggered by many disorders unrelated to cardiovascular disease and a stable baseline with multiple measurements is recommended (Pepys and Hirschfield, 2003).

The most important limitation of this review was, as mentioned earlier, that few of the studies had the primary objective of investigating the independent effects of fibre on CRP. The dietary interventions were restrictive as we were unable to determine whether individual components of the diet accounted for the changes observed. A further limitation of this study was that we could not account for possible racial and gender (Khera et al., 2005) or genetic differences (MacGregor et al., 2004). Effect sizes could not be calculated due to a lack of report on control groups, and the possibility of publication bias remains.

Conclusions

This review shows that, in the presence of weight loss and modified saturated, monounsaturated fatty acid and PUFA intake, increased fibre consumption (3.3 g/MJ) is associated with significantly lower CRP concentrations (↓25–54%). Owing to confounding factors and differential study designs, the physiological mechanisms of the effects of DF on CRP are inconclusive in this review. Potential mechanisms that need investigation include changes in insulin, glucose, adiponectin, IL-6, FFA and TG secretion, turnover or metabolism. More randomized, controlled trials of high- and low-fibre diets are recommended to explore the potential favourable effects of DF on CRP as seen in some epidemiologic studies (Ma et al., 2006) but not in others (Ma et al., 2008). Further research is needed to more fully understand which types of fibre work best and which individuals are most susceptible to its anti-inflammatory effect, so that the long-term goal of reduction in cardiovascular risk can be achieved (King et al., 2007).

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North, C., Venter, C. & Jerling, J. The effects of dietary fibre on C-reactive protein, an inflammation marker predicting cardiovascular disease. Eur J Clin Nutr 63, 921–933 (2009). https://doi.org/10.1038/ejcn.2009.8

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Keywords

  • dietary fibre
  • C-reactive protein
  • cardiovascular disease
  • clinical trials
  • weight loss

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