Cardiometabolic diseases are a leading global health challenge. Their incidence as well as progression is strongly affected by diet. Consumption of Pleurotus ostreatus (P. ostreatus), an edible oyster mushroom rich in functional ingredients (e.g., β-glucans), may improve glucose and lipid metabolism, blood pressure, body weight and appetite sensations. Hence, this systematic review aimed to provide an overview on the effects of P. ostreatus intake on cardiometabolic parameters from clinical trials, taking into account risk of bias (RoB). Relevant studies were investigated for details with consideration of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. The Cochrane Collaboration’s tool was used to assess the RoB. In total, eight trials included observed beneficial effects of P. ostreatus intake on glucose metabolism (reduction in fasting and/or 2 h postprandial glucose) and lipids (decrease in total cholesterol, LDL-cholesterol and/or triglycerides), and some found a reduction in blood pressure. In contrast, body weight did not change. Appetite sensations were not assessed. In most studies, the RoB was high or unclear due to methodological weaknesses and/or inadequate reporting. Thus, P. ostreatus intake may improve cardiometabolic health, but evidence for this is low. Hence, further clinical trials with an adequate study design are warranted to validate these suggestions.
Cardiometabolic diseases such as diabetes mellitus type 2 (DMT2), dyslipidemia, hypertension and obesity are associated with increased morbidity and mortality. They are known to be the major risk factors for cardiovascular diseases (CVDs), which are still the leading cause of death in modern societies worldwide. According to the World Health Organization (WHO), 17.9 million people died from CVDs in 2016, representing 31% of all deaths .
Incidence as well as the progression of these cardiometabolic diseases is strongly affected by behavioral factors such as tobacco use, physical activity and diet . The latter explains current interest in functional food and food ingredients which may improve cardiometabolic health . At the same time, the need for sustainable food production becomes more important due to growing populations and the effects of climatic change, which represents an additional global challenge .
In this respect, edible mushrooms which are part of the usual diet are interesting as an alternative source of nutrients, but also for ecological reasons [4,5]. Pleurotus ostreatus (P. ostreatus), also called oyster mushroom, is one of the most cultivated edible mushrooms worldwide after white button mushroom (Agaricus bisporus, A. bisporus) . P. ostreatus is of particular interest as it is able to colonize and degrade a large variety of lignocellulosic substrates from organic residuals and grows faster than other edible mushrooms . Furthermore, P. ostreatus delivers various bioactive compounds such as β-glucans, which may improve cardiometabolic health [5,7]. P. ostreatus provides approximately twice as many β-glucans as A. bisporus , a dietary fiber that has been gaining much interest due to its beneficial role in the prevention of insulin resistance, dyslipidemia, hypertension, and obesity. The ability of β-glucans to form highly viscous solutions in the human gastrointestinal tract as well as their fermentability is ascribed to play a key role for their health-related benefits which are well known from studies with β-glucans from oats and barley . β-glucans in P. ostreatus are side-chain/branched (1,3;1,6) polysaccharides in contrast to the linear (1,3;1,4) β-glucans in oat and barley . This structural property may be beneficial for effects ascribed to an increase in the viscosity of the chymus as the β-1,6-linked glucose side chain may increase the molecule’s solubility . However, β-glucans in mushrooms are partly crosslinked with chitin chains of the fungal cell wall which can reduce their solubility . Other bioactive compounds which have been found in P. ostreatus may also improve cardiometabolic health. Mevinolin, also known as lovastatin, acts as an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-COA) reductase, and is likely to be involved in hypolipidemic effects by lowering cholesterol biosynthesis . Moreover, several bioactive peptides obtained after in vitro digestion of P. ostreatus have been shown to inhibit the angiotensin converting enzyme . This might reduce blood pressure (BP), provided that such effects would also occur in vivo. Furthermore, P. ostreatus is also rich in phenolic compounds. These may explain the strong antioxidant properties which were demonstrated for extracts in vitro .
There is an increasing number of animal studies with P. ostreatus which observed hypoglycemic [13,14,15], hypolipidemic [14,16], and antioxidant [17,18] effects as well as a reduction in food intake and weight gain . In addition, in vitro and animal studies partly provide valuable suggestions on the underlying biological mechanisms of metabolic actions. For example, phosphorylation of AMP-activated protein kinase, gene expression of glucose transporter 4 (GLUT 4) in muscle and adipose tissue  and the expression of genes involved in β-oxidation increased . In order to assess the efficacy of P. ostreatus intake on cardiometabolic health, it is necessary to systematically investigate the results from human intervention studies and to assess the quality of the studies. However, this has not been performed yet.
Thus, the aim of this systematic review was to investigate whether the intake of P. ostreatus modulates cardiometabolic parameters (glucose and lipid metabolism, blood pressure, body weight (BW) and appetite sensations). We reviewed clinical trials which assessed healthy subjects and subjects suffering from overweight/obesity and/or cardiometabolic diseases. We assessed the risk of bias (RoB) for each study to judge the evidence for cardiometabolic effects.
2. Materials and Methods
This systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines . It was submitted to the International Prospective Register of Systematic Reviews (PROSPERO) database.
2.1. Literature Search Strategy
A systematic literature search was conducted in the PubMed database for human intervention studies which investigated the effect of P. ostreatus intake on cardiometabolic health. For the literature search, the following Medical Subject Heading (MeSH) term was used: ((“edible mushroom” OR “culinary mushroom” OR “pleurotus ostreatus” OR “oyster mushroom”) AND (glucose OR insulin OR HbA1c OR “hypoglycemic effect” OR prediabetes OR “impaired glucose tolerance” OR diabetes OR cholesterol OR triglycerides OR lipids OR “lipid lowering” OR “hypolipidemic effect” OR hyperlipidemia OR “blood pressure” OR cardiometabolic OR “antiatherogenic effect” OR prehypertension OR hypertension OR atherosclerosis OR “body weight” OR appetite OR satiety OR hunger OR overweight OR obesity)). Two filters were applied: English language and human species. The database search, which was performed by one reviewer (L.D.), was finished on 31 January 2020. Eligible articles which were published up to that date were considered for inclusion.
In addition, the reference lists of the included studies were perused to identify further studies of relevance that had not been identified in the PubMed database before.
2.2. Inclusion and Exclusion Criteria
This review focused on intervention studies which investigated the efficacy of P. ostreatus intake on cardiometabolic parameters in adults. Studies were included if they investigated (1) the effect of P. ostreatus as a whole mushroom (fresh, cooked or dried) as well as extracts; (2) parameters of glucose metabolism (e.g., glucose, insulin, HbA1c), lipid metabolism (e.g., triglycerides (TGs), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C)), cardiovascular health (e.g., systolic and diastolic BP) as well as BW and appetite sensations; (3) healthy subjects, subjects with overweight/obesity and/or cardiometabolic disorders (e.g., prediabetes, DMT2, hyperlipidemia, pre/hypertension, atherosclerosis). Studies were excluded for the following reasons: (1) treatment with other edible mushrooms than P. ostreatus; (2) treatment with isolated substances from P. ostreatus (e.g., pure β-glucans or mevinolin) or with mushroom powder or extract additionally enriched with vitamins or functional ingredients; (3) not being a clinical trial; (4) addressing other topics (e.g., anticarcinogenic effects); (5) investigating subjects suffering from severe diseases (e.g., concerning gut, liver, pancreas and kidneys, cancer), other types of diabetes than DMT2 or using medications which might favor cardiometabolic disorders (e.g., glucocorticoids, antiretroviral therapy).
2.3. Study Selection, Data Extraction and Risk of Bias Assessment
Two independent reviewers (L.D. and S.E.) identified relevant studies by analyzing the records using a self-made Excel template which considered the predefined eligibility criteria. First, all items were screened by title and/or abstract to exclude contributions that met exclusion criteria. Afterwards, all remaining studies were assessed for eligibility by reading the full-text article. Any discrepancies in the selection process were discussed until a consensus was reached. Finally, studies which were considered to be eligible were included in this systematic review.
Afterwards, both review authors extracted relevant data independently by using a self-made Excel template: study design, details of the intervention (amount, duration and application of P. ostreatus, including main ingredients based on food analysis) and of the control treatment, participants (sample size, dropout rate, demographics and baseline characteristics), outcomes (parameters on glucose and lipid metabolism, vascular function, BW, appetite sensations), times of measurement on outcome markers, and suggested mechanisms of action. Missing data were partly obtained from study authors. If available, the study registration was checked to complete data. Considering data extraction, discrepancies were also discussed by the authors.
Thereafter, both review authors independently assessed the quality of the included studies on the basis of the Cochrane risk of bias tool  to judge the RoB with regard to the following criteria: (1) adequate randomization method and generation of randomization list before the study (selection bias); (2) concealing treatment allocation from participants and investigators (allocation concealment); (3) blinding of participants and investigators (performance bias); (4) blinding of outcome assessment until completion of statistical evaluation (detection bias); (5) completeness of outcome data, reporting number and reasons of dropouts (attrition bias); (6) registration of study protocol, reporting full endpoints and outcomes according to registration (reporting bias). Furthermore, (7) controlled study design, details on intervention, investigation of outcome markers and on statistical evaluation, potential confounders, estimation of sample size, and comparison of baseline data were considered to assess other bias. Again, a self-made Excel template was used to check these criteria for each study. Discrepancies in the RoB assessment were also resolved through discussion.
3.1. Study Selection and Study Characteristics
After a systematic literature search, 94 records were retrieved from the PubMed database and another 11 publications were found through other sources. After the removal of duplicates, 102 records remained. Based on titles and/or abstracts, 94 records were excluded (reasons: intervention with other mushrooms than P. ostreatus, n = 65; intervention with isolated substances from P. ostreatus, n = 17; considering other topics not related to human health, e.g., cultivation conditions, n = 4; considering biomarkers related to other diseases than cardiometabolic disorders, e.g., cancer, n = 2; in vitro or animal studies, n = 3; no interventional study design, n = 1; investigating HIV-infected individuals under antiretroviral therapy, n = 1; full-text article not available, n = 1). After reading the full-text articles, a further publication was excluded which used another Pleurotus spp. than P. ostreatus for treatment. Finally, eight studies which were presented in seven original contributions were included in the present review. A flow diagram of the identification and selection of studies is shown in Figure 1.
All studies investigated the effect of whole oyster mushrooms. These studies provided fresh or cooked mushrooms , but in most studies, they were ingested in dried form. All trials investigated the effect of regular, daily intake for 7–365 days . Jayasuriya et al. also examined the acute effect as well as the combined effect of chronic and acute intake. Most studies investigated patients suffering from DMT2, dyslipidemia , hypertension and overweight/obesity (BMI data not shown for). In one case, a subgroup of healthy subjects was additionally examined. Outcome markers refer to glucose metabolism, lipid, and BP . Two trials also addressed pro-/antioxidant status and BW , whereas appetite sensations were not determined in any study. For details on study characteristics, see Table 1. Most trials were performed in Bangladesh and further in Slovakia , Germany and in Sri Lanka . With regard to the study design, five trials which were provided in four publications were controlled . These were performed as randomized controlled trial (RCT) or as non-randomized studies, either with a two-arm parallel group design or as a prospective self-controlled study (SCT) in which each participant was its own control . In further trials including the substudy of Jayasuriya et al. on chronic P. ostreatus intake, a control treatment was lacking
3.2. Effects of Oyster Mushroom Intake on Cardiometabolic Parameters
3.2.1. Glucose Metabolism
Khatun et al.  provided cooked P. ostreatus (150 g/d, trice daily 50 g) as part of a meal in exchange for vegetables for 7 days to hospitalized patients with DMT2 or impaired fasting glucose and dyslipidemia. The plasma glucose concentration in fasting state (fasting plasma glucose, FPG) and 2 h after breakfast (2hABF) was reduced on average by 22% and 23%, respectively, after the first treatment with oyster mushrooms. After 1 week without mushrooms, FPG as well as 2hABF increased on average by 13% and 20%, respectively. A second treatment with P. ostreatus for 7 days again induced a mean reduction in FPG by 23% and also in 2hABF by 16%. Sayeed et al.  also provided oyster mushrooms (200 g/d) in exchange for vegetables, but to women with drug-treated DMT2. All investigations were performed bimonthly during an intervention for 1 year. After treatment with P. ostreatus, FPG decreased approximately 12% after 2 months and up to 20% after 1 year compared to baseline but did not change in the control group. Comparable changes in postprandial glucose concentrations were detectable after mushroom treatment (mean reduction approximately 14% after 2 months and approximately 28% after 1 year), but not in the control group. In the uncontrolled study of Choudhury et al. , men with drug-treated DMT2 ingested capsules with sun-dried powdered P. ostreatus (3 g/d; thrice daily amounts of 1 g) for 3 months. After intervention, FPG as well as HbA1c were reduced on average by 18% and 13%, respectively. Jayasuriya et al.  provided lyophilized powdered P. ostreatus (50 mg/kg BW) as suspension to different subgroups (healthy subjects and subjects with dietetically-treated DMT2). In healthy subjects, daily intake of the mushroom suspension for 14 days reduced FPG by 6%. A control treatment was lacking. In a further experiment with the same subjects, postprandial effects were examined by using an oral glucose tolerance test (OGTT) as glucose challenge. The first OGTT was provided 2 h after ingestion of water (control), following a daily intake of P. ostreatus for 14 days. Thereafter, a second OGTT was performed 2 h after bolus ingestion of the mushroom suspension. The glucose concentration in plasma 2 h after OGTT was 16% lower after the intake of the mushroom suspension compared to water, which reflects the combined effect of chronic and acute intake. A further substudy with diabetics investigated the effect of a single preload with mushroom suspension which was ingested 30 min before an OGTT compared to a preload of water (control). This diminished the 2 h glucose approximately 15% and increased the 2 h insulin approximately 22%. Both treatments were performed within a self-controlled trial and were separated by 1 week washout.
3.2.2. Lipid Metabolism
Khatun et al.  also investigated the effects on serum lipids. The decrease in FPG after the first intervention with P. ostreatus was accompanied by a decrease in both TGs (28%) and TC (8%). After 1 week without mushrooms, TGs increased by 11% and TC by 6%. If treatment with mushrooms was repeated, TGs and TC were again reduced by 9% and 13%, respectively. In the study of Sayeed et al. , the decrease in FPG after consumption of oyster mushrooms was also accompanied by a decrease in TGs and TC. This effect was already significant after 2 months (mean reduction of TGs by 19% and of TC by 12%, respectively), with a similar reduction observed after 1 year (TGs 20%, TC 20%) compared to baseline. However, LDL-C remained unchanged. No changes in TGs, TC and LDL-C were observed in the control group. Throughout intervention, TGs, TC and LDL-C were significantly lower in the mushroom than in the control group. The RCT of Schneider et al.  investigated adults with moderate, untreated hyperlipidemia. Daily consumption of a soup providing 30 g of lyophilized P. ostreatus for 3 weeks decreased TGs on average by 23%, whereas TGs increased by 25% in the control group which received a mushroom-free tomato soup instead. The changes in TGs were significantly higher in the mushroom group by 0.8 mmol/Lcompared to the control group. Significant changes in TC and LDL-C were neither detectable within each group nor between the groups. P. ostreatus showed significant hypolipemic effects in an uncontrolled clinical trial of Kajaba et al.  in which participants with primarily combined types of dyslipidemia were treated with 10 g of lyophilized powdered P. ostreatus daily for 6 weeks. TGs, TC and the TC/HDL-C ratio decreased significantly compared to baseline by on average 36%, 22%, and 24%, respectively. A further uncontrolled trial of Choudhury et al. , who provided dried powdered oyster mushrooms (3 g/d for 90 days) to hypertensive men with overweight or obesity, found a mean reduction in TC and LDL-C by 12% and 19%, respectively. In contrast to Kajaba et al. , changes in TGs were not observed. HDL-C was determined in all trials which investigated lipid status, but changes were not detected in any study after intervention with P. ostreatus .
3.2.3. Blood Pressure
The trial of Choudhury et al. , already mentioned above, investigated BP in hypertensive subjects with DMT2. After a daily intake of capsules with powder from lyophilized P. ostreatus for 3 months, SBP and DBP decreased on average by 10% and 11%, respectively. Khatun et al.  also examined BP, but in normotensive subjects who received cooked oyster mushrooms daily for 7 days. Nevertheless, a significant reduction in SBP (4%) and DBP (2%) could also be observed. After consumption of vegetables instead of mushrooms for 7 days (control), DBP increased by 2%, whereas SBP remained unchanged. After retreatment with oyster mushrooms for one week, DBP decreased again by 1%, SBP remained unchanged. Sayeed et al.  provided fresh P. ostreatus to drug-treated women suffering from DMT2 (characteristics/data for BP were not provided) also in exchange for vegetables (control). BP was determined bimonthly during the one-year intervention period. Significant changes in SBP and DBP were not observed, neither within each group nor between the groups.
3.2.4. Pro-/Antioxidant Status
The uncontrolled study of Kajaba et al.  examined the pro-/antioxidant status in adults with primarily combined dyslipidemia in addition to lipids. The concentration of conjugated dienes (CD) in plasma decreased while the activity of glutathione peroxidase (GPX) and the concentration of glutathione (GSH) in erythrocytes increased after 6 weeks of P. ostreatus powder intake. In contrast, superoxide dismutase (SOD) and catalase (CAT) remained unchanged. Schneider et al.  observed a significant decrease in oxidized LDL (oxLDL) by approximately 11% in patients with moderate hyperlipidemia after 3 weeks of treatment with oyster mushrooms, but no changes in the control group. However, the changes in oxLDL between both groups were not significantly different.
3.2.5. Body Weight
BW did not change after consumption of P. ostreatus as well as after control treatment for 1 week and 3 weeks .
3.3. Risk of Bias Assessment
RoB was assessed for each study on the basis of qualitative criteria (Table 2). The judgements are shown in Figure 2. For all trials which were uncontrolled or non-randomized the risk of selection bias (7/8) as well as of missing allocation concealment (7/8) was rated as high. These risks remained unclear in the RCT of Schneider et al. as details on the randomization procedure were lacking. Since participants were never blinded to treatment and details on blinding of investigators were never provided, the risk of performance bias was judged as high for each study (8/8). Risk of detection bias remained unclear for all studies (8/8), as information on blinding of investigators during outcome assessment was not given. Except for the subtrial of Jayasuriya et al. with diabetics suggestions as to the previous registration of the trial in a study register which could have revealed methodological details were missing . A sample size estimation was always lacking . In two studies with a dropout rate of 59% and 66%, respectively, risk of attrition bias was high. In further studies including the subtrial with healthy subjects of Jayasuriya et al. information on dropout and the intended sample size was lacking . Risk of attrition bias was low for the trial of Schneider et al. and for the substudy with diabetics by Jayasuriya et al. where the number of and reasons for dropout were reported or sample size was specified in the study registration . Except for the latter subtrial, there were no indication concerning prospective registration of any trial in a study register. Thus, risk of reporting bias could only be excluded for this subtrial , whereas this remained unclear for further studies . The risk of other bias (8/8) was always high for several reasons: uncontrolled study design and lack of methodological details on intervention , outcome markers (e.g., laboratory method used, period of fasting if fasting blood was collected) , and statistical evaluation . Moreover, potential confounders were not adequately considered (e.g., sour cultivation and ingredients of mushrooms check of compliance nutritional behavior physical activity BW and medication and might have affected the outcome. Furthermore, sample size estimation was always missing . In the subtrial with diabetics, baseline comparisons were missing .