Impact of phytosterol supplementation on metabolic syndrome factors: a systematic review of randomized controlled trials

Abstract

Background

Phytosterols (PSs), plant-like organic structures with close similarity to cholesterol, might be useful therapeutically for hypertension, central obesity, dyslipidemia and hyperglycemia, which are components of metabolic syndrome (MetS). This systematic review aimed to evaluate the effects of phytosterol supplementation on MetS components in randomized clinical trials (RCTs).

Methods

A systematic search of RCTs published in PubMed/Medline, Web of Science, Embase, Cochrane Library, and Google Scholar up to October 18, 2023. was conducted according to the 2020 Preferred Reporting Items of the Guidelines for Systematic Reviews (PRISMA) statement. The research was updated by January 3, 2025. A total of 14 RCTS of PS intervention on MetS factor were included in a preliminary screening of the retrieved literature by Endnote 21. We assessed the quality of all included randomized controlled trials using the Cochrane Collaboration’s Risk of Bias tool.

Results

PS supplementation resulted in a modest improvement in MetS factors. In particular, fasting blood glucose decreased by about 2%, systolic blood pressure decreased by 3–5%, and triglyceride levels dropped by 19–24%. Waist circumference and HDL cholesterol changes were slight, negligible in most cases.

Conclusion

PS supplementation appears to improve blood pressure, triglyceride levels, and other features of MetS. These findings differ from study to study, and treatment periods were frequently shorter. To fully comprehend the long-term advantages, further well-designed research is required.

Supplementary Information

The online version contains supplementary material available at 10.1186/s13098-025-01887-2.

Introduction

Metabolic syndrome (MetS) is a complex disorder characterized by manifestations such as abdominal obesity, increased fasting blood glucose, elevated blood pressure and hyperlipidemia [1]. Health organizations have provided various definitions for metabolic syndrome [2], but the main characteristic shared by all of them is that MetS represents a pathological cluster of risk factors that directly increase the likelihood of developing coronary artery disease [3], atherosclerosis [3], and type 2 diabetes [4]. According to National Cholesterol Education Program (NCEP) Adult Treatment Panel-III (ATP-III) definition [5], developed by Scott Grundy, MetS is diagnosed if three or more of the following factors are met: Increased waist circumference (more than 102 cm for men and more than 88 cm for women), elevated triglycerides (equal to/greater than 150 mg/dL), decreased HDL cholesterol (less than 40 mg/dL in men and less than 50 mg/dL in women), increased blood pressure (equal to/greater than 130.85 mmHg or taking medication to control hypertension) and increased fasting blood glucose (equal to/greater than 100 mg/dL or taking medication to control hyperglycemia). MetS has recently received significant attention due to modern lifestyle and increasing prevalence of obesity worldwide [6].

The prevalence of MetS is recognized as a global concern. The risk of developing MetS increases with age [6], such that more than 59% of individuals in their 60s are affected [6]. The prevalence of MetS in the U.S has increased from 36.7% in 2011 to 41.8% in 2017 [7]. Additionally, 25% of people in Europe are affected by this syndrome [8]. According to the International Diabetes Federation (IDF), the global prevalence of metabolic syndrome varied from 12.5 to 31.4% due to the definition [9].

Various factors, including genetics, environment and lifestyle habits such as obesity, physical inactivity and poor diet, could contribute to the development of MetS [10]. MetS increases the risk of cardiovascular diseases and mortality due to heart disease [11]. It may also lead to the development of fatty liver disease as a complication of the syndrome [12, 13]. Studies have revealed MetS plays a significant role in coronary artery disease [3] particularly in individuals with type 2 diabetes [14]. The secretion of pro-inflammatory compounds from adipose tissue, insulin resistance, elevated free fatty acids in the bloodstream and increased circulating atherogenic lipoproteins, all of which occur in MetS, are involved in the pathophysiology of serious cardiovascular complications associated with this syndrome [10, 15] MetS doubles the risk of developing type 2 diabetes and increases the risk of major cardiovascular events by up to five times [16]. Moreover, MetS is associated with the incidence of neurodegenerative diseases [17], lipid and circulatory system disorders [18], fatty liver [19, 20], cancer [21], atherosclerosis [3], fertility problems [22] and all-cause mortality [23]. Management of MetS involves controlling modifiable risk factors, including lifestyle [6]. Measures such as weight loss, healthy eating and increased physical activity could be effective in controlling and managing MetS [1].

Phytosterols (PSs) are non-nutritive bioactive compounds with a biological structure and function similar to that of cholesterol [24]. The human body cannot synthesize phytosterols, so diet is the only source of these compounds [25]. PSs are primarily found in plant oils, seeds, legumes, nuts, and cereals, and are structurally similar to cholesterol [26]. To date, more than 200 types of PS have been identified in plants [27], with the most abundant being sitosterol, campesterol and stigmasterol, which account for 65%, 30% and 3% of total dietary phytosterols, respectively [25]. PSs contribute to reducing the risk of various cancers by modulating metabolic pathways [28], and exhibit a wide range of functions, including antioxidant [29], anti-tumor [30], anti-inflammatory [24], anti-proliferative [31], antimicrobial [32], anti-diabetic [33], antihypertensive [33] and anti-obesity [33] effects. Moreover, numerous studies have demonstrated the beneficial impact of the intake of PS on lowering LDL cholesterol levels [34]. The National Lipid Association, European Society of Cardiology and European Atherosclerosis Society recommended the intake of phytosterols for hyperlipidemia treatment and management [35]. A typical Western diet contains 300 mg of PSs per day [35], while vegetarian diets could supply 300–600 mg of phytosterols daily [26]. In 2010, FDA approved the health claim for PSs, stating that the intake of 1.3 g of phytosterols and 3.4 g of phytostanols, as a part of the diet low in saturated fatty acids and cholesterol, helps reduce the risk of cardiovascular diseases [36]. As a result, these compounds are incorporated into cholesterol-lowering products in fortified foods such as soy milk, milk, yogurt and margarine, aimed at reducing cholesterol levels [25]. PSs influence cholesterol absorption in the intestines, thereby lowering serum LDL levels and, ultimately, reducing the risk of cardiovascular diseases.

Several studies have been conducted on the intake of phytosterols and its relationship with MetS factors [37–40]. Salehi-Sahlabadi et al. [39] performed a systematic review to evaluate the effect of PS supplementation on blood glucose level, HbA1c and insulin. PS supplementation significantly increased fasting blood glucose in individuals with a BMI below 25 [39]. However, blood glucose level and HbA1c significantly decreased in those receiving 1–2 g of phytosterols per day [39]. Stanasila et al. found that circulating phytosterol level positively affected total cholesterol and LDL level [41]. Moreover, campesterol and sitosterol were positively correlated with increased HDL level [41]. Ghaedi et al. investigated the effect of phytosterol supplementation on blood pressure and indicated PS supplementation could significantly reduce both systolic and diastolic blood pressure [40]. Performing dose-response meta-analysis revealed dosage of less than 2,000 mg reduced diastolic blood pressure, while dosage equal to/greater than 2,000 mg was effective in reducing systolic blood pressure [40]. Investigations have revealed obesity, type 2 diabetes [42, 43] and MetS increase hepatic cholesterol synthesis [44]. Assmann et al. examined the relationship between MetS factors and cholesterol and found that increased cholesterol synthesis and reduced intestinal cholesterol absorption could be associated with the individual’s condition, MetS components and overall severity of the syndrome [45].

While there have been multiple systematic reviews and meta-analyses that have focused mainly on the effect of PS supplementation on particular metabolic parameters (such as blood lipids, blood glucose, and blood pressure), there are not many that examine the effects of PS supplementation concerning the combined effects on the overall profile of MetS factors. Previous reviews have often focused on isolated outcomes, without addressing the combined interaction between MetS components. Therefore, this systematic review aims to fill the existing knowledge gap by thoroughly examining how PS supplementation affects the key components of MetS. This includes looking at blood glucose levels, blood pressure, lipid profiles, and waist circumference, all based on evidence from RCTs.

Methods and materials

The guidelines of Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) [46] are followed in the present study.

Sources of data and necessary searches

An advanced search was conducted to identify essays related to the topic of the study in PubMed/Medline, Web of Science, Embase, Cochrane Library and Google Scholar up to October 18, 2023. The research was updated by January 3, 2025. Several keywords related to the intended intervention and result were combined and used in the advanced search (Complementary Table 1). Additionally, to ensure accuracy, the first 50 pages of the study were checked manually in the Google Scholar database during the searching process. To ensure all the related articles are included in the present study, all sources and references of review articles and previous metadata analyses in this field were also checked manually. Moreover, no filters were applied to the date and language of the articles. Despite this, the search strategy did not include unpublished research in dissertations, conference papers, or gray literature. This strategy ensured that the searches focused on peer-reviewed research, but we recognize that excluding these papers may entail some publication bias.

Choice of the study

The studies included in this review had the following requirements: 1. The study was a Parallel randomized clinical trial. 2- Phytosterols were used as the main intervention. 3- Factors of metabolic syndrome (waist circumference, fasting blood glucose, systolic and diastolic blood pressure, triglyceride and high-density lipoprotein levels in Serum) were reported at the beginning of the study. 4- There was a control or placebo group. Studies with the following conditions were excluded from the research: They had a combined intervention of phytosterol and other nutrients. 2- Not all factors of MetS were reported at the beginning of the study. 3- They used drugs/supplements that affect the levels and function of phytosterols. 4- The study was designed in the form of review articles and metadata analysis, research notes, letters, ecological studies, observational studies, case-control studies, cohort, cross-sectional and all non-randomized/non-parallel clinical trials. Also, to reduce confounding effects and establish the isolated impact of phytosterol supplementation on metabolic syndrome variables, we did not include studies that involved concurrent supplementation of phytosterols with other nutrients (e.g., omega-3 fatty acids, fiber, and antioxidants). Since the outcomes in these studies cannot be attributed to phytosterols alone, including such research would have compromised internal validity.

Data extraction

To extract the required data or review of the study, the full text of the entered studies was reviewed by two authors (F.G. and L.A.). The main data needed include the name of the author, year of publication, place of study, number of participants, demographic data (age and sex), number of people in control and intervention groups, type and amount of intervention, type and amount of placebo, duration of the study, and quantitative evaluation of metabolic syndrome factors (waist circumference, fasting blood glucose, systolic and diastolic blood pressure, and high density lipoprotein), which were collected as mean and standard deviation before and after the intervention and reported in the relevant tables.

Additionally, all the values of the abovementioned factors were reported as mean and standard deviation. In the articles in which the standard error was reported instead of the standard deviation, formula was used to convert it into standard deviation. where the confidence interval was reported, formula was used. In cases where quarters were reported, was used to calculate the standard deviation. In order to calculate the changes of standard deviation, formula was used [47]. Additionally, all the units of MetS factors such as fasting blood glucose, triglyceride and high-density lipoprotein of serum were changed from mmol/L to mg/dL.

Evaluating the quality of articles

The qualitative evaluation of the articles included in this review used the Cochrane risk of bias [48]. Bias related to the selection of patients, randomization, blinding, attrition and data reporting were also assessed. Studies with a high risk of bias in one or more of the above items were classified as high-risk. Studies with an unclear risk of bias in one or more items or not at high risk of bias in any of the above items were classified as moderate risk studies. A study with low risk of bias in all cases was considered low risk. In the present study, 13 articles were identified as low risk of bias [49–60] and 1 study was identified as medium risk of bias [61] (Complementary Table 2).

Results

Characteristics of the studies included in the review

After an advanced search, 4687 articles were identified from the abovementioned studies. One thousand three hundred sixty-seven articles were identified and removed because they were reiterated. By scrutinizing the title and abstract of the articles, 2827 articles were excluded due to not being related to the intervention or outcome. Four hundred ninety-three articles were reviewed regarding inclusion criteria and reporting MetS factors, and 449 were excluded. Finally, the full text of 44 articles was reviewed, of which 12 did not meet the inclusion criteria.

Additionally, nine articles [62–70] used a combination of phytosterol and other nutrients, and there was no distinct subgroup for the intended intervention. The full text of 4 articles was inaccessible [71–73]. Also, a reiterated study [55], a study with a crossover design [74] and a study which was not related to the intervention (phytosterol) [75] were excluded. Another study was also excluded because it reported as median [76] and it was impossible to convert the median to mean. Finally, after reviewing 44 studies, 30 were excluded, and 14 were included in the review. In one of the included studies, phytosterol was examined in two doses (1.6 gr and 2 gr), each included as a separate study. Finally, 15 studies were examined in this review [49–61, 77] (Fig. 1).

Fig. 1.

Flowchart depicting the selection process for studies included in the systematic review

Characteristics of studies

From among the total studies included in this review, 7 studies were conducted in Europe [49], 1 study in the Netherlands [77], 1 study in Greece [61] and 4 studies in Finland [51–53]) and 8 studies in Asia (2 studies in China [55, 60], 1 study in Thailand [56], 1 study in Indonesia [57], 1 study in Hong Kong [59], 1 study in India [50], 1 study in Turkey [54] and 1 study in Iran [58]). Fourteen studies had a double-blind randomized clinical trial design [57–64, 74], and 1 study had a single-blind clinical trial design [61]. The total number of the samples included in the study was 1163 people, from among which 578 people participated in the intervention group and 585 people in the control group. In the populations of 15 studies, only the population of 2 studies [49, 56] were entirely male and 13 other studies included a combination of male and female [50–55, 57–61, 77]. In the general analysis of statistics separately sorted by gender, 47.1% of the participating population were women and 52.9% were men. The duration of intervention in all studies is reported in terms of weeks; There are 8 studies [49, 50, 53–55, 57, 59] with short intervention duration (4 weeks or less), 3 studies [56, 58, 61] with medium intervention duration (5–8 weeks) and 4 studies [51, 52, 60, 77] with long intervention duration (9 weeks or more). Additionally, the participants of 2 studies [58, 60] were suffering from non-alcoholic fatty liver disease; the participants of 6 studies [50, 52–54, 57] were suffering from hypercholesterolemia, the participants of 2 studies [61, 77] were suffering from metabolic syndrome and the participants of 5 studies [49, 51, 55, 56, 59] were healthy people (Table 1).

Table 1.

Characteristics of the included studies

First author (year)	Country	design	Sample size (intervention group) (n=)	age (range)	Gender (f/M)	Intervention (type)	Control (type)	duration (weeks)	Dose of intervention (PS g/day)	Type of participants
Wojciechowska et al. (2003)	Poland	double blind parallel RCT	42 (20)	24.1 (mean)	M	phytosterol add margarine (margarine)	PUFA add margarine (margarine)	4	2.6	healthy
Plat et al. (2009)	The Netherlands	double blind parallel RCT	18 (9)	45–70	F/M (6/12)	yogurt drink + PS + placebo tablets (Drink)	yogurt drink w/o PS + placebo tablets (Drink)	9	2	Met.S patients
Khandelwal et al. (2009)	India	double blind parallel RCT	93 (47)	35–55	F/M (11/82)	yogurt drink + PS (Drink)	yogurt drink w/o PS (Drink)	4	2	mildly hypercholesterolemia subjects
Gylling et al. (2010)	Finland	double blind parallel RCT	49 (25)	18–75	F/M (32 − 17)	vegetable oil-based spread and oat-based drinks enriched with plant stanol ester (Drink)	vegetable oil-based spread and oat-based drinks w/o plant stanol ester (Drink)	10	8.9	healthy
Sialvera et al. (2012)	Greece	single blind parallel RCT	108 (53)	30–65	F/M (48/60)	plant sterol-enriched yogurt mini drink (Drink)	yogurt beverage without phytosterols (Drink)	8	4	Met.S patients
Turpeinen et al. (2012)	Finland	double blind parallel RCT	100 (51)	35–60	F/M (38/66)	spread + bioactive peptides + PS (Spread)	spread w/o bioactive peptides and PS (Spread)	10	2	hypertensive, hypercholesterolemic subjects
Salo et al. (2016) 1.6	Finland	double blind parallel RCT	59 (28)	25–65	F/M (35/24)	yogurt mini drink + PS (Drink)	yogurt mini drink w/o PS (Spread)	4	1.6	moderately hypercholesterolemic subjects
Salo et al. (2016) 2	Finland	double blind parallel RCT	60 (29)	25–65	F/M (42/18)	yogurt mini drink + PS (Drink)	yogurt mini drink w/o PS (Drink)	4	2	moderately hypercholesterolemic subjects
Orem et al. (2017)	Turkey	double blind parallel RCT	65 (32)	25–60	F/M (18/47)	functional black tea with PS (Drink)	placebo powder (w/o PS or tea aroma) (Drink)	4	2	mild hypercholesterolemia
Cheung et al. (2017)	China	double blind parallel RCT	221 (110)	24–79	F/M (180/41)	phytosterol enriched low fat milk (Drink)	conventional low-fat milk (Drink)	3	1.5	healthy
Kietsiriroje et al. (2018)	Thailand	double blind parallel RCT (sub-study)	26 (14)	> 20	M	phytosterols and inulin-enriched soymilk (Drink)	soy milk (Drink)	8	2	healthy
Lestiani et al. (2018)	Indonesia	double blind parallel RCT	88 (43)	24–68	F/M (38/50)	Nutrive Benecol drink + PS (Drink)	same drink w/o PS (Drink)	4	2	hypercholesterolemia subjects
Javanmardi et al. (2018)	Iran	double blind parallel RCT	38 (38)	Mean:42–45	F/M (21/17)	PS capsule (Capsule)	Capsule of starch (Capsule)	8	1.6	NAFLD patients
Chau et al. (2020)	Hong Kong	double blind parallel RCT	159 (82)	19–79	F/M (74/85)	phytosterols-enriched soya drink (Drink)	soya drink w/o phytosterol (Drink)	3	2	healthy
Song et al. (2020)	China	double blind parallel RCT	37 (16)	30–67	F/M (5/32)	Enriched Soymilk powder with PS (Capsule)	vegetable oil blended of rapeseed, sunflower and palm oils (Capsule)	12	2.5	NAFLD patients

Phytosterols interventions

The interventions of these studies are: yogurt drinks (5 studies [50, 53, 61, 77, 78]), butter and margarine (2 studies [49, 52]), phytosterol capsules (2 studies [58, 60]), soy drinks (2 studies [56, 59]), low-fat milk (1 study [55]), black tea (1 study [54]) and commercial drinks (1 study [51]). Generally speaking, the intervention was a drink in 11 studies, a capsule in 2 studies, and butter in 2 studies. The dose of phytosterol in the intervention is less than 2 g in 3 studies [53, 55, 58], 2 g in 8 studies [50, 52, 53, 56, 57, 59, 77, 78], and more than 2 g in 4 studies [49, 51, 60, 61].

Changes in fasting blood glucose

In scrutinizing the effect of phytosterol on fasting blood glucose, the average results and standard deviation before and after the intervention in 6 studies [49, 52, 54, 55, 59, 61] are represented in Table 2. In half of the studies [49, 52, 61], the reduction of relative blood glucose was observed in the intervention group compared to the control group, and the changes of phytosterols before and after the intervention were significant only in one study [61] (P value: 0.03). This study is one-sided blind, and has been conducted in people suffering from MetA. The presence of confounding factors, such as people’s awareness of disease conditions, as well as diets due to MetS, is possible. Although the results of this study were significant, the net effect of supplementation with phytosterols showed a net reduction of 2 units of fasting blood glucose (blood sugar reduction from 101 to 99 mg/dL) (Table 2).

Table 2.

Baseline and post-intervention glucose levels (mean (SD)) in the intervention and control group¹

First author (year)	Sample size (n=)	Pre-test FBS (mg/dl)	Post-test FBS (mg/dl)	Changes in FBS (mg/dl)	Main result	P value
Wojciechowska et al. (2003)	I:20 C:22	I:91.14(7.18) C:91.09(5.07)	I:89.55(5.93) C:90.04(8.53)	I: -1.59(6.64) C: -1.05(7.43)	-	n/a
Turpeinen et al. (2012)	I:51 C:49	I:99.09 (7.2) C:99.09 (10.81)	I: n/a C: n/a	I: -0.36 (7.2) C: -1.8 (6.4)	-	0.322
Sialvera et al. (2012)	I:53 C:55	I: 101 (13.3) C:100 (5.18)	I: 99 (11.8) C: 99(8.14)	I: -2 (12.44) C: -1 (7.13)	-	0.03
Orem et al. (2017)	I:32 C:33	I:89 (10) C:92 (9)	I:89 (8) C: 94 (8)	I: 0 (9.1) C: 2 (8.5)	-	0.820
Cheung et al. (2017)	I:110 C:111	I:89.18(13.29) C:87.56(8.36)	I: n/a C: n/a	I:034(6.39) C: -0.41(6.26)	-	0.379
Chau et al. (2020)	I :82 C:77	I: 88.28 (23.96) C: 86.48(9)	I: n/a C: n/a	I: 0 (5.4) C: -0.36(4.43)	There were no significant changes in blood glucose.	0.831

1. All data are reported in Mean and SD

2. I: intervention, C: control, FBS: fasting blood sugar, n/a: not available

Changes in blood pressure

In examining the systolic blood pressure, 8 studies [49, 51, 52, 54, 55, 59–61] were inserted in Table 3 and Table 4, from among which 7 studies [49, 51, 52, 55, 59–61] showed a decrease in blood pressure in the intervention group compared to the control group, and one study [54] remained unchanged. Although changes in systolic blood pressure showed a reduction between 0 and 5 units in blood pressure before and after the intervention, only 1 study showed significant results. The changes in diastolic blood pressure ranged between 0 and 3.8 units before and after the intervention. From among the 8 studies reviewed in this study, 4 studies [49, 52, 59, 60] showed a reduction in diastolic blood pressure in the intervention group compared to the control group, 2 studies [51, 61] showed no change, and 2 studies [54, 55] showed an increase in diastolic blood pressure. Only one study [51] remained unchanged, and one study [55] showed slight increase in diastolic blood pressure (P value: 0.01) (Table 3 and Table 4).

Table 3.

Baseline and post-intervention SBP levels (mean (SD)) in the intervention and control group¹

First author (year)	Sample size (n=)	Pre-test SBP (mmHg)	Post-test SBP (mmHg)	Changes in SBP (mmHg)	Main result	P value
Wojciechowska et al. (2003)	I:20 C:22	I:121.3 (13.99) C:121.9 (12.86)	I:118.8 (12.62) C:116.7 (11.34)	I: -2.5 C: -5.2	-	n/a
Gylling et al. (2010)	I:25 C:24	I:139 (20) C:134 (19.56)	I:135 (20) C:136 (14.67)	I: -4 (20) C:2 (17.63)	-	0.102
Turpeinen et al. (2012)	I:51 C:49	I:139 (11) C:138 (10)	I: n/a C: n/a	I: -4.1 (6.55) C:0.5 (6.6)	A significant decrease in systolic blood pressure was seen in the active group, compared to placebo at home measurements.	0.007
Sialvera et al. (2012)	I:53 C:55	I:135 (11.11) C:130 (7.4)	I:130 (7.4) C:130 (7.4)	I: -5 (9.79) C: 0 (7.4)	-	< 0.001
Cheung et al. (2017)	I:110 C:111	I:123.3 (17.01) C:122.2 (16.47)	I: n/a C: n/a	I: -2.7 (8.85) C: -1.4 (8.61)	-	0.265
Orem et al. (2017)	I:32 C:33	I:121 (13) C:125 (11)	I:121 (16) C:122 (12)	I: 0 (14.73) C: -3 (11.53)	-	0.770
Chau et al. (2019)	I:82 C:77	I:123 (18.7) C:120 (17.1)	I: n/a C: n/a	I: -3.1 (-3.13) C: -1.3 (6.55)	There were no significant changes in blood pressure.	0.302
Song et al. (2020)	I:16 C:21	I: n/a C: n/a	I: n/a C: n/a	I: -1.23 (11.37) C: 1.75 (12.92)	-	0.80

1. All data are reported in Mean and SD

2. I: intervention, C: control, SBP: systolic blood pressure

Table 4.

Baseline and post-intervention DBP levels (mean (SD)) in the intervention and control group¹

First author (year)	Sample size (n=)	Pre-test DBP (mmHg)	Post-test DBP (mmHg)	Changes in DBP (mmHg)	Main result	P value
Wojciechowska et al. (2003)	I:20 C:22	I:77.5 (7.51) C:76.9 (7.35)	I:73.6 (6.56) C:74.1 (7.33)	I: -3.8 C: -2.8	-	n/a
Gylling et al. (2010)	I:25 C:24	I:78 (20) C:80 (19.44)	I:78 (20) C:80 (19.44)	I: 0 (20) C: 0 (19.44)	-	0.496
Turpeinen et al. (2012)	I:51 C:49	I:87 (7) C:87 (6)	I: n/a C: n/a	I: -0.7 (4.37) C: -0.7 (4.28)	-	0.88
Sialvera et al. (2012)	I:53 C:55	I:85 (7.4) C:85 (7.4)	I:85 (7.4) C:85 (3.7)	I: 0 (7.4) C: 0 (6.4)	-	0.01
Orem et al. (2017)	I:32 C:33	I:77 (16) C:82 (8)	I:80 (8) C:80 (7)	I:3 (13.55) C: -2 (7.54)	-	0.298
Cheung et al. (2017)	I:110 C:111	I:78.8 (10.57) C:77.7 (9.68)	I: n/a C: n/a	I:0.17 (5.59) C:2.1 (5.5)	Phytosterols intake also decreased total cholesterol (P: 0.01).	0.01
Chau et al. (2019)	I:82 C:77	I:81 (11) C:79 (11.5)	I: n/a C: n/a	I: -2.73 (5.38) C: -1.9 (4.85)	There were no significant changes in blood pressure.	0.473
Song et al. (2020)	I:16 C:21	I: n/a C: n/a	I: n/a C: n/a	I: -0.76 (8.09) C: 0.5 (11.55)	-	0.92

1. All data are reported in Mean and SD

2. I: intervention, C: control, DBP: diastolic blood pressure

Changes in triglyceride

Triglyceride was reported in 14 studies [49–55, 57–61, 78] before and after the intervention, and the results are represented in Table 5. The changes before and after the intervention indicated that supplementing with phytosterols can cause a wide range of changes in blood triglyceride levels. Changes in triglyceride levels have been reported as increase or decrease with relatively significant distribution (between + 104 and − 46 mg/dL). Among these, 7 studies [49, 50, 52, 53, 58, 61, 78] have shown a decrease in triglycerides. From among these studies, only 2 studies [61, 77] showed significant changes, both of which showed a significant decrease in triglycerides by -33 and − 46 mg/dL (P value: 0.001) (Table 5).

Table 5.

Baseline and post-intervention TG levels (mean (SD)) in the intervention and control group¹

First author (year)	Sample size (n=)	Pre-test TG (mg/dl)	Post-test TG (mg/dl)	Changes in TG (mg/dl)	Main result	P value
Wojciechowska et al. (2003)	I:20 C:22	I:87.9 (29.2) C:89.8 (35.9)	I:80.9 (28.4) C:88.6 (54.9)	I: -7.0 C: -1.2	-	Not significant
Plat et al. (2009)	I:9 C:9	I:195.5 (86.7) C:198.2 (111.5)	I: n/a C: n/a	I: -20.35 (31.85) C:20.35 (47.78)	TAG was lowered by 27.5%.	0.044
Khandelwal et al. (2009)	I:47 C:46	I:124.7 (60.1) C:140.7 (59.2)	I:113.2 (39.8) C:150.4 (79.6)	I: -11.5 (52.95) C:9.7 (71.61)	-	0.11
Gylling et al. (2010)	I:25 C:24	I:101.7 (35.35) C:97.3 (68.76)	I:110.6 (35.35) C:104.4 (51.88)	I:8.8 (35.35) C:7.0 (62.06)	-	0.739
Sialvera et al. (2012)	I:53 C:55	I:195 (62.2) C:173 (24.4)	I:149 (55.5) C:170 (34.07)	I: -46 (59.1) C: -3.0 (30.42)	Phytosterol supplementation lowered triglyceride levels by 19.1% (P < 0.001).	< 0.001
Turpeinen et al. (2012)	I:51 C:49	I:123.8 (70.79) C:132.7 (70.79)	I: n/a C: n/a	I: -5.3 (38.65) C:8.8 (69.5)	-	0.251
Salo et al. (2016) (1.6)	I:28 C:31	I:108.8 (54.86) C:112.3(42.47)	I:108.8 (55.75) C:114.1 (34.51)	I: -0.8 (46.9) C:1.7 (30.08)	-	Not significant
Salo et al. (2016) (2)	I:29 C:31	I:103.5 (38.05) C:112.3 (42.47)	I:104.4 (32.74) C:114.1 (34.51)	I:0.8 (22.12) C:1.7 (31.08)	-	Not significant
Orem et al. (2017)	I:32 C:33	I:151 (72) C:149 (73)	I:155 (74) C:151 (78)	I:4 (70.02) C:2 (75.6)	-	0.688
Cheung et al. (2017)	I:110 C:111	I:107.0 (53.09) C:101.7 (42.3)	I: n/a C: n/a	I:5.8 (41.87) C:8.2 (41.14)	-	0.674
Lestiani et al. (2018)	I:43 C:45	I:127.2 (67.6) C:122.6 (53.3)	I:134.4 (70.4) C:129.1 (56.8)	I:7.2 (69.04) C:6.5 (55.13)	-	Not significant
Javanmardi et al. (2018)	I:19 C:19	I:152.21 (38.77) C:128.42 (33.69)	I:118.68 (36.42) C:126.00 (41.85)	I: -33.53 (37.65) C: -2.42 (38.42)	there were no significant differences between the two groups in triglycerides.	P1 and P2
Chau et al. (2019)	I:82 C:77	I:92.9 (46.01) C:92.0 (49.55)	I: n/a C: n/a	I:3.5 (38.8) C: 0 (23.72)	There were no significant changes in lipid parameters.	0.535
Song et al. (2020)	I:16 C:21	I: n/a C: n/a	I: n/a C: n/a	I: 104.4 (251.3) C: 33.6 (153.9)	-	0.171

1. All data are reported in Mean and SD

2. I: intervention, C: control, TG: triglyceride

Changes in high density lipoprotein

High-density lipoprotein was also reported in 14 studies [49–55, 57–61, 78], the results of which are reported in Table 6. The results of the studies indicated an increase in the amount of this marker in 6 studies [49, 51, 52, 58–60], no change in 3 studies [54, 57, 61] and a decrease in its amount in 5 studies [50, 53, 55, 77, 78]. The changes ranged from − 2.17 to + 6.7 mg/Dl, and none of the studies showed significant changes (Table 6).

Table 6.

Baseline and post-intervention HDL levels (mean (SD)) in the intervention and control group¹

First author (year)	Sample size (n=)	Pre-test HDL (mg/dl)	Post-test HDL (mg/dl)	Changes in HDL (mg/dl)	Main result	P value
Wojciechowska et al. (2003)	I:20 C:22	I:54.7 (8.2) C:53.3 (10.6)	I:54.9 (9.3) C:51.5 (9.5)	I:0.2 C: -1.8	-	Not significant
Plat et al. (2009)	I:9 C:9	I:37.4 (5.79) C:39.7 (10.03)	I: n/a C: n/a	I: -2.7 (3.47) C: -0.77 (5.4)	The total HDL-C ratio was significantly lowered in all 3 intervention groups.	0.159
Khandelwal et al. (2009)	I:47 C:46	I:37.4 (6.9) C:35.9 (9.6)	I:37.0 (7.7) C:35.1 (8.5)	I: -0.39 (7.33) C: -0.77 (9.1)	-	0.60
Gylling et al. (2010)	I:25 C:24	I:62.1 (17.35) C:67.5 (20.73)	I:63.3 (15.4) C:67.1 (18.87)	I:1.1 (16.46) C: -1.8 (19.86)	-	0.976
Sialvera et al. (2012)	I:53 C:55	I:42 (9) C:43 (9)	I:42 (9) C:43 (9)	I: 0 (9) C: 0 (9)	-	0.66
Turpeinen et al. (2012)	I:51 C:49	I:61.7 (15.44) C:61.7 (15.44)	I: n/a C: n/a	I:0.7 (5.61) C:2.3 (7.57)	-	0.242
Salo et al. (2016) (1.6)	I:28 C:31	I:71.8 (16.21) C:71.4 (17.76)	I:69.8 (16.6) C:69.8 (18.53)	I: -1.93 (5.79) C: -1.54 (5.4)	-	Not significant
Salo et al. (2016) (2)	I:29 C:31	I:70.2 (18.91) C:71.4 (17.76)	I:68.7 (18.53) C:69.8 (18.53)	I: -1.54 (6.17) C: -1.54 (5.4)	-	Not significant
Orem et al. (2017)	I:32 C:33	I:45 (7.6) C:46 (8.7)	I:45 (9) C:46 (9)	I: 0 (8.38) C: 0 (8.85)	-	0.846
Cheung et al. (2017)	I:110 C:111	I:59.0 (15.44) C:57.9 (14.78)	I: n/a C: n/a	I: -2.1 (5.67) C:1.5 (14.91)	-	0.395
Lestiani et al. (2018)	I:43 C:45	I:49.7 (9.7) C:50.1 (10.6)	I:49.7 (11.1) C:49.8 (10.5)	I: 0 (10.47) C: -0.3 (10.55)	-	Not significant
Javanmardi et al. (2018)	I:19 C:19	I:44.42 (5.7) C:49.73 (10.54)	I:45.36 (5.76) C:50.26 (12.48)	I: +0.94 (5.73) C: +0.53 (11.63)	there were no significant differences between the two groups in high-density lipoprotein cholesterol.	P1 or p2?
Chau et al. (2019)	I:82 C:77	I:54.4 (12.35) C:57.1 (15.05)	I: n/a C: n/a	I:0.38 (6.23) C: 1.54 (8.61)	There were no significant changes in lipid parameters.	0.238
Song et al. (2020)	I:16 C:21	I: n/a C: n/a	I: n/a C: n/a	I:6.17 (11.5) C: -0.77 (8.88)	-	0.155

1. All data are reported in Mean and SD

2. I: intervention, C: control, HDL: high density protein

Changes in waist circumference

Waist circumference was examined in three studies before and after the intervention, as reported in Table 7. Two studies [55, 61] showed a decrease in waist circumference, and one study [59] showed an increase. None of the studies indicated significant results.

Table 7.

Baseline and post-intervention WC (mean (SD)) in the intervention and control group¹

First author (year)	Sample size (n=)	Pre-test WC (cm)	Post-test WC (cm)	Changes in WC (cm)	Main result	P value
Sialvera et al. (2012)	I:53 C:55	I:105 (14.07) C:101 (11.11)	I:104 (13.3) C:100 (10.37)	I: -1.0 (13.7) C: -1.0 (10.75)	-	0.06
Cheung et al. (2017)	I:110 C:111	I:80.6 (8.84) C:81.8 (8.54)	I: n/a C: n/a	I: -0.69 (1.84) C: -0.66 (1.74)	-	0.899
Chau et al. (2019)	I:82 C:77	I:81 (9.5) C:80 (10.5)	I: n/a C: n/a	I:0.24 (3.48) C: -0.18 (3.8)	There were no significant changes in waist circumference.	0.464

1. All data are reported in Mean and SD

2. I: intervention, C: control, WC: waist circumference

Discussion

Phytosterols are well-known antinutrients, with their most recognized effect being the reduction of blood cholesterol levels [34]. Due to their structural similarity to cholesterol, these compounds can lower blood cholesterol by up to 40% [79]. However, few studies have investigated the impact of phytosterols on health and other health-related factors. The present research examined the impact of phytosterol supplementation on MetS factors, including fasting blood glucose, systolic and diastolic blood pressure, triglyceride levels, HDL cholesterol concentration, and waist circumference (an indicator of abdominal obesity). Of the 15 studies included, 13 were assessed as having low risk of bias and 1 as moderate risk. The only domain with potential concerns in the moderate-risk study was related to blinding. Most studies demonstrated adequate random sequence generation, allocation concealment, and outcome reporting. The overall methodological quality of the included trials supports the reliability of our findings; however, caution is warranted when interpreting results from studies with unclear or moderate risk in specific domains. The results indicated phytosterol supplementation relatively reduced factors such as fasting blood glucose, systolic and diastolic blood pressure, triglyceride levels, and waist circumference. Our findings are consistent with a recent umbrella review (2024) that found that phytosterol consumption at doses of ≥ 2 g/day for ≥ 8 weeks significantly decreased LDL-C, total cholesterol, and triglyceride levels, with the greatest effects in persons with hypercholesterolemia specifically [33]. In addition, a 2024 systematic review of 28 randomized controlled trials demonstrated that PS supplementation decreased LDL-C and total cholesterol while increasing HDL-C [34]. Also, a 2025 study by Yang et al. on dietary PS intake and cardiovascular risk factors showed that PS intake significantly reduced triglycerides, total cholesterol, LDL, and systolic and diastolic blood pressure. No significant changes were observed in fasting blood glucose, HbA1c, body mass index, or waist circumference [80]. We observed no substantial changes for waist circumference and HDL-C. The findings are similar to recent investigations, which indicate that the impact of phytosterols on HDL-C is relatively subtle compared to other lipid parameters studied, which broadly defined are the primary benefits we can observe are mostly associated with lowering LDL-C and triglycerides [34, 81]. Recent evidence similarly identifies that higher doses (≥ 2 g/day) and sustained durations (> 8 weeks) result in a more pronounced effect and could potentially indicate that dose and duration are the main conducive qualities to successful phytosterol supplementation efficacy [81].

Although phytosterols are classified as antinutrients, their structural similarity to cholesterol can lead these compounds to mimic cholesterol effects in the small intestine and prevent its absorption [82]. Lowering cholesterol levels is the primary effect of phytosterols [83]. However, these compounds could play a beneficial role in other biological processes in the body. Although few mechanistic studies have been conducted on the impact of phytosterols on health, some of their effects could be inferred from experimental and animal studies, e.g., it seems that phytosterols could influence regulatory pathways through transcription by impacting the activation of AMP-activated protein kinase (AMPK) and peroxisome proliferator-activated receptors (PPARs) [84]. AMPK is a crucial modulator of the cell energy response that continuously maintains ATP for metabolic activities [85]. Activation of AMPK pathway is considered a key therapeutic strategy for disorders such as obesity [86], metabolic syndrome [87], type 2 diabetes [88], and hypercholesterolemia [89]. Activation of this pathway could reduce blood lipids and inhibit cholesterol and fat synthesis [90]. AMPK may control lipid metabolism and encourage fatty acid oxidation in adipocytes [91]. AMPK activation, which PSs can stimulate, suppresses adipogenesis by inhibiting two critical enzymes in this pathway [85]. PPARγ, AMPK’s direct substrate, can activate critical enzymes in this pathway [92]. AMPK regulates adipocyte differentiation and maturation and regulates fatty acid oxidation [93]. A transcription factor associated with lipid metabolism, Sterol regulatory element-binding transcription factor 1 (SREBP-1c) can control acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS), two related triglyceride synthase enzymes. According to studies, phytosterols can deactivate SREBP-1c and FAS, activate AMPK, and stop fat formation and fatty acid production [94].

In addition to regulating lipid metabolism via activating the AMPK pathway, it could reduce insulin resistance and improve hyperglycemia [95]. AMPK could increase glucose receptors (GLUT4) translocation in skeletal muscle and white adipose tissue [96]. Also, this compound could enhance PI3K-mediated signaling in an insulin-independent manner [95]. Studies have reported that PSs affect their effects on fat and carbohydrate metabolism regulation and contribute to weight management by increasing adiponectin levels [97].

Although studies have not directly addressed the effect of PSs on blood pressure, PSs may directly and indirectly influence blood pressure [40]. These compounds directly increase the release of prostacyclin [98]. Prostacyclin, secreted from the smooth muscle cells of the vessel walls, reduces peripheral vascular resistance, thereby reducing blood pressure [98].

Some studies have reported that PSs increase adiponectin levels, an adipokine involved in metabolic regulation [97]. Elevated adiponectin levels can activate AMPK, enhancing glucose and lipid metabolism [99]. In vitro studies indicate that PSs inhibit pancreatic lipase secretion and lead to reduced levels of phospholipase A2 [100]. Reduced levels of digestive enzymes may result in decreased fat absorption due to the formation of oleogelation [100]. Their anti-obesity effects further lead to weight loss [101]. Studies have demonstrated that weight loss indirectly reduces systolic and diastolic blood pressure [102].

Ultimately, MetS is associated with low-grade, chronic systemic inflammation in the body [103]. The chronic inflammation could adversely affect biological processes, exacerbating the risks associated with this condition [104]. PSs contribute to reducing systemic inflammation in the body by influencing inflammatory pathways and modulating pro- and anti-inflammatory cytokines, thereby improving the condition of high-risk individuals [105]. However, it seems necessary to conduct precise mechanistic studies to investigate the effect of PSs on MetS factors.

Together, the multiple mechanisms outlined provide a unified rationalization for the favorable changes induced by phytosterols on various elements of MetS. They demonstrate multifactorial actions via activation of AMPK and PPARs, inhibition of lipogenic transcription factors (e.g., SREBP-1c), elevation of adiponectin levels, and improvement of substrate (glucose and lipid) metabolism mechanisms. They may enhance and improve insulin sensitivity, lipid production, stimulate fatty acid oxidation (via mitochondrial and peroxisomal β-oxidation), and limit systemic inflammation. Prostacyclin production stimulated by phytosterols may ultimately lead to reduced vascular resistance and an improved blood pressure framework overall. These pathways suggest phytosterols may be worthwhile as adjunctive therapy for managing MetS, and merit additional clinical/evidence-based and mechanistic considerations.

Among the strengths of this study, it is worth noting that this systematic review was the first to examine the effect of phytosterol supplementation on MetS factors. All studies focused on PS supplements or phytosterol-enriched compounds as interventions related to MetS factors were included in this review. The results indicated the effect of PSs on MetS factors separately, with the effect of PS supplementation on each factor being reported. However, this study faced some limitations. Clinical studies have used PS supplements or PS-enriched compounds as the intervening agent. The compounds in enriched products (such as nutrients found in soy milk, regular milk, yogurt, etc.) may influence research outcomes. Additionally, the number of participants and duration of the intervention vary across studies, which makes it difficult to interpret and generalize the results. Furthermore, some participants had underlying conditions such as hypercholesterolemia, obesity, and MetS, which may affect MetS factors, as well as the interpretation and implementation of lifestyle-related interventions for these individuals. Raising participants’ awareness may lead to positive dietary changes and improvements in MetS factors among at-risk individuals, which could, in turn, contribute to confounding the research results. The variability in the effects of PS supplementation observed across studies can be ascribed to multiple factors. The dosage of PSs varied significantly, ranging from 1.5 to over 2.5 g per day, potentially impacting efficacy. Secondly, the characteristics of participants varied—some studies involved healthy individuals. In contrast, others concentrated on patients with metabolic syndrome, hypercholesterolemia, or non-alcoholic fatty liver disease, which may influence baseline metabolic profiles and responses to intervention. The type of supplementation (e.g., capsules versus fortified foods) and the intervention duration (3 to 12 weeks) likely affected the outcomes. Finally, variations in study design quality, sample size, and risk of bias among trials may have influenced the discrepancies in results. These factors must be taken into account when analyzing the overall findings. Despite the efficacy of meta-analysis in aggregating effect sizes from various studies, we opted against its implementation owing to significant heterogeneity in study design, populations, dosage regimens, and outcome reporting. The variability in baseline characteristics, including healthy, hypercholesterolemic, and NAFLD patients, along with differing intervention forms such as capsules versus food matrices and varying durations from 3 to 12 weeks, resulted in significant clinical and methodological diversity. Additionally, numerous studies indicated incomplete statistical data, such as the absence of confidence intervals or standard deviations, which constrains the reliability of aggregated estimates. We performed a structured narrative synthesis, presenting results by individual components of metabolic syndrome and highlighting study-level differences that may account for variations in findings.

Clinical implications

The findings of this review suggest that phytosterol supplementation, particularly at doses ≥ 2 g/day and over durations exceeding 8 weeks, may modestly improve certain MetS parameters such as triglyceride levels, blood pressure, and fasting glucose. These outcomes support the potential role of phytosterols as a complementary nutritional strategy in individuals at risk of cardiometabolic disorders. Although the observed effects are generally moderate, they may offer added value when combined with standard dietary and lifestyle interventions. Given their safety profile and availability in functional foods, PSs could be considered in dietary recommendations for at-risk populations. However, long-term clinical trials are required to confirm their sustained efficacy and to determine their role in broader clinical practice.

Limitations

It is important to recognize and take into account the many limitations of this review when evaluating the results. First, it is difficult to make firm conclusions or do a highly accurate meta-analysis because to the heterogeneity among the included studies, which includes variations in study design, sample size, duration of intervention, dosage and type of phytosterol supplementation, and outcome variables. Additionally, several studies lacked sufficient statistical details such as standard deviations or confidence intervals. Therefore, a structured narrative synthesis was performed instead of a meta-analysis. Consequently, forest plots were not generated, as the pooling of effect sizes under such variability would have been methodologically inappropriate. This kind of variation makes it difficult to compare findings from different studies and could have an impact on how broadly applicable the conclusions are. Second, the included studies’ quality differed. Some trials had inadequate blinding, small sample sizes, or insufficient follow-up periods, whereas others were well-designed randomized controlled trials with little risk of bias. It’s possible that these methodological restrictions affected the validity and dependability of the results that were published. Third, since research with unfavorable or ambiguous results are less likely to be published, publication bias cannot be completely ruled out. Furthermore, we excluded gray literature and unpublished data, which would have reduced the thoroughness of our research. By carrying out large-scale, high-quality randomized controlled trials with established protocols pertaining to phytosterol type, dosage, duration, and outcome assessment, future research should seek to overcome these shortcomings. Furthermore, to determine which groups gain the most, subgroup studies based on age, sex, baseline lipid profiles, and comorbidities may be helpful. To assess the long-term safety and effects of phytosterol supplementation, longer-term research is also required. Notwithstanding these drawbacks, this study offers insightful information about how PSs may enhance lipid profiles and identifies crucial topics for more research.

Conclusion

The results revealed that phytosterols have different impacts on each metabolic syndrome factor. Some studies have reported positive effects of phytosterols on reducing factors such as triglycerides, fasting blood glucose, and blood pressure. Nevertheless, some research has shown that phytosterols do not impact the variables associated with the MetS. Contradictory findings were found when the literature was reviewed. Variability in study design, quality, and intervention methods limits the findings. Comprehensive, carefully planned, long-term RCTs are required to determine the therapeutic role of phytosterols. The main objectives of future research should be standardizing dosage, determining long-term safety, and analyzing results in various groups.

Supplementary Information

Below is the link to the electronic supplementary material.

Author contributions

L.A. conceptualized the topic; F.GH. searched the databases; L.A and F.GH performed screening and full text review; LA and FGH. performed data extraction; FG and ANT. performed quality assessment; FGH and MK. prepared the first draft of the manuscript; LA. critically revised and edited the manuscript; LA. supervised this project. All authors reviewed and approved the final version of .he manuscript.

Funding

None.

Data availability

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Declarations

Human ethics and consent to participate

Not applicable.

Competing interests

The authors declare no competing interests.