Chlorella for health: evidence from a GRADE-assessed systematic review and dose–response meta-analysis

Abstract

Background

Chlorella species have attracted attention for their potential to improve cardiovascular and metabolic health; however, comprehensive evidence from controlled trials remains limited.

Methods

A comprehensive search of PubMed, CENTRAL, Web of Science, Scopus, and EMBASE databases was conducted up to February 2025. Study quality and certainty of evidence were assessed using the Cochrane Risk of Bias and Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) tools, respectively.

Results

Thirty-three studies were included. Chlorella supplementation led to significant reductions in body fat (Weighted Mean Difference [WMD] = -0.72%; 95% Confidence Interval [CI]: -1.09, -0.35; P < 0.001), body mass index (WMD = -0.29 kg/m²; 95% CI:-0.44, -0.15; P < 0.001), weight (WMD = -1.52 kg; 95% CI:-2.07, -0.97; P < 0.001), waist-to-hip ratio (WMD = -0.01%; 95% CI:-0.01, -0.01; P < 0.001), homeostatic model assessment of insulin resistance (WMD = -0.20; 95% CI:-0.33, -0.08; P = 0.002), insulin (WMD = -0.97 µIU/mL; 95% CI:-1.38, -0.55; P < 0.001), low-density lipoprotein-cholesterol (WMD = -5.70 mg/dL; 95% CI:-8.10, -3.31; P < 0.001), total cholesterol (WMD = -7.02 mg/dL; 95% CI:-9.78, -4.25; P < 0.001), alanine transaminase (WMD = -4.84 IU/L; 95% CI:-6.46, -3.21; P < 0.001), aspartate aminotransferase (WMD = -3.38 IU/L; 95% CI:-4.65, -2.11; P < 0.001), and lactate dehydrogenase (WMD = -14.13 U/L; 95% CI: -25.18 to -3.09; P = 0.012). Additionally, there were significant increases in high-density lipoprotein-cholesterol (WMD = 1.57 mg/dL; 95% CI:0.27, 2.87; P = 0.018).

Conclusions

Chlorella supplementation demonstrates meaningful benefits for cardiometabolic health, with effects influenced by species, dosage, and participant characteristics. While this analysis has some limitations, further long-term studies are required to optimize its clinical application. Overall, Chlorella appears to be a promising supplement that may warrant inclusion in dietary interventions.

Graphical Abstract

Supplementary Information

The online version contains supplementary material available at https://doi.org/10.1186/s13643-026-03276-w.

Introduction

Cardiovascular and metabolic disorders, such as obesity, hypertension (HTN), dyslipidemia, and insulin resistance, are escalating global health challenges due to their significant contributions to morbidity and mortality rates [1]. In 2021, nearly one-third of all deaths worldwide were attributed to these conditions [2]. Consequently, there is an increasing interest in dietary interventions and functional foods that can help mitigate cardiovascular risk and improve metabolic health [3, 4]. Among these interventions, Chlorella species, a green freshwater algae, has garnered attention for its potential therapeutic benefits [5].

Chlorella is rich in bioactive compounds, including chlorophyll, proteins, vitamins, minerals, carotenoids, and dietary fiber, which collectively contribute to its health-promoting properties [6]. These bioactive constituents exert their health-promoting effects through multiple mechanisms, including potent antioxidant activity that combats oxidative stress, anti-inflammatory properties mediated by polyphenolic compounds, modulation of lipid metabolism through phytosterols and dietary fiber, and enhancement of insulin sensitivity via carotenoids and other bioactive molecules [7, 8]. The high chlorophyll content may also influence adipogenesis and promote favorable changes in body composition [9]. Emerging evidence suggests that Chlorella supplementation may improve a variety of risk factors, particularly those related to obesity, lipid profile, and liver function [10–12]. Additionally, Chlorella has shown promise in modulating inflammatory responses, enhancing glycemic control, and reducing oxidative stress [13, 14]. Some studies have also suggested the potential benefits of this microalga in blood pressure regulation, adipokine modulation, and heart rate reduction, though these findings require further validation [15, 16].

Considering the importance of systematic reviews and meta-analyses of controlled trials in clinical decision making, and the lack of any robust and updated meta-analysis on the health benefits of Chlorella spp., this study was undertaken to fill the gaps in the literature by applying a rigorous systematic review and dose–response meta-analysis methodology. Using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework, we performed a thorough evaluation of controlled trials to investigate the associations between determinants such Chlorella dosage and treatment duration, and various health parameters. Advanced statistical methods including meta-regression and dose–response analyses were also employed to assess the efficacy of Chlorella across different populations and health conditions. Our findings will provide valuable insights for clinical and public health recommendations, highlighting Chlorella's potential role in the prevention and management of cardiovascular and metabolic diseases.

Methods

Protocol and registration

This systematic review and meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines [17]. The protocol was prospectively registered in the International Prospective Register of Systematic Reviews (PROSPERO) under the registration number CRD42024597746, ensuring transparency and methodological rigor.

Search strategy, study selection, and data extraction

A comprehensive search was conducted across major databases including PubMed, Web of Science, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), and SCOPUS, for studies published up to February 12, 2025. Databases like ProQuest, which primarily contain dissertations, theses, and selected evidence-based collections (e.g., Health Research Premium Collection), were excluded because they are less centered on primary peer-reviewed trials and could largely overlap with the content of the chosen databases, offering few additional relevant trials for this review. The search strategy combined terms such as ‘Chlorella,’ ‘Chlorellas,’ ‘microalgae,’ ‘C. vulgaris,’ ‘C. pyrenoidosa,’ and ‘clinical trial,’ tailored to each database's indexing systems, including MeSH and EMTREE terms (Supplementary Table 1).

Additional studies were identified through manual search in the reference lists of relevant articles and reviews. Eligible studies were controlled trials assessing the effects of Chlorella supplementation on outcomes including anthropometric measures, blood pressure, glycemic control, lipid profile, liver function tests, oxidative stress markers, leptin levels, and heart rate in adults, with no language restrictions applied. Observational studies, reviews, letters, animal studies, and in vitro research were excluded.

Two independent reviewers (A.J. and H.M.) screened titles and abstracts based on predefined eligibility criteria. Full-text articles deemed relevant were assessed for inclusion, with discrepancies resolved through discussion or, if necessary, by a third reviewer (A.S.). Duplicate articles were removed using EndNote X7, and data were extracted using a standardized Excel form.

The extracted data included author, publication year, geographical location, population characteristics, intervention details, Chlorella dosage, treatment duration, and primary outcomes, including anthropometric indices, blood pressure, glycemic markers, lipid concentrations, liver enzymes, oxidative stress parameters, leptin levels, and heart rate.

Methodological quality assessment and evidence strength evaluation

The methodological quality of included studies was assessed using the Cochrane Risk of Bias 2 tool. Two reviewers (B.P. and N.R.) independently evaluated risk of bias, focusing on randomization, allocation concealment, blinding, completeness of outcome data, and selective reporting. Discrepancies were resolved through discussion or consultation with a third reviewer (A.J.).

The certainty of the evidence was assessed using the GRADE framework, evaluating each outcome based on study limitations, consistency, directness, precision, and risk of publication bias. Two reviewers (B.P. and A.J.) conducted the grading, with a third-party reviewer (A.S.) resolving any disagreements.

Statistical analysis

All statistical analyses were performed using Stata version 15.0 (StataCorp, College Station, Texas). The primary objective was to evaluate the effects of Chlorella supplementation on anthropometric measures, blood pressure, glycemic control, inflammatory biomarkers, lipid profiles, liver function tests, oxidative stress parameters, leptin levels, and heart rate. Pre- and post-intervention means, standard deviations (SDs), and sample sizes were extracted from the included trials. Missing data were calculated or obtained by contacting study authors.

The effects of Chlorella supplementation were expressed as weighted mean differences (WMDs) with 95% confidence intervals (CIs). A random-effects model (DerSimonian-Laird method) was applied to account for variability across studies [18]. Heterogeneity was assessed using the I² statistic, with values of 25%, 50%, and 75% indicating low, moderate, and high heterogeneity, respectively.

Subgroup analyses were conducted based on health condition (healthy vs. overweight/obese vs. chronic diseases [T2DM, HTN, Hypercholesterolemia, NAFLD, Chronic Pulmonary Disease]), intervention approach (Chlorella vs. Chlorella with exercise vs. GABA-rich Chlorella), Chlorella species (C. vulgaris vs. C. pyrenoidosa vs. C. regularis), intervention type (tablet vs. capsule vs. pill), control approach (placebo/usual care vs. exercise), dosage (2000 > mg/day vs. 2000 ≤ mg/day), duration (≤ 8 weeks vs. > 8 weeks), sex (both sex vs. female vs. male), age (40 > years vs. 40 ≤ years), country (Iran vs. Japan vs. Korea vs. others), baseline BMI (healthy weight [≤ 25 kg/m²] vs. overweight/obese [> 25 kg/m²]), and sample size (≤ 20 vs. > 20 participants).

Meta-regression analyses were performed to investigate the effects of Chlorella dosage and intervention duration on the study outcomes [19]. In addition, a non-linear dose–response model was employed to assess the relationship between varying supplementation levels and the observed health effects, aiming to inform evidence-based recommendations regarding optimal dose and duration [20]. Leave-one-out sensitivity analyses were performed to assess the impact of individual studies on the overall results. Publication bias was evaluated using funnel plots, Egger’s tests [21].

Results

Study selection

The study selection process is summarized in Fig. 1. A total of 16,949 records were identified through database searches: PubMed (n = 846), ISI Web of Science (n = 3,864), Scopus (n = 2,360), Embase (n = 9,155), and Cochrane Library (n = 724). After removing 7,663 duplicates, irrelevant studies, and animal studies, 9,286 studies remained for title and abstract screening. Of these, 9,028 were excluded due to the lack of relevance of their title and/or abstract to the main topic of the review, leaving 80 full-text articles for further evaluation. Fifty studies were excluded for various reasons, as detailed in Supplementary Table 2, leaving 30 studies for inclusion. Additionally, three studies were identified through Google Scholar and citation searching, resulting in a final total of 33 studies.

Fig. 1.

Flowchart of study selection for inclusion trials in the systematic review

Study characteristics

The characteristics of the included studies are presented in Table 1. Supplementary Figs. 1–9 display the WMD and 95% CI for changes in a range of outcomes: Body Fat (BF), Body Mass Index (BMI), Body Fat Mass (BFM), Hip Circumference (HC), Waist Circumference (WC), Weight, Waist-to-Hip Ratio (WHR), Diastolic Blood Pressure (DBP), Systolic Blood Pressure (SBP), Fasting Blood Glucose (FBG), Hemoglobin A1c (HbA1c), Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), Insulin, High-Sensitivity C-Reactive Protein (hs-CRP), High-Density Lipoprotein Cholesterol (HDL-C), Low-Density Lipoprotein-Cholesterol (LDL-C), Total Cholesterol (TC), Triglycerides (TG), Albumin, Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Blood Urea Nitrogen (BUN), Creatinine, Gamma-Glutamyl Transferase (GGT), Lactate Dehydrogenase (LDH), Total Protein, Catalase (CAT), Glutathione Peroxidase (GPx), Malondialdehyde (MDA), Superoxide Dismutase (SOD), Total Antioxidant Capacity (TAC), Leptin, and Heart Rate.

Table 1.

Characteristic of included studies in the meta-analysis

Studies. Year (Ref.)	Country	Study design	Health condition	Sample size (Sex)	Sample size (INT/CON)	Trial duration (Week)	Means age & BMI (INT/CON)	Dose of supplement (mg/d)	Type of supplement (INT/CON)	Outcomes
Okuda et al. 1975 [22]	Japan	Controlled trial	Healthy	8 (F)	4/4	12	Age: 20–30/20–30 BMI: NR	5000	Tablet: Chlorella/No supplement	TC
Inoue et al. 1995 [23]	Japan	Controlled trial	HTN	23 (B)	13/10	24	Age: 53.3 ± 6.7/ 54.3 ± 6.3 BMI: NR	1500	Tablet: Chlorella/Usual care	SBP & DBP
Sansawa et al. 2002 [24]	Japan	Controlled trial	Mild hypercholesterolemic	20 (B)	11/9	12	Age: 53 ± 8/ 59 ± 5 BMI: NR	3000	Tablet: Chlorella regularis/Usual care	TC, LDL-C, HDL-C, TG, Lp (a), Apo A-1, Apo B, weight, SBP & DBP
Tsuchida et al. 2003 [25]	Japan	R, PC	High-normal BP and mild HTN	60 (B)	45/15	8	Age: 48.1 ± 8.3/ 42.1 ± 10.8, 52 ± 9.1/ 42.1 ± 10.8 & 48.9 ± 9.6/ 42.1 ± 10.8 BMI: 24.47 ± 2.65/ 25.13 ± 3.52, 24.12 ± 3.40/25.13 ± 3.52 & 22.94 ± 2.86/ 25.13 ± 3.52	2000, 4000 & 6000	GABA-rich Chlorella/ Placebo (lactose)	Weight, BMI, SBP, DBP, HR, TP, Albumin, AST, ALT, ALP, γ-GTP, LDH, TC, TG, LDL-C, HDL-C, BUN, FBG & Creatinine
Shimada et al. 2009 [26]	Japan	R, PC, DB	High-normal BP and Borderline HTN	80 (B)	40/40	12	Age: 50.1 ± 9.2/ 47.9 ± 9.5 BMI: 25.3 ± 4.1/ 26.2 ± 3.5	4000	Tablet: GABA-rich Chlorella/ Placebo (lactose, corn starch, sodium copper chlorophyllin, gardenia green & sucrose ester)	SBP & DBP
Lee et al. 2010 [27]	Korea	R, PC, DB	Healthy smokers	52 (M)	28/24	6	Age: 35.39 ± 6.45/ 38.67 ± 8.76 BMI: 24.7 ± 4.23/ 24.9 ± 2.44	6300	Pill: Chlorella/ Placebo (maltodextrin)	SBP, DBP, GPX, CAT, SOD & TRAP
Otsuki et al. 2011 [28]	Japan	R, PC, Cross-over	Healthy	60 (M)	15/15	4	Age: 20.4 ± 1.16/ 20.4 ± 1.16 BMI: 22.9 ± 3.09/ 23.1 ± 3.09	6000	Tablet: Chlorella (chlorella pyrenoidosa powder)/ Placebo (lactose & colorant)	Weight, Lean body weight, body fat & BMI
Kwak et al. 2012 [29]	Korea	R, PC, DB	Healthy	51 (B)	28/23	8	Age: 36.3 ± 9.63/ 32.6 ± 8.48 BMI: 22.8 ± 2.80/ 22.7 ± 3.45	5000	Tablet: Chlorella/ Placebo (lactose)	IFN-γ, IL-1β, Weight, BMI, SBP, DBP, TG, TC, HDL-C & LDL-C
Panahi et al. 2012 [30]	Iran	R, clinical trial	Chronic pulmonary disease	57 (B)	28/29	8	Age: 49.38 ± 2.84/ 52.42 ± 2.88 BMI: 28.2/ 27.45	2700	Chlorella vulgaris extract + standard anti-asthma/COPD treatment/standard anti-asthma/COPD treatment	GSH, GPX, CAT, SOD, TAS & MDA
Miyazawa et al. 2013 [31]	Japan	R, PC, DB	Healthy	12 (B)	6/6	8	Age: 58 ± 7/ 57 ± 7 BMI: 23.4 ± 3.4/ 22.5 ± 2.5	8000	Tablet: Chlorella (containing 22.9 mg lutein & 5 mg β-carotene)/ Placebo (85% lactose)	Weight, BMI, SBP, DBP, TP, Albumin, Creatinine, Homocysteine, AST, ALT, LDH, ALP, γ-GTP, CPK, Urea, FBG, TC, HDL-C, LDL-C & TG
Otsuki et al. 2013 [32]	Japan	R, PC, SB, Cross over	Healthy	28 (B)	14/14	4	Age: 20.2 ± 1.12/ 20.2 ± 1.12 BMI: NR	6000	Tablet: Chlorella (Chlorella pyrenoidosa)/ Placebo (lasctose & colorant)	SBP, DBP & HR
Ryu et al. 2014 [33]	Korea	R, PC, DB	Mildly hypercholesterolemic	63 (B)	33/30	4	Age: 48.2 ± 8.04/ 50.9 ± 8.76 BMI: 23.9 ± 3.44/ 24.5 ± 2.73	5000	Tablet: Chlorella vulgaris/ Placebo (lactose powder)	TC, TG, HDL-C, LDL-C, VLDL-C, Apo A-1 & Apo B
Umemoto & Otsuki 2014 [34]	Japan	R, PC, DB, Cross over	Healthy	20 (B)	10/10	4	Age: 21.3 ± 0.94/ 21.3 ± 0.94 BMI: 23.3 ± 3.16/ 23.4 ± 3.79	6000	Tablet: Chlorella (Chlorella pyrenoidosa)/ Placebo (lactose & colorant)	Weight, BMI & Peak HR
Otsuki et al. 2015 [16]	Japan	PC, DB	Middle-aged and older	32 (B)	17/15	4	Age: 62.2 ± 1.5/ 63.1 ± 2.3 BMI: 23.6 ± 2.47/ 22.8 ± 3.09	6000	Tablet: Chlorella (Chlorella pyrenoidosa powder)/ Placebo (lactose & colorant)	Weight, BMI, LDL-C, HDL-C, TG, FBG, HbA1c, Insulin, SBP, Mean BP, DBP & HR
Chitsaz et al. 2016 [35]	Iran	R, controlled trial	NAFLD	41 (B)	21/20	8	Age: 43 ± 7.33/ 42 ± 8.33 BMI: 29.44 ± 3.69/ 27.03 ± 1.68	1000	Tablet: Chlorella vulgaris/Usual care	Weight, BMI, WC, TC, LDL-C, HDL-C, TG, ALT, AST & ALP
Zempo-Miyaki et al. 2017 [36]	Japan	R, PC, DB	Healthy	34 (M)	17/17	4	Age: 19.6 ± 1.23/ 20.1 ± 1.23 BMI: 23.3 ± 1.13/ 23.4 ± 1.5	6000	Tablet: chlorella (Chlorella pyrenoidosa)/ Placebo (lactose)	Weight & BFM
Esmaieli et al. 2018 [37]	Iran	R, DB	Obese	32 (F)	16/16	8	Age: 30–45/30–45 BMI: 30.89 ± 0.34/ 30.48 ± 0.43	1200	Tablet: Chlorella vulgaris/No supplement & Chlorella vulgaris + training/training	Weight, BMI, Insulin, FBG & HOMA-IR
Haidari et al. 2018 [14]	Iran	R, PC, DB	Primary dysmenorrhea	44 (F)	22/22	8	Age: 22.68 ± 3.32/ 22.95 ± 3.25 BMI: 23.41 ± 4.84/ 23.02 ± 4.84	1500	Soft gel: Chlorella/ Placebo (paraffin + inactive substance)	Weight, WC, HC, WHR, BMI, hs-CRP & MDA
Govahi et al. 2019 [38]	Iran	R, PC	Overweight	20 (M)	10/10	6	Age: 22.8 ± 2.2/ 22.8 ± 2.2 BMI: 27.8 ± 1.8/ 28.2 ± 1.8	1200	Capsule: Chlorella vulgaris + exercise/ Placebo (sucrose) + exercise	Weight, BMI, BFM, WHR, MDA, PC & NO
Karbalamahdi et al. 2019 [39]	Iran	R, controlled trial	Obese	32 (F)	16/16	8	Age: 26 ± 4/25.50 ± 3.66 & 28.5 ± 1.77/ 25 ± 4.17 BMI: 30.89 ± 0.34/30.48 ± 0.43 & 31.08 ± 0.63/30.55 ± 0.45	1200	Pill: Chlorella vulgaris/No supplement & Chlorella vulgaris + aerobic training/Aerobic training	Weight, BMI, TC, TG, LDL-C, HDL-C & Leptin
Shafeie et al. 2019 [40]	Iran	R, PC	Overweight	20 (M)	10/10	6	Age: 22.78 ± 2.33/22.78 ± 2.33 BMI: 27.8 ± 1.8/28.2 ± 1.8	1200	Tablet: Chlorella vulgaris + HIIT/Placebo (sucrose) + HIIT	Weight, BMI, BFM, WHR, FBG, Insulin, HOMA-IR & IL-6
Vakili et al. 2019 [41]	Iran	R, controlled trial	T2DM	40 (F)	20/20	8	Age: 56 ± 3.82/55.60 ± 4.22 & 55 ± 3.01/56.80 ± 4.21 BMI: 30.19 ± 4.49/28.73 ± 2.58 & 29.80 ± 2.260/30.26 ± 3.82	600	Chlorella vulgaris/No supplement & Chlorella vulgaris + endurance training/Endurance training	Weight, %BF, BMI, AST, ALT & ALP
Samadi et al. 2020 [42]	Iran	R, PC	Overweight	20 (M)	10/10	1	Age: 22.8 ± 2.2/22.8 ± 2.2 BMI: 27.19 ± 1.85/28.51 ± 1.43	1200	Tablet: Chlorella vulgaris/Placebo (dextrose)	IL-6 & HOMA-IR
Chiu et al. 2021 [43]	Taiwan	R, PC, DB, cross over	Healthy	44 (B)	21/23	12	Age: 40–75 BMI: 25.02 ± 2.88/24.53 ± 3.77	135	Water extract: Chlorella pyrenoidosa/Placebo (essence of mushroom, algae water, caramel)	Weight, %BF, BMI, Glutathione, TBARS, 8-OHdG, CAT, SOD, GPX, TC, TG, LDL-C, HDL-C, ALT & AST
Hosseini et al. 2021 [44]	Iran	R, PC, DB	T2DM	75 (B)	36/39	8	Age: 54.75 ± 5.98/55 ± 6.92 BMI: 27.94 ± 5.12/26.73 ± 3.43	1500	Capsule: Chlorella vulgaris/Placebo (starch)	Weight, BMI, HC, WC, SBP, DBP, FBG, HbA1c, Insulin, HOMA-IR, QUICKI, TC, TG, LDL-C & HDL-C
Sanayei et al. 2021 [45]	Iran	R, PC, DB	Overweight & obese	46 (F)	24/22	8	Age: 27.08 ± 4.29/29.27 ± 5.12 & 26.83 ± 5.82/29.09 ± 4.7 BMI: 29.51 ± 2.68/28.66 ± 2.80 & 30.97 ± 3.26/29.98 ± 2.90	900	Capsule: Chlorella vulgaris/ placebo (corn starch) & C. vulgaris + HIIT/Placebo (corn starch) + HIIT	Weight, BMI, WC, HC, WHR, TG, TC, LDL-C, HDL-C, FBS, Insulin & HOMA-IR
Tofighi et al. 2021 [46]	Iran	R, PC	Inactive Obese	40 (M)	20/20	6	Age: 22.56 ± 1.98/23.74 ± 9.54 BMI: 32.76 ± 5.56/31.6 ± 4.54	1200	Capsule: Chlorella vulgaris/Placebo (sucrose) & C. vulgaris + exercise/Placebo (sucrose) + exercise	Weight, BMI, TAC, MDA, SOD, GPx & CAT
Sanayei et al. 2022 [47]	Iran	R, PC, DB	Obese & overweight	46 (F)	24/22	8	Age: 18–35/18–35 BMI: 25–35/25–35	900	Capsule: Chlorella vulgaris/Placebo (corn starch powder) & C. vulgaris + HIIT/Placebo (corn starch powder) + HIIT	Weight, %BF, %FFM, %LBM & %Visceral fat
Amiri mandoulakani et al. 2023 [48]	Iran	Controlled trial	Obese & overweight	40 (F)	20/20	8	Age: 40–65/40–65 BMI: 25 ≤/25 ≤	1200	Tablet: Chlorella/Placebo (sucrose) & Chlorella + HIIT/Placebo (sucrose) + HIIT	Weight, TAC, MDA, WHR & %BF
Sandgruber et al. 2023 [49]	Germany	R, controlled study	Healthy	36 (B)	19/17	2	Age: 20–35/20–35 BMI:  ≤ 30/≤ 30	15,000	NR: Chlorella pyrenoidosa + smoothie (banana, pineapple, kale, mango, dates, avokado,lime juice, wheat grass & mint) + menu plan (MoKaRi)/Menu plan (MoKari)	ALT, AST, GGT, LDH, Albumin, Creatinine, TC, HDL-C, LDL-C, TG, FBG, Insulin & HbA1c
Delfan et al. 2024 [50]	Iran	R, PC, DB	Obese	44 (M)	22/22	12	Age: 23–35/23–35 BMI: 32.6 ± 2/32.3 ± 1.1	1800	Capsule: Chlorella vulgaris/Placebo (flour) & C. vulgaris + IRT/Placebo (flour) + IRT	Weight, BMI, %BF, TG, TC, HDL-C, LDL-C, FBG, Insulin, HOMA-IR, MDA, SOD & TAC
Delfan et al. 2024 [13]	Iran	R, PC, DB	Obese	44 (M)	22/22	12	Age: 23–35/23–35 BMI: 32 ± 2.0/32 ± 1.5	1800	Capsule: Chlorella vulgaris/Placebo (flour) & C. vulgaris + IRT/Placebo (flour) + IRT	Weight, BMI, %BF, FBG, Insulin, HOMA-IR, TG, TC, LDL-C, HDL-C, Leptin & Adiponectin
Tofighi et al. 2024 [51]	Iran	R, PC	Overweight & obese	40 (M)	20/20	12	Age: 29.7 ± 4.1/30.2 ± 4.8 & 30.5 ± 3.9/31.8 ± 3.1 BMI: 32.74 ± 3.45/33.65 ± 1.85 & 32.85 ± 2.65/33.85 ± 1.75	900	Capsule: Chlorella vulgaris/Placebo (corn starch) & C. vulgaris + functional exercise/ Placebo (corn starch) + functional exercise	TNF-α, hs-CRP, GPX, MDA & SOD

Footprint: %FFM Fat Free Mass Percentage, %LBM Lean Body Nass Percentage, 8-OHdG 8-Hydroxyguanosine, ALT Alanine Aminotransferase, ALP Alkaline Phosphatase, Apo A-1 Apolipoprotein A-I, Apo B Apolipoprotein B, AST Aspartate Aminotransferase, B Both sex, BP Blood Pressure, %BF Body Fat Percentage, BFM Body Fat Mass, BMI Body Mass Index, Both, BUN Blood Urea Nitrogen, CAT Catalase, C. vulgaris Chlorella vulgaris, CPK Creatine Phosphokinase, DB Double Blind, DBP Diastolic Blood Pressure, F Female, FBG Fasting Blood Glucose, GABA Gamma-aminobutyric acid, GGT Gamma-glutamyltransferase, γ-GTP Gamma-glutamyl transpeptidase, GPX Glutathione Peroxidase, GSH Total Glutathione, HbA1c Hemoglobin A1c, HC Hip Circumference, HDL-C High-density Lipoprotein Choesrerol, HIIT High-intensity interval training, HOMA-IR Homeostatic Model Assessment for Insulin Resistance, HR Heart Rate, hs-CRP high-sensitivity C-reactive Protein, HTN Hypertension, IFN-γ Interferon-Gamma, IL-1β Interleukin-1 Beta, IL-6 Interleukin-6, IRT Interval Resistance Training, LDH Lactate Dehydrogenase, LDL-C Low-density Lipoprotein Cholesterol, LP (a) Lipoprotein(a), M Male, MDA Malondialdehyde, NAFLD Nonalcoholic Fatty Liver Disease, NO Nitric Oxide, PC Placebo Controlled, PC Protein carbonyls, QUICKI Quick Insulin Sensitivity Check Index, R Randomized, Ref Reference, SBP Systolic Blood Pressure, SOD Superoxide Dismutase activity, T2DM Type 2 Diabetes Mellitus, TAC Total Antioxidant Capacity, TAS Total Antioxidant Status, TBARS Thiobarbituric Acid Reactive Substance, TC Total Cholesterol, TG Triglycerides, TNF-α Tumor Necrosis Factor-alpha, TP Total Protein, TRAP Radical-trapping Antioxidant Parameter, VLDL-C Very-Low-Density Lipoprotein Cholesterol, WC Waist Circumference, WHR Waist-to-Hip Ratio

The studies were conducted between 1975 and 2024 in Iran [13, 14, 30, 35, 42, 44–51], Japan [16, 22, 26, 28, 31, 32, 34, 36], Korea [27, 29, 33], Taiwan [43], and Germany [49]. The age of participants in the intervention groups ranged from 19.6 to 62.2 years. Chlorella supplementation doses ranged from 135 mg/day to 15,000 mg/day, and the intervention duration varied from 1 to 24 weeks. Sample sizes ranged from 8 to 80 participants. The studies included male-only [13, 27, 28, 36, 38, 40, 42, 46, 50, 51], female-only [14, 22, 37, 39, 41, 45, 47, 48], and mixed-sex [16, 23, 26, 35, 43, 44, 49] populations. Conditions addressed included type 2 diabetes mellitus (T2DM) [41, 44], obesity/overweight [13, 37, 40, 42, 48, 50, 51], non-alcoholic fatty liver disease (NAFLD) [35], borderline or diagnosed HTN [23, 25, 26], primary dysmenorrhea [14] is characterized by elevated inflammatory markers and oxidative stress, which are established cardiovascular risk factors, chronic pulmonary disease [30], mild hypercholesterolemia [24, 33], smoking addiction [27], middle-aged adults [16], and healthy individuals [22, 28, 29, 31, 34, 36, 43, 49].

Sample sizes for the intervention and control groups across various outcomes were as follows: BF (n = 288; intervention: 144, control: 144), BMI (n = 727; intervention: 381, control: 346), BFM (n = 74; intervention: 37, control: 37), HC (n = 165; intervention: 82, control: 83), WC (n = 206; intervention: 103, control: 103), weight (n = 867; intervention: 453, control: 414), WHR (n = 170; intervention: 86, control: 84), DBP (n = 433; intervention: 238, control: 195), SBP (n = 433; intervention: 238, control: 195), FBG (n = 401; intervention: 217, control: 184), HbA1c (n = 143; intervention: 72, control: 71), HOMA-IR (n = 281; intervention: 140, control: 141), insulin (n = 329; intervention: 166, control: 163), hs-CRP (n = 84; intervention: 42, control: 42), HDL-C (n = 600; intervention: 321, control: 279), LDL-C (n = 600; intervention: 321, control: 279), TC (n = 576; intervention: 308, control: 268), TG (n = 600; intervention: 321, control: 279), albumin (n = 108; intervention: 70, control: 38), ALP (n = 153; intervention: 92, control: 61), ALT (n = 233; intervention: 132, control: 101), AST (n = 233; intervention: 132, control: 101), BUN (n = 60; intervention: 45, control: 15), creatinine (n = 72; intervention: 51, control: 21), GGT (n = 72; intervention: 51, control: 21), LDH (n = 108; intervention: 70, control: 38), total protein (n = 72; intervention: 51, control: 21), CAT (n = 193; intervention: 97, control: 96), GPx (n = 176; intervention: 89, control: 87), MDA (n = 265; intervention: 132, control: 133), SOD (n = 124; intervention: 62, control: 62), TAC (n = 84; intervention: 42, control: 42), leptin (n = 76; intervention: 38, control: 38), and heart rate (n = 120; intervention: 76, control: 44).

Qualitative data assessment

The quality of the included studies was assessed using the Cochrane Risk of Bias Assessment tool (Table 2). Only three studies were assessed as having fair risk of bias [26, 45, 47], while the remaining studies were classified as poor quality.

Table 2.

Quality of included studies in the meta-analysis

Study, Year (Ref.)	Random sequence generation	Allocation concealment	Blinding of participants & personnel	Blinding of outcome assessment	Incomplete outcome data	Selective outcome reporting	Other sources of bias	Overall quality
Okuda, 1975 [22]	H	H	H	H	L	L	L	Poor
Inoue, 1995 [23]	H	H	H	H	L	L	L	Poor
Sansawa, 2002 [24]	H	H	H	H	L	L	L	Poor
Tsuchida, 2003 [25]	U	H	H	H	L	L	L	Poor
Shimada, 2009 [26]	L	U	L	H	L	L	L	Fair
Lee, 2010 [27]	U	H	U	H	L	L	L	Poor
Otsuki, 2011 [28]	U	H	U	H	U	L	L	Poor
Kwak, 2012 [29]	U	H	L	H	H	L	L	Poor
Panahi, 2012 [30]	U	H	H	H	H	L	L	Poor
Miyazawa, 2013 [31]	U	H	U	H	U	L	L	Poor
Otsuki, 2013 [32]	U	H	L	H	L	L	L	Poor
Ryu, 2014 [33]	U	H	U	H	L	L	L	Poor
Umemoto, 2014 [34]	U	H	L	H	L	L	L	Poor
Otsuki, 2015 [16]	H	H	U	H	U	L	L	Poor
Chitsaz, 2016 [35]	L	H	H	H	L	L	L	Poor
Zempo-Miyaki, 2017 [36]	U	H	L	H	L	L	L	Poor
Esmaieli, 2018 [37]	H	H	L	H	U	L	L	Poor
Haidari, 2018 [14]	L	H	L	H	L	L	L	Poor
Govahi, 2019 [38]	L	H	L	H	L	L	L	Poor
Karbalamahdi, 2019 [39]	U	H	H	H	U	L	L	Poor
Shafeie, 2019 [40]	L	H	L	H	L	L	L	Poor
Vakili, 2019 [41]	L	H	H	H	U	L	L	Poor
Samadi, 2020 [42]	U	H	H	H	L	L	L	Poor
Chiu, 2021 [43]	U	H	U	H	L	L	L	Poor
Hosseini, 2021 [44]	L	H	L	H	H	L	L	Poor
Sanayei, 2021 [45]	L	U	L	H	L	L	L	Fair
Tofighi, 2021 [46]	L	H	L	H	H	L	L	Poor
Sanayei, 2022 [47]	L	H	L	L	L	L	L	Fair
Amiri mandoulakani, 2023 [48]	U	H	L	H	U	L	L	Poor
Sandgruber, 2023 [49]	L	H	H	H	L	L	L	Poor
Delfan, 2024 [50]	U	H	U	H	H	L	L	Poor
Delfan, 2024 [13]	L	H	U	H	L	L	L	Poor
Tofighi, 2024 [51]	U	H	H	H	L	L	L	Poor

Footprint: H high risk of bias, L low risk of bias, U unclear risk of bias

Effects of chlorella supplementation on anthropometric measures

Our study showed statistically significant reductions in BF (WMD = −0.72%; 95% CI: −1.09, −0.35; P < 0.001; I² = 18.0%, P = 0.267) (Supplementary Fig. 1), BMI (WMD = −0.29 kg/m²; 95% CI: −0.44, −0.15; P < 0.001; I² = 8.0%, P = 0.344), weight (WMD = −1.52 kg; 95% CI: −2.07, −0.97; P < 0.001; I² = 2.6%, P = 0.425), and WHR (WMD = −0.01%; 95% CI: −0.01, −0.01; P < 0.001; I² = 0.0%, P = 0.859). In contrast, no significant effects were observed in BFM (WMD = −0.57 kg; 95% CI: −1.30, 0.16; P = 0.129; I² = 0.0%, P = 0.696), HC (WMD = −0.23 cm; 95% CI: −1.70, 1.24; P = 0.758; I² = 0.0%, P = 0.638), and WC (WMD = −0.56 cm; 95% CI: −2.15, 1.02; P = 0.485; I² = 0.0%, P = 0.481).

Sensitivity analyses for BF, BMI, HC, WC, WHR, and weight confirmed that excluding any study did not change the overall results. No evidence of publication bias was found for BF (Egger’s P = 0.555), BMI (Egger’s P = 0.835), HC (Egger’s P = 0.893), or WHR (Egger’s P = 0.247). However, significant publication bias was detected for weight (Egger’s P = 0.002) and WC (Egger’s P = 0.026).

Effects of chlorella supplementation on blood pressure

Our analysis illustrates that there was no significant effect on DBP (WMD = −1.52 mmHg; 95% CI: −3.16, 0.13; P = 0.071; I² = 46.9%, P = 0.036) (Supplementary Fig. 2), while significant reductions were detected in SBP (WMD = −4.58 mmHg; 95% CI: −7.53, −1.64; P = 0.002; I² = 77.9%, P < 0.001).

Sensitivity analyses for SBP indicated that excluding any study did not alter the findings. However, the exclusion of the trial by Kwak et al. [29] (WMD = −2.04 mmHg; 95% CI: −3.52, −0.56) altered the results for DBP. No publication bias was detected for DBP (Egger’s P = 0.525) or SBP (Egger’s P = 0.381).

Effects of chlorella supplementation on glycemic profile

Our findings demonstrated significant reductions in HOMA-IR (WMD = −0.20; 95% CI: −0.33, −0.08; P = 0.002; I² = 73.0%, P < 0.001) (Supplementary Fig. 3) and insulin levels (WMD = −0.97 µIU/mL; 95% CI: −1.38, −0.55; P < 0.001; I² = 44.6%, P = 0.047). However, no significant effects were observed on FBG levels (WMD = −1.21 mg/dL; 95% CI: −3.59, 1.17; P = 0.321; I² = 54.7%, P = 0.005) and HbA1c (WMD = 0.01%; 95% CI: −0.16, 0.17; P = 0.944; I² = 64.6%, P = 0.059).

No evidence of publication bias was found for FBG (Egger’s P = 0.697), HbA1c (Egger’s P = 0.136), or insulin (Egger’s P = 0.368). However, publication bias was detected for HOMA-IR (Egger’s P = 0.001).

Effects of chlorella supplementation on inflammatory markers

Chlorella supplementation significantly reduced hs-CRP levels (WMD: −421.66 ng/mL; 95% CI: −758.52 to −84.81; P = 0.014; I² = 87.1%, P < 0.001) (Supplementary Fig. 4).

Sensitivity analyses for hs-CRP showed that excluding Tofighi et al. [51] (WMD = −479.55 ng/mL; 95% CI: −1216.98, 257.87) and Haidari et al. [14] (WMD: −249.51 ng/mL; 95% CI: −504.31 to 5.28) altered the overall effect. No evidence of publication bias was detected (Egger’s P = 0.357).

Effects of chlorella supplementation on lipid profile

The analysis indicated that Chlorella supplementation significantly increased HDL-C levels (WMD = 1.57 mg/dL; 95% CI: 0.27 to 2.87; P = 0.018; I² = 20.3%, P = 0.203) (Supplementary Fig. 5). Significant reductions were observed in LDL-C (WMD = −5.70 mg/dL; 95% CI: −8.10 to −3.31; P < 0.001; I² = 35.4%, P = 0.060) and TC levels (WMD = −7.02 mg/dL; 95% CI: −9.78 to −4.25; P < 0.001; I² = 27.2%, P = 0.127). However, no significant effect was observed for TG (WMD = −0.60 mg/dL; 95% CI: −4.97 to 3.76; P = 0.786; I² = 54.9%, P = 0.002).

Sensitivity analyses indicated that excluding any study did not alter the findings for LDL-C and TG. However, for HDL-C, excluding Delfan et al. [13] (WMD: 1.30 mg/dL; 95% CI: −0.01 to 2.61) and Delfan et al. [50] (WMD: 1.39 mg/dl; 95%CI: −0.01, 2.80) affected the results. No publication bias was found for LDL-C (Egger's P = 0.223), TC (Egger's P = 0.608), or TG (Egger's P = 0.530), though publication bias was noted for HDL-C (Egger’s P = 0.020).

Effects of chlorella supplementation on liver function

Supplementation with Chlorella resulted in significant reductions in ALT (WMD = −4.84 IU/L; 95% CI: −6.46 to −3.21; P < 0.001; I² = 0.0%, P = 0.539) (Supplementary Fig. 6), AST (WMD = −3.38 IU/L; 95% CI: −4.65 to −2.11; P < 0.001; I² = 5.5%, P = 0.390), and LDH (WMD = −14.13 U/L; 95% CI: −25.18 to −3.09; P = 0.012; I² = 0.0%, P = 0.524). However, no significant effect was observed on albumin (WMD = 0.07 mg/L; 95% CI: −0.07 to 0.21; P = 0.299; I² = 0.0%, P = 0.586), ALP (WMD = −6.65 IU/L; 95% CI: −22.46 to 9.15; P = 0.409; I² = 37.1%, P = 0.146), BUN (WMD = −0.77; 95% CI: −2.05 to 0.51; P = 0.241; I² = 0.0%, P = 0.982), creatinine (WMD = 0.02 mg/dL; 95% CI: −0.06 to 0.09; P = 0.626; I² = 0.0%, P = 0.793), GGT (WMD = −2.68 U/L; 95% CI: −12.65 to 7.28; P = 0.598; I² = 0.0%, P = 0.938), total protein (WMD = −0.15 g/dL; 95% CI: −0.30 to 0.00; P = 0.055; I² = 0.0%, P = 0.934).

Sensitivity analyses for albumin, ALP, ALT, AST, BUN, creatinine, GGT, and total protein indicated that the exclusion of any single study did not alter the overall results. However, the study by Sandgruber et al. [49] (WMD: −5.39 U/L; 95% CI: −23.86 to 13.08) changed the overall effect for LDH. No evidence of publication bias was detected for albumin (Egger's P = 0.372), ALP (Egger's P = 0.761), ALT (Egger's P = 0.419), AST (Egger's P = 0.477), BUN (Egger's P = 0.920), creatinine (Egger's P = 0.581), GGT (Egger's P = 0.252), LDH (Egger's P = 0.766), or total protein (Egger's P = 0.161).

Effects of chlorella supplementation on oxidative stress parameters

Our meta-analysis showed significant effects on CAT (WMD = 15.64 u/g.hb; 95% CI: 2.32, 28.96; P = 0.021; I² = 99.4%, P < 0.001) (Supplementary Fig. 7), MDA (WMD = −1.51 nmol/mL; 95% CI: −2.86, −0.16; P = 0.028; I² = 99.8%, P < 0.001), and SOD (WMD = 19.73 u/g.hb; 95% CI: 13.35, 26.11; P < 0.001; I² = 18.4%, P = 0.294). In contrast, no significant effects were observed for GPx (WMD = 92.87 U/L; 95% CI: −404.44, 590.18; P = 0.714; I² = 98.8%, P < 0.001) or TAC did not show a significant effect (WMD = −0.44 Mmol/L; 95% CI: −1.88, 0.99; P = 0.543; I² = 99.8%, P < 0.001).

Sensitivity analysis for SOD indicated that excluding any individual study did not alter the overall findings. For CAT, excluding Chiu et al. [43] (WMD: 18.99 u/g.hb; 95% CI: −0.11, 38.01) and Tofighi et al. [46] (WMD: 15.32 u/g.hb; 95% CI: −1.74, 32.39) changed the results. Similarly, for GPx, excluding Tofighi et al. [46] (WMD: 339.58 U/L; 95% CI: 63.09, 616.07) affected the outcome. For MDA, excluding Delfan et al. [13] (WMD: −1.50 nmol/mL; 95% CI: −3.01, 0.01), Haidari et al. [14] (WMD: −1.15 nmol/mL; 95% CI: −2.57, 0.26), and Tofighi et al. [46] (WMD = −1.58 nmol/mL; 95% CI: −3.19, 0.04) altered the results. TAC findings were affected by excluding Tofighi et al. [46] (WMD = 0.36 Mmol/L; 95% CI: 0.17, 0.55).

No evidence of publication bias was found for CAT (Egger’s P = 0.331), GPx (Egger’s P = 0.999), MDA (Egger’s P = 0.420), SOD (Egger’s P = 0.250), or TAC (Egger’s P = 0.515).

Effects of chlorella supplementation on leptin

Chlorella supplementation was associated with a significant reduction in leptin levels (WMD = −0.71 ng/mL; 95% CI: −1.27, −0.15; P = 0.012; I² = 0.0%, P = 0.538) (Supplementary Fig. 8). Sensitivity analysis indicated that excluding Delfan et al. [13] (WMD: −0.43 ng/mL; 95% CI: −1.21, 0.35) altered the overall effect of Chlorella on leptin. No publication bias was detected (Egger’s P = 0.789).

Effects of chlorella supplementation on heart rate

No significant effect of Chlorella supplementation on heart rate was observed (WMD = −0.90 bpm; 95% CI: −4.08, 2.28; P = 0.579; I² = 59.4%, P = 0.043) (Supplementary Fig. 9). Sensitivity analysis showed no changes to the overall results after study exclusion. No evidence of publication bias was found (Egger’s P = 0.084).

Subgroup analysis

Chlorella supplementation was found to significantly affect BF, BMI, weight, insulin, HOMA-IR, and HDDL-C in overweight or obese individuals. Reductions in TC and LDL-C were observed in both overweight/obese and healthy participants. ALT and AST levels decreased in healthy individuals as well as those with chronic illnesses. Significant effects on DBP and SBP were observed in individuals with chronic disease. MDA levels were reduced only in healthy individuals.

Chlorella, whether combined with exercise or administered alone significantly affected BF, BMI, weight, and LDL-C. Increases in HOMA-IR, insulin, and HDL-C were observed only with the combination of Chlorella and exercise. Both GABA-rich and pure Chlorella impacted TC and AST, whereas only GABA-rich Chlorella significantly changed SBP and DBP. When supplementation was limited to Chlorella alone, significant effects were observed on ALT and MDA.

Regarding species, C. vulgaris exhibited a more pronounced effect on BF, BMI, weight, HOMA-IR, insulin, and HDL-C. All Chlorella species contributed to reductions in LDL-C, while both C. vulgaris and C. pyrenoidosa were effective in reducing TC, ALT, and AST levels.

Both capsule and tablet forms of Chlorella significantly affected BF, BMI, LDL-C, and TC. The capsule form additionally affected weight, HOMA-IR, insulin, and HDL-C levels. FBG was affected only when the tablet form was administered.

In control groups, placebo or usual care significantly affected SBP, TC, ALT, and MDA, while exercise-based control groups showed greater effects in HDL-C, HOMA-IR, and insulin. BF, BMI, LDL-C, and weight changed under both control approaches.

In terms of dosage, BF, BMI, weight, HOMA-IR, insulin, HDL-C, and MDA showed significant effects with doses < 2000 mg, whereas SBP was more significantly affected by doses ≥ 2000 mg. LDL-C, TC, ALT, and AST demonstrated significant changes across all dosage categories.

Interventions lasting > 8 weeks resulted in greater effects in weight, DBP, FBG, HOMA-IR, insulin, HDL-C, and MDA, whereas durations ≤ 8 weeks showed more significant effects on BF and BMI. Significant changes in SBP, LDL-C, TC, ALT, and AST were observed across all durations.

Chlorella supplementation demonstrated differential effects across sex-specific subgroups. Significant alterations in weight, FBG, HOMA-IR, insulin, and HDL-C were observed exclusively in studies enrolling male participants. SBP and AST showed significant effects only in mixed-sex populations. BF, BMI, and MDA were significantly affected in studies including either male-only or female-only participants. ALT demonstrated significant changes in both mixed-sex and female-only groups. Finally, LDL-C and TC changed across all sex-based subgroups.

Participants younger than 40 years showed significant changes in BMI, weight, HOMA-IR, insulin, HDL-C, and MDA, while those 40 years or older showed significant changes in SBP and DBP. Additionally, BF, LDL-C, TC, ALT, and AST demonstrated significant changes in both age groups.

Country-specific analyses indicated that BF, BMI, weight, HOMA-IR, insulin, HDL-C, and MDA were significantly affected in studies conducted in Iran, whereas DBP and SBP showed greater improvements in studies from Japan. Changes in LDL-C, TC, ALT, and AST were significant in studies conducted in both Iran and Japan.

Baseline BMI influenced alterations in BF, BMI, weight, HOMA-IR, insulin, HDL-C, and MDA among overweight/obese individuals. LDL-C, TC, AST, and ALT were significantly reduced in both healthy and overweight/obese groups. Changes in SBP were observed only in the healthy-weight subgroup.

Sample size also influenced outcomes. Studies including 20 participants or fewer showed significant effects on BMI, SBP, and FBG. Studies with more than 20 participants demonstrated significant effects on HOMA-IR, insulin, HDL-C, and MDA. Significant changes in BF, weight, LDL-C, TC, ALT, and AST were noted in both sample size categories (Table 3).

Table 3.

Description of the analysis and subgroup results of Chlorella supplementation on cardiovascular disease risk factors

	Studies N	Participant N	WMD (95%CI)	P-value	Heterogeneity
					P heterogeneity	I2	P between sub-groups
Analysis and subgroup results of Chlorella supplementation on BF
Overall effect	12	288	−0.72 (−1.09, −0.35)	< 0.001	0.267	18.0%
Health Condition
Healthy	2	74	0.89 (−1.16, 2.94)	0.396	0.409	0.0%	0.271
Overweight or Obese	8	174	−0.81 (−1.23, −0.39)	< 0.001	0.223	25.8%
Chronic Disease	2	40	−0.58 (−1.47, 0.31)	0.200	0.433	0.0%
Intervention Approach
Chlorella	7	181	−0.79 (−1.40, −0.19)	0.010	0.125	39.9%	0.567
Chlorella with Exercise	5	107	−0.57 (−1.03, −0.12)	0.014	0.645	0.0%
GABA-rich Chlorella	-	-	-	-	-	-
Chlorella Species
Chlorella vulgaris	8	174	−1.02 (−1.46, −0.59)	< 0.001	0.422	0.9%	0.083
Chlorella pyrenoidosa	2	74	0.89 (−1.16, 2.94)	0.396	0.409	0.0%
Chlorella regularis	-	-	-	-	-	-
Not mention	2	40	−0.53 (−0.96, −0.10)	0.015	0.437	0.0%
Intervention Type
Tablet	3	70	−0.52 (−0.94, −0.1)	0.016	0.696	0.0%	0.122
Capsule	6	134	−1.15 (−1.67, −0.63)	< 0.001	0.394	3.5%
Pill	-	-	-	-	-	-
Other forms or not mention	3	84	−0.23 (−1.35, 0.90)	0.693	0.234	31.1%
Control Approach
Placebo or Usual care	7	181	−0.79 (−1.40, −0.19)	0.010	0.125	39.9%	0.567
Exercise	5	107	−0.57 (−1.03, −0.12)	0.014	0.645	0.0%
Chlorella Dosage
2000 >	11	258	−0.72 (−1.11, −0.34)	< 0.001	0.214	24.1%	0.632
2000 ≤	1	30	0.00 (−2.94, 2.941)	1.000	-	-
Intervention Duration
8 ≥	7	156	−0.61 (−0.96, −0.251)	0.001	0.813	0.0%	0.991
8 <	5	132	−0.61 (−1.81, 0.59)	0.315	0.073	53.3%
Sex
Both sex	1	44	1.73 (−1.13, 4.59)	0.236	-	-	0.212
Female	6	126	−0.62 (−0.98, −0.26)	0.001	0.730	0.0%
Male	5	118	−0.93 (−1.79, −0.08)	0.032	0.255	25.0%
Intervention Age
40 >	7	164	−1.13 (−1.62, −0.65)	< 0.001	0.449	0.0%	0.044
40 ≤	5	124	−0.72 (−1.09, −0.35)	0.010	0.462	0.0%
Country
Iran	10	214	−0.77 (−1.12, −0.43)	< 0.001	0.330	12.2%	0.209
Japan	1	30	0.00 (−2.94, 2.94)	1.000	-	-
Korea	-	-	-	-	-	-
Other countries	1	44	1.73 (−1.13, 4.59)	0.236	-	-
Baseline BMI
Healthy weight (≤ 25 kg/m2)	2	74	0.89 (−1.16, 2.94)	0.396	0.409	0.0%	0.117
Overweight or Obese (> 25 kg/m2)	10	214	−0.77 (−1.12, −0.43)	< 0.001	0.330	12.2%
Not Reported	-	-	-	-	-	-
Sample size
20 ≥	4	80	−0.54 (−0.93, −0.16)	0.006	0.746	0.0%	0.399
20 <	8	208	−0.88 (−1.55, −0.2)	0.011	0.218	26.4%
Analysis and subgroup results of Chlorella supplementation on BMI
Overall effect	28	727	−0.29 (−0.44, −0.15)	< 0.001	0.344	8.0%
Health Condition
Healthy	7	233	0.06 (−0.47, 0.60)	0.819	1.000	0.0%	0.356
Overweight or Obese	14	278	−0.36 (−0.58, −0.14)	0.001	0.035	44.9%
Chronic Disease	7	216	−0.26 (−0.97, 0.45)	0.478	0.687	0.0%
Intervention Approach
Chlorella	16	488	−0.29 (−0.58, −0.01)	0.045	0.078	35.6%	0.900
Chlorella with Exercise	9	179	−0.35 (−0.56, −0.14)	0.001	0.719	0.0%
GABA-rich Chlorella	3	60	−0.11 (−1.38, 1.17)	0.867	0.990	0.0%
Chlorella Species
Chlorella vulgaris	18	434	−0.36 (−0.57, −0.15)	0.001	0.052	38.0%	0.348
Chlorella pyrenoidosa	4	126	0.08 (−0.61, 0.76)	0.828	0.993	0.0%
Chlorella regularis	-	-	-	-	-	-
Not mention	6	167	−0.01 (−0.72, 0.71)	0.989	1.000	0.0%
Intervention Type
Tablet	9	238	−0.22 (−0.43, −0.01)	0.036	0.441	0.0%	0.683
Capsule	10	269	−0.44 (−0.84, −0.03)	0.035	0.103	38.3%
Pill	2	32	−0.28 (−0.72, 0.16)	0.207	0.068	70.1%
Other forms or not mention	7	188	0.02 (−0.67, 0.71)	0.954	1.000	0.0%
Control Approach
Placebo or Usual care	19	548	−0.28 (−0.53, −0.03)	0.027	0.178	22.9%	0.690
Exercise	9	179	−0.35 (−0.56, −0.14)	0.001	0.719	0.0%
Chlorella Dosage
2000 >	20	522	−0.34 (−0.54, −0.14)	0.001	0.083	32.1%	0.234
2000 ≤	8	205	0.02 (−0.54, 0.58)	0.941	1.000	0.0%
Intervention Duration
8 ≥	23	595	−0.22 (−0.36, −0.07)	0.004	0.950	0.0%	0.417
8 <	5	132	−0.48 (−1.08, 0.13)	0.123	0.007	71.4%
Sex
Both sex	10	335	−0.06 (−0.56, 0.43)	0.803	0.878	0.0%	0.356
Female	9	194	−0.22 (−0.38, −0.06)	0.006	0.514	0.0%
Male	9	198	−0.50 (−0.90, −0.09)	0.017	0.094	41.0%
Intervention Age
40 >	18	423	−0.33 (−0.52, −0.13)	0.001	0.105	30.8%	0.447
40 ≤	10	304	−0.11 (−0.64, 0.43)	0.696	0.886	0.0%
Country
Iran	19	478	−0.35 (−0.56, −0.15)	0.001	0.070	34.6%	0.569
Japan	7	154	−0.01 (−0.66, 0.647)	0.983	1.000	0.0%
Korea	1	51	0.100 (−0.99, 1.19)	0.857	-	-
Other countries	1	44	0.140 (−1.11, 1.39)	0.826	-	-
Baseline BMI
Healthy weight (≤ 25 kg/m2)	10	293	0.04 (−0.46, 0.53)	0.883	1.000	0.0%	0.149
Overweight or Obese (> 25 kg/m2)	18	434	−0.36 (−0.57, −0.15)	0.001	0.052	38.0%
Not Reported	-	-	-	-	-	-
Sample size
20 ≥	15	276	−0.23 (−0.38, −0.08)	0.003	0.903	0.0%	0.653
20 <	13	451	−0.32 (−0.70, 0.05)	0.091	0.062	40.8%
Analysis and subgroup results of Chlorella supplementation on BFM
Overall effect	3	74	−0.57 (−1.30, 0.16)	0.129	0.696	0.0%
Analysis and subgroup results of Chlorella supplementation on HC
Overall effect	4	165	−0.23 (−1.70, 1.24)	0.758	0.638	0.0%
Analysis and subgroup results of Chlorella supplementation on WC
Overall effect	5	206	−0.56 (−2.15, 1.02)	0.485	0.481	0.0%
Analysis and subgroup results of Chlorella supplementation on Weight
Overall effect	34	867	−1.52 (−2.07, −0.97)	< 0.001	0.425	2.6%
Health Condition
Healthy	8	267	0.09 (−1.50, 1.69)	0.909	1.000	0.0%	0.218
Overweight or Obese	18	364	−1.51 (−2.38, −0.63)	0.001	0.073	34.9%
Chronic Disease	8	236	−0.82 (−2.65, 1.00)	0.375	0.977	0.0%
Intervention Approach
Chlorella	20	585	−1.39 (−2.38, −0.40)	0.006	0.144	25.6%	0.676
Chlorella with Exercise	11	222	−0.87 (−1.66, −0.09)	0.030	0.999	0.0%
GABA-rich Chlorella	3	60	−0.40 (−3.80, 3.00)	0.817	0.993	0.0%
Chlorella Species
Chlorella vulgaris	20	480	−1.67 (−2.52, −0.82)	< 0.001	0.158	24.2%	0.200
Chlorella pyrenoidosa	5	160	0.14 (−1.81, 2.09)	0.890	1.000	0.0%
Chlorella regularis	1	20	−2.00 (−7.34, 3.34)	0.463	-	-
Not mention	8	207	−0.35 (−1.66, 0.97)	0.606	1.000	0.0%
Intervention Type
Tablet	13	332	−0.61 (−1.69, 0.46)	0.264	0.998	0.0%	0.490
Capsule	12	315	−1.64 (−2.83, −0.45)	0.007	0.020	51.5%
Pill	2	32	−1.03 (−4.07, 2.02)	0.508	0.708	0.0%
Other forms or not mention	7	188	−0.08 (−2.02, 1.86)	0.934	1.000	0.0%
Control Approach
Placebo or Usual care	23	645	−1.44 (−2.34, −0.54)	0.002	0.226	17.4%	0.352
Exercise	11	222	−0.87 (−1.66, −0.09)	0.030	0.999	0.0%
Chlorella Dosage
2000 >	24	608	−1.40 (−2.15, −0.65)	< 0.001	0.146	23.6%	0.192
2000 ≤	10	259	−0.22 (−1.82, 1.38)	0.784	1.000	0.0%
Intervention Duration
8 ≥	28	715	−0.67 (−1.45, 0.1)	0.087	1.000	0.0%	0.189
8 <	6	152	−1.98 (−3.77, −0.20)	0.030	0.002	73.3%
Sex
Both sex	11	355	−0.37 (−1.80, 1.06)	0.610	0.994	0.0%	0.161
Female	13	280	−0.46 (−1.57, 0.64)	0.408	1.000	0.0%
Male	10	232	−1.91 (−3.15, −0.67)	0.003	0.019	54.8%
Intervention Age
40 >	21	503	−1.50 (−2.33, −0.66)	< 0.001	0.148	24.7%	0.149
40 ≤	13	364	−0.47 (−1.58, 0.64)	0.407	0.999	0.0%
Country
Iran	23	564	−1.47 (−2.23, −0.70)	< 0.001	0.152	23.5%	0.440
Japan	9	208	−0.33 (−2.07, 1.42)	0.715	1.000	0.0%
Korea	1	51	0.30 (−3.67, 4.27)	0.882	-	-
Other countries	1	44	0.43 (−3.33, 4.19)	0.823	-	-
Baseline BMI
Healthy weight (≤ 25 kg/m2)	11	327	0.00 (−1.44, 1.45)	0.996	1.000	0.0%	0.197
Overweight or Obese (> 25 kg/m2)	22	520	−1.49 (−2.27, −0.70)	< 0.001	0.133	25.7%
Not Reported	1	20	−2.00 (−7.34, 3.34)	0.463	-	-
Sample size
20 ≥	18	336	−0.93 (−1.86, −0.00)	0.049	1.000	0.0%	0.777
20 <	16	531	−1.14 (−2.27, −0.02)	0.047	0.022	46.3%
Analysis and subgroup results of Chlorella supplementation on WHR
Overall effect	7	170	−0.01 (−0.01, −0.01)	< 0.001	0.859	0.0%
Analysis and subgroup results of Chlorella supplementation on DBP
Overall effect	12	433	−1.52 (−3.16, 0.13)	0.071	0.036	46.9%
Health Condition
Healthy	5	175	−0.33 (−2.81, 2.15)	0.795	0.163	38.7%	0.217
Overweight or Obese	-	-	-	-	-	-
Chronic Disease	7	258	−2.33 (−4.32, −0.35)	0.021	0.123	40.2%
Intervention Approach
Chlorella	8	293	−0.45 (−2.04, 1.14)	0.579	0.364	8.6%	0.105
Chlorella with Exercise	-	-	-	-	-	-
GABA-rich Chlorella	4	140	−2.97 (−5.58, −0.37)	0.025	0.108	50.6%
Chlorella Species
Chlorella vulgaris	1	75	0.36 (−3.08, 3.80)	0.838	-	-	0.727
Chlorella pyrenoidosa	2	60	−2.40 (−6.14, 1.34)	0.208	0.177	45.1%
Chlorella regularis	1	20	−2.00 (−6.98, 2.98)	0.431	-	-
Not mention	8	278	−1.42 (−3.85, 1.02)	0.254	0.016	59.5%
Intervention Type
Tablet	7	246	−2.01 (−4.67, 0.64)	0.138	0.016	61.5%	0.604
Capsule	1	75	0.36 (−3.08, 3.80)	0.838	-	-
Pill	1	52	0.30 (−3.73, 4.33)	0.884	-	-
Other forms or not mention	3	60	−1.72 (−4.14, 0.71)	0.166	0.378	0.0%
Control Approach
Placebo or Usual care	12	433	−1.52 (−3.16, 0.13)	0.071	0.036	46.9%
Exercise	-	-	-	-	-	-
Chlorella Dosage
2000 >	2	98	−0.23 (−3.39, 2.92)	0.885	0.400	0.0%	0.447
2000 ≤	10	335	−1.65 (−3.51, 0.21)	0.082	0.025	52.7%
Intervention Duration
8 ≥	9	310	−0.65 (−2.15, 0.85)	0.394	0.287	17.5%	0.003
8 <	3	123	−4.55 (−6.65, 2.45)	< 0.001	0.487	0.0%
Sex
Both sex	11	381	−1.69 (−3.45, 0.07)	0.060	0.033	49.1%	0.375
Female	-	-	-	-	-	-
Male	1	52	0.30 (−3.73, 4.33)	0.884	-	-
Intervention Age
40 >	3	131	0.51 (−1.86, 2.87)	0.675	0.248	28.4%	0.042
40 ≤	9	302	−2.54 (−4.27, −0.80)	0.004	0.191	28.5%
Country
Iran	1	75	0.36 (−3.08, 3.80)	0.838	-	-	0.011
Japan	9	255	−2.74 (−4.26, −1.23)	< 0.001	0.297	16.3%
Korea	2	103	1.73 (−1.03, 4.49)	0.218	0.339	0.0%
Other countries	-	-	-	-	-	-
Baseline BMI
Healthy weight (≤ 25 kg/m2)	8	287	−1.68 (−4.10, 0.73)	0.172	0.010	62.0%	0.614
Overweight or Obese (> 25 kg/m2)	1	75	0.36 (−3.08, 3.80)	0.838	-	-
Not Reported	3	71	−1.42 (−3.73, 0.90)	0.230	0.833	0.0%
Sample size
20 ≥	5	92	−1.67 (−3.81, 0.47)	0.126	0.709	0.0%	0.886
20 <	7	341	−1.43 (−3.92, 1.06)	0.261	0.005	67.7%
Analysis and subgroup results of Chlorella supplementation on SBP
Overall effect	12	433	−4.58 (−7.53, −1.64)	0.002	< 0.001	77.9%
Health Condition
Healthy	5	175	−0.42 (−2.76, 1.93)	0.728	0.483	0.0%	0.001
Overweight or Obese	-	-	-	-	-	-
Chronic Disease	7	258	−7.11 (−10.19, −4.04)	< 0.001	0.002	71.4%
Intervention Approach
Chlorella	8	293	−1.11 (−3.13, 0.91)	0.281	0.417	1.6%	< 0.001
Chlorella with Exercise	-	-	-	-	-	-
GABA-rich Chlorella	4	140	−8.15 (−11.33, −4.97)	< 0.001	0.009	74.2%
Chlorella Species
Chlorella vulgaris	1	75	−1.43 (−5.65, 2.79)	0.506	-	-	0.371
Chlorella pyrenoidosa	2	60	−1.80 (−4.94, 1.34)	0.261	0.317	0.0%
Chlorella regularis	1	20	−7.00 (−18.27, 4.27)	0.223	-	-
Not mention	8	278	−5.38 (−9.12, −1.64)	0.005	< 0.001	81.1%
Intervention Type
Tablet	7	246	−5.26 (−10.63, 0.105)	0.055	< 0.001	81.7%	0.002
Capsule	1	75	−1.43 (−5.65, 2.79)	0.506	-	-
Pill	1	52	3.10 (−2.19, 8.39)	0.251	-	-
Other forms or not mention	3	60	−6.64 (−8.56, −4.71)	< 0.001	0.528	0.0%
Control Approach
Placebo or Usual care	12	433	−4.58 (−7.53, −1.64)	0.002	< 0.001	77.9%
Exercise	-	-	-	-	-	-
Chlorella Dosage
2000 >	2	98	−4.13 (−12.46, 4.21)	0.332	0.170	47.0%	0.907
2000 ≤	10	335	−4.66 (−7.90, −1.42)	0.005	< 0.001	80.1%
Intervention Duration
8 ≥	9	310	−3.23 (−5.74, −0.72)	0.012	0.004	64.2%	< 0.001
8 <	3	123	−12.01 (−14.78, −9.23)	< 0.001	0.649	0.0%
Sex
Both sex	11	381	−5.35 (−8.19, −2.50)	< 0.001	< 0.001	74.4%	0.006
Female	-	-	-	-	-	-
Male	1	52	3.10 (−2.19, 8.39)	0.251	-	-
Intervention Age
40 >	3	131	0.16 (−2.35, 2.67)	0.898	0.446	0.0%	< 0.001
40 ≤	9	302	−6.77 (−9.53, −4.00)	< 0.001	0.005	63.9%
Country
Iran	1	75	−1.43 (−5.65, 2.79)	0.506	-	-	0.003
Japan	9	255	−6.59 (−9.57, −3.61)	< 0.001	0.001	70.3%
Korea	2	103	1.39 (−2.21, 4.98)	0.450	0.387	0.0%
Other countries	-	-	-	-	-	-
Baseline BMI
Healthy weight (≤ 25 kg/m2)	8	287	−5.06 (−8.63, −1.48)	0.006	< 0.001	81.0%	0.437
Overweight or Obese (> 25 kg/m2)	1	75	−1.43 (−5.65, 2.79)	0.506	-	-
Not Reported	3	71	−3.72 (−9.34, 1.90)	0.194	0.234	31.2%
Sample size
20 ≥	5	92	−6.57 (−8.46, −4.68)	< 0.001	0.765	0.0%	0.269
20 <	7	341	−3.56 (−8.55, 1.43)	0.162	< 0.001	86.9%
Analysis and subgroup results of Chlorella supplementation on FBG
Overall effect	16	401	−1.21 (−3.59, 1.17)	0.321	0.005	54.7%
Health Condition
Healthy	3	80	−0.12 (−2.82, 2.58)	0.930	0.672	0.0%	0.503
Overweight or Obese	9	186	−2.24 (−4.62, 0.14)	0.065	0.137	35.2%
Chronic Disease	4	135	0.02 (−12.44, 12.48)	0.998	0.003	78.5%
Intervention Approach
Chlorella	8	238	−0.80 (−3.64, 3.48)	0.965	0.011	61.5%	0.563
Chlorella with Exercise	5	103	−2.12 (−5.51, 1.26)	0.219	0.090	50.2%
GABA-rich Chlorella	3	60	−4.86 (−15.04, 5.31)	0.349	0.166	44.3%
Chlorella Species
Chlorella vulgaris	10	261	−1.23 (−4.52, 2.06)	0.465	0.001	67.2%	0.498
Chlorella pyrenoidosa	2	68	0.31 (−2.62, 3.24)	0.836	0.628	0.0%
Chlorella regularis	0	0	-	-	-	-
Not mention	4	72	−3.46 (−9.38, 2.45)	0.251	0.301	17.9%
Intervention Type
Tablet	5	96	−2.41 (−4.74, −0.08)	0.043	0.376	5.4%	0.889
Capsule	7	209	−1.08 (−6.00, 3.85)	0.668	0.001	72.4%
Pill	0	0	-	-	-	-
Other forms or not mention	4	96	−1.92 (−7.54, 3.70)	0.503	0.212	33.4%
Control Approach
Placebo or Usual care	11	298	−0.72 (−4.04, 2.60)	0.672	0.011	56.2%	0.561
Exercise	5	103	−2.12 (−5.51, 1.26)	0.219	0.090	50.2%
Chlorella Dosage
2000 >	10	261	−1.23 (−4.52, 2.06)	0.465	0.001	67.2%	0.801
2000 ≤	6	140	−0.67 (−3.46, 2.12)	0.638	0.382	5.4%
Intervention Duration
8 ≥	12	313	0.06 (−2.56, 2.68)	0.964	0.006	58.1%	0.011
8 <	4	88	−6.63 (−11.07, −2.19)	0.003	0.940	0.0%
Sex
Both sex	7	215	0.73 (−4.32, 5.79)	0.776	0.010	64.5%	0.003
Female	4	78	0.68 (−1.79, 3.15)	0.588	0.862	0.0%
Male	5	108	−5.08 (−7.54, −2.63)	< 0.001	0.898	0.0%
Intervention Age
40 >	10	222	−1.81 (−3.88, 0.26)	0.086	0.131	34.6%	0.542
40 ≤	6	179	0.49 (−6.62, 7.60)	0.892	0.006	69.4%
Country
Iran	10	261	−1.23 (−4.52, 2.06)	0.465	0.001	67.2%	0.791
Japan	5	104	−1.80 (−6.65, 3.06)	0.468	0.292	19.2%
Korea	0	0	-	-	-	-
Other countries	1	36	0.00 (−3.19,3.1 9)	1.000	0.005	54.7%
Baseline BMI
Healthy weight (≤ 25 kg/m2)	5	104	−1.80 (−6.65, 3.06)	0.468	0.292	19.2%	0.789
Overweight or Obese (> 25 kg/m2)	11	297	−1.03 (−3.83, 1.76)	0.469	0.002	64.4%
Not Reported	0	0	-	-	-	-
Sample size
20 ≥	7	124	−2.95 (−5.31, −0.59)	0.014	0.391	4.7%	0.229
20 <	9	277	−0.40 (−3.82, 3.01)	0.817	0.005	63.7%
Analysis and subgroup results of Chlorella supplementation on HbA1c
Overall effect	3	143	0.01 (−0.16, 0.17)	0.944	0.059	64.6%
Analysis and subgroup results of Chlorella supplementation on HOMA-IR
Overall effect	11	281	−0.20 (−0.33, −0.08)	0.002	< 0.001	73.0%
Health Condition
Healthy	0	0	-	-	-	-	0.417
Overweight or Obese	10	206	−0.22 (−0.35, −0.08)	0.001	< 0.001	75.7%
Chronic Disease	1	75	0.05 (−0.57, 0.67)	0.883	-	-
Intervention Approach
Chlorella	6	178	−0.16 (−0.34, 0.02)	0.087	0.004	71.0%	0.476
Chlorella with Exercise	5	103	−0.24 (−0.40, −0.09)	0.002	0.122	45.0%
GABA-rich Chlorella	0	0	-	-	-	-
Chlorella Species
Chlorella vulgaris	11	281	−0.20 (−0.33, −0.08)	0.002	< 0.001	90.4%
Chlorella pyrenoidosa	0	0	-	-	-	-
Chlorella regularis	0	0	-	-	-	-
Not mention	0	0	-	-	-	-
Intervention Type
Tablet	4	72	−0.04 (−0.13, 0.05)	0.410	0.083	55.1%	0.001
Capsule	7	209	−0.37 (−0.55, −0.20)	< 0.001	0.247	23.8%
Pill	0	0	-	-	-	-
Other forms or not mention	0	0	-	-	-	-
Control Approach
Placebo or Usual care	6	178	−0.16 (−0.34, 0.02)	0.087	0.004	71.0%	0.476
Exercise	5	103	−0.24 (−0.40, −0.09)	0.002	0.122	45.0%
Chlorella Dosage
2000 >	11	281	−0.20 (−0.33, −0.08)	0.002	< 0.001	73.0%
2000 ≤	0	0	-	-	-	-
Intervention Duration
8 ≥	7	193	−0.09 (−0.21, 0.02)	0.111	0.017	61.1%	0.023
8 <	4	88	−0.39 (−0.61, −0.16)	0.001	0.175	39.4%
Sex
Both sex	1	75	0.05 (−0.57, 0.67)	0.883	-	-	0.427
Female	4	78	−0.15 (−0.35, 0.06)	0.160	0.033	65.6%
Male	6	128	−0.31 (−0.54, −0.08)	0.010	< 0.001	81.6%
Intervention Age
40 >	10	205	−0.22 (−0.35, −0.09)	0.001	< 0.001	75.7%	0.417
40 ≤	1	75	0.05 (−0.57, 0.67)	0.883	-	-
Country
Iran	11	281	−0.20 (−0.33, −0.08)	0.002	< 0.001	73.0%
Japan	0	0	-	-	-	-
Korea	0	0	-	-	-	-
Other countries	0	0	-	-	-	-
Baseline BMI
Healthy weight (≤ 25 kg/m2)	0	0	-	-	-	-
Overweight or Obese (> 25 kg/m2)	11	281	−0.20 (−0.33, −0.08)	0.002	< 0.001	73.0%
Not Reported	0	0	-	-	-	-
Sample size
20 ≥	4	72	−0.04 (−0.13, 0.05)	0.410	0.083	55.1%	0.001
20 <	7	209	−0.37 (−0.55, −0.20)	< 0.001	0.247	23.8%
Analysis and subgroup results of Chlorella supplementation on Insulin
Overall effect	12	329	−0.97 (−1.38, −0.55)	< 0.001	0.047	44.6%
Health Condition
Healthy	2	68	0.89 (−0.49, 2.28)	0.205	0.549	0.0%	0.019
Overweight or Obese	9	186	−1.14 (−1.50, −0.78)	< 0.001	0.184	29.3%
Chronic Disease	1	75	−0.68 (−2.49, 1.12)	0.458	-	-
Intervention Approach
Chlorella	7	226	−0.71 (−1.47, 0.05)	0.068	0.032	56.4%	0.471
Chlorella with Exercise	5	103	−1.04 (−1.52, −0.56)	< 0.001	0.200	33.2.%
GABA-rich Chlorella	0	0	-	-	-	-
Chlorella Species
Chlorella vulgaris	10	261	−1.13 (−1.46, −0.79)	< 0.001	0.239	22.1%	0.005
Chlorella pyrenoidosa	2	68	0.89 (−0.49, 2.28)	0.205	0.549	0.0%
Chlorella regularis	0	0	-	-	-	-
Not mention	0	0	-	-	-	-
Intervention Type
Tablet	4	84	−0.27 (−1.11, 0.57)	0.532	0.318	14.8%	0.018
Capsule	7	209	−1.24 (−1.59, −0.88)	< 0.001	0.245	24.1%
Pill	0	0	-	-	-	-
Other forms or not mention	1	36	0.60 (−1.08, 2.28)	0.485	0.047	44.6%
Control Approach
Placebo or Usual care	7	226	−0.71 (−1.47, 0.05)	0.068	0.032	56.4%	0.471
Exercise	5	103	−1.04 (−1.52, −0.56)	< 0.001	0.200	33.2%
Chlorella Dosage
2000 >	10	261	−1.13 (−1.46, −0.79)	< 0.001	0.239	22.1%	0.005
2000 ≤	2	68	0.89 (−0.49, 2.28)	0.205	0.549	0.0%
Intervention Duration
8 ≥	8	241	−0.55 (−1.40, 0.29)	0.200	0.080	44.8%	0.175
8 <	4	88	−1.18 (−1.50, −0.86)	< 0.001	0.303	17.5%
Sex
Both sex	3	143	0.32 (−0.84, 1.48)	0.586	0.332	9.4%	0.051
Female	4	78	−1.20 (−2.72, 0.31)	0.120	0.065	58.4%
Male	5	108	−1.16 (−1.44, −0.88)	< 0.001	0.427	0.0%
Intervention Age
40 >	10	232	−1.06 (−1.46, −0.66)	< 0.001	0.083	41.2%	0.233
40 ≤	2	107	0.25 (−1.86, 2.37)	0.814	0.156	50.3%
Country
Iran	10	261	−1.13 (−1.46, −0.79)	< 0.001	0.239	22.1%	0.017
Japan	1	32	1.50 (−0.92, 3.92)	0.224	-	-
Korea	0	0	-	-	-	-
Other countries	1	36	0.60 (−1.08, 2.28)	0.485	0.047	44.6%
Baseline BMI
Healthy weight (≤ 25 kg/m2)	1	32	1.50 (−0.92, 3.92)	0.224	-	-	0.041
Overweight or Obese (> 25 kg/m2)	11	297	−1.05 (−1.42, −0.67)	< 0.001	0.115	35.5%
Not Reported	0	0	-	-	-	-
Sample size
20 ≥	3	52	−0.51 (−1.31, 0.28)	0.206	0.574	0.0%	0.239
20 <	9	277	−1.07 (−1.56, −0.59)	< 0.001	0.033	52.3%
Analysis and subgroup results of Chlorella supplementation on hs-CRP
Overall effect	3	84	−421.66 (−758.52, −84.81)	0.014	< 0.001	87.1%
Analysis and subgroup results of Chlorella supplementation on HDL-C
Overall effect	20	600	1.57 (0.27, 2.87)	0.018	0.203	20.3%
Health Condition
Healthy	5	175	−1.99 (−7.31, 3.34)	0.464	0.042	59.6%	0.026
Overweight or Obese	8	166	2.96 (1.58, 4.35)	< 0.001	0.840	0.0%
Chronic Disease	7	259	−0.06 (−2.30, 2.17)	0.956	0.915	0.0%
Intervention Approach
Chlorella	13	457	1.23 (−0.69, 3.15)	0.208	0.076	38.6%	0.170
Chlorella with Exercise	4	83	2.42 (0.53, 4.30)	0.012	0.867	0.0%
GABA-rich Chlorella	3	60	−4.36 (−11.50, 2.78)	0.231	0.893	0.0%
Chlorella Species
Chlorella vulgaris	11	345	2.30 (1.10, 3.50)	< 0.001	0.717	0.0%	0.112
Chlorella pyrenoidosa	3	112	−2.89 (−12.93, 7.14)	0.572	0.008	79.5%
Chlorella regularis	1	20	3.00 (−9.10, 15.10)	0.627	-	-
Not mention	5	123	−2.43 (−6.35, 1.50)	0.225	0.958	0.0%
Intervention Type
Tablet	6	219	−0.68 (−3.42, 2.05)	0.625	0.975	0.0%	0.041
Capsule	7	209	2.99 (1.57, 4.41)	< 0.001	0.716	0.0%
Pill	2	32	0.99 (−1.77, 3.76)	0.482	0.875	0.0%
Other forms or not mention	5	140	−3.44 (−10.54, 3.66)	0.343	0.030	62.7%
Control Approach
Placebo or Usual care	16	517	0.92 (−0.92, 2.75)	0.328	0.099	32.9%	0.263
Exercise	4	83	2.42 (0.53, 4.30)	0.012	0.867	0.0%
Chlorella Dosage
2000 >	11	326	2.62 (1.40, 3.84)	< 0.001	0.789	0.0%	0.001
2000 ≤	9	274	−2.07 (−4.61, 0.47)	0.110	0.546	0.0%
Intervention Duration
8 ≥	14	448	0.15 (−1.32, 1.62)	0.840	0.468	0.0%	0.001
8 <	6	152	3.77 (2.11, 5.44)	< 0.001	0.972	0.0%
Sex
Both sex	12	434	−0.55 (−2.58, 1.49)	0.599	0.351	9.6%	0.008
Female	4	78	1.79 (−0.45, 4.02)	0.117	0.814	0.0%
Male	4	88	3.70 (1.93, 5.47)	< 0.001	0.856	0.0%
Intervention Age
40 >	10	253	2.00 (0.16, 3.84)	0.033	0.059	45.0%	0.249
40 ≤	10	347	0.41 (−1.59, 2.40)	0.690	0.834	0.0%
Country
Iran	10	282	2.51 (1.26, 3.77)	< 0.001	0.763	0.0%	0.078
Japan	6	124	−2.36 (−7.12, 2.40)	0.331	0.930	0.0%
Korea	2	114	−0.67 (−3.86, 2.53)	0.683	0.611	0.0%
Other countries	2	80	−3.12 (−18.96, 12.73)	0.700	0.002	89.4%
Baseline BMI
Healthy weight (≤ 25 kg/m2)	8	262	−0.21 (−2.65, 2.22)	0.863	0.639	0.0%	0.294
Overweight or Obese (> 25 kg/m2)	11	318	2.09 (0.47, 3.70)	0.011	0.113	35.7%
Not Reported	1	20	3.00 (−9.10, 15.10)	0.627	-	-
Sample size
20 ≥	7	124	0.35 (−2.11, 2.81)	0.780	0.883	0.0%	0.334
20 <	13	476	1.82 (0.15, 3.50)	0.033	0.068	39.9%
Analysis and subgroup results of Chlorella supplementation on LDL-C
Overall effect	20	600	−5.70 (−8.10, −3.31)	< 0.001	0.060	35.4%
Health Condition
Healthy	5	175	−10.69 (−15.81, −5.57)	< 0.001	0.356	8.8%	0.119
Overweight or Obese	8	166	−5.15 (−7.10, −3.21)	< 0.001	0.621	0.0%
Chronic Disease	7	259	−3.72 (−10.79, 3.35)	0.302	0.078	47.2%
Intervention Approach
Chlorella	13	457	−6.23 (−9.73, −2.72)	< 0.001	0.008	55.5%	0.622
Chlorella with Exercise	4	83	−4.34 (−7.33, −1.35)	0.004	0.791	0.0%
GABA-rich Chlorella	3	60	−9.57 (−25.18, 6.04)	0.230	0.736	0.0%
Chlorella Species
Chlorella vulgaris	11	345	−4.13 (−6.74, −1.52)	0.002	0.080	40.2%	0.022
Chlorella pyrenoidosa	3	112	−13.55 (−19.24, −7.87)	< 0.001	0.568	0.0%
Chlorella regularis	1	20	−11.00 (−21.67, −0.33)	0.043	-	-
Not mention	5	123	−5.34 (−13.06, 2.39)	0.176	0.899	0.0%
Intervention Type
Tablet	6	219	−6.48 (−11.18, −1.77)	0.007	0.687	0.0%	0.039
Capsule	7	209	−4.30 (−7.59, −1.01)	0.010	0.023	59.0%
Pill	2	32	−3.13 (−10.10, 3.84)	0.379	0.399	0.0%
Other forms or not mention	5	140	−14.01 (−20.09, −7.92)	< 0.001	0.812	0.0%
Control Approach
Placebo or Usual care	16	517	−6.30 (−9.58, −3.03)	< 0.001	0.023	46.1%	0.385
Exercise	4	83	−5.70 (−8.10, −3.31)	0.004	0.791	0.0%
Chlorella Dosage
2000 >	11	326	−4.90 (−7.84, −1.96)	0.001	0.027	50.6%	0.156
2000 ≤	9	274	−8.54 (−12.62, −4.46)	< 0.001	0.625	0.0%
Intervention Duration
8 ≥	14	448	−5.82 (−10.02, −1.62)	0.007	0.037	44.4%	0.881
8 <	6	152	−5.46 (−7.77, −3.14)	< 0.001	0.305	16.8%
Sex
Both sex	12	434	−6.97 (−12.27, −1.68)	0.010	0.013	54.2%	0.630
Female	4	78	−7.14 (−13.08, −1.19)	0.019	0.287	20.5%
Male	4	88	−4.85 (−6.94, −2.76)	< 0.001	0.808	0.0%
Intervention Age
40 >	10	253	−5.70 (−7.75, −3.65)	< 0.001	0.337	11.5%	0.824
40 ≤	10	347	−6.44 (−12.64, −0.24)	0.042	0.030	51.4%
Country
Iran	10	282	−4.34 (−7.07, −1.62)	0.002	0.066	43.9%	0.012
Japan	6	124	−9.78 (−16.22, −3.35)	0.003	0.975	0.0%
Korea	2	114	−1.56 (−9.13, 6.02)	0.687	0.644	0.0%
Other countries	2	80	−14.80 (−21.41, −8.19)	< 0.001	0.438	0.0%
Baseline BMI
Healthy weight (≤ 25 kg/m2)	8	262	−6.89 (−12.07, −1.71)	0.009	0.522	0.0%	0.536
Overweight or Obese (> 25 kg/m2)	11	318	−5.19 (−8.10, −2.28)	< 0.001	0.017	53.7%
Not Reported	1	20	−11.00 (−21.67, −0.33)	0.043	-	-
Sample size
20 ≥	7	124	−6.01 (−11.23, −0.79)	0.024	0.806	0.0%	0.944
20 <	13	476	−5.79 (−8.74, −2.85)	< 0.001	0.010	54.4%
Analysis and subgroup results of Chlorella supplementation on TC
Overall effect	20	576	−7.02 (−9.78, −4.25)	< 0.001	0.127	27.2%
Health Condition
Healthy	5	151	−9.45 (−15.50, −3.40)	0.002	0.325	14.1%	0.807
Overweight or Obese	8	166	−7.62 (−10.52, −4.73)	< 0.001	0.509	0.0%
Chronic Disease	7	259	−6.44 (−13.87, 0.99)	0.089	0.028	57.5%
Intervention Approach
Chlorella	13	433	−7.42 (−10.74, −4.10)	< 0.001	0.080	38.0%	0.235
Chlorella with Exercise	4	83	−2.92 (−8.70, 2.87)	0.323	0.875	0.0%
GABA-rich Chlorella	3	60	−13.40 (−26.08, −0.72)	0.038	0.293	18.6%
Chlorella Species
Chlorella vulgaris	11	345	−5.67 (−9.12, −2.23)	0.001	0.074		0.297
Chlorella pyrenoidosa	2	80	−14.94 (−24.07, −5.81)	0.001	0.323
Chlorella regularis	1	20	−9.00 (−23.97, 5.97)	0.239	-	-
Not mention	6	131	−8.27 (−14.31, −2.22)	0.007	0.407	1.4%
Intervention Type
Tablet	6	195	−7.91 (−12.06, −3.75)	< 0.001	0.784	0.0%	0.115
Capsule	7	209	−5.34 (−10.31, −0.36)	0.036	0.023	59.1%
Pill	2	32	−2.30 (−10.37, 5.78)	0.578	0.899	0.0%
Other forms or not mention	5	140	−14.37 (−21.51, −7.24)	< 0.001	0.482	0.0%
Control Approach
Placebo or Usual care	16	493	−7.84 (−11.04, −4.64)	< 0.001	0.091	33.9%	0.144
Exercise	4	83	−2.92 (−8.70, 2.87)	0.323	0.875	0.0%
Chlorella Dosage
2000 >	11	326	−5.92 (−9.38, −2.46)	0.001	0.076	40.9%	0.239
2000 ≤	9	250	−9.47 (−14.25, −4.68)	< 0.001	0.407	3.3%
Intervention Duration
8 ≥	13	416	−6.29 (−10.65, −1.93)	0.005	0.060	41.1%	0.396
8 <	7	160	−8.60 (−11.65, −5.54)	< 0.001	0.598	0.0%
Sex
Both sex	11	402	−7.08 (−12.39, −1.77)	0.009	0.039	47.7%	0.971
Female	5	86	−6.93 (−12.09, −1.76)	0.009	0.683	0.0%
Male	4	88	−7.69 (−11.89, −3.49)	< 0.001	0.235	29.5%
Intervention Age
40 >	11	261	−8.01 (−10.82, −5.20)	< 0.001	0.377	7.0%	0.570
40 ≤	9	315	−6.11 (−12.04, −0.18)	0.043	0.070	44.8%
Country
Iran	10	282	−5.70 (−9.37, −2.02)	0.002	0.051	46.5%	0.165
Japan	6	100	−10.27 (−16.72, −3.81)	0.002	0.581	0.0%
Korea	2	114	−3.29 (−11.72, 5.15)	0.445	0.913	0.0%
Other countries	2	80	−14.94 (−24.07, −5.81)	0.001	0.323	0.0%
Baseline BMI
Healthy weight (≤ 25 kg/m2)	7	230	−6.62 (−12.40, −0.85)	0.025	0.565	0.0%	0.685
Overweight or Obese (> 25 kg/m2)	11	318	−6.47 (−10.24, −2.70)	0.001	0.024	51.4%
Not Reported	2	28	−10.70 (−19.62, −1.79)	0.019	0.781	0.0%
Sample size
20 ≥	8	132	−7.16 (−12.20, −2.11)	0.005	0.530	0.0%	0.906
20 <	12	444	−6.78 (−10.32, −3.25)	< 0.001	0.045	45.0%
Analysis and subgroup results of Chlorella supplementation on TG
Overall effect	20	600	−0.60 (−4.97, 3.76)	0.786	0.002	54.9%
Health Condition
Healthy	5	175	5.28 (−11.16, 21.71)	0.529	0.098	48.9%	0.703
Overweight or Obese	8	166	−1.36 (−6.13, 3.40)	0.575	0.001	71.8%
Chronic Disease	7	259	2.23 (−14.00, 18.45)	0.788	0.201	29.8%
Intervention Approach
Chlorella	13	457	−2.27 (−7.30, 2.77)	0.378	0.052	42.6%	0.793
Chlorella with Exercise	4	83	2.64 (−8.22, 13.49)	0.634	< 0.001	83.5%
GABA-rich Chlorella	3	60	12.15 (−31.76, 56.06)	0.588	0.990	0.0%
Chlorella Species
Chlorella vulgaris	11	345	−1.31 (−6.24, 3.62)	0.603	< 0.001	69.6%	0.224
Chlorella pyrenoidosa	3	112	−2.97 (−18.20, 12.27)	0.703	0.201	37.6%
Chlorella regularis	1	20	11.00 (−13.87, 35.87)	0.386	-	-
Not mention	5	123	21.06 (−1.98, 44.09)	0.073	0.969	0.0%
Intervention Type
Tablet	6	219	2.89 (−13.31, 19.11)	0.726	0.125	42.0%	0.608
Capsule	7	209	−0.54 (−5.59, 4.51)	0.834	< 0.001	77.1%
Pill	2	32	2.45 (−26.18, 31.08)	0.867	0.101	62.9%
Other forms or not mention	5	140	−8.12 (−19.33, 3.08)	0.155	0.618	0.0%
Control Approach
Placebo or Usual care	16	517	−2.18 (−6.72, 2.36)	0.347	0.126	29.7%	0.423
Exercise	4	83	2.64 (−8.22, 13.49)	0.634	< 0.001	83.5%
Chlorella Dosage
2000 >	11	326	−0.44 (−5.14, 4.25)	0.853	0.001	66.5%	0.838
2000 ≤	9	274	1.01 (−12.13, 14.16)	0.880	0.150	33.4%
Intervention Duration
8 ≥	14	448	−0.76 (−10.08, 8.55)	0.872	0.078	37.4%	0.903
8 <	6	152	−0.11 (−4.99, 4.77)	0.965	0.001	76.3%
Sex
Both sex	12	434	3.34 (−7.55, 14.23)	0.548	0.104	35.8%	0.681
Female	4	78	−4.40 (−18.78, 9.97)	0.548	0.189	37.1%
Male	4	88	−0.75 (−5.88, 4.37)	0.773	< 0.001	84.7%
Intervention Age
40 >	10	253	−1.95 (−6.61, 2.72)	0.413	0.001	69.5%	0.175
40 ≤	10	347	6.35 (−4.69, 17.40)	0.260	0.340	11.2%
Country
Iran	10	282	−0.66 (−5.45, 4.12)	0.785	0.001	69.3%	0.459
Japan	6	124	11.24 (−3.62, 26.10)	0.138	0.944	0.0%
Korea	2	114	−6.95 (−58.92, 45.01)	0.793	0.026	79.9%
Other countries	2	80	−5.52 (−27.00, 15.95)	0.614	0.185	43.0%
Baseline BMI
Healthy weight (≤ 25 kg/m2)	8	262	5.86 (−8.61, 20.33)	0.427	0.359	9.2%	0.407
Overweight or Obese (> 25 kg/m2)	11	318	−1.65 (−6.33, 3.02)	0.489	< 0.001	69.2%
Not Reported	1	20	11.00 (−13.87, 35.87)	0.386	-	-
Sample size
20 ≥	7	124	7.06 (−5.93, 20.04)	0.287	0.583	0.0%	0.224
20 <	13	476	−1.51 (−6.20, 3.19)	0.530	< 0.001	66.5%
Analysis and subgroup results of Chlorella supplementation on Albumin
Overall effect	5	108	0.07 (−0.07, 0.21)	0.299	0.586	0.0%
Analysis and subgroup results of Chlorella supplementation on ALP
Overall effect	7	153	−6.65 (−22.46, 9.15)	0.409	0.146	37.1%
Analysis and subgroup results of Chlorella supplementation on ALT
Overall effect	9	233	−4.84 (−6.46, −3.21)	< 0.001	0.539	0.0%
Health Condition
Healthy	3	92	−4.31 (−6.14, −2.47)	< 0.001	0.827	0.0%	0.220
Overweight or Obese	-	-	-	-	-	-
Chronic Disease	6	141	−6.82 (−10.39, −3.24)	< 0.001	0.407	1.5%
Intervention Approach
Chlorella	5	153	−5.30 (−7.87, −2.73)	< 0.001	0.215	30.9%	0.851
Chlorella with Exercise	1	20	−5.30 (−11.26, 0.66)	0.081	-	-
GABA-rich Chlorella	3	60	−3.39 (−9.54, 2.77)	0.281	0.624	0.0%
Chlorella Species
Chlorella vulgaris	3	81	−8.73 (−13.50, −3.95)	< 0.001	0.307	15.2%	0.203
Chlorella pyrenoidosa	2	80	−4.39 (−6.30, −2.49)	< 0.001	0.603	0.0%
Chlorella regularis	-	-	-	-	-	-
Not mention	4	72	−3.30 (−7.86, 1.26)	0.156	0.814	0.0%
Intervention Type
Tablet	2	53	−7.50 (−16.67, 1.68)	0.109	0.094	64.3%	0.548
Capsule	-	-	-	-	-	-
Pill	-	-	-	-	-	-
Other forms or not mention	7	180	−4.64 (−6.35, −2.93)	< 0.001	0.727	0.0%
Control Approach
Placebo or Usual care	8	213	−4.80 (−6.49, −3.11)	< 0.001	0.434	0.0%	0.874
Exercise	1	20	−5.30 (−11.26, 0.66)	0.081	-	-
Chlorella Dosage
2000 >	4	125	−6.69 (−10.18, −3.19)	< 0.001	0.197	35.9%	0.161
2000 ≤	5	108	−3.48 (−6.29, −0.67)	0.015	0.917	0.0%
Intervention Duration
8 ≥	8	189	−4.97 (−7.33, −2.62)	< 0.001	0.434	0.0%	0.874
8 <	1	44	−4.71 (−6.96, −2.46)	< 0.001	-	-
Sex
Both sex	7	193	−4.56 (−6.28, −2.84)	< 0.001	0.565	0.0%	0.354
Female	2	40	−7.36 (−13.01, −1.71)	0.011	0.270	17.7%
Male	-	-	-	-	-	-
Intervention Age
40 >	1	36	−3.59 (−7.16, −0.02)	0.049	-	-	0.443
40 ≤	8	197	−5.16 (−6.99, −3.33)	< 0.001	0.495	0.0%
Country
Iran	3	81	−8.73 (−13.50, −3.95)	< 0.001	0.307	15.2%	0.203
Japan	4	72	−3.30 (−7.86, 1.26)	0.156	0.814	0.0%
Korea	-	-	-	-	-	-
Other countries	2	80	−4.39 (−6.30, −2.49)	< 0.001	0.603	0.0%
Baseline BMI
Healthy weight (≤ 25 kg/m2)	5	116	−4.44 (−6.45, −2.42)	< 0.001	0.871	0.0%	0.325
Overweight or Obese (> 25 kg/m2)	4	117	−6.77 (−10.95, −2.59)	0.002	0.151	43.4%
Not Reported	-	-	-	-	-	-
Sample size
20 ≥	6	112	−5.05 (−8.42, −1.69)	0.003	0.638	0.0%	0.980
20 <	3	121	−5.11 (−8.10, −2.12)	0.001	0.169	43.7%
Analysis and subgroup results of Chlorella supplementation on AST
Overall effect	9	233	−3.38 (−4.65, −2.11)	< 0.001	0.390	5.5%
Health Condition
Healthy	3	92	−3.11 (−4.66, −1.55)	< 0.001	0.511	0.0%	0.535
Overweight or Obese	-	-	-	-	-	-
Chronic Disease	6	141	−3.98 (−6.27, −1.69)	0.001	0.232	27.0%
Intervention Approach
Chlorella	5	153	−3.58 (−5.27, −1.89)	< 0.001	0.288	19.9%	0.509
Chlorella with Exercise	1	20	−1.30 (−5.11, 2.51)	0.504	-	-
GABA-rich Chlorella	3	60	−4.00 (−7.10, −0.90)	0.011	0.343	6.7%
Chlorella Species
Chlorella vulgaris	3	81	−4.24 (−8.27, −0.21)	0.039	0.097	57.2%	0.910
Chlorella pyrenoidosa	2	80	−3.31 (−4.91, −1.71)	< 0.001	0.686	0.0%
Chlorella regularis	-	-	-	-	-	-
Not mention	4	72	−3.25 (−6.25, −0.25)	0.034	0.312	16.0%
Intervention Type
Tablet	2	53	−2.64 (−6.69, 1.41)	0.202	0.249	24.6%	0.695
Capsule	-	-	-	-	-	-
Pill	-	-	-	-	-	-
Other forms or not mention	7	180	−3.50 (−4.99, −2.01)	< 0.001	0.316	15.0%
Control Approach
Placebo or Usual care	8	213	−3.61 (−4.92, −2.30)	< 0.001	0.408	2.9%	0.261
Exercise	1	20	−1.30 (−5.11, 2.51)	0.504	-	-
Chlorella Dosage
2000 >	4	125	−3.78 (−6.10, −1.46)	0.001	0.197	35.8%	0.636
2000 ≤	5	108	−3.09 (−4.80, −1.38)	< 0.001	0.465	0.0%
Intervention Duration
8 ≥	8	189	−3.34 (−4.99, −1.70)	< 0.001	0.300	16.5%	0.828
8 <	1	44	−3.66 (−5.99, −1.33)	0.002	-	-
Sex
Both sex	7	193	−3.37 (−4.67, −2.08)	< 0.001	0.696	0.0%	0.689
Female	2	40	−5.11 (−13.48, 3.27)	0.232	0.032	78.3%
Male	-	-	-	-	-	-
Intervention Age
40 >	1	36	−3.00 (−5.20, −0.80)	0.007	-	-	0.694
40 ≤	8	197	−3.55 (−5.21, −1.90)	< 0.001	0.306	15.8%
Country
Iran	3	81	−4.24 (−8.27, −0.21)	0.039	0.097	57.2%	0.910
Japan	4	72	−3.25 (−6.25, −0.25)	0.034	0.312	16.0%
Korea	-	-	-	-	-	-
Other countries	2	80	−3.31 (−4.91, −1.71)	< 0.001	0.686	0.0%
Baseline BMI
Healthy weight (≤ 25 kg/m2)	5	116	−3.48 (−5.25, −1.71)	< 0.001	0.459	0.0%	0.980
Overweight or Obese (> 25 kg/m2)	4	117	−3.51 (−5.83, −1.19)	0.003	0.186	37.6%
Not Reported	-	-	-	-	-	-
Sample size
20 ≥	6	112	−3.59 (−6.38, −0.81)	0.011	0.147	38.8%	0.913
20 <	3	121	−3.42 (−4.89, −1.95)	< 0.001	0.872	0.0%
Analysis and subgroup results of Chlorella supplementation on BUN
Overall effect	3	60	−0.77 (−2.05, 0.51)	0.241	0.982	0.0%
Analysis and subgroup results of Chlorella supplementation on creatinine
Overall effect	4	72	0.02 (−0.06, 0.09)	0.626	0.793	0.0%
Analysis and subgroup results of Chlorella supplementation on GGT
Overall effect	4	72	−2.68 (−12.65, 7.28)	0.598	0.938	0.0%
Analysis and subgroup results of Chlorella supplementation on LDH
Overall effect	5	108	−14.13 (−25.18, −3.09)	0.012	0.524	0.0%
Analysis and subgroup results of Chlorella supplementation on Total Protein
Overall effect	4	72	−0.15 (−0.30, 0.00)	0.055	0.934	0.0%
Analysis and subgroup results of Chlorella supplementation on CAT
Overall effect	5	193	15.64 (2.32, 28.96)	0.021	< 0.001	99.4%
Analysis and subgroup results of Chlorella supplementation on GPx
Overall effect	6	176	92.87 (−404.44, 590.18)	0.714	< 0.001	98.8%
Analysis and subgroup results of Chlorella supplementation on MDA
Overall effect	10	265	−1.51 (−2.86, −0.16)	0.028	< 0.001	99.8%
Health Condition
Healthy	1	44	−4.93 (−6.28, −3.58)	< 0.001	-	-	0.001
Overweight or Obese	8	164	−1.13 (−2.60, 0.34)	0.131	< 0.001	99.9%
Chronic Disease	1	57	−1.43 (−4.77, 1.91)	0.401	-	-
Intervention Approach
Chlorella	6	183	−1.26 (−1.84, −0.68)	< 0.001	< 0.001	97.2%	0.900
Chlorella with Exercise	4	82	−1.44 (−4.27, 1.38)	0.317	< 0.001	99.9%
GABA-rich Chlorella	-	-	-	-	-	-
Chlorella Species
Chlorella vulgaris	7	181	−1.48 (−3.15, 0.18)	0.080	< 0.001	99.9%	0.608
Chlorella pyrenoidosa	-	-	-	-	-	-
Chlorella regularis	-	-	-	-	-	-
Not mention	3	84	−1.00 (−1.81, −0.19)	0.016	< 0.001	96.5%
Intervention Type
Tablet	3	97	−0.06 (−0.37, 0.24)	0.684	0.027	72.4%	< 0.001
Capsule	6	124	−1.49 (−3.24, 0.26)	0.095	< 0.001	99.9%
Pill	-	-	-	-	-	-
Other forms or not mention	1	44	−4.93 (−6.28, −3.58)	< 0.001	-	-
Control Approach
Placebo or Usual care	6	183	−1.26 (−1.84, −0.68)	< 0.001	< 0.001	97.2%	0.900
Exercise	4	82	−1.44 (−4.27, 1.38)	0.317	< 0.001	99.9%
Chlorella Dosage
2000 >	9	208	−1.52 (−2.91, −0.12)	0.033	< 0.001	99.9%	0.962
2000 ≤	1	57	−1.43 (−4.77, 1.91)	0.401	-	-
Intervention Duration
8 ≥	6	181	−2.07 (−4.20, 0.05)	0.056	< 0.001	99.9%	0.242
8 <	4	82	−0.75 (−1.39, −0.11)	0.022	< 0.001	97.8%
Sex
Both sex	1	57	−1.43 (−4.77, 1.91)	0.401	-	-	0.866
Female	3	84	−1.00 (−1.81, −0.19)	0.016	< 0.001	96.5%
Male	6	124	−1.49 (−3.24, 0.26)	0.095	< 0.001	99.9%
Intervention Age
40 >	7	168	−1.94 (−3.57, −0.31)	0.019	< 0.001	99.9%	0.026
40 ≤	3	97	−0.06 (−0.37, 0.24)	0.684	0.027	72.4%
Country
Iran	10	265	−1.51 (−2.86, −0.16)	0.028	0.000	99.8%
Japan	-	-	-	-	-	-
Korea	-	-	-	-	-	-
Other countries	-	-	-	-	-	-
Baseline BMI
Healthy weight (≤ 25 kg/m2)	1	44	−4.93 (−6.28, −3.58)	< 0.001	-	-	< 0.001
Overweight or Obese (> 25 kg/m2)	9	221	−1.15 (−2.57, 0.26)	0.111	< 0.001	99.9%
Not Reported	-	-	-	-	-	-
Sample size
20 ≥	6	120	−1.11 (−3.04, 0.81)	0.257	< 0.001	99.9%	0.428
20 <	4	145	−1.98 (−2.90, −1.06)	< 0.001	< 0.001	96.7%
Analysis and subgroup results of Chlorella supplementation on SOD
Overall effect	6	124	19.73 (13.35, 26.11)	< 0.001	0.294	18.4%
Analysis and subgroup results of Chlorella supplementation on TAC
Overall effect	4	84	−0.44 (−1.88, 0.99)	0.543	< 0.001	99.8%
Analysis and subgroup results of Chlorella supplementation on Leptin
Overall effect	4	76	−0.71 (−1.27, −0.15)	0.012	0.538	0.0%
Analysis and subgroup results of Chlorella supplementation on Heart rate
Overall effect	5	120	−0.90 (−4.08, 2.28)	0.579	0.043	59.4%

Foodprint: ALP Alkaline Phosphatase, ALT Alanine Aminotransferase, AST Aspartate Aminotransferase, BF Body Fat, BMI Body Mass Index, BUN Blood Urea Nitrogen, CAT Catalase, CI Confidence Interval, DBP Diastolic Blood Pressure, FBG Fasting Blood Glucose, GGT Gamma-Glutamyl Transferase, GPx Glutathione Peroxidase, HbA1c Glycated Hemoglobin, HC Hip Circumference, HDL-C High-Density Lipoprotein Cholesterol, HOMA-IR Homeostatic Model Assessment of Insulin Resistance, hs-CRP High-Sensitivity C-Reactive Protein, HTN Hypertension, LDH Lactate Dehydrogenase, LDL-C Low-Density Lipoprotein Cholesterol, MDA Malondialdehyde, SBP Systolic Blood Pressure, SOD Superoxide Dismutase, TAC Total Antioxidant Capacity, TC Total Cholesterol, TG Triglycerides, WC Waist Circumference, WHR Waist-to-Hip Ratio

Meta-regression and non-linear dose–response analysis

Meta-regression analysis demonstrated significant associations between the duration of Chlorella supplementation and reductions in SBP (P = 0.010) and weight (P = 0.048), as well as an increase in HDL-C (P = 0.002), suggesting that longer intervention durations may enhance therapeutic benefits. Additionally, a significant negative association was observed between the dose of Chlorella and HDL-C (P < 0.001), indicating that lower doses may be more effective for increasing HDL-C.

Non-linear dose–response analysis revealed that higher doses were significantly associated with reductions in weight (P = 0.031; approximate dose ≈ 600 mg/day), FBG (P = 0.014; approximate dose ≈ 4,000 mg/day), HDL-C (P < 0.001; approximate dose ≈ 900 mg/day), and ALT (P = 0.042; approximate dose ≈ 1,000 mg/day). In contrast, increasing doses were also linked to elevations in BF (P = 0.006; approximate dose ≈ 600 mg/day), insulin (P = 0.018; approximate dose ≈ 6,000 mg/day), and LDL-C (P = 0.007; approximate dose ≈ 900 mg/day). Furthermore, this analysis identified significant positive associations with intervention duration for SBP (P = 0.012; approximate duration ≈ 6 weeks) and TG (P = 0.048; approximate duration ≈ 8 weeks), as well as a significant negative association for HDL-C (P = 0.004; approximate duration ≈ 4 weeks) (Supplementary Figs. 10–13).

GRADE assessment

Table 4 outlines the GRADE assessment for the certainty of evidence regarding Chlorella supplementation's effects. The quality of evidence for LDL-C, TC, and BMI was rated as moderate, while the evidence quality for BF, weight, DBP, SBP, HDL-C, and TG was categorized as low. The remaining outcomes were classified as having very low-quality evidence.

Table 4.

GRADE profile of Chlorella supplementation on CVD outcomes

Outcomes	Risk of bias	Inconsistency	Indirectness	Imprecision	Publication bias	Number (INT/CON)	WMD (95%CI)	Quality of evidence
BF	Seriousa	Not serious	Not serious	Seriousb	None	144/144	−0.72 (−1.09, −0.35)	⨁⨁◯◯ Low
BMI	Seriousa	Not serious	Not serious	Not serious	None	381/346	−0.29 (−0.44, −0.15)	⨁⨁⨁◯ Moderate
BFM	Seriousa	Not serious	Not serious	Very seriousb,c	None	37/37	−0.57 (−1.30, 0.16)	⨁◯◯◯ Very low
HC	Not serious	Not serious	Serious d	Very seriousb,c	None	82/83	−0.23 (−1.70, 1.24)	⨁◯◯◯ Very low
WC	Serious a	Not serious	Serious d	Very seriousb,c	Publication bias strongly suspected e	103/103	−0.57 (−2.15, 1.02)	⨁◯◯◯ Very low
Weight	Serious a	Not serious	Not serious	Not serious	Publication bias strongly suspected e	453/414	−1.52 (−2.07, −0.97)	⨁⨁◯◯ Low
WHR	Serious a	Not serious	Serious d	Seriousb	None	86/84	−0.01 (−0.01, −0.01)	⨁◯◯◯ Very low
DBP	Serious a	Not serious	Not serious	Seriousc	None	238/195	−1.52 (−3.16, 0.13)	⨁⨁◯◯ Low
SBP	Serious a	Serious f	Not serious	Not serious	None	238/195	−4.58 (−7.53, −1.64)	⨁⨁◯◯ Low
FBG	Very serious a	Serious f	Serious d	Seriousc	None	217/184	−1.20 (−3.59, 1.17)	⨁◯◯◯ Very low
HbA1c	Very serious a	Serious f	Not serious	Very seriousb,c	None	72/71	0.01 (−0.16, 0.17)	⨁◯◯◯ Very low
HOMA-IR	Very serious a	Serious f	Very serious d	Seriousb	None	140/141	−0.20 (−0.33, −0.08)	⨁◯◯◯ Very low
Insulin	Very serious a	Seriousf	Not serious	Seriousb	Publication bias strongly suspected e	166/163	−0.97 (−1.38, −0.55)	⨁◯◯◯ Very low
hs-CRP	Very serious a	Seriousf	Serious d	Seriousb	None	42/42	−421.66 (−758.52, −84.81)	⨁◯◯◯ Very low
HDL-C	Serious a	Not serious	Not serious	Not serious	Publication bias strongly suspected e	321/279	1.57 (0.27, 2.87)	⨁⨁◯◯ Low
LDL-C	Serious a	Not serious	Not serious	Not serious	None	321/279	−5.70 (−8.10, −3.31)	⨁⨁⨁◯ Moderate
TC	Serious a	Not serious	Not serious	Not serious	None	308/268	−7.02 (−9.78, −4.25)	⨁⨁⨁◯ Moderate
TG	Serious a	Not serious	Not serious	Seriousc	None	321/279	−0.60 (−4.97, 3.76)	⨁⨁◯◯ Low
Albumin	Very serious a	Not serious	Not serious	Very seriousb,c	None	70/38	0.07 (−0.07, 0.22)	⨁◯◯◯ Very low
ALP	Very serious a	Not serious	Not serious	Very seriousb,c	None	92/61	−6.65 (−22.46, 9.15)	⨁◯◯◯ Very low
ALT	Very serious a	Not serious	Not serious	Seriousb	None	132/101	−4.84 (−6.46, −3.21)	⨁◯◯◯ Very low
AST	Very serious a	Not serious	Not serious	Seriousb	None	132/101	−3.38 (−4.65, −2.11)	⨁◯◯◯ Very low
BUN	Very serious a	Not serious	Serious d	Very seriousb,c	None	45/15	−0.77 (−2.05, 0.51)	⨁◯◯◯ Very low
Creatinine	Very serious a	Not serious	Serious d	Very seriousb,c	None	51/21	0.02 (−0.06, 0.09)	⨁◯◯◯ Very low
GGT	Very serious a	Not serious	Serious d	Very seriousb,c	None	51/21	−2.68 (−12.65, 7.28)	⨁◯◯◯ Very low
LDH	Very serious a	Not serious	Not serious	Seriousb	None	70/38	−14.13 (−25.18, −3.09)	⨁◯◯◯ Very low
Total protein	Very serious a	Not serious	Serious d	Very seriousb,c	None	51/21	−0.15 (−0.30, 0.00)	⨁◯◯◯ Very low
CAT	Very serious a	Serious f	Not serious	Seriousb	None	97/96	15.64 (2.32, 28.96)	⨁◯◯◯ Very low
GPx	Very serious a	Serious f	Not serious	Very seriousb,c	None	89/87	92.87 (−404.44, 590.18)	⨁◯◯◯ Very low
MDA	Very serious a	Serious f	Serious d	Seriousb	None	132/133	−1.51 (−2.86, −0.16)	⨁◯◯◯ Very low
SOD	Very serious a	Not serious	Serious d	Seriousb	None	62/62	19.73 (13.35, 26.11)	⨁◯◯◯ Very low
TAC	Very serious a	Serious f	Serious d	Very seriousb,c	None	42/42	−0.44 (−1.88, 0.99)	⨁◯◯◯ Very low
Leptin	Very serious a	Not serious	Serious d	Seriousb	None	38/38	−0.71 (−1.27, −0.15)	⨁◯◯◯ Very low
Heart rate	Very serious a	Serious f	Serious d	Very seriousb,c	None	76/44	−0.90 (−4.08, 2.28)	⨁◯◯◯ Very low

Footprint: ALP Alkaline Phosphatase, ALT Alanine Aminotransferase, AST Aspartate Aminotransferase, BF Body Fat, BFM Body Fat Mass, BMI Body Mass Index, BUN Blood Urea Nitrogen, CAT Catalase, CI Confidence Interval, DBP Diastolic Blood Pressure, FBG Fasting Blood Glucose, GGT Gamma-Glutamyl Transferase, HbA1c Hemoglobin A1C, HC Hip Circumference, HDL-C High-Density Lipoprotein Cholesterol, HOMA-IR Homeostatic Model Assessment of Insulin Resistance, hs-CRP High-Sensitivity C-Reactive Protein, INT Intervention Group, LDH Lactate Dehydrogenase, LDL-C Low-Density Lipoprotein Cholesterol, MDA Malondialdehyde, SBP Systolic Blood Pressure, WMD Weighted Mean Difference, SOD Superoxide Dismutase, TAC Total Antioxidant Capacity, TC Total Cholesterol, TG Triglycerides, WC Waist Circumference, WHR Waist-to-Hip Ratio

Explanations

^aDowngraded since more than 50% of the participants were from high-risk bias studies

^bDowngraded since the participants included were less than 400 people

^cDowngraded since the 95% CI crosses the threshold of interest

^dDowngraded for indirectness in the country

^ePublication Bias was detected through Egger and Begg's test. (p-value < 0.05)

^fThe I² value was > 50% (or Heterogeneity among the studies was high)

Discussion

Summary of findings

In this study, data from 33 trials involving 1,304 participants were pooled and analyzed. The findings indicated that Chlorella supplementation significantly improved BF, BMI, weight, WHR, SBP, HOMA-IR, insulin, hs-CRP, HDL-C, LDL-C, TC, ALT, AST, LDH, CAT, MDA, SOD, and leptin. To the authors’ knowledge, this systematic review and dose–response meta-analysis is the first to employ the GRADE methodology to investigate the effects of Chlorella supplementation on cardiometabolic outcomes in adults.

Chlorella supplementation has been shown to effectively reduce BF, BMI, weight, HOMA-IR, and insulin while improving HDL-C levels, particularly in overweight or obese individuals. The benefits of Chlorella were evident across different dosage forms, durations, and participant characteristics. Notably, doses below 2,000 mg improved BF, BMI, weight, HOMA-IR, insulin, HDL-C, and MDA more significantly, while doses above 2,000 mg strongly affected SBP. Supplementation durations of more than eight weeks were particularly effective for weight, DBP, FBG, HOMA-IR, insulin, HDL-C and MDA, while shorter durations were more effective for BF and BMI. The effects were consistent across various age groups and countries, though studies conducted in Iran showed more pronounced benefits on metabolic markers such as BF, BMI, weight, HOMA-IR, insulin, HDL-C, and MDA compared to those in Japan, which showed greater effects on blood pressure. The observed geographical differences between Iranian and Japanese studies warrant careful consideration. Several factors may contribute to these divergent findings. First, dietary patterns differ substantially between these populations: the traditional Iranian diet is characterized by higher consumption of refined carbohydrates, red meat, and saturated fats, potentially creating a metabolic milieu more responsive to Chlorella's lipid-modulating and insulin-sensitizing effects. In contrast, the traditional Japanese diet, rich in fish, fermented foods, and vegetables may confer baseline cardiometabolic protection, leaving less room for metabolic improvement but potentially greater sensitivity to blood pressure modulation. Second, genetic polymorphisms in genes regulating lipid metabolism, antioxidant enzymes, and inflammatory responses differ between East Asian and Middle Eastern populations, potentially influencing individual responses to Chlorella's bioactive compounds. Third, the baseline health status differed substantially: Iranian studies predominantly enrolled overweight/obese individuals with metabolic dysfunction, whereas Japanese studies more frequently included individuals with borderline hypertension or normal weight, which may explain the preferential effects on metabolic versus cardiovascular parameters, respectively. Fourth, methodological variations exist, including differences in commonly used Chlorella species (C. vulgaris predominating in Iranian studies versus C. pyrenoidosa more common in Japanese research), preparation methods, and supplement formulations. Finally, environmental factors such as ambient temperature, physical activity patterns, and stress levels differ between these regions. These multifactorial differences underscore the complexity of translating Chlorella supplementation effects across diverse populations and highlight the importance of population-specific research to optimize therapeutic recommendations.

Chlorella species, particularly C. vulgaris and C. pyrenoidosa, were effective in reducing liver enzymes (ALT and AST) and TC. C. vulgaris was particularly advantageous for BF, BMI, weight, HOMA-IR, and insulin reduction and elevating HDL-C. Significant reductions in LDL-C and TC were observed in both healthy and overweight/obese participants, while liver enzyme levels (ALT and AST) were significantly reduced among healthy individuals and those with chronic diseases. When combined with exercise, Chlorella supplementation led to an increase in HDL-C levels, underscoring the importance of combined interventions for optimizing cardiovascular health. Gender differences were also identified, with reductions in weight, FBG, HOMA-IR, and insulin observed exclusively in males, along with increases in HDL-C.

Comparison with previous studies

Our findings are consistent with previous research demonstrating hypoglycemic, hypolipidemic, anti-inflammatory, and antioxidant effects of Chlorella spp., as well as their role in promoting weight loss and enhancing liver function [35, 41, 45, 49, 51]. However, discrepancies with some studies may arise from variations in study designs, methodologies, or population characteristics. For example, Hosseini et al. reported no significant changes in HDL-C, LDL-C, TC, TG, fasting blood glucose, HbA1c, insulin levels, or insulin resistance after 8 weeks of supplementation with C. vulgaris (1500 mg/day) in patients with T2DM [44]. In contrast, another study noted significant reductions in cardiovascular risk factors, including serum TC, LDL-C, non-HDL-C, and the LDL-C/HDL-C, alongside an increase in uric acid levels after administering 15 g/day of C. pyrenoidosa to healthy participants for two weeks [49].

Contrary to our results, Karbalamahdi et al. found that administering 1200 mg of C. vulgaris to overweight and obese individuals for two months did not significantly affect body weight, BMI, or leptin levels. This may be attributed to the shorter duration and lower dosage of supplementation [15]. Conversely, a randomized controlled trial (RCT) by Mizoguchi et al. reported that consuming 40 tablets/day of C. vulgaris for four months significantly reduced BF percentage, serum TC, and fasting blood sugar levels [52]. Similarly, Mandoulakani et al. demonstrated that combining 300 mg of Chlorella supplementation with interval training significantly increased TAC and decreased MDA, WHR, and BF. This suggests that Chlorella, when combined with exercise, may alleviate oxidative stress associated with obesity [53]. Furthermore, another study revealed that supplementing with C. vulgaris for over two months or at doses exceeding 4000 mg/day significantly reduced both systolic and diastolic blood pressure in hypertensive patients [54]. In diabetic and pre-diabetic patients, one year of Chlorella supplementation was associated with decreased leptin levels [55]. Interestingly, an animal study using Parachlorella beijerinckii, another algae-derived supplement, demonstrated decreased leptin levels in overweight and obese mice [56]. However, other studies reported that C. vulgaris was ineffective in lowering leptin levels in both obese mice and women [15, 57]. These inconsistencies may stem from differences in study design, such as the use of human vs. animal models, variations in participant health status, study duration, dosage, or the specific strain of Chlorella used.

In animal studies, results have also been inconsistent. Mello-Sampayo et al. observed no significant changes in FBG, glucose tolerance, or blood pressure in mice and rats supplemented with C. vulgaris, suggesting that C. vulgaris microalgae may serve as a beneficial carotenoid source with potential human health advantages [58]. Conversely, Mehdinezhad et al. reported that C. vulgaris supplementation at 50 g/kg/day significantly altered body weight and blood sugar levels in diabetic rats, although levels of hs-CRP, an inflammation marker, remained largely unchanged [59]. Additionally, Renju et al. demonstrated that lycopene extracted from Chlorella marinaga significantly reduced fatty liver in rats on a high-cholesterol diet compared to a standard drug, while also exerting potent anti-inflammatory and antioxidant effects, underscoring its therapeutic potential in hyperlipidemia [60].

Mechanisms of action

Dietary modifications and lifestyle interventions are well-established strategies for preventing cardiovascular diseases (CVD) [40]. Chlorella-enriched smoothies have demonstrated efficacy in improving glycemic control, including reductions in HbA1c, a biomarker associated with increased cardiovascular mortality risk [61]. Chlorella pyrenoidosa, rich in fiber, protein, and vitamins D2 and D3, shows potential in reducing CVD risk. Additionally, Chlorella’s high antioxidant content, particularly flavonoids, may enhance insulin sensitivity by modulating glucose uptake and insulin levels [40, 45]. The combination of fibers, carotenoids, and phytosterols in Chlorella contributes to improvements in fasting glucose, HbA1c, cholesterol, TG, and blood pressure [54]. Specifically, Chlorella vulgaris reduces TG by improving insulin sensitivity, limiting lipogenesis, and decreasing free fatty acids [42]. Phytosterols in Chlorella help lower blood cholesterol by reducing intestinal absorption and modifying cholesterol metabolism, an effect likely driven by the synergistic action of bioactive compounds, including phytosterols, fiber, and carotenoids [62, 63]. Moreover, Chlorella vulgaris, with its rich content of lutein, zeaxanthin, and beta-carotene, may reduce LDL-C by decreasing LDL-C receptors on cell membranes, inhibiting cholesterol synthesis, and enhancing LDL-C clearance by macrophages [33, 45].

Furthermore, chlorophyll in Chlorella not only aids in reducing BFM and weight by inhibiting adipogenesis, but also promotes the conversion of white fat into brown fat, which increases energy expenditure. This dual mechanism supports fat reduction and overall metabolic health [9]. The antioxidant properties of chlorophyll may also mitigate inflammation, modulate adipogenesis, and regulate adipocyte metabolism, further supporting weight management in individuals with metabolic disorders [64]. Polyphenolic compounds such as epigallocatechin gallate and flavones present in Chlorella exhibit anti-adipogenic effects by inhibiting preadipocyte differentiation, contributing to reduced fat accumulation and promoting healthier body composition [65]. Additionally, Chlorella’s positive impact on liver function likely plays a role in weight regulation by supporting fat metabolism and detoxification processes [35]. Improved insulin sensitivity further enhances glucose regulation, reducing fat accumulation and promoting weight loss [66].

Although the exact mechanisms underlying Chlorella’s effects on liver enzymes remain unclear, it appears that reductions in BF contribute to improvements in liver enzyme levels. This relationship is likely mediated by enhanced insulin sensitivity, which helps restore normal liver function [35, 67]. Decreasing BF leads to significant changes in liver enzyme profiles, further normalizing liver function [66].

Leptin, an adipokine critical for regulating appetite and energy balance, correlates with BF levels and rises in obesity [68]. Elevated polyphenol levels are associated with an increase in beneficial adipokines, while β-carotene may reduce inflammation by promoting the release of adiponectin from fat cells [50, 69]. Omega-3 fatty acids, known for their anti-inflammatory properties, contribute to higher levels of anti-inflammatory adipokines [70]. As a botanical source of polyunsaturated fatty acids, Chlorella has the potential to enhance adipokine production, further supporting its anti-inflammatory and metabolic benefits.

Numerous studies underscore Chlorella’s antioxidant capacity, which enhances the body's defense against oxidative stress [50]. Chlorella reduces lipid peroxidation by scavenging free radicals and boosting antioxidant defenses, thereby protecting cells from oxidative damage [7]. The polyphenolic compounds in Chlorella also contribute to its anti-inflammatory effects, reducing chronic inflammation and promoting overall health [8]. Additionally, Chlorella is rich in trace minerals, such as selenium, iron, zinc, copper, and manganese, which are essential for the enzymatic activities of GPX, SOD, and CAT, all of which mitigate oxidative stress [71]. Chlorella supplementation reduces cellular protein tyrosine phosphatase levels and inhibits protein kinases associated with chronic inflammation, thus helping to reduce inflammatory responses [72]. Studies also suggest that Chlorella inhibits phospholipase 2 and glutathione S-transferase while suppressing cyclooxygenase and thromboxane A2 activity, resulting in reduced inflammatory markers [51, 73]. Moreover, Chlorella vulgaris’s potential antihypertensive effects may stem from its high levels of omega-3 fatty acids, potassium, and carotenoids, which offer antioxidant and anti-inflammatory benefits, helping to lower blood pressure by reducing vasculartHIS stiffness [44, 74].

Safety and tolerability considerations

While our meta-analysis demonstrates beneficial cardiometabolic effects of Chlorella supplementation, comprehensive clinical evaluation requires careful consideration of safety concerns. The limited safety reporting in our included studies represents a significant evidence gap, as systematic adverse event monitoring was rarely implemented. Based on broader literature, Chlorella supplementation at typical doses appears generally well-tolerated, with the most common adverse effects being mild, transient gastrointestinal symptoms (nausea, bloating, diarrhea) attributable to high fiber content [7, 8]. However, several critical safety concerns warrant attention. Heavy metal contamination (lead, cadmium, mercury, arsenic) and cyanotoxin exposure (particularly microcystins) represent serious risks, as microalgae can bioaccumulate these toxins from cultivation environments [75, 76 ]. Chronic consumption of contaminated products may lead to hepatotoxicity and other severe health consequences, underscoring the importance of sourcing supplements from manufacturers implementing rigorous quality control with third-party testing [77].

The absence of systematic safety monitoring in most included trials prevents definitive conclusions about adverse event frequency in the populations we evaluated. While available evidence suggests reasonable safety when appropriately sourced and used, the benefits documented in our analysis must be weighed against potential contamination risks, drug interactions, and the limitations of current safety data on an individual patient basis.

Clinical implications

The findings of this meta-analysis suggest that Chlorella supplementation may serve as a useful adjunctive intervention for cardiometabolic health management, particularly in overweight and obese individuals. The observed reductions in body weight, BMI, body fat, insulin resistance, and insulin levels, alongside improvements in lipid profile and liver enzymes, represent clinically meaningful improvements when considered collectively. Our dose–response analyses indicate that lower doses (< 2000 mg/day) are optimal for weight management and metabolic improvements, while higher doses (≥ 2000 mg/day) are more effective for blood pressure reduction. Treatment durations exceeding 8 weeks appear necessary to maximize benefits for weight loss, blood pressure control, and insulin sensitivity.

Based on these findings, clinicians may consider recommending Chlorella vulgaris supplementation, preferably in capsule form, as part of comprehensive lifestyle modification programs for patients with mild dyslipidemia, borderline hypertension, or early insulin resistance. The combination of Chlorella with exercise training demonstrated enhanced benefits for insulin resistance and HDL-C levels in our subgroup analyses, supporting an integrative approach. However, Chlorella should complement rather than replace established dietary modifications, physical activity, and pharmacological interventions when indicated. The consistent improvements across multiple cardiovascular risk factors, including inflammation and oxidative stress markers suggest potential benefits beyond individual parameter improvements, though long-term clinical outcomes require further investigation.

Strengths and limitations

This study tried to address the limitations of a prior meta-analysis [54] on Chlorella supplementation in order to provide a more accurate estimation of the effect size. The previous meta-analysis lacked a transparent search strategy and did not adhere to standard reporting guidelines such as PRISMA, resulting in findings that are difficult to reproduce. Additionally, several relevant studies were omitted [22, 30, 34, 78–80], which should have been considered in the referred meta-analysis. There were also errors in some included studies, where intervention group received substances other than Chlorella, such as vitamin E [81, 82 ] and atorvastatin [83]. These confounding variables were not accounted for, thereby making it impossible to attribute the results solely to Chlorella. Further inaccuracies in sample size reporting [23] and misclassification of study durations [84] compromised the statistical validity of the previous meta-analysis. To address these concerns, our review employed a comprehensive search strategy, corrected the misreporting of interventions, and applied the rigorous GRADE criteria to ensure the accuracy and reliability of the evidence. This updated analysis provides a more precise understanding of the clinical effects of Chlorella spp. on a wide range of health-related indices.

A major strength of this meta-analysis is its rigorous methodology. By strictly following the PRISMA guidelines and registering the protocol with PROSPERO, we ensured transparency and reproducibility throughout the process. Our comprehensive search strategy, which included multiple databases and manual reference screening, minimized the risk of missing key studies. Additionally, the use of the GRADE framework enhanced credibility by assessing the quality and consistency of the evidence. Advanced statistical techniques, such as meta-regression and dose–response analysis, allowed us to explore the effects of Chlorella supplementation across diverse populations, providing insights into optimal dosing and treatment durations. The absence of language restrictions and the inclusion of studies published in all languages further enhanced the comprehensiveness of our analysis, allowing us to draw from a broader range of data. Notably, we addressed a gap in the literature by examining different species of Chlorella including C. vulgaris, C. pyrenoidosa, and C. regularis, in our subgroup analyses. Moreover, our inclusion criteria were broad, with no restrictions on publication dates, and all studies followed controlled trials designs, bolstering the robustness of our conclusions.

Despite these strengths, several important limitations must be acknowledged. The geographical concentration of included studies, predominantly from Asia, with only one European study and no representation from North America or Africa, substantially limits the generalizability of findings to populations with different genetic backgrounds, dietary patterns, and healthcare systems. The relatively short intervention durations in most trials preclude definitive conclusions about long-term efficacy and safety, particularly regarding sustained cardiometabolic benefits and potential adverse effects with prolonged use. While the random-effects model accounted for variability, residual confounding factors may still be present. Although we made extensive efforts to minimize publication bias through robust search methods and statistical tests, funnel plot asymmetry and significant Egger's tests for several outcomes suggest that studies with null or negative findings may be underrepresented in the literature, potentially inflating effect estimates.

An important inherent limitation is the predominance of poor-quality primary studies in this field. Only three of the 33 included trials were rated as having fair quality, with the remainder classified as poor quality due to inadequate randomization procedures, lack of allocation concealment, or insufficient blinding. This widespread quality issue is not a limitation of our review methodology but rather reflects the current state of Chlorella supplementation research. Consequently, outcomes with low or very low certainty of evidence according to GRADE assessment, including inflammatory markers, oxidative stress parameters, and several liver function tests should be interpreted with particular caution. Furthermore, substantial heterogeneity exists in Chlorella products across studies, including variations in species (C. vulgaris, C. pyrenoidosa, C. regularis), manufacturing processes, standardization methods, and formulations (tablets, capsules, pills, extracts), which may significantly influence bioavailability and therapeutic effects. We could not systematically account for differences in product quality, purity, bioactive compound concentrations, or manufacturing standards between producers, as this information was rarely reported in primary studies, representing an important unmeasured confounder. Additionally, patient compliance and adherence were inconsistently monitored and reported across trials, introducing potential performance bias in effect estimates. The reliance on different laboratory methods and kits across studies to assess cardiovascular outcomes introduces measurement variability that could affect result interpretation. These methodological limitations underscore the critical need for rigorously designed, adequately powered, long-term, multi-center randomized controlled trials with proper allocation concealment, double-blinding, standardized Chlorella preparations from verified manufacturers, systematic adverse event monitoring, objective compliance measures, and intention-to-treat analysis to establish definitive evidence for Chlorella's effects on cardiometabolic health before clinical recommendations can be definitively established.

Future research directions

Future research should prioritize long-term, multi-center randomized trials to evaluate Chlorella’s effects on metabolic and cardiovascular health more thoroughly. This meta-analysis provides valuable insights that can guide the design of these studies, which should include larger sample sizes and longer intervention durations to produce more reliable results. Trials should also incorporate more diverse populations to enhance the generalizability of findings. Further exploration of the dose–response relationship is essential to identify the most effective dosage and duration of Chlorella supplementation (Fig. 2).

Fig. 2.

Future research directions and priority gaps for Chlorella supplementation in metabolic and cardiovascular health

Although most research has focused on Chlorella’s effects on glycemic control, its potential protective effects on liver and kidney health remain relatively unexplored. Future studies should delve into specific plant components and their distinct health impacts, while investigating the molecular mechanisms underlying Chlorella’s benefits. Advanced techniques in molecular biology and omics could help identify bioactive compounds and their interactions with other dietary components. Additionally, research on Chlorella’s influence on gut microbiota, inflammation, and oxidative stress could provide further insight into its role in managing metabolic and cardiovascular conditions. Finally, integrating Chlorella into functional foods may be a promising approach to support health promotion; however, further high-quality clinical trials are needed before providing evidence-based dietary recommendations.

Conclusion

This meta-analysis demonstrated that Chlorella supplementation significantly benefits cardiovascular and metabolic health by reducing BF, BMI, LDL-C, TC, and liver enzyme levels, while improving insulin sensitivity, HDL-C, and antioxidant status. Lower doses appear to be more effective for weight reduction, whereas higher doses are associated with improved blood pressure. Chlorella's effects vary based on species, dosage, and participant characteristics, with additional benefits observed when combined with exercise. Despite some inconsistencies, our findings align with prior research on Chlorella's hypoglycemic and anti-inflammatory properties. While this analysis has some limitations, further long-term studies are needed to optimize the clinical application of Chlorella spp. Overall, Chlorella appears to be a promising supplement for enhancing cardiometabolic health and may warrants consideration in dietary interventions.

Abbreviations

ALP

Alkaline Phosphatase

ALT

Alanine Aminotransferase

AST

Aspartate Aminotransferase

BF

Body Fat

BFM

Body Fat Mass

BMI

Body Mass Index

BUN

Blood Urea Nitrogen

CAT

Catalase

CI

Confidence Interval

CVD

Cardiovascular Disease

DBP

Diastolic Blood Pressure

FBG

Fasting Blood Glucose

GGT

Gamma-Glutamyl Transferase

GPx

Glutathione Peroxidase

HbA1c

Glycated Hemoglobin

HC

Hip Circumference

HDL-C

High-Density Lipoprotein Cholesterol

HOMA-IR

Homeostatic Model Assessment of Insulin Resistance

hs-CRP

High-Sensitivity C-Reactive Protein

HTN

Hypertension

LDH

Lactate Dehydrogenase

LDL-C

Low-Density Lipoprotein Cholesterol

MDA

Malondialdehyde

NAFLD

Non-Alcoholic Fatty Liver Disease

PRISMA

Preferred Reporting Items for Systematic Reviews and Meta-Analyses

PROSPERO

International Prospective Register of Systematic Reviews

RCT

Randomized Controlled Trial

SBP

Systolic Blood Pressure

SOD

Superoxide Dismutase

T2DM

Type 2 Diabetes Mellitus

TAC

Total Antioxidant Capacity

TC

Total Cholesterol

TG

Triglycerides

WC

Waist Circumference

WHR

Waist-to-Hip Ratio

WMD

Weighted Mean Difference

Authors’ contributions

Conceptualization: Ali Jafari. Data curation: Ali Jafari, Helia Mardani, Niloufar Rasaei. Formal analysis: Ali Jafari, Amirhossein Sahebkar. Investigation: Ali Jafari, Helia Mardani, Niloufar Rasaei, Bahare Parsi Nezhad, Amirhossein Sahebkar. Methodology: Ali Jafari, Amirhossein Sahebkar. Project administration: Ali Jafari, Amirhossein Sahebkar. Software: Ali Jafari, Helia Mardani, Amirhossein Sahebkar. Visualization: Ali Jafari, Bahare Parsi Nezhad. Supervision: Ali Jafari, Amirhossein Sahebkar. Validation: Ali Jafari, Helia Mardani, Bahare Parsi Nezhad, Amirhossein Sahebkar. Writing – original draft: Ali Jafari, Niloufar Rasaei, Bahare Parsi Nezhad. Writing – review & editing: Ali Jafari, Helia Mardani, Bahare Parsi Nezhad, Amirhossein Sahebkar.

Funding

This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors.

Data availability

All relevant data are provided within the manuscript and supplementary file. Additionally, data analyzed for this study are available upon request from the corresponding author.

Declarations

Ethics approval and consent to participate

As a systematic review and meta-analysis, this manuscript did not necessitate review by our institutional clinical ethics committee.

Consent for publication

Not applicable.

Competing interests

Ali Jafari holds an editorial position on the board of Systematic Reviews. The remaining authors report no connections or participation with any organizations or entities that could present a financial interest (such as honoraria, educational funding, speaker bureau involvement, memberships, employment, consulting roles, stock or equity ownership, expert testimony, or patent-licensing agreements) or a non-financial interest (including personal or professional relationships, affiliations, expertise, or beliefs) that might be relevant to the topic or materials addressed in this manuscript.