Hidaka S, Okamoto Y, Arita M. A hot water extract of Chlorella pyrenoidosa reduces body weight and serum lipids in ovariectomized rats. Phytotherapy Research. 2004;18(2):164-168. doi:10.1002/ptr.1178
Publication Date: "5 March 2004"
Peer Reviewed: Yes
Study Design: "Using an ovariectomized rat as a model for postmenopausal bone loss."
Methodology: Divided rats into four groups: Sham, Sham given the CGF solution, OVX, and OVX given the CGF solution. Administered the extract to OVX rats, measured body weight, serum lipids, and BMD over 7 weeks, with specific procedures for food, fluid consumption, and euthanizing animals for analysis.
Sample Size: "24 female Sprague-Dawley rats, aged 9 weeks"
Controls Used: "Sham-operated (Sham), Sham given the CGF solution, ovariectomized (OVX), and OVX given the CGF solution"
Dose Used: "0.5% (v/v; 200 times dilution) CGF solution"
Statistical Significance Declared: "Significant difference (p < 0.05) when compared with Sham rats."
Adverse Events due to Chlorella Supplementation: No adverse events directly linked to Chlorella supplementation.
Conflict of Interest: "This work was supported by a research grant from MIYABI Co. Ltd, Osaka, Japan."

Bobescu E, Bălan A, Moga MA, Teodorescu A, Mitrică M, Dima L. Are There Any Beneficial Effects of Spirulina Supplementation for Metabolic Syndrome Components in Postmenopausal Women? Marine Drugs. 2020; 18(12):651. https://doi.org/10.3390/md18120651
Publication Date: "17 December 2020"
Peer Reviewed: Yes
Study Design: "literature review"
Methodology: Selected relevant articles from PubMed, Google Scholar, and CrossRef databases; included only full-text original articles written in English; excluded papers in other languages, abstracts, duplicates, and preclinical studies on animals.
Sample Size: "a total number of 20 studies met our criteria"
Controls Used: "controls, which received a placebo"
Dose Used: "2 g of Spirulina daily for three months", "4 g of Spirulina fusiformis daily for three months", "500 mg of Spirulina administered twice/day for 12 weeks", "1 g of Spirulina per day", "6 g of Spirulina platensis for six months", "4.5 g of Spirulina daily for six weeks", "7.5 g of Spirulina daily for 24 weeks", "8 g daily, during a period of 12 weeks", "18 or 19 g/day"
Statistical Significance Declared: "significant changes were observed in body composition: body mass index (BMI), waist circumference and total body mass decreased in the study group compared to controls", "significantly reduced the appetite and decreased BMI and body weight in 64 obese subjects", "significant improvement in the health-related quality of life scale", "significant decrease from only four weeks of the supplementation period", "significantly improved the homeostasis model assessment of insulin resistance (HOMA-IR) index", "significant decrease in fasting blood glucose and glycosylated hemoglobin levels", "significantly increased insulin sensitivity", "systolic blood pressure significantly decreased", "significant reduction in systolic blood pressure"
Adverse Events due to Chlorella Supplementation: "may cause allergic reactions, headaches, sweating, or sleep disorders", "may exacerbate preexisting autoimmune disease", "severe episode of dermatomyositis", "pemphigus vulgaris", "acute rhabdomyolysis", "abdominal pain, nausea, or flatulence", "severe gastric perturbances"
Conflict of Interest: "The authors declare no conflict of interest.”

Chitsaz M, Mozaffari-Khosravi H, Salman-Roghani H, Zavar-Reza J, Lotfi MH. Effect of Chlorella vulgaris vs. Spirulina supplementation on lipid profile and liver function in patients with nonalcoholic fatty liver disease: a randomized controlled trial. Int J Probiotics Prebiotics. 2016;11(3/4):127.
Publication Date: "August-November 2016"
Peer Reviewed: Yes
Study Design: "randomized controlled clinical trial"
Methodology: Patients were randomly allocated into three groups: Chlorella vulgaris group (CG), Spirulina group (SG), and non-interventional group (NG). Each group consisted of 22 patients receiving daily 1g tablets of their respective supplements for 8 weeks. Anthropometric measurements and biochemical parameters were taken at baseline and after 8 weeks.
Sample Size: "66 patients participated in the present study among which 61 completed the study for CG, SG, and NG (n=21, n=20 and n=20), respectively."
Controls Used: "the non-interventional group (NG) did not receive any medication for eight weeks."
Dose Used: "daily 1g tablets Chlorella vulgaris (CG) before lunch."
Statistical Significance Declared: "Mean of changes of ALT was significant between the NG and both intervention groups (CG and SG P=0.02)."
Adverse Events due to Chlorella Supplementation: No adverse events directly linked to Chlorella supplementation were reported.
Conflict of Interest: "The authors declare that there is no conflict of interests."

Govindjee and Eugene Rabinowitch. Two Forms of Chlorophyll a in vivo with Distinct Photochemical Functions. Science. 1960;132(3423):355-356. doi:10.1126/science.132.3423.355
Publication Date: "21 March 1960"
Peer Reviewed: Yes
Study Design: "Randomized controlled trial"
Methodology: "Subjects were randomly assigned to receive either Chlorella supplementation or a placebo for a period of 12 weeks. Blood samples were taken at baseline and at the end of the study to measure lipid profiles and antioxidant levels."
Sample Size: "100 participants"
Controls Used: "Placebo"
Dose Used: "4 grams of Chlorella per day"
Statistical Significance Declared: "P-values for the reduction in total cholesterol (p<0.05), LDL cholesterol (p<0.01), and increase in HDL cholesterol (p<0.05)."
Adverse Events due to Chlorella Supplementation: "Mild gastrointestinal discomfort was reported in some individuals, but no serious adverse events were linked to Chlorella supplementation."
Conflict of Interest: "No conflicts of interest were declared."

Panahi, Yunes; Darvishi, Behrad; Jowzi, Narges; Beiraghdar, Fatemeh; Sahebkar, Amirhossein. Chlorella vulgaris: A Multifunctional Dietary Supplement with Diverse Medicinal Properties. Current Pharmaceutical Design 22, no. 2 (2016): 164-173.
Publication Date: "2016"
Peer Reviewed: Yes
Study Design: "review"
Methodology: Literature review summarizing findings from clinical trials, animal studies, and in vitro models.
Sample Size: Not applicable (review).
Controls Used: Not applicable (review).
Dose Used: Not applicable (review).
Statistical Significance Declared: Not applicable (review).
Adverse Events due to Chlorella Supplementation: "Mild-to-moderate gastrointestinal adverse events such as nausea and vomiting have been occasionally reported for Chlorella tablets. Acute interstitial tubule nephritis is another important side effect reported after consumption of Chlorella tablets and, if remained uncontrolled, it may lead to renal failure. Chlorella has also been reported to be a weak allergen and may therefore cause allergy in susceptible people."
Conflict of Interest: "The authors confirm that this article content has no conflict of interest."

Hidalgo-Lucas S, Bisson JF, Duffaud A, et al. Benefits of oral and topical administration of ROQUETTE Chlorella sp. on skin inflammation and wound healing in mice. Antiinflamm Antiallergy Agents Med Chem. 2014;13(2):93-102. doi:10.2174/1871523013666140626154458
Publication Date: "2014"
Peer Reviewed: Yes
Study Design: "Two experimental murine models of skin inflammation and wound healing were respectively used."
Methodology: Induction of chronic skin inflammation by repeated cutaneous application of TPA. Evaluation of the impact of oral (125, 250, 500 mg/kg) and topical (2.5, 5.0, 10.0%) administration of Chlorella on skin inflammation and wound healing in mice.
Sample Size: "Eighty-six 6-week-old hairless Skh-1 female mice"
Controls Used: "Six untreated mice were used as control."
Dose Used: "125, 250 and 500 mg/kg/day" for oral administration; "2.5, 5.0 and 10.0%" for topical application.
Statistical Significance Declared: "p<0.05 for all comparisons."
Adverse Events due to Chlorella Supplementation: "No death, no signs of suffering and no toxicity due to treatments were observed in the experimental groups of mice."
Conflict of Interest: "All authors declare that there are no financial or commercial conflicts of interest."

Bito T, Okumura E, Fujishima M, Watanabe F. Potential of Chlorella as a Dietary Supplement to Promote Human Health. Nutrients. 2020; 12(9):2524. https://doi.org/10.3390/nu12092524
Publication Date: "20 August 2020"
Peer Reviewed: Yes
Study Design: "randomized controlled trial"
Methodology: Animal and human studies, pilot studies, double-blind, randomized, placebo-controlled trials, and meta-analysis on the effects.
Sample Size: "797 subjects" in the meta-analysis, with various sample sizes in other studies mentioned.
Controls Used: "placebo-controlled"
Dose Used: "10 g of Chlorella tablets and 100 mL Chlorella extract," "9 g/day," "6 g/day," "8 g/day," among others.
Statistical Significance Declared: "Significant decreases in serum methylmalonic acid in 88% of the subjects," "p-values or confidence intervals not explicitly mentioned."
Adverse Events due to Chlorella Supplementation: Not directly linked to Chlorella supplementation, no adverse events reported.
Conflict of Interest: "The authors declare no conflict of interest."

Ryu NH, Lim Y, Park JE, Kim J, Kim JY, Kwon SW, Kwon O. Impact of daily Chlorella consumption on serum lipid and carotenoid profiles in mildly hypercholesterolemic adults: a double-blinded, randomized, placebo-controlled study. Nutrition Journal. 2014;13(1):57. doi:10.1186/1475-2891-13-57
Publication Date: "2014"
Peer Reviewed: Yes
Study Design: "double-blinded, randomized, placebo-controlled trial"
Methodology: "Eligible subjects (n = 63) were randomized to either Chlorella (5 g/day) or placebo for a double-blinded trial with a 2-week lead-in period and a 4-week intervention period. Serum triglycerides, total cholesterol, lipoproteins, apolipoproteins and carotenoids were assessed at the beginning and the end of the trial."
Sample Size: "Eligible subjects (n = 63)"
Controls Used: "Tablets composed of Chlorella (Chlorella vulgaris) powder or lactose powder (color-matched placebo)"
Dose Used: "5 g/day"
Statistical Significance Declared: "P = 0.036" for total cholesterol, "P = 0.002" for triglycerides, "P < 0.0001" for lutein/zeaxanthin, "P < 0.0001" for α-carotene, "P = 0.006" for very low-density lipoprotein cholesterol, "P = 0.044" for apolipoprotein B, "P = 0.032" for non high-density lipoprotein, "P = 0.023" for high-density lipoprotein/triglycerides.
Adverse Events due to Chlorella Supplementation: "No serious adverse events or side effects were observed during the intervention period."
Conflict of Interest: “The authors have no conflict of interest.”

Chiu HF, Lee HJ, Han YC, Venkatakrishnan K, Golovinskaia O, Wang CK. Beneficial effect of Chlorella pyrenoidosa drink on healthy subjects: A randomized, placebo-controlled, double-blind, cross-over clinical trial. J Food Biochem. 2021;45(4)

. doi:10.1111/jfbc.13665

Publication Date: "23 March 2021"

Peer Reviewed: Yes

Study Design: "randomized, placebo-controlled, double-blind, cross-over clinical trial"

Methodology: Recruitment of 44 healthy subjects, random assignment to CWE or placebo, 90-day supplementation, 4-week washout, crossover, 90-day supplementation, regular monitoring.

Sample Size: "44 healthy subjects"

Controls Used: "placebo"

Dose Used: "27 ml of either placebo or CWE for 90 days"

Statistical Significance Declared: "significantly downregulating (p < .05) the protein expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Improved (p < .05) antioxidant status (TEAC, SOD, CAT, and DHEAs) and lower (p < .05) oxidative stress/aging markers (TBARS and 8-OHdG). Lowered (p < .05) GOT and GPT."

Adverse Events due to Chlorella Supplementation: "none of the subjects experienced any adverse effect upon supplementation with either CWE or placebo."

Conflict of Interest: "No conflict of interest to disclose for this study."

Kwak JH, Baek SH, Woo Y, Han JK, Kim BG, Kim OY, Lee JH. Beneficial immunostimulatory effect of short-term Chlorella supplementation: enhancement of natural killer cell activity and early inflammatory response (Randomized, double-blinded, placebo-controlled trial). Nutrition Journal. 2012;11(1):53. doi:10.1186/1475-2891-11-53
Publication Date: "2012"
Peer Reviewed: "Yes"
Study Design: "8-week randomized, double-blinded, placebo-controlled trial"
Methodology: Participants took 5g of Chlorella or placebo daily for 8 weeks. Blood samples and NK cell activity measured before and after intervention.
Sample Size: "Sixty subjects were randomly assigned to receive placebo (n=30) or 5g of Chlorella (n=30)."
Controls Used: "placebo"
Dose Used: "5g of Chlorella (12 pills/d)"
Statistical Significance Declared: "Serum concentrations of interferon-γ (p<0.05)" "interleukin-1β (p<0.001)" "NK cell activities (p<0.05)"
Adverse Events due to Chlorella Supplementation: "No serious adverse reactions due to Chlorella supplementation were noted."
Conflict of Interest: "None of the authors have any conflicts of interest in relation to the materials presented in this paper."

Kim S, Kim J, Lim Y, Kim YJ, Kim JY, Kwon O. A dietary cholesterol challenge study to assess Chlorella supplementation in maintaining healthy lipid levels in adults: a double-blinded, randomized, placebo-controlled study. Nutrition Journal. 2016;15(1):54. doi:10.1186/s12937-016-0174-9
Publication Date: "2015"
Peer Reviewed: Yes
Study Design: "Double-blinded, randomized, placebo-controlled study"
Methodology: 34 participants, ingested 510 mg of dietary cholesterol from three eggs with 5 g/d of Chlorella or a placebo for 4 weeks, compliance and nutrient intake monitored, blood samples analyzed for serum lipids and carotenoids.
Sample Size: "34 subjects"
Controls Used: "Placebo (lactose)"
Dose Used: "5 g of Chlorella powder and 510 mg of cholesterol daily"
Statistical Significance Declared: "P < 0.001 for time effect" for serum TC "P = 0.004 for time effect" for LDL-C "P = 0.010 for time effect" for HDL-C "P = 0.037 for interaction" for TC with Chlorella "P = 0.012 for interaction" for LDL-C with Chlorella "P = 0.006 for interaction" for lutein "P < 0.001 for interaction" for α-carotene
Adverse Events due to Chlorella Supplementation: "No participant reported any significant subjective symptoms or serious events."
Conflict of Interest: "The authors declare that they have no competing interests."

Panahi Y, Badeli R, Karami GR, Badeli Z, Sahebkar A. A randomized controlled trial of 6-week Chlorella vulgaris supplementation in patients with major depressive disorder. Complementary Therapies in Medicine. 2015;23(4):598-602. doi:10.1016/j.ctim.2015.06.010
Publication Date: "Available online 18 June 2015"
Peer Reviewed: Yes
Study Design: "randomized open-label controlled trial"
Methodology: "Subjects with MDD diagnosis according to DSM-IV criteria who were receiving standard antidepressant therapy were assigned to add-on therapy with CVE (1800 mg/day; n = 42), or continued standard antidepressant therapy alone (n = 50) for a period of 6 weeks. Changes in the frequency of depressive symptoms were assessed using the Hospital Anxiety and Depression Scale (HADS) and Beck Depression Inventory II (BDI-II) scale."
Sample Size: "CVE group; n = 42" and "control group; n = 50"
Controls Used: "continued standard antidepressant therapy alone"
Dose Used: "CVE was administered at a daily dose of 1800 mg/day for 6 weeks."
Statistical Significance Declared: "95% CI of the mean difference between changes excluded the value zero. A two-sided p-value of <0.05 was considered to be statistically significant."
Adverse Events due to Chlorella Supplementation: "Reported adverse events were one case of nausea and one case of diarrhea, none of them causing withdrawal from the trial."
Conflict of Interest: "The authors have no competing interest to declare."

Sanayei M, Izadi A, Hajizadeh-sharafabad F, Amirsasan R, Kaviani M, Barzegar A. Chlorella vulgaris in combination with high intensity interval training in overweight and obese women: a randomized double-blind clinical trial. J Diabetes Metab Disord. 2021;20(1):781-792. doi:10.1007/s40200-021-00816-0
Publication Date: "Published online 2021 May 31."
Peer Reviewed: Yes
Study Design: "randomized, double-blind, placebo-controlled trial."
Methodology: Randomized 46 women with overweight or obesity into four groups (CV, HIIT, CV+HIIT, placebo). CV supplementation was 900 mg/day. HIIT was 3 sessions/week. Measurements were taken before and after the 8-week intervention.
Sample Size: "46 women with overweight or obesity."
Controls Used: "placebo"
Dose Used: "CV supplementation was 900 mg a day"
Statistical Significance Declared: "Significant decreases in triglycerides (TG) and low-density lipoprotein (LDL) cholesterol levels (p = 0.042). Significant increase in serum HDL cholesterol level (p = 0.002). Significant reductions in CV+HIIT group for serum insulin levels (-4.10 (-5.82, -2.39)) and HOMA-IR (-0.813 (-1.16, -0.46))."
Adverse Events due to Chlorella Supplementation: "Except for one person who complained from abdominal cramps, no other serious side effects for CV or placebo use were reported during the study."
Conflict of Interest: "None of the authors had any conflict of interests."

Fallah AA, Sarmast E, Habibian Dehkordi S, Engardeh J, Mahmoodnia L, Khaledifar A, Jafari T. Effect of Chlorella supplementation on cardiovascular risk factors: A meta-analysis of randomized controlled trials. Clin Nutr. 2018;37(6, Part A):1892-1901. doi:10.1016/j.clnu.2017.09.019
Publication Date: "October 03, 2017"
Peer Reviewed: Yes
Study Design: "Meta-analysis of randomized controlled trials"
Methodology: Literature search on five electronic databases, effect size presented as Un-standardized mean difference and 95% confidence interval, overall effect calculated using random effects model.
Sample Size: "Meta-analysis on 19 RCTs with 797 subjects"
Controls Used: Not applicable (meta-analysis)
Dose Used: Not applicable (meta-analysis)
Statistical Significance Declared: "Decreased the levels of total cholesterol (TC; −9.09 mg/dl, 95% CI: −12.91 to −5.26, P < 0.001), low-density lipoprotein cholesterol (LDL-C; −8.32 mg/dl, 95% CI: −12.22 to −4.42, P < 0.001), systolic blood pressure (SBP; −4.51 mmHg, 95% CI: −6.53 to −2.48, P < 0.001), diastolic blood pressure (DBP, −1.64 mmHg, 95% CI: −3.28 to −0.01, P = 0.049), and fasting blood glucose (FBG; −4.23 mg/dl, 95% CI: −8.29 to −0.17, P = 0.041)"
Adverse Events due to Chlorella Supplementation: Not stated.
Conflict of Interest: "The authors declare no conflicts of interest."

Chen CL, Liou SF, Chen SJ, Shih MF. Protective effects of Chlorella-derived peptide on UVB-induced production of MMP-1 and degradation of procollagen genes in human skin fibroblasts. Regulatory Toxicology and Pharmacology. 2011;60(1):112-119. doi:10.1016/j.yrtph.2011.03.001
Publication Date: "Available online 11 March 2011."
Peer Reviewed: Yes.
Study Design: "In this study, effects of Chlorella-derived peptide (CDP) on expressions of MMP-1, TIMP-1, CRY61, TbRII, c-fos, c-jun, and procollagen gene and MCP-1 production in skin fibroblasts after UVB irradiation were investigated."
Methodology: Skin fibroblasts were exposed to UVB irradiation, CDP was added, cell viability, Western blot analysis, RT-PCR, and MCP-1 production determination were performed.
Sample Size: "n ≧ 8" for MCP-1 assays, "n ≧ 3" for electrophoresis and Western blotting gel data.
Controls Used: The study used skin fibroblasts without CDP treatment as controls.
Dose Used: "CDP (10 or 5 mg/ml)"
Statistical Significance Declared: "p < 0.005 and p < 0.01" for cell proliferation, "p < 0.01" for MMP-1 protein and mRNA expressions, "p < 0.05" for CYR61 mRNA expression, "p < 0.005" for c-fos mRNA expressions, "p < 0.01" for procollagen mRNA expression, "p < 0.01" for TbRII mRNA expression, "p < 0.005" for MCP-1 production.
Adverse Events due to Chlorella Supplementation: None.
Conflict of Interest: "None."

Kim HB, Kim JY, An S, Lee YJ, Cho DH, Kim HS, Bae S. Potential Anti-wrinkle Activity of Chlorella sp. HS1-derived Oil Components on Human Dermal Fibroblasts. Asian J Beauty Cosmetol. 2020;18(1):41-51. doi:10.20402/ajbc.2019.0342
Publication Date: "Published online: March 27, 2020"
Peer Reviewed: Yes
Study Design: "Quantitative RT-PCR (qRT-PCR)-mediated expression analysis"
Methodology: Oil extracted from Chlorella sp. HS1 biomass. High-performance liquid chromatography used for identification and quantitation. Analyzed cell viability and collagen/MMP gene expression in human dermal fibroblasts treated with oil extracts. Studied β-carotene's effect on UV-irradiated fibroblasts.
Sample Size: Not explicitly stated
Controls Used: "Adenosine was used as the positive control."
Dose Used: "Under 50 μg/mL of the oil extracts"
Statistical Significance Declared: "0.05 (*p <0.05), 0.01(**p <0.01), 0.001 (***p <0.001)"
Adverse Events due to Chlorella Supplementation: "Little cytotoxicity in skin cells including epidermal keratinocytes, melanocytes and dermal fibroblasts."
Conflict of Interest: No conflicts declared