A review of recent clinical trials of the nutritional supplement Chlorella pyrenoidosa in the treatment of fibromyalgia, hypertension, and ulcerative colitis.
Merchant RE, Andre CA.Virginia Commonwealth University, Medical College of Virginia, Richmond, VA. Altern Ther Health Med. 2001 May-Jun;7(3):79-91

CONTEXT: It has been suggested that the consumption of natural "whole foods" rich in macronutrients has many healthful benefits for those who otherwise ingest a normal, nonvegetarian diet. One example is dietary supplements derived from Chlorella pyrenoidosa, a unicellular fresh water green alga rich in proteins, vitamins, and minerals.

OBJECTIVE: To find evidence of the potential of chlorella dietary supplements to relieve signs and symptoms, improve quality of life, and normalize body functions in people with chronic illnesses, specifically fibromyalgia, hypertension, and ulcerative colitis.

DESIGN: Double-blind, placebo-controlled, randomized clinical trials. SETTING: Virginia Commonwealth University's Medical College of Virginia. PATIENTS: Fifty-five subjects with fibromyalgia, 33 with hypertension, and 9 with ulcerative colitis.

INTERVENTION: Subjects consumed 10 g of pure chlorella in tablet form and 100 ml of a liquid containing an extract of chlorella each day for 2 or 3 months.

MAIN OUTCOME MEASURES: For fibromyalgia patients, assessments of pain and overall quality of life. For hypertensive patients, measurements of sitting diastolic blood pressure and serum lipid levels. For patients with ulcerative colitis, determination of state of disease using the Disease Activity Index.

RESULTS: Daily dietary supplementation with chlorella may reduce high blood pressure, lower serum cholesterol levels, accelerate wound healing, and enhance immune functions.

CONCLUSIONS: The potential of chlorella to relieve symptoms, improve quality of life, and normalize body functions in patients with fibromyalgia, hypertension, or ulcerative colitis suggests that larger, more comprehensive clinical trials of chlorella are warranted.

Publication Types: Clinical Trial, Randomized Controlled Trial

PMID: 11347287 [PubMed - indexed for MEDLINE]

Nutritional supplementation with Chlorella pyrenoidosa for mild to moderate hypertension.
Merchant RE, Andre CA, Sica DA. Department of Anatomy and Internal Medicine, Virginia Commonwealth University, Medical College of Virginia, Richmond, VA, J Med Food. 2002 Fall;5(3):141-52.

Pharmacological treatment of hypertension reduces the risk of cardiovascular disease; however, randomized, controlled clinical trials and population studies have also shown that abnormally high blood pressure (BP) can be lowered with diet modification and exercise. The objective of this pilot study was to determine whether daily dietary supplementation with 10g Chlorella tablets and 100ml Chlorella extract for 2 months would reduce BP in subjects with a mean sitting diastolic BP (SiDBP) between 90 and 115 mm Hg. Thirty-three people were enrolled and underwent a 4-week washout period from all antihypertensive medications, during which they consumed placebo. At completion of this washout/placebo period, 24 subjects were considered evaluable (i.e., had a SiDBP between 90 and 115 mm Hg) and were continued in the study. After 1 or 2 months of dietary Chlorella supplementation, the average heart rate, sitting systolic BP, and SiDBP changed only slightly; after 2 months of Chlorella consumption, the group's mean SiDBP was 96.5 +/- 6.6. However, a heterogeneous response pattern to Chlorella existed, with 25% (6/24) of the subjects achieving their BP goal (SiDBP less than 90 mm Hg). Furthermore, the BP of nonresponders did not increase significantly above washout values. Quality-of-life questionnaires indicated an overall perception that health had significantly improved in conjunction with Chlorella consumption. The results indicate that, for some subjects with mild to moderate hypertension, a daily dietary supplement of Chlorella reduced or kept stable their SiDBP.

PMID: 12495586 [PubMed - indexed for MEDLINE]

Anti-tumour-promoting glyceroglycolipids from the green alga, Chlorella vulgaris.
Morimoto T, Nagatsu A, Murakami N, Sakakibara J, Tokuda H, Nishino H, Iwashima A.
Faculty of Pharmaceutical Sciences, Nagoya City University, Japan. Phytochemistry. 1995 Nov;40(5):1433-7

Two new monogalactosyl diacylglycerols were isolated from the freshwater green alga, Chlorella vulgaris, as anti-tumour promoters, together with three monogalactosyl diacylglycerols and two digalactosyl diacylglycerols. The new monogalactosyl diacylglycerol containing (7Z,10Z)-hexadecadienoic acid showed a more potent inhibitory effect toward tumour promotion than the other glycerolipids isolated.

PMID: 8534400 [PubMed - indexed for MEDLINE]

Isolation of three high molecular weight polysaccharide preparations with potent immunostimulatory activity from Spirulina platensis, aphanizomenon flos-aquae and Chlorella pyrenoidosa.
Pugh N, Ross SA, ElSohly HN, ElSohly MA, Pasco DS. Department of Pharmacognosy, School of Pharmacy, University of Mississippi, University, Mississippi. Planta Med. 2001 Nov;67(8):737-42

This research describes the identification of three new high molecular weight polysaccharide preparations isolated from food-grade microalgae that are potent activators of human monocytes/macrophages: "Immulina" from Spirulina platensis, "Immunon" from Aphanizomenon flos-aquae, and "Immurella" from Chlorella pyrenoidosa. These polysaccharides are structurally complex and have estimated molecular weights above ten million daltons. All three polysaccharides are highly water soluble and comprise between 0.5 % and 2.0 % of microalgal dry weight. Immunostimulatory activity was measured using a transcription factor-based bioassay for nuclear factor kappa B (NF-kappa B) activation in THP-1 human monocytes/macrophages. Using this system the EC(50) values for these microalgal polysaccharides are between 20 and 110 ng/ml (about 10pM). THP-1 activation was confirmed by measuring immune cytokine mRNA induction using reverse transcriptase-polymerase chain reaction (RT-PCR). Each polysaccharide substantially increased mRNA levels of interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha). These polysaccharides are between one hundred and one thousand times more active for in vitro monocyte activation than polysaccharide preparations that are currently used clinically for cancer immunotherapy.

PMID: 11731916 [PubMed - indexed for MEDLINE]

Expression of human growth hormone by the eukaryotic alga, Chlorella.
Hawkins RL, Nakamura M. Future Project Division, Toyota Motor Corporation, 1, Toyota-cho, Toyota, Aichi 471-8572, Japan. Curr Microbiol. 1999 Jun;38(6):335-41

A method to use Chlorella to express a recombinant heterologous protein that can be recovered from the extracellular medium has been developed. Plasmids are constructed with an extracellular secretion signal sequence inserted between a promoter region and a gene for human growth hormone (hGH). The plasmids also contain a Kanr region which confers resistance to the antibiotic G418. Protoplasts are prepared by enzymatic treatment, and the plasmid is introduced by incubation of the protoplasts with polyethylene glycol and dimethyl sulfoxide. Cells are then grown in the presence of G418, and the medium is collected from 6 days after transfection. hGH is measured by immunoassay, and values for expressed hGH of about 200-600 ng/ml are obtained.

PMID: 10341074 [PubMed - indexed for MEDLINE]

Inhibition of mast cells by algae.
Price JA 3rd, Sanny C, Shevlin D. Department of Pathology, Oklahoma State University Center for Health Sciences, Tulsa, OK. J Med Food. 2002 Winter;5(4):205-10

There is a history of use of algae as foods and as food additives, or nutraceuticals. Although algae are a safe component of human foods and animal feeds, the effects of the algae other than as a source of protein are not clear. We examined the prevalence of an anti-inflammatory activity in selected algae using, as an assay system, the inhibition of histamine release from mast cells. Methanolic extracts of eleven algae were examined for activity to inhibit the release of histamine from mast cells in vitro. This activity was found widely among the samples tested. The activities of these extracts were not uniformly stable in acid methanol. Selected extracts studied further did not separate with the use of size-exclusion filtration filters. LH-20 chromatography suggested at least two main elution areas of activity of the Chlorella extract. In summary, we saw wide phylogenetic dispersion of mast cell inhibition activity, suggesting that this anti-inflammatory property is common in algae. This effect was apparently due to multiple activities within the algal extracts.

PMID: 12639395 [PubMed - indexed for MEDLINE]

Characterization and bioavailability of vitamin B12-compounds from edible algae.
Watanabe F, Takenaka S, Kittaka-Katsura H, Ebara S, Miyamoto E. Department of Health Science, Kochi Women's University, Kochi, Japan. J Nutr Sci Vitaminol (Tokyo). 2002 Oct;48(5):325-31

Substantial amounts of vitamin B12 were found in some edible algae (green and purple lavers) and algal health food (chlorella and spirulina tablets) using the Lactobacillus delbrueckii subsp. lactis ATCC7830 microbiological assay method. Corrinoid-compounds were purified and characterized from these algae to clarify the chemical properties and bioavailability of the algal vitamin B12. True vitamin B12 is the predominate cobamide of green and purple lavers and chlorella tablets. Feeding the purple laver to vitamin B12-deficient rats significantly improved the vitamin B12 status. The results suggest that algal vitamin B12 is a bioavailable source for mammals. Pseudovitamin B12 (an inactive corrinoid) predominated in the spirulina tablets, which are not suitable for use as a vitamin B12 source, especially for vegetarians. algal health food, bioavailability, cobalamin, edible algae, vitamin B12

Publication Types: Review, Tutorial

PMID: 12656203 [PubMed - indexed for MEDLINE]

Nutritional supplementation with Chlorella pyrenoidosa for patients with fibromyalgia syndrome
Merchant RE, Carmack CA, Wise CM. Departments of Anatomy and Internal Medicine, Virginia Commonwealth University, Medical College of Virginia Richmond, VA. Phytother Res. 2000 May;14(3):167-73

Fibromyalgia syndrome is a common, chronic musculoskeletal disorder of unknown aetiology. While available therapy is often disappointing, most patients can be helped with a combination of medication, exercise and maintenance of a regular sleep schedule. The objective of the present study was to determine if adding nutritional supplements derived from the unicellular green alga, Chlorella pyrenoidosa, produced any improvements in the clinical and functional status in patients with moderately severe symptoms of fibromyalgia syndrome. Eligible patients had 2+ palpable tenderness at 11 or more of 18 defined tender points and had a tender point index (TPI) of at least 22.

Each day for 2 months, participants consumed two commercially available Chlorella-based products, 10 g of 'Sun Chlorella' tablets and 100 mL of liquid 'Wakasa Gold'. Any amelioration of symptoms was validated and quantified using semi-objective and subjective outcome measures systematically administered at clinic visits on days 0, 30 and 60 of the diet therapy. Eighteen of the 20 patients enrolled completed the 2 month trial. The average TPI for the group which at onset was 32, decreased to a mean of 25 after 2 months. This decrease was statistically significant (p = 0.01), representing a 22% decrease in pain intensity. Blood samples taken on each occasion indicated no significant alterations in serum chemistries, formed elements, and circulating lymphocyte subsets. Compilations of the results of patient interviews and self-assessment questionnaires revealed that seven patients felt that the dietary supplement had improved their fibromyalgia symptoms, while six thought they had experienced no change, and five believed the symptoms had worsened over the time of the trial. The results of this pilot study suggest that dietary Chlorella supplementation may help relieve the symptoms of fibromyalgia in some patients and that a larger, more comprehensive double-blind, placebo-controlled clinical trial in these patients is warranted. Copyright 2000 John Wiley & Sons, Ltd.

Publication Types: Clinical Trial

PMID: 10815009 [PubMed - indexed for MEDLINE]

Antigenotoxic activity of natural chlorophylls.
Negishi T, Rai H, Hayatsu H. Faculty of Pharmaceutical Sciences, Okayama University, Japan. Mutat Res. 1997 May 12;376(1-2):97-100

Chlorophyllin, a man-made water-soluble form of chlorophyll, is a focus of intensive studies from many laboratories for its antimutagenic and anticarcinogenic properties. Natural chlorophylls, in contrast, have been little studied in this regard. Since yellow-green vegetables are implicated to be protective against human cancers by epidemiological studies, it is important to explore the antigenotoxic properties of natural chlorophylls. Previously, we reported that a chlorophyll sample prepared from Chlorella vulgaris inhibited the mutagenicity of 3-hydroxyamino-1-methyl-5H-pyrido[4,3-b]indole, a direct-acting mutagen, in Salmonella, and that the chlorophyll also showed inhibition of wing spot formation in Drosophila induced by 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2). We have now prepared several samples of chlorophyll from spinach and chlorella, and studied their effect on the genotoxicity of 4-nitroquinoline 1-oxide (4NQO) in Drosophila. The results showed that the genotoxicity of orally given 4NQO was suppressed by simultaneous administration of the chlorophylls. The mechanisms of this inhibition are discussed.

PMID: 9202743 [PubMed - indexed for MEDLINE]

Warfarin therapy and chlorella
Ohkawa S, Yoneda Y, Ohsumi Y, Tabuchi M. Neurology Service, Hyogo Brain and Heart Center at Himeji, Japan. Rinsho Shinkeigaku. 1995 Jul;35(7):806-7

Warfarin potassium (warfarin) is one of anticoagulants. Its anticoagulant effect is induced by inhibiting vitamin K in a complex manner. It is used effectively and safely in preventing cerebral embolism of cardiac origin, provided that thrombotest (TT) values are maintained from 10 to 20%. A 75-year-old man with atrial fibrillation and cardiomyopathy had cerebral embolism in the territory of the right middle cerebral artery. Warfarin therapy was started to prevent the recurrence of embolic stroke. TT values had been well controlled until intake of chlorella, but they rose above the therapeutic limit after its intake. There was no evidence of discontinuing warfarin, or taking drugs containing vitamin K or Natto. Chlorella is one of vitamin K-rich foods. Thus, it may inhibit the anticoagulant effect of warfarin.

PMID: 8777808 [PubMed - indexed for MEDLINE]

Effect of Chlorella vulgaris extracts on murine cytomegalovirus infections.
Ibusuki K, Minamishima Y. Department of Microbiology, Miyazaki Medical College, Japan. Nat Immun Cell Growth Regul. 1990;9(2):121-8

The host-mediated antiviral effect of Chlorella vulgaris extracts (CVE) was evaluated in ICR mice against murine cytomegalovirus (MCMV) infection. Mice treated with 10 mg of CVE on days 3 and 1 before virus challenge survived lethal infection. The protective effect of CVE was shown by a decrease in the infectious viruses replicated in the target organs of CVE-treated ICR mice. CVE also protected mice from histopathological damage to the target organs due to MCMV infection. Both the serum interferon (IFN) level and 2'5'-oligoadenylate (2-5A) synthetase activity were elevated in CVE-treated and MCMV-infected mice, and were higher than those in the control mice. The natural killer (NK) activity of spleen cells, which is otherwise deteriorated by lethal MCMV infection, was remarkably augmented in CVE-treated mice. Neither virocidal nor virostatic activity of CVE on MCMV was seen in vitro. Thus, CVE-induced resistance against MCMV seems to be host-mediated. The protective effect correlated with the augmentation of NK activity of the spleen cells and serum IFN activity, which inhibited replication of MCMV in the target organs and subsequently saved the mice from death.

PMID: 1693753 [PubMed - indexed for MEDLINE]

Chlorella vulgaris culture supernatant (CVS) reduces psychological stress-induced apoptosis in thymocytes of mice.
Hasegawa T, Noda K, Kumamoto S, Ando Y, Yamada A, Yoshikai Y. Research Laboratories, Chlorella Industry Co. Ltd, 1343 Hisatomi, Chikugo City, 833-0056, Fukuoka, Japan. Int J Immunopharmacol. 2000 Nov;22(11):877-85

A glycoprotein prepared from Chlorella vulgaris culture supernatant (CVS) is a biological response modifier (BRM) which exhibits protective activities against tumor metastasis and 5-fluorouracil-induced immunosuppression. We here show that oral administration of CVS prevented significantly the apoptosis of thymocytes in mice undergoing psychological stress in a communication box. Mice were exposed to the emotional stress for 14 days by witnessing other mice being exposed to foot-shock. The numbers in thymocytes, especially CD4(+)CD8(+) population, were decreased significantly and apoptotic cells, as assessed by Annexin V expression, were reciprocally increased after the exposure to the psychological stress. C. vulgaris culture supernatant (CVS) administration significantly suppressed the increase in serum corticosterone level in the psychologically stressed mice. These results suggest that CVS prevents psychological stress and maintain homeostasis in the face of external environmental changes.

PMID: 11090696 [PubMed - indexed for MEDLINE]

Effect of lipophilic extract of Chlorella vulgaris on alimentary hyperlipidemia in cholesterol-fed rats.
Sano T, Kumamoto Y, Kamiya N, Okuda M, Tanaka Y. Department of Chemistry, Kurume University School of Medicine, Fukuoka, Japan. Artery. 1988;15(4):217-24

The effect of glycolipid (GL) and phospholipid (PL) fractions obtained from Chlorella on serum lipid level and fecal excretion of steroids were examined in cholesterol-fed rats. The increase of the level of serum lipids was inhibited by the feeding of GL, PL and Chlorella powder almost the same degree. Fecal excretion of steroids (mostly of cholesterol, deoxycholic and lithocholic acid) was increased by feeding of GL and PL fractions. It is concluded that the feeding of each fraction inhibits the absorption of exogenous steroids and promotes turnover of bile acids in liver to suppress the increase of serum cholesterol level caused by administration of high cholesterol diet.

PMID: 3136759 [PubMed - indexed for MEDLINE]

A novel glycoprotein obtained from Chlorella vulgaris strain CK22 shows antimetastatic immunopotentiation.
Tanaka K, Yamada A, Noda K, Hasegawa T, Okuda M, Shoyama Y, Nomoto K. Research Laboratories, Chlorella Industries Co. Ltd., Fukuoka, Japan. Cancer Immunol Immunother. 1998 Feb;45(6):313-20

A glycoprotein extract (CVS), derived from the unicellular green alga Chlorella vulgaris, strain CK22, exhibited a pronounced antitumor effect against both spontaneous and experimentally induced metastasis in mice. Inhibition of tumor metastasis was enhanced when intratumor administration of CVS was followed by s.c. injection of CVS. Anti-metastatic immunopotentiation was observed in euthymic mice, but not in athymic nude mice. The antitumor activity of CVS was reflected in antigen-specific, T-cell-mediated immunity. Both CD4 and CD8 T cells contributed to the antimetastatic effects, as shown by in vivo depletion experiments with anti-T-cell subset antibodies. Furthermore, CVS caused the recruitment of T cells to the regional lymph nodes and their proliferation in these organs. The CD4-positive population, following CVS injection at the time of tumor rechallenge, displayed a pronounced increase in the proportion of T cells that were CD18 bright, CD44 bright, CD25+, CD54+, CD69+ or CD71+ in the lymph nodes. Thus, CVS induces T cell activation in peripheral lymph nodes in tumor-bearing mice. We conclude that CVS augments antimetastatic immunity through T cell activation in lymphoid organs and enhances recruitment of these cells to the tumor sites. Presurgical treatment with CVS might prevent metastasis or tumor progression.

PMID: 9490201 [PubMed - indexed for MEDLINE]

Experimental biological life support system. Gas exchange between man and microalgae culture in a 30-day experiment.
Kirensky LV, Terskov IA, Gitelson II, Lisovsky GM, Kovrov BG, Okladnikov YN. Moscow, USSR. Life Sci Space Res. 1968;6:37-40

The experiments of a prolonged stay by man in a closed atmosphere regenerated by a biological method have been examined. In the course of the experiment, a study of isolated and compatible links of a gas-closed system of "man-microalgae" was carried out. The main emphasis was placed on the study of the biological compatibility of the links of the system and primarily of the effect of gaseous metabolites built up in the system of man. The dynamics of a number of physiological parameters of the man under experiment were studied. The regular functional tests of the respiratory and cardiovascular system were carried out. An electrocardiogram was made and respiratory rate and pulse were registered. Oxyhemogram investigations and laboratory clinical examinations were also performed, as well as some psychological tests. It was possible to equalize the respiratory gas ratio by the composition of the cultural environment for algae and by the nutrition ration of man. This eliminates time limit for the life maintenance system, especially on microalgae photosynthesis. The results of the experiments permit drawing a conclusion on the biological compatibility of man and microalgae in their prolonged direct gas contact. Thus the possibility of obtaining a balanced atmosphere regeneration system on the basis of counterbalanced gas exchange between man and controlled photosynthesis of algae has been proven experimentally.

PMID: 11982027 [PubMed - indexed for MEDLINE]

The stimulation of tumoricidal peritoneal macrophages can be directly induced by peritoneal implantation of unicellular algae in humans
Vermeil C, Morin O, Le Bodic L. Arch Inst Pasteur Tunis. 1985 Mar-Jun;62(1-2):91-4

The authors explain by what means they have been conducted to use the anti-tumoral power shown by the peptido-glycans produced in the wall of unicellular algae. The first human trials when the algae are introduced in the peritoneal cavity have shown a good tolerance.

PMID: 4091620 [PubMed - indexed for MEDLINE]