CSIRO N Single-cell Oceanography, Israel; and PhD, MarineBiology, NationalInstitute of of thisarticle for theirkindassistance inthepeerreview Research, Australian NationalUniversity, Bioscience, JohnCurtinSchoolofMedical University; Complementary Medicine,RMIT FAMAS, isHead,Departmentof foods duetotheir highconcentrationsof microalgae are deemedtobefunctional and, more recently, dunaliella. These microalgae specieschlorella, spirulina popularity are thenutrient-dense toxins. bio-accumulation ofenvironmental the baseoffoodchainsoastoreduce minimal processing, including thoseat cally produced ‘whole foods’ involving encourage theconsumptionoforgani- -based foods.Many wouldalso Marc Cohen and setting asactive ingredients. from juicebarsandexcipient statustotheclinical As nutrient-richwholefoods,microalgae are moving The Editor thanks Murdoch University Primary Care, DivisionofHealthSciences, PhD, EdD,FACNEM, isProfessor of Foster Several ‘livingfoods’ thathave gained Jenny Jamison , PhD,BSc,DivisionofMolecular increase its dietary intakeof increase itsdietary Australian populationneedsto authorities agree thatthe utritionists andpublic-health Jennifer RJamison , MBBS,BMedSci,PhD, Prof AmiBen-Amotz Prof Paul provide anoverview. , MBBCh, , Profs Marc Cohen people ofcentralAfrica. Mexican andby theKanembu Aztecs for possiblythousandsofyears by asafoodsource having beenharvested with alongtraditionofhumanuse, Spirulina isablue–green cyanobacteria Spirulina and uniquepigments. phyll, carotenoids, ,, icant amountsoflipids,protein, chloro- whole-food nutrients,containingsignif- ir . . 3g NA 0.26mg 8.3mg 0.4g 1.54g 97.6mg 0 180kJ 8800mg 10g 1g 3.9g 8.7g 503mg 119mg 1893kJ 7g 2005 Israel, 29.7g InstituteofOceanography, National e. US CraftTechnologiesInc, 0.0 mg d. 35.4g 2005 1g 4g Australia, MeasurementInstitute, 1600kJ National 0.34mg c. 2005 forstandardreferences (release18), NutrientDatabase USDANational b. 2003 20May, 21May2002;103044178002, 102042170, no. Food Japan ResearchLabs, 1.1g a. 12.9g 67g 1214kJ Lutein/zeaxanthin Betacarotene 8g 24g Chlorophyll 57g Fibre Energy Carbohydrates Total fats Protein Composition ofmicroalgaevs.carrots(per100g) 1 2 There are Spirulina food b FUNCTIONAL FOODS Chlorella carotene, numerous minerals,highlevels B-complex vitamins,chlorophyll, beta- containing upto70percentprotein, from lakes. harvested in tanksundercontrolled conditionsor supplements, forwhichtheyare grown the mostcommonlyusedinnutritional several species of spirulina, although several speciesofspirulina, maxima (recently reclassified as Spirulina platensis Spirulina isrichinnutrients, MARCH / APRIL 2006 a , A. platensis Dunaliella Complementary Medicine and c,d,e by the TGA S. maxima Arthrospira Carrots 3 ) are b 85 SINGLE-CELL FOOD continued

of the essential polyunsaturated fatty acid of oral spirulina (Multinal, New Ambadi Precautions and contraindications γ–linolenic acid, E and unique Estate P/L, Algal Division, Madras, Theoretically, the phenylalanine content pigments, including phycocyanin.1 India) supplementation.6 of cyanobacteria may exacerbate Animal experiments suggest spirulina Despite being promoted for weight phenylketonuria. There is also potential provides a biologically useful but differ- loss, spirulina was trialled 20 years ago for heavy-metal contamination of ently metabolised form of .4 for this indication, and found to have no spirulina harvested naturally from Remarkable claims have been made benefit over placebo.8 contaminated waters; this is more regarding spirulina, which is reputed to One weak randomised trial reported likely with non-spirulina species, such have anti-oxidant, antiviral, antineo- beneficial effects on precancerous oral as Anabaena, Aphanizomenon and plastic, lipid-lowering, hypocholestero- leukoplakia lesions in 115 patients Microcystis.2 laemic, hepatoprotective, anti-allergic and receiving 1 g S. fusiformis (New Ambadi immune-modulatory activities, and has Estates, Madras, India) over 12 months.9 Pregnancy and lactation been promoted as a weight-loss aid. A randomised double-blind trial Data are insufficient to safely However, while preliminary research published last year compared 1 g and recommend the use of spirulina during has shown some promise for some of 2 g daily doses of spirulina (Earthrise pregnancy or breastfeeding. A diet of up these indications and the safety of Nutritionals Inc, Irvine, California) to 30 per cent spirulina did not cause spirulina, human evidence is lacking. with placebo in individuals with allergic any toxic effects in a mouse study.12 rhinitis. The higher dose significantly Indications reduced interleukin–4 levels by 32 per Interactions Spirulina has shown some antiviral cent from phytohaemagglutinin-stimu- Small but statistically significant increases activity in laboratory and animal studies, lated peripheral blood mononuclear cells.10 in alkaline phosphatase and serum and preclinical evidence also suggests were observed in a four-week immunomodulatory, hepatoprotective, Dosage weight-loss study of 15 volunteers anti-allergic and hypocholesterolaemic Spirulina may be sold in capsule, receiving 200 mg/day spirulina tablets.8 effects.2 tablet, flake or powdered form, or as a Following from animal studies that component of ‘green food’ products Chlorella found spirulina effective in lowering containing chlorella, barley grass and Chlorella (Chlorella pyrenoidosa, serum cholesterol and triglyceride levels, wheatgrass, in daily doses ranging from C. vulgarisis) is a freshwater green alga some clinical trials suggest possible 250 mg to 5 g.11 containing 60 per cent protein in the efficacy in humans.5–7 However, these form of amino acids, and betacarotene, trials are methodologically flawed or Adverse effects vitamin D, vitamin B12, , and poorly reported. Spirulina is well tolerated, with headache, enzymes such as pepsin. Chlorella A small trial involving type 2 diabetic muscle pain, facial flushing and sweating provides more bioavailable vitamin B12 patients found beneficial effects on lipids being the only adverse effects reported than spirulina, provided large amounts and fasting blood sugar after two months after oral consumption.2 are consumed.13 It is also an extremely rich souce of the carotenoid lutein, Minerals in whole-food supplements which is found in the macula of the eye. Promoted as a health tonic, anecdotal Ca Mg Na K Cu Zn Fe reports claim chlorella provides diverse benefits through increasing the level of Dunaliella 178 540 823 5 0.4 4 23.5 albumin in the bloodstream, ranging Spirulina 547 330 >999 5 1.1 2 50.5 from improved digestion to accelerated wound healing, retarded ageing processes Chlorelia 201 211 106 5 0.1 1 214 and enhanced immunity.14 Claims Kelp powder 1443 796 >999 7 0.2 3 27 concerning anticarcinogenic activities are based on animal studies of an extract Wheatgrass 937 83 315 6 0.4 2 13.7 isolated from chlorella, not the whole 15 Green barley 384 186 818 6 0.6 2 8.4 plant. Similarly, there is no evidence to

SOURCE: TRACE ELEMENTSINC, US; NATIONAL OCEANOGRAPHIC INSTITUTE, ISRAEL ELEMENTSINC, US; NATIONAL SOURCE: TRACE support claims about the chelating effect

86 Complementary Medicine MARCH / APRIL 2006 FUNCTIONAL FOODS

of chlorella on heavy metals in humans. Super foods comparison: trace elements (mg/100 mg) Indications A pilot study suggested chlorella reduced Mn Cr Se B Co Mo S Li Rb or stabilised sitting diastolic blood Dunaliella 1.8 0.2 1.02 25.4 0.022 0.041 <2000 0.9 0.66 pressure in people with mild-to-moderate hypertension.16 A review of double- Spirulina 2.6 0.53 0.03 0.25 0.13 0.11 <2000 0.093 0.13 blind, placebo-controlled, randomised clinical trials concluded that daily dietary Chlorelia 4 0.06 0.01 0.03 0.038 0.042 <2000 0.01 0.066 supplementation with chlorella may Kelp powder 3.8 0.23 0.69 11.1 0.045 0.094 2426 0.068 0.85 indeed reduce high blood pressure, lower serum cholesterol levels, accelerate Wheatgrass 5.1 0.09 0.04 0.33 0.005 0.05 <2000 0.008 1.0 wound healing and enhance immune functions.17 The authors also recom- Green barley 3.9 0.11 0.15 1.05 0.004 0.066 <2000 0.023 0.51 mended that the potential of chlorella to ELEMENTSINC., US SOURCE: TRACE relieve symptoms, improve quality of life Pregnancy and lactation oxidant, so it is commonly used as a and normalise body functions in patients Data are insufficient to safely source of natural betacarotene in nutri- with fibromyalgia, hypertension or recommend the use of chlorella during tional supplements (Nutrient database ulcerative colitis justified performing pregnancy or breastfeeding. for standard references, release 18). larger, more comprehensive clinical trials. One randomised, double-blind, Interactions Indications placebo-controlled trial in 124 healthy Animal studies suggest some constituents Recent advances in production adults undergoing influenza vaccination may reduce side-effects of technology have allowed the whole dried found that chlorella-derived dietary 5–fluorouracil.20 dunaliella biomass to become commer- supplementation, although failing to cially available.41 To date, most of the increase the antibody response to Dunaliella clinical research on dunaliella has been influenza vaccine in the overall study Dunaliella is a soft-celled microalga on betacarotene-rich whole organism. population, increased the antibody found in many coastal waters and Human studies, however, suggest that response of participants aged 50–55 saltwater lakes. Dunaliella is one of the dunaliella can protect against exercise- years18 — an interesting finding given most salt-tolerant life forms known, and induced asthma31,32, normalise high LDL our ageing population. is adapted to extremely high ultra-violet oxidation in patients with diabetes33 and radiation. To cope with these extreme male hyperlipidaemic smokers34, as well Dosage environments, dunaliella produces very as protect the skin from sun damage35 Capsules, tablets and granules are high levels of osmotic glycerol and the and protect against radiation damage, as available, as is the stand-alone powder. anti-oxidant molecule betacarotene. demonstrated by its use in children The daily dose of dietary supplements of On a per-gram basis, dunaliella has exposed to the Chernobyl disaster.36 chlorella provides 500–3000 mg of the more than twice the chlorophyll and over Animals studies further suggest that intact organism. The therapeutic dose is 6000 times the anti-oxidant content of the natural betacarotene-rich dunaliella unknown.15 spirulina (see table, p 85). Furthermore, protects against GI inflammation37, dunaliella’s soft-cell membrane makes it water-immersion stress38, whole-body Adverse effects easily digestible compared to other irradiation39 and CNS oxygen toxicity.40 Allergic reactions and photosensitivity microalgae with hard cell walls.21 have been reported in some consumers of While dunaliella contains many Dosage chlorella.19 different carotenoids, it is highest in Whole dunaliella is sold as 250–500 mg natural betacarotene, which can make capsules containing approximately eight Precautions/contraindications up to 10 per cent of its dry weight.21 per cent betacarotene. The recommended Some products may be rich in The US Department of Agriculture dose is 1–3 g/day, taken with meals or and may affect the INR of patients using deems dunaliella to be the richest known other dietary fat to increase the bioavail- warfarin.19 source of this important fat-soluble anti- ability of carotenoids.

MARCH / APRIL 2006 Complementary Medicine 89 SINGLE-CELL FOOD continued

Adverse effects Betacarotene in profile No adverse effects from consumption of the whole dunaliella have been reported. While is toxic in high doses, betacarotene is only converted into Carotenodermia may become evident vitamin A as required by the body and is considered to be non-toxic even after a few months of consumption but when given in doses as high as 180 mg/day.22 is harmless and reversible on discontinu- Not all betacarotene is the same. Synthetic betacarotene comprises the ation. all–trans isomer, while natural betacarotene also contains the 9-cis isomer. All-trans betacarotene is converted to vitamin A, which plays an essential role Precautions and contraindications in vision, growth, reproduction, immune function and maintenance of the skin None known. and mucous membranes. The 9-cis isomer contained in natural betacarotene also acts as a powerful anti-oxidant.23 Pregnancy and lactation High intake of betacarotene-containing foods has consistently shown benefits, Data are insufficient to recommend the including prevention of cancer24 and heart disease25, as well as age-related use of dunaliella during pregnancy or macular degeneration and cataract.26 Supplementation with synthetic breastfeeding. betacarotene, however, has produced mixed results, with two studies finding an increased lung-cancer risk in heavy smokers or those with high asbestos Interactions exposure.27,28 This association, however, has not been found with natural None known. betacarotene and authorities continue to recommend intake of betacarotene- rich foods. Clinical implications At doses above 30 mg/day, betacarotene may cause an orange-yellow On a gram-for-gram basis, microalgae colouration of the skin (carotenodermia), which is harmless and reversible on may be the most nutrient-dense food on reducing carotenoid consumption29 and may even be considered desirable.22 earth42, with minimal indigestible struc- This effect is utilised in tanning tablets to produce a natural-looking skin tan.30 tures in contrast to higher or animals, which typically have less than half their dry weight being nutritionally useful.43 Microalgae contain a range of macro- and micronutrients, including chloro- phyll, carotenoids, phytonutrients, amino acids, polysaccharides, essential fatty acids, carbohydrates, vitamins and bioavailable minerals. Thus, in contrast to the reductionist or pharmaceutical approach to that leads to supplementation with only a few (often synthetically produced) nutrients, microalgae provide a holistic mix of nutrients developed over millions of years of evolution. While research is accumu- lating that suggests microalgae has many health benefits, further research is required to determine their clinical appli- cations. ◗ Mudflats in Western Australia, where betacarotene is farmed from Dunaliella salina for commercial use. This area is believed ideal for dunaliella farming, References as it has clean seawater supplies, high UV radiation, an optimal temperature 1 Kay RA. Microalgae as food and supplement. range with very low rain fall Crit Rev Food Sci Nutr 1991;30(6):555–73.

2 Ulbricht CE, Basch EM. Natural Standard COGNIS AUSTRALIA P/L

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Herb & Supplement Reference. St Louis, 23 Ben-Amotz A, et al. Am J Clin Nutr Missouri: Elsevier Mosby, 2005:692–7. 1996;63(5):729–34. 3 Australian Government. Complementary 24 Peto R, et al. Nature 1981;290(5803):201–8. Medicines Evaluation Committee Extracted 25 Kritchevsky SB. Beta-carotene, carotenoids and Ratified Minutes, 52nd meeting, 5 August the prevention of coronary heart disease. J Nutr 2005. Canberra: Therapeutic Goods 1999;129(1):5–8. Administration, 2005. 26 Mayne ST. Beta-carotene, carotenoids, and 4 Cases J, et al. J Agric Food Chem disease prevention in humans. FASEB J 2002;50(13):3867–73. 1996;10(7):690–701. 5 Nakaya N, et al. Cholesterol lowering effect of 27 ATBC Cancer Prevention Study Group. The Spirulina. Nutr Rep Int 1988;37(6):1329–37. effect of and beta carotene on the 6 Mani UV, et al. Studies on the long-term effect incidence of lung cancer and other cancers in of Spirulina supplementation on serum lipid male smokers. New Engl J Med profile and glycated proteins in NIDDM 1994;330(15):1029–35. patients. J Nutraceut 2000;2(3):25–32. 28 Omenn GS, et al. Effects of a combination of 7 Samuels R, et al. Hypocholesterolaemic effect of beta carotene and vitamin A on lung cancer and spirulina in patients with hyperlipidemic cardiovascular disease. New Engl J Med nephrotic syndrome. J Med Food 1996;334:1150–5. 2002;5(2):91–6. 29 Micozzi M, et al. Carotenodermia in men with 8 Becker EW, et al. Nutr Report Internat elevated carotenoid intake from foods and beta- 1986;33(4):565–74. carotene. Am J Clin Nutr 1998;48:1061–4. 9 Mathew B, et al. Nutr Cancer 30 Der Marderosian A, Beutler JA (eds). The 1995;24(2):197–202. Review of Natural Products. St Louis: Facts and 10 Mao TK, et al. Effects of a Spirulina-based Comparisons, 2002. on cytokine production 31 Moreira A, et al. Alergologia e Inmunologia from allergic rhinitis patients. J Med Food Clinica 2004;19(3):110–2. 2005;8(1):27–30. 32 Neuman I, et al. Prevention of exercise-induced 11 PDRhealth. Spirulina. Thomson Healthcare. asthma by a natural isomer mixture of beta- URL http://www.pdrhealth.com/drug_info/ carotene. Annals Allergy, Asthma Immunol nmdrugprofiles/nutsupdrugs/spi_0239.shtml, 1999;82(6):549–53. accessed 18 January 2006. 33 Levy Y, et al. Annals Nutr Metab 12 Chammoro G, et al. Arch Latinoam Nutr 2000;44(2):54–60. 1990;40(1):86–94. 34 Chao JC, et al. Effects of beta-carotene, vitamin 13 Watanabe F, et al. J Nutr Sci Vitaminol C and E on antioxidant status in hyperlipi- 2002;48(5):325–31. demic smokers. J Nutr Biochem 14 Otles S, Pire R. J AOAC Int 2002;13(7):427–34. 2001;84(6):1708–14. 35 Heinrich U, et al. J Nutr 2003;133(1):98–101. 15 American Cancer Society Inc. Chlorella. URL 36 Ben-Amotz A, et al. Radiation Environ Biophys http://www.cancer.org/docroot/ETO/content/E 1998;37(3):187–93. TO_5_3X_Chlorella.asp?sitearea=ETO, 37 Lavy A, et al. Inflamm Bowel Dis accessed 18 January, 2006. 2003;9(6):372–9. 16 Merchant RE, et al. J Med Food 38 Takenaka H, et al. Planta Medica 2002;5(3):141–52. 1993;59(5):421–4. 17 Merchant RE, et al. Altern Ther Health Med 39 Ben-Amotz A, et al. Radiation Environ Biophys 2001;7(3):79–91. 1996;35(4):285–8. 18 Halperin SA, et al. CMAJ 2003;169(2):111–17. 40 Bitterman N, et al. J Appl Physiol 19 PDRhealth. Chlorella. Thomson Healthcare. 1994;76(3):1073–6. URL http://www.pdrhealth.com/drug_info/ 41 Tracton I, Bobrov Z. World’s first organic, nmdrugprofiles/nutsupdrugs/chl_0068.shtml, super-anti-oxidant, wholefood to be released. accessed 18 January 2006. Media release, 23 June 2005, NutriMed Group. 20 Konishi F, et al. Cancer Immunol Immunother 42 Passwater R, Solomon N. Algae: The next 1996;42:268–74. generation of . The Experts’ Optimal 21 Ben-Amotz A, et al. Ann Rev Microbiol Health Journal 1997;1:2. 1983;37:95–119. 43 Bruno JJ. Edible microalgae: A review of the 22 Mathews-Roth MM. Am J Clin Nutr health research. Pacifica, California: Center of 1990;52:500–1. Nutritional Psychology Press, 2001.

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