Chapter 1

Algae: A Way of Life and Health

Ira A. Levine
University of Southern Maine, Lewiston, ME, United States

Chapter Outline
References8

“Vilor Alga” (translated as more vile or worthless than algae) wrote Virgil, the Latin poet, in 30 BCE. Civilizations were aware
of the role of algae in human health long before Virgil. The use of microalgae dates back 1000 years in Asia and 700 years by
the Aztecs, approximately 3700 years after the first documented use of seaweeds. Contrary to the use of microalgae as a func-
tional food or health tonic, there are historical indications of algal-based pathogens, including: The first plaque visited upon
the Pharaoh of Egypt in the Bible’s book of Exodus, which could be considered a reference to a red tide; the Caribbean in the
1500’s (Halstead, 1978); and the South Pacific in 1606 by the Spanish explorer de Quinos (Mills and Passmore, 1988) with
symptoms brought on by ingestion of shell or finfish, direct skin contact, and/or respiratory inhalation.
Microalgae (phytoplankton) are a diverse assemblage of plantlike, predominantly aquatic, unicellular, multicellular,
or colonial forms; photosynthetic; chlorophyll “a” containing organisms found in the atmosphere, on mountain tops, and
200–300 m below the ocean-air interface. The microalgae are evolutionarily diverse occupying two domains, Eukaryota and
Bacteria, and include, but not limited to the, cyanobacteria (blue-green algae), Charophyta (chara), Chlorophyta (green),
Rhodophyta (red), Ochrophyta (brown), Glaucophyta, Euglenophyta, Cryptophyta, Chrysophyta, Bacillariophyceae (dia-
toms), and Dinophyceae (dinoflagellates). The approximately 41,000 described microalgal species are segregated by photo-
synthetic pigment content, carbohydrate food reserve, cell wall components, and flagella construction and orientation. This
eclectic group has evolved over the last 2500 million years (1600–1900 million years older than the seaweeds), occupying
a variety of ecological niches, that is, planktonic, benthic (growing in sand, mud, soil), epilithic, epiphytic (growing on
other algae, seagrasses, and trees), symbiotic relationships with fungi and invertebrates, atmospheric, and in rare occa-
sions, parasitic. There are additional groups of algae, which can form biofilms, colonial formations, mats, and turfs. The
term “microalgae” will include both the eukaryotic and cyanobacterial forms for the sake of discussion in this chapter.
Despite the total number of described microalgae, perhaps only a few hundred species have been investigated thoroughly,
only several dozens of which are fully understood, with their nutritional, health, pathogenic, or commercial potential truly
delineated. There is much work to be done with this eclectic group before we can fully appreciate the value of microalgae
in health and disease prevention. The algae play an essential role as the foundation of all aquatic food webs and in the
production of more than half of our globe’s oxygen. Additionally, via photosynthesis and nitrogen fixation, microalgae act
as major components of the carbon (Falkowski and Raven, 2007) and nitrogen cycles (Fowler et al., 2013), respectively.
As algae in general and microalgae in particular have played an ever increasing role in humans’ diet, health, and well-
being, their utilization and product development have rapidly expanded our appreciation for the diverse phytochemicals
that the algae produce (Table 1.1). Humans augment traditional medical practices by incorporating nutraceuticals and
supplements, thus acknowledging the relationship between health and diet. Microalgae have been a significant component
of mainstream dietary supplements for the past generation. The most common commercially exploited microalgal genera
are Arthrospira (Spirulina), Chlorella, Dunaliella, and Haematococcus. Benefits include: immune system enhancement,
reduction in viral infections and cancer onset, pre- and probiotic effects, increase in hemoglobin concentrations, and the
reduction in blood sugar levels and bacterial populations. Historically, Chlorella and “plankton soup” were utilized as far
back as 1942, to aid leprosy patients by supporting increase in weight, energy, and general health (Barrow and Shahidi,
2008). Additionally, microalgal-sourced, omega 3 and 6 long chain polyunsaturated fatty acids (PUFA’s) are utilized for

Microalgae in Health and Disease Prevention. https://doi.org/10.1016/B978-0-12-811405-6.00001-3

Copyright © 2018 Elsevier Inc. All rights reserved. 1
 2
Microalgae in Health and Disease Prevention
TABLE 1.1 Most Well-Known Phytochemicals Obtained from Microaglae

Phenolics Nitrogen Containing Compounds Sterolics

Antioxidant
Carotenoids Phenolic Acids Stilbenese Vitamins Phycobiliproteins Sterols Stanols Polysaccharides
α-carotene Gallic Resveratrol Provitamin A C-phycocyanin Cholesterol Cholestanol Sulfated
polysaccharides
β-carotene Chlorogenic Vitamin E Allophycocyanin β-sitosterol Stigmastanol Spirulans
Lutein Vanillic Folic acid Phycoerythrin Campesterol β-glucans
Zeaxanthin Syringic Ascorbic acid 24-Methyldiene
cholesterol
Astaxanthin ρ-coumaric Cobalamin Fucosterol

Canthaxanthin Caffeic Vitamin D 22-Dehydro

cholesterol
β-cryptoxanthin Synaptic Stigmasterol
Lycopene Ferulic Brassicasterol
Desmosterol
Methylsterol

Liu, R., 2004. Potential synergy of phytochemicals in cancer prevention: mechanism of action. Journal of Nutrition 134, 3479–3489; Prakash, D., Gupta, C., Sharma, G., 2012. Importance of phytochemicals
in nutraceuticals. Journal of Chinese Medicine Research and Development 1 (3), 70–78 as adopted from Raposo, M., de Morais, A., 2015. Microalgae for the prevention of cardiovascular disease and stroke.
Life Sciences 125, 32–41.
 Algae: A Way of Life and Health Chapter | 1 3

neurological and cardiac development, and support decrease in skin diseases, rheumatism, coronary heart disease, hyper-
tension, cancer, and cholesterol levels (Mata et al., 2010). Haematococcus pluvialis produces the pigment astaxanthin,
which is recently approved as a dietary supplement and is the feed additive responsible for the reddish pink flesh of aqua-
cultured salmon. Astaxanthin ingestion has been linked to antibody production; antitumor and anti-inflammatory activity;
inhibition of colon, bladder, liver, mammary, and oral cancers; decreasing risk of Parkinson’s and Alzheimer’s diseases; and
improvement in cardiovascular health (Mata et al., 2010).
Through adaptive evolution and metabolic diversity, microalgae have developed a variety of bioactive compounds.
While many of these compounds have biomedical properties that benefit human health, few act as neurological and gastro-
intestinal toxins. Curiously, freshwater microalgal-based toxins are produced primarily by cyanobacteria, whereas marine
microalgal-based toxins are produced by dinoflagellates and diatoms. The toxins tend to be heat-stable, tasteless, odorless,
resistant to acids, and cooking has no effect on them (Backer et al., 2004). Table 1.2 includes the toxins, source algae, route
of acquisition, and clinical manifestation.
The use of microalgae, especially Chlorella and Arthrospira, as dietary supplements must be tempered due to potential
contamination from cultivation, harvesting, processing, and/or storage stages of supplement preparation. Contaminations
can include pathogenic alternative species, heavy metals, cyanotoxins, and inorganic arsenic. Quality control and quality
assurance best practices are needed to reduce or eliminate potential contamination sources, and the purchase of supplements
should be restricted to highly qualified and certified producers, packagers, and distribution concerns (Rzymski et al., 2015).
With the continued use and development of algal-based supplements, additional clinical studies and precautions should
be undertaken in the best interest of the public. Rzymski et al. (2015) list a few best practices to follow:
1. It is not advisable to use Chlorella and Spirulina-based products simultaneously.
2. Use of commercial microalgae-based products should be avoided in individuals suffering from renal failure and suscep-
tible to Al compounds due to potentially high level of Al contamination in these supplements.
3. Use of microalgae-based products should be avoided in individuals suffering from autoimmune diseases, as a relapse of
symptoms can occur.
4. Use of microalgae-based products of unknown origin should be avoided.
5. Use of microalgae-based products in infants and children should be limited.
6. All microalgal-based products should be subject to quality screening and safety assessments performed routinely by
independent agencies prior to registration.
7. All microalgae-based products characterized by detectable cyanotoxin content and significant levels of Al and other
toxic metals should be systematically eliminated from the market.
Drug discovery over the past 70 years has resulted in nearly 28,000 compounds isolated from marine organisms, only 7
of which have been approved for human pharmaceutical use. The drug approval pipeline has an additional 26 in phase I or
II trials. The candidates include 23 anticancer, 2 schizophrenia and Alzheimer’s, and 1 chronic pain treatments (Lauritano
et al., 2016). Most of the marine drug discoveries originated in sponges or ascidians which are difficult to culture and whose
standing stocks do not represent a commercial source of finished drug source material. The ease of collection, isolation,
identification, cultivation, harvesting, and extraction of microalgae and their metabolites represent an attractive alternative
research group. Algae’s evolution over the course of 2500 million years, its diversity, and ability to inhabit extreme environ-
ments have resulted in novel defense, communication, and survival techniques, adding to their human drug and nutraceuti-
cal potentiality (Lauritano et al., 2016). Numerous pharmacological activities have been reported and tested (Tables 1.3 and
1.4) such as: allelopathic, anti-inflammatory, anticancer, antiobese, antidiabetic, antiangiogenic, antimalarial, antioxidant,
antibacterial, antiviral, and growth inhibiting properties (Gastineau et al., 2014; Guedes et al., 2013; Mimouni et al., 2012;
Nigjeh et al., 2013; Patterson et al., 1990a,b; Peng et al., 2011; Samarakoon et al., 2013). However, one note of caution
is that drug discovery in microalgae is a function of cultivation of environmental regimes resulting in metabolic plasticity
(Lauritano et al., 2016). Metabolite production and bioactivity levels vary as a function of habitat and seasonality. Primary
and secondary metabolites production and concentration are a function of: growth phase (Vidoudez and Pohner, 2012),
clones (Gerecht et al., 2011), light (Depauw et al., 2012), temperature (Huseby et al., 2013), culturing media (Alkhamis and
Qin, 2015), grazing pressure (Pohnert, 2002), extraction method (Juttner, 2001), and many other factors (Chen et al., 2011).
An example of metabolic plasticity is the elevated inhibition of biofilm formation by Leptocylindrus danicus and L. aporus,
and anticancer activity by Skeletonema marioni in nitrogen and phosphorus starved growth media.
The progress of phycology, the study of algae, within the public consciousness can be summarized by a seminar given by
the author at Middlebury College, Middlebury, Vermont, USA in March 2010, “The Road from Science Geek to Being Cool,
Algal Physiological Ecology: a Global Economic Development Engine.” As algae and algal-based biofuels became a research
and development priority in the United States during the 21st century, the once obscure field is now experiencing a surge of
 4
TABLE 1.2 Microalgal Toxins (Manganelli, 2016; Backer et al., 2004; Morris, 1999)

Microalgae in Health and Disease Prevention

Microalgae Toxin Syndrome Exposure Symptoms/Signs Incubation Time Death Rate Duration
Microcystis Microcystins Hepatotoxin

Planktothrix Neurotoxin

Anabaena

Nostoc

Synechocystis

Cyanobium

Arthrospira

Limnothrix

Phormidium

Hapalosiphon

Nodularia Nodularines Hepatotoxin

Cylindrospermopsis Cylindrospermopsins Cytotoxin

Umezakia

Aphanizomenon

Raphidiopsis

Anabaena

Anabaena Anatoxin-a Neurotoxin

Aphanizomenon

Cylindrospermum

Microcystis

Planktothrix

Raphidiopsis

Oscillatoria Homoanatoxin-a Neurotoxin

Raphidiopsis

Anabaena Anatoxin-a Neurotoxin

Aphanizomenon Saxitoxin Neurotoxin

Anabaena
Lyngbya

Cylindrospermopsis

Cyanobacteria (all) Saxitoxin Gastrointestinal 5–30 min 1%–14% Days

toxin
Paralytic shellfish Ingestion of scal-
poisoning lops, mussels,
clams, cockles

Lyngbya Aplysiatoxin Gastrointestinal

toxin
Lyngbyatoxin
Debromoaplysiatoxin

Microcystis Microviridin J Unknown

Cyanobacteria β-N-Methylamino-l- Neurotoxin

(most) alanine

Azadinium Azaspiracid group Azaspiracid shell-

fish poisoning

Amphidoma

Dinophysis Okadaic acid group Diarrhetic shellfish Eating shellfish Acute gastroenteritis <24 h 0% Days
poisoning harvested from
affected areas,
mussels, oysters,
scallops

Algae: A Way of Life and Health Chapter | 1

Prorocentrum Dinophysis

Dinophysis Pectenotoxin Hepatotoxic

Protoceratium Yessotoxin Cardiotoxic

Lingulodinium

Gonyaulax

Alexandrium Saxitoxin Gastrointestinal Eating shellfish Acute paresthesias and

toxin harvested from other neurologic manifesta-
affected areas tions: may progress rapidly
to respiratory paralysis

Gymnodinium Paralytic shellfish 5–30 min 1%–14% Days

poisoning

Continued

5
 6
TABLE 1.2 Microalgal Toxins (Manganelli, 2016; Backer et al., 2004; Morris, 1999)—cont’d

Microalgae in Health and Disease Prevention

Microalgae Toxin Syndrome Exposure Symptoms/Signs Incubation Time Death Rate Duration
Pyridinium

Pseudo-nitzschia Domoic acid Amnesic shellfish Eating shellfish Gastroenteritis, followed by <24 h 3% Years
poisoning or finfish from neurologic manifestations
affected areas, leading to severe amnesia,
mussels, oysters, coma, and death
scallops
Domoic acid
poisoning

Karenia Brevetoxin Neurotoxin Eating shellfish Gastrointestinal and neuro-

harvested from logic symptoms
affected areas

Gymnodinium Neurotoxic shell- Aerosolized by Respiratory and eye irrita- 0.5–24 h 0% Days
fish poisoning wave action tion when aerosolized

Gambierdiscus Ciguatoxin Ciguatera fish Bioaccumulation Acute gastroenteritis fol- <24 h 0.1%–12% Months
poisoning in marine food lowed by paresthesias and
chain other neurologic symptoms

Prorocentrum Maitotoxin Illness results from

eating large, pre-
dacious reef fish

Alexandrium Cyclic Imines Neurotoxin

Karenia

Vulcanodinium

Prorocentrum

Ostreopsis Palytoxin Neurotoxin

Ostreopsis Ovatoxin

Ostreopsis Ostreocin Neurotoxin

Pfiesteria unknown Pfiesteria associ- Exposure to water Learning and memory defi-
ated syndrome or aerosols ciencies acute respiratory
and eye irritation, acute
confusional syndrome
 Algae: A Way of Life and Health Chapter | 1 7

TABLE 1.3 Algal-Based Compound Preclinical Trials

Porphyridium Hypocholesterolemic Dvir et al. (2000a,b) and Ginzburg et al. (2000)
Antioxidant Tannin-Spitz et al. (2005)

Arthrospira Atherosclerosis prevention Kaji et al. (2004) and Cheong et al. (2010)
Hypocholesterolemic Bertolin et al. (2009) and Nagaoka et al. (2005)
Iwata et al. (1990), Hosoyamada et al. (1991) and
Colla et al. (2002)
Antioxidant and anti-inflammatory Deng and Chow (2010)
Antioxidant and anti-inflammatory Rimbau et al. (1999)

Nannochloropsis Hypocholesterolemic Werman et al. (2003)

Chlorella, Phaeodactylum Antioxidant and anti-inflammatory Guzman et al. (2001)

Adopted from Raposo M., de Morais A. Microalgae for the prevention of cardiovascular disease and stroke. Life Sciences 125, 2015, 32–41.

TABLE 1.4 Microalgal-Based Clinical Studies

Microalgae/ Duration #
Product Dosage (g/Day) (Weeks) Patients Effects References
Arthrospira 2–4 12 30 Decreases plasma cholesterol Ramamoorthy and
Premakumari (1996)
7.5 8 51 Decreases serum cholesterol Kim and Kim (2005)
Decreases plasma apolipoprotein
4.2 8 15 Decreases LDL levels Nakaya et al. (1988)
1 8 23 Decreases total plasma cholesterol Samuels et al. (2002)
Decreases LDL to HDL ratio
4.5 6 36 Decrease in total cholesterol, LDL, Torres-Duran et al.
blood pressure (2007)
2 8 15 Decrease in total cholesterols, LDL to Mani et al. (1998,
HDL ratio 2000)
Decrease in blood sugar and glycated
serum proteins
8 12 ni Decrease in blood pressure and plasma Lee et al. (2008)
total lipids
Astaxanthin ni ni 61 Improved dyslipidemia Yoshida et al. (2010)
0.002 and 0.008 8 14 Decrease in oxidative stress and Park et al. (2010)
inflammation
Increase in immune response
0.006 1.5 20 Improved blood fluidity and circulation Miyawaki et al.
(2008)
Dunaliella 3 14 6 Increase in serum carotenoids and anti- Bobrov et al. (2008)
and oxidant protection
β-carotene
0.56 1.7 60 Decrease in conjugated dienes, increase Ben-Amotz and Levy
in carotenoids (1996)

Adopted from Raposo M., de Morais A. Microalgae for the prevention of cardiovascular disease and stroke. Life Sciences 125, 2015, 32–41.
8 Microalgae in Health and Disease Prevention

notoriety. If studying algae, previous to the renewed interests, was held in such disregard or benign neglect, then why would
anyone dedicate his or her life to algae? Phycology has a long history of remarkable, dedicated scientists and lay practitioners
who have advanced our algal-based knowledge through their tireless field and laboratory efforts. Massive algal collections
were assembled at universities (e.g., University of Texas, Austin, Texas), research institutions (e.g., Bigelow Laboratory for
Ocean Sciences, Boothbay, Maine) and museums (e.g., Bishop Museum, Honolulu, Hawaii). Meticulous anatomical, repro-
ductive, and systematic treatises were published expanding our body of knowledge. Biotechnological methodologies were
incorporated into current molecular genomic, ultrastructure, physiological ecology, and biochemical studies advancing our
understanding of the biology, ecology, systematics, and commercial value of the algae. Algae represent a field of study that is
far from the mainstream science. Phycologists have enjoyed their life’s work in relative obscurity until the recent interest in
algae farming (Cyanotech), algae as a healthy food (blue-green manna), feed, medicine, and biofuel (Exxon). Algae enjoy the
focus and funding so as to move microalgae and its place in health and disease prevention to the forefront in research. The edi-
tors have assembled a group of contributors dedicated to the advancement of algae, experts in their fields, endeavoring to bring
seaweeds and their role in health and disease prevention to a diverse group of readers. Below is a poem dedicated to algae:
The Biology of Algae by R.A. Lewin (1981). Phycol. Newsletter 7:1
The biology of algae is a duty, or a task,
That consumes the better portion of your time
In the sampling of waters from an ocean, or a flask,
Or a snow-field, or a gutter-full of slime.
You get cold, and wet, and grubby; you get dusty, hot, and dry;
You get dian dejected, and defied;
But you’ll find that, if you’re lucky-if you’re good-and if you try,
You can do a little science on the side.

The biology of algae is a pastime, or an art,

That embodies a diversity of skill:
How to mend a pH meter which has somehow come apart,
Or to regulate a microscope or still;
How to edit a proposal, or a chapter of a book;
How to float upon the academic tide;
How to teach a fellow creature how to speak, or how to cook,
And a little bit of science on the side.

The biology of algae is a virtue, or a vice,

That entails some tricky searching of the soul.
It involves the growth of fishes, and the harvesting of rice,
And pollution, and the origins of coal.
It may get us into trouble; it may get us into space;
Its dilemmas are as long as they are wide.
It involves some moral judgements on the future of our race –
And a little bit of science on the side.

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