Researchers’ attention is increasingly focusing on some of the so called “functional foods” which may be useful for their prevention and treatment of life-style-related diseases, for example Metabolic Syndrome. One of these functional ingredients is fucoxanthin (FX), a characteristic carotenoid present in edible brown seaweeds.
BROWN ALGAE
Brown algae (or Phaeophyceae) is a large group of mostly marine multicellular algae, including many seaweeds of colder Northern Hemisphere waters. They play an important role in marine environments, both as food and for the habitats they form. Worldwide there are about 1500-2000 species of brown algae.
Brown algae belong to Heterokontophyta, a large eukaryotic group of organism distinguished most prominently by having chloroplasts surrounded by four membranes, suggesting an origin from a symbiotic relationship between a basal eukaryote and another eukaryotic organism.
They exist in a wide range of sizes and forms. The smallest members of the group grow as tiny, feathery tufts of threadlike cells no more than a few centimeters long. Some species even have a stage in their life cycle that consists of only a few cells, making the entire alga microscopic. Other groups of brown algae grow to much larger sizes. All brown algae are multicellular: there are no known species that exist as single cells or as colonies of cells, and the brown algae are the only major group of seaweeds that does not include such forms.
Brown algae contain chlorophyll a and c, but they get their color from several brownish carotenoid pigments.
FUCOXANTHIN IN BROWN ALGAE
Fucoxanthin belongs to the class of non-provitamin A carotenoids, a class of 40-carbon organic molecules that consists of two groups: xanthophylls (when their structure contains oxygen) and carotenes (without oxygen in chemical formula). FX is a xanthophyll, whose distinct structure includes an unusual allenic bond, epoxide group, and conjugated carbonyl group in polyene chain with antioxidant properties.
It is found as an accessory pigment in the chloroplasts of brown algae, giving them a brown or olive-green color, since fucoxanthin absorbs light primarily in the blue-green to yellow-green part of the visible spectrum.
BENEFITS OF FUCOXANTHIN
Fucoxanthin is now available as a nutritional supplement in capsule form and can be found in health food stores and online.
The increasing popularity of this molecule is certainly due to its anti-obesity effect, primarily detected by murine studies. Furthermore, in recent studies FX has shown a great antioxidant activity, anti-cancer, anti-diabetic and anti-photoaging properties.
The general antioxidant properties of all carotenoids have been suggested as being the main mechanism by which they afford their beneficial health effects. In the last few years the studies have focused on the exceptional ability of FX in modulating the expression of specific genes involved in cell metabolism: this seems to be the main healthy effect of fucoxanthin.
Function of marine carotenoids, 2009
ANTI-OBESITY ACTIVITY
Anti-obese property of fucoxanthin is partly mediated by altering lipid-regulating enzymes, in particolar the role of mitochondrial uncoupling proteins: infact, FX shows antiobesity effect through UCP-1 expression in white adipose tissue.
UCPs are transmembrane proteins that discharge the proton gradient generated in oxidative phosphorylation and are also involved in regulating reactive oxygen species (ROS).
By stimulating the expression of uncoupling protein-1 (UCP-1, also known as thermogenin) gene in the mithocondria of white adipose cells, FX promotes thermogenesis and suppresses lipid accumulation.
THE ROLE OF UCP-1 IN BROWN ADIPOSE TISSUE
This adaptive thermogenesis by UCP1 induction in brown adipose tissue (BAT) plays an important role in energy balance by dissipating excess energy intake as heat to resist body weight gain.
In contrast to other animals, humans have not great amount of BAT. It is abundant in newborns, in whose it is located especially on the back, along the upper half of the spine and toward the shoulder: its function is to avoid hypothermia, which can be life-threatening for neonates (in particular for premature babies).
In adults, most of the mitochondria in brown adipocytes disappears and the tissue becomes similar in function and appearance to white fat. However, BAT is still present in adults in the upper chest and neck.
UCP-1 expression in brown adipose tissue (BAT) is known as a significant component of whole body energy expediture, cause of its role in adaptive thermogenesis, and its dysfunction contributes to the development of obesity.
Sequence analysis of the UCP1 gene in a severe obese population from Southern Italy, 2011.
UCP-1 is situated in the mitochondrial innner membrane, where it is activated by fatty acids and inhibited by nucleotides. UCP1 provides a mechanism for the enormous heat-generating capacity of the tissue.
Fatty acids cause the following signaling cascade: sympathetic nervous system terminals release norepinephrine onto a beta-3 adrenergic receptor on the plasma membrane. This activates adenylyl cyclase, which catalyses the conversion of ATP to cyclic AMP (cAMP). cAMP activates protein kinase A, causing its active C subunits to be freed from its regulatory R subunits. Active protein kinase A, in turn, phosphorylates triacylglycerol lipase, thereby activating it. The lipase converts triacylglycerols into free fatty acids, which activate UCP1, overriding the inhibition caused by purine nucleotides (GDP and ADP). At the termination of thermogenesis, the mitochondria oxidize away the residual fatty acids, UCP1 inactivates and the cell resumes its normal energy-conserving mode.
Its function is to decrease the proton gradient genereted by oxidative phosphorylation, so the releasing of chemical energy generates heat rather than ATP.
UCP1-mediated heat generation in brown fat uncouples the respiratory chain, allowing for fast substrate oxidation with a low rate of ATP production.
UCP1 is related to other mitochondrial metabolite transporters such as the adenine nucleotide translocator, a proton channel in the mitochondrial inner membrane that permits the translocation of protons from the mitochondrial intermembrane space to the mitochondrial matrix.
UCP-1 EXPRESSION IN WHITE ADIPOSE TISSUE
UCP-1 is normally expressed only in brown adipose tissue, not in WAT. However, it's been discovered that FX induces both proteins and mRNA expression of UCP-1 in WAT, leading to oxidation of fatty acid and heat production in white adipocytes. This finding will give a clue for non dietary anti-obesity therapies.
Some metabolic and nutritional studies, carried out on rats and mice at Hokkaido University, had shown a significant WAT weight decrease in fucoxanthin-fed mice, which clearly expressed UCP-1 in their white adipocytes. Those results indicate that fucoxanthin up-regulates the expression of UCP-1 in WAT, which, in the end, may contribute to reducing WAT weight.
FX intake promotes mRNA expression of Adrb3 (b-adrenergic receptor) in WAT: its up-regolation expression is responsible for lipolysis and thermogenesis.
Fucoxanthin induces thermogenesis because it addresses the process of energy distribution at the level of mitochondria, in other words where conversion of fat into energy is taking place.
- Studies were conducted on visceral adipose tissue in mice and investigated the anti-obesity effects of fucoxanthin in diet-induced obesity mice fed with a high-fat diet, supplemented with doses of FX for 6 weeks. Fucoxanthin significatly lowered body weight compared with the control group without altering food intake. In adiposed tissue of fucoxanthin-fed mice, adipocyte sizes and mRNA expression of fatty acid beta-oxidation enzymes were alterd in a dose-dependent manner. The FX supplement led to increase mRNA expression of UCP-1 and UCP-3 in brown adipose tissue and that of UCP-2 in the white adipose tissue. These results suggested that the anti-obesity effect of fucoxanthin could be mediated by altering lipid-regulating enzyme and UCPs in the fat tissues.
Anti-obese property of fucoxanthin is partly mediated by altering lipid-regulating enzymes and uncoupling proteins of visceral adipose tissue in mice.
- One of the most important studies dates back to 2009, when 151 non-diabetic, obese premanopausal women were tested to evaluate the effectiveness of FX supplementation for weight loss. The women were divided in two groups: in one group they were invited to take 600mg of Xanthigen (a phytomedicine containing 300mg of pomegranate seed oil and 300mg of brown seaweed extract with 2.4mg of FX); in the other one, they were given a placebo. The test lasted 16 days. Meanwhile women's diet was reduced to 1800 kcal per day. The results provided a significant reduction of body weight, fat and systolic/diastolic blood pressure, decreased levels of acute-phase proteins (such as C-reactive protein) and a significant increase in resting energy expenditure (REE) measured by indirect calorimetry.
The effects of Xanthigen in the weight management of obese premenopausal women with non-alcoholic fatty liver disease and normal liver fat, 2009.
Therefore, in obese individuals, a significant reduction in body weight and fat results in the down-regolation of inflammatory markes, in addiction to prevents Metabolic Syndrome and type 2 diabetes.
PHARMACOKINETICS OF FUCOXANTHIN
Fucoxanthin absorption rate is generally affected by the composition of food matrix. The solubility of FX in soybean oil and in other vegetable oils is very low, while FX can easily dissolve in medium-chain triacylglycerols (MCT). Studies on mices have shown that the effects of FX with MCT are higher in comparison with FX alone, due to the increase in FX absorption rate and oxidative stability: UCP1 expression and level in WAT was higher when the mice were fed with seaweed lipids containing FX. Therefore, the anti-obesity effect of Fx was increased by mixing Fc with MCT. This suggests that the absorption rate of FX is strongly affected by the presence of other components, especially lipids.
Single and 13-week oral toxicity study of fucoxanthin oil from microalgae in rats, 2011
TOXICITY AND SIDE EFFECTS
As a part of safety evaluation, single and repeated oral dose toxicity study of FX was conducted on male and female mice. In repeated doses studies, no mortality and no abnormal changes in liver, kidney, spleen and gonadal tissues were observed. However, significantly increased total cholesterol concentrations were shown by plasma biochemical analyses in all FX-treated groups.
Because there hasn't been research on fucoxanthin in humans, the possible side effects aren't known. People shouldn't consume large amounts of wakame or other types of seaweed as a source of fucoxanthin. Seaweed is rich in iodine and excessive consumption may result in iodine poisoning. High levels of iodine can interfere with the function of the thyroid gland. Also, consuming excess amounts of iodine-rich foods isn't recommended if there is a known allergy or hypersensitivity to iodine.
Nevertheless, unlike many popular stimulant-type metabolism enhacers (for instance ephedra, caffeine, guaranà), fucoxanthin has no effect on the sympathetic nervous system and can be taken without concerns of cardiovascular exhaustion or blood pressure deregulation. The mode of action of fucoxanthin is such that it bypasses the nervous system and shifts energy balance from producing ATP toward thermogenesis.
Single and repeated oral dose toxicity study of fucoxanthin (FX), a marine carotenoid, in mice, 2009.
OTHER HEALTH PROPERTIES OF FUCOXANTHIN
Carotenoids are important dietary nutrients with antioxidant potential. Firstly, they can quench singlet oxygen: the excess energy of singlet oxygen is transferred to the long central chain of conjugated double bonds in the carotenoid molecule. Another role of carotenoids as antioxidants is attributed to their scavenging of free radicals, which steal an electron from the carotenoid or form an adduct with it. Consequently, the ability of carotenoids to quench singlet oxygen increases with increasing number of conjugated double bands. Fucoxanthin acts as an antioxidant in conditions whereas other carotenoids have practically no quenching abilities. A combination of these distinct properties is very rarely found among naturally occurring food-derived compounds. High levels of oxidative stress are common in many diseases including atherosclerosis, Parkinson’s disease, Alzheimer’s disease, acute myocardial infarction, chronic fatigue syndrome and fibromyalgia.
Thus, FX could become a new weapon to prevent and treat these diseases.
Radical scavenging and singlet oxygen quenching activity of marine carotenoid fucoxanthin and its metabolites, 2007.
The potential antidiabetic effects of fucoxanthin are attributable to the ability of this molecule to induce weight loss and WAT reduction. The adipocyte has recently been recognized as an endocrine cell for its role in the secretion of biologically active mediators, termed adipokines, and some of this adipokines are reported to alter insulin sensitivity and glucose and lipid metabolism in muscle, liver and adipose tissues.
- ACTIVIY ON CARDIOVASCULAR SYSTEM
Because metabolic syndrome is a collection of risk factors that substantially increase the chances of damage in the cardiovascular system, fucoxanthin would be very important to prevent CV damage, since it acts on the reduction of major cardiovascular risk factors (obesity, diabetes, high blood pressure, chronic inflammation, plasma and hepatic triglyceride, and cholesterol concentrations). FX administration in rodents promotes the synthesis of docosahexaenoic acid (DHA) in the liver, resulting in improvements in lipid profile.
FX does not stimulate the central nervous system, meaning it did not cause jitters or lost sleep like caffeine, nicotine, or thyroid hormones. So the FX may have a potential role in the modulation and prevention of human diseases, particularly in reducing the incidence of CVD.
A recent work showed for the first time the protective effect of fucoxanthin against UVB-induced skin photoaging. The results showed that the topical application of FX suppresses UV-induced expression in the skin. The antioxidant activity of FX might be involved in this anti-angiogenic effect.
Protective effect of Fucoxanthin against UVB-induced skin photoaging in hairless mice, 2011.
CONCLUSIONS
The promising results of animal studies should encourage researchers to undertake human clinical trials, since we currently have little information about the correct dosage of FX and its use in preventing and treating specific diseases.
Since chemical synthesis of fucoxanthin is possible but very expensive, the possibility of obtaining this precious carotenoid directly from brown seaweeds should eagerly considered.
Brown seaweeds are also rich in vitamines, minerals, dietary fibers, proteins, PUFAs, polyphenols and iodine, which can be used as an activator of thyrod function.
It shouldn't be forgotten that, as a carotenoid, FX is a powerful antioxidant that protects cells from damage. A diet rich in FX could help to reduce body fat accumulation and to modulate blood glucose and insuline levels, and even provides other health benefits, including improved cardiovascular health, reduction of inflammation (a major cause of heart disease), healthy cholesterol and triglycerides levels, improvements in blood pressure levels, and healthy liver function.
OTHER REFERENCES
Fucoxanthin: a treasure from the sea, 2012
Mechanism of fatty-acid-dependent UCP1 uncoupling in brown fat mitochondria, 2012
Fucoxanthin from edible seaweed, Undaria pinnatifida, shows antiobesity effect through UCP1 expression in white adipose tissues, 2005
Bruce Alberts, Alexander Johnson, Peter Walter & Julian Lewis, Molecular Biology of the Cell, Taylor & Francis Ltd., 5th revised edition, 2008
