SUPPLEMENT MONOGRAPHS FUCOXANTHIN /239 daily can cause borborygmi and bloating. Doses greater than subjects with pseudohypolactasia than in control lactose 50 grams daily can cause cramps and diarrhea. Some are digesters. Am J Clin Nutr. 1999; 69:973-979. more sensitive to FOS and may develop gastrointestinal symptoms at lower doses. Those with lactose intolerance have been reported to experience gastrointestinal symptoms at a dose of 25 grams. Fucoxanthin DOSAGE AND ADMINISTRATION DESCRIPTION FOS are available as nutritional supplements and in function- Fucoxanthin is a marine carotenoid and a member of the al foods. Dosing is variable and ranges from 4 to 10 grams carotenoid family of chemical substances. Fucoxanthin, like daily and sometimes higher. Those who use more than 10 other carotenoids, is a natural fat-soluble pigment (brown, in grams daily should split the dosage throughout the day. the case of fucoxanthin) and is found in algae, including LITERATURE heterokonts and seaweeds, and in diatoms (phytoplankton). Alles MS, de Roos NM, Bakx JC, et al. Consumption of Fucoxanthin is also found in the edible brown seaweeds fructo-oligosaccharides does not favorably affect blood glucose wakame (Undaria pinnatifida), hijiki (Hijikia fusiformis) and and serum lipid concentrations in patients with type 2 diabetes. kombu (Laminaria japonica), as well as in the marine algae Am J Clin Nutr. 1999; 69:64-69. Chrysophyceae, Prymneslophyceae, Bacillariophyceae, Pra- Bouhnik Y, Vahedi K, Achour L, et al. Short-chain fructo- sinophyceae and Phaeophyceae. Fucoxanthin and its metab- oligosaccharide administration dose-dependently increases fecal olites are also typically found in sea organisms that feed on bifidobacteria in healthy humans. J Nutr. 1999; 129:113-116. these carotenoids as conjugates. For example, fucoxanthin Buddington RK, Williams CH, Chen SC, Witherly SA. Dietary esters and fucoxanthinol esters are found in clams. supplement of neosugar alters the fecal flora and decreases activities of some reductive enzymes in human subjects. Am J Fucoxanthin functions in algae as a light-harvesting pigment. Clin Nutr. 1996; 63:709-716. It and chlorophyll are the two major light-harvesting Luo J, van Yperselle M, Rizkalla SW, et al. Chronic pigments in brown algae and diatoms. Fucoxanthin exists in consumption of short-chain fructo-oligasaccharides does not algae in the form of a fucoxanthin-chlorophyll alc protein affect basal hepatic glucose production or insulin resistance in complex, which is associated, in the case of brown algae and type 2 diabetics. J Nutr.2000; 130:1572-1577. diatoms, with photosystem II. The complex transfers light to Ohta A, Baba S, Takizawa T, Adachi T. Effects of fructo- chlorophyll a. The fucoxanthin protein complex shows oligasaccharides on the absorption of magnesium in the homology to the chlorophyll aIb binding polypeptides of magnesium-deficientrat model. J Nutr Sci Vitamino/ (Tokyo). higher plants. 1994; 40:171-180. Ohta A, Motohashi Y, Sakai K, et al. Dietary fructo- Fucoxanthin, as an antioxidant, protects algae against oxygen oligasaccharides increase calcium absorption and levels of toxicity. Its possible protective roles as an antioxidant, as mucosal calbindin-D9K in the large intestine of gastrectomized well as its possible anti-inflammatory and anticancer activi- rats. Scand J Gastroenterol. 1998; 33:1062-1068. ties, have become of interest to researchers in the past Ohta A, Ohtsuki M, Hosoro A, et al. Dietary fructo- decade. More recently, its possible activity as an anti-obesity oligosaccharidesprevent osteopenia after gastrectomy.J Nutr. agent has stimulated research on the carotenoid, mainly in 1998; 128:106-110. Japan. Oku T, Tokunaga T, Hosoya N. Nondigestibility of a new sweetener, "Neosugar," in the rat. J Nutr. 1984; 114:1574-1581. Fucoxanthin is chemically described as [(IS,3R)-3-hydroxy- Pierre F, Perrin P, Champ M, et al. Short-chain fructo- 4-[(3E,5E,7E,9E, lIE, 13E,15E)-18-[( IS,4S,6R)-4-hydroxy- oligosaccharides reduce the occurrence of colon tumors and 2,2,6-trimethyl-70xabicyclo[4.1.0]heptan-l-yl]-3,7, 12, 16- develop gut-associated lymphoid tissue in Min mice. Cancer tetramethyl-17-oxooctadeca-l ,3,5,7,9, 11,13, 15-octaenyli- Res. 1997; 57: 225-228. dene]-3,5, 5-trimethylcyclohexyl] acetate. It is also known Roberfroid MB, Delzenne NM. Dietary fructans. Annu Rev as3'-(Acetyloxy)-6',7' -didehydro-5,6-epoxy-5,5' ,6,6',7,8- Nutr. 1998; 18:117-143. hexahydro-3,5'-dihydroxy-8-oxo-beta,beta-carotene; Sahaafsma G, Meuling WJ, van Dokkum W, Bouley C. Effects (3'S,5'R,6' R)- 3'-acetoxy-5,6-epoxy-3,5'-dihydroxy-6', 7' -di- of a milk product, fermented by Lactobaccillus acidophilus and dehydro-5,6,7 ,8,5' ,6'-hexahydro- 13.I3-carotene-8-one; and with fructo-oligosaccharides added, on blood lipids in male (3S,3' S,5R,5' R,6S,6'R)- 3'-(aacetyloxy)-6',7' -didehydro-5,6- volunteers. Eur J Clin Nutr. 1998;52:436-440. epoxy-5,5' ,6,6',7 ,8-hexahydro-3,5'-dihydroxy-8-oxo-I3,I3- Teuri U, Vapaatalo H, Korpela R. Fructo-oligosaccharides and carotene. Its CAS registry number is 3351-86-8, its empirical lactulose cause more symptoms in-lactose maldigesters and formula is C42Hss06, and its molecular weight is 658.91. .. 240 I FUCOXANTHIN PDR FOR NUTRITIONAL SUPPLEMENTS Fucoxanthin's allenic group (=CH=C=CH-) and 5,6 monoe- and the transition of G) to the S phase. Fucoxanthin was poxide make fucoxanthin a unique chemical structure (see found to inhibit the phosphorylation of Rb. Further, the figure). Fucoxanthin is also classified as an epoxyxantho- kinase activity of cyclin D when joined with its partner phyll or epoxide-containing xanthophyll. Fucoxanthan is kinase CDK4 was suppressed by treatment with fucoxanthin. represented by the following chemical structure. Fucoxanthin also induced activity of the ubiquitin-protea- some pathway leading to degradation of cyclin D and suppressed cyclin D mRNA. Thus, it appears that fucoxan- thin caused the suppression of cyclin D via promotion of proteasomal degradation and repression of cyclin D, leading to cell cycle arrest. Incidentally, apoptosis was not observed in this case Fucoxanthin Fucoxanthin reduced the viability of the human colon Fucoxanthinol is the deacetylated metabolite of fucoxanthin. adenocarcinoma WiDr cell line accompanied by the induc- tion of cell cycle arrest at the GOGIphase of the cycle. In this ACTIONS AND PHARMACOLOGY ACTIONS case, apoptosis of the cells was also reported. In order to Fucoxanthin has antioxidant actIVIty and may have anti- understand the possible mechanism of fucoxanthin's action, cancer, anti-inflammatory and antiobesity activities. a number of factors that regulate the cell cycle were investigated, including the cyclins, the cyclin-dependent MECHANISM OF ACTION kinases (CDKs), the retinoblastoma protein Rb and p21, a Antioxidant activity: Fucoxanthin has demonstrated radical key protein in cell cycle regulation. It was p2l that appeared scavenging and singlet oxygen quenching activities. The to be affected by fucoxanthin. When p2l binds to the CDKs, quenching activity of fucoxanthin against the organic radi- it inhibits their activity. It appeared that fucoxanthin induced cals 1,I-diphenyl-2-picrylhydrazyl (DPPH, a stable free cell-cycle arrest at the GOGIphase in human cancer cells via radical), 12-doxylstearic acid (12DS), and the radical adduct upregulation of the activity of p21. of nitrobenzene with linoleic acid (NB-L) was studied using electron spin resonance (ESR). In the presence of fucoxan- Fucoxanthin was reported to reduce the viability of human thin, the ESR signals for the DPPH, 12DS and NB-L radicals prostate cancer cells via the induction of apoptosis. Apopto- were significantly reduced. Fucoxanthin also has sis induction was characterized by DNA fragmentation, an 2,2'-azinobis(3 -ethyIbenzothiazoline-6-sulfonic acid) increased percentage of hypodiploid cells and cleavages of (ATBS) radical, hydroxyl radical, superoxide anion and procaspase-3 and PARP (poly(ADP-ribose) polymerase. singlet oxygen scavenging activity. Expression of Bax and Bcl-2 proteins, but not Bcl-XL proteins, was reduced. The activation of caspase-3 by Anticancer activity: Fucoxanthin has demonstrated a number fucoxanthin was thought to be the major activity in the of anticancer activities via different mechanisms. induction of apoptosis. Fucoxanthin was found to inhibit the growth of human Fucoxanthin was found to induce apoptosis III human hepatic HepG2 carcinoma cells. In 2007, cancer of the liver promyelocytic leukemia cells. Apoptosis in these cells was was the fourth most common cause of death from cancer. associated with loss of mitochondrial membrane potential, Most of the cases of hepatocellular cancer can be found in but not with an increase in reactive oxygen species. undeveloped countries. Fucoxanthin was shown to reduce Fucoxanthin treatment caused cleavages of procapsase-3 and the viability of HepG2 cells accompanied by the induction of poly (ADP-ribose) polymerase, without any effect on the cell cycle arrest during the GaG) phase of the cell cycle. The protein level of Bcl-2, Bcl-XL or Bax. It was concluded that cell cycle is the series of events that takes place in a cell the fucoxanthin induction of apoptosis was likely due to leading to its replication. The cell cycle consists of four mitochondrial membrane permeabilization and caspase-3 distinct phases Gj, S, G2 and the M phase, where the cell activation. divides forming two new cells. Go is the postmitotic phase prior to G I. Two key classes of regulatory molecules- Anti-inflammatory activity: Endotoxin-induced uveitis (EIU) cyclins and cyclin-dependent kinases (CDKs)-acting in (induced by lipopolysaccharide [LPS]) is an acute, anterior partnership, determine a cell's progress through the cell segment intraocular inflammation (uveitis). Fucoxanthin was cycle. The retinoblastoma protein Rb, a tumor suppressor studied to see how it affected LPS-induced inflammation in protein, prevents excessive growth by inhibiting the cell vitro in a mouse macrophage cell line and in vivo in male cycle when Rb is hypophosphorylated.