Fucoxanthin is a carotenoid structure that is found in seaweed and microalgae, and perhaps the second most famous sea-based carotenoid (of the 750 known carotenoids, over 250 of them are exclusively marine-sourced) behind astaxanthin only. It is hypothesized to comprise up to 10% of all carotenoids in nature and it has a role in gathering light for energy production via forming something known as a chlorophyll a/c-fucoxanthin complex; it is a primary carotenoid that transfers light energy to photosynthetic machinery for energy production in plants (unlike secondary carotenoids such as β-carotene and astaxanthin which prevent excess light from being transferred). It is a component of many dietary seaweeds and is thought to confer health promoting benefits associated with seaweed and the Japanese diet.
Fucoxanthin is a pigment (specifically, a brown pigment and a type of carotenoid) found in seaweed and microalgae that is used to fix light and aid the process of photosynthesis
Fucoxanthin can be found in the following species of seaweed and algae:
Myagropsis myagroides at 9.01mg/g
Dictyota coriacea at 6.42mg/g
Petalonia binghamiae (Vinogradova) at 3.57+/-0.028 mg/g
Hijikia fusiformis (Hijiki)
Turbinaria turbinate at 0.59+/-0.08mg/g
Laminaria japonica (Ma-Kombu)
Phaeodactylum tricornutum (Microalgae) at 15.42-16.51 mg/g
Odontella aurita (Microalgae) at 6.34-20.63mg/g dry weight depending on nitrogen availability
Isochrysis (species of microalgae) at 17mg/g (1.7% dry weight)
Fucoxanthin is found in high levels in seaweed, although it is at even higher levels in microalgae; the level of fucoxanthin found in some particular species may be high enough to actually obtain the benefits of supplementation even when supplementing seaweed products
No fucoxanthin is found in the yolks of the eggs laid by hens fed fucoxanthin although metabolites such as fucoxanthinal are found.
Fucoxanthin shares similar structural properties to the carotenoid class of nutrients like beta-carotene (the standard comparison) and more interesting derivatives like astaxanthin. However, fucoxanthin tends to be more interested in due to it's allenic bond and 5,6-monoepoxide aspects which are fairly unique. It also contains a conjugated carbonyl group with anti-oxidant properties.
There are some related molecules that are deemed metabolites of fucoxanthin but are not from human metabolism, but rather metabolism by the plant source of fucoxanthin (and thus they appear as co-existing nutrients), such as halocynthiaxanthin.
Fucoxanthin is fat-soluble, thus it's absorption is enhanced in the presence of fatty acids (which has been demonstrated by mixing with medium chain triglycerides at 0.9% of the diet in rats) and may be hindered in the presence of fat-blockers, although this latter part is conjecture.
Fucoxanthin is a non-vitamin carotenoid (ie. a carotenoid that does not form Vitamin A in the body) similar to astaxanthin.
Fucoxanthin has been noted to reduce the oxidative stress that is induced by a vitamin A deficiency in the rat, and antioxidant enzyme activities in rats|published=2008 Dec|authors=Ravi Kumar S, Narayan B, Vallikannan B|journal=Eur J Nutr] suggesting that it may circumvent some aspects of vitamin A deficiency.
It appears fucoxanthin has a lesser bioavailability than other carotenoid-class nutrients, while having a greater bioavailability in humans than it does in rats. In comparing two studies on pharmacokinetics in humans and rats the Tmax and AUC followed similar curves in relation to time, but the human Cmax and AUC were 33% and 46% despite being 15% the oral dose.
Fucoxanthin is deacetylated in the intestines to fucoxanthinal, which is distributed through lymphatic tissue after absorption in the same manner as fat-soluble nutrients and fatty acids. and no fucoxanthin nor metabolites around found in the liver prior to first pass metabolism. Fucoxanthinol is the main circulating form of dietary fucoxanthin, insofar that circulating fucoxanthin cannot be determined in some studies due to complete deacetylation.
Paradoxically, fucoxanthin is a molecule which is fat soluble and requires fatty acids in order to be absorbed yet also possesses the ability to inhibit pancreatic lipase and inhibit some degree of fat absorption. The AUC of lymph absorption seems to be comparable between fucoxanthin (2mg/mL in the lumen) and without, suggesting a delayed absorption of triglycerides rather than hindering absorption. No fecal fat test was done in this study. As fucoxanthin is metabolized into fucoxanthinol by a few enzymes, one of which is lipase (the others being cholesterol esterase and carboxylesterase), it is possible that this could be indirect inhibition from competitive antagonism.
Fucoxanthin, via its metabolite fucoxanthinol, is readily taken up in the gut alongside fatty acids
Fucoxanthin is metabolized into predominately fucoxanthinol (deacetylation in the intestines) and Amarouciaxanthin A via the liver(with some other metabolization into Cis-Amarouciaxanthin A and two other unknown compounds). Fucoxanthinol appears to be the compounds responsible for most cardiac and hepatic implications and Amarouciaxanthin A the metabolite responsible for adipocytes (fat cells). Conversion of fucoxanthin into these metabolites has been noted in liver (HepG2) cells and requires NAD(P)+ as a cofactor.
Amarouciaxanthin A has been detected in rats via hepatic conversion after ingestion of Fucoxanthin after 24 hours, but has not been detected in humans in two studies lasting up to 24 hours. It is not know whether or not Amarouciaxanthin A exists in humans or whether it takes longer than 24 hours to be converted.
No fucoxanthin circulates in the blood, as it all gets metabolized to fucoxanthinol; Amarouciaxanthin A has not yet been shown to exist in humans, but it is not known whether this is due to the research conducted being too short or due to inter-species differences
Levels of fucoxanthinol seem to peak in tissues 4 hours after ingestion whereas concentrations of Amarouciaxanthin A peak 24 hours after ingestion. Another study looking at ingestion of 31mg fucoxathin (via Kombu extract dissolved in MCTs), it was found that increases in serum fucoxanthinol were seen until the 4 hour mark, where the next measurement at 8 hours noted a decline and this Tmax was similar in rats at doses of 3.5mg/kg bodyweight. In rats, a serum half-life of 0.92-1.23 days yet an adipose half-life of 2.76-4.81 days.
Fucoxanthinol's serum parameters in humans after 31mg ingestion dissolved in MCTs was a Cmax of 44.2nmol/L, a Tmax of 4 hours or so, a half-life of 7 hours, and an AUC to infinity of 663.7 nmol/l/h.
One other study measured the serum one week after daily ingestion of Wakame at 6.1mg fucoxanthin, and circulating levels of fucoxanthinol were found to be 0.8nmol/L. This study did not actively dissolve the fucoxanthin in fatty acids, and thus this low circulating level may be due to poor absorption.
Higher circulating levels of fucoxanthinol appear to need mixture with fatty acids like Medium Chain Triglycerides (MCTs) for absorption
A study in rats noted that the metabolites of fucoxanthin, fucoxanthinol and Amarouciaxanthin A, appeared to both have affinity for adipose tissue rather than other tissues with 3.13–3.64 μmol/kg partitioned into adipose whereas 1.29–1.80 μmol/kg was recorded for kidneys and liver. In rats, where Amarouciaxanthin A has been recorded, this metabolite appears to be more selective for adipose whereas fucoxanthinol is slightly more evenly distributed.
Beyond the basic metabolites (fucoxanthinol and Amarouciaxanthin A), fucoxanthin can react with nitrate in a sacrifical manner (in protecting receptors from nitrosylation) to form nitrofucoxanthin, which it appears may be anti-cancer in mechanisms.
Additionally, a cis-isomer of fucoxanthinol may exist after ingestion of fucoxanthin.
After metabolism in the liver, Amarouciaxanthin A appears to be deposited and stored for a rather long time in fat cells; this accumulation of Amarouciaxanthin A may be a reason behind it's influences on fat mass being chronic rather than acute.
It has been found that bioaccumulation of fucoxanthin has not occurred in humans at a dose of 0.31mg fucoxanthin over 28 days, which is the average fucoxanthin intake from food sources in Japan.
Bioaccumulation at the level of 100mg/kg bodyweight fucoxanthin in rats is associated with giving the tissue an orange tone, as fucoxanthin and their metabolites do possess pigmentation activity.
A build-up effect occurs over time with sufficiently high (supplemental) dosages of oral fucoxanthin, with no significant toxicity being seen at the lower range of chronic oral intake and a non-toxic coloration of tissue at obscenely high doses
Fucoxanthin, at 1-10uM, has been shown to reduce the changes in CYP3A4 and MRP1 mRNA (-55%) (and CYP3A4 protein content) by rifampin in HepG2 cells; rifampin increases activity of these two proteins, and this attenuation of an increase may play a beneficial role in multidrug resistance associated with cancer treatment. This effect appears to be mechanistically related to the CYP3A4 promoter and MRP1, as it also inhibits hCAR induction of CYP3A4 (88% attenuation) and does not influence PXR nor hCAR activity.
Even without the PXR inducer, fucoxanthin was able to suppress CYP3A4 activity by 21% at 10uM in a concentration dependent manner and reduce protein content by 33% over 24 hours, by decreasing mRNA transcription rates.
May reduce activity of CYP3A4, which is an enzyme that metabolizes more than 50% of pharmaceuticals in existence. Would be prudent to ask a medical doctor about possible interactions.
In fat tissue of rats fed the seaweed Petalonia binghamiae (150mg/kg containing 3.57mg/g fucoxanthin) for 70 days, it appears that supplementation is associated with an increase in AMPK phosphorylation relative to high fat control.
In 3T3-L1 adipocytes, 5-10μM fucoxanthin is able to increase AMPK activity secondary to increasing LKB1 phosphorylation in a concentration dependent manner (1μM not significantly active); this concentration was also sufficient to increase CPT-1a activity.
Fucoxanthin appears to stimulate AMPK activity
Microglia are glial cells (support cells for neurons) that serve as a brain sensor for inflammation and possess an inflammatory response when 'activated' by cytokines that, if prolonged and excessive, contributes to neurotoxicity; supplements and drugs which suppress this inflammatory response, such as Spirulina, are thought to be neuroprotective.
5-50μM fucoxanthin in microglial cells that are treated with the Alzheimer's pigment Aβ42 appears to concentration dependently reduce the secretion of inflammatory signalling molecules (PGE2 and nitric oxide) suggesting an antiinflammatory effect. This appears to be associated with an upregulation of antioxidant enzymes (SOD and glutathione) and a suppression of MAPK activation from Aβ42.
The addition of 0.2% fucoxanthin to the high fat diet of rats is able to increase fecal total lipids (23.6%), fecal cholesterol (28.9%), and fecal triglycerides (135%) relative to high fat control.
Appears to hinder cholesterol and triglyceride absorption, which may be a mechanism underlying both a reduction in cholesterol as well as weight loss effects
Mechanistically, the increase in liver mRNA levels of SREBP-1c, ACC, FAS, and G6PDH (all lipogenic proteins) and suppression of CPT-1 (lipolytic protein) seen with a high fat diet are normalized when the diet includes 0.2% fucoxanthin over four weeks. These changes may occur in rats who are obese prior to fucoxanthin supplementation (and has been noted with 52 days supplementation of 0.083-0.167mg/kg bodyweight fucoxanthin).
At least one study has noted that the suppression of SREBP-1c may be acute following the addition of 200μg/mL Petalonia binghamiae (0.36% fucoxanthin) to 3T3-LI adipocytes.
A few genes and their proteins are increased in the liver in response to an obesogenic diet, and the increase seen appears to be reduced by fucoxanthin in either a rehabilitative (taken after obesity) manner or when taken alongside a high fat diet
In rats fed a high fat diet with 0.2% fucoxanthin for four weeks, there was a trend to decrease triglycerides which has been noted to be statistically significant with 0.083-0.167mg/kg bodyweight fucoxanthin in obese rats (52 days of supplementation) and with 70 days supplementation of Petalonia binghamiae (150mg/kg containing 3.57mg/g fucoxanthin).
associated with fucoxanthin supplementation. The only human study conducted noted a decrease in triglycerides from 177mg/dl to 155mg/dl (non-fatty liver group) and 195mg/dl to 158mg/dl (fatty liver group) after 16 weeks of supplementation.
Preliminary evidence suggest that fucoxanthin reduces triglycerides, reliability of this decrease not fully established
Mechanistically, the increase in HMG-CoA, CYP7A1, and ACAT (cholesterol producing proteins in the liver) seen with a high fat diet appears to be attenuated when the diet has a 0.2% fucoxanthin content.
May prevent increases of cholesterol production in the liver in response to the diet
In rats fed a high fat diet with 0.2% fucoxanthin for four weeks, there is a significant increase in HDL-C relative to high fat control (58%) which was comparable to normal diets.
Possibly due to HDL-C, total plasma cholesterol nonsignificantly increased.
One animal study noted higher total cholesterol levels after consumption of Wakame (168+/-5mg/dl in obese control, 185+/-7 and 192+/-10 in wakame fed groups with no dose-dependence) yet lower LDL levels (9 and 7mg/dl relative to 13 in control) and non-significantly higher HDL levels (66 and 71, relative to 65mg/dl).
When administered to humans at varying dosages, fucoxanthin was able to reduce blood pressure from 138/91mmHG (systolic/diastolic) to 119/79mmHG in persons with fatty liver. In persons without fatty liver, blood pressure dropped from 128/93mmHG to 112/77mmHG.
The diet-induced increase of MCP-1 (a atherogenic cytokine) appears to be prevented with daily ingestion of a wakame supplement containing fucoxanthin in rats.
Mechanistically, in obese rats given a wakame lipid extract containing fucoxanthin was associated with an increase in GLUT4 mRNA concentration in skeletal muscle.
In obese rats given 0.167mg/kg fucoxanthin in the diet for 52 days, a significant decrease in circulating blood glucose is seen relative to obese control. This has also been noted with obese rats given a wakame lipid extract.
Fucoxanthin, at 0.02% of the diet in rats, can significantly reduce blood glucose levels from 389.2+/-23.3mg/dl in diet-induced obese mice to 176.4+/-15.8mg/dl after 2 weeks of supplementation; via increasing GLUT4 translocation and skeletal muscle uptake of glucose. This reduction of blood sugar is unique to diabetic mice, as it does not affect control mice with impaired glucose metabolism.
Interestingly, fucoxanthin can increase the levels of DHA (a component of fish oil) in the liver tissue independent of fish oil supplementation; some anti-diabetic effects of fish oil pertaining to the liver (such as reduction of fatty liver build-up secondary to PPARs) may apply to fucoxanthin. The combination of both these nutraceuticals has been shown to reduce the weight gain and blood glucose associated with diabetic mice as well.
Fucoxanthin appears to have anti-diabetic effects by normalizing the function of skeletal muscle in diabetes; this effect of normalization does not affect non-diabetic animals
In obese rats (from a high fat diet) supplemented with fucoxanthin at 0.083-0.167mg/kg for 52 days, an increase in circulating adiponectin is seen alongside a decrease in leptin and hyperleptinemia has been noted to be suppressed elsewhere.
May increase adiponectin in obese rats
When 0.2% fucoxanthin is added to the rat diet over the course of 4 weeks, the weight gain seen is nonsignificantly attenuated.
An increase in β3-adrenergic receptor content has been noted in white adipose tissue of rats fed fucoxanthin.
Fucoxanthin primarily works via inducing (increasing) activity of Uncoupling Protein 1 (UCP1) in white adipose tissue which uncouples a step in mitochondrial respiration and indirectly increases metabolic rate. Interestingly, higher rates of uncoupling are one of the bioenergetic reasons as to why 'brown' fat is different than white fat. The induction of white adipose UCP1 is important due to low levels of brown adipose in adult humans.
Fucoxanthin has been noted (in rats) to alter various lipid regulating enzymes. It decreases gene expression of the fat-regulating enzymes Malic Enzyme (ME), Glucose-6-Phosphate Dehydrogenase (G6PD), and Fatty acid Synthetase (FAS) in a relatively dose-dependent manner, although the rate of these enzymes is affected less significantly than the genetic signalling. Glycerol-3-phosphate dehydrogenase, an enzyme associated with turing glycerol into triglycerides for storage, has also been shown to be decreased with fucoxanthin metabolites at 10uM.
Increased expression of phosphorylated AMPK and phosphorylated forms of ACC have also been noted to be higher in fucoxanthin-treated animals on a high-fat diet relative to animals without fucoxanthin. When incubated with adult adipocytes at 10uM, fucoxanthin activates AMPK in a dose dependent manner and can increase downstream transcription of CPT-1a, the rate limiting enzyme in fatty acid beta-oxidation. Increasing activity of AMPK/ACC has been found by other researchers, and is more potent with punicic acid alongside the fucoxanthin.
Fucoxanthin and its metabolites also decrease adipocyte differentiation via downregulation of PPAR-y, a protein that encourages adipocyte differentiation. This has also been noted with Xanthigen, a blend of punicic acid (from pomegranate) and fucoxanthin. These in vitro effects are also mirrored by the metabolite Amarouciaxanthin A, which is the one most prominent in adipose tissue after ingestion, as well as the circulating metabolite, fucoxanthinol. Amarouciaxanthin A, the metabolite most prominent in fat cells, appears to be the most potent metabolite in suppressing adipocyte differentiation.
Protein content and mRNA levels of beta(3)adrenergic receptors in white adipose tissue have also been shown to be increased after fucoxanthin supplementation for 15 weeks in rats.
One study done on 151 non-diabetic obese females found that Fucoxanthin (both via a blend called 'Xanthigen' with Pomegranate seed oil, as well as by itself) was able to induce fat loss and increase metabolic rate, although due to this being an exploratory study REE was only measured in 41 participants. Metabolic rate was increased by up to 1915+/-246 kJ/day in the group given 8mg fucoxanthin daily (n=4), but interestingly this increase in metabolic rate only appeared after 16 weeks of supplementation with no acute effects on metabolic rate whatsoever when measured at 2 weeks. The higher doses of fucoxanthin were able to be statistically different from placebo at 5 weeks, with lower doses requiring more time to exert significance.
Overall, weight loss over 16 weeks was 5.5+/-1.4kg in the group with more than 11% fat content in the liver, and 4.9+/-1.2kg in the group with less (11% being the border defining 'Non-Alcoholic Fatty Liver Disease').
Animal studies suggest that fucoxanthin increases fat loss reliably and at very low doses, easily attainable from daily consumption of brown seaweed. The lone human study appears to reflect results in animal research, and fucoxanthin appears to have a moderately potent but highly delayed effect on inducing fat loss; preliminary research, however
Fucoxanthin has been shown to reduce the release if inflammatory cytokines such as IL-6, MCP-1 and TNF-a from adipose tissue of diabetic rats with apparently no effect on non-diabetic rats; suggesting a conditional anti-inflammatory effect which may precede its anti-diabetic effects as MCP-1 and TNF-a are known to be pro-diabetic.
Fuxocanthin, at an oral intake of 0.02% of the diet in rats, has been demonstrated to increase GLUT4 translocation and protein content of the insulin receptor in rat skeletal muscle, and increased Akt phosphorylation in diabetic rats by 1.7-1.8 fold. Skeletal muscle mass appears to mediate many of fucoxanthin's anti-diabetic effects via taking up glucose.
Glucose uptake of skeletal muscle appears to be enhanced when diabetic mice are given fucoxanthin, but the biomarker of this (decreased blood glucose) has been shown to not occur in normal mice. It is possible that fucoxanthin alleviates abnormalities in skeletal muscle function associated with diabetes, but does not indiscriminately enhance glucose uptake (and thus limited usage in healthy individuals for glucose control). More studies would be needed to confirm
A fucoxanthin containing seaweed, Sargassum fusiforme, has been implicated in increasing osteoblast formation while decreasing osteoclast differentiation and theoretically exerting anti-osteoporotic effects.
Fucoxanthin, via inhibiting NF-kB transactivation, has also been implicated in preventing conversion of macrophages to osteoclast-like cells, and also induced apoptosis of these cells. At 2.5uM-5uM, fucoxanthin both reduced conversion to osteoclast-like cells and induced apoptosis in these cells while 10uM reduced cell viability or macrophages.
In DPPH assays, fucoxanthin has been shown to be active with an EC50 value of 0.14mg/mL and elsewhere 12.5-14.8µg/mL, 164.60µM, which are less than the reference of Vitamin C. Many carotenoids do not show direct free radical scavenging properties in DPPH assay (β-carotene, β-cryptoxanthin, zeaxanthin, and lutein) making fucoxanthin somewhat unique in this regard, and the metabolite known as fucoxanthinol appears to be more potent with an EC50 of 153.78µM. Similar trends are seen in an ABTS assay where fucoxanthin appears to scavenge free radicals with an EC50 value of 30µg/mL or 8.94µM; a potency again less than Vitamin C.
Against hydroxyl radicals, fucoxanthin appears to be 7.9-fold less potent than its metabolite fucoxanthinol and 13.5-fold less potent than the reference compound Vitamin E (assessed via chemiluminescence and ESR). That being said, fucoxanthin is still capable of protecting cells from H2O2 induced cytotoxicity to a degree and elsewhere it has been noted to have a potency slightly higher than Trolox yet still less than both astaxanthin, Vitamin E, and quercetin as reference compounds. Fucoxanthin appears to also protect against lipid peroxidation via scavenging peroxyl radicals and can act as a chain breaking antioxidant similar to Vitamin E.
Against singlet oxygen (of which carotenoids are known to sequester) and reactive nitrogen species (ONOO-), fucoxanthin appears to be less antioxidative than β-carotene. It has shown significantly protective properties against hypochlorous acid in vitro exceeding that of cysteine and other carotenoids (lutein and zeaxanthin), but still to a lesser degree than astaxanthin.
Fucoxanthin appears to have direct antioxidative properties, and these antioxidative properties seem to be more general than other carotenoids. That being said, they are not overly potent and have failed to outperform the reference compounds (Vitamin C, Vitamin E, β-carotene) and astaxanthin is another carotenoid compound that seems to generally outperform fucoxanthin
In cells exposed to UV-B irradiation fucoxanthin is able to cause concentration dependent cytoprotection secondary to sequestering reactive oxygen species (ROS), with the increase in ROS seen in cells from radiation (169.31% of baseline) being reduced progressively to 138.65% (5μM), 101.36% (50μM), 85.43% (100μM), and 71.08% (250μM) with 5μM (a somewhat physiologically relevant concentration) sequestering 18.11% of ROS and increasing cell survival from 43.48 to 59.73%.
Appears to be somewhat protective against UV(B) radiation damage secondary to the direct antioxidative properties
In mouse liver cells (BNL CL.2 cell line), fucoxanthin at 5μM appears to activate a gene known as Nrf2 secondary to causing pro-oxidative effects within a cell; a process known as hormesis. Activation of Nrf2 results in activation of the genome's antioxidant response element (ARE) and creation of two antioxidant enzymes known as Heme-oxygenase 1 (HO-1) and NQO1.
In liver cells, fucoxanthin may be able to hormetically induce an antioxidant response from the genome (ARE activation secondary to activatin Nrf2, resulting in HO-1 induction)
Antiinflammatory properties of seaweeds against LPS appears to correlate highly with the fucoxanthin content and be the main contributor of said antiinflammatory effects; accordingly, in LPS-stimulated macrophages fucoxanthin (15-60uM) is able to suppress the inflammatory response as assessed by iNOS and COX-2 induction as well as cytokine and nitric oxide secretion. While fucoxanthin require a high dose to be active, injections of fucoxanthin appear to be as potent as prednisone against LPS-induced inflammation when assessed by a gram per gram basis in rats.
The above antiinflammatory mechanisms are hypothesized to occur secondary to inhibiting translocation of NF-kB since elsewhere fucoxanthin has been noted to inhibit degradation of IκBα, a mechanism that ultimately prevents NF-kB translocation.
Fucoxanthin is able to suppress macrophage activation from LPS, which is a standard antiinflammatory response. While it appears to be quite potent at maximal efficacy (similar to prednisone), maximal efficacy may require an impractically high concentration of fucoxanthin to reach the immune cells and thus not be relevant to oral supplementation
Fucoxanthin and fucoxanthinol have been shown to inhibit proliferation of CD4(+) T-cells in response of IL-17 stimulation, which shows promise in treating disease states associated with TGF(b) and IF-17 related inflammation. This effect on T-cells was not seen with related compounds lutein, lycopene, nor astaxanthin and was not as effective as the research standard of all-trans retinoic acid (ATRA) and these effects were hypothesized to be secondary to Treg cell development via the retinoic acid receptor.
In the intervention on humans, it was found that Xanthigen-600 (contributing 2.4mg fucoxanthin daily) reduced ALT from 48+/-7 to 26+/-7 U/l, AST from 51+/-5 to 29+/-6 U/l, and GGT levels from 47+/-7 to 31+/-5 U/l. 2 weeks after the trial ended, these changes were maintained.
Non-alcoholic Fatty Liver Disease, or NAFLD, is increased deposition of triglycerides and fatty acids in the liver which adversely influences a variety of health parameters. In the intervention on humans, it was found that Xanthigen-600 (contributing 2.4mg fucoxanthin daily) had no effect on liver fat for 8 weeks of supplementation, but then by week 16 reduced liver fat by 15.3+/-4.1% in the group with baseline liver fat over 11% (the study's definition of NAFLD), and by 9.4+/-3.1% in the group with less than 11% baseline liver fat. These effects correlate well with fucoxanthin's effects on adipose tissue, and may be secondary to general fat burning.
Fucoxanthin appears to augment cisplatin induced cytotoxicity in liver cancer cells by inhibiting NF-kB and restoring IκB-α phosphorylation, a synergism that is common to all NF-kB inhibitors since cisplatin can itself promote NF-kB translocation (activation) which prevents apoptosis.
In isolated HeLa cells, 10-80μM fucoxanthin appears to cause concentration-dependent cytotoxicity over 48 hours of incubation with an IC50 of 55.1+/-7.6μM associated with G0/G1 arrest and autophagy; it was said to be secondary to inhibition of mTOR/Akt signalling.
Fucoxanthin shows synergism with Fish Oil, in which 6.9% of fish oil with 0.1% fucoxanthin in the diet is as potent as 0.2% fucoxanthin. This may be due to increased bioavailability, as the inclusion of Medium Chain Triglycerides (MCTs) has also been shown to increase the efficacy of fucoxanthin via increased absorption. Conjugated Linoleic Acid has also been shown to aid fucoxanthin's anti-obesity effects in rats.
Fucoxanthin can also increase hepatic stores of docosahexaenoic acid (DHA) in the liver independent of fish oil supplementation.
Coingestion of fucoxanthin with fatty acids, via increasing intestinal absorption of fucoxanthin and fucoxanthinol (a metabolite) increases the effects of fucoxanthin in the body since more gets into your body
Punicic Acid is a conjugated linoleic acid (structurally different from the standard Conjugated Linoleic Acid known as CLA) derived from Pomegranate. The two molecules have been shown to be synergistic in regards to suppressing adipocyte differentiation and related biomarkers such as: PPARy and C/EBPs, FOXO1 and FOXO3a, SIRT1, Fatty Acid Synthase, and AMPK/ACC phosphorylation. All effects seen were conducive to either suppressing differentation or otherwise preventing lipid accumulation in adipocytes and the synergism was towards anti-obesity. These results were seen in vitro, and are unrelated to increased bioavailability of fucoxanthin.
As assessed by the lone human study on the matter, there is benefit to combining Pomegranate Seed Oil and Fucoxanthin as this study used Xanthigen. Fucoxanthin at 2.4mg raised metabolic rate by 6.39+/-0.17kJ/min at the end of the study while the same dose with Pomegranate extract (300mg) increased it by 7.03+/-0.33kJ/min (a 10% increase) while Pomegranate even at 1500mg had no effect on metabolic rate.
Neither study disclosed interaction with companies invested in Xanthigen.
A relatively weak synergism, but a synergism none-the-less. Pomegranate Seed Oil and possibly Punicic Acid appear to increase the fat loss effects of Fucoxanthin
Despite being stored in the body for long periods (which may lead to overload symptoms in some molecules), toxicity has not been noted in mouse models. When tested for its mutagenicity (ability to produce mutations in DNA), fucoxanthinol (the circulating metabolite of fucoxanthin) came back negative in all in vitro tests and oral dosages of 2,000mg/kg bodyweight were unable to cause short-term adverse effects.