Mitochondrial dysfunction is a common feature of brain disorders. Mitochondria play a central role in oxidative phosphorylation; thus changes in energy metabolism in the brain have been reported in conditions such as Alzheimer’s disease, Parkinson’s disease, and stroke. In addition, mitochondria regulate cellular responses associated with neuronal damage such as the production of reactive oxygen species (ROS), opening of the mitochondrial permeability transition pore (mPTP), and apoptosis. Therefore, interventions that aim to protect mitochondria may be effective against brain disorders. Fucoxanthin is a marine carotenoid that has recently gained recognition for its neuroprotective properties. However, the cellular mechanisms of fucoxanthin in brain disorders, particularly its role in mitochondrial function, have not been thoroughly discussed. This review summarises the current literature on the effects of fucoxanthin on oxidative stress, neuroinflammation, and apoptosis using in vitro and in vivo models of brain disorders. We further present the potential mechanisms by which fucoxanthin protects mitochondria, with the objective of developing dietary interventions for a spectrum of brain disorders. Although the studies reviewed are predominantly preclinical studies, they provide important insights into understanding the cellular and molecular functions of fucoxanthin in the brain. Future studies investigating the mechanisms of action and the molecular targets of fucoxanthin are warranted to develop translational approaches to brain disorders.

Aging is the most prominent risk factor for many diseases, which is considered to be a complicated biological process. The rate of aging depends on the effectiveness of important mechanisms such as the protection of DNA from free radicals, which protects the structural and functional integrity of cells and tissues. In any organism, not all organs may age at the same rate. Slowing down primary aging and reaching maximum lifespan is the most basic necessity. In this process, it may be possible to slow down or stabilise some diseases by using the compounds for both dietary and pharmacological purposes. Natural compounds with antioxidant and anti-inflammatory effects, mostly plant-based nutraceuticals, are preferred in the treatment of age-related chronic diseases and can also be used for other diseases. An increasing number of long-term studies on synthetic and natural compounds aim to elucidate preclinically and clinically the mechanisms underlying being healthy and prolongation of life. To delay age-related diseases and prolong the lifespan, it is necessary to take these compounds with diet or pharmaceuticals, along with detailed toxicological results. In this review, the most promising and utilised compounds will be highlighted and it will be discussed whether they have toxic effects in short/long-term use, although they are thought to be used safely.

Lifestyle-related problems are becoming a major health threat in East Asian countries. Therefore, finding an efficacious nutraceutical for this population is important. One candidate is fucoxanthin (Fx), a carotenoid abundantly found in edible brown seaweed that has been associated with a number of valuable health-promoting benefits. Unfortunately, clinical studies of Fx are limited. In the present study, we aimed to evaluate the effects of Fx on obesity-related parameters in Japanese subjects harbouring an SNP associated with lifestyle-related problems. In all, sixty normal-weight and obese Japanese adults with BMI over 22 kg/m2 were single-blinded and randomly assigned to three Fx-dose cohorts and administered Fx-enriched akamoku oil containing Fx at 0, 1 or 2 mg/d for 8 weeks (n 20 per group). Parameters relating to obesity and serum Fx metabolites were measured before and after intervention, but no significant differences were observed between and within the groups. Despite no changes in visceral fat areas and resting energy expenditures after intervention, we observed a significant decline in HbA1c levels in the 2 mg/d Fx group compared with that in the 0 mg/d group (P < 0·05), which was correlated with an increase in serum fucoxanthinol (Fx metabolite) levels. In addition, HbA1c levels declined more significantly in subjects with G/G alleles of the uncoupling protein 1 (UCP1) gene than in those with the A/A and A/G alleles (P < 0·05). We conclude that although Fx supplementation does not affect visceral fat areas, it may reduce HbA1c levels in those harbouring the thrifty allele of UCP1-3826A/G.

Dietary fucoxanthin has been reported to exert several physiological functions, and fucoxanthinol is considered to be the primary active metabolite of fucoxanthin. However, there is no information about the pharmacokinetics of fucoxanthinol in human subjects. In the present study, eighteen human volunteers were orally administered kombu extract containing 31 mg fucoxanthin, and their peripheral blood was collected 5 min before and 0·5, 1, 2, 4, 8 and 24 h after the treatment. Plasma fucoxanthinol concentrations were measured by HPLC, and the pharmacokinetics of fucoxanthinol were as follows: maximum concentration, 44·2 nmol/l; time at maximum concentration, 4 h; terminal half-time, 7·0 h; area under the curve (AUC) for 1–24 h, 578·7 nmol/l × h; AUC(∞), 663·7 nmol/l × h. In addition to fucoxanthinol, we also attempted to detect amarouciaxanthin A, a hepatic metabolite of fucoxanthinol, using HPLC, but it was not present in the volunteers' plasma. On the other hand, a peak that was suspected to represent the cis-isomer of fucoxanthinol was found in the HPLC chromatogram. By comparing the present results with those of a previous study using mice, we found that the bioavailability and metabolism of fucoxanthinol differ between human subjects and mice.

The pharmacokinetics of dietary fucoxanthin, one of the xanthophylls in brown sea algae, is little understood. In the present study, mice were orally administered fucoxanthin, and the distribution and accumulation of fucoxanthin and its metabolites fucoxanthinol and amarouciaxanthin A were measured in the plasma, erythrocytes, liver, lung, kidney, heart, spleen and adipose tissue. In a single oral administration of 160 nmol fucoxanthin, fucoxanthinol and amarouciaxanthin A were detectable in all specimens tested in the present study, but fucoxanthin was not. The time at maximum concentration (Tmax) of these metabolites in adipose tissue was 24 h, while the Tmax in the others was 4 h. The area under the curve to infinity (AUC∞) of fucoxanthinol in the liver was the highest value (4680 nmol/g × h) among the tissues tested in the present study, while the AUC∞ of amarouciaxanthin A in adipose tissue was the highest value (4630 nmol/g × h). In daily oral administration of 160 nmol fucoxanthin for 1 week, fucoxanthin was also detectable in the tissues even at a low concentration. The amount of fucoxanthinol was 123 nmol/g in the heart and 85·2 nmol/g in the liver. Amarouciaxanthin A in the adipose tissue was distributed at a concentration of 97·5 nmol/g. These results demonstrate that dietary fucoxanthin accumulates in the heart and liver as fucoxanthinol and in adipose tissue as amarouciaxanthin A.

Epoxyxanthophylls (epoxide-containing xanthophylls), a group of carotenoids, are ubiquitously distributed in edible plants. Among them, neoxanthin in green leafy vegetables and fucoxanthin in brown algae have been reported to exhibit an antiproliferative effect on several human cancer cells in vitro. However, there is little information about the intestinal absorption and metabolic fate of dietary epoxyxanthophylls in humans. To estimate the intestinal absorption of neoxanthin and fucoxanthin in humans, we evaluated the plasma epoxyxanthophyll concentrations before and after 1-week dietary interventions with spinach (Spinacia oleracea) and wakame (Undaria pinnatifida). The epoxyxanthophylls and their metabolites in the plasma extracts were determined by HPLC after partial purification and concentration with solid-phase extraction cartridges. Even after 1 week of spinach intake (3·0 mg neoxanthin/d), the plasma concentrations of neoxanthin and its metabolites (neochrome stereoisomers) remained very low (about 1 nmol/l), whereas those of β-carotene and lutein were markedly increased. Similarly, the plasma concentration of fucoxanthinol, a gastrointestinal metabolite of fucoxanthin, was < 1 nmol/l after 1 week of wakame intake (6·1 mg fucoxanthin/d). These results indicated that the plasma response to dietary epoxyxanthophylls was very low in humans even after 1-week intake of epoxyxanthophyll-rich diets.