Metabolism of 11'-α- and 11'-γ-Tocomonoenols in HepG2 Cells Favors the γ-Congener and Results Predominantly in Carboxymethylbutyl-Hydroxychromans.

SCOPE: Tocomonoenols (T1) are little-known vitamin E derivatives naturally occurring in foods. Limited knowledge exists regarding the cellular uptake and metabolism of α-tocomonoenol (αT1) and none about that of γ-tocomonoenol (γT1). METHODS AND RESULTS: The study investigates the cytotoxicity, uptake, and metabolism of αT1 and γT1 in HepG2 cells compared to the α- and γ-tocopherols (T) and -tocotrienols (T3). None of the studied tocochromanols are cytotoxic up to 100 µmol L-1. The uptake of the γ-congeners is significantly higher than that of the corresponding α-forms, whereas no significant differences are observed based on the degree of saturation of the sidechain. Carboxymethylbutyl-hydroxychromans (CMBHC) are the predominant short-chain metabolites of all tocochromanols and conversion is higher for γT1 than αT1 as well as for the γ-congeners of T and T3. The rate of metabolism increases with the number of double bonds in the sidechain. The rate of metabolic conversion of the T1 is more similar to tocopherols than to that of the tocotrienols. CONCLUSION: This is the first evidence that both αT1 and γT1 follow the same sidechain degradation pathway and exert similar rates of metabolism than tocopherols. Therefore, investigation into the biological activities of tocomonoenols is warranted.

Monodopsis subterranea is a source of α-tocomonoenol, and its concentration, in contrast to α-tocopherol, is not affected by nitrogen depletion.

α-Tomonoenols (αT1) are tocochromanols structurally related to tocopherols (T) and tocotrienols (T3), the bioactive members of the vitamin E family. However, limited evidence exists regarding the sources and biosynthesis of tocomonoenols. Nitrogen depletion increases the content of α-tocopherol (αT), the main vitamin E congener, in microalgae, but little is known regarding its effect on other tocochromanols, such as tocomonoenols and tocotrienols. We therefore quantified the concentrations of T, T1, and T3, in freeze-dried biomass from nitrogen-sufficient, and nitrogen-depleted Monodopsis subterranea (Eustigmatophyceae). The identities of isomers of αT1 were confirmed by LC-MS and GC-MS. αT was the predominant tocochromanol (82% of total tocochromanols). αT1 was present in higher quantities than the sum of all T3 (6% vs. 1% of total tocochromanols). 11'-αT1 was the main αT1 isomer. Nitrogen depletion increased αT, but not αT1 or T3 in M. subterranea. In conclusion, nitrogen depletion increased the content of αT, the biologically most active form of vitamin E, in M. subterranea without affecting αT1 and T3 and could potentially be used as a strategy to enhance its nutritional value but not to increase αT1 content, indicating that αT1 accumulation is independent of that of αT in microalgae.

Potentially Beneficial Effects on Healthy Aging by Supplementation of the EPA-Rich Microalgae Phaeodactylum tricornutum or Its Supernatant-A Randomized Controlled Pilot Trial in Elderly Individuals.

Dietary supplements that promote healthy aging are mostly warranted in an aging society. Because of age-related risks, anti-inflammatory and anti-oxidative agents such as microalgae are potential candidates for intervention. In a randomized controlled trial, we tested Phaeodactylum tricornutum (PT), a microalgae rich in eicosapentaenoic acid (EPA), carotenoids, vitamins, and ß-glucans, cultured in bioreactors. In this pilot trial, 19 healthy elderly received supplements for two weeks based on either the whole PT (A), the ß-1,3-glucan-rich PT supernatant (SupB), the combination thereof (A+SupB), or a Comparator product (Comp). The primary outcome variable plasma interleukin-6 was reduced after treatment with A+SupB compared to the Comp group (p = 0.04). The mobility parameters 5 s sit-to-stand test (p = 0.04 in the A group) and by trend gait speed (p = 0.08 in the A+SupB diet) were improved compared to Comp. No treatment effects were observed for fatty acids, compared to Comp but omega-6 to -3 fatty acid ratio (p = 0.006) and arachidonic acid/EPA ratio (p = 0.006) were reduced within group A+SupB. Further, the SupB study product reduced faecal zonulin (p = 0.03) compared to the Comp. The data revealed an anti-inflammatory and potentially anti-oxidative effect of particular PT preparations, suggesting that they might be suitable for effects in healthy elderly.

Vitamin E and carotenoid profiles in leaves, stems, petioles and flowers of stinging nettle (Urtica leptophylla Kunth) from Costa Rica.

BACKGROUND: Local leafy vegetables are gaining attention as affordable sources of micronutrients, including vitamins, pro-vitamin carotenoids and other bioactive compounds. Stinging nettles (Urtica spp.) are used as source of fibers, herbal medicine and food. However, despite the relatively wide geographical spread of Urtica leptophylla on the American continent, little is known about its content of vitamin E congeners and carotenoids. We therefore investigated the particular nutritional potential of different plant structures of wild Costa Rican U. leptophylla by focusing on their vitamin E and carotenoid profiles. RESULTS: Young, mature and herbivore-damaged leaves, flowers, stems and petioles were collected and freeze-dried. Vitamin E and carotenoids were determined by high-performance liquid chromatography after liquid/liquid extraction with hexane. α-Tocopherol was the major vitamin E congener in all structures. Flowers had a high content of γ-tocopherol. Herbivore-damaged leaves had higher contents of vitamin E than undamaged leaves. Lutein was the major and ß-carotene the second most abundant carotenoid in U. leptophylla. No differences in carotenoid profiles were observed between damaged and undamaged leaves. CONCLUSION: The leaves of U. leptophylla had the highest nutritional value of all analyzed structures; therefore, they might represent a potential source of α-tocopherol, lutein and ß-carotene. © 2022 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Tocochromanol Profiles in Chlorella sorokiniana, Nannochloropsis limnetica and Tetraselmis suecica Confirm the Presence of 11'-α-Tocomonoenol in Cultured Microalgae Independently of Species and Origin.

11'-α-Tocomonoenol (11'-αT1) is structurally related to vitamin E and has been quantified in the microalgae Tetraselmis sp. and Nannochloropsis oceanica. However, it is not known whether 11'-αT1 is present in other microalgae independent of species and origin. The aim of this study was to analyze the tocochromanol profiles of Chlorella sorokiniana, Nannochloropsis limnetica, and Tetraselmis suecica and to determine if 11'-αT1 is present in these microalgae. Cultured microalgae were freeze-dried and the presence and identity of α-tocomonoenols were confirmed by LC-MSn (liquid chromatography coupled to mass spectroscopy) and GC-MS (gas chromatography coupled to mass spectroscopy). Tocochromanol profiles were determined by HPLC-FLD (liquid chromatography with fluorescence detection) and fatty acid profiles (as fatty acid methyl esters; FAME) by GC-MS. As confirmed by LC-MSn and GC-MS, 11'-αT1 was the dominant αT1 isomer in cultured microalgae instead of 12'-αT1, the isomer also known as marine-derived tocopherol. αT1 represented less than 1% of total tocochromanols in all analyzed samples and tended to be more abundant in microalgae with higher proportions of polyunsaturated fatty acids. In conclusion, our findings confirm that αT1 is not restricted to terrestrial photosynthetic organisms, but can also accumulate in microalgae of different species, with 11'-αT1-and not the marine-derived tocopherol (12'-αT1)-as the predominant αT1 isomer.

Oral Bioavailability of Omega-3 Fatty Acids and Carotenoids from the Microalgae Phaeodactylum tricornutum in Healthy Young Adults.

The microalgae Phaeodactylum tricornutum (PT) contains valuable nutrients such as proteins, polyunsaturated omega-3 fatty acids (n-3 PUFA), particularly eicosapentaenoic acid (EPA) and some docosahexaenoic acid (DHA), carotenoids such as fucoxanthin (FX), and beta-glucans, which may confer health benefits. In a randomized intervention trial involving 22 healthy individuals, we administered for two weeks in a crossover manner the whole biomass of PT (5.3 g/day), or fish oil (FO) containing equal amounts of EPA and DHA (together 300 mg/day). In an additional experiment, sea fish at 185 g/week resulting in a similar EPA and DHA intake was administered in nine individuals. We determined the bioavailability of fatty acids and carotenoids and assessed safety parameters. The intake of PT resulted in a similar increase in the n-3 PUFA and EPA content and a decrease in the PUFA n-6:n-3 ratio in plasma. PT intake caused an uptake of FX that is metabolized to fucoxanthinol (FXOH) and amarouciaxanthin A (AxA). No relevant adverse effects occurred following PT consumption. The study shows that PT is a safe and effective source of EPA and FX-and likely other nutrients-and therefore should be considered as a future sustainable food item.

Cytotoxicity, cellular uptake, and metabolism to short-chain metabolites of 11'-α-tocomonoenol is similar to RRR-α-tocopherol in HepG2 cells.

Contrary to the major vitamin E congener α-tocopherol, which carries a saturated sidechain, and α-tocotrienol, with a threefold unsaturated sidechain, little is known about the intracellular fate of α-tocomonoenol, a minor vitamin E derivative with a single double bond in C11'-position of the sidechain. We hypothesized that, due to structural similarities, the uptake and metabolism of α-tocomonoenol will resemble that of α-tocopherol. Cytotoxicity, cellular uptake of α-tocomonoenol, α-tocopherol and α-tocotrienol and conversion into the short-chain metabolites αCEHC and αCMBHC were studied in HepG2 cells. α-Tocomonoenol did not show significant effects on cell viability and its uptake was similar to that observed for α-tocopherol and significantly lower than for α-tocotrienol. α-Tocomonoenol was mainly metabolized to αCMBHC in liver cells, but to a lower extent than α-tocotrienol, while α-tocopherol was not metabolized in quantifiable amounts at all. In summary, the similarities in the cytotoxicity, uptake and metabolism of α-tocomonoenol and α-tocopherol suggest that this minor vitamin E congener deserves more attention in future research with regard to its potential vitamin E activity.