Purpose: Adherence to the Mediterranean diet is associated with beneficial health effects, including gastrointestinal disorders. Preclinical studies suggest that omega-3 polyunsaturated fatty acids (n-3 PUFAs), found in Mediterranean foods like nuts and fish, improve intestinal barrier integrity. Here, we assessed possible effects of n-3 PUFAs on barrier integrity in a randomized controlled trial. Methods: We studied 68 women from the open-label LIBRE trial (clinicaltrials.gov: NCT02087592) who followed either a Mediterranean diet (intervention group, IG) or a standard diet (control group, CG). Study visits comprised baseline, month 3, and month 12. Barrier integrity was assessed by plasma lipopolysaccharide binding protein (LBP) and fecal zonulin; fatty acids by gas chromatography with mass spectrometry. Median and interquartile ranges are shown. Results: Adherence to the Mediterranean diet increased the proportion of the n-3 docosahexaenoic acid (DHA) (IG + 1.5% [0.9;2.5, p < 0.001]/ + 0.3% [− 0.1;0.9, p < 0.050] after 3/12 months; CG + 0.9% [0.5;1.6, p < 0.001]/ ± 0%) and decreased plasma LBP (IG − 0.3 µg/ml [− 0.6;0.1, p < 0.010]/ − 0.3 µg/ml [− 1.1; − 0.1, p < 0.001]; CG − 0.2 µg/ml [− 0.8; − 0.1, p < 0.001]/ ± 0 µg/ml) and fecal zonulin levels (IG − 76 ng/mg [− 164; − 12, p < 0.010]/ − 74 ng/mg [− 197;15, p < 0.001]; CG − 59 ng/mg [− 186;15, p < 0.050]/ + 10 ng/mg [− 117;24, p > 0.050]). Plasma DHA and LBP (R²: 0.14–0.42; all p < 0.070), as well as plasma DHA and fecal zonulin (R²: 0.18–0.48; all p < 0.050) were found to be inversely associated in bi- and multivariate analyses. Further multivariate analyses showed that the effect of DHA on barrier integrity was less pronounced than the effect of fecal short-chain fatty acids on barrier integrity. Conclusions: Our data show that n-3 PUFAs can improve intestinal barrier integrity. Trial registration number: The trial was registered prospectively at ClinicalTrials.gov (reference: NCT02087592).

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.

Obesity is characterized by low-grade inflammation and increased gut permeability. Here, we aim to evaluate the effect of a nutritional supplement on these parameters in subjects with overweight and obesity. A double-blinded, randomized clinical trial was conducted in 76 adults with overweight or obesity (BMI 28 to 40) and low-grade inflammation (high-sensitivity C-reactive protein (hs-CRP) between 2 and 10 mg/L). The intervention consisted of a daily intake of a multi-strain probiotic of Lactobacillus and Bifidobacterium, 640 mg of omega-3 fatty acids (n-3 FAs), and 200 IU of vitamin D (n = 37) or placebo (n = 39), administered for 8 weeks. hs-CRP levels did not change post-intervention, other than an unexpected slight increase observed in the treatment group. Interleukin (IL)-6 levels decreased in the treatment group (p = 0.018). The plasma fatty acid (FA) levels of the arachidonic acid (AA)/eicosapentaenoic acid (EPA) ratio and n-6/n-3 ratio (p < 0.001) decreased, and physical function and mobility improved in the treatment group (p = 0.006). The results suggest that hs-CRP may not be the most useful inflammatory marker, but probiotics, n-3 FAs, and vitamin D, as non-pharmaceutical supplements, may exert modest effects on inflammation, plasma FA levels, and physical function in patients with overweight and obesity and associated low-grade inflammation.

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 β-glucans, cultured in bioreactors. In this pilot trial, 19 healthy elderly received supplements for two weeks based on either the whole PT (A), the β-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.

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.