Carotenoids in Health as Studied by Omics-Related Endpoints.

Carotenoids have been associated with risk reduction for several chronic diseases, including the association of their dietary intake/circulating levels with reduced incidence of obesity, type 2 diabetes, certain types of cancer, and even lower total mortality. In addition to some carotenoids constituting vitamin A precursors, they are implicated in potential antioxidant effects and pathways related to inflammation and oxidative stress, including transcription factors such as nuclear factor κB and nuclear factor erythroid 2-related factor 2. Carotenoids and metabolites may also interact with nuclear receptors, mainly retinoic acid receptor/retinoid X receptor and peroxisome proliferator-activated receptors, which play a role in the immune system and cellular differentiation. Therefore, a large number of downstream targets are likely influenced by carotenoids, including but not limited to genes and proteins implicated in oxidative stress and inflammation, antioxidation, and cellular differentiation processes. Furthermore, recent studies also propose an association between carotenoid intake and gut microbiota. While all these endpoints could be individually assessed, a more complete/integrative way to determine a multitude of health-related aspects of carotenoids includes (multi)omics-related techniques, especially transcriptomics, proteomics, lipidomics, and metabolomics, as well as metagenomics, measured in a variety of biospecimens including plasma, urine, stool, white blood cells, or other tissue cellular extracts. In this review, we highlight the use of omics technologies to assess health-related effects of carotenoids in mammalian organisms and models.

Influence of Proteins on the Absorption of Lipophilic Vitamins, Carotenoids and Curcumin - A Review.

While proteins have been widely used to encapsulate, protect, and regulate the release of bioactive food compounds, little is known about the influence of co-consumed proteins on the absorption of lipophilic constituents following digestion, such as vitamins (A, D, E, K), carotenoids, and curcumin. Their bioavailability is often low and very variable, depending on the food matrix and host factors. Some proteins can act as emulsifiers during digestion. Their liberated peptides have amphiphilic properties that can facilitate the absorption of microconstituents, by improving their transition from lipid droplets into mixed micelles. Contrarily, the less well digested proteins could negatively impinge on enzymatic accessibility to the lipid droplets, slowing down their processing into mixed micelles and entrapping apolar food compounds. Interactions with mixed micelles and proteins are also plausible, as shown earlier for drugs. This review focuses on the ability of proteins to act as effective emulsifiers of lipophilic vitamins, carotenoids, and curcumin during digestion. The functional properties of proteins, their chemical interactions with enzymes and food constituents during gastro-intestinal digestion, potentials and limitations for their use as emulsifiers are emphasized and data from human, animal, and in vitro trials are summarized.

Obesity considerations during the COVID-19 outbreak.

The worldwide population is facing a double burden of epidemic, the COVID-19 and obesity. This is even more alarming as obesity increases the COVID-19 severity. However, the relationship between obesity and COVID-19 severity is more complex than a simple association with BMI. In particular, obesity has been associated with low death rates in patients with acute respiratory distress syndrome, a fatal comorbidity to COVID-19, possibly due to the obesity paradox. Also, visceral adiposity could be a major risk factor for COVID-19 severity, due to its immune activation component, release of angiotensin-converting enzyme 2 and involvement in the cytokine storm, hypercoagulability and embolism. A poor antioxidant nutritional status also weakens the immune system, increasing inflammation and infection risk. Moreover, the COVID-19 lockdown might impact lifestyle patterns, mental health and weight bias, worsening the obesity then COIVD-19 situation. On the other hand, health care expenses and productivity loss are expected to increase during the concomitant epidemics. The co-occurrence of obesity and COVID-19 is a major challenge at both public health and economic levels that should urgently be taken into consideration. The identification of COVID-19 weight related risk factors and the development of appropriate weight management programs are needed to tackle the concomitant epidemics.

Whey- and Soy Protein Isolates Added to a Carrot-Tomato Juice Alter Carotenoid Bioavailability in Healthy Adults.

Recent findings suggested that proteins can differentially affect carotenoid bioaccessibility during gastro-intestinal digestion. In this crossover, randomized human trial, we aimed to confirm that proteins, specifically whey- and soy-protein isolates (WPI/SPI) impact postprandial carotenoid bioavailability. Healthy adults (n = 12 males, n = 12 females) were recruited. After 2-week washout periods, 350 g of a tomato-carrot juice mixture was served in the absence/presence of WPI or SPI (50% of the recommended dietary allowance, RDA ≈ 60 g/d). Absorption kinetics of carotenoids and triacylglycerols (TAGs) were evaluated via the triacylglycerol-rich lipoprotein (TRL) fraction response, at timed intervals up to 10 h after test meal intake, on three occasions separated by 1 week. Maximum TRL-carotenoid concentration (Cmax) and corresponding time (Tmax) were also determined. Considering both genders and carotenoids/TAGs combined, the estimated area under the curve (AUC) for WPI increased by 45% vs. the control (p = 0.018), to 92.0 ± 1.7 nmol × h/L and by 57% vs. SPI (p = 0.006). Test meal effect was significant in males (p = 0.036), but not in females (p = 0.189). In males, significant differences were found for phytoene (p = 0.026), phytofluene (p = 0.004), α-carotene (p = 0.034), and ß-carotene (p = 0.031). Cmax for total carotenoids (nmol/L ± SD) was positively influenced by WPI (135.4 ± 38.0), while significantly lowered by SPI (89.6 ± 17.3 nmol/L) vs. the control (119.6 ± 30.9, p < 0.001). Tmax did not change. The results suggest that a well-digestible protein could enhance carotenoid bioavailability, whereas the less digestible SPI results in negative effects. This is, to our knowledge, the first study finding effects of proteins on carotenoid absorption in humans.

Gastric lipase can significantly increase lipolysis and carotenoid bioaccessibility from plant food matrices in the harmonized INFOGEST static in vitro digestion model.

Gastrointestinal digestion of carotenoids has received much attention, as these lipophilic compounds have been related to several health benefits. Most commonly, static digestion models such as the consensus INFOGEST model are employed to study their bioaccessibility from test matrices. However, an aspect that has been much neglected is the use of gastric lipase. Its inclusion to gastro-intestinal (GI) digestion is expected to foster emulsification of lipophilic constituents prior to their incorporation into mixed micelles. In this study, we compared the effect of various lipases from R. niveus, R. oryzae, and rabbit gastric extracts (RGE), at different concentrations (0, 30, and 60 U mL-1), on carotenoid bioaccessibility from several food matrices (tomato juice, spinach, and carrot juice). We also investigated whether co-digestion of pure proteins (whey and soy protein isolates) at 0, 25, and 50% of the equivalent recommended dietary allowance, would interact with carotenoid bioaccessibility in presence or absence of RGE. Lipolysis was also studied. Considering all matrices combined, lipases significantly improved the bioaccessibility of carotenoids (p < 0.001). Compared to other lipases, RGE consistently increased carotenoid bioaccessibility in all tested matrices, by up to 182% (p < 0.001), this effect was partly maintained in the presence of co-digested proteins. Unexpectedly, all 3 lipases improved gastric lipolysis in all matrices, by an average of 10-fold (p < 0.001). In conclusion, only RGE contributed significantly to improving both lipolysis extent and carotenoid bioaccessibility in all tested matrices, while the presence of proteins mitigated the positive effect of lipases on carotenoid bioaccessibility.

Impact of Protein-Enriched Plant Food Items on the Bioaccessibility and Cellular Uptake of Carotenoids.

Carotenoids are lipophilic pigments which have been associated with a number of health benefits, partly related to antioxidant effects. However, due to their poor solubility during digestion, carotenoid bioavailability is low and variable. In this study, we investigated the effect of frequently consumed proteins on carotenoid bioaccessibility and cellular uptake. Whey protein isolate (WPI), soy protein isolate (SPI), sodium caseinate (SC), gelatin (GEL), turkey and cod, equivalent to 0/10/25/50% of the recommended dietary allowance (RDA, approx. 60g/d), were co-digested gastro-intestinally with carotenoid-rich food matrices (tomato and carrot juice, spinach), and digesta further studied in Caco-2 cell models. Lipid digestion, surface tension and microscopic visualization were also carried out. Co-digested proteins positively influenced the micellization of carotenes (up to 3-fold, depending on type and concentration), especially in the presence of SPI (p < 0.001). An increased cellular uptake was observed for xanthophylls/carotenes (up to 12/33%, p < 0.001), which was stronger for matrices with an initially poor carotenoid micellization (i.e., tomato juice, p < 0.001), similar to what was encountered for bioaccessibility. Turkey and cod had a weaker impact. Significant interactions between carotenoids, lipids and proteins were observed during digestion. Co-digested proteins generally improved lipid digestion in all matrices (p < 0.001), especially for carrot juice, though slight decreases were observed for GEL. Protein impact on the surface tension was limited. In conclusion, proteins generally improved both carotenoid bioaccessibility and cellular uptake, depending on the matrices and carotenoid-type (i.e., carotene vs. xanthophylls), which may be relevant under specific circumstances, such as intake of carotenoid-rich food items low in lipids.

Phytochemicals as modifiers of gut microbial communities.

A healthy gut microbiota (GM) is paramount for a healthy lifestyle. Alterations of the GM have been involved in the aetiology of several chronic diseases, including obesity and type 2 diabetes, as well as cardiovascular and neurodegenerative diseases. In pathological conditions, the diversity of the GM is commonly reduced or altered, often toward an increased Firmicutes/Bacteroidetes ratio. The colonic fermentation of dietary fiber has shown to stimulate the fraction of bacteria purported to have beneficial health effects, acting as prebiotics, and to increase the production of short chain fatty acids, e.g. propionate and butyrate, while also improving gut epithelium integrity such as tight junction functionality. However, a variety of phytochemicals, often associated with dietary fiber, have also been proposed to modulate the GM. Many phytochemicals possess antioxidant and anti-inflammatory properties that may positively affect the GM, including polyphenols, carotenoids, phytosterols/phytostanols, lignans, alkaloids, glucosinolates and terpenes. Some polyphenols may act as prebiotics, while carotenoids have been shown to alter immunoglobulin A expression, an important factor for bacteria colonization. Other phytochemicals may interact with the mucosa, another important factor for colonization, and prevent its degradation. Certain polyphenols have shown to influence bacterial communication, interacting with quorum sensing. Finally, phytochemicals can be metabolized in the gut into bioactive constituents, e.g. equol from daidzein and enterolactone from secoisolariciresinol, while bacteria can use glycosides for energy. In this review, we strive to highlight the potential interactions between prominent phytochemicals and health benefits related to the GM, emphasizing their potential as adjuvant strategies for GM-related diseases.

Influence of soy and whey protein, gelatin and sodium caseinate on carotenoid bioaccessibility.

Proteins could alter carotenoid bioaccessibility through altering their fate during digestion, due to emulsifying properties of resulting peptides, or influencing access of digestion enzymes to lipid droplets. In this investigation, we studied whether whey protein isolate (WPI), soy protein isolate (SPI), sodium caseinate (SC) and gelatin (GEL), added at various concentrations (expressed as percentage of recommended dietary allowance (RDA): 0, 10, 25 and 50%) would influence the bioaccessibility of lycopene, ß-carotene or lutein, added as pure carotenoids solubilized in oil, during simulated gastro-intestinal (GI) digestion. Protein and lipid digestion as well as selected physico-chemical parameters including surface tension, ζ-potential and micelle size were evaluated. Adding proteins influenced positively the bioaccessibility of ß-carotene, by up to 189% (p < 0.001), but it resulted in generally decreased bioaccessibility of lutein, by up to 50% (p < 0.001), while for lycopene, the presence of proteins did not influence its bioaccessibility, except for a slight increase with WPI, by up to 135% (p < 0.001). However, the effect depended significantly on the type of protein (p < 0.001) and its concentration (p < 0.001). While ß-carotene bioaccessibility was greatly enhanced in the presence of SC, compared to WPI and GEL, the presence of SPI strongly decreased carotenoid bioaccessibility. Neglecting individual carotenoids, higher protein concentration correlated positively with carotenoid bioaccessibility (R = 0.57, p < 0.01), smaller micelle size (R = -0.83, p < 0.01), decreased repulsive forces (ζ-potential, R = -0.72, p < 0.01), and higher surface tension (R = 0.44, p < 0.01). In conclusion, proteins differentially affected carotenoid bioaccessibility during digestion depending on carotenoid and protein species, with both positive and negative interactions occurring.

Strengthening the Immune System and Reducing Inflammation and Oxidative Stress through Diet and Nutrition: Considerations during the COVID-19 Crisis.

The coronavirus-disease 2019 (COVID-19) was announced as a global pandemic by the World Health Organization. Challenges arise concerning how to optimally support the immune system in the general population, especially under self-confinement. An optimal immune response depends on an adequate diet and nutrition in order to keep infection at bay. For example, sufficient protein intake is crucial for optimal antibody production. Low micronutrient status, such as of vitamin A or zinc, has been associated with increased infection risk. Frequently, poor nutrient status is associated with inflammation and oxidative stress, which in turn can impact the immune system. Dietary constituents with especially high anti-inflammatory and antioxidant capacity include vitamin C, vitamin E, and phytochemicals such as carotenoids and polyphenols. Several of these can interact with transcription factors such as NF-kB and Nrf-2, related to anti-inflammatory and antioxidant effects, respectively. Vitamin D in particular may perturb viral cellular infection via interacting with cell entry receptors (angiotensin converting enzyme 2), ACE2. Dietary fiber, fermented by the gut microbiota into short-chain fatty acids, has also been shown to produce anti-inflammatory effects. In this review, we highlight the importance of an optimal status of relevant nutrients to effectively reduce inflammation and oxidative stress, thereby strengthening the immune system during the COVID-19 crisis.

Whey protein isolate modulates beta-carotene bioaccessibility depending on gastro-intestinal digestion conditions.

Carotenoids are lipophilic phytochemicals; their intake has been associated with reduced chronic diseases. However, their absorption depends on emulsification during digestion and incorporation into mixed micelles, requiring digestive enzymes, gastric peristalsis, bile, and dietary lipids. In this study, we investigated whether whey-protein-isolate (WPI), a commonly consumed protein source, can modulate ß-carotene bioaccessibility in vitro, especially under incomplete digestive conditions, i.e. under low digestive enzyme concentrations. Thus, amounts of pepsin, pancreatin, bile, co-digested lipids and kinetic energy and gastric digestion time were modified, and WPI at concentrations equivalent to 0/25/50% of the protein recommended dietary allowance (approx. 60 g/d) were added to ß-carotene dissolved in oil. WPI enhanced bioaccessibility by up to 20% (p < 0.001), especially under higher simulated peristalsis or reduced amount of dietary lipids. Conversely, they impaired bioaccessibility to one third (p < 0.001) under incomplete digestive conditions. WPI modulated ß-carotene bioaccessibility depending on digestive conditions.

Sea Buckthorn Oil as a Valuable Source of Bioaccessible Xanthophylls.

Sea buckthorn oil, derived from the fruits of the shrub, also termed seaberry or sandthorn, is without doubt a strikingly rich source of carotenoids, in particular zeaxanthin and ß-carotene. In the present study, sea buckthorn oil and an oil-in-water emulsion were subjected to a simulated gastro-intestinal in vitro digestion, with the main focus on xanthophyll bioaccessibility. Zeaxanthin mono- and di-esters were the predominant carotenoids in sea buckthorn oil, with zeaxanthin dipalmitate as the major compound (38.0%). A typical fatty acid profile was found, with palmitic (49.4%), palmitoleic (28.0%), and oleic (11.7%) acids as the dominant fatty acids. Taking into account the high amount of carotenoid esters present in sea buckthorn oil, the use of cholesterol esterase was included in the in vitro digestion protocol. Total carotenoid bioaccessibility was higher for the oil-in-water emulsion (22.5%) compared to sea buckthorn oil (18.0%) and even higher upon the addition of cholesterol esterase (28.0% and 21.2%, respectively). In the case of sea buckthorn oil, of all the free carotenoids, zeaxanthin had the highest bioaccessibility (61.5%), followed by lutein (48.9%), making sea buckthorn oil a potential attractive source of bioaccessible xanthophylls.

Effect of divalent minerals on the bioaccessibility of pure carotenoids and on physical properties of gastro-intestinal fluids.

During digestion, high concentrations of divalent minerals (DMs) can lead to insoluble lipid-soap complex formation, hampering carotenoid bioaccessibility. The effect of varying concentrations (0-1000 mg/L) of calcium, magnesium, zinc and sodium (control) on the bioaccessibility of lutein, neoxanthin, lycopene and ß-carotene, following in vitro gastro-intestinal digestion (GI), was investigated systematically and coupled with physical measurements of the digesta. Addition of DMs significantly decreased (p<0.001) carotenoid bioaccessibility, up to 100% in the case of calcium. Mean half maximal inhibitory concentrations (EC50) for calcium, magnesium and zinc were 270±18, 253±75 and 420±322 mg/L respectively. Increased DM concentrations correlated with decreased viscosity (r>0.9) and decreased carotenoid bioaccessibility. Surface tension of digesta correlated inversely (p<0.05) with the bioaccessibility of carotenoids. This correlation was mineral and carotenoid dependent. Although based on in vitro findings, it is plausible that similar interactions occur in vivo, with DMs affecting the bioaccessibility and bioavailability of carotenoids and other lipophilic micronutrients and phytochemicals.