■ SOURCES OF CAROTENOIDS
Of the more than 700 carotenoids and xanthophylls (oxygencontaining carotenoids) already identified, seven of these are more frequently found in the human diet: α/β-carotene, lycopene, lutein, zeaxanthin, β-cryptoxanthin, and astaxanthin.1 A wide variety of plant foods (vegetables and fruits), maintained throughout the year, represent the main sources of carotenoids for humans. Green fruits (green pepper) and green leafy (e.g., lettuce and spinach) and non-leafy (e.g., artichokes and green asparagus) vegetables provide substantial amounts of lutein and minor proportions α/β-carotene and zeaxanthin. Tomato and derived cooked products (baked, stuffed, or fried) are the main sources of lycopene, despite also providing significant quantities of β-carotene, phytoene, and phytofluene.
Orange- and yellow-colored fruits, seeds, and nonleafy vegetables (mainly roots) are also significant dietary sources of α/β-carotene, zeaxanthin, and β-cryptoxanthin. Carrot is the main contributor to α/β-carotene, but seasonal intake of other orange-colored fruits, such as peach, apricot, and pumpkin, are also good sources of these carotenes in the diet. The main sources of β-cryptoxanthin in the human diet are sweet oranges and mandarins.
Although fruits and vegetables are undeniably the main sources of carotenoids in the human diet, we cannot ignore the contribution of animal-derived foods, such as egg yolk (accounting for important zeaxanthin, lutein, and α/β-carotene sources), dairy products (for α/β-carotene), and salmonid fishes/seafood (main sources of astaxanthin and canthaxanthin). No specific recommendation for daily total carotenoid intake has been officially issued by any nutritional/health organization thus far, e.g., U.S. Food and Drug Administration (FDA) or World Health Organization (WHO), but on the basis of the recommended dietary allowance (RDA) for retinol equivalents in healthy adult males (700−900 μg of retinol equiv/day), a prudent individual daily intake (PIDI) was assumed around 9.0−18.0 mg of total carotenoid/day.1
■ BIOAVAILABILITY AND ABSORPTION
The transfer of carotenoids from food stuff to target tissues and cells depends, obviously, upon many factors, including bioavailability from the food matrix, chemical transformation during digestion (carotenoid ester hydrolysis, cis−trans isomerization, etc.), absorption by the gastrointestinal tract, and transport to different human cells and tissues.4 Moreover, recent findings indicate that host−gut microbiota interactions could afford variable interindividual carotenoid absorption, especially through changes in bile acid/salt composition and concentration and via carotenoid efflux back to intestinal lumen by scavenger receptor-class B type I (SR-BI).5
■ METABOLISM
Within enterocytes, dietary carotenoids may be cleaved by 15,15′-oxygenase 1 (BCO1) and/or 9′,10′-oxygenase 2 (BCO2), despite differences in enzyme/substrate affinities (Km values), resulting in the formation of a wide range of apocarotenals and retinol-derived products (only from provitamin A carotenoids). Although multiple apocarotenoids may be found in circulation after absorption, most carotenoids are found intact in chylomicrons and other circulating lipoproteins after regular and carotenoid-rich meals.4
■ MODES OF ACTION
The health benefits provided by dietary carotenoids foundationally rely on five biological properties: (i) as antioxidants that scavenge and quench reactive redox intermediates of oxidative metabolism, (ii) as electrophiles that enhance endogenous antioxidant systems, (iii) as pro-vitamin A compounds that trigger retinol-mediated pathways, (iv) by suppressing inflammation-related processes mediated by nuclear factor κ-light-chain-enhancer of activated B cells (NFκB) pathway, and/or (v) by directly bonding nuclear receptors (NRs) and other transcription factors in target cells.10
Retinoic acid and apocarotenoids, such as apo-10′-lycopenoic acid and β-apo-14′-carotenal, are ligands of the canonical retinoid acid receptors (RARs) and retinoid X receptors (RXRs), which affects the expression of a vast array of responsive genes involved in cholesterol, fatty acid, Ca2+, and phosphate homeostasis (tissue-dependent affinity), accounting for general organism development.11 Some aldehyde derivatives of metabolized carotenoids also show activity in peroxisome proliferator-activated receptor (PPAR)-triggered genes, mostly by molecular interactions with activator protein 1 and/or CCAAT-enhancer binding proteins (AP-1 and C/EBPs, respectively), which are key components of these signal cascades.1,10
■ CAROTENOIDS IN REDOX METABOLISM
Antioxidant and Pro-oxidant Properties of Carotenoids. As free radical scavengers, carotenoids react with reactive oxygen/nitrogen species (ROS/RNS) by three distinct mechanisms: (i) radical addition/adduct formation, (ii) electron transfer, and (iii) allylic hydrogen abstraction (further details in the classic paper of Young and Lowe).15 However, their antioxidant properties were shown to change with membrane lipid composition, free radical species, pH, temperature, and pO2.15,16 Many studies have also shown that carotenes and xanthophylls have pro-oxidant properties under some circumstances, e.g., when lipid peroxidation is in progression under high pO2. Under these experimental conditions, a higher proportion of carotene-peroxyl radical (Car-OO•) is formed, and unless efficiently eliminated by other antioxidant systems, Car-OO• will propagate lipid peroxidation by further attack on intact unsaturated fatty acid chains in membranes.15
Pro-inflammatory NF-κB/Inhibitory κB Protein (IκB) Pathway.
Many dietary carotenoids also activate EpREresponsive clusters through the NF-κB/IκB pathway.Several apocarotenals, such as β-apo-10′carotenal and lycopene derivatives, directly interact with two key proteins of the NF-κB pathway: the IKKβ (leading to inhibition of its kinase activity) and the p65 subunit.25
“Redox Code”.
Current studies on redox biology suggest that optimal redox balances in subcellular compartments are essential for cell survival as well as phosphorylation and pH control. Therefore, optimum ratios between pro-oxidants and antioxidants also exist for a given metabolic condition.8
Intracellular redox balance directly responds to metabolic changes expressed in terms of [NAD+]/[NADH] and [NADP+]/[NADPH] ratios.27 Upon an excess energy−nutrient supply, an elevated reductive condition is generally imposed on the cell by activation of the PPP, synthesis of NADPH, and subsequent drop of the [NADP+]/[NADPH] ratio, especially in the cytosolic compartment. Under these circumstances, higher levels of endogenous antioxidants are induced (e.g., GSH and thioredoxin), biosynthetic/anabolic processes are triggered, and energy-rich cells are metabolically prompted to undergo proliferation or differentiation processes, depending upon other necessary inter- and intracellular factors.20 In mitochondria, the link between the two nicotinamide-dependent redox switches requires the key enzyme nicotinamide nucleotide transhydrogenase (NNT), which is vital in free radical detoxification and redox balances.19,20,26,27 However, subtoxic ROS/RNS concentrations lead to alterations in cellular and extracellular redox states, accelerating the formation of redox signaling molecules at levels sufficient to upregulate the expression of cytoprotective genes and improving cellular (and compartmental) antioxidant defenses. Besides H2O2, NO•, and GSNO, some lipid peroxidation byproducts, such as 4-hydroxy-2-nonenal (an α,β-unsaturated aldehyde) and nitro-/oxylipids, also activate Nrf2−Keap1 and NF-κB pathways at some levels.8,20 As the oxidative challenge increases in intracellular compartments, higher demands on re-establishing the redox balance toward an overall reductive condition will impose a different scenario, by switching on the transcription of redox-responsive genes that increase antioxidant defenses and turning off other genes that could aggravate oxidative conditions within cells (e.g., by overexpression of oxidases and cytochromes). The overall cellular redox switch (overall, because the redox control is clearly site-specifically determined) could be set to define different phenotypic fates: (i) proliferation/differentiation (when reductive conditions prevail), (ii) a steady-state condition, G0 (mostly sustained by adjustments in the Keap1−Nrf2−EpRE system), (iii) inflammation-like patterns (modulated by NF-κB cascades), (iv) apoptosis (through the AP-1 pathway, if proper apoptotic machinery is available for that cell type), and (iv) necrosis (disseminated and uncontrolled oxidative damage).8,19,20 Inevitably, as a result of variable cellular plasticity and redox responsiveness, different cell types have different oxidative tolerances or redox ranges for each of the phenotypic fates. For example, human hepatocytes have a higher capacity to proliferate and cope with higher oxidative challenges than neurons or glia cells. Apoptosis activation also varies among different human cells.28 Studies on mitochondria suggested that the intracellular superoxide (O2• −) concentrations may directly drive the switch from apoptosis to necrosis, revealing an incremental effect on oxidative conditions associated with an intracellular ATP depletion.29 The hypothetical redox switch in eukaryotic cells and the manner of how different phenotypes are elicited by the redox switches in different plasticity/function cells are summarized in Figure 3 (detailed information in the caption). In summary, the endogenous ROS/RNS production driven by essential cellular processes is normally counteracted by an intricated net of (compartmentalized) antioxidant systems, which respond, for proper adjustments, to many redox-active signaling molecules that trigger endogenous antioxidant defenses. Carotenoids and other antioxidants/pro-oxidants present in the human diet will account for additional disturbances in such redox switches, in either an integrative perspective or a subcellular mode of action. Astaxanthin, for example, has been investigated for a putative mitochondriatargeted activity in vivo.16,30 The bioactive content in food stuff (carotenoid sources), availability, transport, metabolic modification, excretion, etc. will strongly influence their real effect in situ. The role of dietary carotenoids is particularly intriguing because (i) carotenoids possess both antioxidant and prooxidant properties, which is structure-related and dependent upon local physicochemical conditions, (ii) (apo)carotenoids activate the Nrf2−Keap1 pathway, upregulate cellular antioxidant defenses, and rebalance cellular redox conditions, (iii) chemical moieties in their structure also trigger proinflammatory NF-κB cascades, which could enhance the oxidative insult, and (iv) all of the aforementioned properties are modulated by synergism with other dietary carotenoids (apocarotenoids?) and antioxidants, such as ascorbic acid (vitamin C) and α,γ-tocopherols and tocotrienols.18−20
Referência :
J Agric Food Chem. 2018 Jun 13;66(23):5733-5740.