Fucoxanthin, a Functional Food Ingredient: Challenges in Bioavailability.

PURPOSE OF REVIEW: Fucoxanthin is an orange-red xanthophyll carotenoid found in brown seaweeds and known for its many bioactive properties. In recent years, the bioactive properties of fucoxanthin have been widely explored, making it a compound of immense interest for various health applications like anti-cancer, anti-tumour, anti-diabetic and anti-obesity properties. However, the poor bioavailability and instability of fucoxanthin in the gastrointestinal tract have major limitations. Encapsulation is a promising approach to overcome these challenges by enclosing fucoxanthin in a protective layer, such as liposomes or nano-particles. Encapsulation can improve the stability of fucoxanthin by protecting it from exposure to heat, pH, illumination, gastric acids and enzymes that can accelerate its degradation. RECENT FINDINGS: Studies have shown that lipid-based encapsulation systems such as liposomes or nano-structured lipid carriers may solubilise fucoxanthin and enhance its bioavailability (from 25 to 61.2%). In addition, encapsulation can also improve the solubility of hydrophobic fucoxanthin, which is important for its absorption and bioavailability. This review highlights the challenges involved in the absorption of fucoxanthin in the living system, role of micro- and nano-encapsulation of fucoxanthin and their potential to enhance intestinal absorption.

Oxidative stability of lutein on exposure to varied extrinsic factors.

Pre-processing treatments performed on lutein sources can cause it to degrade, generating superfluous metabolites and lowering lutein's bioactivity. However, evidences suggesting extent of reduction in functional stability of lutein on exposure to such treatment conditions are nil. This study is first of its kind, where we attempted to gain clarity on the extent of degradation caused by the changes in temperature (40-100 °C), pH (2-8) and duration of such treatments. Increase (3.9 folds) in lutein loss within an hour at 40 °C occurred when pH was lowered from 8 to 2. Increase (1.7 folds) in lutein loss at neutral pH and 40 °C occurred when duration of exposure was increased from 1 to 4 h. Besides, lutein loss significantly increased on rising the temperature by every 10 °C. The functional stability of lutein in relation to its degradation was also studied by monitoring its radical scavenging activity. While lutein is highly unstable, lutein structure and its respective bioactivity can be significantly (p < 0.05) retained (< 12.44% and > 54.87% respectively) by maintaining the operating conditions at higher pH (7-8) and lower temperatures (40-50 °C) for a short period of time (< 1 h). Supplementary Information: The online version contains supplementary material available at 10.1007/s13197-022-05430-3.

Cow ghee as an efficient carrier to improve oral bioavailability of lutein.

In India, cow-ghee has been used in traditional medicinal preparations to solubilize lipophilic drugs and enhance intestinal absorption. However, reports exploring the role of cow-ghee, naturally rich in saturated fatty acids, in carotenoid chemistry is nil. We attempted to understand the influence of fatty-acid composition of cow-ghee and edible oils on intestinal absorption of lutein in mice. The postprandial plasma lutein level in the mice administered with cow-ghee significantly (p < 0.05) reached the maximum (Cmax-135.76 pmol/mL; AUC-592.80 pmol.h/mL) within 2 h (Tmax). Cow-ghee improved oral bioavailability of lutein by 2.02, 1.41 and 1.66 folds in comparison to control, olive oil and flaxseed oil respectively. Cow-ghee, composed of 69.28% saturated fatty-acids, has the potential to be a delivery vehicle for lutein as evidenced by higher postprandial triglyceride levels. This study is first of its kind which reports the influence of saturated fatty-acids on the oral bioavailability of lutein in an in-vivo system.

Hsp70 overexpression in Drosophila hemocytes attenuates benzene-induced immune and developmental toxicity via regulating ROS/JNK signaling pathway.

Benzene, a ubiquitous environmental chemical, is known to cause immune dysfunction and developmental defects. This study aims to investigate the relation between benzene-induced immune dysfunction and developmental toxicity in a genetically tractable animal model, Drosophila melanogaster. Further, the study explored the protective role of Heat Shock Protein 70 (Hsp70) against benzene-induced immunotoxicity and subsequent developmental impact. Drosophila larvae exposed to benzene (1.0, 10.0, and 100.0 mM) were examined for total hemocyte (immune cells) count, phagocytic activity, oxidative stress, apoptosis, and their developmental delay and reduction were analyzed. Benzene exposure for 48 h reduced the total hemocytes count and phagocytic activity, along with an increase in the Reactive Oxygen Species (ROS), and lipid peroxidation in the larval hemocytes. Subsequently, JNK-dependent activation of the apoptosis (Caspase-3 dependent) was also observed. During their development, benzene exposure to Drosophila larvae led to 3 days of delay in development, and ~40% reduced adult emergence. Hsp70-overexpression in hemocytes was found to mitigate benzene-induced oxidative stress and abrogated the JNK-mediated apoptosis in hemocytes, thus restoring total hemocyte count and improving phagocytotic activity. Further, hsp70-overexpression in hemocytes also lessened the benzene-induced developmental delay (rescue of 2.5 days) and improved adult emergence (~20%) emergence, revealing a possible control of immune cells on the organism's development and survival. Overall, this study established that hsp70-overexpression in the Drosophila hemocytes confers protection against benzene-induced immune injury via regulating the ROS/JNK signaling pathway, which helps in the organism's survival and development.

Antihypertensive activity of orally consumed ACE-I inhibitory peptides.

Food proteins are sources for ACE-I inhibitory peptides that can be extracted by enzymatic hydrolysis exhibiting anti-hypertensive activity. However, these peptides are prone to further degradation by gastrointestinal enzymes during oral consumption. Bio-activity of these peptides is dependent on the resultant peptide post gastrointestinal digestion. To exhibit the bio-activity, they need to be absorbed in intact form. Although studies suggest di and tri-peptides show better ACE-I inhibitory activity, few peptides show altered IC50 values under simulated gastrointestinal digestion. Moreover, ACE-I inhibitory peptides with low IC50 values have not shown effective anti-hypertensive activity in spontaneously hypertensive rats when administered orally. Few ACE-I inhibitory peptides have reported effective reduction in systolic blood-pressure when administered through intravenously. During oral consumption of such peptides, the actual peptide sequence responsible for reducing blood-pressure is a result of breakdown in gastrointestinal tract. The fate of targeted peptides during digestion depends on amino acid sequence of the protein containing the specific site for cleavage where the action of digestive enzymes takes place. Therefore, this review attempts to explain the factors that affect the anti-hypertensive activity of ACE-I inhibitory peptides during oral consumption. It also highlights subsequent absorption of ACE-I inhibitory peptides after gastrointestinal digestion.

Genetic factors involved in modulating lutein bioavailability.

Lutein exhibits effective antioxidant activity conferring protective action against oxidative stress in age-related macular degeneration and cognitive decline. The inability to synthesize these compounds by the human body and the necessity to combat day-to-day oxidative stress prioritizes daily consumption of lutein. However, the bioavailability of the orally consumed lutein largely depends on its gastrointestinal absorption and subsequent metabolism which is in turn governed by various intrinsic and extrinsic factors. One of the most important yet least studied factors is the genetic make-up of an individual. The proteins that partake in the absorption, transportation, metabolism and excretion of lutein are encoded by the genes that experience inter-individual variability. Reports suggest that the unanimous effect of phenotypes resulting from such inter-individual variability in the genes of interest causes modulation of lutein bioavailability which is discussed in detail in this review article. However, despite the available reports, a community-based approach to a larger population is required to obtain a stronger understanding of the relationship between inter-individual variability among these genes and lutein bioavailability. Such an understanding of nutrigenetics could not only pave a way to decipher mechanisms that modulate lutein bioavailability but also help in setting the dosage requirements of each patient.

Nutraceutical approach to enhance lutein bioavailability via nanodelivery systems.

Lutein, a potent dietary carotenoid, has considerable biological activity and confers protection against age-related macular degeneration. Its bioavailability following consumption, however, depends on its rate of degradation. Nanodelivery systems with improved efficacy and stability are currently being developed to increase the bioavailability of lutein. This review examines nutraceutical approaches used in the development of such nanodelivery systems. It describes the methods of lutein preparation, the characteristics of various delivery systems, and the lutein delivery profile. In order to enhance lutein loading, provide electrostatic stabilization, and achieve the controlled release of lutein, adjuvants such as dextran moieties, whey proteins, medium-chain triglycerides, and chitosan polymers can be used to effectively reduce the particle size (< 70 nm) and improve encapsulation efficiency (to 99.5%). The improved bioavailability of lutein via nanocrystals incorporated into rapidly dissolving films for oral consumption is a new area of exploratory research. This review aims to provide clarity about current research aimed at enhancing the bioavailability of lutein through the development of nanodelivery systems.

Risk Factors for Nuclear and Cortical Cataracts: A Hospital Based Study.

PURPOSE: To evaluate risk factors associated with nuclear and cortical cataracts among a hospital based sample of subjects in Southern India. METHODS: In this hospital-based study, 3,549 subjects including 2,090 male and 1,459 female individuals aged 45 years and over were randomly screened for nuclear and cortical cataracts. Lens opacity was graded and classified after pupil dilation using the lens opacities classification system (LOCS) III at the slit lamp. Furthermore, participants were interviewed for lifestyle variables and dietary intake of carotenoids using a structured food frequency questionnaire. RESULTS: Demographic risk factors for cataracts included older age and lower socioeconomic status. Nuclear cataracts were associated with diabetes (OR = 6.34; 95% CI: 2.34-8.92%), tobacco chewing (moderate, OR = 3.04; heavy, OR = 4.62), cigarette smoking (moderate, OR = 1.58; heavy, OR = 1.87) and hypertension (OR = 1.56; 95% CI: 1.25-2.78%). Cortical cataracts were associated with diabetes (OR = 15.03; 95% CI: 7.72-29.2%), tobacco chewing (moderate, OR = 2.16; heavy, OR = 2.32) and cigarette smoking (moderate, OR = 2.20; heavy, OR = 2.97). Higher dietary intake of lutein/zeaxanthin (L/Z) and ß-carotene was associated (P < 0.001) with a lower risk of nuclear and cortical cataracts. CONCLUSION: Higher dietary intake of carotenoids is associated with a lower risk of cataracts. Nuclear and cortical cataracts are associated with various risk factors such as diabetes, hypertension, cigarette smoking and tobacco, similar to studies conducted in other Asian and European populations, irrespective of ethnic origin.

Olive oil improves the intestinal absorption and bioavailability of lutein in lutein-deficient mice.

PURPOSE: To investigate the influence of olive (OO), groundnut (GNO), soybean (SBO), sunflower (SFO), rice bran (RBO), corn (CO), palm (PO) oil or mixed micelle (control) on absorption kinetics and bioavailability of lutein in lutein-deficient mice. Additional aim was to correlate the activity of intestinal triacylglycerol lipase with intestinal and plasma lutein levels. METHODS: After induction of lutein deficiency, mice (n = 165) were divided into eight groups (OO, SFO, GNO, RBO, PO, CO, SBO and control; n = 20/group) and the remaining (n = 5) were used as baseline (0 h). Groups were further divided into four subgroups (n = 5/subgroup) and were intubated with lutein (200 µM) dispersed in different vegetable oils. Plasma and tissue (intestine, liver and eyes), lutein, triglycerides, intestinal triacylglycerol lipases and fatty acid profile of plasma and tissues were measured at different time intervals. RESULTS: The percentage area under the curve value for plasma lutein in OO and GNO was higher by 41.8 and 5.1 %, while it was lower in other groups (18.2-53.3 %), when compared to control. Similarly, the percentage area under the curve for eye lutein in OO and GNO groups was higher by 35.2 and 4.8 %, whereas in other groups it was lower (5.4-69 %) than in control. Results show that olive oil facilitates the lutein absorption more compared to other vegetable oils, which may be due to the difference in fatty acid composition and higher activity of intestinal triacylglycerol lipase. CONCLUSIONS: Dietary olive oil rich in oleic acid improves the bioavailability and accumulation of lutein in lutein-deficient mice by modifying the intestinal triacylglycerol lipase activity.

Dietary and lifestyle risk factors associated with age-related macular degeneration: a hospital based study.

AIM: To establish the frequency, associations and risk factors for age-related macular degeneration (AMD) in hospital population of South India. MATERIALS AND METHODS: In this cross-sectional hospital based study, 3549 subjects (2090 men and 1459 women) above 45 years of age were screened randomly for AMD. Participants underwent ocular evaluation and were interviewed for lifestyle variables and dietary intake of carotenoids by structured food frequency questionnaire. AMD was defined according to the international classifications and grading system. RESULTS: Either form of AMD was detected in 77 (2.2%) participants. Of which, early and late AMD was present in 63 (1.8%) and 14 (0.4%) subjects, respectively. Binary logistic analysis showed that the incidence of AMD was significantly higher with increasing age (Odds ratio [OR] 1.17; 95% CI 1.13-1.22) and diabetes (OR 3.97; 95% CI 2.11-7.46). However, AMD was significant among heavy cigarette smokers (OR 5.58; 95% CI 0.88-7.51) and alcoholics (OR 4.85; 95% CI 2.45-12.22). Dietary lutein/zeaxanthin (L/Z) and ß-carotene intake were associated (P < 0.001) with the reduction in risk for AMD, with an OR of 0.38 and 0.65, respectively. CONCLUSIONS: Higher dietary intake of carotenoids, especially L/Z, was associated with lower risk for AMD. Risk of AMD is higher with increasing age and was prevalent among subjects with diabetes. Cessation of smoking and alcohol may reduce the risk of AMD in this population.

Effect of micellar lipids, dietary fiber and ß-carotene on lutein bioavailability in aged rats with lutein deficiency.

OBJECTIVE: To determine the effect of various dietary components on the intestinal uptake of lutein in aged rats. METHODS: This study determined the time-course (2, 4, 6, 8 h) plasma and tissue responses of a pharmacologic dose of lutein (200 µM) solubilized in mixed micelles with fat (3%, soybean oil), phosphatidylcholine (PC; 3 mM), lysophosphatidylcholine (lysoPC; 3 mM), dietary fiber (pectin, 1.25%), ß-carotene (200 µM), or micelles with no dietary components (control) in aged rats with lutein deficiency. RESULTS: No lutein was detected in the plasma of rats at 0 h indicating the deficiency. After gavages of lutein, the mean percent area under the curve (picomoles per milliliter per 8 h) of plasma lutein in the fat (91.4), PC (218.0), and lysoPC (94.1) groups were higher (P > 0.05), whereas its level in the dietary fiber and ß-carotene groups was lower than the control group. The liver and eye lutein levels of the PC (95.4, 38.67%) and fat (18.2, 143%) groups were significantly higher, whereas the lysoPC (9.6, 27.2%), ß-carotene (19.2, 35.4%), and dietary fiber (3.1, 88.4%) groups were lower than the control group. CONCLUSION: Results indicate that soybean oil and soy phospholipids greatly sway lutein absorption in aged rats with lutein deficiency. The results also suggest that ingestion of lutein with pectin and ß-carotene suppresses lutein absorption. Hence, to improve the absorption of lutein in older adults with macular pigment deficiency, foods with sufficient fat with low dietary fiber and ß-carotene may be suggested.