Effects of term infant formulas containing high sn-2 palmitate with and without oligofructose on stool composition, stool characteristics, and bifidogenicity.

OBJECTIVES: Levels of stool fatty acid soaps and beneficial bacteria differ between formula-fed and breast-fed infants; addition of specific formula ingredients may reduce these differences. This study evaluated the effects of a term infant formula containing high sn-2 palmitate term infant formula (sn-2) or an identical formula supplemented with oligofructose (OF) at 2 concentrations (sn-2+3 g/L OF, sn-2+5 g/L OF) on stool composition, stool characteristics, and fecal bifidobacteria. METHODS: Healthy, term formula-fed infants 7 to 14 days old (n = 300) were randomized in a double-blind manner to receive standard formula (control), sn-2, sn-2+3 g/L OF, or sn-2+5 g/L OF for 8 weeks. Human milk (HM)-fed infants (n = 75) were studied in parallel. Stool samples were collected from all subjects at week 8 for fatty acid soaps and mineral content, and from a subset at baseline and week 8 for bifidobacteria. Stool characteristics were assessed via 3-day diary. RESULTS: The sn-2 group had 46% less stool soap palmitate (P < 0.001) and softer stools than control (20% more mushy soft stools, P = 0.026; 50% fewer formed stools, P = 0.003). Addition of OF resulted in even fewer formed stools versus control (65% fewer for sn-2+3 g/L OF, 79% fewer for sn-2+5 g/L OF), with 5 g/L OF more closely resembling that of HM-fed infants. Both sn-2 (P < 0.05) and sn-2 with OF groups (P < 0.01) had significantly higher fecal bifidobacteria concentrations than control at week 8, not differing from HM-fed infants. CONCLUSIONS: High sn-2-palmitate formulas led to reduced stool soaps, softer stools, and increased bifidobacteria, whereas addition of OF further improved stool consistency. Those modifications brought outcomes in formula-fed infants closer to that in HM-fed infants.

A Rare Case of Streptococcus equi Subspecies Zooepidemicus Bacteremia.

Streptococcus equi subspecies zooepidemicus (S. zooepidemicus) is a zoonotic pathogen that primarily infects horses, pigs, and dogs. Although rare, it has also been shown to infect humans who consume unpasteurized dairy food or have direct contact with horses. Here, we present a case of S. zooepidemicus bacteremia in a patient without a clear mode of transmission. An 86-year-old male with a past medical history of coronary artery disease, heart failure with reduced ejection fraction, complete heart block status post pacemaker, hypertension, hyperlipidemia, and type 2 diabetes mellitus presented to the Emergency Department with fever and chills. He had fevers and rigors for three days but denied weight loss, cough, sore throat, or rashes. In the Emergency Department, vital signs revealed a fever of 101.2 degrees Fahrenheit and a heart rate of 110 with other stable vital signs. The physical exam was unremarkable except for tachycardia, and laboratory work revealed no leukocytosis but elevated inflammatory markers and elevated lactate. Computed tomography of the chest, abdomen, and pelvis did not reveal any source of infection. Blood cultures grew S. zooepidemicus and the Infectious Diseases team was consulted, who started the patient on Penicillin G. Due to concern for pacer-lead infective endocarditis, transthoracic and transesophageal echocardiograms were performed, which did not show valvular vegetations. Repeat blood cultures showed clearance of the infection, and the patient was ultimately discharged on amoxicillin. While our patient denied consuming unpasteurized dairy products or having direct contact with horses, upon further questioning, he did endorse family members who occasionally interacted with horses. This case is valuable as it adds to the sparse literature on S. zooepidemicus infections specifically in humans. Extensive history taking is of utmost importance when a clear source of infection is not easily identifiable. Further research is also needed to better understand the various modes of transmission of this bacterium to better target and caution those at an increased risk of infection.

Association of Fitzpatrick Skin Type with metastatic risk from uveal melanoma in 854 consecutive patients at a single center.

OBJECTIVE: To assess the association of skin color using Fitzpatrick Skin Type (FST) with metastatic risk of uveal melanoma. SUBJECTS: 854 consecutive patients with uveal melanoma and documented FST. METHODS: Retrospective detailed review of patient charts was performed for FST (type I- white, II-fair, III-average, IV-light brown, V-brown, VI-black), clinical details of the patient and the uveal melanoma, tumor cytogenetic classification according to The Cancer Genome Atlas (TCGA), and outcome of melanoma-related metastasis and death. RESULTS: The FST classification was type I (n = 97 patients), type II (n = 665), type III (n = 79), type IV (n = 11), type V (n = 2), type VI (n = 0). A comparison of patient FST (type I vs. II vs. III-V) revealed significant differences in mean age at presentation (64.1 vs. 58.5 vs. 49.8 years, p < 0.001), race white (100% vs. 98% vs. 75%, p < 0.001), presence of ocular melanocytosis (3% vs. 3% vs. 10%, p = 0.01), visual acuity <20/200 at presentation (6% vs. 7% vs. 13%, p = 0.03), genetic results showing TCGA group B tumors (11% vs. 14% vs. 26%, p = 0.01) or TCGA group D tumors (22% vs. 11% vs. 9%, p = 0.01), 10-year incidence of melanoma-related metastasis (25% vs. 15% vs. 14%, p = 0.02) and 10-year incidence of melanoma-related death (9% vs. 3% vs. 4%, p = 0.04). FST was a significant predictor of melanoma-related metastasis (p = 0.02, Hazard ratio 2.3). CONCLUSIONS: Fitzpatrick skin type may be a predictor of melanoma-related metastasis, with metastasis and TCGA Group D tumors being more common in patients with FST I.

A comparison of chinese and american Indian (chumash) medicine.

Chinese and Chumash traditional medical approaches are similar in terms of disease causation, use of acupuncture or healing touch, plants, spiritual and philosophical approaches. This article provides a brief comparison and discussion of Chinese and Chumash traditional medical practices. A table of 66 plants is presented along with Chinese and Chumash uses of each plant. These uses are compared and contrasted.

A Walk in Nature: Sesquiterpene Lactones as Multi-Target Agents Involved in Inflammatory Pathways.

Inflammatory states are among the most common and most treated medical conditions. Inflammation comes along with swelling, pain and uneasiness in using the affected area. Inflammation is not always a simple symptom; more often is part of a defensive response of the body to an external threat or is a sign that the damaged tissue has not healed yet and needs to rest. The management of the pain associated with an inflammatory state could be a tricky task. In fact, most remedies simply quench the pain, leaving the inflammatory state unaltered. This review focuses on sesquiterpene lactones, a class of natural compounds, that represents a future promise in the treatment of inflammation. Sesquiterpene lactones are efficient inhibitors of multiple targets of the inflammatory process. Their natural sources are often ancient remedies with relevant traditional uses in folk medicines. This work also aims to elucidate how these compounds may represent the starting material for the development of new anti-inflammatory drugs.

A three-dimensional dementia model reveals spontaneous cell cycle re-entry and a senescence-associated secretory phenotype.

A hexanucleotide repeat expansion on chromosome 9 open reading frame 72 (C9orf72) is associated with familial amyotrophic lateral sclerosis (ALS) and a subpopulation of patients with sporadic ALS and frontotemporal dementia. We used inducible pluripotent stem cells from neurotypic and C9orf72+ (C9+) ALS patients to derive neuronal progenitor cells. We demonstrated that C9+ and neurotypic neuronal progenitor cells differentiate into neurons. The C9+ neurons, however, spontaneously re-expressed cyclin D1 after 12 weeks, suggesting cell cycle re-engagement. Gene profiling revealed significant increases in senescence-associated genes in C9+ neurons. Moreover, C9+ neurons expressed high levels of mRNA for CXCL8, a chemokine overexpressed by senescent cells, while media from C9+ neurons contained significant levels of CXCL8, CXCL1, IL13, IP10, CX3CL1, and reactive oxygen species, which are components of the senescence-associated secretory phenotype. Thus, re-engagement of cell cycle-associated proteins and a senescence-associated secretory phenotype could be fundamental components of neuronal dysfunction in ALS and frontotemporal dementia.

Growth, stool consistency and bone mineral content in healthy term infants fed sn-2-palmitate-enriched starter infant formula: A randomized, double-blind, multicentre clinical trial.

BACKGROUND: Palmitate in breast milk is predominantly located in the triacylglycerol sn-2 position, while infant formulae contain palmitate predominantly in the sn-1 and sn-3 positions. During digestion, palmitate in the sn-1 and sn-3 positions is hydrolyzed to free palmitic acid that can subsequently complex with calcium to form insoluble soaps; this may partially explain why formula-fed infants have harder stools than breast-fed infants. METHODS: This large (n = 488) randomized, double-blind, multicentre trial investigated whether increasing the sn-2 palmitate content of infant formula improves stool consistency and bone mineral content (measured by dual-energy x-ray absorptiometry), without affecting growth or health. From ∼1 week to 4 months of age, infants were exclusively fed one of three formulae: i) control formula (CF; 16% of total palmitate at sn-2; n = 162), (ii) experimental formula 1 (EF1; 43% of total palmitate at sn-2; n = 166) or (iii) experimental formula 2 (EF2; 51% of total palmitate at sn-2; n = 160). RESULTS: Intention-to-treat analysis showed softer stools in both EF groups (vs. CF) at ages 2 weeks and 1 and 2 months (p ≤ 0.01), but not 3 and 4 months. At 4 months, all groups had similar growth outcomes while bone mineral content was significantly higher in EF1 (p = 0.0012) and EF2 (p = 0.0002) compared with CF. Comparison of reported adverse events up to 12 months revealed no differences among groups. All 3 infant formulae exhibited equally good digestive tolerance. CONCLUSIONS: Formulae enriched in sn-2 palmitate fed in early infancy are safe, improve stool consistency (from 2 weeks to 2 months) and increase bone mineral content (at 4 months).

Safety evaluation of oligofructose: 13 week rat study and in vitro mutagenicity.

Oligofructose (OF), comprised of fructose oligomers with a terminal glucose unit, is a family of oligosaccharides derived from the hydrolysis of inulin. Consumption of OF in animals and humans increases colonic bifidobacteria levels. The present study evaluates the safety of OF in both a 13 week rat feeding study and using in vitro mutagenicity tests. Fecal bifidobacteria levels were also determined by in situ hybridization to assess a biological function of OF. Rats received either a control diet or diets containing one of four doses of OF. Total, HDL, and LDL-cholesterol levels were significantly lower at several time points during the study in groups receiving OF compared to controls with the largest effects occurring in the high dose male animals. Weight gain in the male high dose group was significantly lower at early time points compared to controls but not significantly different at the end of study. As expected, cecal weights increased in a dose-related manner and fecal bifidobacteria levels also demonstrated a dose-related increase. There were no consistent differences in gross pathology or histopathology related to dietary OF. OF did not induce a positive response in the Ames test or chromosomal aberration test with CHO cells. These results demonstrate no adverse effects of OF.

Human milk fatty acid composition from nine countries varies most in DHA.

Many published studies of breast milk FA composition are limited to populations from one or two countries. We aimed to examine the degree to which FA compositions vary across a number of diverse populations. Because diet and maternal adipose stores influence breast milk FA composition, differences in FA composition between groups most likely reflect habitual dietary differences. Approximately 50 breast milk samples (full breast expression) were collected from women in Australia, Canada, Chile, China, Japan, Mexico, Philippines, the United Kingdom, and the United States. The proportion of saturated FA was relatively constant among countries, with the exception of the Philippines, where levels of lauric and myristic acids were elevated (means greater than two times the mean of most other countries). Monounsaturated FA also varied little, with the exception of low levels of oleic acid in the Philippines and high levels of erucic acid in China. Although arachidonic acid (C20:4n-6) levels were similar among all countries (means ranging from 0.36 wt % to 0.49 wt %), mean DHA (C22:6n-3) levels ranged from 0.17 to 0.99 wt %, with the highest levels in Japanese milk and the lowest levels in Canadian and U.S. samples. The results of this study demonstrate that the proportion of saturated and monounsaturated FA are relatively constant across a large number of countries, whereas the level of some of the PUFA, especially DHA, are highly variable.

Heteromeles Arbutifolia, a Traditional Treatment for Alzheimer's Disease, Phytochemistry and Safety.

Background: This study examined the chemistry and safety of Heteromeles arbutifolia, also called toyon or California holly, which is a traditional California Indian food and treatment for Alzheimer's disease. Methods: Plant extracts were examined by HPLC/MS, NMR and other techniques to identify compounds. Volunteers were recruited to examine the acute safety of the plant medicine using a standard short-term memory test. Results: The plant was found to contain icariside E4, dihydroxyoleanenoic acid, maslinic acid, betulin, trihydroxyoxo-seco-ursdienoic acid, catechin, vicenin-2, farrerol, kaempferide and tetrahydroxyoleanenoic acid. These compounds are anti-inflammatory agents that may protect the blood-brain barrier and prevent inflammatory cell infiltration into the brain. The dried berries were ingested by six volunteers to demonstrate the safety of the medicine. Conclusion: The plant medicine was found to contain several compounds that may be of interest in the treatment of Alzheimer's disease. The plant medicine was found to be safe.

Determination of the potency and subunit-selectivity of ribonucleotide reductase inhibitors with a recombinant-holoenzyme-based in vitro assay.

Ribonucleotide reductase (RR) is an important therapeutic target for anticancer drugs. The structure of human RR features a 1:1 complex of two homodimeric subunits, hRRM1 and hRRM2. p53R2 is a newly identified homologue of hRRM2. We have devised a holoenzyme-based in vitro assay for the determination of the potency and subunit-selectivity of small-molecule inhibitors of RR. The assay was implemented using two forms of recombinant RR (hRRM2/hRRM1 and p53R2/hRRM1) and based on their [(3)H]CDP reduction activity. Hydroxyurea was used to standardize the assay. We found that the activities of hRRM2/hRRM1 and p53R2/hRRM1 were decreased by hydroxyurea in a dose-dependent manner. The -NH-OH segment of hydroxyurea was shown to be essential for inhibition. In the presence of Fe(III) and reductants, less inhibition of enzymatic activity by hydroxyurea was observed, especially for p53R2/hRRM1. The potency of four hydroxyurea analogues (Schiff bases of hydroxysemicarbazide, SB-HSC) decreased in the order SB-HSC 21 > SB-HSC 24 > SB-HSC 2 > hydroxyurea (HU) > SB-HSC 29. SB-HSC 2 and SB-HSC 24 inhibited p53R2/hRRM1 significantly more than hRRM2/hRRM1, whereas SB-HSC 21 and SB-HSC 29 showed low subunit-selectivity. Electron paramagnetic resonance (EPR) measurements showed that inhibition of RR was accompanied by reduction of its tyrosyl radical. The method was validated by comparison with data obtained using cell-based assays. We suggest that this novel recombinant-holoenzyme-based in vitro assay is a useful tool for the discovery of more potent and subunit-selective inhibitors of RR.

Detection of a single nucleotide polymorphism in the human alpha-lactalbumin gene: implications for human milk proteins.

Variability in the protein composition of breast milk has been observed in many women and is believed to be due to natural variation of the human population. Single nucleotide polymorphisms (SNPs) are present throughout the entire human genome, but the impact of this variation on human milk composition and biological activity and infant nutrition and health is unclear. The goals of this study were to characterize a variant of human alpha-lactalbumin observed in milk from a Filipino population by determining the location of the polymorphism in the amino acid and genomic sequences of alpha-lactalbumin. Milk and blood samples were collected from 20 Filipino women, and milk samples were collected from an additional 450 women from nine different countries. alpha-Lactalbumin concentration was measured by high-performance liquid chromatography (HPLC), and milk samples containing the variant form of the protein were identified with both HPLC and mass spectrometry (MS). The molecular weight of the variant form was measured by MS, and the location of the polymorphism was narrowed down by protein reduction, alkylation and trypsin digestion. Genomic DNA was isolated from whole blood, and the polymorphism location and subject genotype were determined by amplifying the entire coding sequence of human alpha-lactalbumin by PCR, followed by DNA sequencing. A variant form of alpha-lactalbumin was observed in HPLC chromatograms, and the difference in molecular weight was determined by MS (wild type=14,070 Da, variant=14,056 Da). Protein reduction and digestion narrowed the polymorphism between the 33rd and 77th amino acid of the protein. The genetic polymorphism was identified as adenine to guanine, which translates to a substitution from isoleucine to valine at amino acid 46. The frequency of variation was higher in milk from China, Japan and Philippines, which suggests that this polymorphism is most prevalent in Asia. There are SNPs in the genome for human milk proteins and their implications for protein bioactivity and infant nutrition need to be considered.

Infant formulas with increased concentrations of alpha-lactalbumin.

Human and bovine milk differ substantially in the ratio of whey to casein protein (approximately 60:40 in human milk and approximately 20:80 in bovine milk) and in the proportions of specific proteins. Although current infant formulas closely mimic the ratio of total whey to casein inhuman milk, the concentration of a-lactalbumin (the dominant protein in human milk) is relatively low in formula, whereas beta-lactoglobulin, a protein not found in human milk, is the most dominant whey protein in formula. Because of the differences in the protein profiles of human milk and infant formula, amino acid profiles also differ. To meet all essential amino acid requirements of infants, formula concentrations of protein must be higher than those in human milk. Recently, whey sources with elevated concentrations of alpha-lactalbumin have become available, which permitted the development of formulas with increased concentrations of this protein and decreased concentrations of beta-lactoglobulin. alpha-Lactalbumin is rich in tryptophan, which is typically the limiting amino acid in formula, and as a result, formulas have been developed with lower protein but higher tryptophan concentrations. This type of formula may offer a number of advantages to the neonate, which include producing plasma tryptophan concentrations equal to those found in breastfed infants and obviating the need for the body to dispose of excess nitrogen loads.

Anticancer agents: tumor cell growth inhibitory activity and binary QSAR analysis.

The tumor cell growth inhibitory activities (log 1/GI(50)) of 166 anticancer agents studied at the National Cancer Institute (NCI) in vitro anticancer screening program have allowed us to analyze the relative importance of physicochemical parameters in influencing the inhibitory activities. Increased molecular weight, as measured by the logarithm of molecular weight (log MW), is found to be an important contributor to the tumor cell growth inhibitory activities. The tumor cell growth inhibitory activities in different subpanels of the tumor cells are highly inter-correlated with each other. A simple binary quantitative structure-activity relationship (QSAR) model was derived from the 166 anticancer drugs, based on the tumor cell growth inhibitory activities transformed into a binary (active or inactive) data format. The model obtained can be tested with additional new data, and may be useful to identify active compounds from a large compound library to be included in high throughput screening.

Synthesis, biological evaluation, and quantitative structure-activity relationship analysis of new Schiff bases of hydroxysemicarbazide as potential antitumor agents.

Thirty Schiff bases of hydroxysemicarbazide (Ar-CH=NNHCONHOH) have been synthesized and tested against L1210 murine leukemia cells. The IC(50) values were found to be in a range from 2.7 x 10(-6) to 9.4 x 10(-4) M. A total of 17 out of the 30 compounds had higher inhibitory activities than hydroxyurea (an anticancer drug currently used for the treatment of melanoma, leukemia, and ovarian cancer) against L1210 cells. Six compounds with IC(50) values in micromolar range were 11- to 30-fold more potent than hydroxyurea (IC(50) = 8.2 x 10(-5) M). The partition coefficient (log P) and ionization constants (pK(a)) of a model compound [1-(3-trifluoromethylbenzylidene)-4-hydroxysemicarbazide, 1] were measured by the shake-flask method, and the measured log P was used to derive Hansch-Fujita pi constant of -CH=NNHCONHOH. On the basis of the newly derived pi and those of other moieties, the partition coefficients (SlogP) of the other 29 compounds were calculated by the summation of pi values. Quantitative structure-activity relationship (QSAR) analysis showed that, besides the essential pharmacophore (-NHCONHOH), hydrophobicity (SlogP), molecular size/polarizability (calculated molar refractivity), and the presence of an oxygen-containing group at the ortho position (I) were important determinants for the antitumor activities. In conclusion, the results obtained in this study show that several Schiff bases of hydroxysemicarbazide are potent inhibitors of tumor cells and warrant further investigation as cancer chemotherapeutic agents.

Nutritional and physiologic significance of alpha-lactalbumin in infants.

alpha-Lactalbumin is the major protein in breast milk (20-25% of total protein) and has been described to have several physiologic functions in the neonatal period. In the mammary gland, it participates in lactose synthesis, thereby creating an osmotic "drag" to facilitate milk production and secretion. alpha-Lactalbumin binds divalent cations (Ca, Zn) and may facilitate the absorption of essential minerals, and it provides a well-balanced supply of essential amino acids to the growing infant. During its digestion, peptides appear to be transiently formed that have antibacterial and immunostimulatory properties, thereby possibly aiding in the protection against infection. A novel folding variant ("molten globule state") of multimeric alpha-lactalbumin has recently been discovered that has anti-infective activity and enhances apoptosis, thus possibly affecting mucosal cell turnover and proliferation. Cow milk also contains alpha-lactalbumin, albeit less than human milk (2-5% of total protein in bovine milk), and protein fractions enriched with alpha-lactalbumin may now be added to infant formula to provide some of the benefits of human alpha-lactalbumin.

A multinational study of alpha-lactalbumin concentrations in human milk.

Alpha-lactalbumin, a 14-kD protein, plays a central biochemical role in the mammary gland as the regulatory subunit of lactose synthase, and also plays a nutritional role for the rapidly growing neonate as the protein in highest concentration in human milk. The current study was undertaken to better characterize alpha-lactalbumin concentrations in human milk from a variety of countries. Mature human milk (lactation duration > or =1 month) was collected from at least 50 women from nine different countries on five continents. Alpha-lactalbumin concentration was determined by HPLC. The mean +/- SD for 452 samples was 2.44 +/- 0.64 g/L. The mean value of the samples from the United States was significantly higher than that from any other country, and the mean in Mexico was significantly lower than that from every country except China and Canada. Alpha-lactalbumin concentration decreased with increasing duration of lactation and was positively correlated with total nitrogen. On average, alpha-lactalbumin contributed 16% of the total nitrogen content of human milk and consequently an important part of the amino acid content.

Chemical and pharmacological investigations of Epimedium species: a survey.

More than 130 different compounds have been identified from over 16 species of the Epimedium genus of the Berberidaceae family. Eight of these species have been used in the Traditional Chinese Medicines (TCM) over centuries to treate a wide range of diseases. From in vitro and in vivo experimental data, and preliminary structure-activity relationship (SAR) analysis of the androgenic/anti-estrogenic and anti-oxidant activities of the icariin series of flavonoids and glycosides, the results appear to be consistent with those of known anti-estrogenic flavonoids, such as luteolin. Further QSAR analysis of the different active ingredients is now in progress and will be reported elsewhere. Our survey suggests the possibility of multiple targets and multiple mechanisms of action by Epimedium preparations and their purified compounds. These may serve as leads for further new drug development.

Phytochemical analysis of medicinal plants with kidney protective activities.

In view of the increasing number of patients undergoing kidney dialysis or transplant every year, a survey of the literature on renal protective medicinal plants was undertaken. Most of them are from traditional Chinese medicine (TCM). Although many of the medicinal herbs reported have not been investigated in terms of active chemical ingredients, some do have compounds well characterized. They fall into a wide range of structures. Several groups of compounds with well established activities are discussed. These include: antioxidant phenolic compounds like tannins, flavonoids, isoflavonoids, unsaturated organic acids and lignans; circulation enhancing compounds like saponins, and basic alkaloids with multiple targets (G-protein coupled receptors). Also presented are proinflammatory and antiinflammatory fatty acids like linoleic (n-6) and α-linolenic (n-3) acids, respectively. Attention is also drawn to the plants containing nephrotoxic aristolochic acid. Different directions of future research are also presented. We hope that this review may provide some leads for new drug discovery and development, and more rational application of TCM.

Nutritional influences on visual development and function.

Experiments conducted on many different species reveal a fundamental paradox about the vertebrate eye; it is damaged by its own operation. This vulnerability stems from the need to respond to visible light, often actinic, but also from the intrinsic metabolic and structural state of the eye's internal structures. Photoreceptor outer segments, for instance, have high concentrations of diet-derived long-chain polyunsaturated fatty acids and these membrane lipids are highly prone to peroxidation due to the high oxygen tension of the outer retina. Such a high diathesis for damage would be catastrophic if it were not balanced by an equally impressive system for responding to such stressors. The retina (and to a lesser extent the crystalline lens), for instance, is especially rich in dietary antioxidants such as vitamin E, vitamin C and the macular carotenoids (lutein and zeaxanthin) putatively to retard light-induced oxidative damage. The nutrients that support both essential function (e.g., retinal, the vitamin form of vitamin A, in photopigment) and protection operate in a highly integrated manner. For instance, Vitamin E is a lipophillic chain-breaking anti-oxidant (protecting DHA-rich outer segment membranes) that regenerates itself through reaction with vitamin C (a primary anti-oxidant against aqueous radicals) and is spatially distributed in complement with the carotenoids lutein and zeaxanthin. Nor are these interactions relegated to simply providing protection and the basic elements needed for transduction. Macular lutein and zeaxanthin, for example, improve visual performance (e.g., reduce glare disability and discomfort, speed photostress recovery, and enhance chromatic contrast) through purely optical means (by absorbing short-wave light anterior to the foveal cones). The vulnerability of the eye to exogenous insult, and the sensitivity of the eye to dietary components, is not static: infants have more vulnerable retinas due to clearer lenses and higher metabolic activity; the elderly are more vulnerable due to such factors as increased inflammatory stress and a higher content of photosensitizers (such as lipofuscin) creating cascading oxidative effects. Hence, optimal dietary prophylaxis changes as the eye ages. The eye, perhaps more than most other biological structures, has evolved an exquisite and shifting sensitivity to dietary intake throughout the lifespan, not just for its basic operation (e.g., Vitamin A for transduction), but also for its very preservation.