Emily Mohn Haberlin

Background: Lutein, a dietary carotenoid, is selectively taken up into the retina (measured as macular pigment optical density, MPOD) and brain. Thus, MPOD and brain lutein content are positively associated with cognition in older adults. However, the relationship between serum lutein and cognition is inconsistent. Therefore, serum lutein, which is carried primarily by high-density lipoproteins (HDLs) and to a lesser extent by low-density lipoproteins (LDLs) and very low-density lipoproteins (VLDLs), may not accurately reflect neural lutein levels. Eggs, which modulate circulating lipoproteins, are particularly effective at enriching lutein in neural tissue even when the serum lutein response is small. Methods: This study conducted post hoc analyses of a randomized controlled trial to test the effects of consuming 2 eggs vs. 4 oz. of egg whites daily for 6 months on lutein transport in the circulation, and the subsequent relationship to MPOD and cognitive function in older adults (50–85 years old; 20 women, 21 men). The primary outcome of determine the relationship between lutein contained in HDL and MPOD. A secondary outcome evaluated the relationship between HDL-contained lutein and cognitive function. Blood draws, MPOD measurements, and cognitive assessments were performed at baseline and after 6 months. Results: The change from baseline for MPOD was significant for the egg group (p < 0.05) but not for the egg white group (0.09 ± 0.04 OD vs. 0.02 ± 0.05 OD, respectively). Similarly, the change in the proportion of serum lutein carried by the HDL (LDL+VLDL) was significant in the egg group (59 ± 11% to 67 ± 18%; p < 0.05) but not in the egg white group (67 ± 22 to 60 ± 24%) after 6 months. However, there were no significant differences between groups. When evaluating only participants who increased the proportion of serum lutein carried by HDL in response to egg consumption (n = 14), a trend between this proportion and MPOD was observed (p = 0.07). An increase in the proportion of serum lutein on the HDL was also associated with improved visual memory and learning (p < 0.04). Conclusions: In this study, the relative distribution of serum lutein between the HDL and LDL reflected lutein accumulation in neural tissue and cognitive status in older adults. Thus, further investigation into the effects of eggs on promoting cognitive health by enhancing lutein delivery to the brain is warranted. Clinical Trial Registration: This study was registered at ClinicalTrials.gov (NCT01621646, https://clinicaltrials.gov/study/NCT01621646).

The long-term use of prescription and over-the-counter drugs can induce subclinical and clinically relevant micronutrient deficiencies, which may develop gradually over months or even years. Given the large number of medications currently available, the number of research studies examining potential drug–nutrient interactions is quite limited. A comprehensive, updated review of the potential drug–nutrient interactions with chronic use of the most often prescribed medications for commonly diagnosed conditions among the general U.S. adult population is presented. For the majority of the interactions described in this paper, more high-quality intervention trials are needed to better understand their clinical importance and potential consequences. A number of these studies have identified potential risk factors that may make certain populations more susceptible, but guidelines on how to best manage and/or prevent drug-induced nutrient inadequacies are lacking. Although widespread supplementation is not currently recommended, it is important to ensure at-risk patients reach their recommended intakes for vitamins and minerals. In conjunction with an overall healthy diet, appropriate dietary supplementation may be a practical and efficacious way to maintain or improve micronutrient status in patients at risk of deficiencies, such as those taking medications known to compromise nutritional status. The summary evidence presented in this review will help inform future research efforts and, ultimately, guide recommendations for patient care.

The relationship between α-tocopherol, a known antioxidant, and polyunsaturated fatty acid (PUFA) oxidation, has not been directly investigated in the primate brain. This study characterized the membrane distribution of α-tocopherol in brain regions and investigated the association between membrane α-tocopherol and PUFA content, as well as brain PUFA oxidation products. Nuclear, myelin, mitochondrial, and neuronal membranes were isolated using a density gradient from the prefrontal cortex (PFC), cerebellum (CER), striatum (ST), and hippocampus (HC) of adult rhesus monkeys (n = 9), fed a stock diet containing vitamin E (α-, γ-tocopherol intake: ~0.7 µmol/kg body weight/day, ~5 µmol/kg body weight/day, respectively). α-tocopherol, PUFAs, and PUFA oxidation products were measured using high performance liquid chromatography (HPLC), gas chromatography (GC) and liquid chromatography-gas chromatography/mass spectrometry (LC-GC/MS) respectively. α-Tocopherol (ng/mg protein) was highest in nuclear membranes (p < 0.05) for all regions except HC. In PFC and ST, arachidonic acid (AA, µg/mg protein) had a similar membrane distribution to α-tocopherol. Total α-tocopherol concentrations were inversely associated with AA oxidation products (isoprostanes) (p < 0.05), but not docosahexaenoic acid oxidation products (neuroprostanes). This study reports novel data on α-tocopherol accumulation in primate brain regions and membranes and provides evidence that α-tocopherol and AA are similarly distributed in PFC and ST membranes, which may reflect a protective effect of α-tocopherol against AA oxidation.

Lutein, a carotenoid with anti-oxidant functions, preferentially accumulates in primate brain and is positively related to cognition in humans. Docosahexaenoic acid (DHA), an omega-3 polyunsaturated fatty acid (PUFA), is also beneficial for cognition, but is susceptible to oxidation. The present study characterized the membrane distribution of lutein in brain regions important for different domains of cognitive function and determined whether membrane lutein was associated with brain PUFA oxidation. Adult rhesus monkeys were fed a stock diet (~2 mg/day lutein or ~0.5 μmol/kg body weight/day) (n = 9) or the stock diet plus a daily supplement of lutein (~4.5 mg/day or~1 μmol/kg body weight/day) and zeaxanthin (~0.5 mg/day or 0.1 μmol/kg body weight/day) for 6–12 months (n = 4). Nuclear, myelin, mitochondrial, and neuronal plasma membranes were isolated using a Ficoll density gradient from prefrontal cortex (PFC), cerebellum (CER), striatum (ST), and hippocampus (HC). Carotenoids, PUFAs, and PUFA oxidation products were measured using HPLC, GC, and LC-GC/MS, respectively. All-trans-lutein (ng/mg protein) was detected in all regions and membranes and was highly variable among monkeys. Lutein/zeaxanthin supplementation significantly increased total concentrations of lutein in serum, PFC and CER, as well as lutein in mitochondrial membranes and total DHA concentrations in PFC only (P<0.05). In PFC and ST, mitochondrial lutein was inversely related to DHA oxidation products, but not those from arachidonic acid (P <0.05). This study provides novel data on subcellular lutein accumulation and its relationship to DHA oxidation in primate brain. These findings support the hypothesis that lutein may be associated with antioxidant functions in the brain.

Almonds can decrease glycemic index of co-consumed foods and are a rich source for oleic acid and α-tocopherol. The aim of the randomized, crossover, controlled feeding trial was to examine whether as compared to NCEP step II diet as control (CON), ~60 g/d almonds (ALM) added to CON would improve glucoregulation and cardiovascular disease (CVD) risk factors in 33 Chinese T2DM patients. Forty T2DM patients were enrolled and randomly assigned to receive CON or ALM for 12 wks after a 2-wk. run-in period. Blood and urine samples were collected in the beginning and at the end of each dietary intervention phase for the assessment of biomarkers of glucoregulation, lipid profile, inflammation, and oxidative stress. While ALM had a better overall nutritional quality than CON, neither ALM nor CON improved the glycemic status as the primary study outcome and other CVD risk factors, except the circulating nitric oxide being decreased by ALM compared to CON. Among 27 of 33 patients with the baseline HbA1c ≤8, ALM decreased post-interventional fasting serum glucose and HbA1c by 5.9% and 3.0% as compared to that of CON, respectively (P = 0.01 and 0.04). Mean total and LDL-cholesterol concentrations were not changed by both diets. These results suggest almonds incorporated into healthful diets can improve glycemic status in diabetic patients with a better glycemic control. NCT01656850 , registered 13 January 2012.

The dietary xanthophylls, lutein and zeaxanthin, accumulate in primate retina and brain, and emerging evidence indicates neural lutein content may be beneficial for cognition. Neural xanthophyll content in primates varies greatly among individuals, and genetic factors are likely to be significant contributors. Subspecies of rhesus macaques originating from different geographic locations are known to differ genetically, but the effect of origin on gene expression and carotenoid status has not been determined. The study objective was to determine whether xanthophyll status and expression of carotenoid-related genes, as well as genes with known variants between subspecies, differ between the brains of adult rhesus monkeys of Indian and Chinese origin. Samples of prefrontal cortex, cerebellum, and striatum were collected from adult monkeys (n = 9) fed a standard stock diet containing carotenoids. Serum and brain carotenoids were determined using reverse-phase high-performance liquid chromatography. For each brain region, RNA sequencing and real-time quantitative polymerase chain reaction were used to determine differentially expressed genes between the subspecies. Indian-origin monkeys had higher xanthophyll levels in brain tissue compared to Chinese-origin monkeys despite consuming similar amounts of dietary carotenoids. In a region-specific manner, four genes related to carotenoid and fatty acid metabolism (BCO2, RPE65, ELOVL4, FADS2) and four genes involved in the immune response (CD4, CD74, CXCL12 LTBR) were differentially expressed between Indian- and Chinese-origin monkeys. Expression of all four genes involved in carotenoid and fatty acid metabolism were correlated with brain xanthophyll concentration in a region-specific manner. These results indicate that origin is related to differences in both gene expression and xanthophyll content in the brain. Findings from this study may have important implications regarding genetic diversity, lutein status, and cognition in primates.

Obesity poses one of the biggest challenges facing public health-care professionals. Issues surrounding the development, consequences, and potential for control of obesity are complex. In the midst of the global obesity epidemic, research on prevention and treatment commands great interest, as evidenced by the 33,254 articles yielded from entering the search term “obesity prevention” into PubMed (National Library of Medicine, Bethesda, Maryland). It is a daunting task to stay current with the findings and directions of modern obesity research.