Chung-Jung Chiu

Informing food choices and health outcomes by use of the dietary glycemic index

Considerable epidemiologic evidence links consuming lower glycemic index (GI) diets with good health, particularly upon aging. The GI is a kinetic parameter that reflects the ability of carbohydrate (CHO) contained in consumed foods to raise blood glucose in vivo. Newer nutritional, clinical, and experimental data link intake of lower dietary GI foods to favorable outcomes of chronic diseases, and compel further examination of the record. Based upon the new information there are two specific questions: 1) should the GI concept be promoted as a way to prolong health, and 2) should food labels contain GI information? Further, what are the remaining concerns about methodological issues and consistency of epidemiological data and clinical trials that need to be resolved in order to exploit the benefits of consuming lower GI diets? These issues are addressed in this review.

Dietary Carbohydrate in Relation to Cortical and Nuclear Lens Opacities in the Melbourne Visual Impairment Project

PURPOSE In vitro and in vivo animal studies suggest that dietary carbohydrates play a role in cataractogenesis. Few epidemiologic studies have been conducted to evaluate this association. The objective of this study was to examine the cross-sectional associations between total carbohydrate intake, dietary glycemic index (dGI), and the risk of cortical and nuclear cataracts. METHODS After excluding 864 persons from 2473 eligible participants, 1609 eligible nondiabetic participants (mean age, 57.6 years, 55.9% female) in the Melbourne Visual Impairment Project (VIP) were enrolled. Dietary information derived from a semiquantitative food-frequency questionnaire and cataract status graded by the Wilmer protocol (cortical cataract: opacity >or=4/16; nuclear cataract grade >or=2) were collected. With the use of the generalized estimating approach to logistic regression to account for the lack of independence between the eyes of an individual, the associations between dietary carbohydrates and risk of cataract in eyes with no or a single type (pure) of cataract were examined. RESULTS Multivariate adjustment showed that pure cortical cataract (197 eyes) was significantly associated with total carbohydrate intake (odds ratio [OR] comparing the highest quartile with the lowest quartile = 3.19, 95% confidence interval [CI] = 1.10-9.27; P(trend) = 0.017). The OR for nuclear cataract (366 eyes) comparing the third quartile of dGI with the first quartile (OR = 1.64, 95% CI = 1.02-2.65) was significant, but there was not a consistent dose-response association (P(trend) = 0.75). CONCLUSIONS Carbohydrate intake may be optimized to prolong eye lens function. Because of the high proportion of subjects with missing covariates, these results warrant further study.

High glucose activates ChREBP-mediated HIF-1α and VEGF expression in human RPE cells under normoxia

OBJECTIVE Because retina-damaging angiogenesis is controlled by vascular endothelial growth factor (VEGF) and people with higher glucose intakes are more susceptible to retinal complications that may be due to increased VEGF, it is crucial to elucidate relations between glucose exposure and VEGF expression. We aimed to determine if a carbohydrate response element binding protein (ChREBP) plays a role in the transcriptional up-regulation of hypoxia-inducible factor-1α (HIF-1α) and the downstream VEGF expression in retinal pigment epithelial (RPE) cells exposed to high glucose under normoxic conditions. METHODS ARPE19 cells were exposed to 5.6, 11, 17, 25 and 30 mM glucose for 48 h in serum-free culture media under normoxic (21 % O2) conditions. Protein and mRNA expression of indicated genes were determined by immunoblot analyses and real-time RT-PCR, respectively. An enzyme-linked immunosorbent assay (ELISA) was used to detect the concentrations of VEGF in the media. Immunofluorescence (IF) and chromatin immunoprecipitation (ChIP) for ChREBP were used to demonstrate nuclear translocation and HIF-1α gene promoter association, respectively. RESULTS Immunoblot analyses showed that HIF-1α levels were positively related to levels of glucose exposure between 5.6-25 mM in the RPE cells, indicating the induction and stabilization of HIF-1α by elevated glucose under normoxic conditions. Human lens epithelial cells and HeLa cells did not respond to high glucose, implying that this phenomenon is cell type-specific. Real-time RT-PCR for HIF-1α and VEGF and ELISA for VEGF indicated that high glucose is associated with elevated production of HIF-1α-induced VEGF, an established inducer of neovascularization, in the RPE cells. IF analyses showed that, although ChREBP was expressed under both low (5.6 mM) and high (25 mM) glucose conditions, it appeared more in the nuclear region than in the cytosol of the RPE cells after the high glucose treatment. ChIP analyses suggested a HIF-1α gene promoter association with ChREBP under the high glucose condition. These results imply that RPE cells use cytosolic ChREBP as a glucose sensor to up-regulate HIF-1α expression. CONCLUSION These results suggest a high glucose-induced, ChREBP-mediated, and normoxic HIF-1α activation that may be partially responsible for neovascularization in both diabetic and age-related retinopathy.

Antioxidant Status and Risk for Cataract

Key Points Oxidative insult to lens proteins and proteases, together with limited ability to remove the damaged proteins, are involved in the etiology of age-related cataract. Observational studies indicate elevated levels of intake of antioxidants is associated with diminished prevalence, incidence, or progress of age-related cataract. They imply that having a daily intake of about 250 mg of vitamin C and 90 mg of vitamin E is associated with diminished risk for cataract. Much of this can be obtained from diet. There have been six intervention trails. The results from these are generally inconsistent with the results from the observational trials. It would be worthwhile to determine why the various types of studies are not yielding similar results. Most studies indicate associations between poverty, lack of education, lower socioeconomic status, and increased risk for age-related eye diseases. For such persons, a supplement might be indicated, failing remediation of the situation.

Nutritional Antioxidants, Dietary Carbohydrate, and Age-Related Maculopathy and Cataract

Loss of vision is the second greatest fear, next to death, among the elderly. Age-related cataract (ARC) and maculopathy (ARM) are two major causes of blindness worldwide. There are several important reasons to study relationships between risk for ARC/ARM and nutrition: (1) because it is likely that the same nutritional practices that are associated with prolonged eye function will also be associated with delayed age-related compromises to other organs and perhaps, aging in general; (2) surgical resources are insufficient to provide economic and safe surgeries for cataract and do not provide a widely practicable cure for ARM; (3) there will be considerable financial savings and improvements in quality of life if health is extended, particularly given the rapidly growing elderly segment of ourpopulation.

Dietary glycemia as a determinant of health and longevity.

The role of diet in extending lifespan and healthspan has been the subject of much research and debate. Our recent epidemiological and in vivo data suggest that carbohydrate quality can be a major determinant in prolonging eye health. Additionally, excessive carbohydrate intake can contribute to the exacerbation of many different diseases. The metabolic diversity of the tissues that are affected by excessive carbohydrate intake suggests that dietary carbohydrate quality may affect cellular homeostasis.

Visualization of Dietary Patterns and Their Associations With Age-Related Macular Degeneration

Purpose We aimed to visualize the relationship of predominant dietary patterns and their associations with AMD. Methods A total of 8103 eyes from 4088 participants in the baseline Age-Related Eye Disease Study (AREDS) were classified into three groups: control (n = 2739), early AMD (n = 4599), and advanced AMD (n = 765). Using principle component analysis, two major dietary patterns and eight minor dietary patterns were characterized. Applying logistic regression in our analysis, we related dietary patterns to the prevalence of AMD. Qualitative comparative analysis by operating Boolean algebra and drawing Venn diagrams was used to visualize our findings. Results In general, the eight minor patterns were subsets or extensions of either one of the two major dietary patterns (Oriental and Western patterns) and consisted of fewer characteristic foods than the two major dietary patterns. Unlike the two major patterns, which were more strongly associated with both early and advanced AMD, none of the eight minors were associated with early AMD and only four minor patterns, including the Steak pattern (odds ratio comparing the highest to lowest quintile of the pattern score = 1.73 [95% confidence interval: 1.24 to 2.41; Ptrend = 0.02]), the Breakfast pattern (0.60 [0.44 to 0.82]; Ptrend = 0.004]), the Caribbean pattern (0.64 [0.47 to 0.89; Ptrend = 0.009]), and the Peanut pattern (0.64 [0.46 to 0.89; Ptrend = 0.03]), were significantly associated with advanced AMD. Our data also suggested several potential beneficial (peanuts, pizza, coffee, and tea) and harmful (salad dressing) foods for AMD. Conclusions Our data indicate that a diet of various healthy foods may be optimal for reducing AMD risk. The effects of some specific foods in the context of overall diet warrant further study.

Associations between Periodontal Microbiota and Death Rates

It is conceived that specific combinations of periodontal bacteria are associated with risk for the various forms of periodontitis. We hypothesized that such specificity is also related to human cause-specific death rates. We tested this hypothesis in a representative sample of the US population followed for a mean duration of 11 years and found that two specific patterns of 21 serum antibodies against periodontal bacteria were significantly associated with increased all-cause and/or diabetes-related mortalities. These data suggested that specific combinations of periodontal bacteria, even without inducing clinically significant periodontitis, may have a significant impact on human cause-specific death rates. Our findings implied that increased disease and mortality risk could be transmittable via the transfer of oral microbiota, and that developing personalized strategies and maintaining healthy oral microbiota beyond protection against periodontitis would be important to manage the risk.

Glycemic Index and Age-Related Macular Degeneration

Abstract Carbohydrate is our major energy source, so it is reasonable that metabolism of sugars plays a significant role in aging and disease. Glycemic index (GI) reflects the kinetics of blood glucose levels after ingesting a meal in people both with and without diabetes. Recent data from a wide range of epidemiologic and molecular evidence offer strong support for the conclusion that dietary hyperglycemia is associated with risk for major metabolic disorders, including type 2 diabetes, cardiovascular diseases (CVD), and retinal diseases such as diabetic retinopathy (DR) and age-related macular degeneration (AMD). Therefore, it remains critical to reevaluate the management of carbohydrate nutrition as a means to prevent the onset or progression of these diseases. A low-GI diet should be recommended to those at high risk. In terms of identifying high-risk populations, development of susceptibility biomarkers, exposure biomarkers, and surrogate end points for a disease will be valuable. Future studies should focus on the relationship between management and efficacy of low-GI diets on disease risk. The biochemical mechanisms that link consuming high-GI diets to increased disease risk will need further understanding of the underlying pathogenesis.