Issues pertaining to Mg, Zn and Cu in the 2020 Dietary Reference Intakes for Koreans.

In the current years, it has now become necessary to establish standards for micronutrient intake based on scientific evidence. This review discusses issues related to the development of the 2020 Dietary Reference Intakes for Koreans (KDRI) for magnesium (Mg), zinc (Zn), and copper (Cu), and future research directions. Following issues were encountered when establishing the KDRI for these minerals. First, characteristics of Korean subjects need to be applied to estimate nutrient requirements. When calculating the estimated average requirement (EAR), the KDRI used the results of balance studies for Mg absorption and factorial analysis for Zn, which is defined as the minimum amount to offset endogenous losses for Zn and Mg. For Cu, a combination of indicators, such as depletion/repletion studies, were applied, wherein all reference values were based on data obtained from other countries. Second, there was a limitation in that it was difficult to determine whether reference values of Mg, Zn, and Cu intakes in the 2020 KDRI were achievable. This might be due to the lack of representative previous studies on intakes of these nutrients, and an insufficient database for Mg, Zn, and Cu contents in foods. This lack of database for mineral content in food poses a problem when evaluating the appropriateness of intake. Third, data was insufficient to assess the adequacy of Mg, Zn, and Cu intakes from supplements when calculating reference values, considering the rise in both demand and intake of mineral supplements. Mg is more likely to be consumed as a multi-nutrient supplement in combination with other minerals than as a single supplement. Moreover, Zn-Cu interactions in the body need to be considered when determining the reference intake values of Zn and Cu. It is recommended to discuss these issues present in the 2020 KDRI development for Mg, Zn, and Cu intakes in a systematic way, and to find relevant solutions.

The Potential Use of a Ketogenic Diet in Pancreatobiliary Cancer Patients After Pancreatectomy.

BACKGROUND/AIM: High-carbohydrate diets are generally provided to post-pancreatectomy cancer patients. Low energy density of this diet may obstruct proper energy intake and recovery. This study aimed to assess the effects of high-fat, high-energy ketogenic diet (KD) in these patients. PATIENTS AND METHODS: After pancreatectomy, 9 patients were provided with general diet (GD) while 10 were served KD. Meal compliance, energy intake rate, meal satisfaction and presence of complications were monitored throughout hospital stay. Data on nutritional status, serum lipids and body composition were collected and compared between groups. RESULTS: Meal compliance, energy intake rate and meal satisfaction score were higher in KD. There were no differences in complications, nutritional status and serum lipids. The decrease in body cell mass (BCM) was greater in GD. CONCLUSION: Post-pancreatectomy cancer patients who consumed KD had a higher energy intake and BCM. These results suggest the potential use of KD as an adjuvant anti-cancer therapy.

Rationale, Feasibility and Acceptability of Ketogenic Diet for Cancer Treatment.

Ketogenic diet has been used for more than 80 years as a successful dietary regimen for epilepsy. Recently, dietary modulation by carbohydrate depletion via ketogenic diet has been suggested as an important therapeutic strategy to selectively kill cancer cells and as adjuvant therapy for cancer treatment. However, some researchers insist ketogenic diet to be highly undesirable as ketogenic diet may trigger and/or exacerbate cachexia development and usually result in significant weight loss. This review revisits the meaning of physiological ketosis in the light of this evidence and considers possibility of the use of ketogenic diet for oncology patients. Article search was performed from 1985 through 2017 and finally 10 articles were analyzed. The review focused on the results of human trials for cancer patients and checked the feasibility of using ketogenic diet for cancer patients as adjuvant therapy. The main outcomes showed improvement of body weight changes, anthropometric changes, serum blood profiles, and reduction in novel marker for tumor progression, TKTL1, and increase of ketone body. Lactate concentration was reduced, and no significant changes were reported in the measurements of quality of life. Ketogenic diet may be efficacious in certain cancer subtypes whose outcomes appear to correlate with metabolic status, but the results are not yet supportive and inconsistent. Therefore, it warrants further studies.

A Case Report of the Nutrition Support for a Patient with HELLP Syndrome.

A 30-year-old female patient, 18 weeks gestational age, with no prior medical history was admitted to hospital complaining severe right upper quadrant pain. The patient was admitted to intensive care unit (ICU) after emergency surgery to treat intraperitoneal hemorrhage caused by rupture of liver hematoma. Despite the absence of high blood pressure, the patient was diagnosed with hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome on the basis of abnormal levels of blood aspartate aminotransferase/alanine aminotransferase, lactate dehydrogenase, total bilirubin, direct bilirubin, C-reactive protein (CRP) and platelet along with liver damage and proteinuria. While in ICU, the patient was given total parenteral nutrition (TPN) and enteral nutrition (EN) for -20 days because oral feeding was impractical. In the early stage, TPN supply was not sufficient to meet the elevated nutritional demand induced by disease and surgery. Nevertheless, continuous care of nutrition support team enabled satisfactory EN and, subsequently, oral feeding which led to improvement in patient outcome.

A Study on the Dietary Intake and the Nutritional Status among the Pancreatic Cancer Surgical Patients.

The adequate dietary intake is important to maintain the nutritional status of the patients after pancreatic cancer surgery. This prospective study was designed to investigate the dietary intake and the nutritional status of the patients who had pancreatic cancer surgery. Thirty-one patients (15 men, 16 women) were enrolled and measured body weight, body mass index (BMI), nutritional risk index (NRI), and Malnutrition Universal Screening Tool (MUST). Actual oral intake with nutritional impact symptoms recorded on the clinical research foam at every meal and medical information were collected from electronic medical charts. The rates of malnutrition at admission were 45.1% (14/31) and 28.9% (9/31) by NRI and MUST method, respectively, but those were increased to 87% (27/31) and 86.6% (26/31) after operation on discharge. The median values of daily intake of energy, carbohydrates, fat, and protein were 588.1 kcal, 96.0 g, 11.8 g, and 27.0 g, respectively. Most patients (n = 20, 64.5%) experienced two or more symptoms such as anorexia, abdominal bloating and early satiety. There were negative correlations between C-reactive protein (CRP) levels and the intake of total energy, protein, fat, and zinc. The rates of malnutrition were increased sharply after surgery and the dietary intake also influenced the inflammatory indicators. The results suggested that need of considering special therapeutic diets for the patients who received pancreatic surgery.

Relationship between Serum and Brain Carotenoids, α-Tocopherol, and Retinol Concentrations and Cognitive Performance in the Oldest Old from the Georgia Centenarian Study.

Oxidative stress is involved in age-related cognitive decline. The dietary antioxidants, carotenoids, tocopherols, and vitamin A may play a role in the prevention or delay in cognitive decline. In this study, sera were obtained from 78 octogenarians and 220 centenarians from the Georgia Centenarian Study. Brain tissues were obtained from 47 centenarian decedents. Samples were analyzed for carotenoids, α-tocopherol, and retinol using HPLC. Analyte concentrations were compared with cognitive tests designed to evaluate global cognition, dementia, depression and cognitive domains (memory, processing speed, attention, and executive functioning). Serum lutein, zeaxanthin, and ß-carotene concentrations were most consistently related to better cognition (P < 0.05) in the whole population and in the centenarians. Only serum lutein was significantly related to better cognition in the octogenarians. In brain, lutein and ß-carotene were related to cognition with lutein being consistently associated with a range of measures. There were fewer significant relationships for α-tocopherol and a negative relationship between brain retinol concentrations and delayed recognition. These findings suggest that the status of certain carotenoids in the old may reflect their cognitive function. The protective effect may not be related to an antioxidant effect given that α-tocopherol was less related to cognition than these carotenoids.

Effect of pertussis toxin and herbimycin A on proteinase-activated receptor 2-mediated cyclooxygenase 2 expression in Helicobacter pylori-infected gastric epithelial AGS cells.

Helicobacter pylori (H. pylori) is an important risk factor for chronic gastritis, peptic ulcer, and gastric cancer. Proteinase-activated receptor 2 (PAR2), subgroup of G-protein coupled receptor family, is highly expressed in gastric cancer, and chronic expression of cyclooxygenase-2 (COX-2) plays an important role in H. pylori-associated gastric carcinogenesis and inflammation. We previously demonstrated that H. pylori induced the expression of PAR2 and COX-2 in gastric epithelial cells. Present study aims to investigate whether COX-2 expression induced by H. pylori in Korean isolates is mediated by PAR2 via activation of G(i) protein and Src kinase in gastric epithelial AGS cells. Results showed that H. pylori-induced COX-2 expression was inhibited in the cells transfected with antisense oligonucleotide for PAR2 or treated with Gi protein blocker pertussis toxin, Src kinase inhibitor herbimycin A and soybean trypsin inbitor, indicating that COX-2 expression is mediated by PAR2 through activation of Gi protein and Src kinase in gastric epithelial cells infected with H. pylori in Korean isolates. Thus, targeting the activation of PAR2 may be beneficial for prevention or treatment of gastric inflammation and carcinogenesis associated with H. pylori infection.

Polyunsaturated Fatty Acid Composition of Surgically Removed Hard Exudates in Diabetic Macular Edema.

Three eyes of 2 patients with diabetic macular edema underwent a vitrectomy to remove subfoveal hard exudates. Fatty acid compositions of hard exudates and plasma phospholipids (PL) as an objective estimation of dietary intake were analyzed. Polyunsaturated fatty acids (PUFA) were relatively consistent in hard exudates and PL, but were less abundant in hard exudates. The hard exudates had lower levels of eicosapentaenoic acid (EPA, C20:5 omega3) and docosahexaenoic acid (DHA, C22:6 omega3), which oxidized more readily than other PUFA. Dietary PUFA may be associated with the composition of retinal hard exudates.

Site-specific concentrations of carotenoids in adipose tissue: relations with dietary and serum carotenoid concentrations in healthy adults.

BACKGROUND: Dietary carotenoids are related to a decreased risk of certain diseases. Serum and adipose tissue carotenoid concentrations are used as biomarkers of intake. OBJECTIVES: The objectives of this study were to evaluate site-specific concentrations of carotenoids in adipose tissue and to examine relations between carotenoid concentrations in the diet, serum, and adipose tissue. DESIGN: Healthy adults (12 women and 13 men) participated in this cross-sectional study. Dietary carotenoids over the past year were assessed with a food-frequency questionnaire. Serum and adipose tissue biopsy samples were collected from the abdomen, buttock, and inner thigh for the measurement of carotenoids by HPLC. RESULTS: Many adipose carotenoids were inversely related to percentage body fat, although lycopene was the only carotenoid inversely correlated with all 3 sites. Most of the carotenoids were significantly higher in the abdominal adipose tissue than in the thigh (P < 0.05). Concentrations of alpha-carotene, beta-carotene, 5-cis-lycopene, and total carotenoids were significantly higher in the buttocks than in the thigh (P < 0.05). Concentrations of alpha-carotene, cis-lycopene, and lutein (with or without zeaxanthin) were significantly higher in the abdomen than in the buttocks (P < 0.05). Dietary intake was significantly correlated with serum concentrations of alpha-carotene, beta-carotene, beta-cryptoxanthin, and total carotenoids. Carotenoid intake was significantly correlated with adipose tissue concentrations of alpha-carotene, beta-carotene, beta-cryptoxanthin, cis-lycopene, and total carotenoids (P < 0.05) but varied by site. Of all the adipose tissue sites evaluated, the abdomen showed the strongest correlation with long-term dietary carotenoid intakes and with serum (indicator of short-term intake) for most carotenoids. CONCLUSIONS: Body fat may influence the tissue distribution of carotenoids. Abdominal adipose tissue carotenoid concentrations may be a useful indicator of carotenoid status.

Cognitive findings of an exploratory trial of docosahexaenoic acid and lutein supplementation in older women.

INTRODUCTION: Low dietary intake of docosahexaenoic acid (DHA) and/or foods rich in lutein may be associated with increased risk of cognitive decline in the elderly. SUBJECTS AND METHODS: The cognitive benefit of DHA and lutein in unimpaired elder women was explored in the context of a 4-month, double-blind, intervention trial of DHA and lutein supplementation for eye health. Forty-nine women (aged 60-80 years) were randomized to receive DHA (800 mg/day; n = 14), lutein (12 mg/day; n = 11), a combination of DHA and lutein (n = 14) or placebo (n = 10). Subjects underwent cognitive tests measuring verbal fluency, memory, processing speed and accuracy, and self-reports of mood at randomization and upon completion of the trial. RESULTS: Following supplementation, verbal fluency scores improved significantly in the DHA, lutein, and combined treatment groups (P < 0.03). Memory scores and rate of learning improved significantly in the combined treatment group (P < 0.03), who also displayed a trend toward more efficient learning (P = 0.07). Measures of mental processing speed, accuracy and mood were not affected by supplementation. CONCLUSIONS: These exploratory findings suggest that DHA and lutein supplementation may have cognitive benefit for older adults.

The influence of supplemental lutein and docosahexaenoic acid on serum, lipoproteins, and macular pigmentation.

BACKGROUND: Lutein and docosahexaenoic acid (DHA) may protect against age-related macular degeneration (AMD). Lutein is a component of macular pigment. DHA is in the retina. OBJECTIVE: The objective of this 4-mo study was to determine the effects of lutein (12 mg/d) and DHA (800 mg/d) on their serum concentrations and macular pigment optical density (MPOD). DESIGN: Forty-nine women (60-80 y) were randomly assigned to placebo, DHA, lutein, or lutein + DHA supplement. Serum was analyzed for lutein and DHA (0, 2, and 4 mo). MPOD was determined (0 and 4 mo) at 0.4, 1.5, 3, and 5 degrees temporal retinal eccentricities. Serum was analyzed for lipoproteins (4 mo). RESULTS: There was no interaction between lutein and DHA supplementations for serum lutein and MPOD. The lutein supplementation x DHA supplementation x month interaction was significant for serum DHA response (P < 0.05). In the lutein group, serum lutein increased from baseline at 2 and 4 mo (P < 0.001), and MPOD increased at 3.0 degrees (P < 0.01). In the DHA group, serum DHA increased at 2 and 4 mo (P < 0.0001), and MPOD increased at 0.4 degrees (P < 0.05). In the lutein + DHA group, serum lutein and DHA increased at 2 and 4 mo (P < 0.01), and MPOD increased at 0.4, 1.5, and 3 degrees (P = 0.06, 0.08, and 0.09, respectively). Differences from placebo in lipoprotein subfractions were greatest for the lutein + DHA group (4 mo). CONCLUSIONS: Lutein supplementation increased MPOD eccentrically. DHA resulted in central increases. These results may be due to changes in lipoproteins. Lutein and DHA may aid in prevention of age-related macular degeneration.

A novel form of transducin-dependent retinal degeneration: accelerated retinal degeneration in the absence of rod transducin.

PURPOSE: Rhodopsin mutations account for approximately 25% of human autosomal dominant retinal degenerations. However, the molecular mechanisms by which rhodopsin mutations cause photoreceptor cell death are unclear. Mutations in genes involved in the termination of rhodopsin signaling activity have been shown to cause degeneration by persistent activation of the phototransduction cascade. This study examined whether three disease-associated rhodopsin substitutions Pro347Ser, Lys296Glu, and the triple mutant Val20Gly, Pro23His, Pro27Leu (VPP) caused degeneration by persistent transducin-mediated signaling activity. METHODS: Transgenic mice expressing each of the rhodopsin mutants were crossed onto a transducin alpha-subunit null (Tr(alpha)(-/-)) background, and the rates of photoreceptor degeneration were compared with those of transgenic mice on a wild-type background. RESULTS: Mice expressing VPP-substituted rhodopsin had the same severity of degeneration in the presence or absence of Tr(alpha). Unexpectedly, mice expressing Pro347Ser- or Lys296Glu-substituted rhodopsins exhibited faster degeneration on a Tr(alpha)(-/-) background. To test whether the absence of alpha-transducin contributed to degeneration by favoring the formation of stable rhodopsin/arrestin complexes, mutant Pro347Ser(+), Tr(alpha)(-/-) mice lacking arrestin (Arr(-/-)) were analyzed. Rhodopsin/arrestin complexes were found not to contribute to degeneration. CONCLUSIONS: The authors hypothesized that the decay of metarhodopsin to apo-opsin and free all-trans-retinaldehyde is faster with Pro347Ser-substituted rhodopsin than it is with wild-type rhodopsin. Consistent with this, the lipofuscin fluorophores A2PE, A2E, and A2PE-H(2), which form from retinaldehyde, were elevated in Pro347Ser transgenic mice.

Inhibition of serine-threonine protein phosphatases in monocyte chemoattractant protein-1 expression in Helicobacter pylori-stimulated gastric epithelial cells.

The reversible phosphorylation of proteins controlled by protein kinases and protein phosphatases is a major mechanism that regulates a wide variety of cellular processes, such as inflammation. It has been reported that the activity of at least 30% of all proteins can be regulated by phosphorylation in eukaryotic cells. Among these proteins, mitogen-activated protein kinases (MAPK) and several transcription factors play pivotal roles in inflammation. We previously demonstrated that Helicobacter pylori in a Korean isolate (HP99) induced proinflammatory chemokine expression by activating MAPK and transcription factors, nuclear factor-kappaB (NF-kappaB), and activator protein-1 (AP-1) in gastric epithelial AGS cells. In an attempt to determine the role of phosphorylation-dephosphorylation in HP99-induced inflammation, we analyzed the expression of protein phosphatases, the activation of MAPK and transcription factors, and the production of chemokine MCP-1 in AGS cells stimulated with HP99 (at a bacteria-cell ratio of 300:1) and cultured in the presence or absence of a nonspecific serine-threonine protein phosphatase inhibitor, okadaic acid (OA). Our results showed that HP99 induced the expression of protein phosphatases, PP1 and PP2A in AGS cells as early as 30 min. HP99 induced the activation of MAPK and AP-1, and the production of monocyte chemoattractant protein-1 (MCP-1), which were augmented by pretreatment with 100 nM of OA. Gastric epithelial cells induced the expression of PP1 and PP2A in response to HP99 presumably as a defense mechanism against inflammatory chemokine expression by inhibiting the activation of MAPK and AP-1.

Isoflavone supplements exert hormonal and antioxidant effects in postmenopausal Korean women with diabetic retinopathy.

There is growing evidence that soy isoflavones exert hormonal and antioxidant effects in postmenopausal women. In the present study, 12 postmenopausal Korean women with diabetic retinopathy consumed 2 g of genistein combined polysaccharides (GCP), containing 120 mg of genistein and 57 mg of daidzein, daily for 12 weeks. Blood was collected prior to and after 12 weeks of GCP supplementation for analysis of fasting blood glucose, insulin, lipid profiles, sex hormone-binding globulin (SHBG), estradiol, testosterone, free testosterone, and osteocalcin and activities of glutathione peroxidase (GSH-Px), catalase, and paraoxonase. After GCP supplementation, blood glucose, insulin, total cholesterol, triglyceride, high-density lipoprotein, and low-density lipoprotein cholesterols did not change significantly. However, there were significant increases in SHBG (P < .05) and testosterone (P < .05) and a decrease in estradiol (P < .01). Free testosterone levels were not significantly affected by GCP supplementation. After supplementation, osteocalcin decreased, but the difference was not statistically significant. Although activities of catalase and paraoxonase were unchanged, GSH-Px activity (P < .01) was increased significantly. These findings suggest that GCP supplementation may change the levels of some hormones and improve antioxidant status in postmenopausal Korean women with diabetic retinopathy.

Lutein bioavailability is higher from lutein-enriched eggs than from supplements and spinach in men.

Lutein may be protective against diseases such as age-related macular degeneration (ARMD). At present, data regarding bioavailability of lutein from various sources are insufficient. Healthy men (n = 10) participated in an intervention study with a crossover design. After a 2-wk washout period during which they consumed a low-carotenoid diet, the men were administered 1 of 4 lutein doses (lutein supplement, lutein ester supplement, spinach, and lutein-enriched egg) for 9 d. All lutein doses provided 6 mg lutein except for the lutein ester dose, which provided 5.5 mg lutein equivalents. Serum samples were collected from fasting subjects on d -14, 1 (baseline), 2, 3, and 10 and analyzed for changes in lutein concentration. Triacylglycerol-rich lipoproteins (TRL) were separated from postprandial blood samples (0-24 h) after the first lutein dose and analyzed for lutein concentration. Subjects completed all 4 treatments of the study in random order. Results from repeated-measures 1-way ANOVA showed that the baseline and dose-adjusted lutein response in serum was significantly higher after egg consumption than after lutein, lutein ester, and spinach consumption on d 10. There was no significant difference in TRL response. In conclusion, the lutein bioavailability from egg is higher than that from other sources such as lutein, lutein ester supplements, and spinach. The lutein bioavailability from lutein, lutein ester supplements, and spinach did not differ. This finding may have implications for dietary recommendations that may decrease the risk of certain diseases, e.g., ARMD.

Spontaneous activity of opsin apoprotein is a cause of Leber congenital amaurosis.

Mutations in Rpe65 disrupt synthesis of the opsin chromophore ligand 11-cis-retinal and cause Leber congenital amaurosis (LCA), a severe, early-onset retinal dystrophy. To test whether light-independent signaling by unliganded opsin causes the degeneration, we used Rpe65-null mice, a model of LCA. Dark-adapted Rpe65-/- mice behaved as if light adapted, exhibiting reduced circulating current, accelerated response turn-off, and diminished intracellular calcium. A genetic block of transducin signaling completely rescued degeneration irrespective of an elevated level of retinyl ester. These studies clearly show that activation of sensory transduction by unliganded opsin, and not the accumulation of retinyl esters, causes light-independent retinal degeneration in LCA. A similar mechanism may also be responsible for degeneration induced by vitamin A deprivation.

The activities of antioxidant nutrients in human plasma depend on the localization of attacking radical species.

The oxidation of endogenous antioxidant nutrients in human plasma was determined to examine their activities against free radicals generated in the aqueous and lipid compartments of plasma. Free radicals were induced at a constant rate in the aqueous compartment by the hydrophilic radical generator, 2,2'-azobis-(2-amidinopropane)dihydrochloride (AAPH; 10-20 mmol/L) and in the lipid compartment by the lipophilic radical generator, 2,2'-azobis(4-methoxy-2,4-dimethylvaleronitrile) (MeO-AMVN; 1-2 mmol/L). The depletion of endogenous plasma antioxidant nutrients (lutein, cryptoxanthin, beta-carotene, lycopene, alpha-tocopherol, ascorbic acid, uric acid) was determined after incubation with either AAPH or MeO-AMVN at 37 degrees C using HPLC. The oxidation of the aqueous and lipid compartments of plasma was selectively monitored by a fluorimetric method using either the hydrophilic probe, 2',7'-dichlorodihydrofluorescein (DCFH) or the lipophilic probe, 4,4-difluoro-5-(4-phenyl-1,3-butadienyl)-4-bora-3a, 4a-diaza-s-indacene-3-undecanoic acid (BODIPY 581/591). When plasma was incubated with AAPH, the rates of consumption of the antioxidant nutrients were as follows: ascorbic acid > alpha-tocopherol > uric acid > lycopene > lutein > cryptoxanthin > beta-carotene. When plasma was incubated with MeO-AMVN, alpha-tocopherol and carotenoids were depleted at similar rates and ahead of the major water-soluble antioxidants. Our study indicates that the antioxidant nutrients present in both the lipid and aqueous compartments can remove free radicals generated in plasma, and their activity depends on the localization of the attacking radical species.