Dietary inflammatory index and mortality: a cohort longitudinal study in a Mediterranean area.

BACKGROUND: Higher Dietary Inflammatory Index (DII®) scores are associated with increased morbidity and mortality. However, little is known about the effects of DII on mortality in Mediterranean countries. Therefore, in the present study, we aimed to investigate the potential association between DII scores and overall, cancer and cardiovascular disease (CVD) mortality in people living in a Mediterranean area. METHODS: DII scores were calculated using a validated food-frequency questionnaire. DII scores were then categorised into tertiles. Mortality was ascertained via death certificates. The association between DII scores with overall and cause-specific mortality was assessed via a multivariable Cox's regression analysis and reported as hazard ratios (HRs) with their 95% confidence intervals (CIs). RESULTS: The study included 1565 participants (mean age 65.5 years; females 44.7%). After a median follow-up of 12 years (2005-2017), 366 (23.4%) participants died. After adjusting for 17 potential confounders, people with higher DII scores had an increased risk of death compared to those in the lowest (most anti-inflammatory) tertile (HR = 1.38; 95% CI = 1.04-1.82 for the second tertile; HR = 1.38; 95% CI = 1.03-1.86 for the third tertile). Each 1 SD increase in DII score increased the risk of death by 13%. No association was found between DII scores and cancer or CVD death when considered separately. CONCLUSIONS: Higher DII scores were associated with a significantly higher mortality risk, whereas the association with cause-specific mortality was less clear. These findings highlight the potential importance of diet in modulating inflammation and preventing death.

Pro-inflammatory dietary pattern is associated with fractures in women: an eight-year longitudinal cohort study.

In this study, during 8 years of follow-up, we reported that higher dietary inflammatory index values were associated with a higher risk of incident fractures in women, but not in men, after adjusting for potential confounders. INTRODUCTION: Inflammation is a key risk factor for many adverse outcomes in older people. While diet is a potential source of inflammation, little is known about the impact of inflammatory diet on fractures. Thus, we investigated whether higher Dietary Inflammatory Index (DII)™ ® scores are associated with fractures in a cohort of North American people. METHODS: This longitudinal study with a follow-up of 8 years included 3648 participants (1577 males and 2071 females; mean age = 60.6 years) with/at risk of knee osteoarthritis participating with in the Osteoarthritis Initiative. DII scores were calculated using the validated Block Brief 2000 Food Frequency Questionnaire, categorized into sex-specific quintiles. Information on fractures was obtained through self-reported history of fractures at hip, spine, and forearm. The relationship between baseline DII score and incident fracture was assessed through a Cox's regression analysis, adjusted for potential baseline confounders, and reported as hazard ratios (HRs). RESULTS: During 8 years of follow-up, 560 individuals developed fractures (15.4%). Adjusting for 10 potential confounders, women in the highest DII score quintile (i.e., most pro-inflammatory diet) had a significantly higher risk for fractures (HR = 1.46; 95% CI = 1.02-2.11) compared to women in the lowest quintile. An increase in one standard deviation of DII scores significantly predicted fracture onset in women (adjusted HR = 1.14; 95% CI = 1.02-1.27). The association between DII score and fractures was not significant among men or in the sample as whole. CONCLUSION: Pro-inflammatory diet is associated with a higher incidence of fractures in women but not men.

Potato Consumption Is not Associated with Higher Risk of Mortality: A Longitudinal Study among Southern Italian Older Adults.

OBJECTIVE: The consumption of potatoes is increasing worldwide, but few studies have assessed the association between potato consumption and mortality, particularly in Mediterranean countries. We therefore investigated whether potato consumption is associated with higher risk of death in a large cohort of people living in South Italy. DESIGN: Longitudinal. SETTING: Community-dwelling. MEASUREMENTS: 2,442 participants coming from MICOL and NUTRIHEP studies aged more than 50 years at baseline were followed-up for 11 years. Dietary intake was assessed by means of a Food Frequency Questionnaire. Potato consumption was categorized in quintiles according to their daily consumption (< 3.95, 3.96-8.55, 8.56-15.67, 15.68-22.0, and > 22.0 g/day). Mortality was ascertained through validated cases of death. The association between potato consumption and mortality was assessed through Cox's regression models, adjusted for potential confounders, and reporting the data as hazard ratios (HRs) with 95% confidence intervals (CIs). RESULTS: The 2,442 eligible participants were prevalently males (54.6%) and aged a mean of 64.3±9.3 years. During the 11-year follow-up, 396 (=16.2%) participants died. After adjusting for 12 potential baseline confounders, and taking those with the lowest consumption of potatoes as the reference group, participants with the highest consumption of potatoes did not have an increased overall mortality risk (HR=0.75; 95%CI: 0.53-1.07). Modelling the potato consumption as continuous (i.e. as increase in 10 g/day) did not substantially change our findings (fully-adjusted HR=0.93; 95%CI: 0.84-1.02). CONCLUSION: Overall potato consumption was not associated with higher risk of death in older people living in a Mediterranean area. Future studies are warranted to elucidate the role of potato consumption on all-cause and cause-specific mortality.

Glycated apolipoprotein B and myocardial infarction.

AIMS: To evaluate the association of serum concentrations of glycated apolipoprotein B (ApoBg) with the incidence of myocardial infarction (MI) in subjects with and without diabetes. METHODS: The design is a nested case-control study. The cohort included 5632 subjects over 50 years of age attending the clinical laboratories of a small geographic area in southern Italy. After five years, 4563 subjects were traced and 103 had developed MI. We sampled from the cohort two controls for each incident case of MI, frequency matched for sex and diabetes. ApoBg was measured using a monoclonal antibody. Logistic regression was used for statistical analysis of the data. RESULTS: ApoBg at baseline was higher in subjects who developed myocardial infarction than in controls in both non-diabetic and diabetic subjects (t test, P=0.009 and P=0.05 respectively). MI odds ratio in the third tertile of ApoBg was 2.01 (95% CI 0.93-4.33) in non-diabetic and 2.88 (0.85-9.68) in diabetic subjects (chi-square test for trend; non-diabetics P=0.03, diabetics P=0.06). Serum triglycerides, cholesterol, HDL and LDL cholesterol, glucose and insulin were not associated with MI (P>0.10). CONCLUSION: ApoBg at baseline is directly associated with the development of MI in the following five years in both diabetic and non-diabetic individuals.

Effect of a Low Glycemic Index Mediterranean Diet on Non-Alcoholic Fatty Liver Disease. A Randomized Controlled Clinici Trial.

INTRODUCTION: Non-Alcoholic Fatty Liver Disease (NAFLD) is currently the most common form of liver disease worldwide affecting all ages and ethnic groups and it has become a consistent threat even in young people. Our aim was to estimate the effect of a Low Glycemic Index Mediterranean Diet (LGIMD) on the NAFLD score as measured by a Liver Ultrasonography (LUS). DESIGN: NUTRIzione in EPAtologia (NUTRIEPA) is a population-based Double-Blind RCT. Data were collected in 2011 and analyzed in 2013-14. SETTING/PARTICIPANTS: 98 men and women coming from Putignano (Puglia, Southern Italy) were drawn from a previous randomly sampled population-based study and identified as having moderate or severe NAFLD. INTERVENTION: The intervention strategy was the assignment of a LGIMD or a control diet. OUTCOME MEASURES: The main outcome measure was NAFLD score, defined by LUS. RESULTS: After randomization, 50 subjects were assigned to a LGIMD and 48 to a control diet. The study lasted six months and all participants were subject to monthly controls/checks. Adherence to the LGIMD as measured by Mediterranean Adequacy Index (MAI) showed a median of 10.1. A negative interaction between time and LGIMD on the NAFLD score (-4.14, 95% CI -6.78,-1.49) was observed, and became more evident at the sixth month (-4.43, 95%CI -7.15, -1.71). A positive effect of the interaction among LGIMD, time and age (Third month: 0.07, 95% CI 0.02, 0.12; Sixth month: 0.08, 95% CI 0.03,0.13) was also observed. CONCLUSIONS: LGIMD was found to decrease the NAFLD score in a relatively short time. Encouraging those subjects who do not seek medical attention but still have NAFLD to follow a LGIMD and other life-style interventions, may reduce the degree of severity of the disease. Dietary intervention of this kind, could also form the cornerstone of primary prevention of Type 2 Diabetes Mellitus (T2DM) and cardiovascular disease.

Abnormalities in serum lipoprotein composition in patients with premature coronary heart disease compared to serum lipid matched controls.

Serum lipoprotein composition was examined in 18 male patients (mean age 44 +/- 0.9 years) who had undergone coronary artery by-pass surgery because of premature coronary heart disease (PCHD) and in 18 control subjects, matched with patients for sex, age, body mass index and serum cholesterol and triglyceride. Cholesterol, triglyceride and apolipoprotein B (apo B) concentrations in very low density lipoprotein (VLDL) and in low density lipoprotein (LDL) did not differ in the two groups, but high density lipoprotein (HDL)-cholesterol was significantly lower in PCHD patients (P less than 0.02). Cholesterol/apo B, triglyceride/apo B and phospholipid/apo B ratios in VLDL were significantly higher in patients than in controls (P less than 0.05, P less than 0.01 and P less than 0.001, respectively). The relative VLDL enrichment in cholesterol was mainly due to the non-esterified moiety (P less than 0.01). These VLDL abnormalities as well as the low HDL-cholesterol suggest an impairment of VLDL catabolism in PCHD patients.

Low density lipoprotein receptors and polyamine levels in human colorectal adenocarcinoma.

The low density lipoprotein receptor (LDLR) is a cell surface protein that binds with LDL, providing the cell with cholesterol for new membrane synthesis. Rapidly growing cells have high numbers of LDLRs, and these proteins have also been detected in neoplastic samples of human colorectal mucosa. Polyamines, putrescine, spermidine, and spermine, play an important role in cellular growth, and studies on colorectal cancers have demonstrated higher polyamine levels in neoplastic mucosa samples than in surrounding mucosa. The aim of this study was to investigate LDLR and polyamine levels in the neoplastic tissue of 43 patients (28 males and 15 females) with colorectal adenocarcinoma, using enzymatic immunoassay and high performance liquid chromatography, respectively. Specimens of neoplastic mucosa were considered LDLR-positive or LDLR-negative when the amount of bound human anti-LDLR antibody detected was equal or higher or lower than the cut-off value (0.5 ng of bound anti-LDLR Ab/mg protein), respectively. Twenty-one subjects were LDLR-positive and 22 LDLR-negative. Polyamine levels (nmol/g tissue) were higher in LDLR-positive specimens; this increase was significant for total polyamines (P < 0.05). These findings, reporting the presence of increased polyamine content in LDLR-positive colorectal neoplastic specimens, suggest an association between LDLR levels and gastrointestinal neoplastic proliferative activity.

Prognostic value of low density lipoprotein receptor expression in colorectal carcinoma.

Cancer cells require more cholesterol than normal cells. This requirement seems to be satisfied by a higher HMG-CoA reductase activity or a higher activity of low density lipoprotein receptor (LDLR). We investigated the prognostic value of LDLR in colorectal carcinoma (CRC) patients. The LDLR was evaluated in 90 patients with CRC by ELISA. The survival time and the relative risk of prognostic factors were analyzed by Kaplan-Meier estimates and Cox proportional hazard model. Thirty three cases were LDLR positive (+), while 57 LDLR negative (-). The survival of LDLR(-) patients was shorter than that of LDLR(+). By Cox model, the absence of LDLR and time until metastasis resulted significantly associated with the CRC-related survival. The absence of LDLR in CRC predicts a shorter survival.

Low density lipoprotein receptor and mRNA expression in human colorectal cancer.

BACKGROUND: We have previously show that, 63.3% of colorectal cancers did not express the Low Density Lipoprotein Receptor (LDLR). We now report the findings of a study on the expression of LDLR and its mRNA in neoplastic tissue specimens of human colorectal cancer (CRC), carried out to verify whether the absence of the LDLR in these tumours is reflected by the absence of its transcript. MATERIALS AND METHODS: 32 patients (10 females and 22 males) operated for CRC were included in the study. The LDLR levels were evaluated by immunoenzymatic assay. The LDLR-mRNA, reverse-transcribed and then amplified by polymerase chain reaction, was detected by chromatography. RESULTS: The LDLR protein was present in 12 out of the 32 patients. LDLR-mRNA expression was detected in 17 out of the 32 patients. The absence of the LDLR protein was reflected by the absence of its transcript in 13 out of the 20 tumours; The LDLR mRNA levels were significantly higher in the tumours that did not expres LDLR. CONCLUSION: The variable expression of the LDLR protein and LDLR mRNA in CRC detected in this study suggests the possibility that different therapeutic strategies may be indicated for these tumours.

Enhanced 3-hydroxy-3-methyl-glutaryl coenzyme A reductase activity in human colorectal cancer not expressing low density lipoprotein receptor.

BACKGROUND: We have previously shown that 63.3% of colorectal cancer neoplastic specimens did not express the Low Density Lipoprotein Receptor (LDLR) protein and that the absence of LDLR predicted shorter survival. We now report the findings of a preliminary study on HMG-CoA reductase (HMG-CoAR) activity in neoplastic tissue specimens of human colorectal cancers (CRC) expressing or not expressing LDLR. MATERIALS AND METHODS: The tissue specimens were obtained from 16 patients (10 males and 6 females) undergoing surgical resection for CRC, and previously characterized for LDLR (7 not expressing LDLR and 9 expressing LDLR). HMG-CoAR activity was measured by radiochemical assay using 14C-HMG-CoA as substrate. RESULTS: HMG-CoAR activity was significantly higher in specimens not expressing LDLR than in those expressing LDLR [8.3 pmol/min/mg prot (2.4-16) vs 3.9 pmol/min/mg prot (1.2-7.8), data expressed as median value and the range, p = 0.02, Wilcoxon Rank sum test)]. CONCLUSIONS: The cholesterol requirement in CRC not expressing LDLR may be met by increasing endogenous synthesis. For this reason, the use of HMG-CoA R inhibitors for the treatment of CRC expressing high HMG-CoAR activity-dependence for growth may be clinically important.

Antioxidant effect of short-term hormonal treatment in postmenopausal women.

OBJECTIVES: Recent studies have shown that estrogens alone or in association with progestins can exert an antioxidant effect on Low-Density Lipoprotein (LDL) and lipids of platelet membranes. It has been demonstrated that the oxidative modification of LDLs also involving the formation of lipid peroxides, exerts several biological effects that may contribute to the onset and progression of cardiovascular diseases. Therefore, the aim of our study was to evaluate the effect of short-term treatment with oral estrogens alone and estrogens plus progestin on endogenous and copper-induced serum levels of lipid peroxides in postmenopausal women. METHODS: Thirty-nine postmenopausal women were randomly divided into three groups: group I was treated with oral conjugated equine estrogens (CEE) for 21 days; group II received oral CEE for 21 days and, after 14 days of this treatment, 5 mg/day of medrogestone was added for 7 days; group III did not receive any therapy (controls). Endogenous and copper-induced serum levels of lipid peroxides were determined before and after 21 days of treatment in the two treated groups and in the control group. RESULTS: The serum endogenous levels of lipid peroxides in postmenopausal women did not change after short-term treatment with hormone replacement therapy. Moreover, copper-induced serum levels of lipid peroxides significantly decreased after therapy in both groups I and II. CONCLUSIONS: Our data show that hormone replacement therapy (HRT) inhibits lipid peroxidation and may play a role in preventing cardiovascular diseases.

[Serum lipids and biliary sludge during pregnancy]. / Lipidi sierici e sabbia biliare durante la gravidanza.

We have examined serum lipids and apoprotein levels and the formation of biliary sludge in 56 pregnant women. During pregnancy, 8 women showed biliary sludge which disappeared after delivery. Pregnant women with sludge had serum levels of total cholesterol, triglycerides, LDL-cholesterol and apo-B higher than women without sludge, although it was not statistically significant. Moreover, these women had serum levels of HDL-cholesterol and apoA1 significantly lower and LDL/HDL and apoB/apoA1 ratio significantly higher than the women without sludge. Thus, biliary sludge seems to be associated with serum lipid and apoprotein variations. Further investigations are required to clarify if these variations are also expressed in the bile.

Tumor-induced alterations in lipid metabolism.

Alterations of lipid metabolism have been increasingly recognized as a hallmark of cancer cells. Cancer cells esterify fatty acids predominantly to phospholipids, an essential component of cell membranes. The main pathway along which proliferating cells gain lipids for membrane synthesis is the endogenous mevalonate pathway. Increased synthesis of mevalonate and mevalonate-derived isoprenoids supports increased cell proliferation through activating growth-regulatory proteins and oncoproteins and promoting DNA synthesis. The importance of a better knowledge of metabolic changes in lipogenic enzymes pathways, as well as of the role of each biochemical pathway in carcinogenesis, provides the rationale for in-depth study of the oncogenic signaling important for the initiation and progression of tumors. The dependence of tumor cells on a dysregulated lipid metabolism suggests that the proteins involved in this process may be excellent chemotherapeutic targets for cancer treatment. Here, we confirm the vital link between lipogenesis and cell proliferation, and our recent findings suggest that nutritional intervention is an effective and safe way to reduce cell proliferation in experimental models of carcinogenesis. The olive oil diet significantly reduces the protein activities of lipogenic enzymes associated with cell growth. The use of natural dietary components could potentially assist in the management of subjects with metabolic disorders-related tumors.

Nutrition, metabolism and colorectal cancer.

Colorectal cancer and myocardial infarction are associated at population level and in autoptic studies. Furthermore, they share many blood variables: cholesterol, triglycerides and HDL cholesterol, fructosamine, glycated haemoglobin and glycated apolipoprotein B. These blood variables are intermediates between dietary, mainly saturated fats and high glycemic index and load diets, and colorectal cancer and myocardial infarction. Blood intermediate variables can be used in dietary trials as outcomes, and even to throw light on the pathogenesis of both diseases.

Association between cannabinoid type-1 receptor polymorphism and body mass index in a southern Italian population.

CONTEXT: Endocannabinoids control food intake via both central and peripheral mechanisms, and cannabinoid type-1 receptor (CB1) modulates lipogenesis in primary adipocyte cell cultures and in animal models of obesity. OBJECTIVES: We aimed to evaluate, at the population level, the frequency of a genetic polymorphism of CB1 and to study its correlation with body mass index. DESIGN, SETTING AND PARTICIPANTS: Healthy subjects from a population survey carried out in southern Italy examined in 1992-1993 and older than 65 years (n=419, M=237, F=182) were divided into quintiles by body mass index (BMI). Two hundred and ten subjects were randomly sampled from the first, third and fifth quintile of BMI (BMI, respectively: 16.2-23.8=normal, 26.7-28.4=overweight, 31.6-49.7=obese) to reach a total of 70 per quintile. Their serum and white cells from the biological bank were used to measure the genotype and the blood variables for the study. MEASUREMENTS: Anthropometric parameters, blood pressure, serum glucose and lipid levels were measured with standard methods; genotyping for the CB1 1359G/A polymorphism was performed using multiplex PCR. Statistical methods included chi2 for trend, binomial and multinomial multiple logistic regression to model BMI on the genotype, controlling for potential confounders. RESULTS: We found a clear trend of increasing relative frequency of the CB1 wild-type genotype with the increase of BMI (P=0.03) and, using a multiple logistic regression model, wild-type genotype, female gender, age, glycaemia and triglycerides were directly associated with both overweight (third quintile of BMI) and obesity (fifth quintile of BMI). CONCLUSIONS: Although performed in a limited number of subjects, our results show that the presence of the CB1 polymorphic allele was significantly associated with a lower BMI.

Demonstration of low density lipoprotein receptor in human colonic carcinoma and surrounding mucosa by immunoenzymatic assay.

In order to verify the presence of Low Density Lipoprotein Receptor (LDLR) in cellular membranes isolated from human colonic tissue, samples from the neoplastic colorectum and the normal surrounding mucosa were studied by an enzyme-linked-immunosorbent assay. A monoclonal antibody against the human LDLR was used. The LDLR content revealed a considerable inter-individual variation. In 36 out of 53 cases (68%) there was no LDLR presence in either normal or neoplastic tissue samples. In 5 out of 53 cases (9.4%), LDLRs were detected in both types of tissue samples, in 9 cases out of 53 (17%) LDLRs were present in neoplastic tissue, while in 3 out of 53 cases (5.6%) only in normal mucosa. The anti-LDLR mono-clonal antibody (mAb) binding was significantly higher in neoplastic tissue samples than normal surrounding colonic mucosa ones. Sex, age, body mass index (BMI), serum cholesterol, tumour site, histologic grading and Dukes' stage did not seem to be associated with LDLR presence.

Lipoprotein(a) serum levels in post-menopausal women treated with oral estrogens administered at different times.

The different effects on serum lipoprotein(a) [Lp(a)] levels by administering estrogens at different times of the day (8 a.m. and 8 p.m.) were evaluated in twenty-four post-menopausal women. Patients were assigned to one of the two treatment groups by random sampling numbers. Patients of both groups received 0.625 mg conjugated equine estrogens daily per os for 21 days. Group A patients (n: 9) received the pill at 8 a.m., and group B patients (n: 12) received the pill at 8 p.m. There were no statistically significant differences between the two treatment groups as regards the anthropometric characteristics, the basal values of the Lp(a), the sex steroid and pituitary hormone levels. Administration of conjugated equine estrogens resulted in decreased levels of Lp(a) only in group B after treatment. The different Lp(a) behaviour in the two groups and in the presence of the same serum hormonal levels, seems to be dependent on the existence of a circadian rhythm of the hepatic responsiveness to estrogens, whose expression is higher during evening hours.

Changes in plasma concentrations of atrial natriuretic peptide during the first ten days and the second month of life.

Atrial natriuretic peptide (ANP) was assayed on the 1st, 3rd, 7th and 10th day of extrauterine life and the levels of the hormone were checked after the 2nd month in 12 infants. After an initially rapid increase, with a peak of the 3rd day (45.7 +/- 7 pg/ml the 1st day of extrauterine life and 175 +/- 5 pg/ml on the 3rd day), we can recognise a progressive decrease until the measurement made at 2 months (61.5 +/- 5 pg/ml). The reported data show the important role of ANP in adaption of life after birth. This can be considered as a compensatory response because it represents an attempt to maintain the balance of positive sodium which is essential for the growth of the newborn.

Polyamine biosynthesis in relation to K-ras and p-53 mutations in colorectal carcinoma.

BACKGROUND: Polyamines are important polycations found in high concentrations in gastrointestinal neoplasms, and ornithine decarboxylase is the key enzyme in their biosynthesis. Also genes with oncogenic potential (e.g. K-ras and p53) contribute to neoplastic transformation by modifying normal cellular proliferation and differentiation. Our aim was to evaluate the ornithine decarboxylase activity and polyamine levels in samples of colorectal carcinoma and uninvolved surrounding mucosa from 86 patients (52 men and 34 women) showing different patterns of K-ras/p53 mutations. METHODS: Polyamines were evaluated by high performance liquid chromatography. Ornithine decarboxylase activity was determined using the radiometric method. K-ras and p53 mutations were investigated by PCR followed by restriction fragment length polymorphism (PCR-RFLP) and single strand conformational polymorphism (PCR-SSCP), respectively. Multiple linear regression analysis was used to analyse relationships among polyamine biosynthesis, clinical-pathological variables and K-ras/p53 mutations. RESULTS: ODC activity and polyamine levels were significantly higher in neoplastic samples than in normal surrounding mucosa. K-ras codon 12 mutation was found in 25/86 patients (29.1%) and p53 gene mutation in 41/86 (47.7%). Polyamine biosynthesis was significantly higher in cancers showing K-ras mutation, either with or without p53 mutation [K-ras(+)/p53(-) and K-ras(+)/p53(+)], compared to samples with K-ras wild type [K-ras(-)/p53(-) and K-ras(-)/p53(+)]. Multiple linear regression analysis confirmed this finding. CONCLUSIONS: The present study provides evidence of a close relationship between K-ras mutation and polyamine biosynthesis in human colorectal carcinoma in a way that is largely p53 independent. In addition, our data support the hypothesis of different pathways in colorectal tumorigenesis reflecting different combinations of biochemical parameters and genetic alterations.