Fibromyalgia and Nutrition: An Updated Review.

Due to the lack of specific and standardized treatments for the management of fibromyalgia (FM), available evidence suggests a multidisciplinary approach, and nutrition represents an important therapeutic strategy. This work aims to update the relationship between FM and nutrition, through a review of more recent scientific evidence based on a systematic research on PubMed. Of 66 records initially identified, 26 studies were selected and included in the present work. Although there is not sufficient evidence for the efficacy of specific nutritional protocols, the examined papers indicate a potential role of selected nutrients, micronutrients and food components in managing FM symptoms. However, several concerns persist as nutritional status and/or nutritional integration can improve FM symptoms, without expecting to lead to a remission of the disease. The use of targeted nutritional supplements may be of some relevance for the management of FM, but the up to date evidence remains weak. It is advisable, thus, to perform further studies of higher quality.KEY TEACHING POINTSFibromyalgia (FM) is characterized by chronic and diffuse musculoskeletal pain, often associated with a large set of symptoms.The therapeutic approach of FM include pharmacological and non-pharmacological interventions. Among them, an important role is played by nutrition.Of 66 record screened, 12 studies were included in the present review and five of them were randomized controlled trials. Nevertheless, the overall quality of those trials was scarce.Literature concerning FM and nutritions is growing. However, little evidence suggests that nutrition and/or nutritional intervention play a significant role on FM severity.The results of this review underline the need to carry out clinical studies of higher quality and rigor, possibly RCTs, focused on the role of nutrition in the symptoms and/or severity of FM.

Low concordance between HbA1c and OGTT to diagnose prediabetes and diabetes in overweight or obesity.

BACKGROUND: Glycated haemoglobin (HbA1c) test, introduced for diagnosing prediabetes and diabetes by the American Diabetes Association for some years, is currently under extensive discussion for contradictory data on the concordance between this test and the oral glucose tolerance test (OGTT). HYPOTHESIS: To assess concordance between HbA1c and OGTT to diagnose prediabetes and diabetes in subjects with overweight or obesity, focusing on possible gender-related differences. METHODS: A total of 949 outpatients with overweight or obesity at risk for diabetes (mean age 50 ± 15 years; 660 F) were enrolled and underwent HbA1c test and OGTT. RESULTS: In both genders, HbA1c test identified more patients with prediabetes than OGTT (42% vs 22% in males, 40% vs 18% in females, respectively): a slight concordance between HbA1c and OGTT (60% of total tests in both genders). In subjects diagnosed by OGTT, post-OGTT insulin levels and HOMA INDEX were significantly higher than those found in HbA1c(+) cases. Instead, those diagnosed with HbA1c were significantly older and showed higher uric acid than those with both tests (-). CONCLUSIONS: HbA1c test and OGTT did not reach full concordance for the diagnosis of diabetes and prediabetes in both genders. The two tests likely reflect different physiopathological aspects of dysglycaemia, suggesting that the 'diagnostic thresholds' could be reconsidered in light of the discordance observed.

Oxidative status in treatment-naïve essential thrombocythemia: a pilot study in a single center.

Oxidative stress (OS), due to pro-oxidant species [reactive oxygen species (ROS)] excess not counterbalanced by endogenous antioxidant molecules [e.g., reduced glutathione (GSH)], is involved in the pathogenesis of human cancers, but few data are available on essential thrombocythemia (ET). This study aims to investigate OS in ET off-therapy patients. Thirty ET treatment-naïve patients were compared with 26 age-matched and gender-matched controls. Serum ROS, urinary 8-hydroxydeoxyguanosine, full blood GSH levels, and reduced/oxidized GSH ratio (GSH/GSSG) were measured. Data were adjusted for gender, age, JAK2 mutational status, smoking, dyslipidemia, or hypercholesterolemia requiring drug therapy, antiplatelet therapy, treatment with acetylsalicylic acid, high-sensitive C-reactive protein levels, and absolute monocyte count. ROS and GSH levels were increased in both patients and controls. Patients showed increased GSSG (p = 0.05), reduced GSH/GSSG ratio (p = 0.08), and similar 8-hydroxydeoxyguanosine levels when compared with controls. No differences in OS parameters were found between JAK2-positive and JAK2-negative patients. Confounding factors did not modify the results. Our study suggests an OS condition in a cohort of treatment-naïve ET patients, not associated with JAK2 mutational status or with chronic inflammation situation. GSH/GSSG ratio, altered in ET patients because of increased GSSG levels, showed the presence of higher GSH levels in ET than controls as a possible compensatory mechanism of an excess of pro-oxidant production. Copyright © 2015 John Wiley & Sons, Ltd.

Homocysteine metabolism in children and adolescents with epidermolysis bullosa.

BACKGROUND: Epidermolysis bullosa (EB) belongs to a family of rare heterogeneous, genetic disorders characterized by blistering of the skin and mucous membranes in response to minor mechanical trauma. The involvement of the oral mucosa and oesophagus stenosis is suggested to be responsible for severe nutritional deficiencies, but few studies have till now considered this aspect. This observational study aimed to evaluate homocysteine status in children and adolescents with EB by assessing total plasma homocysteine (tHcy) and metabolically related vitamins (B6, B12, folate) concentrations. METHODS: Twenty EB patients (12 M; age range 0.5-19 years) were evaluated for: plasma tHcy, serum B12 and holotranscobalamin (HoloTC, the active fraction of B12), serum and erythrocyte folate (s-F and Ery-F, respectively), plasma B6 and serum high sensitive C-reactive-protein (hsCRP) levels. Clinical severity was also evaluated through the Birmingham Epidermolysis Bullosa Severity (BEBS) score. A sex and age well-matched population was also enrolled. RESULTS: EB patients showed tHcy levels higher (p = 0.04) and B6 levels lower (p = 0.03) than controls. B12, HoloTC, s-F and ery-F concentrations did not differ between patients and controls. Multiple linear regression analysis showed that tHcy levels were independent of the metabolically related vitamins levels. In addition, serum hsCRP levels were higher in EB patients than in controls (p = 0.003) and correlated negatively with B6 concentrations (r = -0.6; p = 0.009). BEBS score correlated negatively with HoloTC (p = 0.022) and B6 (p = 0.005) levels and positively with age (p = 0.031) and hsCRP levels (p < 0.001). CONCLUSIONS: The assessment of tHcy and metabolically related vitamin levels describes an important aspect of EB patients' nutritional status which can result essential for their long term care. Monitoring B6 levels in EB patients could be particularly important in order to prevent several complications associated with B6 deficiency and to avoid a B6 excess which sustains an inflammatory condition.

An encapsulated juice powder concentrate improves markers of pulmonary function and cardiovascular risk factors in heavy smokers.

OBJECTIVE: Cigarette smoking is associated with reduced pulmonary function and increased risk factors for cardiovascular disease. This randomized placebo-controlled double-blind study evaluated the effects of two different combinations of mixed fruit and vegetable juice powder concentrate (Juice Plus+, NSA, Collierville, TN) on heavy smokers. METHODS: At baseline (T 0) and after 3 months' supplementation (T 1), pulmonary function parameters and cardiovascular risk factors-that is, plasma total homocysteine (tHcy) with related B vitamins and cysteine (tCys) concentrations-were assessed in 75 apparently healthy smokers (aged 49.2 ± 10.6 years, >20 cigarettes/d, duration ≥10 years) randomized into 3 groups: placebo (P), fruit/vegetable (FV) and fruit/vegetable/berry (FVB). RESULTS: T 0: most smokers showed abnormalities in tHcy and tCys concentrations. T 1: respiratory function was unchanged in P and slightly, but not significantly, improved in FV, whereas FVB showed a significant improvement in forced expiratory flow at 25% (FEF25; p < 0.0001 vs P and FV) and significant improvement in CO diffusion lung/alveolar volume (DLCO/VA). FV and FVB (50%) showed significant reduction in tHcy and tCys compared to T 0 ( p < 0.0001) and P ( p < 0.0001). CONCLUSIONS: At T 1, both supplemented groups, but to a greater extent the FVB group, showed improvements in some pulmonary parameters, cardiovascular risk factors, and folate status. The beneficial effects of Juice Plus+ supplementation could potentially help smokers, even if smoking cessation is advisable.

Unbalanced oxidative status in idiopathic sudden sensorineural hearing loss.

An impaired cochlear perfusion seems to be an important etiopathogenetic event in idiopathic sudden sensorineural hearing loss (ISSNHL). Recently, oxidative stress has been proposed as risk factors of microvascular damage. This observational study aimed to evaluate the possible role of oxidative stress in ISSNHL. In thirty-nine ISSNHL patients and seventy healthy subjects serum reactive oxygen species concentrations (ROS) and total antioxidant capacity (TAC) were measured by spectrophotometric methods on F.R.E.E. analyzer (Diacron International, Italy). Moreover, a global oxidative stress index (Oxidative-INDEX), reflecting both oxidative and antioxidant counterparts, was also calculated. 25/39 patients showed oxidative stress due to ROS levels significantly higher than controls (348.2 ± 84.8 vs. 306.75 ± 46.7 UCarr; p = 0.001). The Oxidative-INDEX was significantly higher in patients than in controls (0.75 ± 2.4 vs. -0.0007 ± 1.28 AU, p = 0.03). As oxidative stress is a key determinant in endothelial dysfunction, our findings could suggest vascular impairment involvement in ISSNHL etiopathogenesis.

Insulin resistance and cardiometabolic indexes: comparison of concordance in working-age subjects with overweight and obesity.

PURPOSE: The aim of the study was to evaluate indexes of insulin resistance and cardiometabolic risk in a large population of workers with overweight or obesity, in order to identify a possible efficient, cheap and simple strategy to apply in workers' health surveillance. METHODS: The evaluation of IR and cardiometabolic risk indexes (HOMA, QUICKI, Ty/HDLC, TyG, insuTAG, Castelli risk indexes 1 and 2, non-HDLC, TRL-C, AIP, and VAI) was performed in a population of 1195 working-age subjects with overweight or obesity (322 males, mean age 49 ± 11 years). RESULTS: The prevalence of IR and cardiometabolic risk was higher among males for all indexes. Aging, waist circumference, BMI, blood pressure, glucose, CRP, fibrinogen and uric acid were correlated more frequently with IR/cardiometabolic indexes in women, homocysteine in men. The percentage of the workers identified as insulin resistant (IR+) or at higher cardiometabolic risk greatly vary according to the different index used. CONCLUSION: With a small group of biomarkers and anthropometric measures (fasting glucose and insulin, lipid profile, BMI and waist circumference) is possible to calculate a number of IR/cardiometabolic indexes, which, likely reflecting different pathophysiological aspects also related to gender, might help in a personalized evaluation of IR and cardiometabolic risk. Graphical abstract.

Effects of encapsulated fruit and vegetable juice powder concentrates on oxidative status in heavy smokers.

OBJECTIVE: Long-term cigarette smoking has negative effects on oxidative status, promoting low-density lipoprotein (LDL) oxidation and formation of lipid peroxides. We evaluated the effects of 2 different encapsulated formulas, consisting primarily of mixed juice powder concentrate, on oxidative status compared with placebo. METHODS: This randomized, double-blind, placebo-controlled study was performed on 101 apparently healthy heavy smokers (>20 cigarettes/d, duration >10 years; median age 47 years, range 41-57 years; 54 M) before and after 3 months' supplementation. Subjects were randomized into 3 groups, well matched for sex and age: (1) placebo; (2) fruit/vegetable (FV); and (3) fruit/vegetable/berry (FVB). Analysis of oxidative status was performed on 75 (46 M) compliant subjects (>95% of assigned capsules). Changes in lipid panel parameters, oxidative-INDEX (Oxy-I, calculated on the basis of serum hydroperoxides and total antioxidant capacity measured by spectrophotometric methods), oxidized-LDL (ox-LDL; enzyme-linked immunosorbent assay [ELISA] method), and malondialdehyde (MDA; gas chromatography-mass spectrometry method) in free (fMDA), bound (bMDA), and total (tMDA = fMDA + bMDA) forms are reported. Statistical analysis was performed with R statistical software. RESULTS: After supplementation, compared with placebo, both FV and FVB groups showed a significant decrease in total cholesterol (p < 0.05), ox-LDL (p = 0.03), and fMDA levels (p = 0.004) accompanied by a slight increase in bMDA concentrations, possibly as the result of fMDA conjugation. Moreover, a significant decrease in Oxy-I was found in both active groups compared with placebo (p < 0.001). CONCLUSION: Intervention with both nutraceutical formulations resulted in improvement in some oxidative alterations attributed to long-term cigarette smoking.

Determinants of oxidative stress related to gender: relevance of age and smoking habit.

BACKGROUND: Magnitude and major causes of oxidative stress may be different between sexes, although limitedly addressed in clinical studies with controversial results. The present study aimed to determine whether any gender-related difference exists concerning oxidative stress in a population of 332 subjects of both sexes, in a wide age range, with and without cigarette smoking habit. METHODS: The Oxidative-INDEX was calculated after evaluation of serum hydroperoxides (ROMs) and total antioxidant capacity (OXY) by means of commercial kits (d-ROMs and Oxy-adsorbent Tests, Diacron, Italy) subtracting the OXY standardized variable from the ROMs standardized variable. RESULTS: The Oxidative-INDEX resulted higher in women with respect to men (p<0.001), in smokers (p<0.01) than in non-smokers, and correlated with cigarette number (p<0.01), age (p<0.001), and post-menopausal status (p<0.001). The multivariate analysis identified age, high blood pressure, and smoking habit as factors independently associated with the Oxidative-INDEX in men, whereas cigarette smoking and age represented the independent risk factors for an elevated oxidative stress status in women. CONCLUSIONS: Gender-based differences in oxidative stress levels may provide a biochemical basis for the epidemiologic differences in the disease susceptibility between sexes, and suggest different strategies for risk assessment, diagnosis, and treatment specifically targeted to men and women.

Metal chelation therapy in rheumathoid arthritis: a case report. Successful management of rheumathoid arthritis by metal chelation therapy.

Toxic metals are involved in the pathogenesis of some neurodegenerative and vascular diseases and are known to impair the immune system functions. We report here the case of a patient affected by heavy metal intoxication, who had developed an autoimmune disease. There was evidence of aluminium, cadmium and lead intoxication in a 63-year old Italian woman affected by rheumatoid arthritis (RA). We treated the patient with calcium disodium edetate (EDTA) once a week for a year in order to remove traces of heavy metal intoxication. Oxidative status profile was carried out at the beginning and after 6 months' EDTA chelation. At the end of the treatment, the patient did not show any signs of metal intoxication, RA symptoms and oxidative status improved.

Carotid plaques in patients with long-term lupus nephritis.

OBJECTIVES: To evaluate the prevalence of carotid plaques in patients with long-term lupus nephritis (LN). METHODS: Intima-media thickness (IMT) and carotid plaques were evaluated with ultrasound in 75 patients after a follow-up of LN of 158+/-106 months and in 75 sex -and age-matched controls. Traditional and non-traditional atherosclerotic risks factors were also tested. RESULTS: IMT was not different between LN patients and controls, but 18% of LN patients had carotid plaques in comparison to 2.6% of controls (p=0.004). The LN patients more frequently had hypertension (p=0.0001), hypercholesterolemia (p=0.0001), were overweight (p=0.009), in menopause (p=0.01) than controls. More frequently, LN patients with carotid plaques had renal insufficiency (p=0.03), longer duration of lupus (p=0.05), anti-phospholipid antibodies (p=0.018), high C-reactive protein (p=0.03), high reactive oxygen species (p=0.001) than those without plaques. Patients with plaques were older (p=0.000001), in menopause (p=0.000001) and more frequently had cardio-vascular accidents during observation (p=0.02). The time of exposure to pathological values of systolic and diastolic blood pressure was longer (p=0.000001) and the percentage of pathological values of these variables during the follow-up was higher (p=0.000001) in patients with carotid plaques. At multivariate analysis, older age (p=0.0025), longer time of exposure to pathological values of blood pressure (p=0.015) and of cholesterol (p=0.04) were independent predictors of carotid plaques. CONCLUSIONS: Carotid plaques were more frequently found in LN patients than in controls. Although inflammatory markers and lupus related factors may contribute to the development of atherosclerosis, only traditional risk factors such as age, hypertension and hypercholesterolemia were the independent predictors.

Determination of serum holotranscobalamin concentrations with the AxSYM active B(12) assay: cut-off point evaluation in the clinical laboratory.

BACKGROUND: A reliable early marker is required for diagnosis of cobalamin deficiency. We calculated an appropriate holotranscobalamin (HoloTC) cut-off point for identifying cobalamin deficiency using an immunoenzymatic assay. METHODS: Determination of the cut-off threshold and correlation between HoloTC and the other diagnostic parameters routinely used for vitamin B(12) deficiency [total vitamin B(12) (tB(12)), folate, homocysteine] were measured in 250 routine blood specimens from 107 men (mean age 59.0+/-18.8 years) and 143 women (mean age 54.2+/-23.1 years). The inclusion criterion was serum tB(12) concentration

Free and total plasma malondialdehyde in chronic renal insufficiency and in dialysis patients.

BACKGROUND: Available data about oxidative status in patients with end-stage renal disease (ESRD) or on dialysis are contradictory. The present cross-sectional study aimed to investigate the role of renal insufficiency and dialysis on lipid peroxidation. To separate the effects of uraemia from dialysis-induced stress, we enrolled 26 patients with renal insufficiency on conservative treatment (ESRD), 23 on peritoneal dialysis (PD), 30 on haemodialysis (HD) and 30 controls. METHODS: Plasma malondialdehyde (MDA) levels, both total (tMDA) and free (fMDA), were measured as indexes of oxidative stress by gas chromatography-mass spectrometry. Bound MDA (bMDA) levels were calculated as the difference between tMDA and fMDA. RESULTS: Total and bMDA concentrations were significantly higher in patients than in controls (ESRD > HD > PD). In PD and HD patients, fMDA levels were similar and significantly higher than in ESRD. Multivariate analysis, with tMDA, fMDA and bMDA as dependent variables, showed similar and significant tMDA and bMDA relations with residual renal function (t = -2.160, P = 0.035) and albumin (t = -2.049, P = 0.045). Erythropoietin dose affected only fMDA values (t = -2.178, P = 0.034). CONCLUSIONS: Free and bMDA concentrations identified different MDA patterns. Bound MDA, not excreted by kidneys, accounts alone for high tMDA concentrations in ESRD patients, while both fMDA and bMDA contribute to tMDA values in dialysis patients. These findings show that increased tMDA could be indicative not only of recent lipid peroxidation, and they also highlight the importance of evaluating free, bound and total MDA in patients with reduced renal function in order to assess their oxidative status.

Folate content in different strawberry genotypes and folate status in healthy subjects after strawberry consumption.

Folate is a micronutrient essential in a variety of biological processes, and an adequate dietary folate intake seems to play a crucial role in health promotion and disease prevention. The importance of strawberry as a natural food source of folate has been recognised only recently, and few pilot studies have investigated the impact of strawberry intake on human folate status. In this study, firstly, we evaluated the folate content of different commercial varieties (Alba, Irma, Patty, Adria, Sveva) and advanced selections (AN99.78.51; AN94.414.52; AN00.239.55) of strawberry. Significant differences were observed among genotypes, confirming the breeding approach as a reliable tool to increase folate content in strawberry. Secondly, the variety Sveva was selected for a medium-term strawberry consumption study, in order to check if a 2-weeks strawberry intake could have any effects on folate status and plasma homocysteine levels, in healthy subjects. An average 3.4% increase in serum folate was observed, however without any statistical significance, as shown by reference change value of each analyte in each subject. This study should be considered as a first pilot investigation, and further investigations are strongly hoped to evaluate the potential impact of strawberry consumption on human folate status, particularly in the case of a previously diagnosed deficiency.

HFE gene mutations and oxidative stress influence serum ferritin, associated with vascular damage, in hemodialysis patients.

BACKGROUND/AIMS: Hyperferritinemia has been associated with cardiovascular mortality in hemodialysis patients. The aim of this study was to evaluate whether serum ferritin was affected by iron and oxidative status and by genetic factors (HFE mutations and the Ala9Val MnSOD polymorphism), and to assess the association between ferritin and cardiovascular damage evaluated by ecocolor-Doppler. METHODS: 63 hemodialysis patients were tested for HFE and MnSOD genotype by restriction analysis and oxidative status; vascular damage was assessed by measuring intima-media thickness, and by detecting plaques at carotid and femoral arteries. RESULTS: Ferritin was correlated with transferrin saturation (p = 0.003), decreased iron-specific serum antioxidant activity (p = 0.01), age (p = 0.03), and C282Y and H63D HFE mutations (p = 0.05), but not with the MnSOD polymorphism. Ferritin was associated with advanced vascular damage, as evaluated by the presence of plaques, both at carotid (p = 0.03) and femoral arteries (p = 0.001), the other risk factors being age and low albumin. Low iron-specific antioxidant activity was associated with carotid plaques (p = 0.03). CONCLUSION: In hemodialysis patients, hyperferritinemia reflects a relative increase in iron availability and a decrease in iron-specific antioxidant activity, is favored by HFE mutations, and represents a risk factor for advanced cardiovascular damage.

Gender-related association between uric acid, homocysteine, γ-glutamyltransferase, inflammatory biomarkers and metabolic syndrome in subjects affected by obesity.

AIM: Evaluation of gender-related differences in uric acid (UA), homocysteine and inflammatory biomarkers as metabolic syndrome (MetS) determinants. PATIENTS & METHODS: Anthropometric and routine data were obtained from 825 obese subjects (591 F, mean age 54 ± 14 years). RESULTS: Hyperuricemia was 24% in both genders. Waist circumference, creatinine, triglycerides, C-reactive protein and γ-glutamyltransferase were identified as UA-independent determinants in females and creatinine and insulin in males. Hyperuricemia increased MetS risk in both genders (2.8-fold and 1.5-fold in males and females). CONCLUSION: UA and γ-glutamyltransferase positively relate to MetS in both genders, although inflammatory abnormalities are closer related to UA and MetS in females. These differences in gender physiology may account for epidemiologic gender disparities and help to develop gender-targeted clinical strategies.

Oxidative imbalance in patients with mild cognitive impairment and Alzheimer's disease.

Increasing evidence supports a role of oxidative imbalance, characterized by impaired antioxidant enzymatic activity and increased reactive oxygen species (ROS) production, in mild cognitive impairment (MCI) and Alzheimer's disease (AD) pathogenesis. Hyperhomocysteinemia, another risk factor for AD, also contributes to oxidative damage. Plasma total homocysteine (tHcy) and ROS levels, and total antioxidant capacity (TAC) were determined in 71 AD, 36 MCI and 28 vascular dementia (VaD) patients as well as in 44 age-matched controls. tHcy levels were significantly increased in patients with AD and VaD an a trend towards an increase in multiple domain MCI was observed. TAC was significantly decreased in AD as well as MCI, but not in VaD patients. In AD patients, a negative correlation was found between TAC and disease duration. ROS levels did not differ among groups, but were correlated with age. In conclusion, a pattern characterized by increased tHcy levels and decreased TAC is present in AD as well as MCI patients. While increased tHcy levels were also found in VaD, TAC modifications occur specifically in AD. ROS levels appear to be correlated with age rather than with a specific dementing disorder, thus leading to the hypothesis that oxidative imbalance observed in AD could be due to a decreased TAC.