Influence of short-term selenium supplementation on the natural course of Hashimoto's thyroiditis: clinical results of a blinded placebo-controlled randomized prospective trial.

BACKGROUND: The real efficacy of selenium supplementation in Hashimoto's thyroiditis (HT) is still an unresolved issue. OBJECTIVES: We studied the short-term effect of L-selenomethionine on the thyroid function in euthyroid patients with HT. Our primary outcome measures were TSH, thyroid hormones, thyroid peroxidase antibody (TPOAb), thyroglobulin antibody (TGAb) levels and thyroid echogenicity after 6 months of L-selenomethionine treatment. The secondary outcome measure was serum CXCL10 levels. METHODS: In a placebo-controlled randomized prospective study, we have enrolled untreated euthyroid patients with HT. Seventy-six patients were randomly assigned to receive L-selenomethionine 166 µg/die (SE n = 38) or placebo (controls n = 38) for 6 months. TSH, free T4 (FT4), free T3 (FT3), TPOAb and CXCL10 serum levels were assayed at time 0, after 3 and 6 months. An ultrasound examination of the left and right thyroid lobe in transverse and longitudinal sections was performed. A rectangular region, the region of interest, was selected for analysis. RESULTS: TSH, FT4, FT3, TPOAb, thyroid echogenicity and CXCL10 were not statistically different between SE and control groups at time 0, after 3 and 6 months. In the SE group, FT4 levels were significantly decreased (P < 0.03) after 3 months, while FT3 increased (P < 0.04) after 3 and 6 months versus baseline values. In the control group, the FT3 decreased after 3 and 6 months (P < 0.02) compared to baseline. CONCLUSION: The short-term L-selenomethionine supplementation has a limited impact on the natural course in euthyroid HT. Our results tip the balance toward the ineffectiveness of short-term L-selenomethionine supplementation in HT.

Lifestyle and metabolic approaches to maximizing erectile and vascular health.

Oxidative stress and inflammation, which disrupt nitric oxide (NO) production directly or by causing resistance to insulin, are central determinants of vascular diseases including ED. Decreased vascular NO has been linked to abdominal obesity, smoking and high intakes of fat and sugar, which all cause oxidative stress. Men with ED have decreased vascular NO and circulating and cellular antioxidants. Oxidative stress and inflammatory markers are increased in men with ED, and all increase with age. Exercise increases vascular NO, and more frequent erections are correlated with decreased ED, both in part due to stimulation of endothelial NO production by shear stress. Exercise and weight loss increase insulin sensitivity and endothelial NO production. Potent antioxidants or high doses of weaker antioxidants increase vascular NO and improve vascular and erectile function. Antioxidants may be particularly important in men with ED who smoke, are obese or have diabetes. Omega-3 fatty acids reduce inflammatory markers, decrease cardiac death and increase endothelial NO production, and are therefore critical for men with ED who are under age 60 years, and/or have diabetes, hypertension or coronary artery disease, who are at increased risk of serious or even fatal cardiac events. Phosphodiesterase inhibitors have recently been shown to improve antioxidant status and NO production and allow more frequent and sustained penile exercise. Some angiotensin II receptor blockers decrease oxidative stress and improve vascular and erectile function and are therefore preferred choices for lowering blood pressure in men with ED. Lifestyle modifications, including physical and penile-specific exercise, weight loss, omega-3 and folic acid supplements, reduced intakes of fat and sugar, and improved antioxidant status through diet and/or supplements should be integrated into any comprehensive approach to maximizing erectile function, resulting in greater overall success and patient satisfaction, as well as improved vascular health and longevity.

Olive oil and health: summary of the II international conference on olive oil and health consensus report, Jaén and Córdoba (Spain) 2008.

Olive oil (OO) is the most representative food of the traditional Mediterranean Diet (MedDiet). Increasing evidence suggests that monounsaturated fatty acids (MUFA) as a nutrient, OO as a food, and the MedDiet as a food pattern are associated with a decreased risk of cardiovascular disease, obesity, metabolic syndrome, type 2 diabetes and hypertension. A MedDiet rich in OO and OO per se has been shown to improve cardiovascular risk factors, such as lipid profiles, blood pressure, postprandial hyperlipidemia, endothelial dysfunction, oxidative stress, and antithrombotic profiles. Some of these beneficial effects can be attributed to the OO minor components. Therefore, the definition of the MedDiet should include OO. Phenolic compounds in OO have shown antioxidant and anti-inflammatory properties, prevent lipoperoxidation, induce favorable changes of lipid profile, improve endothelial function, and disclose antithrombotic properties. Observational studies from Mediterranean cohorts have suggested that dietary MUFA may be protective against age-related cognitive decline and Alzheimer's disease. Recent studies consistently support the concept that the OO-rich MedDiet is compatible with healthier aging and increased longevity. In countries where the population adheres to the MedDiet, such as Spain, Greece and Italy, and OO is the principal source of fat, rates of cancer incidence are lower than in northern European countries. Experimental and human cellular studies have provided new evidence on the potential protective effect of OO on cancer. Furthermore, results of case-control and cohort studies suggest that MUFA intake including OO is associated with a reduction in cancer risk (mainly breast, colorectal and prostate cancers).

Circulating adhesion molecules in humans: role of hyperglycemia and hyperinsulinemia.

BACKGROUND: We assessed the role of glucose and insulin in the regulation of circulating levels of soluble intercellular adhesion molecule-1 (sICAM-1) and vascular adhesion molecule-1 (sVCAM-1) in normal subjects and in patients with type 2 diabetes. METHODS AND RESULTS: Plasma glucose concentrations were acutely raised in 10 normal subjects and 10 newly diagnosed, complication-free type 2 diabetic patients and maintained at 15 mmol/L for 2 hours. In normal subjects, plasma sICAM-1, but not sVCAM-1, levels rose significantly (P<0.01) at 1 hour and returned to basal values at 2 hours. In another study, octreotide was infused during the hyperglycemic clamp to block the release of endogenous insulin; this prevented the late fall of plasma sICAM-l levels observed in under control clamp conditions. The diabetic patients had plasma sICAM-1 levels significantly higher (P<0.01) than those of the control subjects; plasma sVCAM-1 levels were similar. Both sICAM-l and sVCAM-1 concentrations did not change significantly during the control hyperglycemic clamp; however, octreotide infusion increased plasma sICAM-1 levels, which remained significantly (P<0.05) above baseline during the whole clamp. In an additional 10 type 2 diabetic patients, overnight euglycemia (plasma glucose 5.5 mmol/L) obtained with the aid of an artificial pancreas or supplementation with l-arginine (10 g PO for 30 days), the natural precursor of NO, normalized the increased plasma sICAM-1 levels. CONCLUSIONS: Acute hyperglycemia increases circulating sICAM-1 levels in normal subjects, whereas the correction of hyperglycemia with insulin or l-arginine supplementation restored to normal levels the increased plasma sICAM-1 levels of type 2 diabetic patients.

Dietary antioxidants for cardiovascular prevention.

The generation of reactive oxygen species (ROS) is associated with life in aerobic conditions. ROS are thought to be implicated in the pathogenesis of various human diseases since they are capable of damaging biological macromolecules such as DNA, carbohydrates and proteins. The organism maintains defense against ROS, including enzymes and low molecular-weight antioxidants. An important source of antioxidants is diet which contains numerous compounds exhibiting antioxidant activity. A shortage of antioxidants in the diet might promote coronary heart disease through accumulation of oxidized LDL in macrophages. However, antioxidants may also influence endothelial functions, smooth muscle cell proliferation, thrombosis and plaque rupture. Consumption of fruits and vegetables, olive oil, red wine and tea is inversely correlated with heart disease rates. These foods are particularly rich in natural antioxidant nutrients, including ascorbate (vitamin C), the tocopherols (vitamin E) and carotenoids. More than 600 naturally occurring carotenoids have been identified. These compounds are plant pigments that provide the bright color of various fruits and vegetables; lycopene, which gives tomatoes their red color, is under active research. Flavonoids are > 4,000 naturally occurring substances which provide color, texture and taste for plant foods. As free radical scavengers, flavonoids inhibit lipid peroxidation, promote vascular relaxation and help prevent atherosclerosis. A sufficient supply with antioxidants from diet might help prevent or delay the occurrence of pathological changes associated with oxidative stress. When diet fails to meet the antioxidant requirement, dietary supplements might be indicated. The recently coined term nutriceuticals describes a variety of nonprescription products that are used to enhance health. The best known are vitamin E, vitamin C, carotenoids, coenzyme Q10, flavonoids and the amino acid L-arginine. Rigorous clinical trials, particularly among high-risk groups, are needed before they can be recommended routinely to patients.

Abnormal rheologic effects of glyceryl trinitrate in patients with non-insulin-dependent diabetes mellitus and reversal by antioxidants.

OBJECTIVE: To evaluate 1) the hemorrheologic and hemodynamic effects of glyceryl trinitrate in patients with non-insulin-dependent diabetes mellitus and 2) the influence of antioxidants on these effects. DESIGN: Case-control study. SETTING: University hospital clinic. PATIENTS: 40 patients with diabetes and no evidence of cardiovascular complications and 40 controls matched for demographic variables and body habitus. INTERVENTIONS: Sublingual glyceryl trinitrate (0.3 mg) and transdermal glyceryl trinitrate patches (10 mg/d). Vitamin E, 300 mg/d orally for 7 days, and glutathione, 600 mg intravenously or intramuscularly, were given to test the effects of antioxidant supplementation. MEASUREMENTS: Systolic, diastolic, and mean arterial pressure and heart rate; left ventricular ejection fraction; platelet aggregation, blood viscosity, and blood filterability in vitro and ex vivo. RESULTS: Compared with controls, patients with diabetes had increased platelet aggregation to adenosine diphosphate (P < 0.005), increased blood viscosity (P < 0.001), and decreased blood filterability (P = 0.041) at baseline; blood pressure, heart rate, and ejection fraction were similar in the two groups. In controls, both sublingual glyceryl trinitrate and transdermal glyceryl trinitrate patches significantly reduced platelet aggregation (-38%; 95% CI, -49% to -27%) and blood viscosity (-8%; CI, -11% to -5%) and increased blood filterability (10%; CI, 7.0% to 13.1%). Slight but significant decreases in blood pressure and ejection fraction and an increase in heart rate were also seen in controls after administration of glyceryl trinitrate (both preparations). In patients with diabetes, glyceryl trinitrate paradoxically increased platelet aggregation (24%; CI, 15% to 33%) and blood viscosity (6%; CI, 2.9% to 8.8%) and decreased blood filterability (-7%; CI, -9.5% to -4.4%); hemodynamic values did not change significantly. In both groups, rheologic responses to glyceryl trinitrate (end concentration, 100 and 200 ng/mL) in vitro were similar to those seen in ex vivo studies. Vitamin E and glutathione normalized rheologic responses to glyceryl trinitrate in patients with diabetes. CONCLUSIONS: Organic nitrates have beneficial effects on blood rheology in controls but not in patients with diabetes, in whom a paradoxical deterioration is seen. Antioxidant supplementation can normalize primary tolerance to the rheologic effects of nitrates in diabetes.

Chronic intake of pharmacological doses of vitamin E might be useful in the therapy of elderly patients with coronary heart disease.

Thirty elderly (mean +/- SEM: 73.8 +/- 2.1 y) nondiabetic, moderately obese (body mass index = 28.3 +/- 0.6 kg/m2) patients with stable effort angina underwent an oral-glucose-tolerance test and a euglycemic hyperinsulinemic glucose clamp before and after vitamin E supplementation (900 mg/d for 4 mo). The study was of a randomized, placebo-controlled, double-blind, and crossover design. Anthropometric indexes were stable throughout the study. Despite similar fasting and 2-h plasma glucose concentrations, vitamin E administration (compared with placebo) lowered fasting (88 +/- 14 and 68 +/- 9 pmol/L, P < 0.02) and 2-h (348 +/- 43 and 263 +/- 28 pmol/L, P < 0.05) plasma insulin concentrations, plasma triglyceride concentrations (1.34 +/- 0.06 and 1.07 +/- 0.03 mmol/L, P < 0.05), and the ratio of plasma LDL to HDL cholesterol (7.64 +/- 0.31 and 5.52 +/- 0.38, P < 0.02). Vitamin E administration was associated with higher nonoxidative glucose metabolism (18.1 +/- 0.5 and 10.6 +/- 0.7 mumol.kg lean body mass-1.min-1, P < 0.03) than was placebo administration during the euglycemic glucose clamp. We conclude that chronic intake of pharmacological doses of vitamin E might be useful in the therapy of elderly insulin-resistant patients with coronary heart disease.

Daily vitamin E supplements improve metabolic control but not insulin secretion in elderly type II diabetic patients.

OBJECTIVE: To investigate the potential metabolic benefits deriving from daily vitamin E administration in type II diabetic patients. RESEARCH DESIGN AND METHODS: Twenty-five type II diabetic patients were invited to randomly take placebo or vitamin E (d-alpha-tocopherol; 900 mg/day) along a similar 3-mo period in a double-blind, crossover procedure. A wash-out period of 30 days separated the two treatment periods. At the end of each treatment period blood samples were drawn for plasma metabolites determination, and an intravenous glucose tolerance test (25 g of glucose as bolus in 3 min) was performed. During this study oral hypoglycemic agents were not discontinued or changed in their dosage. RESULTS: Chronic vitamin E administration reduced plasma glucose (8.3 +/- 0.3 vs. 7.5 +/- 0.2 mM, P > 0.05), triglycerides (2.27 +/- 0.08 vs. 1.67 +/- 0.09 mM, P < 0.02), free fatty acids (786 +/- 116 vs. 483 +/- 64 mM), total cholesterol (6.74 +/- 0.09 vs. 5.50 +/- 0.10 mM, P < 0.05), low-density lipoprotein cholesterol (4.73 +/- 0.11 vs. 3.67 +/- 0.07 mM, P < 0.04), and apoprotein B (1.7 +/- 0.3 vs. 1.0 +/- 0.1 g/L) levels but did not affect beta-cell response to glucose. HbA1 levels (7.8 +/- 0.3 vs. 7.1 +/- 0.5%, P < 0.05) were also significantly lowered after chronic vitamin E administration. CONCLUSIONS: Daily vitamin E supplements seem to produce a minimal but significant improvement in the metabolic control in type II diabetic patients. More studies are necessary before conclusions can be drawn about the safety of vitamin E during long-term administration.

Comparison of nitrendipine and cilazapril in patients with hypertension and non-insulin-dependent diabetes mellitus.

The metabolic and cardiovascular effects of nitrendipine and cilazapril in patients who have elevated blood pressure and non-insulin-dependent diabetes mellitus (NIDDM) were compared. After at least 6 weeks of a washout period, 20 NIDDM patients who had diastolic blood pressure in the range of 90-105 mm Hg received a single-blind placebo for 4 weeks and then were randomized to receive 20 mg nitrendipine once daily and 5 mg cilazapril once daily each for 12 weeks according to a crossover, double-blind procedure. Nitrendipine and cilazapril reduced diastolic blood pressure levels 12% and 13%, left ventricular mass index (LVMI) levels 13% and 12%, and raised whole glucose disposal levels 18% and 19.5%, respectively. Only nitrendipine reduced glucose-stimulated insulin levels. Nitrendipine is as effective as cilazapril in lowering diastolic blood pressure and LVMI levels and in increasing glucose disposal levels in these patients.

Pharmacologic doses of vitamin E improve insulin action in healthy subjects and non-insulin-dependent diabetic patients.

Ten control (healthy) subjects and 15 non-insulin-dependent diabetics underwent an oral glucose-tolerance test and a euglycemic hyperinsulinemic glucose clamp before and after vitamin E supplementation (900 mg/d for 4 mo). In control subjects (placebo-treated vs vitamin E-supplemented subjects, respectively) vitamin E reduced the area under the curve for glucose (344 +/- 21 vs 287 +/- 13 mmol.L-1 x min-1; P < 0.05) and increased total body glucose disposal (39.0 +/- 0.3 vs 47.6 +/- 0.4 mumol.kg lean body mass-1 x min-1; P < 0.05) and non-oxidative glucose metabolism (23.4 +/- 0.2 vs 30.8 +/- 0.3 mumol.kg lean body mass-1 x min-1; P < 0.05). In diabetics (placebo-treated vs vitamin E-supplemented subjects, respectively) vitamin E supplementation reduced glucose area under the curve (614 +/- 129 vs 544 +/- 98 mmol.L-1 x min-1; P < 0.03) and increased glucose disappearance (19.4 +/- 0.4 vs 26.4 +/- 0.7 mumol.kg lean body mass-1.min-1; P < 0.03), total glucose disposal (19.0 +/- 0.7 vs 28.1 +/- 0.4 mumol.kg lean body mass-1 x min-1; P < 0.02), and nonoxidative glucose metabolism (8.5 +/- 0.3 vs 13.9 +/- 0.3 mumol.kg lean body mass-1 x min-1; P < 0.02). Therefore we conclude that administration of pharmacologic doses of vitamin E is a useful tool to reduce oxidative stress and improve insulin action.

Vitamin E reduction of protein glycosylation in diabetes. New prospect for prevention of diabetic complications?

OBJECTIVE: This study evaluated the possibility of inhibiting protein glycosylation in vivo with vitamin E. RESEARCH DESIGN AND METHODS: Two groups of 10 insulin-requiring diabetic patients, matched for duration of disease and metabolic control, received daily vitamin E supplementation of 1200 and 600 mg, respectively, for 2 mo. A third group of 10 diabetic patients, matched for duration of disease and metabolic control, served as the control group and received placebo. Fasting plasma glucose, mean daily plasma glucose, fasting labile HbA1, and glycosylated proteins were measured in the basal state and after 1 and 2 mo of treatment. In addition, hyperglycemic clamp studies were performed in basal state and after 1 mo of vitamin E administration in all patients. RESULTS: Glycemic indices did not show any significant changes during the study, whereas fasting labile HbA, and glycosylated proteins decreased significantly after 1 and 2 mo in patients on vitamin E administration. Stable HbA1 decreased after 2 mo. Mean glycemic incremental area in the hyperglycemic clamp procedure was similar before and after treatment, whereas a significant reduction in mean labile HbA1 incremental area was found after vitamin E supplementation. A significant difference was also found in both fasting and incremental labile HbA1 levels, stable HbA1, and glycosylated proteins between the two groups of diabetic patients on the two doses of vitamin E; the diabetic patients who received the higher dose of vitamin E showed the greater reduction. No significant changes in these parameters were observed in diabetic patients on placebo administration. CONCLUSIONS: These results demonstrate that vitamin E administration may reduce protein glycosylation in diabetic subjects independently of changes in plasma glucose, an effect that may be due to the inhibition of labile glycosylation, the first step of the Maillard reaction. Long-term studies will help establish the usefulness of vitamin E administration for the prevention of diabetic complications.

Calcitonin and the human endocrine pancreas.

The influence of synthetic salmon calcitonin (CT) on paraphysiological endocrine pancreas was investigated in Man. Large dose (100 U) as well as low dose (1 U) of CT inhibits glucose-induced insulin responses, reduces the suppressive effect of glucose on glucagon secretion and impairs glucose tolerance. These effects are not mediated by hypocalcemia. Studies in which theophylline or calcium were infused in addition to CT suggest that the mode of action of CT is mediated via a change in calcium redistribution in the islet cells. The diabetogenic action of CT is not observed in Paget and osteoporotic patients, after prolonged administration of the hormone.