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Identification of hazelnut major allergens in sensitive patients with positive double-blind, placebo-controlled food challenge results.

Pastorello, E.A., S. Vieths, V. Pravettoni, L. Farioli, C. Trambaioli, D. Fortunato, D. Lüttkopf, M. Calamari, R. Ansaloni, J. Scibilia, B.K. Ballmer-Weber, L.K. Poulsen, B. Wütrich, K.S. Hansen, A.M. Robino, C. Ortolani, A. Conti, 2002. Identification of hazelnut major allergens in sensitive patients with positive double-blind, placebo-controlled food challenge results. J Allergy Clin Immunol. 109:563-570.

Background: The hazelnut major allergens identified to date are an 18-kd protein homologous to Bet v 1 and a 14-kd allergen homologous to Bet v 2. No studies have reported hazelnut allergens recognized in patients with positive double-blind, placebo-controlled food challenge (DBPCFC) results or in patients allergic to hazelnut but not to birch. Objective: We characterized the hazelnut allergens by studying the IgE reactivity of 65 patients with positive DBPCFC results and 7 patients with severe anaphylaxis to hazelnut. Methods: Hazelnut allergens were identified by means of SDSPAGE and IgE immunoblotting. Further characterization was done with amino acid sequencing, evaluation of the IgE-binding properties of raw and roasted hazelnut with enzyme allergosorbent test inhibition, assessment of cross-reactivity with different allergens by means of immunoblotting inhibition, and purification by means of HPLC. Results: All the sera from the patients with positive DBPCFC results recognized an 18- and a 47-kd allergen; other major allergens were at molecular weights of 32 and 35 kd. Binding to the 18-kd band was inhibited by birch extract, indicating its homology with the birch major allergen, and abolished in roasted hazelnut. The 47-kd allergen is a sucrose-binding protein, the 35-kd allergen is a legumin, and the 32-kd allergen is a 2S albumin. Patients with severe anaphylactic reactions to hazelnut showed specific IgE reactivity to a 9-kd allergen, totally inhibited by purified peach lipid-transfer protein (LTP), which was heat stable and, when purified, corresponded to an LTP. Conclusions: The major allergen of hazelnut is an 18-kd protein homologous to Bet v 1, and the 9-kd allergen is presumably an LTP. Other major allergens have molecular weights of 47, 32, and 35 kd.

Determination of the allergenicity of various hazelnut products by immunoblotting and enzyme allergosorbent test inhibition.

Wigotzki, M., H. Steinhart, A. Paschke, 2001. Determination of the allergenicity of various hazelnut products by immunoblotting and enzyme allergosorbent test inhibition. Journal of Chromatography B.  756:239–248.

Although allergic reactions to hazelnuts are common especially in Europe, there are only a few investigations with regard to the influence of processing on the IgE-binding potency of hazelnut proteins. In this study the allergenicity of different hazelnut products, such as chocolate, nougat products, croquant or cookies, was examined by sodium dodecyl sulfate– polyacrylamide gel electrophoresis (SDS–PAGE), immunoblotting and enzyme allergosorbent test (EAST) inhibition experiments using sera of 17 hazelnut-allergic individuals. In only a few cases did the immunoblotting experiments yield positive results as regards the allergenicity of the investigated products. By means of EAST inhibition a residual IgE-binding potency could be detected in almost all of the product extracts. Therefore hazelnuts are a potential hazard to allergic people even as an ingredient of processed foods.   

A voluntary registry for peanut and tree nut allergy: Characteristics of the first 5149 registrants.

Background: A voluntary registry of individuals with peanut and/or tree nut allergy was established in 1997 to learn more about these food allergies. Objective: The purpose of this study was to elucidate a variety of features of peanut and tree nut allergy among the first 5149 registry participants. Methods: The registry was established through use of a structured questionnaire distributed to all members of the Food Allergy and Anaphylaxis Network and to patients by allergists. Parental surrogates completed the forms for children under the age of 18 years. Results: Registrants were primarily children (89% of registrants were younger than 18 years of age; the median age was 5 years), reflecting the membership of the Network. Isolated peanut allergy was reported by 3482 registrants (68%), isolated tree nut allergy by 464 (9%), and allergy to both foods by 1203 (23%). Registrants were more likely to have been born in October, November, or December (odds ratio, 1.2; 95% CI, 1.18-1.23; P < .0001). The median age of reaction to peanut was 14 months, and the median age of reaction to tree nuts was 36 months; these represented the first known exposure for 74% and 68% of registrants, respectively. One half of the reactions involved more than 1 organ system, and more than 75% required treatment, frequently from medical personnel. Registrants with asthma were more likely than those without asthma to have severe reactions (33% vs 21%; P < .0001). In comparison with initial reactions, subsequent reactions due to accidental ingestion were more severe, more common outside the home, and more likely to be treated with epinephrine. Conclusions: Allergic reactions to peanut and tree nut are frequently severe, often occur on the first known exposure, and can become more severe over time.

Detection of trace amounts of hidden allergens: hazelnut and almond proteins in chocolate.

Scheibe, B., W. Weissa, F. Ruëff, B. Przybilla, A. Gőrg, 2001. Detection of trace amounts of hidden allergens: hazelnut and almond proteins in chocolate. J Chromatogr B, 756:229–237.

Many patients with immediate type allergy to tree pollen also suffer from intolerance to hazelnuts and almonds. Since rather low levels of hazelnut and almond proteins can provoke an allergic reaction in sensitized individuals, an immunoblot technique has been developed for the detection of potentially allergenic hazelnut and almond proteins in chocolate. Initially, IgE binding hazelnut and almond proteins were detected by immunoprobing with allergic patients’ sera. For routine analysis, patients’ sera were substituted with polyclonal rabbit antisera, and sensitivity was enhanced by the use of a chemiluminescent detection method. This technique allowed the detection of less than 0.5 mg of hazelnut or almond proteins per 100 g of chocolate (=5 ppm). It was applied for routine screening purposes in product quality control as well as for optimization of cleaning steps of filling facilities to minimize cross contamination during production.

A randomized controlled trial of a moderate fat, low energy diet compared with a low fat, low energy diet for weight loss in overweight adults.

McManus, K., L. Antinoro, F. Sacks, 2001.  A randomized controlled trial of a moderate fat, low energy diet compared with a low fat, low energy diet for weight loss in overweight adults. Int J Obesity.25:1503-11.

CONTEXT: Long-term success in weight loss with dietary treatment has been elusive. OBJECTIVE: To evaluate a diet moderate in fat based on the Mediterranean diet compared to a standard low-fat diet for weight loss when both were controlled for energy. DESIGN: A randomized, prospective 18 month trial in a free-living population. PATIENTS: A total of 101 overweight men and women (26.5 – 46 kg/m2). INTERVENTION: (1) Moderate-fat diet (35% of energy); (2) low-fat diet (20% of energy). MAIN OUTCOME MEASUREMENTS: Change in body weight. RESULTS: After 18 months, 31/50 subjects in the moderate-fat group, and 30/51 in the low fat group were available for measurements. In the moderate-fat group, there were mean decreases in body weight of 4.1 kg, body mass index of 1.6 kg/m2, and waist circumference of 6.9 cm, compared to increases in the low-fat group of 2.9 kg, 1.4 kg/m2 and 2.6 cm, respectively; P ≤ 0.001 between the groups. The difference in weight change between the groups was 7.0 kg. (95% CI 5.3, 8.7). Only 20% (10/51) of those in the low-fat group were actively participating in the weight loss program after 18 months compared to 54% (27/50) in the moderate-fat group, (P <0.002). The moderate-fat diet group was continued for an additional year. The mean weight loss after 30 months compared to baseline was 3.5 kg (n=19, P=0.03). CONCLUSIONS: A moderate-fat, Mediterranean-style diet, controlled in energy, offers an alternative to a low-fat diet with superior long-term participation and adherence, with consequent improvements in weight loss.

Hazelnut allergy: A double-blind, placebo-controlled food challenge multicenter study.

Ortolani, C., B.K. Ballmer-Weber, K.S. Hansen, M. Ispano, B. Wüthrich, C. Bindslev-Jensen, R. Ansaloni, L. Vannucci, V. Pravettoni, J. Scibilia, L.K. Poulsen, E.A. Pastorello, 2000. Hazelnut allergy: A double-blind, placebo-controlled food challenge multicenter study. J Allergy Clin Immunol. 105:577-581.

Background: Tree nuts are a common cause of food allergy in Europe. However, few studies deal with real food allergy to hazelnuts in subjects believed to be allergic to this food. Objective: We sought to select subjects with a history of allergic reactions on ingestion of hazelnut and determine how many of these have true allergy by means of the double-blind, placebo-controlled food challenge (DBPCFC). Methods: Eighty-six subjects with a history of symptoms after hazelnut ingestion were recruited from 3 allergy centers (Milan, Zurich, and Copenhagen). All subjects underwent skin prick tests (SPTs) with aeroallergens and hazelnut, as well as having their specific hazelnut IgE levels determined. Diagnosis of clinical relevant food allergy was made on the basis of the DBPCFC. Results: Sixty-seven (77.9%) of 86 subjects had a positive DBPCFC result; 8 were placebo responders, and 11 were nonresponders. Of the 11 nonresponders, 4 had positive open-challenge test results. Of the DBPCFC-positive subjects, 87% also had positive skin test responses to birch pollen extract. Specific IgE determination for hazelnut (positive CAP response ≥0.7 kU/L [ie, class 2]) showed a sensitivity of 0.75, a positive predictive value (PPV) of 0.92, a specificity of 0.16, and a negative predictive value (NPV) of 0.05. Skin tests with commercial hazelnut extract produced a sensitivity of 0.89, a PPV of 0.92, a specificity of 0.05, and an NPV of 0.05. Skin tests with natural food produced a sensitivity of 0.88, a PPV of 0.94, a specificity of 0.27, and an NPV of 0.15. Conclusion: This study shows that hazelnut is an allergenic source that can cause real food allergy, as confirmed by DBPCFC. Skin and IgE tests demonstrated reasonable sensitivity and PPV but a very low specificity and NPV, thus implying that these should not be used to validate the diagnosis of food allergy to hazelnut.

Specific immunoglobulin E to peanut, hazelnut and brazil nut in 731 patients: similar patterns found at all ages.

Pumphrey, R.S.H., P.B. Wilson, E.B. Faragher, S.R. Edwards, 1999. Specific immunoglobulin E to peanut, hazelnut and brazil nut in 731 patients: similar patterns found at all ages. Clin Exp Allergy. 29:1256-1259.

Background: Previous studies have reported reactions to an increasing range of nuts as patients with nut allergy grow older. Most patients with symptoms suggesting nut allergy have specific IgE to more than one nut. Furthermore, fatal reactions have followed eating nuts different from any causing the deceased’s previous reactions. Objective: To explore the pattern of specific IgE to three distantly related nuts in patients of all ages with nut allergy. Methods: This study includes all patients referred to our laboratory for nut allergy testing from January 1994 to August 1998 who were tested for peanut, hazelnut and brazil nut, and had specific IgE to at least one of these nuts. All tests were performed using the Pharmacia Unicap system. Results: Seven hundred and thirty-one patients (age 7 months to 65 years, median 6.6 years) had specific IgE > 0.35 kUA/L to at least one of these three nuts: 282 had IgE to one nut, 130 to two nuts, and 319 to all three nuts. When analysed by gender and age quartile, very similar patterns were found in all subgroups though significant age trends and age interactions were found for IgE to individual nuts and combinations of nuts. Conclusions: The probability of a patient with nut allergy having specific IgE to a particular combination of peanut, hazelnut and brazil nut is similar, whatever their age or sex. The apparent increase in multiple nut reactivity with increasing age may therefore be due to exposure of previously unchallenged sensitivity. The frequency of multiple-nut specificity is sufficiently high that patients should always be tested for allergy to a range on nuts if they have a history of reacting to any nut.

Hazelnut supplementation enhances plasma antioxidant potential and lowers plasma cholesterol levels.

Durak, I., I. Koksal, M. Kacmaz, S. Buyukkocak, B.M. Cimen, H.S. Ozturk, 1999.  Hazelnut supplementation enhances plasma antioxidant potential and lowers plasma cholesterol levels. [Letter to the Editor].  Clin Chim Acta. 284(1):113-5.

In this study, 30 healthy medical students added 1 gram of hazelnuts per kilogram of body weight per day to their normal daily diet for 30 days.  Total cholesterol was lowered by 6%, LDL by 19%, while HDL increased 7% and triglycerides 25% compared to baseline values.  Plasma antioxidant potential (AOP) also increased by 20

Nuts and their bioactive constituents: effects on serum lipids and other factors that affect disease risk.

Kris-Etherton, P.M., S. Yu-Poth, J. Sabaté, H.E. Ratcliffe, G. Zhao, T.D. Etherton, 1999.  Nuts and their bioactive constituents: effects on serum lipids and other factors that affect disease risk. Am J Clin Nutr.70 (suppl.):504S-11S.

Because nuts have favorable fatty acid and nutrient profiles, there is growing interest in evaluating their role in a heart-healthy diet. Nuts are low in saturated fatty acids and high in monounsaturated and polyunsaturated fatty acids. In addition, emerging evidence indicates that there are other bioactive molecules in nuts that elicit cardioprotective effects. These include plant protein, dietary fiber, micronutrients such as copper and magnesium, plant sterols, and phytochemicals. Few feeding studies have been conducted that have incorporated different nuts into the test diets to determine the effects on plasma lipids and lipoproteins. The total- and lipoprotein-cholesterol responses to these diets are summarized in this article. In addition, the actual cholesterol response was compared with the predicted response derived from the most current predictive equations for blood cholesterol. Results from this comparison showed that when subjects consumed test diets including nuts, there was a ~25% greater cholesterol-lowering response than that predicted by the equations. These results suggest that there are non-fatty acid constituents in nuts that have additional cholesterol-lowering effects. Further studies are needed to identify these constituents and establish their relative cholesterol lowering potency.

Nutritional composition of hazelnuts and its effects on glucose and lipid metabolism.

Alphan, E., M. Pala, F. Ackurt, T. Yilmaz, 1997.  Nutritional composition of hazelnuts and its effects on glucose and lipid metabolism. In: Kosal AI, Oky Y, Gunes NT, eds. Proceedings of the Fourth International Symposium on Hazelnut. Acta Hort. 445:305-10.

Turkey holds the first place is the world with respect to hazelnut production and export. Besides its economic importance, the high nutritional value of hazelnut makes it a special food. Hazelnuts are rich in protein, complex carbohydrates, dietary fiber, iron, calcium, potassium and vitamin E. Nutritional analyses conducted in our laboratories have revealed a high protein content (16.9%). Its protein quality (66.6%) is also high in comparison to many proteins of plant origin. It appeared to be one of the best sources of plant origin for iron (5.8 mg/100g), calcium (160.0 mg/100 g), and zinc (2.2 mg/100g), which are the most important minerals for growth and development. Hazelnuts were also found to be rich in potassium(655 mg/100g), which is necessary for nerve stimulation and functioning of muscle tissue. Hazelnuts were found to be good sources for vitamins B1 (0.33 mg/100g), and B2 (0.12 mg/100g), and very good sources for vitamin B6 (0.24 mg/100g) and Vitamin E (31.4 mg/100g). VitaminsB2 and B6 are especially important nutrients for the school-age children. The hazelnut is also the second best source of vitamin E after plant oils. This vitamin is essential for the normal functioning of muscle tissue and the reproduction system. It protects the organism against cancer. Vitamin E also prevents the hemolysis of erythrocytes, and thus protects the body against anemia. Chemical and nutritional compositions of hazelnut are shown in table. 1 (Pala et al., 1995).  The average fat content of hazelnuts analyzed in our laboratories was found to be 62.7% and 82% of this high yield was assessed to be oleic acid. This monounsaturated fatty acid was shown by many workers to increase the level of high density lipoprotein (HDL), in blood. HDL, in turns, lowers blood cholesterol and thus protects against atherosclerosis. According to a long term survey conducted in the United States over 20,000 subjects (Loma Linda University, 1990), the risk of death from coronary heart disease is lowered by half in people consuming nuts at least once a day as compared with those who don’t. Because of their chemical and nutritional compositions, hazelnuts have potential beneficial health effects. Diet is a cornerstone of therapy for patients with non-insulin-dependent diabetes mellitus (NIDDM). The goal of diet therapy in patients with diabetes is not only to improve control of hyperglycemia but also to reduce the risk of coronary heart disease by optimizing plasma lipid levels. Currently recommended high carbohydrate, low fat diets increase triglyceride and lower high density lipoprotein (HDL) cholesterol concentrations (Garg et al., 1988; Koskinen et al., 1992