Intake of dietary fat and fat subtypes and risk of premenstrual syndrome in the Nurses' Health Study II.

Approximately 8-20 % of reproductive-aged women experience premenstrual syndrome (PMS), substantially impacting quality of life. Women with PMS are encouraged to reduce fat intake to alleviate symptoms; however, its role in PMS development is unclear. We evaluated the association between dietary fat intake and PMS development among a subset of the prospective Nurses' Health Study II cohort. We compared 1257 women reporting clinician-diagnosed PMS, confirmed by premenstrual symptom questionnaire and 2463 matched controls with no or minimal premenstrual symptoms. Intakes of total fat, subtypes and fatty acids were assessed via FFQ. After adjustment for age, BMI, smoking, Ca and other factors, intakes of total fat, MUFA, PUFA and trans-fat measured 2-4 years before were not associated with PMS. High SFA intake was associated with lower PMS risk (relative risk (RR) quintile 5 (median=28·1 g/d) v. quintile 1 (median=15·1 g/d)=0·75; 95 % CI 0·58, 0·98; P trend=0·07). This association was largely attributable to stearic acid intake, with women in the highest quintile (median=7·4 g/d) having a RR of 0·75 v. those with the lowest intake (median=3·7 g/d) (95 % CI 0·57, 0·97; P trend=0·03). Individual PUFA and MUFA, including n-3 fatty acids, were not associated with risk. Overall, fat intake was not associated with higher PMS risk. High intake of stearic acid may be associated with a lower risk of developing PMS. Additional prospective research is needed to confirm this finding.

Good Fats versus Bad Fats: A Comparison of Fatty Acids in the Promotion of Insulin Resistance, Inflammation, and Obesity.

Recently, debate has erupted in both the scientific community and throughout the lay public around whether a low-fat or low-carbohydrate diet is better for weight loss. In other words, is it better to cut fat or cut carbohydrate for weight loss. However, going beyond this debate (fat versus carbohydrate), are questions around whether certain fatty acids are worse for promoting insulin resistance, inflammation, and obesity. The overall evidence in the literature suggests that medium-chain saturated fats (such as lauric acid, found in coconut oil) and monounsaturated fat (oleic acid, found in olive oil) are less likely to promote insulin resistance, inflammation, and fat storage compared to long-chain saturated fatty acids (such as stearic acid found in large quantities in butter, but particularly palmitic acid found in palm oil) especially when consumed on top of a diet moderate in refined carbohydrates. Compared to long-chain saturated fats, lauric acid and oleic acid have an increased fatty acid oxidation rate, are more likely to be burned for energy and less likely to be stored in adipose tissue, and thus promote increased energy expenditure. Omega-6 polyunsaturated fatty acids (PUFAs), such as linoleic acid, as found in vegetable oils may contribute to obesity, whereas omega-3 PUFA may be protective. Importantly, both olive oil as part of a Mediterranean diet, and omega-3 from fish and fish oil have been proven to reduce risk of cardiovascular (CV) events.

Potential cutaneous hypersensitivity reaction to an inactive ingredient of thyroid hormone supplements in a dog.

BACKGROUND: Although discussions about allergic reactions to thyroid supplements abound on professional forums, there is almost no information in the literature on these specific idiosyncratic drug reactions. ANIMAL: A dog with a history of hypothyroidism-associated weight gain and mild lethargy was prescribed levothyroxine tablets (0.018 mg/kg twice daily). After 19 days the dog developed a severe skin condition that was responsive to levothyroxine withdrawal, and antibiotic and glucocorticoid therapy. Three weeks later a different levothyroxine tablet was prescribed. Within 48 h the dog developed a more severe cutaneous reaction that resolved with drug discontinuation and appropriate topical care. OBJECTIVES: To confirm a possible hypersensitivity reaction and identify its chemical target. METHODS AND RESULTS: The two prescribed levothyroxine formulations shared two inactive ingredients: magnesium stearate and polyvinylpyrrolidone. Nine months after discontinuation of thyroid supplement, a formulation without either of these two compounds was used for a second re-challenge. There was no recurrence of the drug reaction and after 1.5 years of treatment the dog remains normal. CONCLUSIONS AND CLINICAL IMPORTANCE: These elements strongly suggest that this dog had an idiosyncratic reaction (likely immune-mediated) against one or both inactive ingredients in the first two formulations of levothyroxine. We are not aware of any previous confirmed delayed hypersensitivity to a thyroid supplement in a dog with the likely chemical trigger being an inactive ingredient rather than the therapeutic agent itself. We hope that this case will raise awareness about allergic reactions to thyroid supplements and allergic reactions to inactive formulation components.

Stearic acids at sn-1, 3 positions of TAG are more efficient at limiting fat deposition than palmitic and oleic acids in C57BL/6 mice.

In the present study, we investigated the effect of long-acyl chain SFA, namely palmitic acid (16:0) and stearic acid (18:0), at sn-1, 3 positions of TAG on obesity. Throughout the 15 weeks of the experimental period, C57BL/6 mice were fed diets fortified with cocoa butter, sal stearin (SAL), palm mid fraction (PMF) and high-oleic sunflower oil (HOS). The sn-1, 3 positions were varied by 16:0, 18:0 and 18:1, whilst the sn-2 position was preserved with 18:1. The HOS-enriched diet was found to lead to the highest fat deposition. This was in accordance with our previous postulation. Upon normalisation of total fat deposited with food intake to obtain the fat:feed ratio, interestingly, mice fed the SAL-enriched diet exhibited significantly lower visceral fat/feed and total fat/feed compared with those fed the PMF-enriched diet, despite their similarity in SFA-unsaturated fatty acid-SFA profile. That long-chain SFA at sn-1, 3 positions concomitantly with an unsaturated FA at the sn-2 position exert an obesity-reducing effect was further validated. The present study is the first of its kind to demonstrate that SFA of different chain lengths at sn-1, 3 positions exert profound effects on fat accretion.

Avaliação comparativa do efeito dos ácidos graxos oléico, palmítico e esteárico sobre biomarcadores do processo aterosclerótico / Comparative evaluation of fatty acids, oleic, palmitic and stearic, effects on atherosclerosis biomarkers

A aterosclerose é classificada como enfermidade crônica não transmissível e é considerada uma das principais causas de morte e morbidade em vários países, incluindo o Brasil. Entre as possíveis causas de sua gênese está o hábito alimentar, especificamente o consumo de ácidos graxos, principalmente saturados e trans. Ácidos graxos saturados possuem características biológicas e fisico-químicas diferentes dos insaturados. Os mais abundantes na dieta humana são o palmítico e esteárico. Sua associação com acometimentos cardiovasculares vem sendo cada vez mais investigada, principalmente os que possuem mais de dez carbonos em sua cadeia interferindo no metabolismo de lipoproteínas podendo desencadear todo o processo aterosclerótico. A indústria de alimentos vem desenvolvendo algumas tecnologias opcionais para reduzir ou eliminar ácidos graxos trans, em especial, o elaídico, dentre elas a modificação no processo de hidrogenação que aumenta a quantidade de ácidos graxos saturados. Alguns alimentos industrializados necessitam de uma grande quantidade de ácidos graxos saturados promovendo um aumento no teor de ácido palmítico e esteárico, sendo este último considerado um ácido graxo saturado neutro, mas dependendo da concentração utilizada, pode contribuir no decréscimo da HDL-c (High Density Lipoprotein), dentre outras alterações deletérias. Desta forma, investigar as alterações de determinados parâmetros biológicos diante da mudança da proporção de ácidos graxos saturados, respeitando o teor total de lipídios de uma dieta é a base deste estudo. Foram realizados ensaios em material biológico para a determinação dos seguintes parâmetros: 1) Atividade de enzimas antioxidantes; 2) Peroxidação lipídica em tecidos; 3) Lipidograma; 4) Determinação do perfil de ácidos graxos de tecidos e rações e 5) Expressão de genes relacionados com o processo aterosclerótico (ICAM-1, VCAM-1, CD36 e MCP-1). A determinação da atividade de enzimas antioxidantes foi realizada considerando somente as enzimas Catalase (CAT) e Superóxido Dismutase (SOD), por se tratarem de enzimas com alteração expressiva no processo aterogênico, na ocorrência de disfunção endotelial. Neste trabalho, foi analisada a atividade das referidas enzimas no tecido hepático e cardíaco, onde não foram constatadas alterações. O mesmo processo biológico que estimula a produção excessiva de espécies reativas pode levar ao aumento da peroxidação lipídica, principalmente de ácidos graxos polinsaturados das membranas celulares, em tecidos como fígado, cérebro e coração. A peroxidação lipídica apresentou diferenças significativas no tecido hepático. O grupo alimentado com ração enriquecida com tripalmitato apresentou peroxidação lipídica aumentada em relação ao grupo controle. Correlacionando com o perfil de ácidos graxos do tecido hepático, notamos que houve maior incorporação de ácido palmítico nesse tecido, que por apresentar configuração linear, quando incorporado à membrana celular, pode levar à disfunção e possível suscetibilidade a danos, como a peroxidação. No tecido cardíaco e no tecido cerebral não foram observadas alterações e diferenças entre os tratamentos. O lipidograma consiste na quantificação de lipoproteínas e frações lipídicas, compondo o perfil lipídico no plasma sanguíneo. Os resultados obtidos mostraram que o colesterol total foi significativamente menor no grupo controle, assim como triacilglicerol e LDL colesterol (LDL-c). Já HDL colesterol (HDL-c) está reduzida no grupo que recebeu ração suplementada com ácido palmítico, assim como este grupo apresentou parâmetros aumentados nas dosagens de triacilglicerol e colesterol total. Os grupos alimentados com ração suplementada com triestearato e trioleato apresentaram resultados intermediários para a dosagem de HDL-c, com valores tendendo ao grupo suplementado com tripalmitato. Em relação à dosagem de LDL-c, foi constatada diferença entre os grupos suplementados e o grupo controle. Destaca-se que não houve diferença entre a dosagem entre os grupos suplementados. Portanto, o grupo alimentado com dieta enriquecida com ácido oleico (monoinsaturado) equipara-se aos grupos alimentados com dietas enriquecidas com ácido esteárico e palmítico (saturados). O perfil de ácidos graxos do tecido hepático mostrou uma porcentagem elevada de ácido palmítico no grupo alimentado com ração enriquecida com o mesmo ácido graxo, com diferença estatística em relação aos demais grupos. Já em relação ao ácido esteárico, não houve diferenças significativas entre os grupos. Em compensação, o teor de ácido oleico no grupo suplementado com este mesmo ácido graxo e com ácido palmítico foi significativamente diferente em relação aos demais, com valores superiores. Este resultado demonstra que não houve dessaturação do ácido esteárico a oleico, ao menos neste modelo. No tecido cardíaco, foi observado o mesmo comportamento. No tecido cardíaco não houve diferença estatística significativa da concentração de ácidos graxos, indicando que não houve incorporação ou dessaturação. Ressalta-se que de acordo com determinação realizada utilizando a técnica de cromatografia gasosa, as rações apresentavam em sua composição o teor de lipídios adequado ao modelo animal e as proporções de ácidos graxos alteradas como proposto no objetivo deste trabalho. Em relação às moléculas de adesão e quimiocinas (VCAM-1, ICAM-1, CD-36 e MCP-1) relacionadas com o processo aterosclerótico, houve somente alteração na molécula CD-36 no grupo alimentado com ração enriquecida com trioleato, com redução em relação aos demais. Mas, as moléculas de adesão relacionadas com o processo inicial da aterogênese, a expressão gênica realizada através da técnica de q-RT-PCR não foi relevante, não apresentando diferença entre os tratamentos. Conclui-se, portanto, que os tratamentos aplicados ao modelo animal selecionado possui o potencial de alterar lipoproteínas plasmáticas, mas não de manter a continuidade e desencadear o processo inflamatório relacionado à aterogênese

Atherosclerosis is chronic a non-communicable disease considered one of a major cause of morbidity and mortality in several countries, including Brazil. Among all the possible causes of their genesis the dietary habit of high fatty acid intake, especially saturated and trans fatty acids is the most important. Saturated and unsaturated fatty acids possess different biological and physicochemical characteristics. The most abundant fatty acid in the human diet are palmitic and stearic and they association with cardiovascular events has been increasingly investigated, especially those one with more than ten carbons in its chain which interfers in the lipoproteins metabolism and can initiate the atherosclerotic process. The food industry has developed some optional technologies to reduce or eliminate the presence of trans fatty acids in foods, in particular elaidic, which after the hydrogenation process increases the saturated fatty acids content. Some industrialized foods requires a large amount of saturated fatty acids that promote an increase of palmitic and stearic content, the last fatty acid mentioned is considered a neutral saturated fatty acid that can contribute to the decrease in HDL-c (High Density lipoprotein), depending on the concentration used, among other deleterious changes. Thus, investigate changes of specifics biological parameters in response to consumption of different saturated fatty acids, respecting the total content of lipids in a normolipidic diet is the aim of this study. Assays were conducted to determine the following parameters in the tissues: 1) Activity of antioxidant enzymes, 2) Lipid peroxidation, 3) Lipidogram; 4) Fatty acid composition 5) Expression of genes related the atherosclerotic process (ICAM-1, VCAM-1, CD36 and MCP- 1). The determination of the activity of antioxidant enzymes was carried out considering only the enzymes Catalase (CAT) and Superoxide Dismutase (SOD), because they are enzymes more sensitive and readily available in changes resulted of an atherosclerotic process with endothelial dysfunction. In the study, no changes were observed in activity of these enzymes in the liver and heart. The same biological process that stimulates the overproduction of reactive species can lead to increased lipid peroxidation, especially of polyunsaturated fatty acids present in cell membranes of tissues such as liver, brain and heart. The group fed with diet enriched with tripalmitate showed increased lipid peroxidation compared to control group. Correlating this information with the fatty acid profile in liver tissue, we noted that there was a greater incorporation of palmitic acid, which exhibit linear configuration when incorporated into the cell membrane and can lead to dysfunction and higher susceptibility to damages such as oxidation. No differences were observed in the others tissues analyzed. The lipidogram is the quantification of lipoprotein and lipid fractions, composing the lipid profile in blood plasma. The results showed that total cholesterol was significantly lower in the control group, as well triglyceride and LDL cholesterol (LDL-c). HDL cholesterol (HDL-C) concentration is reduced and triacylglycerol and cholesterol increased n the group fed with diet supplemented with palmitic. The groups fed with diets supplemented with tristearate and trioleate presented intermediate results for the measurement of HDL-c, with values tending to the group supplemented with tripalmitate. Regarding LDL-c levels, significant differences were observed between the supplemented groups and the control group. Emphasis that there was no difference between the dosage between the supplemented groups. Therefore, the group fed with oleic acid (monounsaturated) supplemented diet equates to the groups fed with diets enriched with stearic and palmitic acid (saturated). The fatty acid profile of liver tissue showed a high percentage of palmitic acid in the group fed with diet enriched with the same fatty acid, with a statistical difference compared to the other groups. In relation to stearic acid, there were no significant differences between groups. As compensation, the oleic acid content in the group supplemented with the same fatty acid and palmitic acid was significantly higher when compared to the others. This result demonstrates that no desaturation of stearic acid to oleic happened in this experimental model. In cardiac tissue there was no statistically significant difference in the concentration of fatty acids, indicating no incorporation or desaturation. Regarding adhesion molecules and chemokines (VCAM-1, ICAM- 1, CD-36 and MCP-1) related to the atherosclerotic process, there was only change in the gene expression of CD-36 molecule in the group fed diet enriched with trioleate, with reduction in relation to others. No other alterations were observed. In conclusion, we verified that the consumption of the different fatty acids in this experimental model has potential to alter lipoproteins levels but not to iniciate or maintain the inflammatory process associated with atherogenesis

Inflammation of the hypothalamus leads to defective pancreatic islet function.

Type 2 diabetes mellitus results from the complex association of insulin resistance and pancreatic ß-cell failure. Obesity is the main risk factor for type 2 diabetes mellitus, and recent studies have shown that, in diet-induced obesity, the hypothalamus becomes inflamed and dysfunctional, resulting in the loss of the perfect coupling between caloric intake and energy expenditure. Because pancreatic ß-cell function is, in part, under the control of the autonomic nervous system, we evaluated the role of hypothalamic inflammation in pancreatic islet function. In diet-induced obesity, the earliest markers of hypothalamic inflammation are present at 8 weeks after the beginning of the high fat diet; similarly, the loss of the first phase of insulin secretion is detected at the same time point and is restored following sympathectomy. Intracerebroventricular injection of a low dose of tumor necrosis factor α leads to a dysfunctional increase in insulin secretion and activates the expression of a number of markers of apoptosis in pancreatic islets. In addition, the injection of stearic acid intracerebroventricularly, which leads to hypothalamic inflammation through the activation of tau-like receptor-4 and endoplasmic reticulum stress, produces an impairment of insulin secretion, accompanied by increased expression of markers of apoptosis. The defective insulin secretion, in this case, is partially dependent on sympathetic signal-induced peroxisome proliferator receptor-γ coactivator Δα and uncoupling protein-2 expression and is restored after sympathectomy or following PGC1α expression inhibition by an antisense oligonucleotide. Thus, the autonomic signals generated in concert with hypothalamic inflammation can impair pancreatic islet function, a phenomenon that may explain the early link between obesity and defective insulin secretion.

Allergic contact dermatitis from 12-hydroxystearic Acid and hydrogenated castor oil.

A 34-year-old male experienced severe allergic contact dermatitis from 12-hydroxystearic acid in a lip balm and from hydrogenated castor oil in an underarm deodorant. He also had a positive patch-test reaction to bis-diglyceryl polyacyladipate-2, which is present in the implicated lip balm and which itself contains 12-hydroxystearic acid. He was also incidentally found to have contact allergy to ricinoleic acid and castor oil. Ricinoleic acid is the principal fatty acid in castor oil, whereas 12-hydroxystearic acid is the principal fatty acid in hydrogenated castor oil. These two fatty acids are each 18-carbon 12-hydroxylated fatty acids, differing only in degree of saturation. The lack of patch-test reactivity to the analogous nonhydroxylated fatty acids, stearic acid (C18:0), and oleic acid (C18:1) indicates that 12-hydroxylation was required for allergenicity in this patient. In addition, serial dilution testing demonstrated that saturation of the hydroxylated C18 fatty acid enhanced its allergenicity.

Impact of portacaval anastomosis on plasma fatty acid profile in cirrhosis: a randomized 24-month follow-up study.

BACKGROUND: Portacaval anastomosis has an hypolipemic effect in familial hypercholesterolemia and in healthy animals. In cirrhosis, it raises serum cholesterol, but there is no information on its effect upon plasma fatty acids. However, indirect data suggest that portacaval shunting might contribute to the polyunsaturated fatty acid deficit of these patients. We assessed the effect of portacaval anastomosis on plasma fatty acid profile in cirrhosis. METHODS: Forty-four Child-Pugh class A/B bleeding cirrhotics were randomized to be treated with portacaval anastomosis (n = 20) or nonsurgical therapy (n = 24). Fatty acid profile in plasma total lipids, alcohol intake, anthropometry, Child-Pugh score, serum cholesterol, triglycerides, and antioxidant micronutrients were assessed before and 3, 6, 12, 18, and 24 months after surgery or the start of nonsurgical therapy. Time course of plasma fatty acids was assessed using unbalanced repeated measures models with the above mentioned variables acting as covariates. RESULTS: No changes in the time course of percent plasma saturated, monounsaturated, and essential fatty acids were found between groups. Percent long-chain omega-6 and omega-3 polyunsaturated fatty acids decreased during follow-up in shunted patients compared with controls (p = .007 and p < .0005). However, this was not due to a true decrease in polyunsaturated fatty acid levels but to greater increases in saturated and monounsaturated fatty acid concentrations in shunted patients compared with control patients (p = .047 and p = .006). CONCLUSIONS: Portacaval anastomosis does not worsen plasma polyunsaturated fatty acid deficiency in cirrhosis. However, by increasing saturated and monounsaturated fatty acids, it further decreases plasma lipid unsaturation.

Herman Award Lecture, 1992: lipid nutrition--a personal perspective.

In the 1950s excess dietary fat was thought to be a risk factor for development of atherosclerosis. Over the ensuing years we have examined and given advice concerning first, saturation and unsaturation, and later, specific fatty acids such as oleic and stearic acids. Current work is further refining the delineation of fatty acids that might be harmful. Eventually, we will probably again cite excess fat as the problem.