Efficacy and tolerability of a lotion containing triethyl citrate, ethyl linoleate, and GT peptide-10 in the adjuvant treatment of hidradenitis suppurativa: Real-life data.

Hidradenitis suppurativa (HS) is a chronic disorder of terminal follicular epithelium in the apocrine gland-bearing areas. The long term therapy is based mainly on topical and/or systemic antibiotic use that could result in antibiotic resistance. The aim of our study was to present the real-life experience based on the efficacy and tolerability of a novel lotion containing triethyl-citrate, ethyl-linoleate, and g-peptide-10 in the treatment of mild to moderate HS that has already shown effectiveness in acne treatment. This was an open-label study on 30 patients of both sexes affected by HS. Patients were divided into two groups: 15 with Hurley I and 15 with Hurley II-III. The subjects were treated with the topical lotion, three-times-daily for eight weeks, with control at 4 (T1 ) and eight weeks (T2 ). Any other concomitant treatment (both topical and/or systemic) was avoided during study period. Improvement was observed in both Sartorius score grading system and inflammatory and noninflammatory lesion counts. The novel lotion has proved to be effective and well-tolerated topical agent alone or in association with other topical and/or systemic tratments in HS, without side effects.

Lizhong Decoction Ameliorates Ulcerative Colitis in Mice via Regulation of Plasma and Urine Metabolic Profiling.

OBJECTIVE: To elucidate the mechanism of Lizhong Decoction (LZD) in treating dextran sodium sulfate (DSS)-induced colitis in mice based on metabonomics. METHODS: Thirty-six mice were randomly divided into 6 groups, including normal, model, low- (1.365 g/kg), medium- (4.095 g/kg) and high dose (12.285 g/kg) LZD and salazosulfadimidine (SASP) groups, 6 mice in each group. Colitis model mice were induced by DSS admistration for 7 days, and treated with low, medium and high dose LZD extract and positive drug SASP. Metabolic comparison of DSS-induced colitis and normal mice was investigated by using ultra-performance liquid chromatography coupled to quadrupole time-of-flight mass (UPLC-Q-TOF/MS) combined with Metabolynx™ software. RESULTS: The metabolic profiles of plasma and urine in colitis mice were distinctly ameliorated after LZD treatment (P<0.05). Potential biomarkers (9 in serum and 4 in urine) were screened and tentatively identified. The endogenous metabolites were mainly involved in primary bile acid, sphingolipid, linoleic acid, arachidonic acid, amino acids (alanine, aspartate, and glutamate), butanoate and glycerophospholipid metabolism in plasma, and terpenoid backbone biosynthesis, glycerophospholipid and tryptophan metabolism in urine. After LZD treatment, these markers notably restored to normal levels. CONCLUSIONS: The study revealed the underlying mechanism of LZD on amelioration of ulcerative colitis based on metabonomics, which laid a foundation for further exploring the pathological and physiological mechanism, early diagnosis, and corresponding drug development of colitis.

Associations Between Linoleic Acid Intake and Incident Type 2 Diabetes Among U.S. Men and Women.

OBJECTIVE: To investigate the association between intakes of n-6 polyunsaturated fatty acids (PUFAs) and type 2 diabetes risk in three prospective cohort studies of U.S. men and women. RESEARCH DESIGN AND METHODS: We followed 83,648 women from the Nurses' Health Study (NHS) (1980-2012), 88,610 women from NHSII (1991-2013), and 41,771 men from the Health Professionals Follow-Up Study (HPFS) (1986-2012). Dietary data were collected every 2-4 years by using validated food-frequency questionnaires. Self-reported incident diabetes, identified biennially, was confirmed by using a validated supplementary questionnaire. RESULTS: During 4.93 million person-years of follow-up, 18,442 type 2 diabetes cases were documented. Dietary n-6 PUFAs accounted for 4.4-6.8% of total energy, on average, and consisted primarily of linoleic acid (LA) (≥98%). In multivariate-adjusted models, hazard ratios (95% CIs) of type 2 diabetes risk comparing extreme n-6 PUFA quintiles (highest vs. lowest) were 0.91 (0.85, 0.96) (P trend = 0.002) for total n-6 PUFAs and 0.92 (0.87, 0.98) (P trend = 0.01) for LA. In an isocaloric substitution model, diabetes risk was 14% (95% CI 5%, 21%) (P = 0.002) lower when LA isocalorically replaced saturated fats (5% of energy), 17% (95% CI 9%, 24%) (P < 0.001) lower for trans fats (2% of energy), or 9% (95% CI 17%, 0.1%) (P = 0.047) lower for carbohydrates (5% of energy). Replacing n-3 PUFAs or monounsaturated fats with LA was not significantly associated with type 2 diabetes risk. CONCLUSIONS: Our study provides additional evidence that LA intake is inversely associated with risk of type 2 diabetes, especially when replacing saturated fatty acids, trans fats, or carbohydrates.

The safety of evening primrose oil in epilepsy.

The concern that evening primrose oil might cause epilepsy or seizures, or reduce the threshold for seizures, originated from two papers published in the early 1980s. These original reports are re-examined, and the association of evening primrose oil with seizures is shown to be spurious. Not only are linoleic acid and gamma-linolenic acid safe in epilepsy, with prolonged oral administration of linoleic acid and alpha-linolenic acid (in a 4:1 mixture) protecting rats from having seizures in four different epilepsy models, but the evening primrose oil-derived omega-6 fatty acid arachidonic acid inhibits sodium ion currents and synaptic transmission, while the evening primrose oil-derived eicosanoid prostaglandin E(1) appears to have anticonvulsant activity. In light of these findings, it is suggested that formularies should now remove seizures or epilepsy as a side-effect of evening primrose oil, and should remove a history of seizures or epilepsy as a contraindication to taking evening primrose oil.

Conjugated linoleic acids: are they beneficial or detrimental to health?

Conjugated linoleic acids (CLAs) comprise a family of positional and geometric isomers of linoleic acid (18:2n-6; LA) that are formed by biohydrogenation and oxidation processes in nature. The major dietary sources of these unusual fatty acids are foods derived from ruminant animals, in particular dairy products. The main form of CLA, cis-9, trans-11-18:2, can be produced directly by bacterial hydrogenation in the rumen or by delta-9 desaturation of the co-product vaccenic acid (trans-11-18:1) in most mammalian tissues including man. The second most abundant isomer of CLA is the trans-10, cis-12-18:2 form. Initially identified in grilled beef as a potential anti-carcinogen a surprising number of health benefits have subsequently been attributed to CLA mixtures and more recently to the main individual isoforms. It is also clear from recent studies that the two main isoforms can have different effects on metabolism and cell functions and can act through different cell signalling pathways. The majority of studies on body compositional effects (i.e. fat loss, lean gain), on cancer and cardiovascular disease attenuation, on insulin sensitivity and diabetes and on immune function have been conducted with a variety of animal models. Observations clearly emphasise that differences exist between mammalian species in their response to CLAs with mice being the most sensitive. Recent studies indicate that some but not all of the effects observed in animals also pertain to human volunteers. Reports of detrimental effects of CLA intake appear to be largely in mice and due mainly to the trans-10, cis-12 isomer. Suggestions of possible deleterious effects in man due to an increase in oxidative lipid products (isoprostanes) with trans-10, cis-12 CLA ingestion require substantiation. Unresponsiveness to antioxidants of these non-enzymatic oxidation products casts some doubt on their physiological relevance. Recent reports, albeit in the minority, that CLAs, particularly the trans-10, cis-12 isomer, can elicit pro-carcinogenic effects in animal models of colon and prostate cancer and can increase prostaglandin production in cells also warrant further investigation and critical evaluation in relation to the many published anti-cancer and anti-prostaglandin effects of CLAs.

Differential effects of dietary linoleic acid on mouse skin-tumor promotion and mammary carcinogenesis.

On the basis of reports of rat mammary- and pancreas-tumor models, we hypothesized that an increase in consumption of linoleic acid (LA) would also cause an enhancement in mouse skin-tumor promotion. SEN-CAR mice were placed on diets containing 0.8%, 2.2%, 3.5%, 4.5%, 5.6%, 7.0%, or 8.4% LA, 1 week after initiation with 7,12-dimethylbenz(a)anthracene and 3 weeks before starting promotion with 12-O-tetradecanoylphorbol-13-acetate. An inverse correlation (r = -0.92) was observed between papilloma number and level of LA; however, there was little difference in tumor incidence. A relationship between diet and carcinoma incidence was also found. The fatty acid composition of epidermal phospholipids reflected the dietary LA levels. 12-O-Tetradecanoylphorbol-13-acetate-induced epidermal prostaglandin E2 levels generally decreased with increasing dietary LA. To determine whether this inverse correlation between dietary LA and tumor yield was due to species differences or organ-model differences, a mammary carcinogenesis experiment was performed. SENCAR mice were fed the 0.8%, 4.5%, and 8.4% LA diets. All mice received 6 mg 7,12-dimethylbenz(a)anthracene, administered intragastrically at 1 mg/week. Tumor appearance was delayed in the 0.8% LA diet group, and a positive dose-response relationship between dietary LA and mammary-tumor incidence was observed. These studies suggest that the effect of dietary LA on tumor development is target tissue specific rather than species specific.

Trophic effects of essential fatty acids on pig skin.

The daily oral administration of 3 ml of two oils (So-5407 and So-1129) containing essential fatty acids (EFAs) for 16 weeks resulted in a transient increase in cell proliferative activity in the skin of female Large White pigs. The So-5407 oil contained 7% gamma-linolenic acid (GLA) whereas So-1129 was an oil of similar composition, but with no GLA. Hyperplasia of the epidermis was observed after the administration of both oils, and this was characterized by an increase in the size of the rete pegs. The maximum effect occurred at 4 weeks after the start of oil administration, at which time the number of viable cell layers had increased by a factor of approximately 1.5, and mean epidermal thickness (excluding the stratum corneum) was approximately 40% greater than that of the epidermis prior to oil administration. There was a marked increase in the labelling index (LI) of the basal cell layer of the epidermis in pigs receiving So-5407. Maximum LIs were quantified at 4 weeks after the start of administration and were 18.8 +/- 1.3% and 13.1 +/- 1.7% for pigs receiving So-5407 and So-1129, respectively. After this time the LI declined progressively and had returned to values within normal limits (P > 0.1) by 8 weeks after the start of administration of both oils. A similar pattern of change in the LI was seen in the follicular epithelium, although the peak values at 4 weeks after the start of oil administration of 12.2 +/- 1.8% and 10.8 +/- 0.9 for the groups receiving So-5407 and So-1129, respectively, were lower than in the epidermis. Labelled cells were also counted in the papillary dermis and maximum values were again seen at 4 weeks after the start of oil administration. Of the two oils, So-1129 had the greatest effect, with the number of labelled cells in the papillary dermis being a factor of three to four-fold higher than in skin prior to oil administration, between 2 and 12 weeks after the start of administration.

Can linoleic acid contribute to coronary artery disease?

The adipose tissue concentration of linoleic acid was positively associated with the degree of coronary artery disease (CAD) in a cross-sectional study of 226 patients undergoing coronary angiography. Linoleic acid concentration in adipose tissue is known to reflect the intake of this fatty acid. These results are therefore indicative of a positive relationship between linoleic acid intake and CAD. The platelet linoleic acid concentration was also positively associated with CAD. After confounding factors were allowed for, the eicosapentaenoic acid concentration in platelets was inversely associated with CAD for men, and the docosapentaenoic acid concentration in platelets was inversely associated with CAD for women; results consistent with several other studies that suggest that fish, and omega-3 fatty acids derived from fish and fish oils, can beneficially influence macrovascular disease.

Influence of dietary linoleic acid on experimental human breast cancer cell metastasis in athymic nude mice.

The effects of linoleic acid (LA), an omega-6 fatty acid precursor for prostaglandin biosynthesis, on the later stages of human breast cancer cell metastasis were studied by the intravenous injection of tumor cells into nude mice (). MDA-MB-435 cells were grown as solid tumors in donor mice fed a 12% or 2% LA-containing diet. These cells were harvested, and injected via a tail vein into recipient mice also fed a 12% LA (Group 1) or 2% LA (Group 2) diet. Other groups were fed 12% LA (Group 3) or 2% LA (Group 4), but injected with the cells grown in vitro in a low-LA culture medium. At necropsy 8 weeks later, the incidence of metastatic lung nodules was higher in Group 1 high LA donor/high LA recipient mice (p<0.001), and, to a lesser degree, Group 2 low LA donor/low LA recipient mice (p<0.05) compared with Groups 3 or 4. The extent of metastasis was significantly higher in Group 1 compared with any of the other groups, including metastasis to the ovaries, which occurred in 27% of the Group 1 mice. These findings show that LA, most likely by increased synthesis of cyclooxygenase products, stimulates metastasis, at least in part, by direct effects on the tumor cells, rather than on potential metastatic sites in the host.

Reduction by linoleic acid of the severity of experimental allergic encephalomyelitis in the guinea pig.

This paper reports the effects of supplementation of the diet with linoleic acid on the severity of experimental allergic encephalomyelitis (EAE) in guinea pigs. Clinical signs of disease (e.g. paresis, paraplegia, urinary incontinence), weight loss, frequency of perivascular lesions in the central nervous system and ability of isolated lymph node cells to respond to myelin basic protein in vitro were all reduced by linoleic acid supplementation. Linoleic acid was effective when fed at a dose of 0.5 ml/day from 7 to 21 days after sensitization of the animals with basic protein, i.e., before and during the time in which clinical signs normally appeared. The same daily dose fed from 7 days before to 7 days after sensitization, i.e., ceasing about 7 days before the normal time of appearance of clinical signs, produced no significant effect. Feeding linoleic acid to normal guinea pigs significantly altered the fatty acid composition of their serum and lymph nodes, but not of their brain. Of several possible explantations for the protective effect of lineolic acid in EAE, we considered action by this essential fatty acid on the immune system most likely.

Polyunsaturated fatty acids in the low-birth-weight infant.

The essentiality of certain PUFAs is related to their capability to be incorporated into lipids and to act as precursor in the formation of prostaglandins. Via phospholipids the EFA's influence the physico-chemical characteristics of biomembranes. EFAs are metabolized differently from nonessential PUFAs. While the nonessential fatty acids are metabolized rapidly, the organism tends to conserve the stores of EFAs. Inhibitions and competitions among the EFAs of the three series (oleic, linoleic, and alpha-linolenic) have been demonstrated. Apparently, for any given chain length the more unsaturated fatty acid has a greater affinity for the enzyme system responsible for further elongation and desaturation. EFAs are also necessary for the proper utilization of the saturated fatty acids. Vitamin E and pyridoxine seem to be involved in EFA metabolism. Normal growth of infants is dependent upon an adequate supply of EFA. The human fetus, like the adult, is unable to synthesize the EFAs, which must therefore be derived from the maternal circulation and pass through the placenta. In the fetus, increased concentration of the polyenoic fatty acids with advanced gestational age may result from increased activity of the fetomaternal unit by preferential transfer of these FAs. Enzymatic activity in the placenta or the fetus may also be responsible for desaturation and elongation of these EFAs. Several clinical manifestations have been ascribed in the human infant to prolonged EFA deficiency; however, none of these findings was noted in a group of sick newborn infants with very rapid onset of deficiency. Platelet dysfunction, decreased prostaglandin biosynthesis and turnover and altered pulmonary surfactant are among the effects of EFA deficiency on infants. Supplementation of the EFAs by the diet, parenterally or by the inunction of oil rich in linoleic acid, were reported to alleviate the symptoms of EFA deficiency. The minimal estimated requirement of linoleic acid is 1% of calories and 4% is an optimal intake. Most diets, including human breast milk, infant formulas and parenteral fat emulsions, far exceed the optimal intake of linoleic acid. Relatively little is known about the possible effects of high levels of linoleate in the diet; however, early studies suggest an adverse effect on platelet function, prostaglandin biosynthesis, pulmonary gas exchange and immune function.

Dietary linoleic acid is required for development of experimentally induced alcoholic liver injury.

We had previously hypothesized that linoleic acid (LA) was essential for development of alcoholic induced liver injury in our rat model. Male Wistar rats were fed a nutritionally adequate diet (25% calories as fat) with ethanol (8-17 g/kg/day). The source of fat was tallow (0.7% LA), lard (2.5% LA) or tallow supplemented with linoleic acid (2.5%). Liver damage was followed monthly by obtaining blood for alanine aminotransferase assay and liver biopsy for assessment of morphologic changes. Enzyme and histologic changes (fatty liver, necrosis and inflammation) in the tallow-linoleic acid-ethanol fed animals were more severe than in the lard-ethanol group. The tallow ethanol group did not show any evidence of liver injury. Our results strongly support our hypothesis that LA is essential for development of alcoholic liver disease in our rat model.

Liver subcellular fatty acid profiles of chicks fed diets containing hydrogenated fats and varying linoleate levels.

Day-old male broiler chickens were fed semipurified diets containing 5% lipid from one of four different lipid sources: corn oil (CO), partially hydrogenated soybean oil (HSBO), a spent restaurant grease (SRG) and a purified mixture of triolein, tripalmitin and tristearin (OPS). Diets CO and HSBO contained adequate amounts of linoleic acid, but diets SRG and OPS were deficient in linoleate. In addition, SRG and HSBO contained trans isomers of 16:1 and 18:1. The diets were fed for 3 wk to determine the effects of low linoleate levels and trans isomers on fatty acid profiles in liver microsomes, mitochondria and cytosol. Chicks fed HSBO had the highest body weights, while those fed SRG and OPS had the lowest. The incidence and severity of dermatitis were similar for all treatments. The proportions of linoleate and arachidonate in lipids from liver subcellular fractions were reduced significantly in chicks fed OPS and SRG; however, levels of 20:3 omega 9 were not increased. Feeding HSBO, which is high in both linoleate and linolenate, resulted in higher levels of 18:3 omega 3 and 20:5 omega 3 in liver subcellular fractions and lower levels of 20:4 omega 6 than those seen in chicks fed CO. The isomeric forms of 18:1 present in the partially hydrogenated fats (HSBO and SRG) appeared to be incorporated into the lipids of liver fractions. The results of this study show that dietary lipids influence fatty acid profiles of chick liver microsomes, mitochondria and cytosol. Decreases in linoleate and arachidonate in these organelles occur before overt essential fatty acid (EFA), deficiency signs in chicks fed EFA-deficient diets.

Cardiopathogenicity of rapeseed oils and oil blends differing in erucic, linoleic, and linolenic acid content.

Male Wistar rats were fed semipurifed diets containing 20% fat for 25 weeks. Ten different oils or oil blends were employed, including rapessed oils, simulated rapeseed-type oils, and modified rapeseed-type oils. Safflower, soybean, and hydrogenated coconut oils served as control oils. Histopathological examination of the cardiac tissue was conducted at the end of the study and an incidenceseverity rating assigned to the lesions induced by each fat. Oils containing high levels of erucic acid (26-30%) induced the most severe cardiac necrosis, irrespective of the source of erucic acid (rapeseed oil or nasturtium oil). Increasing the linoleic: :linolenic acid ratio of the high erucic oils to that of soybean oil failed to reduce necrosis, but the absence of linolenic acid from a high erucic acid oil blend resulted in a markedly reduced lesion incidenceseverity rating, comparable to those obtained for low erucic acid rapessed oil and soybean oil which were similar. Lowest lesion incidence was obtained with safflower oil and hydrogenated coconut oil. We have postulated that linolenic acid plays a role in the etiology of cardiac necrosis observed when rats are fed diets containing low erucic acid rapeseed oils.

The combined role of atheroma, cholesterol, platelets, the endothelium and fibrin in heart attacks and strokes.

In 1920 the typical American diet was rich in cholesterol and fat, especially saturated animal fat, with one-third the polyunsaturated vegetable fat as now; yet in that year, death from myocardial infarction (MI) in the United States was so rare that it had no name or medical recognition. In 1960, when MI deaths in the United States had soared to an alarming rate of 600,000, orthodox medicine concluded that cholesterol and saturated animal fat in food caused elevated cholesterol in blood, which caused cholesterol in atheroma, which in turn caused death from MI and strokes. It is suggested that human atheroma is made up mostly of fibers of either collagen or fibrin, smooth-muscle cells or dead smooth-muscle cells, that it contains but little cholesterol, and that it is present in both men and women and in populations having little or no MI as well as in those where MI is the greatest cause of death. It is suggested that MI is largely caused by coronary blood clots formed at the site of a break in the coronary artery endothelium; that the introduction of a new, unnatural dietary fatty acid--trans-trans linoleic acid--in margarine and refined vegetable oils in the 1920s, by inducing a deficiency of beneficial prostaglandin E1 (PGE1) while greatly increasing harmful thromboxane A2 (TXA2), caused vasoconstriction while the clumping of platelets was greatly increased, giving rise to the coronary blood clots that either cause or are part of the fatal process of MI. It is suggested that in fostering the increase of dietary trans-trans linoleic acid in polyunsaturated vegetable fats at the expense of saturated animal fat, orthodox medicine is fostering a principle cause of MI as the cure.

[Linoleic acid and the immune system. Controversies about lipid emulsions]. / Acido linoleico y sistema inmune. Controversias sobre las emulsiones lipídicas.

The selection of a given lipidic function for nutritional backup requires not only knowledge of the metabolism of the different existing lipidic emulsions and of their specific therapeutic indications, but also of their contraindications and controversies because, apart from their calorific value, the contribution of liposoluble vitamins and their function in preventing essential fatty acid deficiencies, we know that they are powerful metabolic modulators. This in associated with the fact that manipulation of dietary lipids (enteral or parenteral) can affect and modulate the response to the disease, attack or infection by improving or impairing the different immune functions. This review is focused on the scientific publications which have examined the varying effects of lipidic emulsions, in quantity and in quality (particularly linoleic acid) on the immune system, on the fatty acid composition of the cellular membranes and on the production of and prostaglandins and leukotrienes. An update is given of the known interrelation between lipids and immunity, with appraisal of triglycerides and long-medium -- and short-chain fatty acids, mixtures of medium -- and long-chain triglycerides, the proportions between infinity-3/infinity-6, and structured lipids.

[Studies on the influence of long-term doses of lipid peroxide generators on rat pancreas].

The role of oxygen derived free radicals or tissue lipid peroxides in the pathogenesis of chronic pancreatitis has not been established. To evaluate long-term effects of tissue lipid peroxides in the pathogenesis of chronic pancreatitis, we treated Wistar male rats with 2,2'-azo-bis-(2-amidino-propane) dihydrochloride (AAPH) and/or linoleic acid (LA) for 3 or 6 months. Rats were divided into eight groups. A: Saline-treated rats for 3 months as control, B: AAPH 40 mg/kgw intraperitoneally, twice a week for 3 months, C: LA 0.5 ml/kgw intraperitoneally, every other week for 3 months, D: AAPH and LA for 3 months, E: Saline-treated for 6 months, F: AAPH for 6 months, G: LA for 6 months, H: AAPH and LA for 6 months. The results were as follows: Lipid peroxide contents of the pancreas were elevated in groups: C, D, G and H. Histological examination revealed epithelial hyperplasia of large pancreatic ducts, vacuolization of ductal epithelium, intraepithelial neutrophilic infiltration, periductal mononuclear cell infiltration (ductulitis and peri-ductulitis), and sporadically in the lobules, destruction of acinar cells, neutrophilic infiltration and ductular proliferation in the same groups. These findings indicate that tissue damage was more severe in the pancreatic ducts than in the acinar cells, however no damage was seen in the endocrine pancreas. Vitamin E content of the pancreas was decreased in groups: B, C, D, F, G and H. Tissue glutathione peroxidase (GSH-Px) activity was increased in groups: D and H. Tissue catalase activity was increased in groups: D, G and H, but no change of superoxide dismutase (SOD) activity was seen in any of the groups. These results indicate that vitamin E may play the role of the main scavenger in the situation of a smaller dose of lipid peroxides, but when larger doses are administered, GSH-Px may play the main role as the scavenger in this experimental system.