Margarine

Am. J. Respir. Crit. Care Med., Volume 163, Number 1, January 2001, 277-279
Margarine Consumption and Allergy in Children
GABRIELE BOLTE, CHRISTIAN FRYE, BERND HOELSCHER, INES MEYER, MATTHIAS WJST, and JOACHIM HEINRICH
GSF National Research Center for Environment and Health, Institute of Epidemiology, Neuherberg, Germany
Dietary fat consumption is hypothesized to influence atopy development by modulation of IgE production. The aim of our study was to assess whether margarine consumption is associated with allergic sensitization and diseases in children. Data of a cross-sectional health survey in 1998-1999 comprising 2,348 children age 5 to 14 yr were analyzed. Information on type of fat used as spread during the past 12 mo, children's health, and sociodemographic factors were gathered by questionnaire. Allergic sensitization to common aeroallergens was assessed by specific serum IgE. Compared with butter consumption, margarine consumption was associated with allergic sensitization (adjusted odds ratio 1.30 [95% confidence interval: 1.01 to 1.67]) and with rhinitis symptoms during the past 12 mo (1.41 [1.01 to 1.97]). Sex-stratified analysis showed that these associations were limited to boys (boys: sensitization 1.57 [1.12 to 2.20], rhinitis symptoms 1.76 [1.12 to 2.78]; girls: sensitization 0.99 [0.67 to 1.46], rhinitis symptoms 1.03 [0.63 to 1.70]). No statistically significant relation was observed between exclusive margarine consumption and ever physician-diagnosed hay fever or asthma in all children. In conclusion, the sex difference in the association of margarine consumption with allergic sensitization was in accordance with the higher IgE concentrations and atopy prevalence in boys compared with girls. Increased intake of certain polyunsaturated fatty acids might further stimulate IgE production in boys.
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Bilaga 2

1: Eur Respir J 1997 Jan;10(1):6-12 Related Articles, Books, LinkOut

Dietary fat and asthma: is there a connection?

Black PN, Sharpe S

Dept of Medicine University of Auckland Auckland Hospital, New Zealand.

[Record supplied by publisher]

The last two decades have seen an increase in the prevalence of asthma, eczema, and allergic rhinitis in developed countries. This increase has been paralleled by a fall in the consumption of saturated fat and an increase in the amount of polyunsaturated fat in the diet. This is due to a reduction in the consumption of animal fat and an increase in the use of margarine and vegetable oils containing omega-6 polyunsaturated fatty acids (PUFAs), such as linoleic acid. There is also evidence for a decrease in the consumption of oily fish which contain omega-3 PUFAs, such as eicosapentaenoic acid. In a number of countries, there are social class and regional differences in the prevalence of allergic disease, which are associated with differences in the consumption of PUFAs. Linoleic acid is a precursor of arachidonic acid, which can be converted to prostaglandin E2 (PGE2), whereas eicosapentaenoic acid inhibits the formation of PGE2. PGE2 acts on T-lymphocytes to reduce the formation of interferon-gamma (IFN-gamma) without affecting the formation of interleukin-4 (IL-4). This may lead to the development of allergic sensitization, since IL-4 promotes the synthesis of immunoglobulin E (IgE), whereas IFN-gamma has the opposite effect. Changes in the diet may explain the increase in the prevalence of asthma, eczema and allergic rhinitis. The effects of diet may be mediated through an increase in the synthesis of prostaglandin E2 which in turn can promote the formation of immunoglobulin E.

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Bilaga 3

1: Int Arch Allergy Appl Immunol 1985;78(1):30-2 Related Articles, Books

Detection of soy protein in soy lecithin, margarine and, occasionally, soy oil.

Porras O, Carlsson B, Fallstrom SP, Hanson LA

[Record supplied by publisher]

Samples of soy lecithin, soy oil and margarine were tested for the presence of soy proteins by an inhibition technique using ELISA. All but one of the soy lecithin samples contained soy protein, as did some of the soy oil and margarine samples. The positive margarines contained only about 25% as much soy protein as the soy lecithin preparations. The presence of soy proteins in these soy products might account for hitherto unrecognized exposure to soy proteins in various foods.

Bilaga 4

THE LANCET, VOL 353, June 12, 1999

Intake of trans fatty acids and prevalence of childhood asthma and allergies in Europe

Stephan K Weiland, Erika von Mutius, Anika Husing,
M Innes Asher, on behalf of the ISAAC Steering Committee

Intake of certain polyunsaturated fatty acids, particularly n-3 and n-6 fatty acids, has been associated with the development of asthma and allergies in children, but little is known whether the configuration (cis or trans) of these fatty acids plays a role. We investigated the association between intake of trans fatty acids and the prevalence of childhood asthma and allergies in ten European countries. Detailed data on the intake of trans fatty acids and other fatty acids in 14 European countries have recently been provided by a collaborative study that used representative market baskets per country. Trans fatty acids occur in dairy products, fat of ruminant animals, and industrially hydrogenated vegetable fats (such as margarine). The International Study of Asthma and Allergies in Childhood (ISAAC) has studied the prevalence of asthma, allergic rhinoconjunctivitis, and atopic eczema in children aged 13-14 years in 155 centres around the world using standardised written and video questionnaires. Prevalence estimates were available for 55 study centres in ten countries with data on fatty acid intake: Belgium ( 1 study centre), Finland (4), France (5), Germany (2), Greece (1), Italy (13), Portugal (4), Spain (8), Sweden (2), UK (15). Linear regression analysis was used to assess the association between the 12-month prevalence of symptoms of asthma (wheeze), allergic rhinoconjunctivitis (runny nose with itchy eyes), and atopic eczema (flexural dermatitis) in those aged 13-14 years and the intake of fatty acids using the country estimate for all centres in the respective countries.
There was a positive association between the intake of trans fatty acids (expressed as percent of energy intake) and the prevalence of symptoms of asthma, allergic rhinoconjunctivitis, and atopic eczema (figure). After adjustment for gross national product of the country all these associations remained statistically significant (p<0,001), as was the association with the prevalence of asthma symptoms during the last year assessed by the video questionnaire (p<0,05, data not shown). The associations tended to be stronger when the analyses were restricted to estimates of trans fatty acid intake from sources that contain predominantly hydrogenated vegetable fat, such as oils, biscuits, cakes, and chips. Similarly consistent associations were not seen for intake of monounsaturated or polyunsaturated fatty acids in cis configuration.
Ecological studies allow comparison of populations with large differences in exposures, but an observed association between populations does not necessarily exist also between individuals. The estimates of trans fatty acid intake could therefore also be markers for other factors that affect the prevalence of childhood atopy. However, it has been reported that trans fatty acids influence the desaturation (eg, impaired delta6-desaturase activity) and chain elongation of n-6 and n-3 fatty acids into precursors of inflammatory mediators, such as prostaglandins and leukotrienes, and that these effects may be stronger for trans fatty acids from hydrogenated vegetable fat than from animal fat.
Furthermore, among infants increased trans fatty acid plasma levels have been associated with changes in the fatty acid composition of plasma lipids similar to those seen in individuals with atopic diseases. Trans fatty acids have been a typical part of the "western" diet and the hypothesis that they may play a part in the development of childhood asthma and allergies seems worth pursuing.

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Bilaga 5

1: J Allergy Clin Immunol 2000 Nov;106(5):962-7 Related Articles, Books, LinkOut

Influence of refining steps on trace allergenic protein content in sunflower oil.

Zitouni N, Errahali Y, Metche M, Kanny G, Moneret-Vautrin DA, Nicolas JP, Fremont S

Laboratoire de Biochimie Medicale et Pediatrique, Faculte de Medecine (U 308), Nancy, France.

[Record supplied by publisher]

BACKGROUND: Although allergy to sunflower seed and oil is a relatively rare occurrence, several cases of sunflower seed allergy have been observed, and we have already described one case of anaphylaxis after eating sunflower oil and margarine. OBJECTIVE: The aim of our study was to determine and characterize the allergens from sunflower oil at the different steps of the refining process: crude pressed oil (step A), acidification and neutralization (step B), pregumming by centrifugation (step C), washing (step D), bleaching (step E), gumming by filtration (step F), and deodorization (step G). METHODS: A sample of oil from each step of the process (steps A to G) was heat extracted with PBS. The protein concentration of each extract was evaluated by using the micro-Bradford assay. Samples were run on SDS-PAGE. The immunoblot was performed with the serum of a patient sensitized to sunflower seed and oil. RESULTS: The extracts obtained after each step reveal a decrease in total protein concentration from 13.6 microg/mL to 0. 22 microg/mL. The result of SDS-PAGE shows 5 bands, from 67 kd to 145 kd, with the most abundant being the 67-kd protein. The amount of this protein decreases after each step of the process. It is, however, still present in trace amounts in the refined oil. The 67-kd protein, which is mainly present in the crude oil and slightly in the refined oil, has been shown to be allergenic. CONCLUSION: Because of the presence of allergenic proteins, refined sunflower oil may pose a threat to people highly sensitized to sunflower seeds.

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Bilaga 6

1: Med Pr 1977;28(1):61-3 Related Articles, Books

[Allergy to chromium and nickel in workers employed in margarine production].

[Article in Polish]

Lada-Jagas R

[Record supplied by publisher]

The paper presents the cycle of margarine production with special attention to the process of hardening of vegetable oils using nickel formate as catalyst. Test examination (patch tests) was carried out with standard set and nickel formate in 10 workers of hardening department and 24 female workers of packing room. In 2 workers contact dermatitis caused by sensitization to nio nickel formate was observed. In 5 workers was found latent allergy to nickel and in 12 female workers latent allergy to chromium and nickel. In the control group containing intellectual workers, uniform in regard to sex and age, the results of patch tests were negative.

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Bilaga 7

Transplantation 1977 Oct;24(4):263-7 Related Articles, Books, LinkOut

Immunosuppression with polyunsaturated fatty acids in renal transplantation.

McHugh MI, Wilkinson R, Elliott RW, Field EJ, Dewar P, Hall RR, Taylor RM, Uldall PR

A double-blind controlled trial has been undertaken to assess the value of a preparation containing polyunsaturated fatty acids (PUFA) in human cadaveric renal transplantation. Eighty-nine patients were studied and followed for 6 months after transplantation. Forty-four took the PUFA preparation and 45 the placebo (oleic acid). Other immunosuppression was standardised. Functional graft survival was significantly better in the PUFA group than in those taking the placebo during the first 3 to 4 months post-transplant. At 6 months, however, although the difference between the groups persisted, it was no longer statistically significant. Complications were equally distributed between the groups.

Bilaga 8
1: J Nutr 1996 Mar;126(3):681-92 Related Articles, Books, LinkOut

Dietary butter protects against ultraviolet radiation-induced suppression of contact hypersensitivity in Skh:HR-1 hairless mice.

Cope RB, Bosnic M, Boehm-Wilcox C, Mohr D, Reeve VE.

Department of Veterinary Pathology, University of Sydney, New South Wales, Australia.

Dietary fats modulate a wide variety of T cell functions in mice and humans. This study examined the effects of four different dietary fats, predominantly polyunsaturated sunflower oil, margarine, and predominantly saturated butter, clarified butter, on the T cell-mediated, systemic suppression of contact hypersensitivity by ultraviolet radiation in the Skh:HR-1 hairless mouse. Diets containing either 200 g/kg or 50 g/kg butter or clarified butter as the sole fat source protected against systemic photoimmunosuppression, whether the radiation source was unfiltered ultraviolet B (280-320 nm) or filtered solar simulated ultraviolet radiation (290-400 nm), in comparison with diets containing either 200 or 50 g/kg margarine or sunflower oil. There was a linear relationship (r > 0.9) between protection against photoimmunosuppression and the proportion of clarified butter in mice fed a series of 200 g/kg mixed fat diets that provided varying proportions of clarified butter and sunflower oil. The dietary fats did not modulate the contact hypersensitivity reaction in unirradiated animals. The observed phenomena were not primary due to the carotene, tocopherol, cholecalciferol, retinol, lipid hydroperoxide or the nonfat solid content of the dietary fats used and appeared to be a result of the different fatty acid composition of the fats.

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A Prospective Study of Association
of Monounsaturated Fat and Other Types
of Fat With Risk of Breast Cancer

Alicja Wolk, PhD; Reinhold Bergström, PhD; David Hunter, MD; Walter Willett, MD; Håkan Ljung, MSc; Lars Holmberg, MD; Leif Bergkvist, MD; Åke Bruce, MD; Hans-Olov Adami, MD

Background: Animal studies suggest that monounsaturated and polyunsaturated fat may have opposite effects on the risk of breast cancer.

Methods: We performed a population-based prospective cohort study, including 61 471 women aged 40 to 76 years from 2 counties in central Sweden who did not have any previous diagnosis of cancer; 674 cases of invasive breast cancer occurred during an average follow-up of 4.2 years. All subjects answered a validated 67-item food frequency questionnaire at baseline. Cox proportional hazards models were used to obtain adjusted rate ratio (RR) estimates with 95% confidence intervals (CIs).

Results: After mutual adjustment of different types of fat, an inverse association with monounsaturated fat and a positive association with polyunsaturated fat were found. The RR for each 10-g increment in daily intake of monounsaturated fat was 0.45 (95% CI, 0.22-0.95), whereas the RR for a 5-g increment of polyunsaturated fat was 1.69 (95% CI, 1.02-2.78); the increments correspond to approximately 2 SDs of intake in the population. Comparing the highest quartile of intake with the lowest, we found an RR of 0.8 (95% CI, 0.5-1.2) for monounsaturated fat and 1.2 (95% CI, 0.9-1.6) for polyunsaturated fat. Saturated fat was not associated with the risk of breast cancer.

Conclusions: Our results indicate that various types of fat may have specific opposite effects on the risk of breast cancer that closely resemble the corresponding effects in experimental animals. Research investigations and health policy considerations should take into account the emerging evidence that monounsaturated fat might be protective for risk of breast cancer.

Arch Intern Med. 1998;158:41-45

Bilaga 3

Cancer Causes Control 1995 Nov;6(6):545-50 Related Articles, Books, LinkOut

Olive oil, other dietary fats, and the risk of breast cancer (Italy).

la Vecchia C, Negri E, Franceschi S, Decarli A, Giacosa A, Lipworth L

Istituto di Statistica Medica e Biometria, Universita di Milano, Italy.

Data from a multicenter case-control study on breast cancer conducted in Italy have been used to analyze the relationship of olive oil and other dietary fats to breast cancer risk. Cases were 2,564 women hospitalized with histologically confirmed, incident breast cancer. Controls were 2,588 women admitted to the same network of hospitals for acute, non-neoplastic, non-hormone related, non-digestive tract disorders. Cases and controls were interviewed between 1991 and 1994 using a validated food-frequency questionnaire. The data were modelled through multiple logistic regression controlling for demographic and reproductive breast-cancer risk factors, energy intake and, mutually, for types of dietary fat. For olive oil, compared with the lowest quintile, the odds ratios (OR) were 1.05, 0.99, 0.93, and 0.87 for increasing quintiles of intake; in a model postulating linear logit increase, the OR per unit (30 g) was 0.89 (95 percent confidence interval [CI] = 0.81-0.99, P = 0.03). Among other oils or fats considered, the OR for the highest level of intake was 0.72 (CI = 0.6-0.9) for a group of specific seed oils (including safflower, maize, peanut, and soya) compared with nonusers. The ORs for the highest cf lowest level of intake were 0.80 for mixed or unspecified seed oils, 0.95 for butter, and 0.96 for margarine. The study, based on a large dataset from various Italian regions, shows an inverse relationship of breast cancer risk with intake of olive oil and other vegetable oils, but not with butter or margarine.
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Bilaga 4

: Int J Cancer 1999 Mar 1;80(5):704-8 Related Articles, Books, LinkOut

Diet and cancer of the prostate: a case-control study in Greece.

Tzonou A, Signorello LB, Lagiou P, Wuu J, Trichopoulos D, Trichopoulou A

Department of Hygiene and Epidemiology, University of Athens Medical School, Goudi, Greece.

The nutritional aetiology of prostate cancer was evaluated in Athens, Greece, through a case-control study that included 320 patients with histologically confirmed incident prostate cancer and 246 controls without history or symptomatology of benign prostatic hyperplasia or prostate cancer, treated in the same hospital as the cases for minor diseases or conditions.
Among major food groups, milk and dairy products as well as added lipids were marginally positively associated with risk for prostate cancer. Among added lipids, seed oils were significantly and butter and margarine non-significantly positively associated with prostate cancer risk, whereas olive oil was unrelated to this risk. Cooked tomatoes and to a lesser extent raw tomatoes were inversely associated with the risk for prostate cancer. In analyses focusing on nutrients, rather than foods, polyunsaturated fats were positively and vitamin E inversely associated with prostate cancer. We conclude that several nutrition-related processes jointly contribute to prostate carcinogenesis.
Bilaga 5
TITLE: A case-control study of risk factor for renal cell cancer in northern Italy.
AUTHORS: Talamini R; Baron AE; Barra S; Bidoli E; La Vecchia C; Negri E; Serraino D; Franceschi S
AUTHOR AFFILIATION: Epidemiology Unit, Aviano Cancer Center, Italy.
SOURCE: Cancer Causes Control 1990 Sep;1(2):125-31.
CITATION IDS: PMID: 2102282 UI: 91338373
ABSTRACT: A hospital-based case-control study of renal cell cancer was conducted in northern Italy between 1986 and 1989, with 240 cases of renal cell cancer (150 males and 90 females), and 665 controls (445 males and 220 females) chosen on the basis of age, sex, and area of residence. No associations were found between renal cell cancer and: body mass index (BMI); number of cigarettes smoked; age at starting to smoke; years of smoking; consumption of wine, beer, spirits, coffee, decaffeinated coffee; tea; intake of animal protein, fruits, and vegetables; various reproductive factors; hormonal use; sexual habits; sexually transmitted diseases; or selected occupational exposures. The odds ratio (OR) was above unity in smokers (OR = 1.34 for greater than or equal to 15 cigarettes/day), but the trends in risk with dose or duration were not statistically significant. Significant positive associations were found between renal cell cancer and sources of fat intake, especially margarine (OR for highest vs lowest intake = 1.71), and oils (OR = 1.89) whereas carrot intake showed a negative association (OR = 0.62). Also, a history of nephrolithiasis and multiple episodes of cystitis showed weak positive associations (OR = 2.00, 95 percent confidence interval (CI) 1.07-3.73; and OR = 1.60, 95 percent CI 0.95-2.70, respectively).

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Bilaga 6

TITLE: Diet and pancreatic cancer: a case-control study.
AUTHORS: Norell SE; Ahlbom A; Erwald R; Jacobson G; Lindberg-Navier I; Olin R; Tornberg B; Wiechel KL
SOURCE: Am J Epidemiol 1986 Dec;124(6):894-902.
CITATION IDS: PMID: 3776972 UI: 87046023
ABSTRACT: In a population-based case-control study carried out in Sweden in 1982-1984, the authors examined the association of pancreatic cancer with several dietary factors, coffee, alcohol, and tobacco. Analyses were based on 99 cases, 138 population controls, and 163 hospital controls. The cases were persons aged 40-79 years diagnosed with cancer of the exocrine pancreas at three surgical departments in Stockholm and Uppsala. The risk increased with higher consumption frequency of fried and grilled meat in the comparison with each series of controls (e.g., relative risk (RR) = 1.7 (90% confidence interval (CI) = 1.1-2.7) for weekly intake and RR = 13.4 (90% CI = 2.4-74.7) for almost daily intake, in the comparison with population controls). Furthermore, associations were found with other fried or grilled foods, but not with meat other than fried or grilled. The risk also increased with the intake of margarine (e.g., RR = 9.7 (90% CI = 3.1-30.2) for 15+ g of margarine on a slice of bread, in the comparison with population controls). In contrast, no excess risk was associated with high intake of butter. A low risk was associated with frequent consumption of fruits and vegetables, particularly carrots (RR = 0.3 (90% CI = 0.2-0.7)) and citrus fruits (RR = 0.5 (90% CI = 0.3-0.9)) for almost daily intake. No consistent associations were found with coffee, artificial sweeteners or alcohol consumption, but a threefold increase in risk was associated with smoking at least one pack of cigarettes per day.

Bilaga 7

TITLE: [Relation of fat consumption to colorectal cancer mortality in a Venezuelan population]
VERNACULAR TITLE: Relacion entre el consumo de grasas y la mortalidad por cancer colorrectal en la poblacion venezolana.
AUTHORS: Malave H; Mendez Castellano H; Malave I
AUTHOR AFFILIATION: Centro de Medicina Experimental, Instituto Venezolano de Investigaciones Cientificas, Caracas.
SOURCE: Arch Latinoam Nutr 1992 Jun;42(2):110-7.
CITATION IDS: PMID: 1341850 UI: 94091926
ABSTRACT: Epidemiologic and experimental studies have pointed to an association between fat intake and colorectal carcinogenesis. In the present work we have studied the correlation between fat intake and mortality caused by colorectal cancer in the venezuelan population. For this purpose, we have calculated the correlation coefficients between the ingestion of total fat, visible fat (vegetable oil, margarine, butter, mayonnaise) as well as non-visible fat (that contained in other foods) and the mortality rate by colorectal cancer with data from nine venezuelan states and geographical regions. The highest lipid consumption and mortality rates were observed in the more developed states. There was a positive and significant correlation between total as well as visible fat consumption and colorectal cancer mortality (r = 0.756 p < 0.02, and r = 0.958, p < 0.001; respectively). In contrast, there was no significant correlation between the consumption of non visible fats and colorectal mortality (r = 0.543, p < 0.05). More than 80% of the visible fats ingested in Venezuela are constituted by vegetable oil and margarine, which contain a high proportion of polyunsaturated fatty acids. Based on the above, is possible to infer that colorectal carcinogenesis in Venezuela is associated to the uptake of unsaturated fat, and that measures leading to the prevention of this disease should be based on the reduction in the consumption of total and unsaturated lipids.

Bilaga 8

Oncology 1984;41(2):101-5 Related Articles, Books, LinkOut

Effects of margarine on hepatocarcinogenesis by N,N'-2, 7-fluorenylenebisacetamide in mice.

Yanagi S, Tsuda H, Sakamoto M, Fuse E, Ito N

The effect of a safflower margarine on hepatocarcinogenesis by N,N'-2, 7-fluorenylenebisacetamide was compared with that of safflower oil from which the margarine was made. A high-dextrin diet was used as a control for the two high-fat diets. The number of surviving mice in the margarine group at the end of the experiment was significantly lower compared with both the dextrin and the oil groups. A significantly high incidence of hepatic nodules type 2 was observed in the margarine group, whereas most liver tumors in both the dextrin and the safflower oil groups were of HN type 1 (p less than 0.05). Hepatocellular carcinomas were induced in some mice in all the groups. However, no statistical difference was found among the three dietary groups. Thus the difference in the types of the hepatic nodules among the three groups was not reflected in the incidence of hepatocellular carcinoma.
Bilaga 9
Cancer Detect Prev 1994;18(6):415-20 Related Articles, Books, LinkOut

Comparative effects of milk, yogurt, butter, and margarine on mammary tumorigenesis induced by 7,12-dimethylbenz(a)anthracene in rats.

Yanagi S, Yamashita M, Ogoshi K, Imai S

Department of Biochemistry, Nara Medical College, Japan.

The effects of margarine and butter on mammary tumorigenesis were compared in the first experiment. Altering the levels of dietary margarine and butter influenced the development of mammary tumors induced with 7,12-dimethylbenz(a)anthracene (DMBA) in rats. Margarine enhanced tumorigenesis dose dependently in both the incidence and the number of mammary tumors. On the other hand, butter that was substituted for margarine did not show any enhancing effects. Inasmuch as butter is made from cow's milk, the effect of cow's milk was studied in the second experiment. It was expected that milk might inhibit mammary tumorigenesis. Contrary to our expectations, however, milk and yogurt did not inhibit but enhanced the DMBA-induced mammary tumorigenesis. It remains to be elucidated whether the enhancing effect was caused by some specific factors in milk or by the difference in energy or nutrient intakes.

Bilaga 10

Transplantation 1977 Oct;24(4):263-7 Related Articles, Books, LinkOut

Immunosuppression with polyunsaturated fatty acids in renal transplantation.

McHugh MI, Wilkinson R, Elliott RW, Field EJ, Dewar P, Hall RR, Taylor RM, Uldall PR

Conjugated linoleic acid and the control of cancer and obesity.

Pariza MW, Park Y, Cook ME

Food Research Institute, Department of Food Microbiology and Toxicology, University of Wisconsin-Madison, 53706-1187, USA. [email protected]

The effects of conjugated linoleic acid (CLA) in animals are reviewed. In most of the CLA preparations that have been investigated to date for biological activity, two CLA isomers are present in about equal concentrations: cis-9,trans-11 CLA, and trans-10,cis-12 CLA. The occurrence of these isomers in foods and their production by rumen microorganisms are discussed. Potential mechanisms of action as regards the effects of CLA on cancer and body composition are reviewed, including recent evidence that body composition changes are produced by the trans-10,cis-12 CLA isomer. Evidence is presented indicating that CLA may modulate cellular response to tumor necrosis factor-alpha (TNF-alpha). The mechanistic implications of this finding are considered.
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Mammary cancer prevention by conjugated dienoic derivative of linoleic acid.

Ip C, Chin SF, Scimeca JA, Pariza MW

Department of Surgical Oncology, Roswell Park Cancer Institute, Buffalo, New York 14263.

Conjugated dienoic derivative of linoleic acid (CLA) is a collective term which refers to a mixture of positional and geometric isomers of linoleic acid. It is a naturally occurring substance in food and is present at higher concentrations in products from animal sources. The present study reports that synthetically prepared CLA is an effective agent in inhibiting the development of mammary tumors induced by dimethylbenz(a)anthracene. Rats were fed either the AIN-76A basal diet or the same diet supplemented with 0.5, 1, or 1.5% CLA by weight. These diets were started 2 weeks before carcinogen administration and continued until the end of the experiment. The total number of mammary adenocarcinomas in the 0.5, 1, and 1.5% CLA groups was reduced by 32, 56, and 60%, respectively. The final tumor incidence and cumulative tumor weight were similarly diminished in rats fed the CLA-containing diets. In general, there appeared to be a dose-dependent protection at levels of 1% CLA and below, but no further beneficial effect was evident at levels above 1%. Chronic feeding of up to 1.5% CLA produced no adverse consequences in the animals. Analysis of the phospholipid fraction from liver and mammary tumor extracts showed that only the c9,t11 isomer of CLA was incorporated and that the level of incorporation increased with dietary intake. An interesting property of CLA is its ability to suppress peroxide formation from unsaturated fatty acid in a test-tube model (Cancer Res., Ha et al. 50: 1097-1101, 1990). In view of this information, the amount of thiobarbituric acid-reactive substances (lipid peroxidation products) present endogenously in liver and mammary gland was quantitated. The feeding of CLA (for either 1 or 6 months) resulted in a decrease in the extent of lipid peroxidation in the mammary gland, but such a suppressive effect was not detected in the liver. It should be noted that maximal antioxidant activity was observed with only 0.25% CLA in the diet, whereas maximal tumor inhibition was achieved at about 1% CLA. Hence there is a discrepancy between the antioxidant efficacy of CLA and its anticarcinogenic potency, suggesting that some other mechanisms might be involved in cancer protection. Unlike the stimulatory effect of linoleic acid in carcinogenesis (Cancer Res., Ip et al., 45: 1997-2001, 1985), the reaction of CLA in cancer prevention is specific, and CLA is more powerful than any other fatty acid in modulating tumor development.

Bilaga 121: Rev Med Interne 1998 Apr;19(4):247-54 Related Articles, Books, LinkOut

[UV-induced immunosuppression and skin cancers].

[Article in French]

Meunier L, Raison-Peyron N, Meynadier J.

Service de dermatologie-allergologie-photobiologie, Hopital Saint-Eloi, Montpellier, France.

INTRODUCTION: The increased incidence of skin cancers is due to modifications of our behavior toward solar exposure. Photocarcinogenesis represents the sum of complex and intricate events that lead to the occurrence of skin cancers. CURRENT KNOWLEDGE AND KEY POINTS: In epidermal cells UV light induces lesions of DNA that lead to modifications in oncogene and tumor suppressor gene expression. UV-induced immunosuppression is also important for tumoral promotion. UV exposure decreases the number of Langerhans cells in the epidermis and modifies their antigen-presenting cell capacity. Numerous experimental data obtained in animal models clearly indicate the existence of a relationship between UV-induced immune suppression and skin cancers. In humans, growing evidence suggests that skin cancers and photoimmunosuppression are linked. FUTURE PROSPECTS AND PROJECTS: Better knowledge of mechanisms involved in UV-induced immune suppression is essential for developing new strategies aimed at photoprotection and cancer prevention.
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Bilaga 13
1: Recent Results Cancer Res 1995;139:69-86 Related Articles, Books, LinkOut

Skin cancer and warts in immunosuppressed renal transplant recipients.

Leigh IM, Glover MT.

Department of Dermatology, Royal London Hospital Trust, UK.

Non-melanoma skin cancer (NMSC) is increasingly recognised as a complication of long-term immunosuppression and has been particularly studied in renal transplant recipients (RTR). A population study of renal transplant recipients has been performed with analysis of those features contributing to a high rate of detection of NMSC, such that 40% patients with fair skin have NMSC 5 years after transplantation. 90% of the total patient population have warts 5 years after transplantation, many being atypical and in sun-exposed sites. Therefore, contributory factors in these patients include not only the global immunosuppression, ultraviolet radiation (UVR)-induced mutagenesis and photoimmunosuppression, but also the widespread presence of human papillomavirus (HPV) infection, including the unusual epidermodysplasia verruciformis (EV)-associated cutaneous oncogenic HPV.

Bilaga 14
1: Cancer Lett 1996 Nov 29;108(2):271-9 Related Articles, Books

Dependence of photocarcinogenesis and photoimmunosuppression in the hairless mouse on dietary polyunsaturated fat.

Reeve VE, Bosnic M, Boehm-Wilcox C.

Department of Veterinary Pathology, University of Sydney, NSW, Australia.

A series of semi-purified diets containing 20% fat by weight, of increasing proportions (0, 5%, 10%, 15% or 20%) of polyunsaturated sunflower oil mixed with hydrogenated saturated cottonseed oil, was fed to groups of Skh:HR-1 hairless mice during induction and promotion of photocarcinogenesis. The photocarcinogenic response was of increasing severity as the polyunsaturated content of the mixed dietary fat was increased, whether measured as tumour incidence, tumour multiplicity, progression of benign tumours to squamous cell carcinoma, or reduced survival. At the termination of the study approximately 6 months following the completion of the 10-week chronic UV irradiation treatment, when most mice bore tumours, the contact hypersensitivity (CHS) reactions in those groups supporting the highest tumour leads (fed 15% or 20% polyunsaturated fat), were significantly suppressed in comparison with the mice bearing smaller tumour loads (fed 0, 5% or 10% polyunsaturated fat). When mice were exposed acutely to UV radiation (UVR), a diet of 20% saturated fat provided almost complete protection from the suppression of CHS, whereas feeding 20% polyunsaturated fat resulted in 57% suppression; the CHS of unirradiated mice was unaffected by the nature of the dietary fat. These results suggest that the enhancement of photocarcinogenesis by the dietary polyunsaturated fat component is mediated by an induced predisposition to persistent immunosuppression caused by the chronic UV irradiation, and supports the evidence for an immunological role in dietary fat modulation of photocarcinogenesis in mice.

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Bilaga 15
Vol.3 Suppl.1 20-25, 1996
Protection from ultraviolet radiation pathology by topical and systemic agents

Vivienne E REEVE Ranald B COPE Meira BOSNIC Caroline KERR Christa BOEHM-WILCOX

Department of Veterinary Pathology, University of Sydney, NSW 2006, Australia

Correspondent : Reeve V E

The immunosuppression induced by UV radiation, which is mediated in part by the formation in the UV-irradiated epidermis of cis-urocanic acid, has been postulated to be a prerequisite for the promotion phase of photocarcinogenesis. A number of systemic factors have been demonstrated in our laboratory to provide protection both from photoimmunosuppression or exogenous cisurocanic acid-induced immunosuppression, and from photocarcinogenesis in mice, thus supporting the fundamental hypothesis. These include the H2 histamine receptor antagonist, cimetidine; the dipeptide carnosine beta-alanylhistidine) ; saturated dietary fats, such as hydrogenated sunflower oil or butter, compared with polyunsaturated dietary fats such as sunfiower oil or margarine ; and the nonsteroidal antiinflammatory drug, indomethacin. On the other hand, topical sunscreens have been demonstrated to protect from photocarcinogenesis in mice under certain limited experimental conditions, but there is controversy concerning their ability to protect from photoimmunosuppression, and a demonstrated lack of correlation with their prevention of cisurocanic acid formation in mouse skin. It will be shown that the immunoprotective capacity of topical UVB-absorbers in sunscreens appears to be unrelated to their anti-erythema capacity, and to depend on their chemical nature. There is thus lack of understanding of the relationship between sunscreen exposure, immunity and photocarcinogenesis in the mouse, and of the significance of these observations to sunlight exposure through sunscreens in humans.
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1: J Nutr 1996 Mar;126(3):681-92 Related Articles, Books, LinkOut

Dietary butter protects against ultraviolet radiation-induced suppression of contact hypersensitivity in Skh:HR-1 hairless mice.

Cope RB, Bosnic M, Boehm-Wilcox C, Mohr D, Reeve VE.

Department of Veterinary Pathology, University of Sydney, New South Wales, Australia.

Polyunsaturated fatty acids may impair blood glucose control in type 2 diabetic patients.

Vessby B, Karlstrom B, Boberg M, Lithell H, Berne C

Department of Geriatrics, Uppsala University, Sweden.

Fifteen patients with Type 2 diabetes were given two diets rich in either saturated fat or polyunsaturated fat in alternate order over two consecutive 3-week periods on a metabolic ward. Both diets contained the same amount of fat, protein, carbohydrates, dietary fibre, and cholesterol. The proportions of saturated, monounsaturated and polyunsaturated fatty acids in the saturated fat diet were 16, 10, and 5%-energy and in the polyunsaturated fat diet (PUFA) 9, 10, and 12%-energy. The PUFA diet contained a high proportion of n-3 fatty acids. Metabolic control improved significantly in both dietary periods, due to both qualitative dietary changes and a negative energy balance. The serum lipoprotein concentrations decreased on both diets but the serum lipids were significantly lower after the PUFA diet (serum triglycerides -20%, p = 0.001; serum cholesterol -5%, p = 0.03; VLDL-triglycerides -29%, p less than 0.001; and VLDL-cholesterol -31%, p = 0.001) than after the saturated fat diet. Average blood glucose concentrations during the third week were significantly higher fasting (+15%, p less than 0.01), and during the day at 1100 h (+18%, p less than 0.001) and 1500 h (+17%, p = 0.002) on PUFA than on the saturated fat diet. Significantly higher blood glucose levels were also recorded with a standard breakfast, while the sum of the insulin values was lower (-19%, p = 0.01). HbA1c did not differ significantly between the two dietary periods.

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THE LANCET VOL 341: APRIL 24, 1993

SIR, - There seem to be three possible explanations for Professor Willet and colleagues findings, First, trans fatty acids, as previously shown, result in an increase in total or low-density-lipoprotein cholesterol, or possibly, a small decrease in high-densitylipoprotein (HDL) cholesterol similar to saturated fatty acids; second, they have an independent effect on the risk of cardiovascular disease; and third, trans fatty acid intake is a marker for other nutrients or behavioural characteristics that are associated with the risk of coronary heart disease. The Nurses Study provides no independent measurements of blood lipoprotein concentrations, blood pressure, or other risk factors. Thus, the relation between the trans fatty acids and risk factors related to cardiovascular disease could not be measured.

We have analysed the relation between reported margarine intake and risk factors among 540 premenopausal women at baseline in the Healthy Women Study. Dietary information was obtained from food frequency and 24 h recall. Frequent users were defined as having margarine four or more times per week (n= 259, 48 %). Frequent users weighed about 2,3 kg more (p=0,05) than infrequent users; they had significantly lower HDL2 cholesterol (0,53 vs 0,59 mmol/L) and lower total HDL cholesterol concentrations. They also had higher total cholesterol (4,84 vs 4,71 mmol/L; p=0,07); higher triglyceride (0,99 vs 0,90 mmol/L; p=0,04); and higher apo B (l,75 vs 1,66 mikromol/L; P = 0,04); and the log of 2 h blood insulin after glucose load was also higher (0,31 vs 0,28 nmol/L). Despite the fact that margarine consumers weighed over 2 kg more than infrequent consumers, they reported roughly the same caloric intake (1700 calories) and similar levels of physical activity. The Nurse Study had previously reported only 1200 -1400 calorie intakes for similarly aged women
The food frequency questionnaire, as used in the Nurses and other studies, provides a poor estimate of individual dietary intake of fat and specific fats or caloric intake. There is a substantial
underestimation of caloric intake compared with body size. The Nurses Study previously noted that the mean fat intake (75g) was the same for nurses with body mass index (BMI) of 21 or more and for those with BMI of 29 or more. It is highly unlikely that this difference is attributable to exercise. We suspect that most of the missing calories are fat calories. It is obvious that women who consume more margarine; baked goods, and cookies, are eating more fat, have higher saturated fat calories, are probably fatter; and, obviously, are consuming more trans fatty acids.
Without better dietary data and risk factor measurements, it cannot be determined in the Nurses Study whether there is causal link between trans fatty acids and cardiovascular risk factors. Second, - because there are no measurements of the other cardiovascular risk factors, whether the trans fatty acids have an independent effect on cardiovascular disease cannot be established. Third, because of the weakness of the instrument in measuring dietary intake, it is impossible to determine whether the results are related to trans fatty acids or some other measures of dietary intake.

Department of Epidemiology
Graduate School of Public Healt
University of Pittsburgh
Pittsburgh, Pennsylvania 15261, USA
Lewis H. Kuller

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Free Radic Biol Med 1994 Oct;17(4):367-72 Related Articles, Books

Is insulin resistance influenced by dietary linoleic acid and trans fatty acids?

Simopoulos AP.

Center for Genetics, Nutrition and Health, Washington, DC.

The incidence of obesity, noninsulin-dependent diabetes mellitus (NIDDM), hypertension, and coronary artery disease has increased in the developed world. At the same time, major changes in the type and amount of fatty acid intake have occurred over the past 40-50 years, reflected in increases in saturated fat (from both animal sources and hydrogenated vegetable sources), trans fatty acids, vegetable oils rich in linoleic acid, and an overall decrease in long chain polyunsaturated fatty acids (arachidonic acid, eicosapentaenoic acid, and docosahexaenoic acid--C20-C22). Recent findings that C20-C22 in muscle membrane phospholipids are inversely related to insulin resistance, whereas linoleic acid is positively related to insulin resistance, suggest that diet may influence the development of insulin resistance in obesity, insulin-dependent diabetes mellitus (IDDM), hypertension, and coronary artery disease (including asymptomatic atherosclerosis and microvascular angina). These conditions are known to have genetic determinants and have a common abnormality in smooth muscle response and insulin resistance. It is proposed that the current diet influences the expression of insulin resistance in those who are genetically predisposed. Therefore, clinical investigations are needed to evaluate if lowering or preventing insulin resistance through diet by increasing arachidonic acid, eicosapentaenoic acid, and docosahexaenoic acid, while lowering linoleic acid and decreasing trans fatty acids from the diet, will modify or prevent the development of these diseases.

Lancet 1994 May 21;343(8908):1268-71 Related Articles, Books, LinkOut
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Metabolic consequences of dietary trans fatty acids.

Mann GV.

The epidemic of coronary heart disease in the western world followed the introduction of partially hydrogenated fats in food. Exposure to trans fatty acids (TFA) in those foods can explain the observed sex and age differences in serum cholesterol concentrations and coronary heart disease (CHD), the cholesterolaemic response to pregnancy, and national differences in rates of CHD. There is evidence that TFA can be innocuously used for muscular work. I propose that the TFA in partially hydrogenated fats impair lipoprotein receptors during energy surfeit, leading to hypercholesterolaemia, atherogenesis, obesity, and insulin resistance. A series of feasible experiments is proposed to examine this hypothesis.

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J. Nutr. Biochem., 1990, vol. 1, April

Dietary trans fatty acids modulate erythrocyte membrane fatty acyl composition and insulin binding in monkeys

Dennis E. Barnard, (1,2) Joseph Sampugna, (1) Elliott Berlin, (3) Sam J. Bhathena, (3) and Joseph J. Knapka (2)

(1) Department of Chemistry and Biochemistry, University of Maryland, College Park, MD, USA
(2) Veterinary Resources Branch, Division of Research Services National Institutes of Health, U.S.
Department of Health and Human Services Bethesda MD, USA
(3) Beltsville Human Nutrition Research Center, Agricultural Research Service, U.S. Department
of Agriculture, Beltsville, MD, USA

The substitution of trans- for half of the cis-monounsaturated fatty acids in the diet of Macaca fasicularis monkeys resulted in alterations in erythrocyte fatty acid composition and insulin receptor properties but not in membrane fluidity. Both cis and trans diets contained 10% fat and similar fatty acid compositions, except that approximately 50% of the cis-octadecenoate (c-18:1) in the cis diet was replaced with trans-octadecenoate isomers (t-l8:1) in the trans diet. Compared with the cis diet, the trans diet resulted in the incorporation of approximately 11 % t-18:1, an approximately 16 % decrease in total saturated fatty acids, and an approximately 20 % increase in 18: 2(n-6) in erythrocyte membrane lipids. The increase in 18:2(n-6) may reflect on homeostatic mechanisms designed to maintain overall membrane fluidity, as no diet-related changes in fluidity were observed with diphenylhexatriene steady state fluorescence polarization. Values observed for insulin binding and insulin receptor number were higher and binding affinity was lower in monkeys fed the cis diet. In the absence of an effect on overall membrane fluidity, altered receptor activity suggests that insulin receptor activity is dynamic, requiring specific, fluid membrane subdomains or highly specific fatty acid-protein interactions.

Keywords: trans Fatty acids: insulin binding: membrane fluidity

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Belury, M.A., A. Mahon, and L. Shi. Role of conjugated linoleic acid (CLA) in the management of type 2 diabetes: Evidence from Zucker diabetic (fa/fa) rats and human subjects (Abstract AGFD 26). American Chemical Society 220th National Meeting. August 20-24. Washington, D.C.
(Se även Science News, March 3, 2001; Vol. 159, No. 9)

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Trans Fatty Acid Consumption May Increase Risk for Type 2 Diabetes

Salmerón, Jorge, et al. Dietary fat intake and risk of type 2 diabetes in women. Am J Clin Nutr 2001;73:1019-26.

Salmerón et al. studied the relationship between the consumption of saturated or unsaturated fats and the onset of type 2 diabetes. The 84,000 women subjects from the Nurse's Health Studies were aged 35-59 years old at the inception of the study in 1980. Over the 14-year course of the study, 2,507 cases of type 2 diabetes were diagnosed. Neither total fat intake nor saturated fat intake was associated with the incidence of diabetes, but high consumption of trans fatty acids strongly increased the risk for the disease. The authors estimate that replacement of 2% of calories in the American diet represented by trans fatty acids with similar amounts of calories as polyunsaturated fats could result in a 40% reduction in the incidence of type 2 diabetes. In an accompanying editorial, Clandinin and Wilke cautioned against extrapolating the results from this large population study to individuals, especially since trans fatty acids represent a relatively small part of the American diet.

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1: J Indian Med Assoc 1998 Oct;96(10):304-7 Related Articles, Books, LinkOut

Choice of cooking oils--myths and realities.

Sircar S, Kansra U.

Department of Medicine, Safdarjang Hospital, New Delhi.

In contrast to earlier epidemiologic studies showing a low prevalence of atherosclerotic heart disease (AHD) and type-2 dependent diabetes mellitus (Type-2 DM) in the Indian subcontinent, over the recent years, there has been an alarming increase in the prevalence of these diseases in Indians--both abroad and at home, attributable to increased dietary fat intake. Replacing the traditional cooking fats condemned to be atherogenic, with refined vegetable oils promoted as "heart-friendly" because of their polyunsaturated fatty acid (PUFA) content, unfortunately, has not been able to curtail this trend. Current data on dietary fats indicate that it is not just the presence of PUFA but the type of PUFA that is important--a high PUFA n-6 content and high n-6/n-3 ratio in dietary fats being atherogenic and diabetogenic. The newer "heart-friendly" oils like sunflower or safflower oils possess this undesirable PUFA content and there are numerous research data now available to indicate that the sole use or excess intake of these newer vegetable oils are actually detrimental to health and switching to a combination of different types of fats including the traditional cooking fats like ghee, coconut oil and mustard oil would actually reduce the risk of dyslipidaemias, AHD and Type-2 DM.

Margarine is healthy?? Yes of course, and pigs have wings.

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