No increase in risk of hip fracture at high serum retinol concentrations in community-dwelling older Norwegians: the Norwegian Epidemiologic Osteoporosis Studies.

BACKGROUND: Norway has the highest hip fracture rates worldwide and a relatively high vitamin A intake. Increased fracture risk at high intakes and serum concentrations of retinol (s-retinol) have been observed in epidemiologic studies. OBJECTIVE: We aimed to study the association between s-retinol and hip fracture and whether high s-retinol may counteract a preventive effect of vitamin D. DESIGN: We conducted the largest prospective analysis of serum retinol and hip fracture to date in 21,774 men and women aged 65-79 y (mean age: 72 y) who attended 4 community-based health studies during 1994-2001. Incident hip fractures occurring up to 10.7 y after baseline were retrieved from electronic hospital discharge registers. Retinol determined by high-pressure liquid chromatography with ultraviolet detection in stored serum was available in 1154 incident hip fracture cases with valid body mass index (BMI) data and in a subcohort defined as a sex-stratified random sample (n = 1418). Cox proportional hazards regression weighted according to the stratified case-cohort design was performed. RESULTS: There was a modest increased risk of hip fracture in the lowest compared with the middle quintile of s-retinol (HR: 1.41; 95% CI: 1.09, 1.82) adjusted for sex and study center. The association was attenuated after adjustment for BMI and serum concentrations of α-tocopherol (HR: 1.16; 95% CI: 0.88, 1.51). We found no increased risk in the upper compared with the middle quintile. No significant interaction between serum concentrations of 25-hydroxyvitamin D and s-retinol on hip fracture was observed (P = 0.68). CONCLUSIONS: We found no evidence of an adverse effect of high serum retinol on hip fracture or any interaction between retinol and 25-hydroxyvitamin D. If anything, there tended to be an increased risk at low retinol concentrations, which was attenuated after control for confounders. We propose that cod liver oil, a commonly used food supplement in Norway, should not be discouraged as a natural source of vitamin D for fracture prevention.

Cod liver oil intake and incidence of asthma in Norwegian adults--the HUNT study.

BACKGROUND: Cod liver oil is an important source of vitamin D, but also contains other fat-soluble components such as vitamin A. Before 1999, the cod liver oil formula in Norway contained a high concentration of vitamin A (1000 µg per 5 ml). High vitamin A status is associated with increased risks of several chronic diseases. OBJECTIVE: To investigate the association between cod liver oil intake and asthma development. METHODS: In the Nord-Trøndelag Health Study, a total of 25 616 Norwegian adults aged 19-55 years were followed up from 1995-1997 to 2006-2008. Current analysis based on 17 528 subjects who were free of asthma and had complete information on cod liver oil intake at baseline. Cod liver oil intake was defined as daily intake ≥ 1 month during the year prior to baseline. Incident asthma was reported as new-onset asthma during the 11-year follow-up. RESULTS: Of the 17 528 subjects, 18% (n=3076) consumed cod liver oil daily for ≥ 1 month over the past year. Cod liver oil intake was significantly associated with incident asthma with an OR of 1.62 (95% CI 1.32 to 1.98) after adjustment for age, sex, daily smoking, physical activity, education, socio-economic status, family history of asthma, and body mass index (BMI). The positive association was consistent across age (< 40/≥ 40 years), sex (men/women), family history of asthma (yes/no) and BMI subgroups (< 25/≥ 25 kg/m(2)). CONCLUSIONS: Intake of cod liver oil with high vitamin A content was significantly associated with increased incidence of adult-onset asthma.

Oxidised fish oil does not influence established markers of oxidative stress in healthy human subjects: a randomised controlled trial.

Intake of fish oil reduces the risk of CHD and CHD deaths. Marine n-3 fatty acids (FA) are susceptible to oxidation, but to our knowledge, the health effects of intake of oxidised fish oil have not previously been investigated in human subjects. The aim of the present study was to investigate markers of oxidative stress, lipid peroxidation and inflammation, and the level of plasma n-3 FA after intake of oxidised fish oil. In a double-blinded randomised controlled study, healthy subjects (aged 18-50 years, n 54) were assigned into one of three groups receiving capsules containing either 8 g/d of fish oil (1.6 g/d EPA+DHA; n 17), 8 g/d of oxidised fish oil (1.6 g/d EPA+DHA; n 18) or 8 g/d of high-oleic sunflower oil (n 19). Fasting blood and morning spot urine samples were collected at weeks 0, 3 and 7. No significant changes between the different groups were observed with regard to urinary 8-iso-PGF2α; plasma levels of 4-hydroxy-2-hexenal, 4-hydroxy-2-nonenal and α-tocopherol; serum high sensitive C-reactive protein; or activity of antioxidant enzymes in erythrocytes. A significant increase in plasma level of EPA+DHA was observed in both fish oil groups, but no significant difference was observed between the fish oil groups. No changes in a variety of in vivo markers of oxidative stress, lipid peroxidation or inflammation were observed after daily intake of oxidised fish oil for 3 or 7 weeks, indicating that intake of oxidised fish oil may not have unfavourable short-term effects in healthy human subjects.

A matrix assisted laser desorption ionization time-of-flight mass spectrometry investigation to assess the composition of cod liver oil based products which displayed a different in vivo allergenic power.

Cod liver oil is a well-known "nutraceutical", which contains a wide range of substances, including triacylglycerols (TAGs), mono- and di-acylglycerols, free fatty acids, vitamins and n-3 polyunsaturated fatty acids. Topically applied, cod liver oil contributes to faster wound healing and improvement in skin quality. We recently reported a case of allergic contact dermatitis to cod liver oil contained in a topical ointment, in whom the patch test reaction with the ointment containing cod liver oil at a concentration of 40% was stronger than the reaction induced by a pure cod liver oil at the same concentration. We hypothesized that the different reactivity could be explained by differences in composition of the two products. In order to verify this hypothesis, we assessed the composition of those products using a matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS). The results obtained showed that the spectra of the ointment and of the cod liver oil samples were very similar, even if a major number of peaks were observable in the higher mass range of the spectra relevant to the analysis of the ointment sample, that have been assigned to higher molecular weight TAGs. Our results suggest that the different reactivity to the two products could be due to differences in the amount of contained TAGs. TAGs may favor the penetration of the allergen(s) or may be the direct culprit substances, taking into account that TAGs have been reported to have sensitizing properties.

Relationship of fish and cod oil intake with adult asthma.

BACKGROUND: A diet rich in fish or cod oil might possibly reduce the risk for asthma and atopic diseases. However, previous studies show conflicting results and no studies have assessed the potential long-term effects of childhood fish intake on adult asthma. OBJECTIVE: To investigate whether childhood and adult fish and cod oil intake was related to adult asthma. METHODS: In a large population-based study, Respiratory Health in Northern Europe (RHINE), 16 187 subjects aged 23-54 years answered a postal questionnaire. The relations of fish and cod oil intake with asthma symptoms and asthma were analysed using multiple logistic and Cox regression analyses, with adjustment for gender, adult hayfever, smoking, age, body mass index, household size, dwelling, parental education and centre, and for maternal smoking and family history of hayfever and asthma in a subsample (n=2459). RESULTS: Subjects from Iceland and Norway reported much more frequent intake of fish both in childhood and adulthood as compared with subjects from Sweden, Estonia and Denmark. Current fish intake less than weekly in adults was associated with more asthma symptoms, while more frequent fish intake did not appear to decrease the risk further. No dose-response association was found between childhood fish intake and adult asthma, but those who never ate fish in childhood had an increased risk for asthma and earlier asthma onset. Adult consumption of cod oil had a u-shaped association with asthma, with the highest risks in those taking cod oil never and daily. CONCLUSION: A minimum level of weekly fish intake in adulthood was associated with protection against asthma symptoms in this large North-European multi-centre study. Subjects who never ate fish in childhood were at an increased risk for asthma. Both indicate a possible threshold effect of fish on asthma.

Relationship between high consumption of marine fatty acids in early pregnancy and hypertensive disorders in pregnancy.

OBJECTIVE: To investigate whether there is a relationship between maternal intake of cod-liver oil in early and late pregnancy and hypertensive disorders in pregnancy. DESIGN: An observational prospective study. SETTING: Free-living conditions in a community with traditional fish and cod-liver oil consumption. POPULATION: Four hundred and eighty-eight low-risk pregnant Icelandic women. METHODS: Maternal use of cod-liver oil, foods and other supplements was estimated with a semiquantitative food frequency questionnaire covering food intake together with lifestyle factors for the previous 3 months. Questionnaires were filled out twice, between 11 and 15 weeks of gestation and between 34 and 37 weeks of gestation. Supplements related to hypertensive disorders in pregnancy, i.e. gestational hypertension and pre-eclampsia, were presented, with logistic regression controlling for potential confounding. MAIN OUTCOME MEASURES: Gestational hypertension, pre-eclampsia, cod-liver oil and multivitamins. RESULTS: The odds ratio for developing hypertensive disorders in pregnancy for women consuming liquid cod-liver oil was 4.7 (95% CI 1.8-12.6, P= 0.002), after adjusting for confounding factors. By dividing the amount of n-3 long-chain polyunsaturated fatty acids (n-3 LCPUFA) into centiles, the odds ratio for hypertensive disorders across groups for n-3 LCPUFA suggested a u-shaped curve (P = 0.008). Similar results were found for gestational hypertension alone. Further, the use of multivitamin supplements without vitamins A and D in late pregnancy doubled the odds of hypertensive disorders (OR 2.4, 95% CI 1.0-5.4, P= 0.044). CONCLUSIONS: Consumption of high doses of n-3 LCPUFA in early pregnancy, or other nutrients found in liquid cod-liver oil, may increase the risk of developing hypertensive disorders in pregnancy.

Complimentary and alternative medicine use among patients starting warfarin.

The use of complimentary and alternative medicines (CAM) among the UK population is on the increase. For patients requiring warfarin therapy, it is important to maintain an adequate and safe level of anticoagulation. As some forms of CAM can interact with warfarin, it is imperative that any patient considered for warfarin, is asked about their use of CAM. Our report describes the incidence and type of CAM usage among patients about to start or recently commenced on warfarin therapy attending our outpatient anticoagulant clinic. All patients attending clinic for the first time were seen by a pharmacist. A retrospective analysis of the pharmaceutical care plans for all patients seen during 2003 were analysed regarding the degree of CAM usage. Of 631 care plans reviewed, 170 (26.9%) patients were taking some form of CAM. Ninety-nine (58% of all CAM users) were taking a CAM that could interact with warfarin; the commonest forms were cod-liver oil capsules and garlic capsules. We conclude that many patients new to warfarin therapy were significant users of CAM, many of which had the potential to interact with warfarin. By taking a full drug history, potential CAM/warfarin interactions could be avoided.

Diet and risk of cutaneous malignant melanoma: a prospective study of 50,757 Norwegian men and women.

The relationship between dietary habits and subsequent risk of cutaneous malignant melanoma (CMM) was studied in 25,708 men and 25,049 women aged 16-56 years attending a Norwegian health screening in 1977-1983. Linkage to the Cancer Registry of Norway and the Central Bureau of Statistics of Norway ensured a complete follow-up until December 31, 1992. Diet was recorded through a semi-quantitative food-frequency questionnaire at the time of screening, and 108 cases of CMM were identified during follow-up. Use of cod liver oil supplementation and intake of polyunsaturated fat were associated with significant increased risk and drinking coffee with significant decreased risk of CMM in women. Adjusting for height, body mass index, body surface area, education, smoking or occupational or recreational physical activity did not change the results. No significant association was found between the incidence of CMM and any of the dietary factors in men. Important aspects are residual confounding by sun exposure and social class, as well as concern with multiple comparisons.

[Clinical evaluation of aiconol side effects]. / Klinicheskaia otsenka pobochnykh éffektov preparata éikonol.

In the study of 164 patients with atherogenic dyslipidemia the authors studied side effects of aiconol, concentrated cod liver oil. Its lipid component contains not less than 18% of omega-3 polyunsaturated fatty acids (PUFA). All the patients were divided into 4 groups: 51 subjects of group 1 received aiconol in the form of oil, 35 subjects of group 2 had protein dietetic caviar prepared from animal proteins with addition of 3% aiconol, 38 subjects of group 3 were given protein-oil emulsion containing 20% aiconol and 40 patients of group 4 took gelatin aiconol in capsules. Side effects of the above food ingredients enriched with omega-3 PUFA were found to be of metabolic nature. These manifested most evidently in patients on oil aiconol incorporating both maximal doses of omega-3 PUFA and the largest amounts of inert constituents acting as additional fat load on the liver and pancreas. Group 1 patients also suffered from aggravated chronic gastrointestinal, hepatic and pancreatic disorders. Because of reduced quantities of omega-3 PUFA in the diets of group 2, 3 and 4 patients, they displayed much less severe side effects.

[Contaminating substances in 22 over-the-counter fish oil and cod liver oil preparations: cholesterol, heavy metals and vitamin A]. / Begleitende Inhaltsstoffe in 22 OTC-Fischöl- und Lebertranpräparaten: Cholesterin, Schwermetalle und Vitamin A.

Fish oil capsules are increasingly used by self-medicating patients. We studied 22 commercial fish oil and menhaden oil preparations in respect to accompanying substances that could be harmful. The substances measured were: cholesterol as determined by gas liquid chromatography, heavy metals measured by atomic absorption, and vitamin A as determined by high-performance liquid chromatography (HPLC). The contents of cholesterol and heavy metals were in ranges which can be regarded as negligible; the content of vitamin A in menhaden oils, however, was found in amounts which warrant that pregnant women do not exceed the dosage as recommended by the manufacturers.

Malondialdehyde excretion by subjects consuming cod liver oil vs a concentrate of n-3 fatty acids.

Urinary malondialdehyde (MDA), an indicator of lipid peroxidation in the diet and in the tissues, was determined in human adults consuming a supplement of n-3 fatty acids derived from a pharmaceutical grade of cod liver oil (CLO) without added antioxidants vs a concentrate of n-3 acids containing dodecyl gallate and vitamin E. MDA excretion increased immediately in the subjects consuming CLO but remained unchanged in those ingesting the concentrate for 50 days. The increase in the subjects taking CLO was attributable to MDA in the oil. The results indicate that consuming unstabilized fish oils as a source of n-3 fatty acids may entail exposure to potentially toxic products of lipid peroxidation.