Potential Safety Issues With Combined Use of Dietary Supplements and Medication – Focus on Interactions

The use of dietary supplements (DS) is widespread and tends to increase with age and female gender. DS use can in some situations represent a safety risk for patients. For instance, concomitant use of medication and dietary supplements, particularly herbal remedies, may cause clinically significant pharmacological interactions. The study underlying this chapter aimed to investigate the prevalence of potentially clinically significant DS-medication interactions in a general population of middle-aged women. The study is a questionnaire survey among Norwegian women born between 1943 and 1957. Data were collected from 2002 to 2006 as a part of the Norwegian Women and Cancer study (NOWAC). The participants listed all medications and all DS they had used during the previous week. The reported DS were checked for interaction potential in combination with medication, using the Natural Medicines database. The study population comprised 3,970 women, of whom 1,885 combined medication and dietary supplements. Overall, 630 (16% of the total population) used a DS-medication combination with a potential for at least one clinically significant interaction. Of these, 132 women used herb-medication combinations, 63 used combination(s) that represented more than two interactions, and three used combinations classified as a major health risk. There is considerable potential for clinically significant medication-supplement interactions in a general population such as the one described in the study. Although few of the identified interactions represent a major health risk, the findings indicate that health personnel should take supplements into account when assessing the safety of medication use among their patients

Sex hormones and gene expression signatures in peripheral blood from postmenopausal women - the NOWAC postgenome study

<p>Abstract</p> <p>Background</p> <p>Postmenopausal hormone therapy (HT) influences endogenous hormone concentrations and increases the risk of breast cancer. Gene expression profiling may reveal the mechanisms behind this relationship.</p> <p>Our objective was to explore potential associations between sex hormones and gene expression in whole blood from a population-based, random sample of postmenopausal women</p> <p>Methods</p> <p>Gene expression, as measured by the Applied Biosystems microarray platform, was compared between hormone therapy (HT) users and non-users and between high and low hormone plasma concentrations using both gene-wise analysis and gene set analysis. Gene sets found to be associated with HT use were further analysed for enrichment in functional clusters and network predictions. The gene expression matrix included 285 samples and 16185 probes and was adjusted for significant technical variables.</p> <p>Results</p> <p>Gene-wise analysis revealed several genes significantly associated with different types of HT use. The functional cluster analyses provided limited information on these genes. Gene set analysis revealed 22 gene sets that were enriched between high and low estradiol concentration (HT-users excluded). Among these were seven oestrogen related gene sets, including our gene list associated with systemic estradiol use, which thereby represents a novel oestrogen signature. Seven gene sets were related to immune response. Among the 15 gene sets enriched for progesterone, 11 overlapped with estradiol. No significant gene expression patterns were found for testosterone, follicle stimulating hormone (FSH) or sex hormone binding globulin (SHBG).</p> <p>Conclusions</p> <p>Distinct gene expression patterns associated with sex hormones are detectable in a random group of postmenopausal women, as demonstrated by the finding of a novel oestrogen signature.</p

Internet Use for Obtaining Medicine Information: Cross-sectional Survey

Background: The internet is increasingly being used as a source of medicine-related information. People want information to facilitate decision-making and self-management, and they tend to prefer the internet for ease of access. However, it is widely acknowledged that the quality of web-based information varies. Poor interpretation of medicine information can lead to anxiety and poor adherence to drug therapy. It is therefore important to understand how people search, select, and trust medicine information. Objective: The objectives of this study were to establish the extent of internet use for seeking medicine information among Norwegian pharmacy customers, analyze factors associated with internet use, and investigate the level of trust in different sources and websites. Methods: This is a cross-sectional study with a convenience sample of pharmacy customers recruited from all but one community pharmacy in Tromsø, a medium size municipality in Norway (77,000 inhabitants). Persons (aged ≥16 years) able to complete a questionnaire in Norwegian were asked to participate in the study. The recruitment took place in September and October 2020. Due to COVID-19 restrictions, social media was also used to recruit medicine users. Results: A total of 303 respondents reported which sources they used to obtain information about their medicines (both prescription and over the counter) and to what extent they trusted these sources. A total of 125 (41.3%) respondents used the internet for medicine information, and the only factor associated with internet use was age. The odds of using the internet declined by 5% per year of age (odds ratio 0.95, 95% CI 0.94-0.97; P=.048). We found no association between internet use and gender, level of education, or regular medicine use. The main purpose reported for using the internet was to obtain information about side effects. Other main sources of medicine information were physicians (n=191, 63%), pharmacy personnel (n=142, 47%), and medication package leaflets (n=124, 42%), while 36 (12%) respondents did not obtain medicine information from any sources. Note that 272 (91%) respondents trusted health professionals as a source of medicine information, whereas 58 (46%) respondents who used the internet trusted the information they found on the internet. The most reliable websites were the national health portals and other official health information sites. Conclusions: Norwegian pharmacy customers use the internet as a source of medicine information, but most still obtain medicine information from health professionals and packet leaflets. People are aware of the potential for misinformation on websites, and they mainly trust high-quality sites run by health authorities

Plasma Fatty Acid Ratios Affect Blood Gene Expression Profiles - A Cross-Sectional Study of the Norwegian Women and Cancer Post-Genome Cohort

This paper is part of Karina Standahl Olsen's doctoral thesis, available in Munin at http://hdl.handle.net/10037/5442High blood concentrations of n-6 fatty acids (FAs) relative to n-3 FAs may lead to a “physiological switch” towards permanent low-grade inflammation, potentially influencing the onset of cardiovascular and inflammatory diseases, as well as cancer. To explore the potential effects of FA ratios prior to disease onset, we measured blood gene expression profiles and plasma FA ratios (linoleic acid/alpha-linolenic acid, LA/ALA; arachidonic acid/eicosapentaenoic acid, AA/EPA; and total n-6/n-3) in a cross-section of middle-aged Norwegian women (n = 227). After arranging samples from the highest values to the lowest for all three FA ratios (LA/ALA, AA/EPA and total n-6/n-3), the highest and lowest deciles of samples were compared. Differences in gene expression profiles were assessed by single-gene and pathway-level analyses. The LA/ALA ratio had the largest impact on gene expression profiles, with 135 differentially expressed genes, followed by the total n-6/n-3 ratio (125 genes) and the AA/EPA ratio (72 genes). All FA ratios were associated with genes related to immune processes, with a tendency for increased pro-inflammatory signaling in the highest FA ratio deciles. Lipid metabolism related to peroxisome proliferator-activated receptor γ (PPARγ) signaling was modified, with possible implications for foam cell formation and development of cardiovascular diseases. We identified higher expression levels of several autophagy marker genes, mainly in the lowest LA/ALA decile. This finding may point to the regulation of autophagy as a novel aspect of FA biology which warrants further study. Lastly, all FA ratios were associated with gene sets that included targets of specific microRNAs, and gene sets containing common promoter motifs that did not match any known transcription factors. We conclude that plasma FA ratios are associated with differences in blood gene expression profiles in this free-living population, and that affected genes and pathways may influence the onset and progression of disease

Hormone replacement therapy use and plasma levels of sex hormones in the Norwegian Women and Cancer Postgenome Cohort – a cross-sectional analysis

<p>Abstract</p> <p>Background</p> <p>Hormone replacement therapy use (HRT) is associated with increased breast cancer risk. Our primary objective was to explore hormone levels in plasma according to HRT use, body mass index (BMI) and menopausal status. A secondary objective was to validate self-reported questionnaire information on menstruation and HRT use in the Norwegian Women and Cancer postgenome cohort (NOWAC).</p> <p>Methods</p> <p>We conducted a cross-sectional study of sex hormone levels among 445 women aged 48–62 who answered an eight-page questionnaire in 2004 and agreed to donate a blood sample. The samples were drawn at the women's local general physician's offices in the spring of 2005 and sent by mail to NOWAC, Tromsø, together with a two-page questionnaire. Plasma levels of sex hormones and Sex Hormone Binding Globulin (SHBG) were measured by immunometry. 20 samples were excluded, leaving 425 hormone measurements.</p> <p>Results</p> <p>20% of postmenopausal women were HRT users. The plasma levels of estradiol (E₂) increased with an increased E₂dose, and use of systemic E₂-containing HRT suppressed the level of Follicle Stimulating Hormone (FSH). SHBG levels increased mainly among users of oral E₂preparations. Vaginal E₂application did not influence hormone levels. There was no difference in BMI between HRT users and non-users. Increased BMI was associated with increased E₂and decreased FSH and SHBG levels among non-users. Menopausal status defined by the two-page questionnaire showed 92% sensitivity (95% CI 89–96%) and 73% specificity (95% CI 64–82%), while the eight-page questionnaire showed 88% sensitivity (95% CI 84–92%) and 87% specificity (95% CI 80–94%). Current HRT use showed 100% specificity and 88% of the HRT-users had plasma E₂levels above the 95% CI of non-users.</p> <p>Conclusion</p> <p>Users of systemic E₂-containing HRT preparations have plasma E₂and FSH levels comparable to premenopausal women. BMI has an influence on hormone levels among non-users. NOWAC questionnaires provide valid information on current HRT use and menopausal status among Norwegian women who are between 48 and 62 years old.</p

Dietary supplement user patterns among Norwegian middle-aged women

Source at http://www.ntfe.no/i/2019/1/tfe-2019-01b-25. Journal home page at http://www.ntfe.no/.Formål - Å beskrive forbruksmønsteret av kosttilskudd blant middelaldrende norske kvinner med tanke på sammenheng med brukerkarakteristika, inkludert legemiddelbruk og sosioøkonomiske faktorer. Metode - Studien er en tverrsnittsanalyse av spørreskjemadata fra 3231 deltakere (født 1943-57) i Kvinner og kreftstudien. Data ble innsamlet i 2003-2006, responsrate 72 %. Resultat - Prevalensen av kosttilskuddbruk (bruk siste uke) var 71 % (2297 av 3231 kvinner), mens 48 % brukte kosttilskudd og legemidler samtidig. Omega-3 og vitaminer/mineraler var de mest brukte kosttilskuddkategoriene. Blant kosttilskuddbrukerne var det 60 % som brukte mer enn ett produkt mens 12 % brukte fire eller flere. Bruk var assosiert med høyere alder, utdanning og inntekt, samt legemiddelbruk og markører for sunn livsstil (fysisk aktivitet, lav kroppsmasseindeks, ikke-røyker). Tilsvarende sammenheng ble også funnet for omfang av bruk (antall rapporterte produkter). Sammenhengen legemiddel-kosttilskuddbruk skyldtes hovedsakelig høyt kosttilskuddbruk blant kvinner som tok legemidler for mindre alvorlige lidelser samt for muskel/ledd/smerte og hjertekarsykdom. Konklusjon - Det er omfattende bruk av kosttilskudd blant middelaldrende norske kvinner. Kosttilskuddbruk er assosiert med utdanning, livsstils- og helserelaterte faktorer, inkludert legemiddelbruk. Sistnevnte er et risikomoment som helsepersonell bør være oppmerksomme på.Background - Our study describes characteristics of DS use among middle-aged Norwegian, including medication use and socioeconomic factors. Material and methods - This is a cross-sectional analysis of questionnaire data from 3231 women (born 1943-57) from the Norwegian Women and Cancer study, data collected in 2003-2006, response rate 72%. Results - The prevalence of DS use (during past week) was 71% (2297 of 3231 women), while 48% used dietary supplement and medication concurrently. Omega-3 and vitamin/minerals were the most frequent categories. Among users, 60% used more than one supplement and 12 % used four or more. Use was associated with higher age, education, income, medication use and markers of a healthy lifestyle (physical activity, lower body mass index, non-smoking). Similar associations were found for extent of DS use (number of products). The association between medication and supplement use was primarily due to high supplement use among women taking medication for less serious disorders and for muscle/joint/pain and cardiovascular disease. Interpretation - Dietary supplements were extensively used among middle-aged Norwegian women. Use was associated with socioeconomic, lifestyle and health-related factors, including medication use which implies a risk that health personnel should be aware of

Self-reported medication use among coronary heart disease patients showed high validity compared with dispensing data

Objective - To validate self-reported use of medications for secondary prevention of coronary heart disease (CHD) in a population-based health study by comparing self-report with pharmacy dispensing data, and explore different methods for defining medication use in prescription databases. Study design and setting - Self-reported medication use among participants with CHD (n = 1483) from the seventh wave of the Tromsø Study was linked with the Norwegian Prescription Database (NorPD). Cohen’s kappa, sensitivity, specificity, and positive and negative predictive values were calculated, using NorPD as the reference standard. Medication use in NorPD was defined in three ways; fixed-time window of 180 days, and legend-time method assuming a daily dose of one dosage unit or one defined daily dose (DDD). Results - Kappa-values for antihypertensive drugs, lipid-lowering drugs and acetylsalicylic acid all showed substantial agreement (kappa ≥0.61). Validity varied depending on the method used for defining medication use in NorPD. Applying a fixed-time window gave higher agreement, positive predictive values and specificity compared with the legend-time methods. Conclusion - Self-reported use of medication for secondary prevention of CHD shows high validity when compared with pharmacy dispensing data. For CHD medications, fixed-time window appears to be the most appropriate method for defining medication use in prescription databases

Self-reported medication information needs among medication users in a general population aged 40 years and above – the Tromsø study

Purpose: To determine the prevalence and associated factors of self-reported medication information needs among medication users in a general population aged 40 years and above – The Tromsø Study. Methods: Cross-sectional study of medication users (n=10,231) among participants in the Tromsø Study, a descriptive analysis of questionnaire data and multivariable logistic regression (n=9,194). Results: Sixteen percent of medication users expressed a need for more information about own medications. Overall, medication users agreed to a higher degree to have received information from the GP compared to the pharmacy. Concerned medication users and those disagreeing to have received information about side effects had the highest odds for needing more information (OR 5.07, 95% CI 4.43–5.81) and (OR 2.21, 95% CI 1.83–2.68), respectively. Medication users who used heart medications (e.g., nitroglycerin, antiarrhythmics, anticoagulants) (OR 1.71, 95% CI 1.46–2.01), medication for hypothyroidism (OR 1.36, 95% CI 1.13–1.64) or had moderately health anxiety had expressed need for medication information. Whereas medication users with lower education, those that never used internet to search for health advice, and medication users who disagreed to have received information about reason for-use were associated with lower odds (OR 0.75, 95% CI 0.62–0.91), (OR 0.85, 95% CI 0.74–0.98) and (OR 0.68, 95% CI 0.53–0.88), respectively. Conclusion: This study demonstrated that there is need for more information about own medications in a general population aged 40 years and above and shed light on several characteristics of medication users with expressed information need which is important when tailoring the right information to the right person

Menstrual factors, reproductive history, hormone use, and Urothelial carcinoma risk: A prospective study in the EPIC cohort

Background: Urothelial carcinoma (UC) is the predominant (95%) bladder cancer subtype in industrialised nations. Animal and epidemiological human studies suggest that hormonal factors may influence UC risk. Methods: We used an analytic cohort of 333,919 women from the European Prospective Investigation into Cancer and Nutrition Cohort (EPIC). Associations between hormonal factors and incident UC (overall and by tumour grade, by tumour aggressiveness, and by non-muscle invasive UC) risk were evaluated using Cox proportional hazards models. All models were stratified by age at recruitment and study centre, and adjusted for smoking status and intensity, and fruit and vegetable intakes. Results: During a mean of 15 years of follow-up, 529 women developed UC. In a model including number of full-term pregnancies (FTP), menopausal status, and menopausal hormone therapy (MHT) showed an inverse association between, number of FTP was inversely associated with UC risk (HR≥5vs1=0.48, 0.25-0.90; P-trend in parous women=0.010) and MHT-use (compared to non-use) was positively associated with UC risk (HR=1.27, 1.03-1.57), but no dose-response by years of MHT-use was observed. No modification of HRs by smoking status was observed. Finally, sensitivity analysis in never-smokers showed similar HR patterns for number of FTP and no association between MHT-use and UC risk. Association between MHT-use and UC risk only remained significant in current-smokers. No heterogeneity of the risk estimations in the final model was observed by tumour aggressiveness or by tumour grade. A positive association between the MTH-use and non-muscle invasive UC risk was observed. Conclusion: Increasing number of FTP may reduce UC risk. Our results provided limited evidence for a role of MHT-use in UC risk due to residual confounding by tobacco. Impact: More detailed studies on parity are needed to understand the possible effects of perinatal hormone changes in urothelial cells