The PlantLIBRA consumer survey: Findings on the use of plant food supplements in Italy.

BACKGROUND: Food supplements, and in particular those containing botanicals (plant food supplements, PFS), have in recent decades been of great interest both to consumers and to food/pharmaceutical industries. OBJECTIVES: The aim of this paper is to examine replies by Italian consumers to the PlantLIBRA consumers' survey in order to: 1) assess the behaviour of an Italian population with respect to the use of PFS, and to compare it with that of other 5 countries involved in the whole survey; 2) identify different habits in the 4 Italian cities selected according to their geographical distribution; 3) collect independent information on the actual intake of PFS and consumers' behaviour. SUBJECTS/SETTING: 397 Italian consumers enrolled, 187 males (49.5%) and 191 female (50.5%). The distribution of subjects among the 4 cities included was: Milan 99; Venice 90; Rome 96 and Catania 96. RESULTS: The interest in PFS in Italy is high, the prevalence of "regular" consumers being 22.7%. Some differences were observed between the 4 cities involved: the pattern of use during the year was specific to each city; consumers in Milan reported reasons to use PFS significantly different from those in the whole Italian sample and did not indicate supermarkets as an important place of purchase; respondents from Rome and Catania more frequently used family doctors and pharmacists as a source of recommendation. Some significant difference among cities, sex and age groups were observed when the most frequently used botanicals were ranked. CONCLUSIONS: The results provide new insights on the socio-economic characteristics and lifestyle of Italian PFS consumers, on their reasons for and pattern of use, and on their behaviour and expectations. The value of this information is not restricted to the specific country (Italy) but allows for a more general evaluation of the pattern of use, according to habits and geographical area.

Usage of Plant Food Supplements (PFS) for weight control in six European countries: results from the PlantLIBRA PFS Consumer Survey 2011-2012.

BACKGROUND: Obesity is increasing worldwide and weight-control strategies, including the consumption of plant food supplements (PFS), are proliferating. This article identifies the herbal ingredients in PFS consumed for weight control and by overweight/obese dieters in six European countries, and explores the relationship between their consumption and their self-reported BMI. METHODS: Data used were a subset from the PlantLIBRA PFS Consumer Survey 2011-2012, a retrospective survey of 2359 PFS consumers. The survey used a bespoke frequency-of-PFS-usage questionnaire. Analyses were performed in two consumer subsamples of 1) respondents taking the products for "body weight reasons", and 2) "dieters for overweight/obesity", to identify the herbal ingredients consumed for these reasons. The relationship between the 5 most consumed herbal ingredients and self-reported BMI in groups 1 and 2 is explored by comparing BMI proportions of consumers vs. non-consumers (using Chi-squared test). RESULTS: 252 PFS (8.8 %) were consumed for "body weight reasons" (by 240 PFS consumers); 112 PFS consumers (4.8 %) were "dieting for overweight/obesity". Spain is the country where consuming herbal ingredients for body weight control and dieting were most popular. Artichoke was the most consumed herbal ingredient. Considering only the 5 top products consumed by those who responded "body weight", when using the total survey sample, a greater proportion of BMI ≥ 25 was observed among consumers of PFS containing artichoke and green tea as compared to non-consumers (58.4 % vs. 49.1 % and 63.2 % vs. 49.7 % respectively). Considering only the 5 top products consumed by "dieters" and using only the "dieters" sample, a lower proportion of BMI ≥ 25 was observed among pineapple-containing PFS consumers (38.5 % vs. 81.5 %); however, when using the entire survey sample, a greater proportion of BMI ≥ 25 was observed among artichoke-containing PFS consumers (58.4 % vs. 49.1 %). CONCLUSIONS: A comparison of results among the scarce publications evaluating the use of weight-loss supplements at the population level is limited. Nevertheless every hint is important in finding out which are the self-treatment strategies used by overweight/obese individuals in European countries. Although limited by a small sample size, our study represents a first attempt at analysing such data in six EU countries. Our findings should encourage the conduction of further studies on this topic, long-term and large sample-sized studies, ideally conducted in the general population.

Adverse Effects of Plant Food Supplements Self-Reported by Consumers in the PlantLIBRA Survey Involving Six European Countries.

BACKGROUND: The use of food supplements containing botanicals is increasing in European markets. Although intended to maintain the health status, several cases of adverse effects to Plant Food Supplements (PFS) have been described. OBJECTIVES: To describe the self-reported adverse effects collected during the European PlantLIBRA PFS Consumer Survey 2011-2012, with a critical evaluation of the plausibility of the symptomatology reported using data from the literature and from the PlantLIBRA Poisons Centers' survey. SUBJECTS/SETTING: From the total sample of 2359 consumers involved in the consumers' survey, 82 subjects reported adverse effects due to a total of 87 PFS. RESULTS: Cases were self-reported, therefore causality was not classified on the basis of clinical evidence, but by using the frequency/strength of adverse effects described in scientific papers: 52 out of 87 cases were defined as possible (59.8%) and 4 as probable (4.6%). Considering the most frequently cited botanicals, eight cases were due to Valeriana officinalis (garden valerian); seven to Camellia sinensis (tea); six to Ginkgo biloba (Maidenhair tree) and Paullinia cupana (guarana). Most adverse events related to the gastrointestinal tract, nervous and cardiovascular systems. CONCLUSIONS: Comparing the data from this study with those published in scientific papers and obtained by the PlantLIBRA Poisons Centers' survey, some important conclusions can be drawn: severe adverse effects to PFS are quite rare, although mild or moderate adverse symptoms can be present. Data reported in this paper can help health professionals (and in particular family doctors) to become aware of possible new problems associated with the increasing use of food supplements containing botanicals.

Usage of plant food supplements across six European countries: findings from the PlantLIBRA consumer survey.

BACKGROUND: The popularity of botanical products is on the rise in Europe, with consumers using them to complement their diets or to maintain health, and products are taken in many different forms (e.g. teas, juices, herbal medicinal products, plant food supplements (PFS)). However there is a scarcity of data on the usage of such products at European level. OBJECTIVE: To provide an overview of the characteristics and usage patterns of PFS consumers in six European countries. DESIGN: Data on PFS usage were collected in a cross-sectional, retrospective survey of PFS consumers using a bespoke frequency of PFS usage questionnaire. SUBJECTS/SETTING: A total sample of 2359 adult PFS consumers from Finland, Germany, Italy, Romania, Spain and the United Kingdom. DATA ANALYSES: Descriptive analyses were conducted, with all data stratified by gender, age, and country. Absolute frequencies, percentages and 95% confidence intervals are reported. RESULTS: Overall, an estimated 18.8% of screened survey respondents used at least one PFS. Characteristics of PFS consumers included being older, well-educated, never having smoked and self-reporting health status as "good or very good". Across countries, 491 different botanicals were identified in the PFS products used, with Ginkgo biloba (Ginkgo), Oenothera biennis (Evening primrose) and Cynara scolymus (Artichoke) being most frequently reported; the most popular dose forms were capsules and pills/tablets. Most consumers used one product and half of all users took single-botanical products. Some results varied across countries. CONCLUSIONS: The PlantLIBRA consumer survey is unique in reporting on usage patterns of PFS consumers in six European countries. The survey highlights the complexity of measuring the intake of such products, particularly at pan-European level. Incorporating measures of the intake of botanicals in national dietary surveys would provide much-needed data for comprehensive risk and benefit assessments at the European level.

Bioequivalence of two omega-3 fatty acid ethyl ester formulations: a case of clinical pharmacology of dietary supplements.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: • Omega-3 fatty acids are dietary components, present in the body with variable blood concentrations. • Bioavailability evaluations of ethyl ester preparations are hampered by the difficulty in achieving similar concentrations of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in the preparations being compared. This may require questionable corrections for baseline concentrations. • If repeated doses are given, this may lead to errors because of variable dietary fish intake. If a single dose is selected, this needs to be large, since omega-3 LC-PUFA are present in many compartments. WHAT THIS STUDY ADDS: • We selected subjects with uniform omega-3 background concentrations, to obtain comparable results at the end of treatment. • Testing bioequivalence of two formulations with different EPA : DHA ratios led to single dose intakes of 12 g, which were well tolerated. • In spite of clear differences in EPA : DHA ratios between the two preparations, plasma ratios did not differ and bioequivalence could be well ascertained. AIM: To evaluate the bioequivalence of two omega-3 long chain polyunsaturated fatty acid (n-3 LC-PUFA) ethyl ester preparations, previously shown not to be bioequivalent in healthy subjects, with the objective of providing a guideline for future work in this area. METHOD: A randomized double-blind crossover protocol was chosen. Volunteers with the lowest blood concentrations of n-3 LC-PUFA were selected. They received the ethyl esters in a single high dose (12 g) and eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) blood concentrations were analyzed after fingerprick collection at intervals up to 24 h. RESULTS: Differently from a prior study, the pharmacokinetic analysis indicated a satisfactory bioequivalence: for the AUC(0,24 h) 90% CI of the ratio between the two formulations were in the range for bioequivalence (for EPA 0.98, 1.04 and for DHA 0.99, 1.04) and the same was true for C(max) and t(max) (90% CI were 0.95, 1.14 and 1.10, 1.25 for EPA and 0.88, 1.02 and 0.84, 1.24 for DHA). CONCLUSION: This study shows that, in order to obtain reliable bioequivalence data of products present in the daily diet, certain conditions should be met. Subjects should have low, homogeneous baseline concentrations and not be exposed to food items containing the product under evaluation, e.g. fish. Finally, as in the case of omega-3 fatty acids, selected doses should be high, eventually with appropriate conditions of intake.

Post-prandial endothelial dysfunction in hypertriglyceridemic subjects: molecular mechanisms and gene expression studies.

OBJECTIVE: Triglyceride-rich lipoproteins (TGRLs) are a cardiovascular risk factor and induce endothelial dysfunction. In the present study, we investigated the effects of post-prandial TGRLs from type IV hyperlipidemic subjects on endothelial activation addressing the effects of the lipoproteins on intracellular pathways and gene expression. METHODS: Thirty fasted hypertriglyceridemic patients were given an oral fat load (OFL) and blood samples were collected before the OFL (T0) and 2, 4, 6 and 8h thereafter. Endothelial function, determined as flow-mediated dilatation of the brachial artery, was assessed at the same time points. TGRLs were isolated at T0 and T4 (PP-TGRL) for in vitro studies. RESULTS: Compared with TGRLs, PP-TGRLs induced to a larger extent phosphorylation of p38 MAPK, CREB and IKB-alpha in human endothelial cells and increased the DNA binding activity of CREB, NFAT and NF-kappaB. Furthermore, PP-TRGLs upregulated the expression of several pro-inflammatory genes including vascular cell adhesion molecule-1 (VCAM-1), PECAM-1, ELAM-1, intercellular adhesion molecule-1 (ICAM-1), P-selectin, MCP-1, interleukin-6 (IL-6), TLR-4, CD40, ADAMTS1 and PAI-1. CONCLUSION: These effects may relate to the severe impairment of endothelial function seen during the post-prandial phase in hypertriglyceridemic patients.

In vitro isolation of circulating endothelial progenitor cells is related to the high density lipoprotein plasma levels.

Circulating endothelial progenitor cells (EPCs) play an important role in post natal neovascularization. High density lipoproteins (HDL) protect the vascular wall from atherosclerosis. The role exerted by HDL on EPCs physiology is unknown. In this study we investigated whether the levels of plasma HDL can modulate the number of EPCs. The number of EPCs was evaluated in 24 subjects as the number of endothelial colony-forming unit (e-CFU) growth in culture. The number of AC133 positive progenitor cells present in the gate of the CD34 bright positive lymphocytes was also evaluated. Plasma levels of HDL, triglycerides and total cholesterol/HDL cholesterol ratio correlated with the number of e-CFU (r=0.62, P=0.006; r=-0.54, P=0.019, and r=-0.61, P=0.007 respectively), but not with the number of CD34/AC133 positive progenitor cells. In vitro, the incubation of the mononuclear cellular fraction with HDL did not increase the number of e-CFU in culture, whereas LDL and VLDL reduced the number of e-CFU. Our results indicate that human HDL plasma levels directly relate to the number of circulating endothelial progenitor cells that can be isolated in vitro, as determined by the number of e-CFU.

Lipoprotein remnants and endothelial dysfunction in the postprandial phase.

The objective of this work was to study whether changes in remnant lipoprotein (RLP) plasma levels during the postprandial phase relate to alterations of the endothelial function. Fasted patients (15 moderately dyslipidemic men) were given an oral fat load (OFL), and blood samples were collected before the OFL ingestion (T0) and 2, 4, 6, and 8 h (T2, T4, T6, T8) thereafter. Endothelial function, determined as flow-mediated dilatation (FMD) of the brachial artery, was assessed at the same time points. Triglyceridemia peaked between T4 (5.48 +/- 0.64 mmol/liter) and T6 (5.34 +/- 0.89 mmol/liter) and decreased at 8 h (4.36 +/- 0.87 mmol/liter) after the OFL. FMD decreased significantly 6 h after the OFL consumption (from 16.03 +/- 1.32% to 11.53 +/- 1.42%, P < 0.01). Cholesterol in RLPs increased steadily up to 6 h and decreased at 8 h (T0 0.53 +/- 0.10, T6 0.81 +/- 0.11, T8 0.73 +/- 0.13 mmol/liter). Fasting levels of triglycerides and cholesterol-RLPs (C-RLPs) correlated significantly with FMD at baseline. The decrease in endothelial function at 6 h also significantly correlated with the area under the curve of triglycerides (R = 0.53, P = 0.04). Postprandial C-RLPs (area under the curve), however, showed the best correlation with the decrease of FMD (R = 0.63, P = 0.012). The correlation persisted in a multivariate analysis. We concluded that C-RLPs contribute significantly to the endothelial dysfunction occurring during the postprandial lipemia.

Apolipoprotein C-II deficiency presenting as a lipid encephalopathy in infancy.

An infant presented with massive hyperchylomicronemia and a severe encephalopathy. MRI showed marked lipid deposition throughout the brain. Despite the normalization of the biochemistry, there was little clinical improvement, and at 18 months of age she has severe developmental delay, a strikingly abnormal MRI. Apolipoprotein C-II, the lipoprotein on chylomicrons responsible for the activation of lipoprotein lipase, was not detectable in blood. Analysis of the APO C-II gene revealed a novel homozygous point mutation, 1118C-->A. Subsequently, another sibling has been born with the same homozygous mutation and similar biochemistry but, perhaps because of early treatment, a normal neurological outcome.

5-methyltetrahydrofolate restores endothelial function in uraemic patients on convective haemodialysis.

BACKGROUND: Hyperhomocysteinaemia is an independent risk factor for the development of atherosclerosis. In patients with chronic renal failure, the administration of folic acid or its metabolites reduces but does not normalize plasma homocysteine concentrations. Furthermore, homocysteine induces endothelial dysfunction by an increased inactivation of nitric oxide. METHODS: We examined the effect of the active metabolite of folic acid, 5-methyltetrahydrofolate (5-MTHF), 45 mg/week i.v. for 10 weeks, combined during the last 2 weeks with vitamin B12, 500 microg s.c. twice weekly, on homocysteinaemia and endothelial function in 15 patients undergoing convective haemodialysis. Endothelial function was evaluated by B-mode ultrasonography on the brachial artery. Flow-mediated dilation (FMD) was recorded during reactive hyperaemia produced by inflation of a pneumatic tourniquet. Nitroglycerine-mediated dilation (NMD) was recorded after administration of isosorbide dinitrate. Finally, the presence of the thermolabile variant of methyltetrahydrofolate reductase (t-MTHFR) was assessed by genotype analysis. RESULTS: Plasma homocysteine concentrations fell by 47% after treatment with 5-MTHF alone and by a further 13.6% after the addition of vitamin B12. The reduction was more marked in homo- and heterozygous patients than in normal genotypes for t-MTHFR. Flow-mediated endothelial vasodilation, measured by ultrasonography of the brachial artery, improved after administration of 5-MTHF (12.52+/- 2.47% vs. 7.03+/-1.65%; P<0.05), but there were no further changes following the addition of vitamin B12. CONCLUSIONS: Our study demonstrated that 5-MTHF administration not only reduced plasma homocysteine but also improved endothelial function in uraemic patients undergoing convective haemodialysis.