Raspberry ketone in food supplements--High intake, few toxicity data--A cause for safety concern?

Raspberry ketone (4-(4-hydroxyphenyl)-2-butanone) is marketed on the Internet as a food supplement. The recommended intake is between 100 and 1400 mg per day. The substance is naturally occurring in raspberries (up to 4.3 mg/kg) and is used as a flavouring substance. Toxicological studies on raspberry ketone are limited to acute and subchronic studies in rats. When the lowest recommended daily dose of raspberry ketone (100 mg) as a food supplement is consumed, it is 56 times the established threshold of toxicological concern (TTC) of 1800 µg/day for Class 1 substances. The margin of safety (MOS) based on a NOAEL of 280 mg/kg bw/day for lower weight gain in rats is 165 at 100 mg and 12 at 1400 mg. The recommended doses are a concern taking into account the TTC and MOS. Investigations of raspberry ketone in quantitative structure-activity relationship (QSAR) models indicated potential cardiotoxic effects and potential effects on reproduction/development. Taking into account the high intake via supplements, the compound's toxic potential should be clarified with further experimental studies. In UK the pure compound is regarded as novel food requiring authorisation prior to marketing but raspberry ketone is not withdrawn from Internet sites from this country.

Evaluating the health impact of increased linseed consumption in the Danish population.

Consumption of linseeds has been suggested to have beneficial effects on human health. However, toxic constituents of linseed may compromise these benefits. We conducted a quantitative risk-benefit assessment to evaluate the overall health impact of increasing linseed intake up to 45 g/day in the Danish population (15-74 years). We quantified the risks associated with increased cadmium exposure and the benefits associated with increased intake of dietary fibre. Increased intakes of alpha-linoleic acid (ALA) were included in a sensitivity analysis. The overall health impact of different linseed intake scenarios was estimated in terms of Disability-Adjusted Life Years (DALYs). We found that the beneficial effects of linseed due to increased intake of dietary fibre outweighed the adverse health effects due to increased cadmium exposure in all scenarios. Up to 670 DALYs/100,000 individuals could be averted per year by increasing linseed consumption in the Danish population. The estimated beneficial health impact increased further when including ALA in the assessment. Different sources of uncertainty might affect the results, and more research is needed on both the health effects associated with intake of linseed and its constituents, and the bioavailability of ALA and cadmium from linseed to further improve the risk-benefit assessment.

Allergenicity evaluation of quinoa proteins - A study in Brown Norway rats.

The popularity of quinoa seeds has increased in the last decade due to their high nutritional value and natural gluten-free composition. Consumption of new proteins may pose a risk of introducing new allergies. In the present study the immunogenicity and sensitising capacity of quinoa proteins were assessed in a dose-response experiment in Brown Norway rats in comparison to proteins from spinach and peanut. Cross-reactivity between quinoa proteins and known allergens was evaluated by in silico analyses followed by analyses with 11 selected protein extracts and their anti-sera by means of ELISAs and immunoblotting. Further, an in vitro simulated gastro-duodenal digestion was performed. Quinoa proteins were found to have an inherent medium to high immunogenicity and sensitising capacity, being able to induce specific IgG1 and IgE levels higher than spinach but lower than peanut and elicit reactions of clinical relevance similar to peanut. Quinoa proteins were generally shown to resist digestion and retain capacity to bind quinoa-specific antibodies. Quinoa proteins were shown to be cross-reactive with peanut and tree nut allergens as high sequence homology and antibody cross-binding were demonstrated. Present study suggests that quinoa pose a medium to high level of allergenicity that should be further investigated in human studies.

Intake of Food Supplements, Caffeine, Green Tea and Protein Products among Young Danish Men Training in Commercial Gyms for Increasing Muscle Mass.

Sixty-three men (15-35 years of age) regularly training in Danish gyms and supplement users were interviewed about the use of supplemental protein and food supplements, intake of caffeine- and (-)-epigallocathechin-3-gallate (EGCG)-containing supplements and beverages and any experienced adverse effects. Protein powder (60%), fish oil (54%) and multivitamin/mineral supplements (41%) were the most popular products. The daily supplementary protein intake (mean 0.42 g/kg body weight, users only) in adult men contributed substantially to their protein intake and exceeded the recommended allowance (0.83 g/kg body weight) for six adult participants (14%). Thirty-eight percent of the adult men exceeded the daily caffeine intake presumed to be safe (400 mg) with coffee as the main contributor. Thirty percent drank green tea and among this percentage, two participants had an extreme daily intake (1.5 and 2 -L). EGCG intake could not be estimated from the food supplements due to the lack of label information. Eighteen participants (29%) reported having experienced adverse effects but seventeen did not consult a physician or report the adverse effect to the Danish food authority. The most common adverse effects were insomnia, shaking, headache and palpitations, itching of the skin and stinging. Pre-workout products accounted for 53% of the adverse effects. Three adverse effects came after intake of two brands of supplements known to have contained substances such as 1,3-dimethylamine or derivatives of phenylethylamines previously having caused serious adverse effects.

Quinoa (Chenopodium quinoa Willd.) Seeds Increase Intestinal Protein Uptake.

SCOPE: Within the last decade, quinoa seeds have gained much popularity as a new food and have recently been proposed as an appropriate food for early introduction in infants. Quinoa contains high levels of saponins, which are known for their adjuvant activity and effect on the intestinal barrier function. The aim of this study is to investigate the impact of quinoa on intestinal permeability and inflammation in comparison with the positive controls; cholera toxin (CT), and capsaicin. METHODS AND RESULTS: The effect of quinoa on intestinal barrier function and inflammation is investigated in vitro using a Caco-2 cell line and in vivo using a Brown Norway rat model. Effects in vivo are analyzed by protein uptake, histology, gene expression, antibody levels, and flow cytometry. Quinoa and the positive controls all increased the intestinal permeability, but distinct patterns of absorbed protein are observed in the epithelium, Peyer's patches, lamina propria, and serum. The quinoa-mediated effect on intestinal barrier function is found to be distinct from the effect of the two positive controls. CONCLUSION: The findings demonstrate the ability of quinoa to increase intestinal permeability and to promote compartment-specific protein uptake via mechanisms that may differ from CT and capsaicin.

Effect of rapeseed oil-derived plant sterol and stanol esters on atherosclerosis parameters in cholesterol-challenged heterozygous Watanabe heritable hyperlipidaemic rabbits.

Rapeseed oil (RSO) is a novel source of plant sterols, containing the unique brassicasterol in concentrations higher than allowed for plant sterol blends in food products in the European Union. Effects of RSO sterols and stanols on aortic atherosclerosis were studied in cholesterol-fed heterozygous Watanabe heritable hyperlipidaemic (Hh-WHHL) rabbits. Four groups (n 18 per group) received a cholesterol-added (2 g/kg) standard chow or this diet with added RSO stanol esters (17 g/kg), RSO stanol esters (34 g/kg) or RSO sterol esters (34 g/kg) for 18 weeks. Feeding RSO stanol esters increased plasma campestanol (P < 0.001) and sitostanol (P < 0.001) and aortic campestanol (P < 0.05) compared with controls. Feeding RSO sterol esters increased concentrations of plasma campesterol (P < 0.001), sitosterol (P < 0.001) and brassicasterol (P < 0.001) and aortic campesterol (P < 0.01). Significantly lower plasma cholesterol (P < 0.001) was recorded in the treated groups after 3 weeks and throughout the study. LDL-cholesterol was reduced 50 % in the high-dose RSO sterol ester (P < 0.01) and high-dose RSO stanol ester (P < 0.001) groups compared with controls. Atherosclerotic lesions were found in three rabbits in each of the RSO stanol ester groups and in one in the RSO sterol ester group. Aortic cholesterol was decreased in the treated groups (P < 0.001) in response to lowering of plasma cholesterol induced by RSO sterol and stanol esters. In conclusion, RSO stanol and sterol esters with a high concentration of brassicasterol were well tolerated. They were hypocholesterolaemic and inhibited experimental atherosclerosis in cholesterol-fed Hh-WHHL rabbits. A significant uptake of plant sterols into the blood and incorporation of campesterol and campestanol into aortic tissue was recorded.

Risk management and risk assessment of novel plant foods: concepts and principles.

Worldwide 30 food plants deliver 95% of human daily intake of plant food calories and around 300 other plant species are delivering the last 5%. These some 300 food plants are likely to be considered traditional in Europe, while the nearly 7000 other plant species traditionally used in the human food supply in other parts of the world may be considered novel in Europe. Novel food regulation is already in force in the European Community, Australia/New Zealand and in Canada where the novel plant foods need to go through a premarket assessment procedure. This paper propose criteria and definitions to be used in determining novelty of a plant food and also propose a safety assessment approach for novel plant food with no or limited documented history of safe consumption. A 2-step management procedure is recommended for a smooth introduction of fruits and vegetables; first to establish the novelty and second to define and commit resources for the safety assessment. The procedure builds upon the use of a worldwide network of global, regional, local and ethnobotanical positive lists for food plants to guide the decision on novelty at the first step and to enable the safety assessment at the second step.

Are wild and cultivated flowers served in restaurants or sold by local producers in Denmark safe for the consumer?

New Nordic Food has within the last decade received much media coverage with chefs of top restaurants using wild plants for foods. As part of a control campaign, the Danish Veterinary and Food Administration visited 150 restaurants and local food producers from May-October 2016 and investigated their use of plants picked from the wild, cultivated in private gardens or market gardens. Among the species used were the flowers from 23 plants. Here we present a safety evaluation of these flowers based on published phytochemical investigations and toxicological data in humans, farm animals, pets, or experimental animals. Of the 23 flowers reviewed, nine contained compounds with toxic or potentially toxic effects if eaten, two contained unidentified toxic compound(s), and four were flowers from plants with potentially toxic compounds present in other plant parts or related species. Many of the flowers may be considered novel, since a use to a significant degree in Europe prior to 15 May 1997 before Regulation (EC) 258/97 on novel food and novel food ingredients came into force could not be established. In conclusion, this review illuminates a striking lack of chemical and toxicological data of many of the proposed wild or cultivated flowers for food use.

An oral Brown Norway rat model for food allergy: comparison of age, sex, dosing volume, and allergen preparation.

The purpose of the presented experiments was to study the possibility of using the Brown Norway rat as a model for food allergy in our laboratory. Specific serum IgE against ovalbumin (OVA) was induced after dosing male and female Brown Norway rats daily by gavage for 35 days. The influence of various preparations of allergen: OVA grade II, OVA grade V, and fresh egg white, age (4 versus 8 weeks), dosing volumes, and animal suppliers was studied. A general finding was that females had statistically significantly higher specific IgE and IgG titres and number of responders than males. Egg white preparation, age, dosing volume, and animal supplier did not statistically significantly influence the median IgE and IgG titres and number of responders. The difference between immune responses in males and females could not be attributed to variations in daily intake of OVA or exposure via the lung. In our hands, the oral Brown rat food allergy model gives rise to a moderate number of IgE responders, 13-38 and 38-75% in males and females, respectively. For further experiments with this model in our laboratory, females seem the sex of choice.

In utero exposure to diethylstilboestrol or 4-n-nonylphenol in rats: number of sertoli cells, diameter and length of seminiferous tubules estimated by stereological methods.

The effects on testis weight and histopathology were studied in 11-day-old male Wistar rats after prenatal exposure to peanut oil (control), diethylstilboestrol 30 microg/kg b.wt./day, or 4-n-nonylphenol 75 mg/kg b.wt./day from gestational day 11 to 18. Additionally, the diameter and length of seminiferous tubules, and the number of Sertoli cells were investigated with stereological methods. Such unbiased methods have not previously been applied on testis diameter and length or on Sertoli cell number of 11-day-old rats. In the control group, the mean length of the seminiferous tubule was 3.0 m+/-0.6, the mean diameter of the seminiferous tubule was 83 microm+/-6, and the mean number of Sertoli cells was 26.1x10(6)+/-4.6. No differences in testis weight, histopathology, or length or diameter of the seminiferous tubules were observed in the diethylstilboestrol and nonylphenol exposed groups when compared to the control group. In the diethylstilboestrol-treated group, a statistically significant decrease in the number of Sertoli cells was observed (P<0.01) when compared to the control group, whereas nonylphenol had no effect. The result suggests that diethylstilboestrol decreases Sertoli cell proliferation in the foetal testis and furthermore indicate that oestrogens may pose a risk to the reproductive capacity in sensitive species, including man.