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Trigonelline is a bioactive pyridine alkaloid that occurs naturally in high concentrations in coffee (up to 7.2 g/kg) and coffee by-products (up to 62.6 g/kg) such as coffee leaves, flowers, cherry husks or pulp, parchment, silver skin, and spent grounds. In the past, coffee by-products were mostly considered waste and discarded. In recent years, however, the use of coffee by-products as food has attracted interest because of their economic and nutritional value and the environmental benefits of sustainable resource use. Their authorization as so-called novel foods in the European Union may lead to increased oral exposure of the general population to trigonelline. Therefore, the aim of this review was to assess the risk to human health of acute and chronic exposure to trigonelline from coffee and coffee by-products. An electronic literature search was performed. Current toxicological knowledge is limited, with few human data available and a lack of epidemiological and clinical studies. There was no evidence of adverse effects after acute exposure. No conclusion can be drawn on chronic exposure to isolated trigonelline due to the lack of data. However, trigonelline ingested as a component of coffee and coffee by-products appears to be safe for human health, based on the safe traditional use of these products.

Chlorogenic and isochlorogenic acids are naturally occurring antioxidant dietary polyphenolic compounds found in high concentrations in plants, fruits, vegetables, coffee, and coffee by-products. The objective of this review was to assess the potential health risks associated with the oral consumption of coffee by-products containing chlorogenic and isochlorogenic acids, considering both acute and chronic exposure. An electronic literature search was conducted, revealing that 5-caffeoylquinic acid (5-CQA) and 3,5-dicaffeoylquinic acid (3,5-DCQA) are the major chlorogenic acids found in coffee by-products. Toxicological, pharmacokinetic, and clinical data from animal and human studies were available for the assessment, which indicated no significant evidence of toxic or adverse effects following acute oral exposure. The current state of knowledge suggests that long-term exposure to chlorogenic and isochlorogenic acids by daily consumption does not appear to pose a risk to human health when observed at doses within the normal range of dietary exposure. As a result, the intake of CQAs from coffee by-products can be considered reasonably safe.

Cannabidiol (CBD) is a naturally occurring, non-psychotropic cannabinoid of the hemp plant Cannabis sativa L. and has been known to induce several physiological and pharmacological effects. While CBD is approved as a medicinal product subject to prescription, it is also widely sold over the counter (OTC) in the form of food supplements, cosmetics and electronic cigarette liquids. However, regulatory difficulties arise from its origin being a narcotic plant or its status as an unapproved novel food ingredient. Regarding the consumer safety of these OTC products, the question whether or not CBD might be degraded into psychotropic cannabinoids, most prominently tetrahydrocannabinol (THC), under in vivo conditions initiated an ongoing scientific debate. This feature review aims to summarize the current knowledge of CBD degradation processes, specifically the results of in vitro and in vivo studies. Additionally, the literature on psychotropic effects of cannabinoids was carefully studied with a focus on the degradants and metabolites of CBD, but data were found to be sparse. While the literature is contradictory, most studies suggest that CBD is not converted to psychotropic THC under in vivo conditions. Nevertheless, it is certain that CBD degrades to psychotropic products in acidic environments. Hence, the storage stability of commercial formulations requires more attention in the future.

Coffee bean harvesting incurs various by-products known for their long traditional use. However, they often still end up being a waste instead of being used to their full potential. On the European market, coffee cherry (cascara) products are not yet common, and a novel food approval for beverages made from coffee cherry pulp was issued only recently. In this article, exposure and risk assessment of various products such as juice, jam, jelly, puree, and flour made from coffee cherry pulp and husk are reviewed. Since caffeine in particular, as a bioactive ingredient, is considered a limiting factor, safe intake will be derived for different age groups, showing that even adolescents could consume limited quantities without adverse health effects. Moreover, the composition can be influenced by harvesting methods and processing steps. Most interestingly, dried and powdered coffee cherry can substitute the flour in bakery products by up to 15% without losing baking properties and sensory qualities. In particular, this use as a partial flour substitute is a possible approach to counteract rising grain prices, transport costs, and disrupted supply chains, which are caused by the Russia–Ukraine war and changing climatic conditions. Thus, the supply of affordable staple foods could be partially ensured for the inhabitants of countries that depend on imported wheat and cultivate coffee locally by harvesting both beans and by-products.

Roasted coffee silver skin is a coffee by-product, the uses of which are currently limited, e.g., as fertilizer, for energy production, or animal feed. Due to a low content of fat and carbohydrates combined with a high content of fiber, polyphenols and proteins, roasted silver skin is a valuable possible food ingredient. Potential applications include partial flour replacement in bakery products, as antioxidant and providing protein or fiber sources in sports or functional foods. As no relevant consumption of isolated silver skin occurred before 1997 in the European Union (EU), it was classified as a novel food in need of premarketing approval. Novel food applications must meet legal requirements for compositional and toxicological information. This review presents information on silver skin composition and toxicological studies. Several in vitro studies and subchronic in vivo studies are available with negative results, not suggesting a need for further studies on carcinogenic effects, reproduction, or chronic toxicity. All available studies so far concluded that no toxic effects of silver skin were found or are to be expected. For a novel food application in the EU, further in vitro studies on mutagenic potential may be needed to close a formal data gap.

The coffee plant Coffea spp. offers much more than the well-known drink made from the roasted coffee bean. During its cultivation and production, a wide variety of by-products are accrued, most of which are currently unused, thermally recycled, or used as animal feed. The aim of this review is to provide an overview of novel coffee products in the food sector and their current legal classification in the European Union (EU). For this purpose, we have reviewed the literature on the composition and safety of coffee flowers, leaves, pulp, husk, parchment, green coffee, silver skin, and spent coffee grounds. Some of these products have a history of consumption in Europe (green coffee), while others have already been used as traditional food in non-EU-member countries (coffee leaves, notification currently pending), or an application for authorization as novel food has already been submitted (husks, flour from spent coffee grounds). For the other products, toxicity and/or safety data appear to be lacking, necessitating further studies to fulfill the requirements of novel food applications.

Cannabidiol (CBD), a non-psychotropic main component of the Cannabis plant, has been approved as a drug in the European Union (EU) under the name “Epidyolex”. However, its approval process as a food ingredient under the Novel Food Regulation was paused by the European Food Safety Authority (EFSA) due to a lack of safety data. Nevertheless, there is a growing, unregulated market in which CBD is advertised with various health claims and dosage instructions. Of particular concern is its toxic effect on the liver and possible reproductive toxicity in humans. Studies suitable for calculating the benchmark dose were identified from the available data. Animal studies yielded a benchmark dose lower confidence limit (BMDL) of 43 mg/kg bw/day, which translates into a safe human dose of approximately 15 mg/day. Only the Lowest-Observed-Adverse-Effect Level (LOAEL) of 4.3 mg/kg bw/day could be identified from the human data. This updated risk assessment confirmed a health-based guidance value (HBGV) of 10 mg/day based on human LOAEL. Despite the existing data gaps, preliminary regulation appears advisable because the current form of the gray CBD market is unacceptable from the standpoint of consumer safety and protection.

Coffee and coffee by-products, such as coffee cherries, coffee flowers, coffee leaves, green beans, roasted coffee, instant coffee, spent coffee grounds, and silverskin, contain a complex mixture of bioactive compounds that may exhibit both genotoxic and antimutagenic effects. This article evaluates in vitro studies on the genotoxic potential of coffee and coffee by-products, with a focus on different preparation methods, roasting processes, and key chemical constituents. Furthermore, given the growing interest in utilizing coffee by-products for novel food applications, this review sought to identify knowledge gaps regarding their safety. The impact of metabolic activation, particularly the role of enzymatic detoxification and bioactivation, was examined to better understand the effects on genetic material. The findings suggest that while certain compounds in coffee can induce DNA damage under specific conditions, the overall evidence does not indicate a significant genotoxic risk to consumers. However, further studies, particularly in vivo and human studies, appear necessary to ensure the requirements of novel food applications for some coffee by-products.

The Nagoya Protocol on Access and Benefit-sharing (ABS) of the Convention on Biological Diversity (CBD) is a fundamental international agreement that plays a crucial role in the protection and equitable utilization of plant genetic resources. While this agreement is essential for conservation and sustainable use, it presents specific challenges to coffee research and industry. One major issue is the requirement to obtain prior informed consent (PIC) from the source country or community, which can be a complex and time-consuming process, especially in regions with limited governance capacity. Additionally, the mandates of this agreement necessitate benefit-sharing with the source community, a requirement that poses implementation challenges, particularly for small businesses or individual researchers. Despite these challenges, the importance of the Nagoya Protocol in the coffee sector cannot be overstated. It contributes significantly to the conservation of coffee genetic resources and the sustainable utilization of these resources, ensuring fair distribution of benefits. To address the complexities presented by this international framework, coffee researchers and industry need to engage proactively with source countries and communities. This includes developing clear and equitable benefit-sharing and implementing strategies for compliance. This article explores the impact of the Nagoya Protocol on the coffee industry, particularly emphasizing the need for balancing scientific investigation with the ethical considerations of resource sharing. It also discusses practical strategies for navigating the complexities of this agreement, including research focused on authenticity control and the challenges in conducting large-scale coffee studies. The conclusion underscores the potential for international collaboration, particularly through platforms like the International Coffee Organization (ICO), to harmonize research activities with the ethical imperatives of the Nagoya Protocol.

Approximately 8 million tons of dates (Phoenix dactylifera) are produced globally each year. The seeds of the fruit, which make up 10–15% of its weight, are typically discarded. Date seed coffee is a sustainable food system innovation rooted in the traditions of high date-producing regions. Dating back to the late 19th century, date seed coffee has evolved from a historical coffee substitute to a modern caffeine-free alternative. Date seed coffee has a long history of consumption in the European Union (EU). This indicates that it may not require novel food authorization. The composition of date seeds is evaluated in this review and a toxicological risk assessment for date seed coffee is conducted. Subchronic studies show that consuming date seed or date seed coffee has no adverse effects. Therefore, currently unavailable chronic toxicity, carcinogenicity, and reproductive toxicity studies may be unnecessary. However, for a comprehensive evaluation, it is recommended to conduct an in vitro mutagenicity test. This review provides information on the safety of date seed coffee and highlights the need for further research.