Table of Contents

  • The Nordic Committee of Senior Officials for Food Issues is an advisory body of the Nordic Council of Ministers which co-ordinates Nordic work in the field of food and nutrition. The Nordic Working Group on Food Toxicology and Risk Evaluation (NNT) has been given the responsibility by the Committee to promote co-operation and co-ordination among Nordic countries in matters relating to food toxicology and risk assessment.

  • Den här rapporten sammanfattar tillgänglig epidemiologisk information om sambandet mellan intaget av koffein och andra metylxantiner hos kvinnor i barnafödande ålder och skadliga effekter via den gravida kvinnan på fostret och hennes barn. De skadliga effekter av metylxantiner som studerats är påverkan på fertiliteten, och risken för att drabbas av en spontan abort, föda ett barn med medfödda missbildningar, för tidig födsel, tillväxthämning under fosterstadiet och beteendepåverkan av fostret, de nyfödda eller småbarn. Varje epidemiologisk studie som fokuserat på något av dessa samband har granskats med ett kritiskt öga (kapitel 10-17), varefter en sammanvägd slutsats formulerats för vardera av dessa tänkbara samband.

  • Caffeine from natural sources has been consumed and enjoyed by humans throughout the world for centuries. The widespread natural occurrence of caffeine in a variety of plants undoubtedly played a major role in the long-standing popularity of caffeine-containing products, especially beverages. It was only during the last century that consumers became exposed to caffeine as a food additive as well. Although commercial manufacturers argue that adding caffeine to beverages enhances flavour, it is difficult to not suspect that there is an attempt to create products whose effects resemble those of naturally occurring caffeine.

  • The discovery of caffeine has been excellently reviewed by B.A. Kihlman in his book 'Caffeine and Chromosomes' (1977). Although not called caffeine or 1,3,7-trimethylxanthine at the time, German and French workers discovered the compound independently by in the early 1820s. In the book 'Neueste Phytochemische Entdeckungen zur Begründung einer wissenschaftlichen Phytochemie', Ferdinand Runge (1820) described a substance with basic properties which he had isolated from green coffee beans, and which he termed 'Kaffebase'. This publication appears to contain the first detailed description of caffeine. However, during the same year his German colleague F. von Giese (1820) reported in a letter to Scherer's 'Allgemeine nordische Annalen der Chemie für die Freunde der Naturkunde und Arzneiwissenschaft' that he had found a new alkaloid in extracts of coffee beans. He called the alkaloid 'Kaffeestoff', but subsequently declared it to be identical with Runge's 'Kaffebase' (von Giese, 1821).

  • Caffeine has a wide distribution within the plant kingdom. In section 3.1. it was mentioned that caffeine was detected early on in coffee beans (Coffea arabica), tea leaves (Camellia sinensis), leaves of Ilex paraguariensis (maté), guaraná paste (Paullinia sorbilis), and kola nuts (Cola acuminata). After these early discoveries it has been found in many other plants, mainly members of the Dicotyledoneae. Altogether it is produced by a large number of species belonging to at least twenty-eight genera over seventeen families in thirteen orders of plants. A non-exhaustive list of such plants is given in Table 3, which also indicates which plants are used for preparation of beverages.

  • The fact that caffeine and other methylxanthines are found in so many plant species raises the question of how and why these substances are formed. Are they produced by a separate metabolic pathway, or as byproducts of nucleic acid metabolism? Is the production of methylxanthines of value to the plants? These and other questions are dealt with in excellent recent reviews on the biosynthesis and metabolism of caffeine and related purine alkaloids in plants (Suzuki et al., 1992; Baumann, 1996; Ashihara and Crozier, 1999).

  • During several centuries man has enjoyed food and beverages containing stimulating ingredients such as methylxanthines. This chapter presents the most important food sources of methylxanthines, as well as the pharmaceuticals containing caffeine, which are commonly used in the Nordic countries. The food sources are presented in alphabetical order, beginning with products naturally containing methylxanthines: cocoa, coffee, guaraná, maté, tea, and yoco. The most abundant methylxanthine is caffeine, a substance present in the majority of hot beverages consumed today (Table 4). Thereafter, foodstuffs and drugs with added synthetic caffeine are mentioned. It should be stressed that certain older data on the methylxanthine content of various food products should be interpreted with care, since the chemical techniques used to identify and quantify the compounds were inadequate.

  • Total caffeine intake may differ considerably between individuals of the same nationality, but only a few studies have investigated individual caffeine intake. Most estimates are on the population level. The estimated average caffeine exposure in different countries is presented in Table 36.

  • Because methylxanthines exert several pharmacological actions, which may be therapeutically used, it is only natural that their absorption, fate and excretion in the mammalian organism have attracted special interest. Since this report deals with the assessment of epidemiological studies evaluating the relationship between intake of methylxanthines and adverse effects on women and their foetuses, this chapter is heavily focused on human pharmacokinetics. Some information is also given on the pharmacokinetics of various types of experimental animals. Although bacteria and fungi have been found to be capable of degrading methylxanthines, degradation of methylxanthines by these organisms is not further mentioned in the report. It should be noted that the majority of the studies on absorption, distribution and metabolism of methylxanthines have been performed with pure compounds, not with foods containing these substances.

  • A detailed discussion regarding the pharmacological actions of methylxanthines is beyond the scope of this report. Excellent reviews have been written by Nehlig et al. (1992), Sawynok and Yaksh (1993), Fredholm (1995), Sawynok (1995), Garrett and Griffiths (1997) and Fredholm et al. (1999). This chapter will shortly review general aspects of the pharmacological and toxicological actions of methylxanthines in man. No data from studies in experimental animals will be discussed.