Vitamin supplementation

An apple a day keeps the doctor away – you may have heard the phrase more than once, as it has become so famous that translated versions circulate in a number of modern languages [‘una mela al giorno toglie il medico di torno’]. More than three millennia before the concept of vitamins became common knowledge, ancient Egyptian and Babylonian text described a diet of liver to cure night blindness (Dowling & Wald 1958). However, it took mankind a very long time to, from there, discover vitamins. The transoceanic voyages of the Renaissance led to long periods of time in which sailors were deprived of fruit or vegetables, prompting the scurvy epidemic (Jacob 1996). Explorers as early as Vasco da Gama of the late 15th century witnessed the curative effects of lemons and oranges on scurvy victims (Rajakumar 2001), and the Portuguese, on Saint Helena, ‘planted vegetables and nurseries with which passing ships were marvellously sustained, [. . .] ‘wild groves’ of oranges, lemons and other fruits that ripened all the year round’ (Livermore 2004). Saint Helena, at that time, was the popular stopping point for homebound ships from Asia, and a special boat service seems to have existed to shuttle recovering, but weak scurvy victims back to the Portuguese mainland. It took another 250 years until the Scottish physician James Lind described the preventive effects of citrus fruit intake in a treatise on scurvy. Until that time, when the Royal Navy quickly put Lind’s suggestions into action and British sailors soon became known as limeys, the deadly vitamin C deficiency is estimated to have claimed the lives of at least two million seafarers worldwide. Casimir Funk, a Polish chemist working at Lister Institute in London, discovered in 1911 what he called ‘vitamins’: tiny amounts contained in food could cure deadly diseases, a biomedical quantum leap at a time when nutritional deficiencies were common and fatal. Hungarian physiologist Albert Szent-Gy€ orgyi von Nagyr apolt won the Nobel Prize in Physiology or Medicine in 1937 for discovering vitamin C and the flavonoids. Vitamin C has had an incredible career since then, both in biomedical science and as a marketable supplement for its (perceived) health benefits, mostly for its antioxidant properties. As other animals (and many plants), humans balance their oxidative states through complex systems of antioxidants, such as glutathione, proand antioxidant enzymes such as catalase and superoxide dismutase, or the dietary uptake of antioxidant vitamins (Zuo et al. 2015a). While randomized clinical trials with supplements of beta-carotene, vitamin A and vitamin E singly or in different combinations found no effect on mortality rate and cancer risk or may even increase cancer risk, vitamin C may marginally shorten the duration of the common cold (Hemil€a & Chalker 2013). Vitamin E has shown some preventive effects regarding atherosclerotic events in hypercholesterolaemic animal models, however, not through direct radical scavenging, but rather by modulating VEGF/VEGF-R2 expression (Chistiakov et al. 2015a). Most antioxidant dietary supplements do, as far as we know today, not improve health nor are they effective in preventing diseases. Vitamin supplementation, if administered, especially in the context of nutritional studies, should always be specified (Khanal et al. 2015). Nevertheless, healthy oxidative states in different systems within the human body are crucial and are being studied meticulously, as hopes for a beneficial therapeutic intervention other than mere dietary supplementation remain high (Lambert et al. 2015, Baez 2016, Heyman et al. 2016). Markers of oxidative state may be used in the diagnosis of acute mountain sickness (Dietze & Patzak 2016). Antioxidant systems play a crucial role in the physiological function of the respiratory (Zuo et al. 2015b) and cardiovascular (Csat o et al. 2015) (Chytilov a et al. 2015) systems and provide potential therapeutic targets (Poudyal 2016, Tanajak et al. 2016). In vascular endothelial cells, a robust relation between biophysical characteristics of blood flow and the oxidative state of the vessel wall has been established (Chistiakov et al. 2015b). Flavonoids have recently been identified as non-competitive P2Y2 antagonists (reviewed in Kishore et al. 2015, Menzies et al. 2015), while vitamin D3 exerts an immunomodulatory function by the induction of tolerogenic cells (Ganea et al. 2015). Another important research focus is on the interaction of vitamins and their receptors, be it with carrier proteins (Rueth et al. 2015) or, for example, in receptor heterodimer formation (Gnocchi et al. 2016), modifying their effects. Mankind has accumulated an incredible treasure of information on nutrition and the values of certain components such as vitamins. However, when one