# Volatiles in Berries: Biosynthesis, Composition, Bioavailability, and Health Benefits
## 4 Bioavailability of Berry Volatiles  
The definition of bioavailability by the U.S. Food and Drug Administration (FDA) is \"the rate and extent to which the active ingredient or active moiety is absorbed from a drug product and becomes available at the site of action\" [108]. More proper meaning is the part of ingested compound reaching the systemic circulation and specific site where it is available in the body [109]. Investigating the bioavailability of a compound is important to find the clinical relevance of the health-promoting activities of the bioactive compound in our body [110]. Thus, it is necessary to study the absorption, distribution, metabolism, and excretion of bioactive compounds. Bioavailability can be variable due to many different factors, including chemical structure, physical state, solubility, route of administration, and distribution via biotransformation and excretion [111; 112]. Based on solubility, volatile compounds and essential oils are relatively more nonpolar hydrophobic compounds than polyphenols that are more polar hydrophilic nutraceuticals [113; 114]. Regarding the route of administration, volatile compounds are more suitable for pulmonary administration through inhalation, while polyphenols are normally administrated orally [115]. Oral administration generally takes, on average, 30-90 min of action, while inhalation of gaseous compounds takes, on average, only 2-3 min [116]. The bioavailability of volatiles is largely affected by volatility, instability, and hydrophobicity [117]. Although there are many types of research conducted about the identification and quantification of berry volatiles, information is still lacking on the bioavailability of berry volatiles in animals and humans [118]. In this review, bioavailability studies of essential oils and herbal medicinal products that contain volatiles commonly present in berries were selected to estimate the bioavailability of volatile berry compounds. Unfortunately, the studies found are limited and mostly include animal models. Most of the bioavailability studies of essential oils showed that the volatile compounds in essential oils are rapidly absorbed and eliminated after pulmonary, dermal, and oral administration [115]. The compounds were mostly metabolized and eliminated within an hour of elimination half-life through the kidney after phase-II conjugation or CO\({}_{2}\) exhalation. In [PERSON] et al., the absorption, distribution, and excretion of d-limonene, a monoterpene in many essential oils but also found in black raspberries and blackberries, were investigated in rats [119]. \({}^{14}\)C-labeled d-limonene was orally administered to 21 male Wistar rats. The maximum radioactivity was obtained 2 h after administration in blood and 1-2 h after administration in tissues. High radioactivity in the liver, kidney, and blood became not significant after 48 h. The excretion of d-limonene was 60% in urine, 5% in feces, and 2% in expired CO\({}_{2}\) in 48 h. About 25% of administered d-limonene was eliminated in bile in 24 h in bile duct cannulated rats. Biotransformation studies of (+)-limonene in humans showed that the main metabolites of biotransformation were perillic acid, dihydroperillic acid, and limonene-10-ol, and their glucuronides, perillyl alcohol, p-mentha-1,8-dien-carboxylic acid, cis- and trans-dihydroperillic acid, limonene, 1,2-diol and limonene-8,9-diol [120]. Dermal application of \(\alpha\)-pinene on humans (ointment) and mice (bath) resulted in rapid absorption in plasma, reaching maximum plasma levels in 10 min of application [115]. Inhalation of \(\alpha\)-pinene in humans resulted in 61% absorption of \(\alpha\)-pinene [115]. However, only 4-6% of \(\alpha\)-pinene was found to be absorbed in the blood. In \(\alpha\)-pinene dermal and pulmonary administration studies [115], the half-life was short in the \(\alpha\)-phase (5 min) and longer in the \(\beta\)-phase (26-38 min).