received depends on the animal’s food intake, and achieving a
constant dosage (in mg per kg of animal per day) might not be
feasible. It is recommended that powdered supplemented diets
and carotenoid emulsions are prepared every 2 days, to prevent
the degradation of carotenoids. It is also important to verify the
composition and stability of the food extracts enriched in
carotenoids.
11. The dose to be used in animal studies will depend on the
carotenoid or carotenoids under study. For beta-carotene, it
is prudent not to exceed ~Âfourfold the average intake in
humans, which is about 4 mg per day in European countries
[9]. When establishing the experimental doses, it might also be
important to take into account the daily average total carotenoids intake (~9.5 to 16 mg per day), as a reference. The body
surface area (BSA) normalization method [47] is often used to
convert drug doses from animal to human studies, despite
recent controversy. Controversy arises because BSA does not
take into account physiologic and pharmacokinetic data
beyond body surface, and hence may entail oversimplification
of dose conversion [48]. In any case, the idea after BSA or
other conversion equations is to find a dosage for humans that
will allow for therapeutic concentrations of the molecule of
interest at the cellular targets, in order to replicate benefits
observed in animal models, without toxicity. As an example, a
daily oral dose of 2.5 mg of carotenoid per kg of body weight in
mice is, based on the BSA equation, equivalent to 12 mg of
carotenoids per day for a 60 kg person, which is within the
average intake of carotenoids in humans [9]. This dose can be
achieved by feeding a diet containing 30 mg of carotenoid per
kg of diet, in mice of 30 g of body weight eating 2.5 g of diet
per day.
Acknowledgments
BS is the recipient of a “La Caixa” Foundation predoctoral contract
at the University of Balearic Islands. The group is a member of the
European COST-Action EUROCAROTEN (CA15136; EU
Framework Programme Horizon 2020), and the Spanish Network
of Excellence CaRed (BIO2015-71703-REDT and BIO201790877-REDT; Agencia Estatal de Investigacio ´ n, MICIU/
FEDER, EU). CIBER de Fisiopatologı ´a de la Obesidad y Nutricio ´ n
(CIBERobn) is an initiative of the ISCIII (Spanish Government).
414
Joan Ribot et al.
constant dosage (in mg per kg of animal per day) might not be
feasible. It is recommended that powdered supplemented diets
and carotenoid emulsions are prepared every 2 days, to prevent
the degradation of carotenoids. It is also important to verify the
composition and stability of the food extracts enriched in
carotenoids.
11. The dose to be used in animal studies will depend on the
carotenoid or carotenoids under study. For beta-carotene, it
is prudent not to exceed ~Âfourfold the average intake in
humans, which is about 4 mg per day in European countries
[9]. When establishing the experimental doses, it might also be
important to take into account the daily average total carotenoids intake (~9.5 to 16 mg per day), as a reference. The body
surface area (BSA) normalization method [47] is often used to
convert drug doses from animal to human studies, despite
recent controversy. Controversy arises because BSA does not
take into account physiologic and pharmacokinetic data
beyond body surface, and hence may entail oversimplification
of dose conversion [48]. In any case, the idea after BSA or
other conversion equations is to find a dosage for humans that
will allow for therapeutic concentrations of the molecule of
interest at the cellular targets, in order to replicate benefits
observed in animal models, without toxicity. As an example, a
daily oral dose of 2.5 mg of carotenoid per kg of body weight in
mice is, based on the BSA equation, equivalent to 12 mg of
carotenoids per day for a 60 kg person, which is within the
average intake of carotenoids in humans [9]. This dose can be
achieved by feeding a diet containing 30 mg of carotenoid per
kg of diet, in mice of 30 g of body weight eating 2.5 g of diet
per day.
Acknowledgments
BS is the recipient of a “La Caixa” Foundation predoctoral contract
at the University of Balearic Islands. The group is a member of the
European COST-Action EUROCAROTEN (CA15136; EU
Framework Programme Horizon 2020), and the Spanish Network
of Excellence CaRed (BIO2015-71703-REDT and BIO201790877-REDT; Agencia Estatal de Investigacio ´ n, MICIU/
FEDER, EU). CIBER de Fisiopatologı ´a de la Obesidad y Nutricio ´ n
(CIBERobn) is an initiative of the ISCIII (Spanish Government).
414
Joan Ribot et al.