20
M. A. Asson-Batres
dose vitamin A sidesteps the highly regulated biochemical processes that parse out,
deliver, store, or remove vitamin A and its derivatives in response to physiological
demand and potential retinoid toxicity. A great deal of work is still needed to resolve
controversies and answer fundamental questions regarding optimal ways to ascertain, maintain, and restore levels of vitamin A and to delineate the effects of age,
other micronutrients, and environmental factors on vitamin A action.
Future Directions
Although it took … 50 years to come up with mechanistic explanations, such as those
enshrined in the [retinoic acid] paradigm, the full complexity of vitamin A action is
underappreciated to this day (Hammerling 2016a, b).
Beyond tackling obvious unanswered questions regarding the processes and mechanisms governing identified roles of vitamin A in living systems, fundamental insight
in two important areas is yet needed to drive vitamin A and retinoid research forward.
How Much Vitamin A Do Animals Need for Optimal Health
and Longevity?
As discussed above, vitamin A deficiency is often defined by a serum retinol concentration <0.70 μmol/l. However, reliance on this measurement is problematic because
vitamin A levels in serum only show a drop when vitamin A deficiency is extreme.
This means that cases of hypervitaminosis (due to excessive intake of vitamin A supplements, for example) or moderate vitamin A deficiency (due to dietary insufficiency
or pathology) that still have the potential to compromise normal tissue function or
homeostasis would be masked by this measurement. An alternative approach is to
use a retinol isotope dilution (RID) technique that indirectly estimates hepatic vitamin A levels (Lietz et al. 2016; Quadro 2016). This technique has the potential to
more accurately gauge vitamin A status in well-fed animals because the liver is the
repository for most of the vitamin A reserves in mammals.
However, RID has some important downsides, (a) in cases where the liver is
depleted of vitamin A, RID falls short because it does not include vitamin A reserves
found in extrahepatic tissues. Currently, the contribution of extrahepatic tissue stores
during times of vitamin A depletion or deficiency is unknown; (b) validation studies
indicate that the RID technique provides an accurate estimate of liver vitamin A stores
for groups of individuals, but it does not provide a precise estimate of liver vitamin
A stores for individual participants; (c) the technique has not been optimized for
infants <12 months of age or for lactating or pregnant women; and (d) the technique
cannot be carried out in the field or in care centers where the necessary equipment
or laboratory set up is unavailable.
M. A. Asson-Batres
dose vitamin A sidesteps the highly regulated biochemical processes that parse out,
deliver, store, or remove vitamin A and its derivatives in response to physiological
demand and potential retinoid toxicity. A great deal of work is still needed to resolve
controversies and answer fundamental questions regarding optimal ways to ascertain, maintain, and restore levels of vitamin A and to delineate the effects of age,
other micronutrients, and environmental factors on vitamin A action.
Future Directions
Although it took … 50 years to come up with mechanistic explanations, such as those
enshrined in the [retinoic acid] paradigm, the full complexity of vitamin A action is
underappreciated to this day (Hammerling 2016a, b).
Beyond tackling obvious unanswered questions regarding the processes and mechanisms governing identified roles of vitamin A in living systems, fundamental insight
in two important areas is yet needed to drive vitamin A and retinoid research forward.
How Much Vitamin A Do Animals Need for Optimal Health
and Longevity?
As discussed above, vitamin A deficiency is often defined by a serum retinol concentration <0.70 μmol/l. However, reliance on this measurement is problematic because
vitamin A levels in serum only show a drop when vitamin A deficiency is extreme.
This means that cases of hypervitaminosis (due to excessive intake of vitamin A supplements, for example) or moderate vitamin A deficiency (due to dietary insufficiency
or pathology) that still have the potential to compromise normal tissue function or
homeostasis would be masked by this measurement. An alternative approach is to
use a retinol isotope dilution (RID) technique that indirectly estimates hepatic vitamin A levels (Lietz et al. 2016; Quadro 2016). This technique has the potential to
more accurately gauge vitamin A status in well-fed animals because the liver is the
repository for most of the vitamin A reserves in mammals.
However, RID has some important downsides, (a) in cases where the liver is
depleted of vitamin A, RID falls short because it does not include vitamin A reserves
found in extrahepatic tissues. Currently, the contribution of extrahepatic tissue stores
during times of vitamin A depletion or deficiency is unknown; (b) validation studies
indicate that the RID technique provides an accurate estimate of liver vitamin A stores
for groups of individuals, but it does not provide a precise estimate of liver vitamin
A stores for individual participants; (c) the technique has not been optimized for
infants <12 months of age or for lactating or pregnant women; and (d) the technique
cannot be carried out in the field or in care centers where the necessary equipment
or laboratory set up is unavailable.