Newsletter 02 2006.pdf - Sight and Life

SIGHT AND LIFE 12
NEWSLETTER 2/2006
Richard Kuhn
George Wald
ure of night blindness (pupillary
response) (21), subject-friendly
collection of blood specimens
(dry blood spots) for subsequent
quantitative analysis either in the
field or at a base laboratory (22)
and assessing whole body stores
(isotope dilution) (23). The application
of new intrinsic carotenoid
labeling methods offers greater
ability to trace individual carotenoids
from vegetables containing
them in their natural matrices to
their uptake from the gut and utilization:
hence, to a more accurate
measure of bioavailability (24).
Programs
Intervention programs are moving
beyond strictly distributing
nutrient supplements. These
programs are becoming more
integrated and viewed more
holistically within the context of
undernutrition, underdevelopment
and poverty. Micronutrient
fortified foods that can address
both specific deficiencies and caloric
undernutrition are available
in many countries. They include
vitamin A fortified sugar, oils, and
some cereals, to name a few, but
access by the poor at greatest
risk still varies greatly, especially
in rural areas with limited market
access. And public health measures
including promotion and
support for breastfeeding, expanded
immunization coverage,
parasite control programs, and
home-based control of severe diarrheal
disease have contributed
to decreased infectious morbidity
and mortality and, hence,
improved individual and national
HAPC Oomen
development. Although improvements
are occurring in availability
of potable water and environmental
sanitation, the UN reports
(Los Angeles Times, March 10)
that over 1.1 billion living in impoverished
communities remain
without safe water. Yet in spite of
all the progress made, including
distribution of over 400 million
vitamin A capsules annually (18),
vitamin A deficiency remains a
significant public health problem.
A diet inadequate in vitamin A-
containing food sources is the
underlying cause of deficiency.
Yet until recently food-based approaches
that impact on underlying
causes of underdevelopment,
undernutrition and micronutrient
deficiencies were the step-child
intervention least attractive to
international funding agencies.
How did we get from
there (1960) to here
(2006)? Some significant
decade milestones
1960–1970: Progress
in understanding basic
metabolism
The decade of the 1960s was the
period that in my reflective view
was noted mostly for advances in
understanding the basic metabolism
of vitamin A and provitamin A
carotenoids. Central cleavage of
beta-carotene in James Olson’s
(25) and DeWitt Goodman’s (26)
laboratories by enzymes isolated
from the gut and liver of rats advanced
knowledge of bioconversion
mechanisms. In humans,
efficient uptake of dietary retinol
and conversion of β-carotene to
retinal, esterification to retinyl
esters, transport of the esterified
product in lymph chylomicra and
hepatic uptake from chylomicra
remnants were demonstrated (27).
Retinol binding protein (RBP) was
isolated and partially characterized
in 1968, and subsequently
its role in hepatic mobilization and
transport of retinol as holo-RBP
complexed with transthyretin was
defined (28). Understanding of
the reversible formation of single,
bi- and trimolecular complexing
clarified how the exchange
of retinol from blood to tissues
occurred without loss through
kidney filtration. Furthermore, the
concepts revealed in defining the
metabolism of RBP provided the
basis in the following two decades
for a new indirect assessment of
depleted hepatic stores, the relative
dose response (RDR) in my
laboratory (29), its modification
(MRDR) in James Olson’s laboratory
(30) and its current broad use
in assessment of vitamin A status
in human and animal studies.
On the public health front progress
was slow. In 1964 the first ‘guestimate’
of the global magnitude
of deficiency was made. The approximation
of 20,000 to 100,000
affected children was based
largely on interviews and subjective
information on the prevalence
of eye signs (31), which did not
generate political support for
large intervention programs, even
though severe vitamin A deficiency
in children was very evident in
developing countries, often associated
with PEM, and too often
inappropriately managed leading
to irreversible blindness, if the patient
survived. Many of us involved
in international child health issues
during the 1960s were appalled
by the lack of attention to this
preventable public health scourge,
but there was no organized group
to champion the cause at a political
level and attract substantial
funds for prevention.