Newsletter 02 2006.pdf - Sight and Life

SIGHT AND LIFE 14
NEWSLETTER 2/2006
1980–1990: Retinoid
revolution in the lab and
recognition that ocular
signs were the tip of the
iceberg in the field
Retinoid biochemistry experienced
a renaissance late in the
century when nuclear retinoid
receptors were identified and
their pleiotrophic effects recognized
in 1987 (38). This was the
beginning of research that has
identified how retinoic acid influences
a multitude of gene actions
that regulate differentiation and
cellular growth and functions.
This revolution is on-going with
new effects on functions being
reported regularly.
On the public health scene,
though nutritional biochemists
had argued vehemently at the
1974 meeting in Jakarta that
health consequences went far
beyond the eye-based on animal
studies – ophthalmologists were
unconvinced. The data systematically
collected in Indonesia
by Alfred Sommer (an ophthalmologist/epidemiologist)
and
colleagues during the decade of
the 1980s documented the prevalence
of vitamin A deficiency in
the country and provided a firmer
basis for projecting the extent of
the problem in four other Asian
countries, i.e. 200,000–400,000
corneal cases and 4–8 million
non-corneal cases (39). The team
also elucidated the underlying
epidemiological associations that
led to clustering of deficiency in
affected populations. The epidemiologic
studies associated the
lack of diversity in child diets,
including lack of animal products
and carotenoid-containing fruits
and vegetables, with deficiency.
The survey and epidemiological
studies set the stage for the large
randomly designed, controlled
intervention trial that first established
in humans the mortality
risk associated with deficiency
(40,41) that six decades earlier
had been reported in animals
(10). The announcement at an
IVACG meeting late in the 1980s
of a 27% reduction in mortality
was met with skepticism by the
scientific community, including
myself, who found it difficult to
believe that such a large effect
could occur from supplementation
without also addressing the
prevalence of other diseases
and unsanitary environmental
conditions. Subsequently preschool
child mortality associated
with deficiency was confirmed,
though variable in magnitude,
in Nepal (42), in Ghana (43), and
in India (44), but not in Sudan
(45), after administering highdose
vitamin A capsules every
4 or 6 months. Child mortality
was also reduced in Indonesia
(46) by regular intake of fortified
monosodium glutamate, and in
India (47) by providing a low-dose
weekly supplement, potentially
obtainable through food sources.
Meta-analyses using data from
the major trials concluded that
on average, a 23–30% increase
in mortality is associated with
deficiency (48-50).
1990–2000: Progress on the
political front
Political progress marked the
decade of the 1990s. UNICEF’s
World Summit for Children in 1990
was the ideal situation to call attention
to the striking mortality reduction
benefit expected by correcting
vitamin A deficiency. All
the ingredients were assembled
to launch a major international
offensive against the deficiency
as a public health scourge. The
mortality risk was established
and a short-term cost-effective
intervention was available in
the form of high-dose vitamin A
supplements. A persuasive, passionate,
committed champion in
the person of James Grant, then
director of UNICEF, was poised to
effectively mobilize the high-level
political commitment needed
from member states to launch
a major international offensive.
This broad political commitment
was achieved. The commitments
were reinforced at subsequent
international meetings in Canada
in 1991, sponsored by several
bilateral and international groups,
at the International Conference
on Nutrition in 1992, sponsored
by WHO/FAO and in 1996 at the
WHO/FAO World Food Summit
in Rome. The emphasis from the
beginning was on expanding the
distribution of high-dose vitamin A
supplements. Little support was
available for alternative strategies.
Supplement distribution
was greatly facilitated when, in
the latter part of 1990, distribution
was linked to the WHO Expanded
Program of Immunization’s (EPI)
initiative of National Immunization
Days (NID) for eradication
of polio. This initiative provided
a contact with preschool-aged
children with minimal additional
resources for delivery of the vitamin
A capsule and is credited
with success in greatly expanding
coverage. NIDs have now ceased
and countries are finding alternative
mechanisms for sustaining
the high coverage rates.
Food fortification in developing
countries received minor attention
until midway in the decade,
in spite of the successful fortification
of sugar in Central America
(51). Primitive development of
the food industry and absence of
regulatory controls were considered
deterrents. But the need for
a more sustainable intervention
than periodic supplementation
was recognized. The initiative
for universal fortification of salt
with iodine was making great
inroads into relieving iodine deficiency
disorders in developing
countries, even in remote areas.
Salt iodination advocates pushed
their success as a model for vitamin
A fortification, even though
no comparable universally safe
and acceptable food vehicle for
vitamin A was available. Today, as
noted earlier, there is momentum
behind vitamin A fortification pro-