Nutrition Research Reviews (1998), 11, 115-131
Nutrition intervention strategies to combat zinc
deficiency in developing countries
Rosalind S. Gibson and Elaine L. Ferguson
Department of Human Nutrition, University of Otago, Dunedin, New Zealand
Widespread zinc deficiency is likely to exist in developing countries where staple
diets are predominantly plant based and intakes of animal tissues are low. The
severe negative consequences of zinc deficiency on human health in developing
countries, however, have only recently been recognized. An integrated approach
employing targeted supplementation, fortification and dietary strategies must be
used to maximize the likelihood of eliminating zinc deficiency at a national level
in developing countries. Supplementation is appropriate only for populations
whose zinc status must be improved over a relatively short time period, and when
requirements cannot be met from habitual dietary sources. As well, the health
system must be capable of providing consistent supply, distribution, delivery and
consumption of the zinc supplement to the targeted groups. Uncertainties still exist
about the type, frequency, and level of supplemental zinc required for prevention
and treatment of zinc deficiency. Salts that are readily absorbed and at levels that
will not induce antagonistic nutrient interactions must be used. At a national level,
fortification with multiple micronutrients could be a cost effective method for
improving micronutrient status, including zinc, provided that a suitable food
vehicle which is centrally processed is available. Alternatively, fortification could
be targeted for certain high risk groups (e.g. complementary foods for infants).
Efforts should be made to develop protected fortificants for zinc, so that potent
inhibitors of zinc absorption (e.g. phytate) present either in the food vehicle and/or
indigenous meals do not compromise zinc absorption. Fortification does not
require any changes in the existing food beliefs and practices for the consumer and,
unlike supplementation, does not impose a burden on the health sector. A quality
assurance programme is required, however, to ensure the quality of the fortified
food product from production to consumption. In the future, dietary modifica-
tion/diversification, although long term, may be the preferred strategy because it is
more sustainable, economically feasible, culturally acceptable, and equitable, and
can be used to alleviate several micronutrient deficiencies simultaneously, without
danger of inducing antagonistic micronutrient interactions. Appropriate dietary
strategies include consumption of zinc-dense foods and those known to enhance
zinc absorption, reducing the phytic acid content of plant based staples via enzymic
hydrolysis induced by germination/fermentation or nonenzymic hydrolysis by
soaking or thermal processing. All the strategies outlined above should be
integrated with ongoing national food, nutrition and health education programmes,
to enhance their effectiveness and sustainability, and implemented using nutrition
education and social marketing techniques. Ultimately the success of any approach
for combating zinc deficiency depends on strong advocacy, top level commitment,
a stable infrastructure, long term financial support and the capacity to control
Rosalind S. Gibson and Elaine L. Ferguson
quality and monitor and enforce compliance at the national or regional level. To be
cost effective, costs for these strategies must be shared by industry, government,
donors and consumers.
Micronutrient deficiencies are a widespread public health concern. Dietary inadequacies of
iodine, vitamin A, and iron are presently estimated to adversely affect the health, mental and
physical function, and survival of more than 2 billion people in the world, even though such
inadequacies have been documented for more than a decade. In contrast, the severe negative
effects of zinc deficiency on human health in developing countries have only recently been
recognized by the United Nations. Zinc was omitted from the United Nations (1991) micro-
nutrient priority list, in part because of a lack of awareness of the importance of zinc in human
nutrition; the nonspecific clinical features of zinc deficiency (i.e. impaired growth and immune
function, poor appetite and taste acuity); lack of a recognized sensitive and specific index of
zinc status; and finally a lack of data on the zinc and antinutrient content of local staple foods in
developing countries. In retrospect the omission of zinc from the United Nations micronutrient
priority list was very unfortunate because zinc deficiency in developing countries is likely to be
as prevalent as nutritional iron deficiency.
The first cases of human zinc deficiency, described in the 1960s, were male adolescents
from the Middle East consuming plant based diets containing high levels of antinutrients,
known to inhibit zinc absorption: intakes of flesh foods were low (Prasad ef al. 1963). This
dietary pattern is common not only in the Middle East but in many other developing countries.
During childhood, zinc deficiency causes stunting and impaired cognitive function and
increases the incidence and severity of acute and persistent diarrhoea, acute lower respiratory
infections, and possibly the incidence of malaria caused by Plasmodium falciparum (Ham-
bidge, 1997). In pregnancy, zinc deficiency may contribute to complications and low birth
weight (Tamura & Goldenberg, 1996). Additionally, some non-nutritional factors may
exacerbate any deficiency of zinc, and at the same time compromise iron status. These include
chronic intestinal blood loss through parasite infections such as hookworm (Stoltzfus ef al.
1997), chronic haemolysis induced by malaria and schistosomiasis (Williams & Naraqi, 1979),
and for women of child-bearing age, menstruation and frequent reproduction cycling (Halberg,
1992). Interactions with other micronutrients may result in zinc deficiency exacerbating other
micronutrient deficiency states (e.g. vitamin A ) (Udomkesmalee et al. 1990).
With the recognition of the impact of zinc deficiency on human health comes the need to
develop programmes to combat this deficiency, preferably by incorporating zinc into pre-
existing micronutrient intervention strategies. This review examines possible intervention
strategies to combat zinc deficiency in developing countries.
Three nutrition intervention strategies have been used with varying success to combat
deficiencies of vitamin A, iron and iodine: supplementation, fortification and dietary diversi-
fication/modification. These same strategies can also be designed to simultaneously alleviate
zinc deficiency with only a modest addition to the overall costs of the programme. Imple-
mentation of these strategies in developing countries requires the combined resources of
government, industry, public health educators, donors, scientists, nongovernmental organiza-
tions and consumers.
Zinc nutrition intervention strategies
In developing countries, supplementation programmes are expensive short term strategies that
rely heavily on donor support and individual compliance. They are only appropriate for
populations where the micronutrient status, such as the zinc status, must be improved over a
relatively short time period. Supplementation is appropriate when the requirements cannot be
met from habitual dietary sources (e.g. pregnant women, low birthweight infants, infants and
children with acute or persistent diarrhoea and those recovering from severe malnutrition).
Furthermore, a health system capable of providing a consistent supply, distribution, delivery
and consumption of the zinc supplement to the targeted group(s) is also required. All too often
supplementation programmes have failed because of poor compliance, poor coverage, absence
of commitment at the national and community levels and poorly designed communication
messages. Increased burden to already overloaded health care delivery systems may also be a
contributing factor (Gillespie et al. 1991).
More qualitative research is required to understand the complex reasons for poor com-
pliance in supplementation programmes. In iron supplementation programmes, poor com-
pliance has often been linked with the onset of side effects. However, behavioural barriers are
also implicated, especially during pregnancy when long term medication is thought to be
harmful to the baby or result in a bigger baby and therefore delivery difficulties (Galloway &
Zinc supplements can be given alone or as a component of multimicronutrient supplements
such as prenatal iron and folate. Care must be taken when formulating these multimicronutrient
supplements to use salts that are readily absorbed, and levels that will not induce antagonistic
interactions among major and trace elements. For zinc, possible interactions between zinc and
calcium (Wood & Zheng, 1997), zinc and non-haem iron (Solomons, 1986) and zinc and
copper (Yadrick et al. 1989; Fischer et al. 1984) should be considered.
When given alone, zinc supplements should be administered in the fasting or post-
absorptive state to avoid any dietary components interfering with zinc absorption (Oelshlegel &
Brewer, 1977). In contrast, multimicronutrient supplements should be consumed with food
because the presence of the ligands in food appears to minimize the inhibitory effect of non-
haem iron on zinc absorption (Valberg et al. 1984; Sandstrom et al. 1985; Walsh et al. 1994)
and vice versa (Crofton et al. 1989; Yadrick et al. 1989; Brown et al. 1997).
There are currently three major barriers to effective zinc supplementation programmes.
The first is the high frequency of the dose required. Most of the zinc in the human body exists in
nonlabile pools (e.g. muscle and bone) and is not normally released during zinc deprivation
(Aggett & Comerford, 1995). Furthermore, daily rather than intermittent doses of zinc were
required to produce a body growth response that fully compensated for a previously deficient
zinc intake in rats (MomciloviG, 1995). Hence, unlike iron supplements, weekly or twice
weekly doses may not be as effective as smaller doses given daily. Bates et al. (1993) gave
70 mg zinc as zinc sulphate twice weekly for 1.25 years in a double-blind zinc supplementation
study of Gambian infants but did not observe any significant effect of the zinc supplement on
biochemical indices of zinc status. Small changes in arm circumference, an improvement in
urinary 1actulose:creatinine molar ratio (an index of intestinal permeability) and a trend
towards fewer malaria episodes were observed.
Secondly, uncertainty still exists about the best type of zinc salt to use in relation to
bioavailability and side effects. Both salt-solubility-dissolution and intragastric pH are known
to influence oral zinc absorption (Sturniolo et al. 1991). Human studies of zinc absorption from
zinc ascorbate, methionine, histidine, citrate, gluconate, picolinate, oxide and aminoate, mea-
Rosalind S. Gibson and Elaine L. Ferguson
sured by the oral zinc tolerance method, have given varying and sometimes conflicting results
(Barrie et al. 1987; Scholmerich et al. 1987; Prasad et al. 1993; Rosado et al. 1993; Henderson
et al. 1995). Prasad & co-workers (1993) recommended oral zinc acetate because it is well
tolerated and readily available, especially at low intragastric pH, and is comparable and/or
superior to zinc sulphate and zinc aminoate; others advocate using zinc methionine and zinc
histidine despite their association with increased urinary zinc excretion (Scholmerich et al.
1987; Rosado et al. 1993). Zinc oxide is poorly absorbed, the low solubility at the basic pH of
the small intestine preventing it from dissociating in the gastrointestinal tract (Prasad et al.
1993; Wolfe et al. 1994; Henderson et al. 1995). In a study of pregnant adolescents receiving
prenatal supplements of iron and elemental zinc as oxide or sulphate, plasma zinc levels of
those receiving the supplemental zinc oxide (25 mg Zn) remained at levels comparable to those
of the unsupplemented women; only those receiving the zinc sulphate (20 mg Zn) supplement
had increased plasma zinc concentrations (Wolfe et al. 1994). To date, most zinc supple-
mentation studies in humans have used either the sulphate, acetate, gluconate, or amino acid
chelates of zinc (Gibson et al. 1989; Cavan et al. 1993; Gibson, 1994; Sazawal et al. 1995;
Rosado et al. 1997). More research is necessary on the mechanisms underlying the absorption
and utilization of zinc to identify the most effective dietary zinc supplement.
The current recommended preventive doses of supplemental zinc for infants and children
are 5 mg/d for children less than 5 years, and 10 mg/d for those over 5 years (Gibson et al.
1989; Tomkins el al. 1993), although in some developing countries where the zinc status is
likely to be very poor, even higher doses may be necessary (Gibson, 1994; Sazawal et al. 1995).
During pregnancy, preventive doses of 20-25mg elemental zinc per day, generally as zinc
sulphate, have been most frequently used (Swanson & King, 1987; Tamura & Goldenberg,
1996). At this level of zinc supplementation (i.e. 25mg Zn as zinc sulphate), significant
improvements in birth weight and head circumference were reported in the infants of otherwise
healthy African American zinc-supplemented women with below average initial plasma zinc
levels compared with their counterparts receiving a placebo (Goldenberg et al. 1995). Routine
zinc supplementation may be advisable in early adolescence in countries where zinc deficiency
is likely to be endemic, to ensure that women enter pregnancy with optimal zinc nutriture.
For children with protein-energy malnutrition and persistent diarrhoea, a daily treatment
dose of -4mg/kg body weight of elemental zinc is recommended, preferably given in two
daily doses as a syrup. For a male child 6-8 years old this corresponds to 80mg/d. Such zinc
supplements dramatically reduce stool volume and diarrhoea duration (Sachdev et al. 1990),
and improve intestinal permeability and thus appetite (Roy et al. 1992). Chronic overdosage of
zinc (i.e. 100-300mg Zn/d for adults) may induce copper deficiency (Prasad et al. 1978) and
alterations in the immune response and serum lipoprotein levels (Chandra, 1984). Some of
these disturbances may also occur at lower doses (i.e. 50mg Zn/d) although the data are
conflicting and require confirmation (Hooper et al. 1980; Freeland-Graves et al. 1982; Black et
al. 1988; Yadrick et al. 1989). Doses of 25-35 mg Zn/d do not appear to pose a health hazard
(Smith, 1994). Overt toxicity symptoms such as nausea, vomiting, epigastric pain, lethargy and
fatigue may occur with extremely high zinc intakes (Fosmire, 1990).
Fortification with multiple micronutrients including zinc could be a cost effective sustainable
method for improving zinc status at a national level in countries where zinc deficiency is
endemic. Alternatively, fortification can be targeted in specific regions and/or for certain high
Zinc nutrition intervention strategies
risk groups (e.g. weaning foods for infants) within a country. Fortification does not require any
changes in the existing food beliefs and practices of the consumer and, unlike supplementation,
does not impose a burden on the health sector. Moreover, because the cost of fortification is
borne by industry and the consumer, the costs to governments are generally low. Multiple
micronutrient fortification is more cost effective than single fortification and, like supple-
mentation, requires both an efficient production and distribution system within the country to
A critical factor determining the selection of the food product to be fortified is whether it is
consumed either widely or preferentially by the at-risk groups. For fortification programmes to
be effective, at least 50% of the population at risk of zinc deficiency should consume the
potential food vehicle throughout the year. Also, intakes of the food product at a relatively low
level of consumption must be sufficient to provide adequate zinc to the population most at risk
of deficiency, whereas at higher consumption levels there should be no risk of toxicity. A guide
on the collection of food consumption levels for potential food vehicles is available (Fitz-
Gerald, 1997). Information on methods of storage, food processing and preparation of the
potential food vehicle must also be available to assess any potential losses of the fortificant
Fortification also requires a food vehicle which is centrally processed, temperature stable,
technologically and economically fortifiable, and undergoes no changes in taste, texture and
appearance during storage. Prior to commercial production, the absorption of zinc from dif-
ferent indigenous meals containing the fortified food vehicle must be quantified. If the potential
food vehicle and/or the indigenous meals contain potent inhibitors of zinc absorption (e.g.
phytate), the added zinc (and iron), like the intrinsic zinc and iron, will be poorly absorbed, and
hence have limited effect on the zinc and iron status of the consumer. In such cases, efforts
should be made to develop protected fortificants for zinc (i.e. fortificants that prevent zinc from
binding to phytic acid), similar to those developed for iron.
Successful fortification also depends on the availability of an appropriate fortificant. It
must be readily absorbed and utilized, resistant to any dietary inhibitors of zinc absorption,
safe, stable, acceptable, and have no effect on the organoleptic qualities of the food vehicle.
Currently, in industrialized countries, zinc oxide is most frequently used for fortifying cereals
because it is a cheap white powder that causes no organoleptic problems. However, because it
is insoluble at high intragastric pH, it has only low to moderate bioavailability (Henderson et
al. 1995). In experimental rat studies based on zinc in the tibia, zinc from zinc oxide was said
to have 61 % availability relative to zinc sulphate (Wedekind & Baker, 1990). It is possible
that its solubility could be improved by the concomitant addition of certain organic chelators
(e.g. cysteine) (Desrosiers & Clydesdale, 1989). Heptahydrate zinc sulphate has also been
used in the past in the US for fortifying blended foods (Combs et al. 1994). Although it is
better absorbed than zinc oxide, it is six times more expensive and is not resistant to dietary
Sodium iron EDTA is an example of a bioavailable protected iron compound strongly
recommended for use in developing countries because it does prevent iron from binding with
the phytic acid in cereals (INACG, 1993), and may even enhance absorption of other intrinsic
inorganic iron (Viteri et al. 1995). However, although it is better absorbed, it is six times more
expensive than ferrous sulphate. Sodium iron EDTA also apparently increases the absorption of
zinc from meals containing phytic acid (Davidsson et al. 1994) and such EDTA-containing
compounds may be the fortificant of choice for developing countries.
Concern about whether intakes of EDTA could exceed the FAO/WHO (1993) acceptable
daily intake level (2.5 mg/kg) led Beaton (1995) to estimate intakes of EDTA for various age
Rosalind S. Gibson and Elaine L. Ferguson
groups based on data on food consumption from Kenya. Calculated mean intakes for even the
highest intake group (school children) were well below the FAO/WHO (1993) acceptable daily
intake. Research must be pursued however on the possible influence and physiological effect of
EDTA-containing compounds on absorption of potentially toxic metals (Pb, Hg, Al, Mn)
The amounts of micronutrients currently added to cereals in most industrialized countries
are generally based on restoration levels (i.e. adding enough to refined flour to restore the level
to that of the unrefined cereal). In developing countries zinc should be added at levels that are
higher than that normally present in the natural food substances (i.e. true fortification). Some of
the factors that must be taken into account when selecting the fortificant level have already
been discussed in relation to choice of the potential food vehicle. They include per capita
consumption of the food vehicle; food preparation and processing methods of the food vehicle;
dietary components that inhibit or enhance the bioavailability of the fortificant; possible
antagonistic interactions with other multimicronutrient fortificants; prevalence of zinc defi-
ciency within the target population; and estimated requirements for zinc (Lotfi et al. 1996).
Details on how to calculate the optimal fortificant levels for a food product are given in
FitzGerald (1997). If the fortified food vehicle is consumed by both adults and children, careful
attention must be given to prevent excessive intakes of zinc by young children whose
requirements are less. Obviously, the fortification level must take into account the toxic
threshold level for zinc for normal individuals. The US daily reference dose (RfD) is set at
0.3 mg/kg, based on a lowest-observed-adverse-effect level (LOAEL) of 1-0 mg/kg. The RfD
represents an estimate of a daily exposure (including sensitive subgroups) that is likely to be
without appreciable risk of deleterious effects during a lifetime (US EPA, 1992). Discussion of
the appropriateness of the US RfD is given in Smith (1994).
The cost of fortifying food staples is relatively low compared with their total cost. Beaton
(1995) estimated the additional cost of fortifying milled cereals with a multimicronutrient
premix for refugee feeding to be about US$37/MT, of which only about US$lO/MT is for the
cost of the micronutrient additions. Combs et al (1994) estimated the cost of a micronutrient
premix for US corn-soy blended food to be approximately US$S/MT; cost for zinc alone (as
zinc sulphate monohydrate) at the level of 240g/MT was US$l.lO/MT.
To date, multiple micronutrient fortificants that include zinc have been used with only a
limited number of food vehicles. Foods in the US that are frequently enriched or fortified with
zinc and iron include flour, bakery goods, breakfast cereals, cereals, macaroni and infant
formulas and infant foods. Stable isotope studies indicate that the level of iron currently used
to fortify foods in the US has no adverse effect on zinc absorption (Combs et al. 1994).
In 1995 Action Internationale Contra la Faim (AICF) formulated a micronutrient premix
powder to be added to cereal/pulse based diets for supplementary feeding programmes. For-
tificant levels were calculated to sustain health or growth or recovery from mild/moderate
malnutrition and are not adequate for treating frank deficiencies. The zinc salt recommended
was heptahydrate zinc sulphate. The recommended levels were expressed in nutrient density
terms using the EU Population Reference Intake (CEC, 1994) and the UK Reference Nutrient
Intake (COMA, 1991) and adjusted to take into account the health, dietary and environmental
status of refugees. Details of the composition and derivation of the levels for the premix are
given in Golden et al. (1995). Table 1 compares the levels (per 100 kcal) in cereal/pulse based
diets, fortified with the AICF micronutrient premix, with the micronutrient densities recom-
mended by Beaton (1995) for a cereal fortification premix. The latter premix, unlike that of the
AICF, was designed for addition to the cereal based diet of the general population of refugees
in Africa, and not targeted specifically for those with mild’/moderate malnutrition. Two
Zinc nutrition intervention strategies
Table 1. Proposed levels for micronutrient fortificants (per 100 kcal food) based on cereal/legume
mixtures for refugee feeding
Vitamin 812 (ng)
Folic Acid (pg)
Vitamin C (mg)
Pantothenic acid (mg)
Vitamin A (pg)
Vitamin D (pg)
Vitamin E (mg)
Vitamin K (pg)
* levels for mild/moderately malnourished refugees; ** levels for general population of refugees
AICF, Action lnternationale Contra la Faim
micronutrient fortificant levels are given: one based on the FAO/WHO basal requirement and
the other on the corresponding normative requirement estimates (FAO/WHO, 1988; WHO,
1996). Note that the zinc level using the AICF micronutrient fortificant, expressed per 100 kcal,
is between the two levels based on the basal and normative requirement estimates formulated
by Beaton (1995). The levels of calcium, iron and copper for the two were selected to minimize
risk of antagonistic interactions (Wood & Zheng, 1997; Solomons, 1986; Yadrick et al. 1989;
Cook e f al. 1991).
The World Health Organization (WHO) has also produced a micronutrient premix powder
for treating infants and children in refugee camps with severe malnutrition and persistent
diarrhoea (ISGPD, 1996). The zinc salt used in this premix is zinc gluconate. The safety and
effectiveness of this premix for treating severe malnutrition in refugee camps in Africa has
recently been established.
There is also an urgent need in developing countries to fortify complementary foods with
multimicronutrients. Table 2 presents selected major and trace mineral densities of three
complementary foods used in sub-Saharan Africa (Gibson et al. 1997). The mineral densities
are compared with the corresponding desired nutrient densities for complementary foods cal-
culated by Brown et al. (1997). The estimates are for an infant 9-1 l months old, assuming an
average volume and composition of breast milk and three 250 gram meals/d. Note that the
nutrient densities for calcium, zinc, and iron in the three complementary foods are well below
the desirable levels. The high phytate : zinc molar ratios of the diets exacerbate the situation as
Rosalind S. Gibson and Elaine L. Ferguson
Table 2. Nutrient density (per 100 kcal) of three weanling porridges compared with nutrient density
desired for child of 9-1 1 months
maize 80 Yo, 70 %, groundnuts
soya 20 YO
20 YO, sorghum 10 Yo
Unrefined maize potato 70 %,
green leaves 19 Yo,
cowpeas 9 YO, oil 2 Yo
H, high bioavailability; L, low bioavailability; Phy, phytate
the availability of the minerals is likely to be low. Nutrient densities for niacin, riboflavin and
vitamin A may also be inadequate depending on the composition of the complementary foods
and the amount and composition of breast m i l k consumed (NAS, 1991).
In some developing countries where zinc deficiency is widespread, no centrally processed
food vehicle exists. In these circumstances, fortification at the village or household level using
vitamin/mineral premix powders may be an alternative strategy. Bressani et a 1 (1972) inves-
tigated the feasibility of community based fortification of lime soaked maize in Guatemala and
devised some innovative strategies for enforcing quality control at the village level. For
example, the miller was supplied with a series of labelled cups such that if a householder came
with maize weighing 8 kg, cup #8 would be used to measure out the amount of premix to be
added to an 8 kg batch of maize.
Techniques have also been developed for use in developing countries for the fortification of
unmilled whole cereal grains. These include coating, infusion or the use of extruded grain
analogues. Addition of the fortified grains to normal unfortified grains generally occurs at the
rate of 1 : 200. To date both the difficulty of completely masking the fortified whole grains in the
final mixture and their cost have limited the application of these techniques (Lotfi et al. 1996).
Finally, a quality assurance programme is essential to ensure the quality of fortified food
products from production to consumption. Both internal monitoring within the production plant
and external monitoring by independent agencies is required; details of these strategies are
summarized in Lotfi et al. (1996). Governments can facilitate successful quality assurance
programmes by developing standards and associated legislation and enforcing the regulations.
Quality control for fortification programmes at the village or household level is likely to prove
To be successful at a national level, fortification must be mandated by government reg-
ulations that eliminate competition with unfortified products, ensure quality and safety of the
zinc-fortified foods and honest and fair practices in marketing them. As well, governments can
assist national fortification policies by exempting imported food technology and fortificant
mixes from tariffs.
The efficacy of all fortification programmes should be tested under the conditions of
normal distribution and in the appropriate dietary setting before they are released on the market.
After their implementation, steps should be taken to monitor and evaluate both the effect of and
compliance with the programme. Ultimately, to be successful, fortification must be a profitable
business proposition, although costs may be shared by industry, government, donors and
consumers (Gillespie et al. 1991).
Zinc nutrition intervention strategies
Both supplementation and fortification rely on a stable infrastructure and require financial
support on a long standing sound economic basis. However, the third strategy, dietary mod-
ification/diversification, is a more sustainable, long term, economically feasible, equitable, and
culturally acceptable strategy which can be used to alleviate several micronutrient deficiencies
simultaneously without risk of antagonistic interactions. It involves changes in food selection
patterns and/or traditional household methods for preparing and processing indigenous foods,
with the overall goal of enhancing the availability, access, and utilization of foods with a high
content and bioavailability of zinc throughout the year. To implement effective dietary stra-
tegies, knowledge of the local dietary patterns, food beliefs, preferences and taboos is required,
as well as the ability to change attitudes and practices.
In those developing countries where diets are predominantly cereal based and fermented
cereals are not widely consumed, the major causative factor of zinc deficiency is not low zinc
intakes, but poor zinc absorption. In contrast, for countries with diets based on starchy roots and
tubers, low zinc intakes are a major determinant of zinc deficiency because these staples are
poor sources of dietary zinc (Gibson, 1994). A variety of methods are therefore appropriate to
combat zinc deficiency. The more important of these methods are outlined briefly below. Each
aims to increase the total zinc intake and/or the absorption of dietary zinc.
Improved cereal varieties
Intakes of zinc can be increased by persuading farmers to grow new cereal varieties. Some of
these have higher zinc concentrations than earlier strains and tolerate zinc deficient soils. These
‘zinc-efJicient genotypes’ are also more disease resistant, have improved seedling vigour,
enhanced germination and a higher grain yield (Graham et al. 1992). Hence their use will not
decrease crop productivity or increase costs to farmers. For some cereals (e.g. maize), the
genetic potential exists to increase the level of methionine in the mature maize kernel. This is
important because enhanced zinc absorption has been reported in rats fed mature maize kernels
with dietary supplements of methionine or cysteine (House et al. 1996). Reducing the phytic
acid concentration of certain cereals by plant breeding is also now a feasible strategy for
enhancing zinc absorption (Raboy, pers. comm.).
Addition o f enhancers of zinc absorption
Zinc absorption can be enhanced by the increased consumption of foods such as cellular animal
proteins (meat, poultry and fish). Certain sulphur amino acids (methionine and cysteine) and
cysteine-containing peptides, released during the digestion of cellular animal proteins, and
organic acids (e.g. citric and lactic acid) produced during fermentation enhance zinc absorption,
and can counteract the negative effect of phytic acid, even when levels of zinc in the diet are
only modestly increased (Sandstrom et al. 1989). The mechanism is unclear: naturally
occurring mineral chelates may exist in animal protein (Scott & Zeigler, 1963). Alternatively,
soluble ligands with zinc may be formed which facilitate zinc absorption (Snedeker & Greger,
1983) or prevent the formation of the insoluble zinc-phytate complex (Sandstrom et al. 1980).
Rosalind S. Gibson and Elaine L. Ferguson
Modified milling practices
The phytic acid content of cereals which have the acid localized in the outer aleurone layer (e.g.
wheat, rice, sorghum) or in the germ (e.g. maize) can be reduced by modifying milling prac-
tices (O’Dell et al. 1972). Careful milling can also reduce the dietary fibre content, which may
enhance zinc absorption to some degree. For legumes such as peas and beans, the cotyledons
and not the seed coat contain most of the phytate so that when the coat is removed, the phytate
content actually increases.
Soaking to reduce phytic acid content
Most plant based foods contain some phytase enzymes (myo-inositol hexaphosphate phos-
phohydrolases) (EC 220.127.116.11), although in dry or dormant seeds activity is negligible. Phytase
enzymes hydrolyse phytic acid (myo-inositol hexaphosphate; IP6) to lower inositol phosphates
(IP4-IP1) which do not form insoluble complexes with zinc (Lijnnerdal et al. 1989). Hence,
knowledge of the optimal conditions for enhancing phytase activity in plant based diets is
The level of endogenous phytase activity in cereals depends on the species and variety. It is
high in rye and wheat but very low in maize and sorghum, the two cereal staples of sub-Saharan
Africa (Table 2) (Gibson et al. 1997). Soaking can activate endogenous cereal phytases,
although conditions must be controlled as the activity depends on the pH of the medium and
temperature; pH 5.0-4.5 appears to be optimal for cereal phytases (Cheryan, 1980). Soaking at
room temperature initiates optimal endogenous phytase activity in maize (2ka mays), white
sorghum (Sorghum bicolor), and soyabeans, whereas for wheat (Triticum aestivum) and several
varieties of beans such as mung beans (Phaseolus aureus) and lima beans (P. lunatus), tem-
peratures of about 60°C are optimal.
Soaking has also been advocated as a practical, nonenzymic, household method to reduce
the phytic acid content of certain cereals (e.g. maize), and most legumes, including soyabeans.
Some of the phytic acid in these staples is stored in a relatively water-soluble form such as
sodium or potassium phytate, and hence can be removed by diffusion. The reported proportion
of water-soluble phytate ranges from 10 % in defatted sesame meal to 70-97 % in red kidney
beans, corn germ and soy flakes (De Boland et al. 1975; Chang et al. 1977). Discrepancies in
the reported levels of soluble phytate in these staples can be attributed to variations in the
conditions used to extract the phytic acid, particularly the pH, and the confounding effects of
protein, calcium and magnesium ions (Tabekhia & Luh, 1980). Soaking may also remove other
antinutrients such as saponins and polyphenols.
Germination to increase phytase activity
Germination increases phytase activity in seeds through induction and/or de novo synthesis;
phytase levels may increase by 23-588 % after 2-3 days depending on the cereal (Table 3).
Phytase-induced reductions in inositol hexaphosphate content after 2-3 d germination of
cereals can range from 52 % for rice to 21-28 % for white corn (Table 4). The concentration of
minerals (including zinc) and other nutrients (e.g. protein, nucleic acids, certain amino acids,
water-soluble B vitamins) do not change during germination; any reported increases may arise
from losses as a result of transpiration during sprouting (Lorenz, 1980). Nevertheless, germi-
Zinc nutrition intervention strategies
Table 3. Change in phytase activity during germination
% Increase in
phytase activity treatment days germination
Corn, yellow, US
Corn, white, US
Table 4. Myeinositol hexaphosphate content (mg/l O O g dry weight) of selected cereals before
and after germination
Corn, white, Malawi
Corn, white, US
nation decreases the tannin content of some beans (e.g. Viciufubu) and red sorghum, owing to
the formation of complexes with proteins and the gradual degradation of oligosaccharides
To enhance phytase-induced phytate hydrolysis, some germinated cereal flour can be
added to ungerminated cereal flours. For example, the addition of 10 % germinated maize flour
to maize dough was reported to decrease the phytic acid content of kenkey in Ghana by 56 %
(Amoa & Muller, 1975); even greater phytate reductions can be achieved if these doughs or
flour slurries are incubated at the optimal temperature, pH, and time, to maximize phytase
During the germination of cereals, but not legumes, the activity of a-amylase (EC 18.104.22.168)
increases, resulting in the hydrolysis of amylose and amylopectin to dextrins and maltose
(Lorenz, 1980). As a result, the addition of germinated cereal flours (at levels of 5-10%)
reduces the viscosity of thick cereal porridges prepared from flour concentrations of between 20
and 25 %. Such porridges have an initial viscosity of possibly 50 000 CP and this is reduced to
an easy-to-swallow semi-liquid consistency (i.e. 3000 cP) suitable for infant feeding without
further dilution with water (Mosha & Svanberg, 1990) (Table 5). Consequently, gruels with a
higher energy density (4.2kJ/g v. 0-84kJ/g) and zinc content, but lower [Phy]/[Zn] molar
ratios, can be prepared and used for infant feeding. Care must be taken to ensure that all
pomdges and doughs prepared from germinated flours are decontaminated by heating prior to
Rosalind S. Gibson and Elaine L. Ferguson
Table 5. Changes in viscosity of rice porridge (25 YO dry matter) after the addition of germinated
Amount of germinated sorghum added (%)
Modified from Gopaldas et a/. (1 986).
use, because germination increases the concentration of Enterobacteriaceae, fungi, Bacillus
spp. etc. including potential pathogenic and toxigenic species (Nout, 1993).
Fermentation to increase microbial phytase activity
Fermentation induces phytate hydrolysis via the action of microbial phytases (EC.22.214.171.124)
which can originate either from the microflora on the surface of the seeds, or by inoculation
with microbial starter cultures (Chavan & Kadam, 1989). The microbial activity results in
organic acid production, hence lowering the pH of the cereal dough or flour slurry below the
optimal range for cereal phytases (i.e. pH 5.0-4.5). The exogenous microbial phytases then
assume a greater role as their activities remain optimal over a lower and broader pH range (i.e.
2.5-5.5) than cereal phytases (4.5-5.5). Fermentation should be carried out for at least 16-24
hours at 25-30°C to ensure that the pH of the cooked dough or porridge falls to a level that
reduces the growth of diarrhoeal pathogens (i.e. < pH 3.8) (Mensah et al. 1991).
Use of an enrichment inoculum is preferred because the time required to achieve phytate
hydrolysis is reduced; reductions of up to 95 % in the IP-5 and IP-6 content have been reported
after fermentation at 25-30°C for 16-24h. Use of high tannin cereals should be avoided
because the tannins inhibit phytase activity and also further inhibit the bioavailability of iron
(Svanberg et al. 1993). Starter cultures derived from natural, lactic-acid-fermented millet or
maize gruel prepared by the traditional ‘back-slopping’ method using anaerobic fermentation at
30°C can be used to inoculate the flour slurries or doughs. Alternatively, commercial phytase
enzymes prepared from moulds (e.g. Aspergillus oryzae or A. niger) that are stable over an even
wider pH (3.5-7.8) and temperature range can also be used (Turk & Sandberg, 1992; Sandberg
et al, 1996), although their high cost precludes their use in many developing countries at the
Fermentation has several other advantages: it ,reduces the energy required for cooking and
improves the safety of the final food product because the reduced pH inhibits growth of
diarrhoeal pathogens; antimicrobial substances may also be produced during fermentation.
To date, in vivo comparisons of the bioavailability of zinc (and iron) in fermented and
unfermented cereal based foods such as porridges prepared for infant and child feeding are not
available. Increases in in vitro measurements of soluble iron have been reported in porridges
fermented with togwa as an enrichment inoculum, with and without the addition of commer-
cially prepared phytase enzyme (Svanberg & Sandberg, 1988; Svanberg et al. 1993).
Zinc nutrition intervention strategies
Fermented with soaking
5 ; ;
Flours produced from germinated and nongerminated staples can be mixed together and then
soaked and fermented using a microbial starter culture. Such a combination of strategies can
result in large reductions in the phytic acid content. The addition of germinated flours increases
the amount of endogenous phytase activity present. Soaking prior to the addition of the starter
culture allows for both diffusion of soluble phytates and a longer incubation time in the optimal
pH range for endogenous cereal phytases before microbial activity lowers the pH. Addition of a
starter culture provides a source of microbial phytases which can hydrolyse phytic acid until the
pH falls to < 3.8. This takes between 16 and 24 h, after which the fermented flours are mixed
with water to form slumes and then cooked to form porridges. This combination of strategies
can reduce the phytic acid content by as much as 90 % (Fig. 1) while simultaneously enhancing
zinc absorption, protein quality, protein digestibility, microbiological safety, and keeping
quality, yet decreasing toxins such as haemagglutinins and cyanide (Svanberg et al. 1993).
Caution must be used when evaluating the effect of enzymic and nonenzymic hydrolysis of
phytate in plant based staples. Inconsistencies arise because of differences in methods for the
phytate and phytase assays (Xu et al. 1992). Phytase activity is generally based on the amount
of released inorganic phosphate or inositol (Lolas & Markakis, 1977). The latter could also be
produced by nonspecific phosphates acting upon some lower inositol phosphates or organic
sources other than phytates. Therefore, it is preferable to use the HPLC method to determine
phytase activity v i a monitoring changes in inositol hexaphosphate levels after incubation under
optimal conditions for phytase activity (Sandberg & Andersson, 1988). The HPLC method
should also be used to separate, identify, and quantify the other higher and lower myo-inositol
phosphates (Lehrfeld, 1989).
Widespread zinc deficiency is likely to exist in developing countries where diets are pre-
dominately plant based and intakes of animal tissues are low. An integrated approach
employing targeted supplementation, fortification and dietary strategies must be used to
Rosalind S. Gibson and Elaine L. Ferguson
maximize the likelihood of eliminating zinc deficiency at a national level. The strategies must
also be integrated with ongoing national food, nutrition, and health education programs to
enhance their effectiveness and sustainability, and implemented using nutrition education and
social marketing techniques.
Successful implementation and sustainability of these strategies will require increased
awareness of the importance of zinc in human health among bilateral and nongovernment
agencies, the scientific community, and the general public. The strategies must also be co-
ordinated in developing countries at the international, national and local levels among gov-
ernment, education, public health and industry. An international network on zinc nutriture in
developing countries might promote such coordination.
Ultimately the success of any approach for combating zinc deficiency depends on strong
advocacy, top level commitment, a stable infrastructure, long term financial support, and the
capacity to control quality and monitor and enforce compliance at the national or regional level.
To be cost effective, costs for these strategies must be shared by industry, government, donors
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