User:CFCF/Zinc deficiency

Zinc deficiency in animals is defined either qualitatively as insufficient zinc to meet the needs of the body, or quantitatively as a serum zinc level below the normal range of 60 - 130 mcg/dL. Zinc deficiency can also occur in plants and soil.

Poor appetite
Especially in young and elderly

Taste
smell and memory are also connected with zinc.

Acrodermatitis enteropathica
This condition is a zinc deficiency due to a congenital absence of the ZIP4 zinc transport protein.

Anorexia
Zinc deficiency may cause a decrease in appetite which can degenerate into anorexia or anorexia nervosa. Appetite disorders, in turn, cause malnutrition and, notably, inadequate zinc intake. Anorexia itself is a cause of zinc deficiency, thus leading to a vicious cycle: the worsening of anorexia worsens the zinc deficiency. The use of zinc in the treatment of anorexia has been advocated since 1979 by Bakan. At least 15 trials showed that zinc improved weight gain in anorexia. A 1994 randomized, double-blind, placebo-controlled trial showed that zinc (14 mg per day) doubled the rate of body mass increase in the treatment of anorexia nervosa. This phenomenon is known as malnutrition-induced malnutrition: many other nutrients can contribute to this phenomenon
 * Esophageal squamous cell carcinoma (ESSC) - Zinc deficiency is also implicated in the pathogenesis of ESCC in many populations, including persons with chronic alcohol consumption. Abnet et al. provided the strongest evidence of an association between dietary zinc deficiency and ESSC in a high-incidence area by establishing an inverse relationship between zinc concentration in biopsy samples and the subsequent risk of developing ESCC. In a rat model, chronic zinc deficiency induces an inflammatory gene signature that fuels development.
 * Cognitive and motor function impairment - Cognitive and motor function may also be impaired in zinc deficient children. Zinc deficiency can interfere with many organ systems especially when it occurs during a time of rapid growth and development when nutritional needs are high, such as during infancy. In animal studies, rats who were deprived of zinc during early fetal development exhibited increased emotionality, poor memory, and abnormal response to stress which interfered with performance in learning situations. Zinc deprivation in monkeys showed that zinc deficient animals were emotionally less mature, and also had cognitive deficits indicated by their difficulty in retaining previously learned problems and in learning new problems. Human observational studies show weaker results.  Low maternal zinc status has been associated with less attention during the neonatal period and worse motor functioning.  In some studies, supplementation has been associated with motor development in very low birth weight infants and more vigorous and functional activity in infants and toddlers. Plasma zinc level has been associated with many psychological disorders. However, the nature of this relationship remains unclear in most instances. An increasing amount of evidence suggests that zinc deficiency could play a causal role in the etiology of depression. Preliminary clinical trials suggest that zinc may be an effective treatment.
 * Diarrhea and pneumonia - Zinc deficiency contributes to an increased incidence and severity of both diarrhea and pneumonia.  Studies have shown that zinc treatment results in a 25 percent reduction in duration of acute diarrhea and a 40 percent reduction in treatment failure or death in persistent diarrhea. The studies determined that a ten-day therapy of zinc treatment can considerably reduce the duration and severity of diarrheal episodes, decrease stool output, and lessen the need for hospitalization. Zinc may also prevent future diarrhea episodes for up to three months. The current World Health Organization recommendation for diarrhea control includes the use of 20 mg per day of zinc supplementation for 10 to 14 days (10 mg per day for infants under the age of six months). A zinc taste test may have potential for diagnosing deficiency.
 * Dysmenorrhea - High doses of zinc, prevents dysmenorrhea.
 * Hunger - the influence of zinc on hunger is complex and probably depends upon the status of other nutrients, the developmental stage of the animal, and percentage body fat. Some research groups have argued for a role of zinc deficiency decreasing appetite, while others have shown zinc ingestion can reduce feelings of hunger by increasing leptin levels.  There is evidence that the way zinc influences hunger depends on the sodium/osmotic status of the organism, with low sodium/low zinc levels increasing hunger and high sodium/low zinc levels decreasing it.  An organism with a low level of zinc has an increased susceptibility to hypoosmotic stress and cell rupture.  Thus if the osmotic pressure is too low the organism may be inclined to eat to raise osmolality and prevent osmotic shock. It should be noted that zinc is known to affect osmolality by increasing sodium retention. In rats, the "first visible sign" of zinc deficiency is a decreased appetite.

Hypotonic fluids can exacerbate some symptoms
Zinc protects cells against hypotonicity. Drinking too much hypotonic fluid (long term, 4+ months) during zinc deficiency can cause skin lesions which are red, scaley, and hairless. These lesions will blister slightly after drinking hypotonic fluids and these same blisters will scab only after restoring osmolarity. Low sodium intakes have also been shown to directly reduce zinc retention

Birth defects
Zinc deficiency during pregnancy can negatively affect both the mother and fetus. Animal studies indicate that maternal zinc deficiency can upset both the sequencing and efficiency of the birth process. An increased incidence of difficult and prolonged labor, hemorrhage, uterine dystocia and placental abruption has been documented in zinc deficient animals. These effects may be mediated by the defective functioning of estrogen via the estrogen receptor, which contains a zinc finger protein. A review of pregnancy outcomes in women with acrodermatitis enteropathica, reported that out of every seven pregnancies, there was one abortion and two malfunctions, suggesting the human fetus is also susceptible to the teratogenic effects of severe zinc deficiency. However, a review on zinc supplementation trials during pregnancy did not report a significant effect of zinc supplementation on neonatal survival.

Testosterone deficiency
Zinc is required by men to produce testosterone.

Vitamins A and D
Plasma zinc levels have been found to be dependent upon vitamins A and D. This suggests that a Vitamin A or D deficiency could cause a secondary zinc deficiency and that for treatment of zinc deficiency one should ensure adequate vitamin A and D intake.

Signs of zinc deficiency include diarrhea, and wasting of body tissues. A lack of zinc can contribute to acne. Eyesight, taste,    smell and memory are also connected with zinc. A deficiency in zinc can cause malfunctions of these organs and functions. Congenital abnormalities causing zinc deficiency may lead to a disease called acrodermatitis enteropathica.

Anorexia
Zinc deficiency may cause a decrease in appetite which can degenerate into anorexia or anorexia nervosa. Appetite disorders, in turn, cause malnutrition and, notably, inadequate zinc intake. Anorexia itself is a cause of zinc deficiency, thus leading to a vicious cycle: the worsening of anorexia worsens the zinc deficiency. The use of zinc in the treatment of anorexia has been advocated since 1979 by Bakan. At least 15 trials showed that zinc improved weight gain in anorexia. A 1994 randomized, double-blind, placebo-controlled trial showed that zinc doubled the rate of body mass increase in the treatment of anorexia nervosa (AN). Deficiency of other nutrients such as tyrosine and tryptophan (precursors of the monoamine neurotransmitters norepinephrine and serotonin, respectively), as well as vitamin B1 (thiamine) could contribute to this phenomenon of malnutrition-induced malnutrition.

Cancer
Zinc deficiency is also implicated in the pathogenesis of Esophageal Squamous Cell Carcinoma (ESCC) in many populations, including persons with chronic alcohol consumption. Abnet et al. provided the strongest evidence of an association between dietary zinc deficiency and Esophageal Squamous Cell Carcinoma in a high-incidence area by establishing an inverse relationship between zinc concentration in biopsy samples and the subsequent risk of developing ESCC. In a rat model, chronic zinc deficiency induces an inflammatory gene signature that fuels Esophageal Squamous Cell Carcinoma development.

Cognitive and motor function impairment
Cognitive and motor function may also be impaired in zinc deficient children. Zinc deficiency can interfere with many organ systems especially when it occurs during a time of rapid growth and development when nutritional needs are high, such as during infancy. In animal studies, rats who were deprived of zinc during early fetal development exhibited increased emotionality, poor memory, and abnormal response to stress which interfered with performance in learning situations. Zinc deprivation in monkeys showed that zinc deficient animals were emotionally less mature, and also had cognitive deficits indicated by their difficulty in retaining previously learned problems and in learning new problems. Human observational studies show weaker results. Low maternal zinc status has been associated with less attention during the neonatal period and worse motor functioning. In some studies, supplementation has been associated with motor development in very low birth weight infants and more vigorous and functional activity in infants and toddlers. Plasma zinc level has been associated with many psychological disorders. However, the nature of this relationship remains unclear in most instances. An increasing amount of evidence suggests that zinc deficiency could play a causal role in the etiology of depression. Preliminary clinical trials suggest that zinc may be an effective treatment.

Diarrhea and pneumonia
Zinc deficiency contributes to an increased incidence and severity of diarrhea and pneumonia. Studies have shown that zinc treatment results in a 25 percent reduction in duration of acute diarrhea and a 40 percent reduction in treatment failure or death in persistent diarrhea. The studies determined that a ten-day therapy of zinc treatment can considerably reduce the duration and severity of diarrheal episodes, decrease stool output, and lessen the need for hospitalization. Zinc may also prevent future diarrhea episodes for up to three months. The current World Health Organization recommendation for diarrhea control includes the use of 20 mg per day of zinc supplementation for 10 to 14 days (10 mg per day for infants under the age of six months). A zinc taste test may have potential for diagnosing deficiency.

Dysmenorrhea
High dose of zinc, prevents dysmenorrhea.

Hunger
The influence of zinc on hunger is complex and probably depends upon the status of other nutrients, the developmental stage of the animal, and percentage body fat. Some research groups have argued for a role of zinc deficiency decreasing appetite, while others have shown zinc ingestion can reduce feelings of hunger by increasing leptin levels. There is evidence that the way zinc influences hunger depends on the sodium/osmotic status of the organism, with low sodium/low zinc levels increasing hunger and high sodium/low zinc levels decreasing it. An organism with a low level of zinc has an increased susceptibility to hypoosmotic stress and cell rupture. Thus if the osmotic pressure is too low the organism may be inclined to eat to raise osmolality and prevent osmotic shock. It should be noted that zinc is known to affect osmolality by increasing sodium retention. In rats, the "first visible sign" of zinc deficiency is a decreased appetite.

Hypotonic fluids can exacerbate some symptoms
Zinc protects cells against hypotonicity. Drinking too much hypotonic fluid (long term, 4+ months) during zinc deficiency can cause skin lesions which are red, scaley, and hairless. These lesions will blister slightly after drinking hypotonic fluids and these same blisters will scab only after restoring osmolarity. Low sodium intakes have also been shown to directly reduce zinc retention

Pregnancy
Zinc deficiency during pregnancy can negatively affect both the mother and fetus. Animal studies indicate that maternal zinc deficiency can upset both the sequencing and efficiency of the birth process. An increased incidence of difficult and prolonged labor, hemorrhage, uterine dystocia and placental abruption has been documented in zinc deficient animals. These effects may be mediated by the defective functioning of estrogen via the estrogen receptor, which contains a zinc finger protein. A review of pregnancy outcomes in women with acrodermatitis enteropathica, reported that out of every seven pregnancies, there was one abortion and two malfunctions, suggesting the human fetus is also susceptible to the teratogenic effects of severe zinc deficiency. However, a review on zinc supplementation trials during pregnancy did not report a significant effect of zinc supplementation on neonatal survival.

Sexual health of men
Zinc is required by men to produce testosterone. Thus, zinc deficiency can lead to less testosterone production in men and hence show up with the symptoms associated with low testosterone.

Vitamins A and D
Plasma zinc levels have been found to be dependent upon vitamins A and D. This suggests that a Vitamin A or D deficiency could cause a secondary zinc deficiency and that for treatment of zinc deficiency one should ensure adequate vitamin A and D intake.

Increased utilization
Exercising, childhood growth, and pregnancy all increase utilization.

Dietary deficiency
A diet which is high in phytate containing whole grains and/or high in zinc poor processed foods can result in zinc deficiency. Conservative estimates suggest that 25% of the world's population is at risk of zinc deficiency.

The following table summarizes by source most of the foods with significant quantities of zinc. The quantity in milligrams and the percent daily value (%DV) (that is, the percent daily requirement) in that quantity is stated for the seven most concentrated sources of zinc.
 * Animal sources
 * Cooked oysters - 5.5 mg (44% DV)
 * Beef - especially organic, grass fed: one rib eye fillet 14.2 mg (95% DV)chicken and pork - 3 oz 4.3 mg, (28% DV)
 * Dairy - especially organic, grass fed
 * Liver - especially organically grown
 * Plant sources
 * Cereal grasses- wheat, wheat germ (4.7 mg/oz, 31% DV), oats, barley, rye, wild grasses
 * Greens - organic, locally grown highest: spinach (100 G 0.5 mg, 4% DV), dandelion, romaine, broccoli,    cilantro, basil, cabbage, green peas
 * Seeds - pumpkin (one oz. 2.9 mg, 19% DV), sunflower
 * Nuts - cashews (1.6 mg/oz, 10% DV), basil nuts, pecans, walnuts
 * Sea vegetables
 * Beans
 * Other vegetables - mushrooms

Defective ZIP4 transport
Although common, it is often mild and unsuspected, and if absent causes acrodermatitis enteropathica.

Damaged or absent enterocytes
Numerous small bowel diseases causing generalized malabsorption result in zinc deficiency.

Increased loss
Exercizing, high alcohol intake, and diarrhea all increase loss. Changes in intestinal tract absorbability and permeability due, in part, to viral, protozoal, and bacteria pathogens may also encourage fecal losses of zinc.

Chronic disease
Wilson's disease, sickle cell disease, chronic kidney disease, chronic liver disease have all been associated with zinc deficiency. It can also occur after bariatric surgery, mercury exposure and tartrazine.

Although marginal zinc deficiency is often found in depression, low zinc levels could either be a cause or a consequence of mental disorders and their symptoms.

Treatment
Zinc supplementation has been shown to reduce the time period of diarrhea in infants more than six months by about 10 hours.

To combat zinc deficiency, four intervention strategies can be used. Providing micronutrients, including zinc, to humans is one of four solutions to major global problems identified in the Copenhagen Consensus from an international panel of economists.
 * Supplementation using medicines
 * Food fortification through the incorporation of zinc additives in food
 * Dietary modification/diversification
 * Agronomic biofortification through zinc fertilization.

Central Anatolia, in Turkey, was a region with zinc-deficient soils and widespread zinc deficiency in humans. In 1993, a research project found that yields could be increased by 6 to 8-fold and child nutrition dramatically increased through zinc fertilization. Through a partnership with Cukurova University, the State and the private company TOROS Agri Industry Group, zinc was added to fertilizers. While the product was initially made available at the same cost, the results were so convincing that Turkish farmers significantly increased the use of the zinc-fortified fertilizer (1 per cent of zinc) within a few years, despite the repricing of the products to reflect the added value of the content. Today, nearly 10 years after the identification of the zinc deficiency problem, the total amount of zinc-containing compound fertilizers produced and applied in Turkey reached a record level of 300,000 tonnes per annum. It is estimated that the economic benefits associated with the application of Zn-fertilizers on Zn deficient soils in Turkey is around US$ 100 million per year. Zinc deficiency in children has been dramatically reduced.

The amount of zinc absorbed by the human body is a function of dietary intake of both zinc and phytate (a phosphate storage compound that chelates zinc), because the ratio between these two substances affects the bioavailability of zinc. Meeting the needs for absorbed zinc requires an increase in the zinc content and/or a decrease in the phytate content.

Significant historical events
Zinc was first discovered to be essential to the growth of an organism (Aspergillus niger) in 1869. In 1929 Lutz measured zinc in numerous human tissues using the dithizone technique and estimated total body zinc in a 70 kg man to be 2.2 grams. Zinc was found to be essential to the growth of rats in 1933. In 1939 beriberi patients in China were noted to have decreased zinc levels in skin and nails. In 1940 zinc levels in a series of autopsies found it to be present in all tissues examined. In 1942 a study showed most zinc excretion was via the feces. In 1950 a normal serum zinc level was first defined, and found to be 17.3 - 22.1 micromoles/liter. In 1956 cirrhotic patients were found to have low serum zinc levels. In 1963 zinc was determined to be essential to human growth, three enzymes requiring zinc as a cofactor were described, and a report was published of a 21 year old Iranian man with stunted growth, infantile genitalia, and anemia which were all reversed by zinc supplementation. In 1972 fifteen Iranian rejected army inductees with symptoms of zinc deficiency were reported: all responded to zinc. In 1973 the first case of acrodermatitis enteropathica due to severe zinc deficiency was described. In 1974 the National Academy of Sciences declared zinc to be an essential element for humans and established a recommended daily allowance. In 1978 the Food and Drug Administration required zinc to be in total parenteral nutrition fluids. In 2002 the zinc transporter protein ZIP4 was first identified as the mechanism for absorption of zinc in the gut across the enterocyte. By 2014 over 300 zinc containing enzymes have been identified, as well as over 1000 zinc containing transcription factors.

Plants, crops, and soils
Zinc is an essential micronutrient needed not only by people but also by crops. Almost half of the world’s cereal crops are deficient in zinc, leading to poor crop yields. Many agricultural countries around the world are affected by zinc deficiencies. In China, zinc deficiency occurs on around half of the agricultural soils, affecting mainly rice and maize.

In India, zinc-deficient soils occupy almost 50% of the agricultural area and are a critical constraint on yield, but crops are highly responsive to zinc fertilization.

In Turkey, major yield and quality benefits in wheat have been obtained with the widespread use of zinc fertilizers, where half of the cereal growing land is zinc-deficient.

Research has shown that areas with zinc-deficient soils are often regions with widespread zinc deficiency in humans.

A basic knowledge of the dynamics of Zn in soils, understanding of the uptake and transport of Zn in plant systems and characterizing the response of plants to Zn deficiency are essential steps in achieving sustainable solutions to the problem of Zn deficiency in plants and humans.

Fertilization
Experiments show that soil and foliar application of zinc fertilizer can effectively increase grain zinc and reduce the phytate:zinc ratio in grain. People who eat bread prepared from zinc enriched wheat show a significant increase in serum zinc, suggesting that the zinc fertilizer strategy may be a viable commercial approach to address zinc deficiencies in humans.

Where zinc deficiency is a limiting factor, zinc fertilization can increase crop yields. Balanced crop nutrition supplying all essential nutrients, including zinc, is a cost effective management strategy. Even with zinc-efficient varieties, zinc fertilizers are needed when the available zinc in the topsoil becomes depleted.

Plant breeding, including modern biotechnology, can improve:

Zinc uptake capacity of plants under soil conditions with low chemical availability of zinc; Zinc translocation, thus elevating zinc content in edible crop parts rather than the rest of the plant; Zinc bioavailability. For optimal efficiency, zinc-efficient genotypes should be associated with complementary soil crop management (including fertilization) to ensure adequate zinc uptake by roots and thus enhance zinc nutrition of crops and humans