The Effect of Micronutrient Deficiencies on Child Growth: A Review of Results from Community-Based Supplementation Trials

Growth retardation is highly prevalent in developing countries and is associated with several adverse outcomes throughout life. Inadequate intakes of dietary energy and protein and frequent infections are well-known causes of growth retardation. However, the role of specific micronutrient deficiencies in the etiology of growth retardation has gained attention more recently. Micronutrient deficiencies are highly prevalent in low-income countries, and the most probable causes are low content in the diet and poor bioavailability. More than half of preschool children are anemic, and an estimated 75 million and 140 million  preschool children have clinical and subclinical vitamin A deficiencies, respectively. Less information is available on the prevalence of zinc deficiency, although it has been estimated recently that about half of the world’s population is at risk of inadequate intake of absorbable zinc.

Attained height is the result of the interaction between genetic endowment and both macro- and micronutrient availability during the growth period. Longitudinal growth occurs through a process of cell proliferation, the addition of new cells to the growth plate of the bone and hypertrophy, resulting in the expansion of the growth plate . Although the control of bone growth in its different phases is not entirely understood, the key roles of growth hormone  (GH)3 and insulin-like growth factor I (IGF-I) have been identified. IGF-I receptors are found predominantly in proliferating bone chondrocytes, and IGF-I itself stimulates synthesis of collagen and proteoglycans. These physiological functions explain the role of IGF-I in linear growth. Furthermore, GH itself and its effect on IGF-I synthesis exert a direct effect on growth.

Nutrition plays a key role in the control of linear growth through a variety of mechanisms. Evidence from animal models indicates that energy and protein restriction reduces IGF-I plasma concentration, which returns to normal after replenishment. The impact of reduced protein intake appears to be larger than that observed with energy restriction. The association between nutritional status and the IGF-I system also has been observed in humans: IGF-I is reduced during acute protein deficiency (kwashiorkor) and protein-energy malnutrition in children. Some micronutrients also affect the IGF-I system. For example, it is well documented that zinc deficiency in rats causes not only growth retardation but also a decrease in both IGF-I plasma concentration and GH receptors, which return to normal after zinc repletion. Additionally, through its influence on the GH/IGF-I system, zinc deficiency has been observed to affect bone metabolism. The role of zinc in growth also may be explained in part through its participation in DNA synthesis.

Studies on rats also have shown similar decreases in plasma IGF-I concentrations with depletion of potassium, magnesium or thiamine, which return to normal after repletion of these nutrients. Copper also is involved in growth through its role in cross-linking collagen fibers, and manganese deficiency is associated with skeletal abnormalities, including retarded growth, which may be mediated through defects in proteoglycan physiology in the growth plate. Vitamin D and calcium deficiencies also affect bone development, as manifested through the condition known as rickets.

Vitamin A was first identified as the growth-promoting factor “A.” Studies in the 1920s–1930s demonstrated arrested growth, especially of weight in rats, after acute vitamin A depletion . However, even today effects of vitamin A on linear growth, bone formation and body composition in animals are less clear Judisch et al.  found that anemic children were small for their age and that their growth rates accelerated when treated with iron. Since then, however, evidence for the effect of iron deficiency on growth has been equivocal.

Deficiencies of some micronutrients, such as iron, magnesium and zinc, result in anorexia . Therefore, these nutrient deficiencies also may contribute to growth retardation indirectly by reducing the intake of other growth-limiting factors, such as energy and protein. Also, several micronutrients, including zinc, iron and vitamin A, are associated with immune function and risk of morbidity, which in turn affect growth . Therefore, micronutrient deficiencies may have an indirect effect on growth by increasing the prevalence or severity of morbidity and anorexia.

Micronutrients have a substantial impact on a woman’s health throughout her entire life. Every woman needs a constant, balanced, and adequate supply of all essential nutrients throughout her lifetime

Micronutrients have a substantial impact on a woman’s health throughout her entire life. Every woman needs a constant, balanced, and adequate supply of all essential nutrients throughout her lifetime.

Many women do not get enough of the micronutrients they need, however. Both in the U.S. and worldwide, inadequate intakes are far too common. Deficiencies of the following

nutrients are particularly common:
• Vitamin D • B vitamins • Calcium
• Zinc • Iron

In addition to low dietary intake, other factors can contribute to micronutrient deficiencies,

• genetic factors

• poor absorption

• drug-nutrient interactions

• acute and chronic health conditions

• stress

• normal processes of aging

The fact is that many women cannot get adequate amounts of some nutrients without supplementing their diets.

Research Shows the Importance of Micronutrients to Women’s Health
Breast Health

Breast health issues are one of the most common reasons why women consult their health care practitioners. Research suggests that several micronutrients play key roles in breast health, including iodine, B vitamins, vitamin D, calcium, and vitamin C.2–4 Uterine and Ovarian Health
Micronutrient status plays a major role in the overall health and function of the uterus and ovaries, which can be affected by a variety of health issues. Research suggests that supplementation with B vitamins, calcium, and vitamin D may support uterine and ovarian health.

Menstrual Cycle Health
Many women experience physical and emotional challenges relating to their menstrual cycle, and research suggests that several micronutrients support a healthy menstrual cycle—including increased B vitamins, vitamin C, magnesium, and zinc.7–9 Urinary Tract Health Women are at greater risk for urinary tract health issues than men. Statistically at least one-third of American women will develop urinary tract health issues, which also become more frequent with age. Recent research found that adequate vitamin D intake may protect against urinary health issues.

Anxiety and Mental Health

Mental health challenges are much more prevalent in women than men, and research continues to investigate the importance of vitamins and minerals for mental health. Higher intakes of vitamin D and magnesium have been associated with improved mental health and function.11,12

Birth Control / Contraceptives
Oral contraceptives have been shown to lower levels of B vitamins, vitamin C, and zinc in the body, causing researchers to recommend that women taking contraceptives should pay close attention to
their vitamin and mineral intake and consider supplementation.
Conception and Pregnancy Many women know the importance of vitamins and minerals during pregnancy, but recent research also emphasizes the importance of micronutrient status in the time period before conception. Micronutrient deficiencies can also negatively impact fertility. B vitamins, vitamin D, iodine, selenium, antioxidants, iron, and vitamin A have been shown to be key nutrients in fertility and maternal, fetal, and infant health.

Postpartum Mood

Postpartum mood challenges are common—affecting at least 12–16% of mothers. Studies have linked low intakes of micronutrients with increased incidence of mood issues, and have suggested that supplementation can help maintain healthy mood in postpartum women. B vitamins, selenium, vitamin D, and magnesium have been suggested to promote healthy mood. Menopausal and Bone Health
Menopause can affect women’s nutritional needs, and research has shown that B vitamins and vitamin D are particularly important. Minerals are also crucial after menopause, since one of the most significant changes associated with perimenopause and post menopause is a decrease in mineral
levels, which can negatively impact bone health in particular. Magnesium, zinc, and calcium are all important minerals to support postmenopausal bone health.

1. Seibel M. Fertil Steril 1999;72(4).
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3. Zhang SM. Curr Opin Obstet Gynecol 2004;16(1):19–25.
4. Lazzeroni M, et al. Breast 2011;20(Suppl 3):S36–41.
5. Killicdag EB, et al. Hum Reprod 2005;20(6):1521–8.
6. Firouzabadi Rd, et al. Complement Ther Clin Pract 2012;18(2):85–8.
7. P.O. Chocano-Bedoya, et al. Am J Clin Nutr 2011 May;93(5):1080–6.
8. De Souza MC, et al. J Womens Health Gend Based Med
9. Abraham G. J Reprod Med 1983;28:446–64.
10. O Hertting, et al. PLoS One 2010;Dec 14;5(12):e15580.
11. Zender R, et al. Nurs Clin N Am 2009;44(3):355–364.
12. Murphy P, et al. J Midwifery Women’s Health 2008;53:440–446.
13. Veninga KS. J Nurse Midwifery 1984;29(6):386–90.

14. Webb JL. J Reprod Med 1980;25(4):150–6.

15. Allen LH. Am J Clin Nutr 2005;81(5):1206S–1212S.

16. Davison KM, et al. Can J Psychiatry 2012;57(2):85–92.
17. Leung BM, et al. J Am Diet Assoc 2009;109(9):1566–75.
18. Mokhber N, et al. J Matern Fetal Neonatal Med
19. Jacka FN, et al. J Affect Disord in press 2012.
20. Seibel MM. Fertil Steril 1999;72(4):579–91.
21. Grochans E, et al. Magnes Res 2011;24(4):209–14.
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Micronutrient Deficiencies a Major Cause of DNA Damage

Micronutrient Deficiencies a Major Cause of DNA Damage


University of California, Berkeley, California 94720-3202, USA

ABSTRACT: Deficiencies of the vitamins B12, B6, C, E, folate, or niacin, or of iron or zinc mimic radiation in damaging DNA by causing single- and doublestrand breaks, oxidative lesions, or both. The percentage of the population of the United States that has a low intake (<50% of the RDA) for each of these eight micronutrients ranges from 2% to 20+ percent. A level of folate deficiency causing chromosome breaks occurred in approximately 10% of the population of the United States, and in a much higher percentage of the poor. Folate deficiency causes extensive incorporation of uracil into human DNA (4 million/cell), leading to chromosomal breaks. This mechanism is the likely cause of the increased colon cancer risk associated with low folate intake. Some evidence, and mechanistic considerations, suggest that vitamin B12 and B6 deficiencies also cause high uracil and chromosome breaks. Micronutrient deficiency may explain, in good part, why the quarter of the population that eats the fewest fruits and vegetables (five portions a day is advised) has about double the cancer rate for most types of cancer when compared to the quarter with the highest intake. Eighty percent of American children and adolescents and 68% of adults do not eat five portions a day. Common micronutrient deficiencies are likely to damage DNA by the same mechanism as radiation and many chemicals, appear to be orders of magnitude more important, and should be compared for perspective. Remedying micronutrient deficiencies is likely to lead to a major improvement in health and an increase in longevity at low cost.

Low micronutrient intake may accelerate the degenerative diseases of aging through allocation of scarce micronutrients by triage

Low micronutrient intake may accelerate the degenerative diseases of aging through allocation of scarce micronutrients by triage

  1. Contributed by Bruce N. Ames, October 6, 2006 (received for review September 20, 2006)


Inadequate dietary intakes of vitamins and minerals are widespread, most likely due to excessive consumption of energy-rich, micronutrient-poor, refined food. Inadequate intakes may result in chronic metabolic disruption, including mitochondrial decay. Deficiencies in many micronutrients cause DNA damage, such as chromosome breaks, in cultured human cells or in vivo. Some of these deficiencies also cause mitochondrial decay with oxidant leakage and cellular aging and are associated with late onset diseases such as cancer. I propose DNA damage and late onset disease are consequences of a triage allocation response to micronutrient scarcity. Episodic shortages of micronutrients were common during evolution. Natural selection favors short-term survival at the expense of long-term health. I hypothesize that short-term survival was achieved by allocating scarce micronutrients by triage, in part through an adjustment of the binding affinity of proteins for required micronutrients. If this hypothesis is correct, micronutrient deficiencies that trigger the triage response would accelerate cancer, aging, and neural decay but would leave critical metabolic functions, such as ATP production, intact. Evidence that micronutrient malnutrition increases late onset diseases, such as cancer, is discussed. A multivitamin-mineral supplement is one low-cost way to ensure intake of the Recommended Dietary Allowance of micronutrients throughout life.

Poor nutrition has been linked to an increased risk of many diseases, including cancer, heart disease, and diabetes. The human diet requires both macronutrients, which are the main source of calories, and micronutrients (≈40 essential minerals, vitamins, and other biochemicals), which are required for virtually all metabolic and developmental processes. The leading dietary sources of energy in the United States are abundant in carbohydrates and fats (1) but deficient in micronutrients (i.e., they are energy-dense and nutrient-poor) (2). Such foods are inexpensive and tasty and as a consequence are consumed excessively, particularly by the poor (3). Thus, even in the United States (4), inadequate intake of some vitamins and minerals is common (Table 1). Suboptimal consumption of micronutrients (4) often accompanies caloric excess (688) and may be the norm among the obese and contribute to the pathologies associated with obesity.

Significant chronic metabolic disruption may occur when consumption of a micronutrient is below the current Recommended Dietary Allowance (RDA) (710) but above the level that causes acute symptoms. When one component of the metabolic network is inadequate, there may be a variety of repercussions in metabolism, including acceleration of degenerative diseases. The optimum intake of each micronutrient necessary to maximize a healthy lifespan remains to be determined and could even be higher than the current RDA, particularly for some populations (710). For example, folic acid intakes above the RDA appear to be necessary to minimize chromosome breaks (1011).

Concurrent micronutrient deficiencies in lactating mothers and their infants

Concurrent micronutrient deficiencies in lactating mothers and their infants in Indonesia.

  • Division of Human Nutrition and Epidemiology, Wageningen University, Netherlands.



Deficiencies of vitamin A, iron, and zinc are prevalent worldwide, affecting vulnerable groups such as lactating women and infants. However, the existence of concurrent deficiencies has received little attention.


The aim was to investigate the extent to which deficiencies of vitamin A, iron, and zinc coexist and the nutritional relation between lactating mothers and their infants.


In a cross-sectional survey in rural West Java, Indonesia, 155 lactating mothers and their healthy infants were assessed anthropometrically and blood, urine, and breast-milk samples were obtained.


Marginal vitamin A deficiency was found in 54% of the infants and 18% of the mothers. More than 50% of the mothers and infants were anemic and 17% of the infants and 25% of the mothers were zinc deficient. There was a strong interrelation between the micronutrient status of the mothers and infants and the concentrations of retinol and beta-carotene in breast milk. Vitamin A deficiency in infants led to an increased risk of anemia and zinc deficiency (odds ratios: 2.5 and 2.9, respectively), whereas in mothers the risk of anemia and iron deficiency (odds ratios: 3.8 and 4.8, respectively) increased. In infants, concentrations of insulin-like growth factor I were related to concentrations of plasma retinol and beta-carotene but not to zinc.


Micronutrient deficiencies were prevalent in West Java. The micronutrient status of lactating mothers and that of their infants were closely related; breast milk was a key connecting factor for vitamin A status. Furthermore, concurrent micronutrient deficiencies appeared to be the norm.