Topic of the Month

Micronutrients in human development – Part 1

July 1, 2013

Micronutrient requirements differ according to the individual. They can vary according to stage of life, gender, health status, lifestyle habits, possible hereditary metabolic disorders and environmental influences. At certain stages of life, the importance of and need for individual micronutrients is particularly high, for example in pregnancy and when breastfeeding, for children and youths during the growth phase, and in old age. Micronutrient intakes that do not meet the needs of earlier stages of life in particular can increase chances of developing chronic illnesses later in life, such as osteoporosis or heart disease. It is therefore important to ensure an adequate intake of vitamins, minerals, trace elements, essential fatty acids and other nutrients from the very beginning.


Optimal nutrient intake some months before conception as well as in the first few weeks of pregnancy can be crucial to a successful pregnancy. Besides an adequate folic acid intake, a variety of different nutrients are involved in the healthy development of the child in the womb. Adequate intake during childhood and adolescence is also of great importance, enabling complete bodily growth and mental development. While micronutrient requirements are exceptionally high during adolescence, diets insufficient in micronutrients are very common, parti-cularly among teenagers. The nutrients most often lacking are the B vitamins and vitamin C, as well as iron, zinc and calcium, which are needed for increased energy requirements and the structure of the various organs.   

Nervous system

Sufficient micronutrient intake is already important some months before conception, i.e., when planning a pregnancy. It promotes a successful pregnancy and the development of a healthy baby. Most of the decisive development processes of the fetus occur in the first eight weeks of pregnancy, i.e., at a time when many women don’t yet even know that they are pregnant. The embryo’s brain and spinal cord – the central nervous system that originates from the so-called neural tube – are almost fully formed by the end of the eighth week. In the following weeks of life, more new nerve cells (neurons) are formed – approximately 250,000 a minute. At the same time, the periphery nervous system is developing, which connects the brain and spinal cord with the (effector) organs. Once all important brain structures have developed, the neurons build cell protuberances: dendrites, to detect impulses, and an axon surrounded by glial cells with synaptic endings for stimulus conduction and transmission. Another important development in early childhood brain development is the development of a lipid-rich layer (myelin sheath) that (electrically) isolates axons. This process begins in the brain only shortly before the birth and lasts until the second year of life. At birth, the brain of an infant contains around 100 billion neurons, the same number for adults. The nerve cells of the newborn, however, are not yet fully developed or well-networked. The number of synapses connecting neurons with one another drastically increases in the first three years of life. Connected with this rapid growth of synapses is the speed at which the brain gains in weight. The number of synapses reached by age 3 remains relatively constant until around age 10. From then until adolescence, irrelevant synapses (around half) are degraded while the necessary pathways between neurons (for the discovered, the learned, the experienced and the absorbed) are strengthened. This development continues until the person’s death: unnecessary synapses are eliminated, and those frequently used are intensified. At the same time, new synapses are always forming, particularly in the frame of memory processes. It has only recently become known that new neurons still form well into old age. Throughout their development, neuronal structures are very vulnerable to harmful external influences, which also include nutrient deficiencies.

Folate plays a decisive role in the development of a functional nervous system (therefore preventing birth defects). Women should ideally have a good intake of folate or its synthetic form, folic acid, as early as at the time of fertilization in order to protect against the risk of a neural tube defect (“open spine”) or anen-cephaly (“hydrocephalus”). Given that the majority of pregnancies occur unplanned and are also not noticed straight away, experts advise all women of child-bearing age to take 400 micrograms of folic acid daily in the form of a supplement as a precautionary measure (1). However, nowhere near all women between the ages of 15 and 45 follow this recommendation (2). As a second effective nutritional strategy for the containment of neuronal malformations in newborns, many countries have already enriched their basic foodstuffs, particular-ly flour, with folic acid (3). The development of cognitive (e.g. linguistic) abilities appears to be positively influenced by a targeted intake of folic acid from the beginning of the pregnancy (4), whereas an insufficient intake of folic acid during pregnancy could increase the child’s risk of later developing hyperactivity (5), emotional problems and behavioural problems (6). New research is providing evidence that sufficient folate intake even after the birth is very important, as it can still positively influence the development of the nervous system and cognitive abilities during childhood (7).

The healthy development of the nervous system also requires a sufficient intake of vitamins B6 (pyrido-xine), B7 (biotine) and B12 (cyanocobalamin). Biotine plays a role in the correct conversion of the informa-tion contained in the genetic material – an important property of the rapidly growing and very quickly separating fetal nerve cells (8). Vitamin B6 is necessary above all for the synthesis of nucleic acid (9). Vitamin B12 is involved in various methylation reactions, above all of DNA, via which gene activation takes place, affecting cell differentiation and organ development (10). Vitamin B12 is also necessary for the production of myelin, which protects the nerve cells and enables the rapid transfer of electrical impulses between the neurons. Vitamin B12 deficiency can reduce myelin production or even promote its degradation, which can lead to a slowdown in nerve reactions and loss of coordination (e.g. when walking) (11).

Besides B vitamins, numerous other micronutrients are essential for the normal development of the (central) nervous system before birth and in the newborn (12). It is therefore important to have a good intake of iodine during pregnancy and while breastfeeding, as this is necessary for the development of nerve growth factors and therefore for the brain development of the unborn child. Iodine deficiency can cause hypothyroi-dism in the mother, which can impair the mental development of the child during pregnancy and can lead to irreversible brain malfunction in the infant (13, 14). This can later lead above all to impairments in language intelligence and reading ability among the children (15). Iodine deficiency should also be avoided at all cost in (young) children in order to ensure proper functioning of the thyroid gland (16, 17). Enriching salt with iodine is a strategy used by many countries to prevent iodine deficiency (18).

Essential fatty acids – particularly the omega-3 fatty acid docosahexaenoic acid (DHA) – are also vital to the development of the nervous system. As a fatty acid component of phospholipids, DHA is an integral part of membranes, above all those of nerve cells. Up to 97 percent of omega-3 fatty acids in the brain consist of DNA. Epidemiological investigations and intervention studies have indicated that supplementation with DHA during pregnancy and while breastfeeding can have a positive impact on children’s brain development (19). New research has suggested that increased blood levels of vitamin D3 in mothers, particularly during the first three months of pregnancy, can promote the development of their children’s mental and psychomotor abili-ties (20).

Iron is necessary for the production of hemoglobin in red blood cells and is therefore involved in supplying all organs, including the nervous system, with oxygen. Iron deficiency in childhood can impair not only bodily growth but also mental development (21). Children’s and adolescents’ iron requirements are very high – a twelve-year-old boy needs 25% more iron than his adult father, for example. Iron deficiency is the most widespread nutrient deficiency among this age group. Even small disruptions to iron supply can lead children and adolescents to develop iron deficiency and then gradually anemia (lack of blood cells), which manifests itself as tiredness, deteriorating performance or a lack of concentration (22, 23). Iron also seems to provide targeted support for the development of those brain cells that produce myelin (so-called oligodendrocytes) (24), and functions as a cofactor for various enzymes that synthesize neurotransmitters (25).

From adolescence, the protection of the nerve cells against reactive and destructive oxygen radicals becomes more and more important with age. Regular intakes of antioxidant micronutrients such as beta-carotenevitamins E and C, and selenium can contribute very early on to the prevention of neurodege-nerative diseases (26).     

Bones, teeth and tissues

A human adult skeleton is made up of 208 to 214 bones (depending on the person) and only reaches full development at around 20 years of age. The child’s skeleton starts developing as early as the first three months of pregnancy, slowly hardening from the sixth month. Ossification centers develop in the still cartilaginous bones, which get bigger and then merge together. The bones – the strongest body tissue after the teeth – support the organism and protect its organs. Stimulated by nerve impulses, the muscles move the various parts of the skeleton as needed. Bones also house hematopoietic (red) bone marrow and yellow bone marrow, which contains fat as a reserve store. In children, all bones contain hematopoietic bone marrow, while in adults it is only contained in a few bones. Given that bone thickness peaks between age
25 and 30, after which bone substance can only be preserved, ensuring a good nutrient intake throughout childhood and adolescence is vital. Tooth development begins around day 40 after fertilization with the development of germinal elements for 20 milk teeth. Healthy milk teeth, the first of which come to the surface at around six months of age, are the precondition for the (generally 32) permanent healthy teeth, which follow at between 6 and 17 years of age. Many organs are formed while the embryo is developing; it begins with the development of the brain, eyes and heart in the first two weeks of embryogenesis and ends after roughly eight weeks with the beginning of fetal development, during which organ development and tissue differentiation takes place. A sufficient micronutrient intake during pregnancy is necessary for all of these processes.

Numerous micronutrients are involved in the development and maintenance of healthy bones. Together with phosphatecalcium forms the main component of bones (and teeth) and particularly – together with orga-nic, elastic connection tissue – bone hardness. Calcium requirements are slightly higher during pregnancy. Insufficiency or even a deficiency should be avoided at all cost in order to prevent the development of rickets (softening of bones accompanied by deformity and growth disturbance) in infanthood or early childhood (27).

Equally important for rickets prophylaxis is vitamin D, which on the one hand is necessary for the integra-tion of calcium and phosphate into the bones (mineralization) and on the other regulates uptake into the kidneys of minerals from the intestine and the retention of pre-urine. Should a vitamin D deficiency be present, calcium can only be absorbed from the intestine in insufficient quantities. The resulting calcium deficiency leads to an insufficient integration of calcium and phosphate into the growing bone, which thus becomes increasingly deformable (28). To promote bone metabolism in the mother and the unborn child, a targeted daily intake of vitamin D via supplementation is recommended during pregnancy and while breast-feeding, as well as for infants (29, 30).

Also important for the development of healthy bones are: fluorides, which stimulate the production and improve the organic matrix of bone via bone cells (osteoblasts); magnesium, which (together with calcium) contributes to the mineralization of the bones; and vitamin K, which is required for the production of the calcium-binding protein osteocalcin, an integral component of the bone matrix (31).

Sufficient intakes of calcium and vitamin D are also necessary for healthy prenatal tooth development (32). After this, the hardening of the teeth with fluoride is decisive in strengthening them against attacks by acids from caries bacteria or direct acid exposure from food. For this reason, fluoride tablets are used for infants. As soon as the young child’s first tooth has broken through, it is recommended to regularly use fluoride toothpaste.

As early as pregnancy, care should be taken to ensure that the maturing organism is supplied with enough vitamin A, which is necessary for the separation and renewal of organ and tissue cells. A lack of vitamin A can have a negative effect on birth weight (33). An uptake of very high doses of vitamin A during pregnancy can also be harmful (teratogenic) to the embryo (34). To avoid exceeding the upper tolerable intake amount of vitamin A, it is recommended to achieve the necessary intake of vitamin A via beta-carotene (precursor of vitamin A). The body converts as much of it into vitamin A as required.

Magnesium also plays an important role in the development and function of soft tissues: it is jointly respon-sible for the transmission of impulses to the nerves and muscle cells as well as the stabilization of mem-branes, proteins and nucleic acids (35). A balanced magnesium metabolism is therefore important prior to the birth as well as throughout childhood and adolescence. In terms of generally protecting the membranes, proteins and other cellular components against oxidative damage caused by the effect of reactive oxygen molecules, it is recommended to ensure an adequate supply of antioxidants (e.g. beta-carotene, vitamin Evitamin C andselenium). 

Immune system

The human immune system consists of cells and organs that develop well before birth. The quantity and activity of the immune cells changes during a person’s development. The newborn immune system is still immature and vulnerable to a range of infectious diseases above all because of the relative immaturity of
T and B lymphocytes (white blood cells), which are some of the most important defense cells. Unspecific defense mechanisms in the newborn are also not yet fully developed. The skin and mucous membranes, for example, can still be permeated by germs, and defense cells are not as good at attaching to the attacker. Antibodies transmitted through the mother’s milk protect the newborn during this temporary suppression of defenses. Certain micronutrients play a key role in the production as well as development and maintenance of the immune system from the very beginning.

Vitamin D strengthens the immune system in that it has a decisive impact on the functioning and activity of T lymphocytes. Studies have shown that vitamin D activates the immune cells and encourages them to separate so that immune defense is strengthened. After contact with a pathogen, lymphocytes form "vitamin D recognition proteins" on the cell surface. Contact with the vitamin results in a proliferation of immune cells, which then turn against the pathogen (36). Vitamin D also seems to have a positive influence on strong autoimmune reactions in children such as allergies and asthma (37, 38).

Vitamin A also promotes the protective activity of T lymphocytes against antigens, which cause infections and inflammation. It also makes it more difficult for germs to enter by ensuring a moist surface of the mucous membranes (39). Vitamin E can also positively influence T lymphocyte functioning (40). Vitamin C has been described as having an antiviral effect (in particular against influenza viruses) in very early stages of infection in that it produces interferons (41).

The omega-3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) appear to support the immune system in various ways. The anti-inflammatory properties in particular of EPA can cause a reduced production of inflammatory factors (e.g. interleukins and tumor necrosis factors) (42). The immune suppressing properties in particular of DHA can protect children against the development of allergies or atopic dermatitis through a sufficient intake during pregnancy (43, 44).

A good supply of zinc and magnesium should be ensured for an intact immune system during childhood and adolescence. Studies have shown that zinc has an impact on the innate immune system, which forms the first line of defense against pathogens (before the adaptive immune response effectively targets antibodies and T cells). A meta-analysis came to the conclusion that an intake of zinc within the first 24 hours can reduce the duration and severity of coughs and sneezes (45). Magnesium has been shown to stimulate the immune system and have anti-inflammatory effects (through the suppression of inflammatory mediators) (46).


  1. De-Regil L. M. et al. Effects and safety of periconceptional folate supplementation for preventing birth defects. Cochrane Database Syst Rev. 2010; (10).
  2. Folic acid for the prevention of neural tube defects: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2009; 150(9):626-631.
  3. Botto L. D. et al.  International retrospective cohort study of neural tube defects in relation to folic acid recommendations: are the recommendations working?  BMJ. 2005; 330(7491):571.
  4. Roth C. et al. Maternal Use of Folic Acid Supplements in Early Pregnancy Associated With Reduced Risk of Severe Language Delay in Children. JAMA. 2011; 306(14):1566-1573.
  5. Schlotz W. et al. Lower maternal folate status in early pregnancy is associated with childhood hyperactivity and peer problems in offspring. Journal of Child Psychology and Psychiatry. 2010; 51(5): 594–602.
  6. Steenweg-de Graaff J. et al. Maternal folate status in early pregnancy and child emotional and behavioral problems: the Generation R Study.   Am J Clin Nutr. 2012; 95(6):1413-1421.
  7. Breimer L. H. and Nilsson T. K. Has folate a role in the developing nervous system after birth and not just during embryogenesis and gestation? Scand J Clin Lab Invest. 2012; 72(3):185-191.
  8. Zempleni J. and Mock D. M. Marginal biotin deficiency is teratogenic. Proc Soc Exp Biol Med. 2000;
  9. Simpson et al. Micronutrients and women of reproductive potential: required dietary intake and consequences of dietary deficiency or excess. Part I - Folate, Vitamin B12, Vitamin B6. J Matern Fetal Neonatal Med. 2010; 23(12):1323-1343.
  10. Chmurzynska A. Fetal programming: link between early nutrition, DNA methylation, and complex diseases. Nutr Rev. 2010; 68(2):87-98.
  11. Lebel C. et al. Microstructural maturation of the human brain from childhood to adulthood. NeuroImage. 2008; 40(3):1044-1055.
  12. Morse N. L. Benefits of docosahexaenoic acid, folic acid, vitamin D and iodine on foetal and infant brain development and function following maternal supplementation during pregnancy and lactation. Nutrients. 2012; 4(71):799-840.
  13. Mansourian  A. R. A review on the metabolic disorders of iodine deficiency. Pak J Biol Sci. 2011;
  14. Loewenthal L. Study links iodine deficiency in pregnancy with poor cognitive outcomes in children. BMJ. 2013; 346:3365.
  15. Bath S. C. et al. Effect of inadequate iodine status in UK pregnant women on cognitive outcomes in their children: results from the Avon Longitudinal Study of Parents and Children (ALSPAC). Lancet. Published online May 2013.
  16. Assessment of iodine deficiency disorders and monitoring their elimination: a guide for programme managers. World Health Organization, 2007.
  17. de Benoist B. et al. Iodine deficiency in 2007: global progress since 2003. Food and nutrition bulletin. 2008; 29(3):195-202.
  18. WHO: Recommended iodine levels in salt and guidelines for monitoring their adequacy and effectiveness. 1996.
  19. Ryan A. S. et al. Effects of long-chain polyunsaturated fatty acid supplementation on neurodevelopment in childhood: a review of human studies. Prostaglandins Leukot Essent Fatty Acids. 2010; 82(4-6):305-314.
  20. Morales E. et al. INMA Project. Circulating 25-hydroxyvitamin D3 in pregnancy and infant neuropsychological development. Pediatrics. 2012; 130(4):913-920.
  21. Lozoff B. Iron deficiency and child development. Food and nutrition bulletin. 2007; 28(4):560-571.
  22. Micronutrient deficiencies: iron deficiency anemia. 2011.
  23. Thomas D. G. et al. The role of iron in neurocognitive development. Developmental Neuropsychology. 2009; 34(2):196-222.
  24. Todorich B. et al. Oligodendrocytes and myelination: the role of iron. Glia. 2009; 57(5):467-478.   
  25. Beard J. Iron. In: Bowman B. A, Russell R. M., eds. Present knowledge in nutrition. Washington, D.C.: ILSI Press. 2006; 430-444.
  26. Bourre J. M. Effects of nutrients (in food) on the structure and function of the nervous system: update on dietary requirements for brain. Part 1: micronutrients. J Nutr Health Aging. 2006; 10(5):377-385.
  27. Prentice A. Nutricional Ricktes around the world. J Steroid Biochem Mol Biol. 2013; 136:201-206.
  28. Young B. E. et al.  Maternal vitamin D status and calcium intake interact to affect fetal skeletal growth in utero in pregnant adolescents. Am J Clin Nutr. 2012; 95(5):1103-1112.
  29. American College of Obstetrics and Gynecology. Vitamin D - Screening and Supplementation During Pregnancy. Committee Opinion. No. 495; 2011.
  30. Paxton G. A. et al.  Vitamin D and health in pregnancy, infants, children and adolescents in Australia and New Zealand: a position statement. Med J Aust. 2013; 198(3):142-143.
  31. Devlin M. J. et al. Maternal perinatal diet induces developmental programming of bone architecture.
    J Endocrinol. 2013; 217(1):69-81.
  32. Radlović N. et al. Vitamin D in the light of current knowledge. Srp Arh Celok Lek. 2012; 140(1-2):
  33. Clagett-Dame M. and Knutson D. Vitamin A in reproduction and development. Nutrients. 2011; 3(4):
  34. Institute of Medicine. Food and Nutrition Board. Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc. Washington, DC: National Academy Press; 2001.
  35. Gontijo-Amaral C. et al. Oral magnesium supplementation in children with cystic fibrosis improves clinical and functional variables: a double-blind, randomized, placebo-controlled crossover trial. Am J Clin Nutr. 2012; 96(1):50-56.
  36. Iijima H. et al. The importance of vitamins D and K for the bone health and immune function in inflammatory bowel disease. Curr Opin Clin Nutr Metab Care. 2012; 5(6):635-640.
  37. Wagner C. L. et al. The role of vitamin D in pregnancy and lactation: emerging concepts. Womens Health (Lond Engl). 2012; 8(3):323-340.
  38. Maalmi H. et al. The impact of vitamin D deficiency on immune T cells in asthmatic children: a case-control study. J Asthma Allergy. 2012; 5:11-19.
  39. Ross A. C.  Vitamin A and retinoic acid in T cell-related immunity. Am J Clin Nutr. 2012; 96(5):
  40. Pae M. et al.  The role of nutrition in enhancing immunity in aging. Aging Dis. 2012; 3(1):91-129.
  41. Kim Y. et al. Vitamin C Is an Essential Factor on the Anti-viral Immune Responses through the Production of Interferon-α/β at the Initial Stage of Influenza A Virus (H3N2) Infection. Immune Netw. 2013; 13(2):
  42. Calder P. C. n-3 Fatty acids, inflammation and immunity: new mechanisms to explain old actions. Proc Nutr Soc. 2013; 14:1-11.
  43. Foolad N. et al. Effect of nutrient supplementation on atopic dermatitis in children: a systematic review of probiotics, prebiotics, formula, and fatty acids. JAMA Dermatol. 2013; 149(3):350-355.
  44. Romero V. C. et al. Developmental programming for allergy: a secondary analysis of the Mothers, Omega-3, and Mental Health Study. Am J Obstet Gynecol. 2013; 208(4):316.e1-6.
  45. Maggini S. et al. Essential role of vitamin C and zinc in child immunity and health. J Int Med Res. 2010; 38(2):386-414.
  46. Sugimoto J. et al. Magnesium decreases inflammatory cytokine production: a novel innate immunomodulatory mechanism. J Immunol. 2012; 188(12):6338-6346.