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Nutritional interventions during adolescence and their possible effects.

Nutrition is one of the most important factors affecting pubertal development. Increasing demands for energy proteins and micronutrients are necessary to cope with the rapid linear pubertal growth and development, change in body composition, and increased physical activity. Adequate nutrition is a key permissive factor for the normal timing and tempo of pubertal development. Severe primary or secondary malnutrition also can adversely delay the onset and progression of puberty. The higher incidence of anorexia nervosa and bulimia in adolescents imposes a nutritional risk on pubertal development. Here we provide an overview of nutritional requirements (macronutrients and micronutrients) necessary to cope with these changes. In addition, we discuss possible nutritional interventions trials and their effects on several aspects of growth and development in undernourished and stunted adolescents, in low- and middle-income countries (LMIC), who require nutritional rehabilitation. This mini review sums up some important findings in this important complex that link between nutrition, nutritional interventions, and pubertal development. (www.actabiomedica.it)


Introduction
Puberty entails a progressive nonlinear process starting from prepubescent to full sexual maturity through the interaction and cooperation of biological, physical, and psychological changes. Nutrition is one of the most important factors affecting the onset and progression of pubertal development. Adequate nutrition is a key permissive factor for the normal timing and tempo of pubertal development. Puberty triggers a growth spurt, which increases nutritional needs including macro and micronutrients. Increased caloric, protein, iron, calcium, zinc, and folate needs must be provided during this critical period of rapid linear growth and bone accretion. Moderate and severe primary or secondary malnutrition can adversely modulate the onset and progression of puberty. The higher incidence of nutritional deficiencies and anorexia nervosa in adolescents imposes a nutritional risk on pubertal development and final adult stature.
Here we provide an overview of nutritional requirements (macronutrients and micronutrients) necessary to cope with these changes. In addition, we discuss possible nutritional interventions trials and their effects on several aspects of growth and development in undernourished and stunted adolescents, in low-and middle-income countries, who require nutritional rehabilitation (1).

Pubertal growth spurt and nutritional requirements
Nutrition during adolescence should meet the following objectives: • Provide the necessary nutrients to meet the demands of physical and cognitive growth and development.
• Provide adequate stores for illness or pregnancy.
• Prevent adult onset of diseases related to nutrition e.g., cardiovascular diseases, diabetes, osteoporosis, and cancer • Encourage healthy eating habits and lifestyle.
According to the Dietary Guidelines for Americans 2010, girls ages 9 to 13 generally require 1.400 to 2.200 calories and teen boys ages 14 to 18 require 2000 to 3200 calories per day to maintain healthy body weights. Girls ages 14 to 18 usually need 1.800 to 2.400 calories/daily during puberty. Active pubescent girls require more calories than those with low activity levels ( Table 1). Teenage athletes who regularly participate in vigorous sports training may require up to 5,000 calories per day (2).

Tracking changes in dietary intake during puberty and their determinants in different populations
Understanding changes in dietary intake during puberty could aid the mapping of dietary interventions for primary prevention. Few studies available describing habitual dietary intake during puberty, differ in terms of study design, follow-up period, data collection methods, age of subjects, and study location. Dietary behaviors observed, range from specific food items or food groups to broader dietary patterns, including a range of foods (3)(4)(5)(6)(7)(8)(9).
An assessment of the current diet and nutritional status in many Asian and African countries proved deficient intake of macro and/or micronutrients in a large proportion of adolescents (Table 2) (10)(11)(12)(13).
Review of optimal Mediterranean diet (MD) adherence in children and adolescents in southern European countries (Spain, Italy, Cyprus, Greece) showed that the major determinants of adherence to a traditional MD pattern in southern European countries rely on social and demographic factors. Children and adolescents may be the age-groups with the most deteriorated MD profile. In Spain, 49.4% of adolescents demonstrated intermediate adherence. In Greece, in the greater Athens area the overall adherence to the MD was poor. In Cyprus, more than one third of the children followed a poor-quality diet. The authors highlighted a need for nutrition education programs are not limited to children and adolescents but also include parents, teachers, and physicians (14,15).

Dietary patterns and timing of puberty: Effects of quantitatively high-calorie diet on puberty onset
Several lines of evidence support the interplay of nutritional status, energy balance, and hormones in the regulation of growth and pubertal development. Fre- quently, children with obesity are taller for their age, with accelerated linear growth and advanced skeletal maturation, and tend to mature earlier than lean children. Secular trends toward a declining age at puberty onset with correlated changes in body weight have been reported in economically advanced countries. This has been attributed to excess calorie intake along with reduced physical activity in children (16,17).
Feeding juvenile female rhesus monkeys born and raised with a high-calorie diet results in acceleration of body growth (weight, length, and BMI) and precocious menarche. These changes were associated with increased leptin and IGF-I levels throughout the experiment. These findings supported the importance of the quantity of caloric intake as an important factor in determining the onset and progression of puberty (18).
In a prospective study conducted in the United States, intake of sugar-sweetened beverages (SSBs) was associated with early sexual development in 5,583 girls. Premenarcheal girls who consumed >1.5 servings of SSBs per day at ages 9-14 years had a statistically significant 24% higher probability of menarche during follow-up than did girls who consumed ≤2 servings of SSBs weekly after adjusting for sociodemographic and maternal characteristics, physical activity, and total caloric intake. In another prospective study of girls from the United States, every standard deviation of caffeine every SD of aspartame intake at 10 years of age was related to a 22% and 20 % higher risk of early menarche. (<11 years of age) after adjusting for potential confounding variables. Neither fructose nor sucrose intake was related to the timing of puberty (19,20).
In a Chinese study, three distinct dietary patterns, "traditional diet", "unhealthy diet", and "protein diet" were established. Neither the "traditional diet" pattern nor the "protein diet" pattern showed any association with precocious puberty. The "unhealthy diet" pattern was significantly positively associated with precocious puberty in both and girls. The relationship remained positive only for girls (OR = 1.25, 95% CI = 1.04-1.49) after adjustment for age and BMI but statistically nonsignificant after further adjustment for socioeconomic factors in both boys and girls (21).
In an Iranian study on 568 girls, three dietary patterns were defined, i.e., balanced pattern, high calorie and fat pattern and high protein diet pattern. Data from the multivariate regression analysis showed that both balanced dietary pattern and high protein diet pattern were protective factors for precocious puberty, while high calorie and fat pattern was risk factors (22) Effects of different quantity and quality of protein intake on puberty Some evidence indicates that animal protein intake during childhood may be related to the earlier onset of puberty. In a small study of girls from the United States, total animal protein intake at 3-8 years of age was related to earlier menarche and age at peak height velocity (APHV). Among German boys and girls, intakes of total and animal protein at 5-6 years of age were related to early APHV, menarche in girls, and voice break in boys (23,24).
Gunther et al. (24) reported that protein intake from cow milk and other dairy was related to earlier pubertal growth spurts and APHV among 112 German In India, 12,124 adolescents in villages of 10 states consumed grossly inadequate green leafy vegetables, fruits, pulses, and milk. The mean nutrient intakes were below the RDA in all adolescent age groups irrespective of sex, and 50% were not getting even 70% of their daily requirements of energy Doku et al. 2013. (11) In Ghana, 31% of those ages 12-18 years ate breakfast fewer than four days a week, 56 percent rarely ate fruits, 48 percent rarely ate vegetables, and boys were more physically active than girls. Barugahara et al. 2013. (12) In Uganda, girls ages 11-14 years achieved only 30% for folate, 36 % for energy, 54 %for iron and riboflavin, 59% for protein, 61% for vitamin A, 89% for vitamin C, and 92% for fiber of the WHO daily requirements. Alam et al, 2010. (13) In Bangladesh, 32% of adolescent girls were stunted. The overall dietary knowledge was low, and 36% were not aware of the importance of taking extra nutrients during adolescence for growth spurt.
boys and girls. Similarly, in a prospective study of 134 Iranian girls, those with milk intake at ≥ 34 g per day, at 9 years of age, had higher odds of early menarche at or before age 12 years than did girls with milk intake at <34 g per day. Using data from the National Health and Nutrition Examination Survey, Wiley et al. (25) found that higher milk consumption at ages 5-12 years among 2,057 girls from the United States was associated with an earlier age at menarche. However, these findings were not supported in other studies (26,27).
Other studies suggested that animal protein increased the risk and plant protein decreased the risk of early menarche. Of protein-containing food groups, intakes of poultry and low-fat dairy were marginally associated with a higher risk of early menarche. The odds of early menarche were reduced with higher intake of plant protein. These findings suggested that partly substitution of animal protein with plant sources during childhood may postpone menarche's timing. (28)(29)(30).
The potential effects of animal foods, especially dairy, on the timing of puberty have been attributed to a protein-mediated stimulation of IGF-1 secretion. Higher circulating levels of this hormone during childhood have been related in some studies to an earlier onset of puberty (31).

Micronutrients and a possible effect on pubertal development
Micronutrient requirements increase during puberty; thus, prepubertal micronutrient status may influence the timing of sexual maturation. Evidence on the effects of micronutrients on the timing of puberty is insufficient and inconsistent. In a randomized controlled trial among 160 Gambian boys, those supplemented with calcium for 12 months had an earlier APHV and shorter adult stature than did boys in the control group (32). In a randomized study among 144 Swiss girls, those supplemented with calcium from ages 7.9 to 8.9 years reached menarche earlier than did girls who received the placebo (33).
Kissinger and Sanchez reported a statistically significant, positive association between iron intake and age at menarche among 230 girls from the United States (34). In a small, randomized trial of 17 Iranian children, those supplemented with zinc had an earlier initiation of puberty compared with children assigned to the placebo group (35). In another randomized controlled trial of 102 boys ages 13.6 to 15.5 years with short stature and delayed puberty, supplementation with iron and vitamin A resulted in faster testicular growth (36). In the study by Maclure et al. (37), vitamin A intake was strongly associated with earlier menarche.

Dietary Fat and Polyunsaturated Fatty Acid Intakes during Childhood may affect Puberty Timing Independent of protein intake. Among 3425 girls and 2495 boys, children with higher intakes of total fat and PUFA have been more likely to reach their puberty at an earlier age. Associations were not attenuated on additional adjustment for childhood dietary protein intake. (38) Global prevalence of under-nutrition and nutritional stunting in adolescents
Under-nutrition is the most important cause of growth retardation worldwide. Poverty in the poor countries and self-induced food restriction in the rich countries or malabsorption and chronic systemic diseases are the main causes. There are an estimated 1.8 billion adolescents in the world, with 90% residing in low-and middle-income countries (LMIC). Nutritional deficiencies, suboptimal linear growth, and undernutrition are major public health problems (38,39).
The prevalence of moderate and severe underweight (undernutrition) is highest in South Asia; one in 5 girls aged 5-19 years and nearly one-third of their male peers are underweight. According to the Global School-Based Student Health Survey, more than 10% of surveyed girls were underweight in Mauritius, Sudan, Bangladesh, Maldives, Cambodia, and Vietnam.
In 2016, the mean BMI estimates for youths aged 10-19 in South Asia, Southeast Asia, East Africa, West Africa, and Central Africa were <20 for both male and female adolescents. The lowest BMI were seen in Ethiopia, Niger, Senegal, India, Bangladesh, Myanmar, and Cambodia (40,41).
Health surveys in 58 countries showed that the distribution of height-for-age z-scores (HAZ) for these adolescents a quarter of girls are 2 or more SDs below the mean height-for-age as compared to the WHO/CDC reference population (42). The limited published estimates of stunting in girls aged 15-19 ranged from 52% in Guatemala and 44% in Bangladesh to 8% in Kenya and 6% in Brazil (43).

The effect of chronic childhood malnutrition on pubertal growth and development
Chronic primary or secondary malnutrition leads to serious consequences including impaired growth, de-layed pubertal development, osteopenia, osteomalacia, anemia, and different syndromes caused by deficiency of vitamins, minerals, essential fatty acids and amino acids, and trace elements (Table 3 and figure 1) (1,44).
Pubertal growth and development were compared in 342 privileged, urban children and 347 impoverished rural adolescents from Kenya. Measurements of height, weight, upper arm circumference, and triceps skinfolds revealed marked differences between the two study groups just before the onset of sexual maturation. These differences were also found in the early stages of puberty but notable catch-up was evident throughout the later period of the maturational process. Early stages of sexual maturity were delayed by 3 yr. in malnourished boys with a 2.1 years lag in the age of onset of menarche in rural girls. Derived estimates of body fat as well as direct anthropometry revealed that the onset of puberty is not size related under the circumstances of chronic childhood malnutrition (45).

Hormonal mediation of delayed puberty during chronic malnutrition (Figure 1)
Hormonal adaptation mediates delayed puberty in situations with suboptimal nutrition to prolong growth of the individual and to delay reproductive  ability until conditions to support reproduction exist (46). Current understanding of energy sufficiency or insufficiency signalling pathways considers the HPGaxis to re-activate. Research using animal models revealed new factors important in energy homeostasis.
Leptin levels are directly related to adipose stores and act within the hypothalamus to adjust energy requirements. The gradual increases in GnRH are highly sensitive to body energy reserves that are influenced by leptin. In chronic undernutrition, leptin levels are low, and there is a loss of leptin permissive action (53). Ghrelin is secreted from the stomach because of energy insufficiency and acts as an inhibitory control on puberty onset in girls (54).
Kisspeptin also stimulates directly and indirectly the GnRH neurons that drive HPG axis maturation and puberty onset. Elucidation of the leptin/Kiss pathways require further study, but recent discoveries support a direct connection in undernutrition between leptin deficiency, reduced Kiss1 mRNA expression and reduced kisspeptin immunoreactivity (55)(56)(57).

Required interventions to manage nutritional problems in adolescents
Adolescent health and development require many interventions including health education; supportive parenting; nutrition; immunization; psychosocial support; prevention of injuries, violence, harmful practices and substance abuse; sexual and reproductive health information and services; management of communicable and non-communicable diseases.
To respond to the diverse needs of adolescents, different interventions are needed in different coun-tries and communities. A review of the situation in selected South-East Asian countries showed acute scarcity of programs targeted at adolescents in the Region. The major underlying reason for the widespread lack of policies and programs for improving health and nutritional status of adolescents in the Region is a lack of age and sex-disaggregated data on health and nutritional status of adolescents at the national level. Scarcity of trained health providers and adolescentfriendly health centers to deal with the special needs of adolescents are important reasons for the neglect of adolescents in public health programs (58,59).

Strategies for managing adolescent undernutrition
The main strategies suggested for improving adolescent nutrition include food-based strategies like dietary modification and food fortification, for ensuring adequate nutrition at household level; addressing behaviour modification to bring about dietary change in adolescents. This can be achieved through schoolbased nutrition interventions, using a social marketing approach, behaviour change through communication and mobilizing families and communities; control of micronutrient deficiencies; regular nutrition assessment and counselling of adolescents; care of adolescents during pregnancy and postnatal period; intersectoral linkages at community level and building linkages with adolescent friendly health services (60).

Catch up growth in in low-and middle-income countries without intervention
Catch-up growth (CUG) from longitudinal cohorts LMIC without intervention showed inconsistent CUG and stunting recovery.
In a longitudinal study in Bangladesh, Svefors et al. (61) enrolled 1094 children at birth and followed their growth until age 10. The prevalence of stunting was highest at 2 years (50%) decreasing to 29% at 10 years.
In South Africa, Stein et al. (62) followed up 1918 subjects from birth to twenty years. They reported that progression through puberty modifies the relation between prepubertal and adult anthropometry. Bosch et al. (66), in Bangladesh, followed 707 children from birth to 12-16 years. They reported that adolescent stunting was associated with childhood stunting and childhood underweight. Adair et al. (67), in Philippines enrolled 2011 children at birth; and followed them to age 12. Of the 1,252 children stunted at 2 years of age, 379 (30.3%) were not stunted at age 8.5, and 407 (32.5%) were not stunted at age 11-12. Only 1.3% of 11-year-old and 5.1% of 12-year-old girls achieve menarche. Among girls who achieved menarche, there was less stunting.

Effects of nutritional interventions in adolescents with undernutrition (Figure 2)
The evidence for effective interventions to address nutritional problems in LMICs is mostly weak. Few studies have systematically examined nutritional interventions in settings where dietary inadequacy and micronutrient deficiencies exist. From high income countries (HICs), there is some evidence on interventions for eating disorders, although much further work is needed in these settings as well (68).

Protein based supplementation intervention in adolescents living in LMIC
A total of 7 protein-based intervention trials provided data to calculate an effect on linear growth were identified. Five studies contained multiple treatment groups, each providing either 2 or 3 data sets. Most of the studies were conducted in LMICs, including 1 in Africa, 2 in East Asia and the Pacific, and 3 in South Asia. The number of subjects in each study ranged from 35 to 190, with mean ages of subjects ranging from 33 to 161 mo. At baseline, 6 study populations had a mean HAZ <-2. Protein supplements were administered as either meat, cow milk (liquid or powder), amino acid-supplemented rice or wheat, casein, whey, or high-protein diets. The duration of supplementation ranged from 0.69 to 24 mo. Most datasets (85%) had a positive effect on size (69)(70)(71)(72)(73)(74)(75)(76)(77)(78).

Micronutriments and protein supplementation (Figure 2)
The most studied micronutrient is calcium, as calcium absorption and bone mineralization have been shown to increase during early pubertal development among girls with consequences for long-term bone health. Supplementation with calcium, however, has been found to be of limited benefit even in settings where calcium intake was low. For example, in a Gambian cohort of children 10.3 years (Tanner stage 1) at enrolment, calcium supplementation (1,000 mg/day) increased bone mineral content of digital radius but had no impact on bone size or linear growth (79)(80)(81).
In a systematic review, several effective nutritional interventions were identified across a wide range of ages, duration, and baseline status; few studies were from LMICs. The overall findings were that interventions with zinc, vitamin A, multiple micronutrients, and protein had a significant impact on improving height; the effect size increases in linear growth ranged from 0.05 HAZ for vitamin A to 0.68 HAZ for protein. Interventions including iron, calcium, iodine, and food supplements showed no significant benefit, although sample sizes for the pooled studies for these were low (approximately 500-1,100). The sample size for the protein studies was low (n = 939), and yet the effect size was the highest. The multiple micronutrient intervention had modest significant benefits and may be a better way to combine provision of individual nutrients (82).
Randomized trials of iron supplementation have been shown to significantly improve hemoglobin concentrations among adolescents based on pooled analysis of 7 studies. However, there was a lack of significant impact on linear growth. This nutritional intervention may be worth considering, given the benefit of iron supplementation on cognition in school age children (83,84).

Home fortification of foods with multiple micronutrient powders (MNP) for health and nutrition (Figure 2)
Food fortification is defined as the practice of adding vitamins and minerals to commonly consumed foods during processing to increase their nutritional value. It is a proven, safe, and cost-effective strategy for improving diets and for the prevention and control of micronutrient deficiencies. In 2008 and 2012, the Copenhagen Consensus ranked food fortification as one of the most cost-effective development priorities. (85,86) While mandatory food fortification has been used as a strategy to prevent micronutrient deficiencies in HIC, it is still less common in LMICs where food systems are not delivering nutritionally adequate diets due the production and consumption of just a few major starchy food crops (maize, rice, wheat) with low micronutrient content and/or bioavailability (phytate). In the past two decades, food fortification has become increasingly popular in LMICs for several reasons, including rapid urbanization and increasing household purchasing power, leading to a greater proportion of the population relying on processed foods (87,88).
Numerous country-level studies on the impact of food fortification on micronutrient status have shown positive results. A review in 2013 assessed the effects and safety of home (point-of-use) fortification of foods with multiple micronutrient powders on nutritional, health, and developmental outcomes in children. The intervention was consumption of food fortified at the point of use with multiple micronutrient powders formulated with at least iron, zinc and vitamin A compared with placebo, no intervention or the use of iron containing supplements, which is the standard practice. They included eight trials (3748 participants) conducted in LIC countries in Asia, Africa and the Caribbean, where anaemia is a public health problem. Home fortification with MNP reduced anemia by 31% and iron deficiency by 51% in infants and young children when compared with no intervention or placebo. However, authors did not find an effect on growth. In comparison with daily iron supplementation, the use of MNP produced similar results on anaemia and hemoglobin concentrations (89). In Costa Rica, an evaluation of the impact of iron fortification on anemia prevalence found a significant decrease at the national level in the prevalence of anemia among children and adolescents from 19 to 4% (90).
In Indonesia, a study conducted in two districts of West Java from 2011 to 2012 assessed the effects of large-scale fortification on the vitamin A status of women and children and found that fortified oil increased vitamin A intake close to the recommended nutrient intakes, contributing on average 38-40% among older children and adolescents (91).
A systemic review in 2014 suggested that micronutrient supplementation among adolescents (Predominantly females) can significantly decrease anemia prevalence. Interventions to improve nutritional status among "pregnant adolescents" showed statistically significant improved birth weight, decreased low birth weight, and preterm birth (93).
The WHO recommends iron-folic acid (IFA) supplementation for non-pregnant menstruating girls in contexts with high rates of anemia (94). On the other hand, another systematic review performed (2017) in both HICs and LIMCs did not find significant association between the effect of multiple micronutrient fortification on child growth outcomes such height/ length-for-age z-score (HAZ/LAZ) in 8 studies (n =2889 participants; low-quality evidence) (95).
In addition, two recent reviews on fortified complementary foods (iron, folic acid, calcium, and vitamin D) in adolescents were uncertain of the effect of MMN fortification on hemoglobin concentrations, calcium supplementation on total body bone mineral content (BMC), calcium plus vitamin D supplementation on total body BMC, and zinc supplementation on zinc levels. Fortified foods were associated with more diarrhea episodes (96,97).

Protein energy supplementation
Adolescent pregnancy is common in LMIC. In pregnant women in general, especially if they are undernourished, PES increased mean birth weight and decreased the risk of low birth weight, small-for-gestational-age births, and stillbirths. However, no studies have been conducted specifically on adolescent mothers (98).

Oral nutritional supplements (ONS) and ready to use therapeutic food (RUTF)
RUTF is an energy-dense, mineral-and vitaminenriched food that requires no preparation and is specifically designed to treat severe acute malnutrition (SAM). RUTF has a similar nutrient composition to F-100 therapeutic milk, which is used to treat SAM in hospital settings. RUTF has significant advantages over liquid-based diets. The paste is oil-based with low water activity and, as such, can be stored at home with little risk of microbial contamination. It is easy to use, digestible and affordable at acceptable cost (99)(100)(101).
Ready-made oral nutritional supplements (ONS) are designed for children and available on prescription typically provide 2.4 kcal/ml or 1.5 kcal/ml in 125 ml and 200 ml bottles. One possible strategy to improve nutrient intake in children and adolescents with falter-ing growth is to reduce ONS volume by increasing the energy and nutrient density. Therefore, these formulas may be used in underweight children and adolescents with volume sensitivity or those with poor appetite (102).
ONS and RUTF proved to be effective in the management of underweight infants and young children with undernutrition. However, the major global focus of health has been on children under the age of 5 years, while older children (aged 6-9 years) and adolescents (aged 10-19 years) have not received the due attention until lately (103)(104)(105).
A controlled trial investigated the effects of energy dense pediatric ONS versus standard ONS in old children and adolescents with low BMI or low weight gain per day (WGD) (n= 34). ONS were randomized to high caloric ONS (cONS) (n =22) or standard ONS (sONS) (n = 12) for a year. Results showed that the WGD, height growth velocity (GV: cm/year), and Ht-SDS increased significantly, in both groups, during the year of ONS. The use of the cONS resulted in significantly greater mean total WGD and BMI-SDS after 6 months and 1 year, compared to the sONS group. The increase in insulin-like growth factor 1 (IGF1-SDS) was significantly higher in the cONS groups versus the sONS group. Moreover, the WGD was correlated significantly with the height GV during the year of ONS intake (106).
However, the cost of current standard RUTF and OSN is one of the major obstacles to their use in community-based management programs. In addition, the high prevalence of undesirable effects (nausea, vomiting and diarrhea) attributed to RUTF may hinder RUTF acceptability and adherence in some participants (107).

Supplement (mis)use in healthy adolescents
Although supplements may be necessary and safely consumed in certain specific situations, most healthy adolescents do not need them. Studies have indicated high prevalence of dietary supplement usage by adolescents that ranged from 10% to 74%. These supplements with no or little evidence of beneficial effects in healthy adolescents include proteins, amino acids, beta-hydroxy-beta-methyl butyrate, carnitine, creatine, vitamins, caffeine, and bicarbonate. The widespread use of these unnecessary dietary supplements among adolescents predisposes them to significant health risks (108)(109)(110)(111).

Conclusion
Consuming an adequate and balanced healthy diet during the fast phase of pubertal growth spurt is necessary to assure proper growth and normal pubertal development. Excessive intake of some types of proteins, fat, minerals, and vitamins may lead to early puberty. Whereas, malnutrition of macro (proteins essential amino acids) , calories, essential fatty acids) and some micronutrients (iron, zinc, vitamin D ) can markedly delay the onset and/or delay the progress of growth and bone accretion during this critical period of growth (Figure 1). Although some studies suggested positive effect/s of food fortification with micronutrients and supplying more proteins and calories (RUTF and/or ONS) in malnourished children and adolescents (Figure 2), however long term-controlled studies are still highly required to support their positive effect on linear growth and pubertal development.

Conflicts of interest:
Each author declares that he or she has no commercial associations (e.g. consultancies, stock ownership, equity interest, patent/licensing arrangement etc.) that might pose a conflict of interest in connection with the submitted article.