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Baby Food and Infant Formulas

Infant nutrition

Infant nutrition consists of two phases:
1. Diet solely of breast milk or breast milk substitutes (first 4-6 months)
2. Diet with breast milk or breast milk substitutes supplemented with weaning food (at the earliest from 5 months, at the latest from 7 months.

If a mother is unable to or does not breastfeed, breast milk substitutes can be given to healthy, full-term infants:
a - Infant formula can replace breast milk from birth onwards and like breast milk is suitable as the sole source of food for the first four to six months. After that infant formula plus weaning food can be given throughout the first year of life. In Germany and in the European Union there are four types of infant formula:
- based on cow's milk protein with lactose as the sole carbohydrate.
- based on cow's milk protein with other carbohydrates besides lactose
- based on soy bean protein isolate (N.B.: this food is only lactose-free in Germany)
- based on partially hydrolysed (cleaved) protein (name HA). This initial food is intended for non-breast fed infants from families with a history of allergies.

b - Follow-on formula can replace breast milk at the earliest from the fifth month onwards. It is not suitable from birth onwards as it is not adapted to the needs of the very young infant. There is no compelling reason to switch from infant formula to follow-on formula.

c - Weaning food is the name for all dietary foods intended specifically for infants (and small children) which should supplement the diet with breast milk or breast substitute products at the earliest from the 5th month and at the latest from the 7th month onwards. It is recommended that weaning food be selected which corresponds to the Ernährungsplan des Forschungsinstituts für Kinderernährung in Dortmund (Nutrition Plan of the Research Institute for Children's Nutrition in Dortmund) and to use them in the stipulated sequence.

Both for infant bottle formula and weaning food products there are especially stiff statutory provisions concerning the composition, the use of additives (colouring agents, flavourings, preservatives are banned), the bacteriological requirements and the limit values for residues and contaminants which are uniform throughout the European Union

How to feed a baby, recommendations of UK FSA

The UK Food Standards Agency promulgates the following advices on how to feed a baby.


According to the advice of the Agency breastfeeding is best for babies. It should continue exclusive breastfeeding for six months, the longer the better. Continue to give breast milk or formula milk until it is at least a year old. A change to follow-on milk isn't necessary at any stage.

Infant formula

Infant formula is the only alternative to breast milk. Cows' milk is not suitable as a drink until a baby is a year old because it contains too much salt and protein, and not enough iron and other nutrients, to meet your baby's needs.

Starting on solid foods

The amount of solid foods may be gradually increased, beginning from the sixth month so that by twelve months, solid foods become the main part of your baby's diet, with breast or formula milk making up the balance. FSA says that commercial baby foods can be useful but should not replace family foods altogether. It is cheaper than buying baby foods, you'll know what the ingredients are, and your baby will get used to eating like the rest of the family.

Meat and fish-free babyfood for vegetarians

The FSA recommends to make sure to give two servings a day of pulses (such as red lentils, beans or chickpeas), or tofu to make sure they get all the energy and nutrients they need. The vitamin C in fruit and vegetables helps the absorption of iron, fruit and vegetables at mealtimes should therefore not be forgotten at baby's meal.

Avoid the following foods: The FSA recommends to avoid


Babies up to 6 months old should have less than 1g salt a day. From 7 months to a year old they should have a maximum of 1g salt a day.


Avoid adding sugar to the food or drinks you give your baby. If you give your baby stewed sour fruit, such as rhubarb, you could sweeten it with mashed banana, breast or formula milk.


Honey can contain a type of bacteria that may produce infant botulism. Honey should therefore be avoided for babies under one year, after that age the intestine matures and the bacteria can't grow.

Other foods to avoid up to six months

Because of possible allergies babies under six years old should not be fed with:

Wheat-based foods containing gluten

This includes bread, wheat flour, breakfast cereals and rusks.

Nuts and seeds

This includes peanuts, peanut butter and other nut spreads. Peanuts can be given from six months old onwards, if you always crush or flake them.


Fish and shellfish

Hydrolysed protein infant formulas

might be prescribed a GP if a baby has an allergy to cows' milk.

Soya-based infant formulas

They should only be fed on the advice a GP or health visitor. Babies who are allergic to cows' milk may also be allergic to soya.

Goats' milk infant formulas and follow-on formulas based on goats' milk protein

are not suitable for babies, and have not been approved for use in Europe. Since the levels of lactose are similar in both milks, formulas derived from goats' milk are also unsuitable for babies that are lactose-intolerant. Pasteurised goats' and sheep's milk can be used once a baby is a year old. Start using full-fat milks in cooked foods, and full-fat milk products, such as yoghurt after the age of six month.


The FSA says that water is the best alternative drink to milk, but fully breastfed babies don't need any water until they start eating solid food. For babies under six months old, take water from the mains tap in the kitchen and boil it.

Fruit juice

FSA comments that Fruit juices, such as orange juice, are a good source of vitamin C, particularly for vegetarian diet or breastfed babies, however fruit juice should not be given to babies under six month.

However, vitamin C might help our bodies absorb iron from a meal, so you may be advised to give diluted fruit juice with your child's meals after six months, In this case, give very dilute juice (one part juice with ten parts cooled, boiled water) in a feeding cup and at mealtimes only.

Introducing fish in diet of low-aged children protects of asthma [3]

According to Kiefte-de Jong et al. 2012, children born in Rotterdam, the Netherlands, who ate fish for the first time between the ages of 6 and 12 months but had no dietary fish intake at 14 months were less likely to have asthma symptoms, such as wheezing and shortness of breath, as preschoolers. The protective effect of fish was not seen when they first ate fish when they were younger than 6 months or eating no fish in their first year of life. Diets high in fish, vegetables, and fruit have been found to protect pregnant women and school-aged children from asthma.

The authors concluded that early life exposure to n-3 polyunsaturated fatty acids (n-3 PUFA) protects against developing asthma, and there is a specific window of opportunity between the age of 6 and 12 months which causes the protection effect of fish against asthma. The study was part of the Generation R Study, a multiethnic prospective birth cohort in Rotterdam.

Infant Formula Regulations

For US laws, Regulations, and Guidance please refer to the US FDA/CFSAN Infant Formula Homepage under Program Area: Infant Formula

The new European baby food regulation

[4] [5]
The new regulations of the Commission Directive 2006/141/EC amending Directive 1999/21/EC on baby food is focused on the nutritional value of the formula to satisfy the nutritional requirements of the infant.

FSA says the rules will help parents and carers to clearly tell the difference between infant formula, which can be used for the first six months, and follow-on formula, which is only to be used after six months.

It also hopes to make sure labelling and advertising is in line with the principles laid out in the European code, on infant formula and follow-on formula and amending Directive 1999/21/EC.

Baby Milk Action say advertisements for formula are putting mothers off breastfeeding, and campaign for a complete ban.

Baby Milk Action is a non-profit organisation which aims to save lives and to end the avoidable suffering caused by inappropriate infant feeding. [6]

A marketing code was introduced in 1981 to regulate the marketing of breastmilk substitutes. Companies continue to violate its provisions.

The Infant and Dietetic Foods Association (IDFA) wants to delay by two years the regulation to come into force applying for a judicial review [7].

UK infant and follow-up formula may keep current labels

According to a notice of FSA the UK High Court has ruled that manufacturers may continue to produce (and retailers may continue to sell) infant and follow-on formula bearing the current labels until 1 January 2010. After this time, they will have to ensure that products are labelled in accordance with the new labelling rules in the 2007 regulations. The judgement does not affect the rules relating to advertising of infant and follow-on formula, which apply immediately.

The implementation of new European legislation on infant and follow-on formula. infant and follow-on formula legislation was announced by the Department of Health and the Food Standards Agency in November. It is designed to introduce stricter controls on labelling and advertising of all types of formulae to ensure that breastfeeding is not undermined by the marketing and promotion of such products.

Codex Alimentarius: Draft Revised Standard for Infant Formula and Formulas for Special Medical Purposes Intended for Infants

[9] [10] [11]
The Codex in its ALINORM 05/28/26(2004) - 06/29/26(2005) and 07/30/26 Rev(2006) lays down the standard for the composition of infant formulas. Highlights of this standard are:
Definition of infant formula
Infant formula means a breast-milk substitute specially manufactured to satisfy, by itself, the nutritional requirements of infants during the first months of life up to the introduction of appropriate complementary feeding. Infant formula is so processed by physical means only and so packaged as to prevent spoilage and contamination under all normal conditions of handling, storage and distribution in the country where the product is sold. The term infant means a person not more than 12 months of age.

Essential Composition
Infant formula is a product based on milk of cows or other animals and/or other ingredients which have been proven to be suitable for infant feeding. The nutritional safety and adequacy of infant formula shall be scientifically demonstrated to support growth and development of infants.
All ingredients and food additives used shall be gluten-free.

Essential and semi-essential amino acids in breast milk
For an equal energy value the formula must contain an available quantity of each essential and semi-essential amino acid at least equal to that contained in the reference protein (breast-milk as defined in Annex 1.

Infant formula prepared ready for consumption in accordance with instructions of the manufacturer shall contain per 100 ml not less than 60 kcal (250 kJ) and not more than 70 kcal (295 kJ) of energy.

Isolated amino acids may be added to Infant Formula only to improve its nutritional value for infants. Essential and semi-essential amino acids may be added to improve protein quality, only in amounts necessary for that purpose. Only L-forms of amino acids shall be used.

Nutrients of infant formula
Nutrients in 100 g/ml are given in table 3.1.3 of the Standard.

Optional Ingredients
In addition to the compositional requirements listed under 3.1, other ingredients may be added in order to provide substances ordinarily found in human milk and to ensure that the formulation is suitable as the sole source of nutrition for the infant. Only L(+) producing lactic acid cultures may be used.

Vitamin Compounds and Mineral Salts
Vitamins and minerals added should be selected from the Advisory Lists of Mineral Salts and Vitamin Compounds for Use in Foods for Infants and Children (CAC/GL 10-1979). [12]

Specific Prohibition
The product and its components shall not contain commercially hydrogenated oils and fats and shall not have been treated by ionizing radiation.

Food Additives
In this standard part 4. the permitted food additives are grouped as thickening agents, emulsifiers, pH adjusting Agents, Antioxidants and packaging gas (propellants).

The standard sets a maximum level of lead of 0.02 mg/kg (in the ready-to-use product)

The product should comply with the appropriate sections of the following codes: Fill of Container
In the case of products in ready-to-eat form, the fill of container shall be: Labelling Labelling should comply with Guideline: Labelling should contain:

The Name of the Food

The name of the product shall be either "Infant Formula" or any appropriate designation indicating the true nature of the product, in accordance with national usage.

The sources of protein in the product shall be clearly shown on the label.

If cow's milk is the only source of protein, the product may be labelled "Infant Formula Based on Cow's Milk".

A product which contains neither milk or any milk derivative shall be labelled "contains no milk or milk products" or an equivalent phrase.

Products containing not less than 0.5 mg Iron (Fe)/ 100 kilocalories shall be labelled "Infant Formula with added Iron".

Or Products containing less than 0.5 mg Iron (Fe)/ 100 kcal shall be labelled with a statement to the effect that when the product is given to infants over the age of four months, their total iron requirements must be met from other additional sources.

Periconceptional supplementation of micronutritients

Iron supplementation for infants and development of brain

Lozoff and colleagues 2003 suggest that unsupplemented infants responded less positively to the physical and social environment and blame it to iron deficiency on the developing brain. The authors recommend iron supplementation in the first year of life.

Supplementation of vitamin A or iron alone did not improve growth, but multimicronutrient does [20]

Usha Ramakrishnan and colleagues 2004 in a meta-analyses of randomized controlled intervention trials assessing the effects of vitamin A, iron, and multimicronutrient interventions on the growth of children under 18 years old found that suplementation of vitamin A or iron alone did not improve child growth. Multimicronutrient, however, improved children growth.

Combined iron and zinc supplementation of infants [21]

Emorn Wasantwisut and colleagues 2006 found in a study that iron supplementation improved hemoglobin, iron status, and ponderal growth, whereas zinc supplementation improved zinc status. The authors concluded that for infants, combined iron and zinc supplementation is preferable to iron or zinc supplementation alone.

Undernutrition during gestation and infancy leads to gene changes linked to disease resistance [22]

A study of Khulan et al. 2012 supports the hypothesis that undernutrition during gestation and infancy predisposes to ill health in later life. The researchers suggest that micronutrient supplementation might be a cause of methylation of foetal genes which control the immune system.

Such changes were found by the authors in the DNA of cord blood and in a 9 months after birth. The authors stress that children born in Gambia during the wet season were at higher risk of infections than children born in the dry season. During the wet season less food is available as compared to the dry season. The reduced supply of micronutrients during the wet season may weaken the immune system due to a methylation of genes linked to disease resistance.

The link of nutrition and methylation of genes during and after gestation was demonstrated by supplementation of micronutrients of pregnants compared to a group without supplementation. Of micronutrients. The authors suggest that periconceptional nutrition in humans is an important determinant of newborn whole genome methylation patterns but may also influence postnatal development.

Intrauterine exposures mediated by maternal diet may also affect risk of cardiovascular disease, obesity, and type 2 diabetes. Cooper et at 2012 studied the DNA methylation at 12 differentially methylated regions (DMRs) was analysed in cord blood samples of pre- and periconceptional micronutrient supplementation which included folate, zinc, and vitamins A, B, C, and D. [23]

Prenatal dietary supplementation trials on the impact on risk of diseases such as CVD [24]

Trials investigating the effect of maternal supplementation of protein-energy, multiple-micronutrient and Ca on CVD risk in offspring were assessed by Hawkesworth 2009. Lower systolic blood pressure at 2 years of age in Nepal were reported. However no blood pressure reduction was found in the protein-energy trial in Guatemala trial, where only a reduction of fasting glucose and body composition was reported. No association between supplementation and CVD.

In The Gambia no association has been found between prenatal protein-energy supplementation and markers of CVD risk including body composition, blood pressure and fasting glucose and insulin in childhood and adolescence. [25]

The author concluded that four trials presented little evidence of an effect of maternal Ca supplementation on offspring blood pressure has been demonstrated in four trials, except reduced risk of high systolic blood pressure in one trial.

Bioavailability of zinc gluconate salts compared with zinc from yeasts

Zinc is, after iron, the most important trace elements in the body,being related to a healthy immune system, influence memory, muscle strength and endurance in adults.

According to Thomas Tompkins and colleagues compared the bioavailability of zinc gluconate and zinc from yeasts in two studies presented in 2007.

The first study found zinc yeast to have significantly less loss in the faeces, accounting for a gain in net zinc balance, while, in comparison, zinc gluconate supplementation resulted in net loss of zinc through the faeces. [26]

In the second study Tomkins and colleagues wrote that zinc-enriched yeast was 3.7 times more bioavailable than the zinc gluconate and that copper-enriched yeast was 1.4 times more bioavailable than the Cu gluconate. Lallemand Health Ingredients is waiting for the approval from EFSA for the mineral enriched yeast supplement. [27]

Food choice has little influence on iron status

Dietary intake was not significantly correlated with hemoglobin concentrations according to a study by Inger Öhlund and colleagues. The authors found in this study that the consumption of meat products had a positive effect on serum ferritin concentrations and mean corpuscular volume in boys.

In healthy, well-nourished children with a low prevalence of iron deficiency, the mother's but not the father's hemoglobin was significantly associated with that of her child, but the authors could not explain its reason.

Infant social-emotional behaviour and iron deficiency

Lozoff and colleagues 2008 assessed the dose-response relationships between severity of iron deficiency (ID) and infant social-emotional behaviour. The authors found a linear effects of poorer iron status for shyness (increasing, maternal rating), orientation-engagement, and soothability (decreasing, examiner ratings).

The authors stress that iron deficiency without anemia is not detected by common screening procedures and is more widespread than the other form, and social-emotional behaviour can profoundly influence the care-giving environment, with repercussions for overall development.

Does iron-fortified formula slow development in children?

Infant formulas are fortified in USA with 12 mg/L of iron to prevent iron-deficiency anaemia whereas Europe generally uses a lower amount; in the UK, the limit for iron in cows milk based infant formula is 1.5mg/100 kcal and 2,0 mg/100 kCal. [31]

According to Betsy Lozoff and colleagues iron-fortified baby formula may pose a developmental risk to children who do not need iron supplementation. The authors found that ten years after receiving formula containing 12 mg/L of iron as infants, children had lower scores across a battery of developmental tests compared with children given formula containing 2.3 mg/L of iron.
The authors, however call for more studies on this subject before any change is warranted.

Infant motor development and iron

According to Shafir and colleagues 2008 poorer motor function in iron deficient infants with and without anemia were found, Whereas non anemic iron deficiency were classified by the authors as particularly concerning, since it is not detected by common screening procedures and is more widespread than the anemic form.

List of Ingredients A complete list of ingredients shall be declared on the label in descending order of proportion.

Declaration of Nutritive Value It should contain:

Other labelling requirements

Basic informations of the Codex guidelines for infant formulas
The Codex guidelines for infant formulas was based on the recommendations on the compositional requirements for a global infant formula standard from Koletzko et al (2005) from the European Society for Pediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) which had formed an International Expert Group (IEG) collecting data for the guidelines. [33]

One important conclusion of the IEG was that infant formulae should only contain components in such amounts that serve a nutritional purpose or provide another benefit. The inclusion of unnecessary components, or unnecessary amounts of components, may put a burden on metabolic and other physiologic functions of the infant. [33]

Carlo Agostoni and Magnus Domellöf in an editoral in 2005 presented a list of recommended concentrations of nutrients in infant formulae 1977-2005 which helped to fill a data gap. [34]

Reduction of severity of diarrhoea with fermented infant formulae [35]
Carlo Agostini and colleagues in an analysis found only limited published data on the effects of fermented infant and follow-up formulae. In these products the lactic acid producing bacteria are heat inactivated after the fermentation. Only 2 studies mentioned that some fermented infant formulae may reduce the occurrence or severity of infectious diarrhoea in infants.

The authors recommend further studies on the effects of fermented infant formulae on infectious diarrhoea and other relevant outcomes Available data do not allow general conclusion on this matter.

Swedish study recommends reduction of saturated fats in infancy

Inger öhlund and colleagues in a study of Swedish infants between 6 and 12 month old, published in 2008, found that total fat intake complied with the Nordic recommendations, but polyunsaturated fatty acids of 5.6% was to low and saturated fatty acids with 15,1% of total energy was too high. The authors found that high polyunsaturated fatty acids intake was associated with lower total serum cholesterol, lower low-density-lipoprotein cholesterol and apolipoprotein B in girls but not in boys.

The authors stress that higher polyunsaturated fatty acids and lower saturated fatty acids intakes may reduce total cholesterol and lower low-density-lipoprotein cholesterol LDL-C early in life. The authors recommend to focus on fat quality rather than on quantity to lower serum lipid concentrations in early childhood.

Studies related to infant formulas

The Euro-Growth Study on infant food

The Euro-Growth Study of milk feeding (Freeman, van't Hof, Haschke 2000) found that at the age of I month, 52% of the infants were exclusively breast fed and 26% were exclusively formula fed.
At the age of 9 months, 18% of infants were fed only cow's milk.
At the ages of 3, 4, and 5 months, 50%, 67%, and 95% of infants were fed solid foods, respectively.

The study found high rates of breast-feeding initiation are found in Umea, Sweden, and in Athens, Greece; and low rates in Dublin, Ireland, in Toulouse, France, and in Glasgow, United Kingdom. The authors concluded that the use of cow's milk as the main milk drink before the age of 12 months is still common in certain European centres.

Leptin in infant formulas to prevent late obesity

Claire C. Stocker and colleagues (2007) report that supplementing infant rats' diets with the hormone leptin resulted in adult animals that did not fat or develop diabetes, even when fed a high-fat diet. The researchers concluded that leptin levels during pregnancy and lactation can affect the development of energy balance regulatory systems in their offspring.

Stocker points out that the absence of leptin is known to disrupt the development of energy balance regulatory mechanisms. Adding leptin to infant formulas could turn baby foods more similar to the composition of mother milk similar which contains leptin.

Breastfeeding may often not be possible because of health situation of the mother or for comodity reasons. Thus well balanced infant formulas replicating the healthy profile of breast milk as far as possible are essential for the fist months of life. This article started a discussion on leptin.

Leptin in new UK baby food [39]
In UK new infant formula with leptin will be lauched in late 2007 with the intention to protect from obesity and diabetes into adulthood. Leptin is present in milk but not in infant formulas. Adding leptin could restore natural composition of baby food.


Leptin is a hormone that plays a key role in regulating energy intake and energy expenditure, including the regulation (decrease)of appetite and metabolism.Leptin is produced by adipose tissue and interacts with six types of receptor (LepRa-LepRf). LepRb is the only receptor isoform that contains active intracellular signaling domains.

This receptor is present in a number of hypothalamic nuclei, where it exerts its effects. Importantly, leptin binds to the Ventral Medial nucleus of the hypothalamjus, known as the satiety center. Binding of leptin to this nucleus signals to the brain that the body has had enough to eat - a sensation of satiety.

Leptin-sensitizing agents to treat obesity

Leptin is an appetite-suppressing hormone secreted by fat tissue. It was proposed to treat obesity, however, obese persons were found to develop leptin resistance.

Umut Ozcan and colleagues 2009 found that elevated leptin secretion increased the stress on a part of the brain, the endoplasmic reticulum, which assembles proteins and folds them into their appropriate configurations. Under stress the endoplasmic reticulum produces unfolded protein in the hypothalamus of obese mice resulting in results in severe leptin resistance and obesity.

The stress triggers the production of unfolded proteins, that tries to relieve the stress by increasing the level of molecular "chaperones," which assist in protein folding, and by blocking more proteins from coming in.

The authors suggest a new treatment of obesity with chemical chaperones, 4-phenyl butyric acid (PBA), and tauroursodeoxycholic acid (TUDCA), which were found to decrease endoplasmic reticulum stress and act as leptin-sensitizing agents.

Ways to tackle overweight

Absorption of fat molecules
Xenical (orlistat), Roche's (Basel, Switzerland) drug that blocks the breakdown and absorption of about 30% of dietary fats.
Studies on a fatty acid transporter (FATP4) which blocks the uptake of fatty acids which result from the digestion of fat may replace Xenical.

Thyreoid hormones stimulating thermogenesis to burn off excessive caused loss of bone calcium.
Increasing the expression of uncoupling proteins (UCPs) to create heat and thus reduce risk of obesity and agonists of the beta3-adrenergic receptor which also targets the energy output, are being studied.

Feeling of satiety
Peptides produced by the gastrointestinal system and pancreas such as cholecystokinin (CCK), and others include neuromedin B, gastrin-releasing peptide, and enterostatin naturally regulate peripheral feelings of satiety and the amount of food consumed.

Centrally acting appetite suppressants in weight-reducing drugs such as Redux (dexfenfluramine) and fenfluramine in combination with phentermine (acts as a noradrenaline reuptake inhibitor) in the fen-phen diet drug were approved by FDA in 1996 and withdrawn in the same year because of link to heart valve damage. [43]
Dexfenfluramine boosted serotonin levels by stimulating its release and inhibited its reuptake. The American Home Products (AHP) company is being sued for withholding and concealing informations on the safety of the drug. The company still researches on serotonergic control systems, however, it concentrates on mice studies targeting the 5-HT2c subtype of receptor 5-HT.

Leptin, a fat-regulating hormone
Jeffrey Friedman and his team (2002) discovered the "ob" gene, which underlies the gross obesity in the ob/ob strain of mice. Injecting leptin back into the ob/ob mice appetites were reduced and the excess weight was lost. [44]

Jeff Flier, an obesity researcher at Harvard's Beth Israel Deaconess stressed the fact that high levels of endogenous leptin in obese people had been found, suggesting that sensitivity to leptin is lost and cannot be restored by further elevation of the compound. The company Amgen is still working on new formulations on the product. It has been used successfully to treat a handful of severely obese children who have an inherited deficiency in the hormone.

Researchers now suspect that obese people appear to be resistant to leptin because the hormone is not transported into the brain.

Leptin is produced by fat cells, circulating in the blood to the hypothalamus where it works through a number of nuclei and pathways to reset the body's weight controller. As fat levels increase, leptin levels rise, triggering a reduction of food intake and increasing metabolism.

Leptin inhibits the release of neuropeptide Y (NPY), a small protein that increases appetite.

Leptin effects
Leptin is related to the alfa-melanocyte-stimulating hormone (alfa-MSH), which is actually a fragment of the precursor protein POMC.alfa-MSH acts through the MCR-4 receptor to reduce appetite.

Leptin increases the production of the SOCS-3 (suppressor of cytokine signaling-3) protein, which terminates its activity at the leptin receptor. The SOCS-3 a regulator of the leptin signaling pathways in healthy individuals, it is overactive in obese patients.

Researchers of Johns Hopkins University discovered that malonyl coenzyme A inhibits NPY independently of leptin, decreasing appetite in mice and might lead to eight loss in humans.

Ciliary neurotrophic factor (CNTF)
George Yancopoulos of Regeneron tested Axokine (ciliary neurotrophic factor, CNTF) as a treatment of a disease noted that the drug used the same signaling pathway as leptin with the effect of weight reduction. There are hope that the drug has better effects compared with leptin, but it must be injected, because it is not stable by oral intake.

Fatty acid synthase inhibitors (cerulenin and compound C75) [45]
Francis P. Kuhajda and colleagues (2000) identified a link between anabolic energy metabolism and appetite control. According to the authors treating mice with fatty acid synthase (FAS) inhibitors (cerulenin and a synthetic compound C75) inhibited feeding and caused a dramatic weight loss. C75 inhibited expression of the prophagic signal neuropeptide Y in the hypothalamus and acted in a leptin-independent manner that appears to be mediated by malonyl-coenzyme A. They conclude that FAS may become important in feeding regulation.

Fatty acid synthase (FAS) and carnitine palmitoyltransferase-1 [46]
Gabriele V. Ronnett and colleaugues (2006) say that fatty acid synthase (FAS) catalyzes the synthesis of long-chain fatty acids, whereas the breakdown of fatty acids by beta-oxidation is regulated by carnitine palmitoyltransferase-1, the rate-limiting enzyme for the entry of fatty acids into the mitochondria for oxidation.

Studies indicate that inhibition of FAS or stimulation of carnitine palmitoyltransferase-1 using cerulenin or synthetic FAS inhibitors reduces food intake with resulting weight loss. compounds also increase energy consumption. The authors say that at least part of C75's effects is mediated by modulation of adenosine monophosphate-activated protein kinase, a member of an energy-sensing kinase family, and conclude that these effects could be useful in obesity therapy.

Leptin and melanocortin activity on the hypothalamus [47]
Shimizu and colleagues (2007) note that the brain hypothalamus coordinates extra-hypothalamic regions to maintain energy homeostasis through the regulation of food intake and energy expenditure. According to these authors leptin and pro-opiomelanocortin (POMC)-derived alfa-melanocyte-stimulating hormone are key anorectic molecules, and the leptin receptor and POMC gene are both expressed in the hypothalamic arcuate nucleus. Data support the concept of a leptin-independent melanocortin signaling system in the regulation of energy homeostasis.

The position of the charity Weight Concern [48]
According to Dr. Ian Campbell, medical director of the charity Weight Concern leptin has proved to be a great disappointment, and most of us have plenty and true deficiencies are rare. Obese people tend to have higher than normal levels.

Hydrolysed protein infant formulas

Short- and long-term effects of feeding hydrolysed protein infant formulas

Rzehak and colleagues 2009 analysed differences of body mass index (BMI) of infants fed with partially hydrolysed whey (pHF-W), extensively hydrolysed whey (eHF-W), extensively hydrolysed casein (eHF-C), or cow-milk formula (CMF) and infants exclusively breastfed.

The authors report no differences in BMI in all groups, except the extensively hydrolysed casein (eHF-C) group,which presented a lower weight gain in the first year of life, but not later with no long-term consequences of different formulas on BMI.

Protein hydrolysate formulas, feeding behaviour and growth of infants

Mennella and colleagues 2011 assessed differences in feeding behaviour and growth of infants of ages 0.5 to 7.5 months, fed with an extensively protein hydrolysate formula compared with infants fed with cow-milk formula. Anthropometric Z-scores were calculated using the World Health Organization growth standards. [51]

Infants fed with protein hydrolysate formula presented lower weight-for-length z scores, slower weight gain velocity, and consumed less formula to satiation than infants fed with cow-milk formula.

The authors call for more studies on longer-term effects of hydrolysed protein diets focusing on later development of obesity, diabetes, other diseases, long-term consequences of the early growth differences associated with infant formulas, and how it differs from breastfeeding.

Soybased infant formulas could reduce severity of diarrhea in infants

Acccording to Andres and colleagues 2007, rotavirus infections cause acute gastroenteritis in children and are responsible forfive percent of all child deaths globally. Infection affects almost all children within their first 5 years of life. Soy-based infant formula, containing high levels of isoflavones were found to have antiviral activity on numerous viruses. The authors found that genistin was responsible for the inhibition of rotavirus activity of the isoflavones from soy.

The authors suggest that the modulation of isoflavone composition and concentration of infant formulas may reduce the severity of rotavirus infection in human and production animals.

Infant formula made from soy protein is no substitute for cow's milk products

Soya formula for infants should only be administered on doctor's advice
According to the German Federal Institute for Risk assessment (BfA) If a mother is unable to breastfeed her baby, she can fall back on infant formula from the drug store or supermarket. However, soybeans contain high concentrations of isoflavones genistein and daidzein.

Besides isoflavones, soy formula may also contain phytate. The natural plant component can influence the intake of minerals and trace elements. Furthermore, soybeans may also contain higher amounts of the plant component, phytate. Professor Dr. Dr. Andreas Hensel, President of the Federal Institute for Risk Assessment (BfR), comments, "Infant formula and follow-up formula made from soy protein should only be administered on medical grounds and then only under medical supervision."

The Health Committee of New Zealand recommends that the current mandatory label on soy-based infant formula should be amended to read: "Breastmilk is best for babies. Soy-based formulas have a high phytoestrogen content, which may pose a risk for the long-term reproductive health of infants. Before you decide to use this product, consult your doctor or nurse for advice." [54]

Infant botulism

Botulism in infants 6 weeks to 1 year of age was first recognized as a distinct clinical entity in 1976. This form of botulism results from growth and toxin production by C. botulinum within the intestinal tract of infants rather than from ingestion of a food with preformed toxin. It is usually caused by C. botulinum types A or B, but a few cases have been caused by other types.botulism has been diagnosed in most U.S. states and in every populated continent except Africa.

Honey, a known source of C. botulinum spores, has been implicated in some cases of infant botulism. In studies of honey, up to 13% of the test samples contained low numbers of C. botulinum spores.Heat treatment is not sufficient to destroy C. botulinum spores, but the high sugar content of the honey prevents the spores from germinating. Normal adults are not at risk of botulism from eating honey; however, the gastrointestinal tracts of young infants (under one year of age) may promote spore germination.

For this reason, the FDA, the Centers for Disease Control and Prevention (CDC), and the American Academy of Pediatrics recommend not feeding honey to infants under one year old.

German BFR concerned about 3-MCPD in refined oil and derived products

According to the Federal Institute for Risk Assessment (BfR) the substance 3-monochloropropane-1,2-diol (3-MCPD) may be formed when fat-containing foods that also contain salt are exposed to high temperatures during production. It has been detected in numerous heated foods, for instance in dark brown toast, infant formula and follow-up formula. During the production of fats and oils, 3-MCPD fatty acid esters may be formed from 3-monochloropropane-1,2-diol when the fats and oils are heated to high temperatures.

The BfR recommends that concerted action be taken to lower the levels of 3-MCPD esters in infant formula and follow-up formula, contain varying amounts of dried powder and water. The Institute recommends that mothers who are unable to breastfeed their infants and give them infant formula should continue to do so. Infants who are not breastfed there is no alternative to formula and follow-up formula. Mothers should not switch to cow, goat or horse milk either as they do not contain some of the essential nutrients that infants need.

Detected levels of 3-MCPD fatty acid esters
The BfR found that the amounts of 3-MCPD fatty acid esters detected in edible oils and fats were in the four to five digit microgram range. The highest level of 11,206 micrograms per kilogram (microg/kg) was found in deep-frying fat. In the infant formula and follow-up formula examined the highest level identified was 4,196 microg/kg in the fat content. For this food it amounts to around 25 percent of the dried powder.

The BfR stresses that it is unknown whether 3-MCPD fatty acid esters have the same toxic properties as free 3-MCPD. No data are available but it cannot be ruled out that free 3-MCPD is formed from most of the fatty acid esters during digestion.

According to the BfR men who consume 100 g of vegetable margarine with the highest detected level of 3-MCPD fatty acid esters daily would exceed the TDI five-fold, assuming that 3-MCPD fatty acid esters are fully converted into free 3-MCPD. Following tis assumption, intakes of formula and follow-up formula, infants would exceed the TDI three to twenty-fold.

Risk for infants and consumers
According to the BFR there are many uncertanties of a risk assessment. However, assuming that toxicological effects of 3-MCPD on animals can be translated to humans or that there is large scale conversion of 3-MCPD fatty acid esters into 3-monochloropropane-1,2-diol, then the expected long-term exceeding of the TDI is not acceptable in the opinion of BfR particularly as children and adults ingest 3-MCPD from other sources, too. Any short-term exceeding of the TDI value would, by contrast, not present a safety concern.


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See also: Related OurFood News
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