The Journal of Nutrition

The Use of Whey or Skimmed Milk Powder in Fortified Blended Foods for Vulnerable Groups: A Literature Review

The Use of Whey or Skimmed Milk Powder inFortified Blended Foods for Vulnerable Groups1,2

Camilla Hoppe, Gregers S. Andersen, Stine Jacobsen, Christian Mølgaard, Henrik Friis,Per T. Sangild, and Kim F. Michaelsen*

Department of Human Nutrition, Faculty of Life Sciences, University of Copenhagen, DK-1958 Frederiksberg, Denmark

Abstract

Fortified blended foods (FBF), especially corn soy blend, are used as food aid for millions of people worldwide, especially

malnourished individuals and vulnerable groups. There are only a few studies evaluating the effect of FBF on health

outcomes, and the potential negative effect of antinutrients has not been examined. Different lines of evidence suggest

that dairy proteins have beneficial effects on vulnerable groups. Here we review the evidence on the effects of adding

whey or skimmed milk powder to FBF used for malnourished infants and young children or people living with HIV or AIDS.

Adding whey or skimmed milk powder to FBF improves the protein quality, allowing a reduction in total amount of protein,

which could have potential metabolic advantages. It also allows for a reduced content of soy and cereal and thereby a

reduction of potential antinutrients. It is possible that adding milk could improve weight gain, linear growth, and recovery

from malnutrition, but this needs to be confirmed. Bioactive factors in whey might have beneficial effects on the immune

system and muscle synthesis, but evidence from vulnerable groups is lacking. Milk proteins will improve flavor, which is

important for acceptability in vulnerable groups. The most important disadvantage is a considerable increase in price.

Adding 10–15% milk powder would double the price, which means that such a product should be used only in well-defined

vulnerable groups with special needs. The potential beneficial effects of adding milk protein and lack of evidence in

vulnerable groups call for randomized intervention studies. J. Nutr. 138: 145S–161S, 2008.

Introduction

This article is one component of a Food Aid Quality Enhance-ment Project to enhance product quality and improve nutrient

delivery to recipients of U.S. food aid commodities. The projectis coordinated by SUSTAIN, a U.S. nongovernmental organiza-tion that uses science and technology to improve nutrition indeveloping countries. The article will assess the value of addingwhey protein (WPRO)3 to fortified-blended foods (FBF) to im-prove their nutritional value. The potential impact of using otherdairy products, especially skimmed milk powder (SMP), willalso be evaluated, as it has been used in many other food aidproducts and is widely available.

FBF is used on a very large scale to feed populations in lowincome countries, especially malnourished individuals and vul-nerable groups. The most common FBF are corn soy blend (CSB)and wheat soy blend (WSB). They are made from wheat or cornas the main staple, soy flour to improve the protein quality, avegetable oil source, and a mix with mineral-vitamins to fortifythe blend. Most of the FBF is donated by the United States anddelivered by the World Food Program (WFP).

The recipes are developed to provide a balanced intake ofessential nutrients for growth and development of youngchildren and for malnourished individuals. They were originallydeveloped by the U.S. Agency for International Development inthe 1960s. They are designed to be energy and nutrient dense,and, as they are precooked, they are easily prepared into anenergy-dense porridge that is easy for children to eat. However,very few studies have evaluated the effect of FBF in malnour-ished and vulnerable groups. Raw soy contains considerable

1 Published in a supplement to The Journal of Nutrition. The review was sup-

ported in part by funding from Sustain as part of a Food Aid Quality Enhancement

Project and an unrestricted grant from the United States Dairy Export Council.

Guest Editor disclosure: Writing of the review was in part supported by funding

from SUSTAIN and an unrestricted grant from the US Dairy Export Council,

which is also stated in the acknowledgments. K. F. Michaelsen has received

research grants from the Danish Dairy Research Foundation to perform research

on the effect of milk whey on growth.2 Author disclosures: K. F. Michaelsen, C. Hoppe, and C. Mølgaard have received

research grants from the Danish Dairy Research Foundation to perform research

on the effect of milk whey on growth. P. T. Sangild has received research funding

from Arla Foods amba. G. S. Andersen, S. Jacobsen, and H. Friis, no conflicts of

interest.3 Abbreviations used: AA, amino acid; BCM, body cell mass; b-LG, b-lactoglobulin;

BMD, bone mineral density; CSB, corn soy blend; CSM, corn soy milk; DSM, dried

skim milk, same as NDM and SMP; F-100, therapeutic milk; FBF, fortified blended

food; GMP, glycomacropeptide; GSH, glutathione; IGF, insulin-like growth factor;

IOM, Institute of Medicine; MT, metric ton; NDM, nonfat dry milk, same as DSM

and SMP; PDCAAS, protein digestibility corrected amino acid score; PE%, protein

energy percentage; PLWHA, people living with HIV and AIDS; RUTF, ready-to-use

therapeutic food; SMP, skimmed milk powder, same as DSM and NDM; WFP,

World Food Programme; WP, whey powder; WPC, whey protein concentrate;

WPI, whey protein isolate; WPRO, whey protein; WSB, wheat soy blend; WSM,

wheat soy milk.

* To whom correspondence should be addressed. E-mail: kfm@life.ku.dk.

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amounts of antinutrients (such as antitrypsin) that potentiallyinterfere with protein digestibility and mineral absorption. Theprocessing of FBF is designed to reduce antinutritional factors,but the actual decrease in antinutritional factors has not beendocumented clearly. The efficacy of cereal- and legume-basedsupplementary feeding in large-scale programs has not beenconclusively demonstrated (1–3).

WFP held a technical review on its FBF in Rome in July 2005,which also dealt with the potential use of milk or milk productsin FBF. The objective was to review the appropriateness of theproduct specifications vis-a-vis nutritional requirements of spe-cific target groups, including protein content and qualities,keeping the overall cost of the products in mind. One point ofdiscussion was a number of recent studies highlighting the roleof foods of animal origin in ensuring child growth and devel-opment. The level of antinutritional factors in the blends wasalso discussed. One conclusion was the need to develop special‘‘convalescent’’ foods for moderately undernourished children.Also, it was concluded that the benefits of including SMP in FBFand in new foods for malnourished children should be reviewed.In terms of formulation, it was recommended that FBF form25% of the total ration/diet, and it was suggested that a conva-lescent food should supply a minimum of 50% of energy intakeduring an initial phase of 1–6 wk.

The main aim of this review is to evaluate whether or notthere is research to support substituting some of the vegetable orlegume protein in the blends with dairy protein. Two centralareas are covered. One is to evaluate data on the potential effectsof improved protein quality on health outcomes, and the otheris to assess evidence on potential positive health effects of bio-logically active compounds in milk, especially whey.

The review focuses on 2 important vulnerable groups,namely people living with HIV and AIDS (PLWHA) andmalnourished infants and young children. Both groups haveincreased nutritional needs because of infections and differentdegrees of malabsorption, have a low muscle mass and therebyincreased nutritional needs for catch-up growth, and also oftenhave poor appetites.

A spectrum of nutritional conditions pertain to the popula-tions receiving food aid, including nonmalnourished individualsin need of food, vulnerable groups and individuals with mod-erate malnutrition, and those with severe malnutrition. FBFwithout any animal foods will be sufficient to support thosewithout malnutrition. SUSTAIN is currently assessing theirsuitability as complementary foods for nonmalnourished andmoderately malnourished infants, and preliminary findingssuggest that dilution of the cooked FBF may negatively impactenergy and nutrient density and infants’ ability to consumeadequate quantities based on their average stomach capacity.During the last decade, a special diet (therapeutic foods, F-100,produced by several manufacturers) in which the only proteinsource is milk has proven to be very effective in hospital-basedtreatment of severely malnourished children and has reducedmortality considerably (4). Recently, a new kind of therapeuticfood, ready-to-use therapeutic food (RUTF), has been used inhome-based treatment programs of both severely and moder-ately malnourished children (5–7). Most of the RUTF contains aconsiderable amount of milk powder. If FBF fortified with dairyprotein is introduced as a special food or a ‘‘convalescent’’ foodto selected vulnerable groups, it may fill a gap between plant-based FBF and RUTF wherein about half of the protein or moreis dairy protein. Consequently, this review also briefly summa-rizes the composition and main results obtained using thera-peutic foods including RUTF.

FBF

FBF consist of a mixture of cereals, pulses, fats, vitamins, andminerals intended to provide a balanced intake of essentialnutrients for vulnerable groups. These comprise the original FBF,namely corn soy blend (CSB) and wheat soy blend (WSB).However, other types of FBF exist based on sorghum and soy,bulgur, wheat and soy, or combinations of cereals with heat-treated soy in its full fat form or as defatted flour. There are alsoFBF that contain milk, corn soy milk (CSM) and wheat soy milk(WSM), described in more detail below, but they are not widelyused, mainly because of the higher cost. WFP has also supportedthe manufacture of locally designed and produced FBF, includ-ing Unimix in Kenya, Famix in Ethiopia, Likin Phali in Malawi,and Indiamix in India.

WFP distributed almost 300,000 metric tons (MT) FBF in2006: .207,000 MT was bought in Italy, Belgium, and develop-ing countries, and 88,000 MT was received as in-kind donations,mainly from the United States (WFP, personal communication).Assuming that FBF provided ;25% of the energy intake [500 kcal(2.1 MJ)] of those receiving it, the amount would be sufficient tosupply ;6.5 million people for a whole year.

The nutritional quality of FBF is improved through theaddition of soy, and the product is fortified with essential micro-nutrients. Because they are precooked and distributed as flour,they require only limited amounts of fuel for cooking and aresimple to prepare and microbiologically safe. Furthermore, theycan be produced relatively inexpensively. However, WFP is atpresent reconsidering the formulation to upgrade the nutritionalvalue.

The ingredients (cereals and legumes) are heat treated beforemilling to improve digestibility and to reduce levels of anti-nutrients and cooking times. The FBF is fortified with a vitaminand mineral mix.

Types of FBF. CSB and WSB are by far the most widely usedFBF. They contain cornmeal or wheat flour, soybeans, and amineral-vitamin mix. CSB consists of ;80% maize and 20%soy, and WSB consists of ;75% wheat and 25% soy. WFP hasgiven specifications for the energy, protein, and fat content of theblends (Table 1). However, according to the U.S. specifications(8), the energy content is somewhat lower [CSB 376 kcal/100 g(1.57 MJ/100 g) and WSB 355 kcal/100 g (1.49 MJ/100 g)], andthe protein content also differs (CSB 16.0 g/100 g and WSB 21.5g/100 g). In recipes for CSB and WSB, the content of soy flour(defatted) is 22 and 20%, respectively (9).

TABLE 1 Nutritional value of commonly used food-aidcommodities according to WFP1

Energy Fat Fat Protein Protein

kcal/100 g MJ/100 g E% g/100 g E%

FBF

CSB 380 1.60 14.2 18.0 18.9

WSB 370 1.55 14.6 20.0 21.2

CSM 380 1.60 14.2 20.0 21.1

Ingredients

Wheat (cereal) 330 1.39 4.1 12.3 14.9

Corn (meal) 360 1.51 8.8 9.0 10.0

Soy (flour, full fat) 380 2.00 41.6 37.2 31.0

Dairy products

SMP 360 1.51 2.5 36.0 40.0

Dried whole milk 500 2.10 48.6 25.0 20.0

1 Adapted from (150).

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FBF with milk as SMP are available but have not been usedvery much, mainly because of the price. Recipes for both CSMand WSM have been developed. Both of these have 15% (wt:wt)SMP. In both recipes, the amount of soy has been reduced by ;4–5% to compensate for the higher protein content. We have notbeen able to find any studies evaluating the effects on growth orrecovery from malnutrition with these milk blends or studies thathave compared effects of CSM or WSM with FBF with no milk.

Therapeutic foods

Therapeutic foods are mainly intended for the treatment ofsevere malnutrition in children and are outside the scope of thisarticle. They will, however, be described briefly, as the proteinsource in these products is either 100% milk protein (therapeuticmilk or F-100) or mainly based on milk protein (RUTF). F-100consists of 42% milk powder (SMP), equivalent to 11% ofenergy from proteins. Thus, all protein is milk protein. RUTFnutritional composition is quite close to that of the F-100therapeutic milk, but the major difference is that F-100 is given asa milk with an energy density of ;1 kcal/g (4.2 kJ/1 g), whereasRUTF is fat-based pastes with a very low water content and anenergy density that is ;5 times as high [5 kcal/g (21 kJ/g)]. Somemanufacturers add whey powder (WP) to RUTF together withSMP. The rationale for adding WP is not the potential biologicaleffects of whey but rather that WP is less expensive than SMP,has a better protein quality, and might have some technologicaladvantages. Therapeutic milk/F-100 and RUTF have been verysuccessful in supporting growth and reducing mortality inseverely malnourished children, and it is plausible that part ofthis effect could be related to the high milk content, as discussedlater.

Milk and powdered dairy products

Milk is an excellent source of a number of nutrients, and itsproteins are easily obtained and used in various contexts, whichpositions them among the best-characterized proteins chemically,physically, and genetically. Mature bovine milk contains ;3.5%protein (10,11). The main protein fractions of bovine milk arecasein and whey, which account for ;80% and 20%, respectively.The major casein products are as1-, as2-, g-, and k-casein. Themajor WPRO include b-lactoglobulin (b-Lg), a-lactalbumin,immunoglobulins (Ig), serum albumin, and lactoferrin, all ofwhich possess specific biological activity (11,12). There are alsoseveral minor proteins with specific biological activities.

Whole milk powder. The main difference between whole milkpowder and the other powdered products is the fat content. Animportant reason that whole milk powder is not used much infood aid is the short shelf life because the fat gets rancid easily.The alternative to milk fat, vegetable oil, has a longer shelf lifeand is less expensive.

SMP. SMP, which is also called nonfat dry milk (NDM) or driedskim milk (DSM), is characterized by having a low fat (0.8 g/100g) content. SMP has a high nutritional value and is a source ofhigh-quality animal protein (36 g/100 g). SMP has a carbohy-drate content of 52 g/100 g, which is predominantly lactose.When stored in cool conditions with low humidity, it has anaverage shelf life of 3 y.

Whey. Whey is a collective term referring to the serum or liquidpart of milk that remains dissolved in the aqueous portion afterthe coagulation of casein into curd during the manufacture ofcheese, where most of the fat and casein have been used in the

cheese-making process. The remnant whey is high in bothlactose and minerals (13). Currently there are 2 major basictypes of whey available, sweet and acid (sour) (14). Acid whey isobtained during the production of acid-coagulated cheeses suchas cottage and cream cheese, and sweet whey originates from themanufacture of rennet-coagulated and hard cheese. The biolog-ically active casein glycomacropeptide is present only in sweetwhey (14). The concentration of calcium in acid whey is ;2-foldhigher than that in sweet whey.

Whey powder, concentrates, and isolates. WP, which isdried whey, has a typical protein content of 11–14.5% and alactose content of 63–75%. WPRO is, however, processed intowhey protein concentrate (WPC) with different concentrations,usually ranging from 34–80%, and as whey protein isolate(WPI) containing at least 90% protein.

Protein quality

One of the main arguments for adding whey or SMP to FBF is toimprove the protein quality. Improved protein quality allows fora reduction of the total amount of protein needed, which isbeneficial both for economic reasons, as the amount of soy mightbe reduced, and for metabolic reasons, as metabolizing surplusnitrogen is not efficient.

Protein quality indexes. High protein quality is defined asprotein that supports maximal growth. The various proteinquality indexes include 1 or more factors related to the AA pro-file, digestibility, and the presence of inhibiting or biologicallyactive components in the food ingested.

Until recently, protein efficiency ratio was the most widelyused index for evaluating protein quality. It is defined as bodyweight gain divided by the amount of test protein consumed by ayoung growing rat. Consequently, different growth patternsbetween rats and humans are a concern when protein efficiencyratio is used (15).

Protein digestibility-corrected amino acid score (PDCAAS) isa more recent evaluation method of protein quality and has beenadopted by FAO and WHO (16) as the preferred method ofevaluating protein quality in human nutrition.

PDCAAS represents the AA available after protein digestion,that is, the content of the first limiting essential AA in a testprotein divided by the content of the same AA in a referencepattern of essential AA (17). The index further includes truedigestibility defined as the true digestibility of the test protein,measured in a rat assay, thereby taking into consideration fac-tors influencing the digestion of the protein (15). The maximumPDCAAS value is 1.0, meaning that 100% or more of therequirement of essential AA is achieved. A score above 1.0 isrounded down to 1.0. However, several limitations must beconsidered when PDCAAS is used: the validity of using theprotein requirement of children in a reference AA pattern andthe validity of using true digestibility and the truncation ofvalues above 100%, which limits the information providedabout the potency of a specific protein source to counteract andbalance inferior proteins in mixed diets (17).

Protein quality of FBF and ingredients. Plant protein sourcesprovide 65% of the world’s supply of edible protein, with themain contributors being cereal, especially wheat, rice, and corn.Soy is also used as a source of protein in blends designed for foodaid programs, such as WSB and CSB, because of its favorablecontent and constitution of AA. Although plant products are agood source of protein and certain plant products contain much

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higher levels of some AA than animal sources, no plant sourceprovides optimal levels of all 9 essential AA. When the AAprofiles of the major plant staple food sources are comparedwith human muscle tissues, it appears that the limiting AA ofcorn is tryptophan, and in soy the sulfur-containing AA methi-onine and cysteine. Further, all plant sources with the exceptionof soy have a uniformly lower lysine content. In low-incomecountries, problems with satisfying AA needs are mainly relatedto monotonous diets. However, for mixed diets based on, forexample, both cereals and legumes, requirements are often fullyachieved because the products complement each other and com-pensate for the insufficient protein quality (18).

The PDCAAS of corn, wheat, and soy are 0.35, 0.37, and0.93, respectively (Table 2). However, in the blended foods, theAA patterns of the ingredients complement each other, resultingin relatively better PDCAAS values, e.g., the PDCAAS of CSBand WSB are 0.65 and 0.64, respectively. If milk is added, as inCSM and WSM, the PDCAAS increases to 0.81 and 0.76,respectively. Digestibility of protein in traditional diets fromlow-income countries is considerably lower than that of a typicalWestern diet. This is a result of the presence of less refined cerealand grain legumes, which contain less digestible proteinfractions and high levels of insoluble fiber.

The influence of adding whey or SMP to FBF on protein

quality. To evaluate the potential effects of adding powderedmilk to protein quality, we calculated the quality (PDCAAS) andamount of protein of theoretical blends of FBF where the cerealor soy has been replaced by different amounts of either whey orSMP (Table 3).

PDCAAS is partly based on the content of the first limitingAA, as previously discussed. In accordance with the generalknowledge that limited lysine can pose a problem in vegetable-based food sources, the first limiting AA of blends in Table 3 isgenerally lysine because of the low lysine content in either cornor wheat. There is, however, an exception in 2 blends (seefootnote 5 of Table 3), where the first limiting AA is tryptophan,which is a consequence of the content of fairly concentratedwhey, which balances out the lack of lysine.

In general, CSB has a slightly higher PDCAAS than WSB.Also, blends with reduced soy content have a lower PDCAASthan blends in which soy is not reduced. It is not surprising thatproducts adding the same amount of WPC80% as WPC34%have considerably higher PDCAAS, as it contains more thandouble the amount of protein. The lower PDCAAS of blendscontaining SMP in comparison with whey-containing blends isexplained by a lower content of lysine in SMP.

The addition of the milk powders results in considerableincreases in protein energy percentages as expected, from thelevel of 17.2–21% in CSB and WSB in blends with no milk up tolevels ;20–25% when 5–20% milk powder is added. Further-

more, when milk is a considerable part of the protein, thedigestibility and, thereby, the bioavailability of the protein willbe higher as reflected in the higher PDCAAS.

In general, blends containing 10% WPC80% possess slightlyhigher PDCAAS than blends containing 20% WPC34% as 10%WPC80% contain slightly more protein than 20% WPC34%.

Soy flour has approximately the same protein content asSMP and WPC34%. Thus, exchanging soy for 1 of the 2 milkpowders will result in approximately the same protein energypercentage (PE%), but the protein quality will increase from thehigher PDCAAS of milk products.

It is beyond the scope of this article to develop detailedrecipes. This can be done by linear programming where proteinenergy percentage, protein quality (PDCAAS), fraction ofprotein that should be milk protein, lactose content, and fatenergy percentage should be taken into consideration.

Antinutritional factors. Antinutritional factors are mainlypresent in pulses, grain, and legumes and can impair intake,uptake, or utilization of other food and feed components (19).These factors can be difficult to measure, and the Codex Com-mission has not yet set standards for these factors. Importantantinutrients include lectin, hemagglutinins, saponins, antitryp-sin, antichymotrypsin, thiaminase, and phytate.

Raw soy is the most concentrated source of trypsin inhibitors.Trypsin inhibitors are not restricted to their effect on trypsin butmay also inhibit other proteases that contain serine in the activesite. Tannins are present in various plants, including cereal grainsand legume seeds and possess the ability to precipitate proteinsin aqueous solutions, making them less available for digestionand absorption. Phytates are found primarily in seeds, nuts, andgrains and interfere with zinc and iron absorption as well as thebioavailability of other essential mineral nutrients. Furthermore,phytates are able to bind proteins in the gastrointestinal tract andnegatively influence the activity of digestive enzymes.

Although it has often been mentioned that soy contains highlevels of antinutrients, we have not been able to identify studieswith FBF that have clearly demonstrated a negative effect of suchantinutrients. Studies on infant formula based on soy proteinshow that there are no major differences in growth comparedwith cow’s milk-based formula (20). However, soy-based infantformulas contain soy protein isolates that have a low contentof phytate (1–2%), which is considerably lower than that inFBF using crude toasted soy. In a recent comment from theESPGHAN Committee on Nutrition, it was recommended thatsoy formulas be used for specific reasons only, as they may havenutritional disadvantages and contain high levels of phytate andphytoestrogens with unknown long-term effects (20). Addition-ally, in piglets, WPRO stimulate small intestinal and bodygrowth relative to a corresponding isocaloric and isoproteinousdiet with soy hydrolysate (21).

TABLE 2 Products and their protein quality indexes

Amino acidsWPI . 90%

(151)WPC80%

(152)WPC34%

(151)SMP(151)

F-100(153)

CSM(153,154)

WSM(153,154)

CSB(153,154)

WSB(153,154)

Soy-flour(raw) (153)

Cornmeal(153,154)

Wheatflour (153)

g/100 g protein

Total essential 47.79 46.33 48.43 44.22 44.21 39.71 36.91 37.87 34.17 37.52 38.35 30.05

Total BCAA 22.82 21.69 22.51 21.46 21.48 19.38 17.51 18.47 15.98 17.00 20.97 15.12

Total sulfur-containing AA 5.07 5.41 4.23 3.27 3.26 3.20 3.35 3.21 3.35 2.82 3.92 4.04

Protein, g/100 g product 100 79.89 35.00 33.50 15.97 19.97 20.62 17.43 20.02 36.54 9.44 10.65

Protein indices (PDCAAS) (17) 1.14–1.67 1.14–1.61 1.14–1.49 1.24 1.24 0.81 0.76 0.65 0.64 0.93 0.35 0.25–0.37

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Cost of milk, types of whey, FBF, and FBF components

The price of commodities used for FBF and relief feeding is anessential factor in deciding the composition of blends and rations.Table 4 presents typical prices of milk products, FBF, cereals, andlegumes as of March 2007. In recent years there have been con-siderable fluctuations of the world market prices on dairy prod-ucts, and during the first half of 2007, there have been markedincreases. Whey has traditionally been an inexpensive surplusproduct from cheese production and has been used to feed pigs.SMP and WPC (34 and 80%) are the products that may be rel-evant to add to FBF, as they are the cheapest per unit protein. Upto 2006, WPC34% has been ;25 to 33% cheaper than SMP.Other whey types are more expensive per kilogram protein, andunprocessed WP with 13% protein is more expensive than SMPand WPC34%, when compared as price per kilogram protein.

Based on a simple calculation of the amounts, not takingextra costs of mixing and other technical aspects into account,adding for example 10% SMP or WPC34% to CSB will increasethe price of the product by about two-thirds to US$0.58/kg andUS$0.60/kg.

Vulnerable groups

In many low-income countries, large proportions of the popu-lation are nutritionally vulnerable, and food aid is often aimedmainly at vulnerable groups. Traditionally, infants and youngchildren, pregnant and lactating women, and the elderly areregarded as nutritionally vulnerable. Other groups are patients

with recurrent acute or chronic infections such as those with TBand HIV/AIDS. During the last few decades, the number ofPLWHA has increased dramatically, and it has been realized thatthis group has considerable nutritional problems.

PLWHA. According to United Nations Programme on HIV/AIDS (22), as many as 4.1 million people became newly infectedwith HIV during 2005, bringing the total number of peopleliving with HIV to 38.6 million. With .23 million AIDS deathsso far, and many more weakened by HIV infection, the epidemichas consequences that are already brutally felt in most familiesand communities in the hardest-hit countries and has a devas-tating impact on social and economic development.

Based on considerable animal and human data, conceptualframeworks describing possible 2-way relations between nutri-tion and specific infectious diseases have been developed. In brief,most infectious diseases may impair nutritional status, and im-paired nutritional status or decreased intake may affect the riskand severity of infectious diseases (23).

The conceptual framework also applies to various nutrientsand HIV infection. However, because it has become clear thatoxidative stress—an effect of the infection in the absence ofadequate intake of antioxidants—directly leads to increasedreplication of HIV in the cells, HIV-specific conceptual frame-works have been developed, and the current data on the relationbetween nutrition and HIV have been reviewed (24).

HIV infection may affect the nutritional status of individualsin various ways. It may have a direct biological effect onnutritional status, and it may have indirect effects that aremediated through reduced food production or cash income, and,hence, reduced access to food. The biological effects result fromHIV disease causing an acute-phase response or local lesions,which may reduce intake and absorption and increase utilizationand loss of nutrients. There is evidence to suggest that even earlyasymptomatic HIV infection affects absorption of nutrients andalso increases resting energy expenditure.

Based on a WHO consultation, it is recommended thatasymptomatic HIV-infected individuals increase their energyintake by 10% and that those with symptomatic disease increasetheir intake by 20–30%. However, regarding proteins, the WHOconsultation concluded (25):

TABLE 4 Typical prices of SMP, WP, and FBF. March 20071

Commodity US$/kg product US$/kg protein

SMP 2.35 6.73

WPI . 90% 7.26 8.07

WPC80% 6.27 7.84

WPC34% 2.64 7.76

WP (13%) 1.10 9.17

CSB2 0.38 (0.36–0.40) 2.18

WSB2 0.47 (0.40–0.54) 2.35

1 Sources: USDA, National Agricultural Statistics Service and WFP.2 Values are means (ranges).

TABLE 3 PDCAAS of different blends with and without milk powder1

Blends with reduced cereal content1 Blends with reduced soy content2 Blends with no soy content3

CSB2 WSB CSB WSB Corn Wheat

PDCAAS (PE%)

Basic blend4 0.65 (17.2) 0.64 (21.0) 0.65 (17.2) 0.64 (21.0) 0.35 (9.5) 0.37 (13.9)

1 5% WPC34% 0.73 (18.5) 0.71 (22.0) 0.69 (16.5) 0.67 (20.3) 0.50 (10.8) 0.49 (14.9)

110% WPC34% 0.80 (19.7) 0.77 (23.1) 0.73 (15.8) 0.71 (19.7) 0.62 (12.1) 0.60 (15.9)

120% WPC34% 0.92 (22.2) 0.89 (25.2) 0.82 (14.5) 0.78 (18.4) 0.82 (14.5) 0.78 (18.1)

1 5% WPC80% 0.82 (20.8) 0.80 (24.4) 0.80 (18.9) 0.77 (22.6) 0.67 (13.1) 0.64 (17.3)

110% WPC80% 0.925 (24.4) 0.92 (27.3) 0.885 (20.5) 0.88 (24.4) 0.81 (16.8) 0.83 (20.6)

1 5% SMP 0.71 (18.4) 0.69 (22.0) 0.67 (16.6) 0.65 (20.3) 0.46 (10.8) 0.46 (14.9)

110% SMP 0.76 (19.6) 0.74 (23.1) 0.68 (15.8) 0.66 (19.6) 0.56 (12.0) 0.54 (15.9)

120% SMP 0.85 (22.1) 0.82 (25.1) 0.72 (14.4) 0.69 (18.3) 0.72 (14.4) 0.68 (18.0)

1 The amount of dairy powder (WPC or SMP) added to the blend replaced by the same amount of cereal (corn in CSB and wheat in WSB),

whereas the amount of soy is unchanged.2 The amount of dairy powder (WPC or SMP) added to the blend replaced by the same amount of soy, whereas the amount of cereal (corn

in CSB and wheat in WSB) is unchanged.3 The blends consist only of cereal (corn or wheat) and dairy powder (WPC or SMP) in different ratios.4 Basic blends: CSB; 80% corn, 20% soy. WSB; 79% wheat, 21% soy.5 The limiting amino acid is tryptophan. In the other blends lysine is the limiting amino acid.

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There are insufficient data at present to support anincrease in protein intake for PLWHA above normalrequirements for health, i.e., 12% to 15% of total energyintake. Participants were aware of the published nutri-tional guidance suggesting increased protein intake duringHIV infection, but they concluded that these recommenda-tions were not based on rigorously conducted studies (25).

Similarly, there are no recommendations regarding quality ofthe protein.

It is likely that even early HIV infection leads to changes inthe structure and function of the intestinal tract, which isaccompanied by malabsorption of nutrients. An HIV enterop-athy has been described, characterized by villous atrophy andcrypt hyperplasia (26). With more advanced disease andfrequent episodes of diarrhea, malabsorption becomes increas-ingly common and contributes to wasting.

Infants and young children. Infants and young children areespecially vulnerable to malnutrition because of their high growthvelocities and consequent high energy and nutrient needs.

According to UNICEF, 31% of children under 5y suffer frommoderate or severe stunting, with 42% in the least-developedcountries (27). About 10% of the children in low-incomecountries have moderate or severe wasting, and .10 millionchildren die each year in low-income countries before they reachthe age of 5 y, equivalent to 7 of every 100 children (27). It hasbeen estimated that in more than half of the deaths, malnutritionis a contributing factor to mortality.

The ages up to ;18 mo are specifically vulnerable. There is adramatic decline in nutritional status from birth up to ;18 mo inweight for age (underweight), length for age (stunting), andweight for length (wasting) (Fig. 1). Thereafter, there is nofurther decline, indicating that the children grow at a velocity atthe same level as the reference population.

A very common complication to malnutrition in youngchildren is recurrent or persistent diarrhea. Long periods ofgastrointestinal infections will affect the mucosa of the intestine,resulting in an atrophic mucosa and thereby malabsorption ofnutrients, in a further deterioration of the nutritional status.Young children are also more sensitive to the effects of anti-nutrients, e.g., phytate, in that absorption of several minerals,such as iron and zinc, is impaired.

Recommended protein intake for vulnerable groups. Thereare 2 main methods of expressing recommendations for proteinintake: as safe level of protein intake expressed as grams perkilogram body weight per day or as a safe range of PE% in thediet. The safe levels of protein intake according to the new WHO/FAO report on protein requirement (16) are given in Table 5.

Safe ranges for protein energy percentage are given by theU.S. Institute of Medicine (IOM) (28). The ranges [acceptablemacronutrient distribution ranges (AMDR)] are 5–20 PE% forchildren of 1–3 y, 10–30 PE% for children of 4–18 y, and 10–35PE% for adults. The recommendations are developed forhealthy individuals living in industrialized countries. There isconsiderable uncertainty in the lower values of these safe ranges.A PE% based on the recommended protein intake, which shouldbe regarded as a minimum PE% in the diet, may be calculatedfrom the recommended protein intake and the mean energyrequirements per kilogram body weight (29). The value is 5.3PE% at 6 mo, gradually falls to 4.3 PE% at 2 y, and thenincreases gradually again to 8.7 PE% at 17 y.

A basic assumption for recommendations on protein intakeis that the energy requirement is met. Otherwise, some ofthe protein will be oxidized to provide energy. In a situation inwhich the total diet remains unknown, as when planning specialfoods for vulnerable groups, it makes more sense to giverecommendations on protein content of diets as PE%. This is inaccord with the approach suggested by Waterlow in 1992 (30).Waterlow also calculated the PE% needed for catch-up growthassuming different rates of catch-up. A young child would need adiet with 8 PE% for a catch-up of 5 g � kg21 � d21 and 10.4 PE%for a catch-up of 10 g � kg21 � d21. In the new WHO/FAO reporton protein requirements (16), the corresponding values aresomewhat lower; 6.9 PE% for a catch-up of 5 g � kg21 � d21 and8.9 PE% for a catch-up of 10 g � kg21 � d21. For comparison,F-100, which is intended for treatment of severely malnourishedchildren, has a PE% of 11 with a PDCAAS of 1.24. In severalstudies (31), it has been shown that it is possible to obtain meanweight gain ;10–15 g � kg21 � d21 in severely malnourishedchildren using F-100.

An important consideration regarding protein requirementsto vulnerable groups is the fact that infections are common.According to the new WHO/FAO report on protein requirements

FIGURE 1 The nutritional status of children under 5 y in the world,

expressed as SD scores (Z-scores) relative to the WHO growth ref-

erence that was used up to 2006 (155). Reproduced with permission

from Pediatrics, American Academy of Pediatrics (155).

TABLE 5 Safe level of protein intake for weaned infants,children, and adolescents per kilogrambody weight1

All Girls Boys

Age Safe levels2 Age Safe levels2 Age Safe levels2

y g/(kg d) y g/(kg d) y g/(kg d)

0.5 1.31 11 0.90 11 0.91

1 1.14 12 0.89 12 0.90

1.5 1.03 13 0.88 13 0.90

2 0.97 14 0.87 14 0.89

3 0.90 15 0.85 15 0.88

4 0.86 16 0.84 16 0.87

5 0.85 17 0.83 17 0.86

6 0.89 18 0.82 18 0.85

7 0.91

8 0.92

9 0.92

10 0.91

1 Adapted from (16).2 The safe level of protein intake is calculated as the mean requirement 1 1.96 SD.

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(16), estimates for the extra allowances needed in individualswith infectious diseases are between 10% for mixed intestinalparasites, .25% for untreated tuberculosis, and 50% inindividuals with symptom-free HIV. There are no differentia-tions in these figures according to age group.

The focus of this article is on vulnerable groups with no ormoderate malnutrition. Thus, there is only a moderate need forcatch-up. A PE% of 8 in a blend of vulnerable groups would besufficient if the PDCAAS were 1.0 and the whole diet werecovered by the blend. However, because the whole diet is notsupposed to be covered, a PE% of 10–12 would compensatesomewhat for a lower protein content and quality in theremaining diet. Aiming for a PE% of 12 would also allow for aPDCAAS below 1.0, e.g., at 0.80. In the following calculations,we will thus aim for a blend with a PE% ;12 and a PDCAAS notmuch below 0.8.

Potential effects of milk on vulnerable groups

Animal-source foods in malnutrition. Whey is an animalprotein, and potential effects of interventions with whey couldbe caused by the general characteristics of an animal foodsource, e.g., the AA pattern or the minerals. Therefore, it isrelevant to discuss the general aspects of feeding animal foods tomalnourished individuals.

A number of studies have examined the association betweenintake of animal-source foods and growth and development(physical and mental), morbidity (including nutritional anemia),and immune function (3,32–36). In an observational study fromKenya, Mexico, and Egypt, positive associations between intakeof animal-source foods and growth in weight and length werefound, even after controlling for socioeconomic factors (37).Similar findings have been obtained in Peru (38), in New Guinea(39), and in Central America (40). Iron, zinc, and vitamin B-12contents of animal-source foods in addition to good proteinquality may contribute to these findings.

In a study in Kenya, the effect of meat and milk on growthwas examined in schoolchildren who were randomized to ameat, milk, or energy supplement compared with a controlgroup without a supplement (41). Children in each of the sup-plemented groups gained ;0.4 kg (10%) as compared withchildren in the control group, but only those receiving the animalfoods gained more lean body mass. In the subgroup of childrenwith a lower baseline height-for-age z-score (#1.4), a positiveeffect of milk supplements on height gain was shown, suggestingthat the effect of milk on linear growth may be superior to thatof other animal-source foods.

Potential effects of milk protein constituents. The biologicalactivities of several bioactive proteins and peptides obtainedfrom milk proteins and their physiological roles have been ex-amined in animal studies and in a limited number of interventionstudies in humans. Proposed functions of WPRO are mainly relatedto the immune or digestive system (42). It has been speculatedthat some of the effects of whey or other milk proteins could becaused by peptides formed after digestion in the gastrointestinaltract (43–47). There is an extensive interest in the potential use ofbioactive milk components, such as b-lactglobulin, a-lactalbumin,lactoferrin, and glycomacropeptide, in infant formula, clinicalnutrition, and functional foods. Using specific bioactive milkcomponents in FBF or other foods used in relief feeding is atpresent not realistic because of the cost issue.

Lactose maldigestion and intolerance. The lactose contentof both SMP and low whey concentrates (WPC34%) is ;50%

as opposed to the more concentrated isolates (WPI90%), whereit is ;1%. In WPC80% it is ;10%. Because the WPI are muchmore expensive than WPC and therefore not relevant for low-cost food aid products, it is appropriate to consider to whatdegree lactose maldigestion and intolerance are relevant prob-lems for feeding malnourished patients with high-lactose-content milk components.

Lactose maldigestion and intolerance develop after earlychildhood, at about age 3–5 y in many populations. It is esti-mated that lactose maldigestion is present in 75% of the world’spopulation (48). Lactose intolerance is characterized by symp-toms that are primarily gastrointestinal and include flatulence,cramping, abdominal pain, nausea, distention, bloating, anddiarrhea.

Solomons et al. (49) assessed the effect of using lactose-containing and lactose-hydrolyzed formulas based on cow’s milkin the rehabilitation of severely malnourished children. Morediarrheas were experienced by the group receiving the lactose-containing formula, but the overall recovery was satisfactory inboth cohorts, and there were no differences in rates of growth,body protein repletion, restoration of energy reserves, or in-testinal functions. In a meta-analysis of studies treating childrenwith diarrhea with either lactose-containing or lactose-free diets,it was concluded that most children with acute diarrhea cansafely be treated with undiluted lactose-containing milks. It wasfurther stated that children should be fed continuously duringillness with their usual diets (50).

Miller et al. (51) observed that lactose malabsorption was acommon finding in HIV-infected children and was less commonin an age-matched group of control children. However, lactosemalabsorption was not associated with higher rates of diarrheaor growth failure.

F-100 is used extensively in the treatment of severe malnu-trition, a condition in which diarrhea is frequent and likely tocause considerable intestinal atrophy and therefore low lactase.Although it has not been strictly documented, there is a generalimpression that lactose intolerance is not a major problem inrehabilitation of severely malnourished children (52). F-100contains 42% SMP, and with a lactose content of ;50% in SMP,;20% of the dry matter and 15% of the energy content in thisdiet comes from lactose. Thus, it seems that a reduction of thelactose content in milk-based diets for severe malnutrition offersno appreciable advantages, and the use of milk as the proteinsource for rehabilitation is not contraindicated (31,49,53). Thisis supported by the conclusion of a recent meta-analysis (54). Itshould be kept in mind that ;40% of the energy in human milkcomes from lactose, about twice as much as in cow’s milk, andthat human milk is considered an ideal food, even during periodsof diarrhea.

Some studies in piglets have shown a positive effect ongrowth of adding lactose to a cereal-based diet, most likelybecause lactose is a carbohydrate with high bioavailability (55).

In conclusion, the lactose content of FBF is not likely to be aproblem. There is ;50% lactose in WPC34% or SMP, but theamount of milk in FBF will be small, perhaps 10–20%, and theFBF will constitute only a part of the energy intake, perhaps 25–50%. Furthermore, such blends will not be intended for severelymalnourished individuals, who have low levels of lactase.

Bone. Adding SMP or whey to the diet of vulnerable groupsliving mainly on a vegetarian diet may have positive effects onbone mineralization.

It has been shown that very low calcium intake in some areas,especially in Africa, can be the main reason for bone diseases

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such as rickets despite high sun exposure and normal vitamin Dstatus (56–61). Furthermore, supplementing with calcium caneliminate symptoms such as leg pain and radiological signs ofrickets (57). It may, therefore, be especially important to ensurea sufficient calcium intake during periods with nutritionalrehabilitation. Protein supplements for rehabilitation should,therefore, normally also contain calcium. However, the FBF isenriched with calcium as part of the mineral mix.

It was earlier believed that high animal protein intake had anegative influence on calcium balance because individuals withhigh nondairy animal protein intake usually have higher urinecalcium excretion (62). However, newer studies have shown thatanimal protein also seems to have a stimulating influence oncalcium absorption, so the overall effect on calcium balancenormally will be neutral (63). Furthermore, in the elderly, withthe appropriate intakes of vitamin D and calcium, giving proteinsupplements to correct an inadequate protein intake increasescirculating insulin-like growth factor (IGF)-1 levels, improvesclinical outcomes after hip fracture, and prevents bone mineraldensity (BMD) loss at the proximal femur (64).

Some studies, mostly with animals, have examined the effectof WPRO on bone metabolism. In cells it has been shown thatWPRO may stimulate osteoblasts (bone-forming cells) (65) andinhibit osteoclasts (bone-resorbing cells) (66). It has also beenshown that WPRO may enhance bone strength in both growing(67) and ovariectomized rats (66,68). In ovariectomized ratstudies, the control diet protein was casein compared with caseinplus some extra WPRO (66,68). Recently, rat studies haveshown an antiresorptive effect (69) and bone density-maintain-ing effect (70) of the acidic protein fractions isolated frombovine milk whey. Only a few human studies examining theeffect of whey on bones have been published. In a study fromJapan, whey (a special type called the basic protein fraction,MBP) has been shown to increase BMD in adult (71) andmenopausal women (72). No studies on the effect of WPRO onBMD in adult men, children, or adolescents have been pub-lished.

From the literature it is not possible to state whether milkprotein or whey, compared with other protein sources, will havea positive effect on the bones in malnourished individuals. A lowcalcium intake from a diet with no animal foods could have anegative influence on bones. However, the blends discussed inthis review are fortified with a sufficient level of calcium.

Milk and linear growth. In a recent article (73) summarizinghuman observational and intervention studies, it was concludedthat cow’s milk seems to have a positive effect on linear growth.

The strongest evidence that cow’s milk stimulates lineargrowth comes from observational studies in both infants (74,75)and preschool children (32,76–78) and from intervention studies(79–86) in low income countries that show considerable effects.Additionally, observational studies from well-nourished popu-lations show an association between milk intake and growth(87). These results suggest that milk has a growth-stimulatingeffect even in situations where the nutrient intake is adequate.This effect is supported by studies showing that milk intakestimulates circulating levels of the growth factors insulin (88)and IGF-1 (89,90), which suggests that at least part of thegrowth-stimulating effects of milk occur through the stimulationof the IGF. Because the biological purpose of milk is to supportthe newborn during a period of high growth velocity, such aneffect seems plausible, and the ‘‘milk hypothesis,’’ put forwardby Bogin (91), proposes that a greater consumption of milkduring infancy and childhood will result in taller adult stature.

Adding cow’s milk to the diet of stunted children is, therefore,likely to improve linear growth.

Whey stimulates levels of insulin in circulation in bothpostprandial (92) and fasting (93) states. However, becausecasein seems to increase circulating IGF-1 (93), it could bespeculated that the entire milk protein with both whey andcasein is needed to obtain the complete positive effect of milk onlinear growth.

Muscle mass. PLWHA and malnourished infants and youngchildren have decreased whole-body protein synthesis and netmobilization of proteins into free AA. WPRO are easily digestedand have high metabolic efficiency, giving the protein a highbiological value compared with other milk proteins. WPROmight influence body cell mass (BCM) in several ways. WPROcontain the highest concentration of BCAA available from anyfood protein source. BCAA must be present in the muscle cells topromote protein synthesis (14). Circulating BCAA are uniqueamong AA because they are metabolized for energy by musclerather than by the liver, thus helping to increase carbohydrateavailability and counteract muscle protein breakdown. There-fore, BCAA might be exceptional among AA in their ability toprovide an energy source during wasting and thus decreasemuscle breakdown and aid recovery. However, this theory has,to our knowledge, not been clinically studied.

In addition, during starvation and malnutrition, the levels ofinsulin are greatly reduced, thus in part mediating the loss of bodyprotein because insulin is known to inhibit proteolysis (94). In ahealthy individual, there is a rise in circulating insulin to initiatethe response to feeding, which is thought to be a major factor incontrolling the retention of absorbed AA (95). Increases in AAconcentrations, particularly of the BCAA, induce similar effectsto those of insulin. In a healthy subject these 2 factors appear toact synergistically. However, because insulin levels are decreasedduring starvation and malnutrition, intake of BCAA might bemore important for inhibition of body protein breakdown (94).Also, as antiretroviral therapy and especially the group of AIDSretroviral drugs, which are protease inhibitors, cause lipodystro-phy and metabolic syndrome (96–98), an increased intake ofBCAA may be especially beneficial for PLWHA.

However, because glucagon levels also are decreased inmalnourished individuals, the insulin-to-glucagon ratios may bemore important than the absolute concentration of either insulinor glucagon (94,99). Although the percentage of AA thatstimulate the secretion of insulin is the same in casein andWPRO, the higher proportion of BCAA in whey results in asynergistic effect with insulin on protein metabolism (94).Moreover, the number of AA that stimulate glucagon secretion issubstantially lower in WPRO than in casein. Hence, thecatabolic effect of glucagon, which counterbalances insulin inthe acute control of protein, is less after a whey-protein meal.

WPRO are also rich in arginine and lysine. Arginine and lysineare among the AA thought to possibly stimulate growth hormone,which is an anabolic hormone. AA composition of WPRO is verysimilar to that of skeletal muscle (100), providing almost all of theAA in approximate proportion to their ratios in muscle. Logically,it can be supposed that this compatibility would position whey asan effective anabolic supplement, although it should be recog-nized that the nonessential AA contribute little to the overallresponse (101).

Immune system and glutathione. Whey contains a relativelyhigh proportion of sulfur-containing AA, especially cysteine.This might be of particular value in conditions of immune

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activation in that the high cysteine content of whey may sparetissue protein because acute phase proteins, which are producedin response to immune challenge, are inordinately enriched incysteine.

Infection with HIV results in a progressive impairment ofimmune function, especially a decline in the amount of themembrane glycoproteins CD4, ultimately leading to opportu-nistic infections and malignancies of AIDS (102). Impairedantioxidant defense may play a role in the immunopathogenesisof HIV infection (103–105). Also, in severe malnutrition, as inkwashiorkor, an impairment of the antioxidant defense isobserved (106–110). Reactive oxygen species and a consequentdepletion of antoxidants have been suggested as the etiology ofkwashiorkor (111,112). Interestingly, it has been reported thatblood levels of glutathione (GSH) are low, as in the case of HIV-positive patients. Based on the antioxidant hypothesis, a recentstudy from Malawi tested the effect of antioxidant supplemen-tation in children with kwashiorkor in Malawi but did not findan effect (110).

GSH is a cysteine-containing tripeptide (g-glutamyl-cysteinyl-glycine) that is regarded as the major intracellular redox buffer-ing principle (105,113). Finally, GSH provides reducing powerfor the maintenance of other antioxidants, e.g., ascorbic acid(vitamin C), vitamin E, and b-carotene (113). HIV patients areoften depleted of GSH and other antioxidants (114), and GSHlevels are reduced in children with kwashiorkor (106).

WPRO is rich in the AA cysteine, which is the main source ofthe sulfhydryl group of GSH. Therefore, an increased intake ofwhey may be beneficial in GSH-depleted indivduals, such asPLWHA and children suffering from kwashiorkor.

Oxidant/antioxidant imbalance can occur in obstructiveairway disease as a result of ongoing inflammation. GSH playsa major role in pulmonary antioxidant protection. Awhey-basedoral supplement increased whole-blood GSH levels and pulmo-nary function in 1 patient who had obstructive lung disease andlow whole-blood GSH levels (115). The potential for suchsupplementation in pulmonary inflammatory conditions de-serves further study.

Gastrointestinal development and recovery. Malnutritionand HIV infection have detrimental effects on the health of thegastrointestinal tract. In a review by Playford et al. (116), it ismentioned that the growth and development of intestinal cellsare positively influenced by components of milk and whey,including growth factors and peptides. Glycomacropeptideexhibits prebiotic activity (117), and lactose can be enzymati-cally hydrolyzed to form monosaccharides, which are readilyutilized by bifido bacteria, thus contributing to better function-ing of the digestive tract (42). Glutamine (13% in casein and4.6% in whey) might be an important fuel source for the smallintestine, although results of its therapeutic effects indicatelimited efficacy (118,119). Thus, although there is a plausiblemechanism whereby an individual with gastrointestinal dys-function may benefit from whey, this theory has not yet beentested (101).

Evidence from animal studies

Numerous animal studies are available on the effects of bovinemilk products on early life growth patterns. Well-controlledanimal studies clearly offer a potential to improve our under-standing of the mechanisms whereby milk components affect thebody during health and disease.

As an omnivorous species with a gastrointestinal tract similarto that in humans, the pig is believed to be 1 of the best animal

models for human nutrition and for studies on milk diets in earlylife (120). At 3–5 wk of age, pigs are generally subjected toabrupt (premature) weaning from mother’s milk onto a vegetable-based diet, often resulting in significant anorexia, gastrointes-tinal disease (weanling diarrhea), and increased mortality. It islikely that results from weanling pigs reflect the responses inmalnourished and growth-stunted infants in the transition phasefrom milk to solid food.

It is widely recognized that young weanling pigs achievebetter growth performance with milk-based diets than withisocaloric diets containing similar amounts of nutrients derivedfrom corn-soy diets (55,121–123). The potential explanation forthis positive effect includes a better overall PDCAAS value formilk protein (124), faster stomach emptying (120), lowerantinutrient levels, and higher levels of milk bioactive substancesleading to better gut health (55,125). Part of the beneficial effectof milk products is also believed to arise specifically from thehigh digestibility and beneficial luminal effects of milk lactose,which are present not only in the very nutrient-sensitive periodjust after weaning (55) but also in older and healthier piglets,especially those showing slowest growth postweaning (126).

The milk casein fraction has been shown to affect intestinalstructure and function in weanling pigs (127), and this couldbe via its content of immunomodulatory glycomacropeptides(128). Generally however, casein does not seem to explain thehigh digestibility and growth performance in weanling pigsreared on milk diets (129,130). More likely, it is the wheyfraction that contains bioactive factors to exert improved guthealth, digestibility, and growth beyond the effects explainedsolely by the contents of highly digestible lactose and protein.Hence, spray-dried whey products have become widely used toenhance health and growth performance for weanling pigs. Evenbetter performance and gut health are achieved when colostralprotein rather than whey-derived protein is included in weanlingdiets (131). This probably reflects even higher concentrations ofbioactive factors in colostral whey than in milk whey.

The responses seen in weanling pigs may resemble thosein malnourished weanling infants but could also be valid duringthe entire period from birth. In immunocompromised, stuntednewborn pigs, WPRO stimulated small intestinal and bodygrowth, relative to a corresponding isocaloric and isoproteinousdiet with soy hydrolysate (21). The effects of casein on gut andbody growth were intermediate, but it is noteworthy that caseinincreased bone mineral deposition, whereas WPRO exertedeffects mainly on soft tissue growth (organs, muscle, fat). Theresults confirm not only that milk proteins are clearly superior tovegetable proteins (soy hydrolysate) in supporting growth in sicknewborns but also that whey and casein proteins exert differ-ential effects on the different parts of the body.

Because the weanling pig is a very appropriate model forvulnerable infants and young children during the weaningperiod, and because these studies have been strictly controlled,these results from animal studies are relevant and support thehypothesis that there will be positive effects of adding whey orSMP. However, the growth velocity of piglets is very high, andresults seen in piglets may overestimate the effects in humans,underlining the need for strictly controlled relevant studies inhumans.

Intervention studies with whey in

vulnerable populations

PLWHA. The use of WPRO in vulnerable populations, such asthose affected by HIV infection, has been suggested as a meansto improve health. If inadequate intake of protein increases the

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progression of HIV infection, increasing the intake or quality ofprotein, from whey or other sources, may have beneficial effectson HIV infection. However, the question addressed here iswhether WPRO has specific effects on the course of HIVinfection per se, i.e., effects that are not merely explained by theprovision of high-quality proteins. Providing whey to peoplewith inadequate intake of protein may be beneficial whether ornot they have HIV infection. However, it may be useful todistinguish between 1) whether effects of whey are over andabove the effects of other high-quality proteins, and 2) whethereffects are general or HIV-specific, i.e., affecting the course ofHIV infection. However, it is complex to distinguish whethereffects are general or HIV-specific. As for the latter, an effect onlean body mass is likely to be general, if not explained by HIV-specific effects on CD4 count and viral load.

WPRO is rich in the AA cysteine, which is the main source ofthe sulfhydryl group of the GSH. HIV patients are often depletedof GSH and other antioxidants (114). When put on antiretro-viral treatment, HIV infected patients will experience a pro-nounced decline in viral load and an increase in CD4 counts,which will be accompanied by an improvement in GSH-redoxstatus and increase in levels of antioxidant vitamins (132).However, if they are not on HIV treatment, the resulting oxida-tive stress may increase viral replication and hence progressionof HIV to AIDS or death. Therefore, it has been suggested thatWPRO might increase GSH-levels and thus reduce progressionof HIV.

Four studies have examined the effect of whey in PLWHA(Table 6). A pilot study was done on 3 HIV-infected individuals(133). The patients were clinically stable and given a WPC inamounts increasing from 8 to 39 g/d for 3 mo. The bloodmononuclear cell GSH content was below normal at baselinebut increased in all 3, whereas there were no effects on variousserum protein concentrations. However, weight gains werebetween 2 and 7 kg. According to the authors, this pilot studywill serve as a basis for a much larger clinical trial, whichapparently has not been conducted or published.

In a study among 30 clinically stable HIV-infected individualswith CD4 counts ,300 cells/mL, 45 g of WPRO was given dailyfor 14 d. Special commercial whey products were used calledProtectamin or Immunocal (134). The production processeswere distinct, with a lower isolation temperature (,72�C) forImmunocal. The protein content ranged from 75 to 95% with afat content of 0–6%. Plasma GSH increased significantly in the15 patients receiving Protectamin but not in the 15 patientsreceiving Immunocal. The authors claim that the study was adouble-blinded clinical trial and that short-term oral supple-mentation with WPRO increased plasma GSH levels. However,because there was no control group and only before-aftercomparison, the conclusion does not seem to be valid. All thepatients receiving Immunocal were, therefore, openly switchedto Protectamin for an additional 51/2 mo (135). After the full 6mo of supplementation, the mean plasma GSH was significantlyhigher than at baseline. Again, because the study was in fact nota randomized, controlled trial, the increase in plasma GSHcannot be attributed to the intervention with whey.

Another small study was done among 30 HIV-infectedwomen with BCM ,90% of normal values and the same datapublished in 2 articles (136,137). The body composition of thepatients was thoroughly assessed before and after a 6-wk controlperiod before the intervention, and then the patients wererandomized to WPRO, progressive resistance exercise, or bothfor 14 wk. The authors claim that both interventions had effectson various outcomes. However, there was no proper controlgroup, and, although data were not presented, there seemed tobe no differences between the intervention groups.

A so-called prospective, double-blind trial was conductedamong 18 vertically HIV-infected children on antiretroviraltherapy (138). The children were between 12 and 72 mo. Half ofthe children received a WPC, and the other half received aplacebo (maltodextrin, same amount of energy) or nothing. It isnot clear how allocation to treatment was done, but the studywas apparently not randomized. Also, it is not clear to whatextent the groups were comparable at baseline with respect to

TABLE 6 Whey intervention studies with PLWHA

Reference Study type n Subjects Study period Whey type (amount) Name Control Effect

Agin et al.,

2000, 2001

(136,137)

Randomized

intervention

study

30 Women

(28–66 y)

14 wk Undenatured bovine

derived whey

protein powder

(1.0 g � kg21 � d21)

Optimune 1) Exercise Weight gain as

fat (P ¼ 0.002).

2) Exercise and

whey combined

No significant change in

BCM, skeletal muscle,

strength or QOL.

Bounous et al.,

1993 (133)

Pilot study

(intervention)

3 White men 3 mo 75% WPC

(8.4 g/d increasing

to 39.2 g/d)

Immunocal None Weight gain.

No change in serum

proteins. Increased GSH.

Micke et al.,

2001, 2002

(134,135)

Prospective

double-blind

randomized

30 25 male, 5 female

(42 6 9.8 y)

2 wk 45 g whey/d Protectamin (P) GSH levels: Increased in

P-group (P ¼ 0.004),

no change in I-group.

No change in TNF-a,

IL-2, and IL-12.

Immunocal (I)

Moreno et al.,

2006 (138)

Prospective

double-blind

clinical trial

18 10 boys, 8 girls

(1.98–3.67 y)

4 mo 79% WPC (20% of

protein increasing

to 50% of protein)

1) Maltodextrin Increase in GSH in whey

group (P ¼ 0.018).

TCD4/CD8 increased

nonsignificantly

(P ¼ 0.116). Occurrence

of coinfections lowered

nonsignificantly

(P ¼ 0.058).

2) None

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relevant risk factors and how double-blinding was maintained.The supplements were given for 4 mo, and the effects onerythrocyte GSH, CD4 counts, and morbidity were assessed.An increase in erythrocyte GSH was observed in the whey-supplemented group but not in the control group. No tests weredone to compare the change over time in the 2 interventiongroups. There were no effects on CD4 count.

In conclusion, there is no convincing evidence that whey hasbeneficial effects on antioxidant status, immunological param-eters, or HIV-specific outcomes. Most studies had not onlyinadequate power but also flawed design. For example, mosttrials were based on before-after comparisons, and a beneficialchange is, therefore, possibly attributable to the effects of otherexposures, e.g., season. Furthermore, details of composition orprocessing of the supplements are not known. Some of the datasuggest that whey may increase GSH levels. If GSH depletionimpairs immune function or increases viral load, whey supple-ments might reduce progression of HIV, but this is speculative.However, if the GSH depletion is secondary to oxidative stress inthe background of low dietary intake of antioxidants, then itseems likely that antioxidant supplementation will be equallybeneficial and probably less expensive. There is a need forsoundly conducted intervention studies of the effect of WPROon HIV specific outcomes.

Infants and young children. A number of studies haveevaluated the effects of adding milk to the diet of vulnerablegroups of infants and young children. However, we have notbeen able to find published studies that have examined the effectof adding whey to the diet, and especially not studies that havecompared FBF with and without milk in infants and youngchildren.

It is beyond the scope of this article to go through theliterature of the effects of adding milk to the diet. In the previoussections ‘‘Animal-Source Foods in Malnutrition’’ and ‘‘Milk andLinear Growth,’’ we have summarized some of the literaturesuggesting that there might be specific positive effects of addingmilk to diets of infants and young children, especially if theirdiets are mainly vegetable based. Such effects are likely to bemuch more pronounced in infants and young children who arenot being breast-fed.

It is not possible to evaluate to what degree the effects seen instudies using milk or milk powder result from special effects ofthe whey fraction, as whey constitutes only ;20% of the proteinin milk powder, and milk is often covering only a limited part ofthe energy intake.

An increasing number of publications have reported thatRUTF is very effective in home-based treatment of infants andyoung children with severe malnutrition. Although this articledoes not focus on treatment of severe malnutrition, we find itrelevant to describe in brief some of the studies that focus onmore moderate malnutrition, which is common among vulner-able groups such as infants and young children and HIVpatients.

The content of milk is high in most RUTF. Typically .50%of the protein comes from milk. In some of the products part ofthe milk protein is WP (Plumpy Nut, Nutriset and BP-100, Com-pact A/S). The reasons for adding whey to these products arebasically lower price, better taste (high lactose content), andtechnological.

Studies in Malawi (5–7), Chad (139), Ethiopia (140), andSenegal (141) have shown that RUTF is readily consumed byseverely malnourished children and that they promote weightgain, both during regular nutritional rehabilitation and in ref-

ugee conditions. In summary, RUTF, which has a high content ofmilk, seems to improve weight gain, but whether this is causedby the higher energy density, the fact that RUTF is more con-venient, or because of the milk content, is not known.

In hospital-based clinical nutrition in industrialized coun-tries, there has been some interest in the differences in effectsof tube-feeding formulas based on whey or casein. Formulascontaining only whey or only casein and formulas with differentratios of casein and whey are available in the market. However,most formulas for enteral feeding of children in the Europeanmarket are made from casein or are casein predominant. Wehave not been able to find studies with relevant comparison ofthe effects of these formulas. From discussions with theproducers of formulas for enteral feeding, it is our impressionthat casein has been used traditionally because it was lactose-free. The reason for using whey in some formulas has mainlybeen the faster gastric emptying. As far as we are aware, it hasnot been because of other potential effects of WPRO.

In conclusion, there are no studies showing specific effectsof WPRO in infants and young children in either well-nourishedor malnourished populations. A number of studies show thepositive effects of milk and animal foods on growth and de-velopment, especially in populations in low-income countrieswith a diet mainly based on plant-source foods, and there are nostudies that have compared weight gain in infants and youngchildren receiving FBF with and without the addition of milk.However, the 5 times higher energy density and the convenienceof a RUTF could explain the differences.

Considerations for formulations of FBF with milk

A crucial factor in the discussion of improving FBF is the cost ofthe product. Adding milk-based powders will increase the cost ofthe products considerably. Adding 15% WPC34% will doublethe price of a CSB, based on prices in early 2007 (Table 4).Adding 15% SMP, which has approximately the same amount ofprotein as WPC34%, will result in a slightly cheaper product.Whey is traditionally a surplus product from cheese production.However, with the increasing interest in using whey in manydifferent technical applications in the food sector, and also withan increasing interest in using whey as a food supplement in the‘‘health food’’ sector, its cost has gone up. WPC34% wasconsiderably cheaper than SMP, ;25–33% cheaper up to early2007. Other milk powder products, such as whey concentrateswith more protein or whey isolates, are considerably moreexpensive per kilogram protein than WPC34% and SMP.

The increased price of a FBF with milk protein should be seenin relation to the target groups and the potential beneficialeffects. The improved blends are aimed at vulnerable groups thatare likely to be moderately malnourished and are at risk ofdeveloping severe malnutrition. We find it likely that blendscontaining SMP or WPC powder will be more effective inimproving the nutritional status of the vulnerable children andthereby also protect against development of severe malnutrition,which is associated with considerable morbidity and mortalityand is also expensive to treat. However, we acknowledge thatthere is a need for randomized studies to show whether FBFcontaining milk protein has beneficial effects compared withFBF without milk.

Amount and type of milk protein. Replacing the 20% (wt:wt)soy in a CSB (almost all the soy) by 20% (wt:wt) WPC34%increases the PDCAAS from 0.65 to 0.82 (Table 3). If SMP isused instead, the PDCAAS would increase less, to 0.72.

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Adding SMP or WPC allows for a reduced content of soy orcereal in the blend, which will increase the protein availability.With a higher PDCAAS it is also possible to reduce the amountof protein. First, protein is expensive, and it is thus not feasibleto use protein as an energy supply. Second, it might be a strain onthe compromised metabolic systems in malnourished individualsor PLWHA if surplus protein had to be metabolized to energy.The nutritional quality of the FBF will, therefore, be improved ifSMP or WPC is added, both by an increase in the quality and adecrease in the quantity of protein.

As discussed in an earlier section, a PE% of 8 in a blend tovulnerable groups would be sufficient, if the PDCAAS were 1.0and the whole diet were covered by the blend. A PE% of 8 wouldalso allow for the extra need for moderate catch-up growth ininfants and young children. However, it might be marginal forindividuals with infectious diseases (16). Because the whole dietis not supposed to be covered by a fortified blend, a PE% of 10–12 would compensate somewhat for a lower protein content andquality in the remaining diet. Aiming for a PE% of 12 would alsoallow for a PDCAAS somewhat below 1.0, e.g., 0.80.

The fraction of protein that should come from milk is difficultto determine. The higher the fraction, the more likely it is thatthere will be a positive effect on weight gain and linear growth,but the price will also increase considerably. If the milk protein iswhey, any potential bioactive effect of whey is also likely to behigher if the whey content is higher. However, our literaturereview has not been able to find documentation for such effects.The higher the milk protein fraction from milk, the lower anypotential effects of antinutrient effects from soy and the cerealswill be. Again, such effects are not well documented. A sug-gestion is that one-third to half of the protein should come frommilk to make an impact. In trials to test if there is a beneficialeffect of adding milk to FBF, it is recommended to start the trialswith blends with half of the protein from milk tested againstblends with no milk.

A blend with a PE% of 12, a PDCAAS of 0.80, and with one-third to half of the protein from milk seems to be a reasonablecompromise to aim for. A blend with 15% WPC34%, 85%corn, and no soy would result in 40% of the protein comingfrom milk protein, a PDCAAS value of 0.73 and a PE% of 13.3.For comparison CSB has a PDCAAS value of 0.65 and a PE% of17.2, and WSB has a PDCAAS value of 0.64 and PE% of 21.0,according to U.S. specifications (8).

Flavor and satiating effect. Both flavor and the satiating effectof a blend are likely to influence energy intake, which is crucialin feeding vulnerable groups. Adding milk powder to the blendsinfluences flavor. Adding only 2–5% of SMP to a blend gives it amilky and also creamy flavor, even though there is no fat in SMP.The flavor of whey is more neutral, but with no negative effectson the flavor of the blends. Both SMP and WPC34% have;50% (wt:wt) lactose, and the use of these products adds asweet taste. Flavor is important for acceptability of the productfor the vulnerable groups, and especially in malnourished youngchildren, the intake is likely to increase if the flavor is sweet. Ifthe addition of milk powder results in a considerable increase inprotein intake, a high protein intake could also directly result ina blunting of the appetite (16).

Adding a milk protein powder to a blend is likely to affectsatiety. WPRO are categorized as fast proteins and caseins asslow proteins, according to the pace at which AA emerge in thecirculation after ingestion (142). Whey appears to provide amore satiating effect than casein does (143) after a meal, butthere are no data available on the effect on energy intake over a

longer time. Whey is absorbed rapidly from the intestine, andthis might potentially lead to better overall nitrogen balance andpostprandial protein utilization (144).

Energy density, fat content, and quality. Because individualsin vulnerable population groups may need a high energy intakefor recovery, it is fundamental that the products have a highenergy density. This has been considered in the formulation ofFBF, which aims at having an energy density of 1 kcal/g (4.2 kJ/g),which is usually regarded as being sufficient, but in reality theenergy density is often lower. FBF may be provided with oil, butthe dosage is critical because a too-high oil content will decreasethe nutrient density. However, increasing the energy densityfurther by adding more oil in the blends should be considered. InCSB and WSB, the fat energy percentage is ;14, which is lowcompared with recommendations for feeding infants and youngchildren. Reviews focused on low-income countries havesuggested that there is a risk of a negative effect on growth ifthe fat energy percentage of the whole diet is below 22 to 25(145,146). It is likely that a main reason for the very positiveeffects of RUTF is the very high energy density of the product,5 times as high as a CSB-based porridge.

Another important aspect to consider when formulating animproved blend is the fat quality, especially the amount ofpolyunsaturated fatty acids and the (n-3):(n-6) fatty acid ratio,as it might have effects on growth, cognitive development,immune function, and oxidative stress. Soybean oil has afavorable fatty acid profile, so if soy is eliminated from blendswhere soybeans that are not defatted are used, it should beconsidered to add soybean oil or other oils with a high (n-3) fattyacid content, such as canola oil.

Lactose. Lactose maldigestion and intolerance are common inmany populations (48). However, it seems that milk consump-tion allows adequate growth of children, even when they aremalnourished and have diarrhea (147). The content of lactose inboth SMP and WPC34% is ;50 g/100 g. Thus, assuming anenergy content of 400 kcal/100 g (1.68 MJ/100 g) dry FBF, thelactose content of such a blend will be 100 g/L if the blendcontains 20% SMP or WPC34%, which is equivalent to alactose content ;10% of both weight and energy content.Adding 15% SMP or WPC34% will likewise result in a lactosecontent in the blend of 7.5%. We find it unlikely that such a lowlactose content is a problem, even in individuals with lactasedeficiency. The lactose content will add sweetness to the taste,which is likely to be positive.

Studies in pigs have suggested that lactose could also have apositive effect on growth because of its high digestibility, en-hanced calcium absorption, and beneficial luminal effects (126).

Minerals and vitamins. FBF is fortified with a mineral-vitaminmix. Different mineral-vitamin mixes are used. If WPC34% orSMP is added to FBF, the content of calcium, phosphorus, andzinc especially will increase, especially if SMP is used because itcontains almost twice the amount as WPC34%. If phosphorus isnot added to the mineral mix, the extra phosphorus is importantbecause a considerable part of the phosphorus in the blends isbound by phytate and thus not available. There are severalstudies showing a close inverse relation between plasma phos-phate in the malnourished and death (148). If it is decided to addwhey or SMP to the FBF, the composition of the mineral mixesshould be evaluated to decide if there is a need for adjustments.With vegetable sources in FBF, most of the phosphorus can be inthe form of phytic acid, inositol hexaphosphate, which is the

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storage form of phosphorus for the plant. Thus, approximateanalysis of the FBF for total phosphorus is not sufficient. Becausedairy products contain bioavailable phosphorus, adding SMP orWPC to FBF will be favorable if it is not included in the mineral-vitamin mix.

The absorption of the minerals calcium, iron, and zinc iscompetitive. Therefore, it should be kept in mind that a highcalcium content might decrease the absorption of iron and zinc.This may affect the iron and zinc status in individuals whose soleor main diet for a period consists of FBF.

The mineral-vitamin mix used for blended foods includesB-12, which is of special interest in low-income countries wherethe intake of animal foods is often low or nil (149). The level offortification is ;1.2 mg/100 g (Table 1). Furthermore, milkpowder is a good source of B-12. If 15% SMP is added to a FBF,this will increase the B-12 content with ;0.6 mg/100 g.

Technical aspects. There are technical issues to consider whenformulating new blends with milk protein. Most of these are notconsidered in this article. Whey contains many different specificproteins that may have specific beneficial effects. When produc-ing the blends, processing should be performed in a manner tominimize protein denaturation. If FBF is made into porridge thatshould boil, e.g., for 10 min to overcome water contaminationissues, some denaturation might occur, thereby reducing poten-tial beneficial health effects of specific proteins.

There are both advantages and disadvantages of adding milkprotein (as either SMP or WPC) to FBF and advantages anddisadvantages of adding WPC in comparison to SMP (Table 7).

From our study, it is clear that the scientific evidence forbeneficial effects of adding milk protein to FBF is not verystrong. The strongest evidence comes from the studies of RUTF

with a high proportion of protein being milk protein, whichshow a high weight gain and successful recovery. However, mostof these studies focus on young children with severe malnutri-tion, and the RUTF typically contains a high milk protein con-tent and energy density, and they often cover a large proportionof the energy intake. Other important evidence comes fromstudies of young pigs.

Because the addition of milk protein to FBF increases theprice considerably, there is a need to document the beneficialeffects before implementing these blends in programs to vulner-able groups. It is beyond the scope of this article to suggestdetailed trial designs, but we will highlight some areas that needfurther studies.

Recommendations on research

There is a need to perform strict controlled intervention studiescomparing FBF with and without milk protein. These studiesshould be performed in vulnerable groups where it is likely thatadding milk protein would result in important health benefitsthat would justify a considerably more expensive product. Suchgroups could be moderately malnourished infants and youngchildren and PLWHA.

Animal studies should also be considered. Pigs are a usefulmodel for humans, especially regarding the gastrointestinalfunction. Piglets during the weaning period, when the gastro-intestinal tract is vulnerable and mortality is high, present anespecially relevant model for the weaning period in human popu-lations where malnutrition and persistent diarrhea are common.

Flavor, satiating effect, fat content, and energy density arelikely to affect energy intake, which is crucial in feeding ofvulnerable and malnourished groups. It will be possible toexamine this in short-term crossover studies in relevant vulner-able groups fed different blends with and without whey or SMPad libitum. The outcome in such studies would be the energyintake from the blends.

Acknowledgments

The following persons have helped us with important informa-tion and valuable discussions. We thank the staff at SUSTAIN,especially Lisa Fleige; Alicja Budek and Pernille Kæstel,Department of Human Nutrition, and Helene Hausner andAre Hugo Pripp, Department of Food Science, University ofCopenhagen, Denmark; Gitte Graverholt, Arla Foods, Arhus,Denmark; Jan Are Heldal, Compact, Bergen, Norway; AntonyMichalik and Hauke Kuhn, Fonterra (Europe), Hamburg,Germany; Lars Børje Sjøberg, previously Semper, Sweden;Mamane Zeilana, Nutriset, France; Ceri Green, JosephineGarvey, and Martin von Eert, Nutricia, The Netherlands;Stuart Allison and Richard Lowe, Insta Products, Nairobi,Kenya; Tina van den Briel, World Food Program; Andre Briend,World Health Organization; Pieter Dijkhuizen, previouslyWorld Food Program; Mark Manary, Washington UniversitySchool of Medicine, St. Louis, MO; Michael Golden, Professor,Consultant, Ireland; Peter Garlick, Professor, Department ofAnimal Sciences, University of Illinois.

Literature Cited

1. Beaton GH, Ghassemi H. Supplementary feeding programs for youngchildren in developing countries. Am J Clin Nutr. 1982;35:863–916.

TABLE 7 Effects of adding WPC or SMP to FBF

Adding WPC or SMP to FBF

Advantages Improves the protein quality, measured as PDCAAS.

With improved protein quality it is possible to reduce the total

amount of protein in the blend, which could have potential

metabolic advantages.

Allows for a reduced content of soy and cereal and thereby a

reduction of potential antinutritional effects.

Likely to improve weight gain, linear growth, and recovery from

malnutrition, but studies are needed to confirm this.

Improves flavor; SMP more so than WPC.

Disadvantages Increases the price considerably, which is an important limiting

factor in all relief feeding.

Adds lactose to the product, which could potentially have

negative effects, but which is not likely to be important in

the amounts suggested.

Using whey (WPC34%) compared with SMP

Advantages Has been 25–33% less expensive up to early 2007.

Has a slightly better protein quality measured as PDCAAS, but

not likely to be important.

Potential beneficial effects on the immune system and muscle

synthesis have been suggested, but convincing evidence is

lacking. Relevant to perform studies to examine this further.

We have not been able to identify studies suggesting that

casein-dominated milk powders such as SMP have

advantages over whey.

Disadvantages Might in the future be more expensive than SMP.

Might not be as widely available as SMP.

Does not improve flavor to the same degree as SMP.

Milk proteins in fortified blended foods 157S

at AR

LA F

OO

DS

on January 27, 2016jn.nutrition.org

Dow

nloaded from

2. Brown KH, Dewey KG, Allen L. Complementary feeding of youngchildren in developing countries: A review of current scientificknowledge. Geneva: World Health Organization; 1998.

3. Allen LH, Gilliard D. What works? A review of the efficacy andeffectiveness of nutrition interventions. Geneva, in collaboration withthe Asian Development Bank, Manila: ACC/SCN; 2001.

4. Ashworth A, Chopra M, McCoy D, Sanders D, Jackson D, KaraolisN, Sogaula N, Schofield C. WHO guidelines for management ofsevere malnutrition in rural South African hospitals: effect on casefatality and the influence of operational factors. Lancet. 2004;363:1110–5.

5. Patel MP, Sandige HL, Ndekha MJ, Briend A, Ashorn P, ManaryMJ. Supplemental feeding with ready-to-use therapeutic food inMalawian children at risk of malnutrition. J Health Popul Nutr.2005;23:351–7.

6. Sandige H, Ndekha MJ, Briend A, Ashorn P, Manary MJ. Home-based treatment of malnourished Malawian children with locallyproduced or imported ready-to-use food. J Pediatr GastroenterolNutr. 2004;39:141–6.

7. Maleta K, Kuittinen J, Duggan MB, Briend A, Manary M, Wales J,Kulmala T, Ashorn P. Supplementary feeding of underweight, stuntedMalawian children with a ready-to-use food. J Pediatr GastroenterolNutr. 2004;38:152–8.

8. SUSTAIN. U.S. specifications for FBFs. 2006.

9. World Food Programme. Food and Nutrition Handbook. Annex 3.2Rome, World Food Programme; 2000.

10. Fox PF, McSweeney PLH. Dairy chemistry and biochemistry.London: Thomson Science; 1998.

11. Severin S, Wenshui X. Milk biologically active components asnutraceuticals: review Crit Rev Food Sci Nutr. 2005;45:645–56.

12. Jensen RG. Handbook of milk composition. New York: AcademicPress; 1995.

13. FAO. Milk by-products, skim milk, buttermilk, whey. Rome: FAO;2006.

14. Walzem RL, Dillard CJ, German JB. Whey components: millennia ofevolution create functionalities for mammalian nutrition: what weknow and what we may be overlooking. Crit Rev Food Sci Nutr.2002;42:353–75.

15. Schaafsma G. The protein digestibility-corrected amino acid score(PDCAAS)—a concept for describing protein quality in foods andfood ingredients: a critical review. J AOAC Int. 2005;88:988–94.

16. FAO/WHO. Protein and amino acid requirements in humans. Reportof a joint FAO/WHO Expert Consultation. Technical Report Series,No 935. Geneva: WHO/FAO; 2008. In press.

17. Schaafsma G. The protein digestibility-corrected amino acid score.J Nutr. 2000;130:1865S–7S.

18. Millward DJ. The nutritional value of plant-based diets in relation tohuman amino acid and protein requirements. Proc Nutr Soc. 1999;58:249–60.

19. Sarwar G. The protein digestibility-corrected amino acid scoremethod overestimates quality of proteins containing antinutritionalfactors and of poorly digestible proteins supplemented with limitingamino acids in rats. J Nutr. 1997;127:758–64.

20. Agostoni C, Axelsson I, Goulet O, Koletzko B, Michaelsen KF,Puntis J, Rieu D, Rigo J, Shamir R, et al. Soy protein infant for-mulae and follow-on formulae: a commentary by the ESPGHANCommittee on Nutrition. J Pediatr Gastroenterol Nutr. 2006;42:352–61.

21. Bjørnvad CR, Thymann T, Budek AZ, Nielsen DH, Mølgaard C,Michaelsen KF, Sangild PT. Gastrointestinal and body growth incolostrum-deprived piglets in response to whey, casein or soy proteindiets. Livest Sci. 2007;109:30–3.

22. UNAIDS. 2006 Report on the global AIDS epidemic. UNAIDS, 2006.Available from: www.unaids.org/en/hiv_data/2006globalreport/.

23. Friis H. Micronutrients and infection: an introduction. In: Friis H,editor. Micronutrients and HIV infection. Boca Raton: CRC Press;2001. p. 1–21.

24. Friis H. Micronutrients and HIV infection: A review of currentevidence. Trop Med Int Health. 2006;11:1849–57.

25. WHO. Nutrient requirements for people living with HIV/AIDS:report of a technical consultation. Geneva: World Health Orga-nization; 2003.

26. Ullrich R, Zeitz M, Heise W, L’age M, Hoffken G, Riecken EO. Smallintestinal structure and function in patients infected with humanimmunodeficiency virus (HIV): evidence for HIV-induced enteropa-thy. Ann Intern Med. 1989;111:15–21.

27. UNICEF. The state of the World’s children. Oxford: OxfordUniversity Press; 2006.

28. Institute of Medicine. Dietary reference intakes for energy, carbohy-drate, fiber, fat, fatty acids, cholesterol, protein, and amino acids.Washington, DC: IOM; 2002.

29. Nordic Council of Ministers.Nordic nutrition recommendations2004. 4 ed. Copenhagen: Nordic Council; 2005.

30. Waterlow JC. Protein-energy malnutrition. Oxford University PressMontreal, Canada; 1992.

31. WHO. Management of severe malnutrition: a manual for physiciansand other senior health workers. Geneva: WHO; 1999.

32. Allen LH. Nutritional influences on linear growth: a general review.Eur J Clin Nutr. 1994;48:S75–89.

33. Siekmann JH, Allen LH, Bwibo NO, Demment MW, Murphy SP,Neumann CG. Kenyan school children have multiple micronutrientdeficiencies, but increased plasma vitamin B-12 is the only detectablemicronutrient response to meat or milk supplementation. J Nutr.2003;133:3972S–80S.

34. Murphy SP, Allen LH. Nutritional importance of animal sourcefoods. J Nutr. 2003;133:3932S–5S.

35. Bwibo NO, Neumann CG. The need for animal source foods byKenyan children. J Nutr. 2003;133:3936S–40S.

36. Grillenberger M, Neumann CG, Murphy SP, Bwibo NO, Weiss RE,Jiang L, Hautvast JG, West CE. Intake of micronutrients high inanimal-source foods is associated with better growth in rural Kenyanschool children. Br J Nutr. 2006;95:379–90.

37. Murphy SP, Beaton GH, Calloway DH. Estimated mineral intakes oftoddlers: predicted prevalence of inadequacy in village populations inEgypt, Kenya, and Mexico. Am J Clin Nutr. 1992;56:565–72.

38. Marquis GS, Habicht JP, Lanata CF, Black RE, Rasmussen KM. Breastmilk or animal-product foods improve linear growth of Peruviantoddlers consuming marginal diets. Am J Clin Nutr. 1997;66:1102–9.

39. Smith T, Earland J, Bhatia K, Heywood P, Singleton N. Linear growthof children in Papua-New-Guinea in relation to dietary, environmen-tal and genetic-factors. Ecol Food Nutr. 1993;31:1–25.

40. Black ER. Zinc for child health. Am J Clin Nutr. 1998;68:476S–479S.

41. Grillenberger M, Neumann CG, Murphy SP, Bwibo NO, van’t Veer P,Hautvast JG, West CE. Food supplements have a positive impact onweight gain and the addition of animal source foods increases leanbody mass of Kenyan schoolchildren. J Nutr. 2003;133:3957S–64S.

42. Shah NP. Effects of milk-derived bioactives: an overview. Br J Nutr.2000;84:S3–10.

43. Schlimme E, Meisel H. Bioactive peptides derived from milk-proteins—-structural, physiologicalandanalyticalaspects. Nahrung. 1995;39:1–20.

44. Meisel H. Bioactive peptides from milk proteins: a perspective forconsumers and producers. Aust J Dairy Technol. 2001;56:83–92.

45. Baldi A, Ioannis P, Chiara P, Eleonora F, Roubini C, Vittorio D.Biological effects of milk proteins and their peptides with emphasison those related to the gastrointestinal ecosystem. J Dairy Res.2005;72:66–72.

46. Meisel H. Multifunctional peptides encrypted in milk proteins.Biofactors. 2004;21:55–61.

47. Torres-Llanez Mde J, Vallejo-Cordoba B, Gonzalez-Cordova AF.Bioactive peptides derived from milk proteins. Arch Latinoam Nutr.2005;55:111–7.

48. Wardlaw GM, Hampl JS, DiSilverstro RA. Perspectives in nutrition.6 ed. New York: McGraw-Hill; 2004.

49. Solomons NW, Torun B, Caballero B, Flores-Huerta S, Orozco G.The effect of dietary lactose on the early recovery from protein-energy malnutrition. I. Clinical and anthropometric indices. Am JClin Nutr. 1984;40:591–600.

50. Brown KH. Dietary management of acute diarrheal disease: contem-porary scientific issues. J Nutr. 1994;124:1455S–60S.

51. Miller TL, Orav EJ, Martin SR, Cooper ER, McIntosh K, Winter HS.Malnutrition and carbohydrate malabsorption in children withvertically transmitted human immunodeficiency virus 1 infection.Gastroenterology. 1991;100:1296–302.

158S Supplement

at AR

LA F

OO

DS

on January 27, 2016jn.nutrition.org

Dow

nloaded from

52. WHO. Management of severe malnutrition: A manual for physiciansand other senior health workers. WHO, Geneva, 1999.

53. Torun B, Solomons NW, Caballero B, Flores-Huerta S, Orozco G,Pineda O. The effect of dietary lactose on the early recovery fromprotein-energy malnutrition. II. Indices of nutrient absorption. Am JClin Nutr. 1984;40:601–10.

54. Savaiano DA, Boushey CJ, McCabe GP. Lactose intolerance symp-toms assessed by meta-analysis: a grain of truth that leads toexaggeration. J Nutr. 2006;136:1107–13.

55. Mahan DC. Efficacy of dried whey and its lactalbumin and lactosecomponents at two dietary lysine levels on postweaning pig perfor-mance and nitrogen balance. J Anim Sci. 1992;70:2182–7.

56. Pettifor JM. Rickets. Calcif Tissue Int. 2002;70:398–9.

57. Oginni LM, Sharp CA, Badru OS, Risteli J, Davie MW, Worsfold M.Radiological and biochemical resolution of nutritional rickets withcalcium. Arch Dis Child. 2003;88:812–7.

58. Oginni LM, Worsfold M, Sharp CA, Oyelami OA, Powell DE, DavieMW. Plasma osteocalcin in healthy Nigerian children and in childrenwith calcium-deficiency rickets. Calcif Tissue Int. 1996;59:424–7.

59. Sharp CA, Oginni LM, Worsfold M, Oyelami OA, Risteli L, Risteli J,Davie MW. Elevated collagen turnover in Nigerian children withcalcium-deficiency rickets. Calcif Tissue Int. 1997;61:87–94.

60. Eyberg CJ, Pettifor JM, Moodley G. Dietary calcium intake in ruralblack South African children. The relationship between calcium intakeand calcium nutritional status. Hum Nutr Clin Nutr. 1986;40:69–74.

61. Thacher TD, Fischer PR, Pettifor JM, Lawson JO, Isichei CO,Reading JC, Chan GM. A comparison of calcium, vitamin D, or bothfor nutritional rickets in Nigerian children. N Engl J Med. 1999;341:563–8.

62. Hu JF, Zhao XH, Parpia B, Campbell TC. Dietary intakes andurinary excretion of calcium and acids: a cross-sectional study ofwomen in China. Am J Clin Nutr. 1993;58:398–406.

63. Pannemans DL, Schaafsma G, Westerterp KR. Calcium excretion,apparent calcium absorption and calcium balance in young andelderly subjects: influence of protein intake. Br J Nutr. 1997;77:721–9.

64. Rizzoli R, Ammann P, Chevalley T, Bonjour JP. Protein intake andbone disorders in the elderly. Joint Bone Spine. 2001;68:383–92.

65. Takada Y, Aoe S, Kumegawa M. Whey protein stimulated theproliferation and differentiation of osteoblastic MC3T3–E1 cells.Biochem Biophys Res Commun. 1996;223:445–9.

66. Takada Y, Kobayashi N, Kato K, Matsuyama H, Yahiro M, Aoe S.Effects of whey protein on calcium and bone metabolism in ovari-ectomized rats. J Nutr Sci Vitaminol (Tokyo). 1997;43:199–210.

67. Kelly O, Cusack S, Cashman KD. The effect of bovine whey proteinon ectopic bone formation in young growing rats. Br J Nutr. 2003;90:557–64.

68. Toba Y, Takada Y, Yamamura J, Tanaka M, Matsuoka Y, KawakamiH, Itabashi A, Aoe S, Kumegawa M. Milk basic protein: a novel pro-tective function of milk against osteoporosis. Bone. 2000;27:403–8.

69. Kruger MC, Plimmer GG, Schollum LM, Haggarty N, Ram S,Palmano K. The effect of whey acidic protein fractions on bone lossin the ovariectomised rat. Br J Nutr. 2005;94:244–52.

70. Kruger MC, Poulsen RC, Schollum L, Haggarty N, Ram S, PalmanoK. A comparison between acidic and basic protein fractions fromwhey or milk for reduction of bone loss in the ovariectomised rat. IntDairy J. 2006;16:1149–56.

71. Aoe S, Toba Y, Yamamura J, Kawakami H, Yahiro M, Kumegawa M,Itabashi A, Takada Y. Controlled trial of the effects of milk basicprotein (MBP) supplementation on bone metabolism in healthy adultwomen. Biosci Biotechnol Biochem. 2001;65:913–8.

72. Aoe S, Koyama T, Toba Y, Itabashi A, Takada Y. A controlled trial of theeffect of milk basic protein (MBP) supplementation on bone metabolismin healthy menopausal women. Osteoporos Int. 2005;16:2123–8.

73. Hoppe C, Molgaard C, Michaelsen KF. Cow’s milk and linear growthin industrialized and developing countries. Annu Rev Nutr. 2006;26:131–73.

74. Dewey KG, Peerson JM, Brown KH, Krebs NF, Michaelsen KF,Persson LA, Salmenpera L, Whitehead RG, Yeung DL. Growth ofbreast-fed infants deviates from current reference data: a pooledanalysis of US, Canadian, and European data sets. World HealthOrganization Working Group on Infant Growth. Pediatrics. 1995;96:495–503.

75. Michaelsen KF, Petersen S, Greisen G, Thomsen BL. Weight, length,head circumference, and growth velocity in a longitudinal study ofDanish infants. Dan Med Bull. 1994;41:577–85.

76. Martorell R, Klein RE. Food supplementation and growth-rates inpreschool-children. Nutr Rep Int. 1980;21:447–54.

77. Ruel MT. Milk intake is associated with better growth in LatinAmerica: Evidence from the Demographic and Health Surveys.FASEB J. 2003;17:A1199.

78. Allen LH, Backstrand JR, Stanek EJ, Pelto GH, Chavez A, Molina E,Castillo JB, Mata A. The interactive effects of dietary quality on thegrowth and attained size of young Mexican children. Am J Clin Nutr.1992;56:353–64.

79. Orr JB. Milk consumption and the growth of school-children. Lancet.1928;1:202–3.

80. Tanner JM, Whitehouse RH, Takaishi M. Standards from birth tomaturity for height weight height velocity and weight velocity—British children 1965. Arch Dis Child. 1966;41:613–35.

81. Tanner JM, Whitehouse RH, Takaishi M. Standards from birth tomaturity for height weight height velocity and weight velocity—British children 1965. Arch Dis Child. 1966;41:454–71.

82. Malcolm LA. Growth retardation in a New-Guinea boarding schooland its response to supplementary feeding. Br J Nutr. 1970;24:297–305.

83. Morgan AF, Hatfield GD, Tanner MA. A comparison of the effect ofsupplementary feeding of fruits and milk on the growth of children.Am J Dis Child. 1926;32:839–49.

84. Dreizen S, Currie C, Gilley EJ, Spies TD. The effect of milksupplements on the growth of children with nutritive failure. 2.Height and weight changes. Growth. 1950;14:189–211.

85. Baker IA, Elwood PC, Hughes J, Jones M, Moore F, Sweetnam PM. Arandomised controlled trial of the effect of the provision of freeschool milk on the growth of children. J Epidemiol CommunityHealth. 1980;34:31–4.

86. Du X, Zhu K, Trube A, Zhang Q, Ma G, Hu X, Fraser DR,Greenfield H. School-milk intervention trial enhances growth andbone mineral accretion in Chinese girls aged 10–12 years in Beijing.Br J Nutr. 2004;92:159–68.

87. Hoppe C, Udam TR, Lauritzen L, Molgaard C, Juul A, MichaelsenKF. Animal protein intake, serum insulin-like growth factor I, andgrowth in healthy 2.5-y-old Danish children. Am J Clin Nutr.2004;80:447–52.

88. Hoppe C, Molgaard C, Vaag A, Barkholt V, Michaelsen KF. Highintakes of milk, but not meat, increase s-insulin and insulin resistancein 8-year-old boys. Eur J Clin Nutr. 2005;59:393–8.

89. Hoppe C, Molgaard C, Juul A, Michaelsen KF. High intakes ofskimmed milk, but not meat, increase serum IGF-I and IGFBP-3 ineight-year-old boys. Eur J Clin Nutr. 2004;58:1211–6.

90. Holmes MD, Pollak MN, Willett WC, Hankinson SE. Dietarycorrelates of plasma insulin-like growth factor I and insulin-likegrowth factor binding protein 3 concentrations. Cancer EpidemiolBiomarkers Prev. 2002;11:852–61.

91. Bogin B. Milk and human development: An essay on the ‘‘milkhypothesis’’. Antropologia Portuguesa. 1998;15:23–36.

92. Frid AH, Nilsson M, Holst JJ, Bjorck IM. Effect of whey on bloodglucose and insulin responses to composite breakfast and lunch mealsin type 2 diabetic subjects. Am J Clin Nutr. 2005;82:69–75.

93. Hoppe C, Mølgaard C, Vaag A, Michaelsen KF. The effect of seven-day supplementation with milk protein fractions and milk mineralson IGFs and glucose-insulin metabolism. Scand J Food Nutr. 2006;50:46.

94. Garlick PJ, Reeds PJ. Proteins. In: Garrow JS, James WPT, editors.Human nutrition and dietetics. 9 ed. London: Churchill Livingstone;1993. p. 56–76.

95. Prod’homme M, Rieu I, Balage M, Dardevet D, Grizard J. Insulin andamino acids both strongly participate to the regulation of proteinmetabolism. Curr Opin Clin Nutr Metab Care. 2004;7:71–7.

96. Grinspoon S, Carr A. Cardiovascular risk and body-fat abnormalitiesin HIV-infected adults. N Engl J Med. 2005;352:48–62.

97. Estrada V, Martinez-Larrad MT, Gonzalez-Sanchez JL, de Villar NG,Zabena C, Fernandez C, Serrano-Rios M. Lipodystrophy andmetabolic syndrome in HIV-infected patients treated with antire-troviral therapy. Metabolism. 2006;55:940–5.

98. Haugaard SB, Andersen O, Storgaard H, Dela F, Holst JJ, Iversen J,Nielsen JO, Madsbad S. Insulin secretion in lipodystrophic HIV-

Milk proteins in fortified blended foods 159S

at AR

LA F

OO

DS

on January 27, 2016jn.nutrition.org

Dow

nloaded from

infected patients is associated with high levels of nonglucose

secretagogues and insulin resistance of beta-cells. Am J Physiol

Endocrinol Metab. 2004;287:E677–85.

99. Fruhbeck G. Protein metabolism. Slow and fast dietary proteins.

Nature. 1998;391:843–5.

100. Bergstrom J, Furst P, Noree LO, Vinnars E. Intracellular free amino acidconcentration in human muscle tissue. J Appl Physiol. 1974;36:693–7.

101. Ha E, Zemel MB. Functional properties of whey, whey components,

and essential amino acids: mechanisms underlying health benefits for

active people. J Nutr Biochem. 2003;14:251–8.

102. Muller F, Aukrust P, Svardal AM, Berge RK, Ueland PM, Froland SS.

The thiols glutathione, cysteine, and homocysteine in human immu-

nodeficiency virus (HIV) infection. In: Watson RR, editor. Nutrients

and foods in AIDS. 1 ed. Boca Raton: CRC Press; 1998. p. 35–69.

103. Buhl R, Jaffe HA, Holroyd KJ, Wells FB, Mastrangeli A, Saltini C,

Cantin AM, Crystal RG. Systemic glutathione deficiency in symp-

tom-free HIV-seropositive individuals. Lancet. 1989;2:1294–8.

104. Staal FJ, Roederer M, Israelski DM, Bubp J, Mole LA, McShane D,

Deresinski SC, Ross W, Sussman H, et al. Intracellular glutathione

levels in T cell subsets decrease in HIV-infected individuals. AIDS Res

Hum Retroviruses. 1992;8:305–11.

105. Staal FJ, Ela SW, Roederer M, Anderson MT, Herzenberg LA,

Herzenberg LA. Glutathione deficiency and human immunodefi-

ciency virus infection. Lancet. 1992;339:909–12.

106. Golden MH. Issues in kwashiorkor. Lancet. 1994;343:292.

107. Golden MH, Ramdath D. Free radicals in the pathogenesis of

kwashiorkor. Proc Nutr Soc. 1987;46:53–68.

108. Becker K, Pons-Kuhnemann J, Fechner A, Funk M, Gromer S, GrossHJ, Grunert A, Schirmer RH. Effects of antioxidants on glutathione

levels and clinical recovery from the malnutrition syndrome

kwashiorkor—a pilot study. Redox Rep. 2005;10:215–26.

109. Fuchs GJ. Antioxidants for children with kwashiorkor. BMJ. 2005;330:1095–6.

110. Ciliberto H, Ciliberto M, Briend A, Ashorn P, Bier D, Manary M.

Antioxidant supplementation for the prevention of kwashiorkor in

Malawian children: randomised, double blind, placebo controlledtrial. BMJ. 2005;330:1109–11.

111. Golden MH. Oedematous malnutrition. Br Med Bull. 1998;54:

433–44.

112. Scherbaum V, Furst P. New concepts on nutritional management of

severe malnutrition: the role of protein. Curr Opin Clin Nutr Metab

Care. 2000;3:31–8.

113. De Bono DP. Free radicals and antioxidants in vascular biology: the

roles of reaction kinetics, environment and substrate turnover. QJM.

1994;87:445–53.

114. Look MP, Rockstroh JK, Rao GS, Kreuzer KA, Barton S, Lemoch H,

Sudhop T, Hoch J, Stockinger K, et al. Serum selenium, plasma

glutathione (GSH) and erythrocyte glutathione peroxidase (GSH-Px)-

levels in asymptomatic versus symptomatic human immunodefi-

ciency virus-1 (HIV-1)-infection. Eur J Clin Nutr. 1997;51:266–72.

115. Lothian B, Grey V, Kimoff RJ, Lands LC. Treatment of obstructive

airway disease with a cysteine donor protein supplement: a case

report. Chest. 2000;117:914–6.

116. Playford RJ, Macdonald CE, Johnson WS. Colostrum and milk-

derived peptide growth factors for the treatment of gastrointestinal

disorders. Am J Clin Nutr. 2000;72:5–14.

117. Brody EP. Biological activities of bovine glycomacropeptide. Br J

Nutr. 2000;84:S39–46.

118. Buchman AL. Glutamine: commercially essential or conditionally es-

sential? A critical appraisal of the human data. Am J Clin Nutr. 2001;74:

25–32.

119. Campos FG, Waitzberg DL, Teixeira MG, Mucerino DR, Kiss DR,Habr-Gama A. Pharmacological nutrition in inflammatory bowel

diseases. Nutr Hosp. 2003;18:57–64.

120. Darragh AJ, Moughan PJ. The three-week-old piglet as a model

animal for studying protein digestion in human infants. J PediatrGastroenterol Nutr. 1995;21:387–93.

121. Makkink CA, Berntsen PJ, op den Kamp BM, Kemp B, Verstegen

MW. Gastric protein breakdown and pancreatic enzyme activities in

response to two different dietary protein sources in newly weanedpigs. J Anim Sci. 1994;72:2843–50.

122. Nessmith WB, Jr., Nelssen JL, Tokach MD, Goodband RD,Bergstrom JR. Effects of substituting deproteinized whey and(or)crystalline lactose for dried whey on weanling pig performance.J Anim Sci. 1997;75:3222–8.

123. McCracken BA, Zijlstra RT, Donovan SM, Odle J, Lien EL, GaskinsHR. Neither intact nor hydrolyzed soy proteins elicit intestinal inflam-mation in neonatal piglets. JPEN J Parenter Enteral Nutr. 1998;22:91–7.

124. Moughan PJ. Dietary protein quality in humans—an overview.J AOAC Int. 2005;88:874–6.

125. Friesen KG, Goodband RD, Nelssen JL, Blecha F, Reddy DN, ReddyPG, Kats LJ. The effect of pre- and postweaning exposure to soybeanmeal on growth performance and on the immune response in theearly-weaned pig. J Anim Sci. 1993;71:2089–98.

126. Mahan DC, Fastinger ND, Peters JC. Effects of diet complexity anddietary lactose levels during three starter phases on postweaning pigperformance. J Anim Sci. 2004;82:2790–7.

127. Hampson DJ. Attempts to modify changes in the piglet smallintestine after weaning. Res Vet Sci. 1986;40:313–7.

128. Wang B, Yu B, Karim M, Hu H, Sun Y, McGreevy P, Petocz P, Held S,Brand-Miller J. Dietary sialic acid supplementation improves learn-ing and memory in piglets. Am J Clin Nutr. 2007;85:561–9.

129. Giesting DW, Easter RA. Effect of protein source and fumaric acidsupplementation on apparent ileal digestibility of nutrients by youngpigs. J Anim Sci. 1991;69:2497–503.

130. Officer DI, Batterham ES, Farrell DJ. Comparison of growthperformance and nutrient retention of weaner pigs given diets basedon casein, free amino acids or conventional proteins. Br J Nutr.1997;77:731–44.

131. Dunshea FR, Van Barneveld RJ. Colostrum protein isolate enhancesgut development, growth performance and plasma IGF-I and II inneonatal pigs. Asia Pac J Clin Nutr. 2003;12:S40.

132. Aukrust P, Muller F, Svardal AM, Ueland T, Berge RK, Froland SS.Disturbed glutathione metabolism and decreased antioxidant levelsin human immunodeficiency virus-infected patients during highlyactive antiretroviral therapy - potential immunomodulatory effects ofantioxidants. J Infect Dis. 2003;188:232–8.

133. Bounous G, Baruchel S, Falutz J, Gold P. Whey proteins as a foodsupplement in HIV-seropositive individuals. Clin Invest Med. 1993;16:204–9.

134. Micke P, Beeh KM, Schlaak JF, Buhl R. Oral supplementation withwhey proteins increases plasma glutathione levels of HIV-infectedpatients. Eur J Clin Invest. 2001;31:171–8.

135. Micke P, Beeh KM, Buhl R. Effects of long-term supplementationwith whey proteins on plasma glutathione levels of HIV-infectedpatients. Eur J Nutr. 2002;41:12–8.

136. Agin D, Kotler DP, Papandreou D, Liss M, Wang J, Thornton J,Gallagher D, Pierson RN. Effects of whey protein and resistanceexercise on body composition and muscle strength in women withHIV infection. In Vivo Body Comp Stud. 2000;904:607–9.

137. Agin D, Gallagher D, Wang J, Heymsfield SB, Pierson RN, Kotler DP.Effects of whey protein and resistance exercise on body cell mass,muscle strength, and quality of life in women with HIV. AIDS. 2001;15:2431–40.

138. Moreno YF, Sgarbieri VC, da Silva MN, Toro AA, Vilela MM.Features of whey protein concentrate supplementation in children withrapidly progressive HIV infection. J Trop Pediatr. 2006;52:34–8.

139. Briend A, Lacsala R, Prudhon C, Mounier B, Grellety Y, Golden MH.Ready-to-use therapeutic food for treatment of marasmus. Lancet.1999;353:1767–8.

140. Collins S, Sadler K. Outpatient care for severely malnourishedchildren in emergency relief programmes: a retrospective cohortstudy. Lancet. 2002;360:1824–30.

141. Diop EHI, Dossou NI, Ndour MM, Briend A, Wade S. Comparisonof the efficacy of a solid ready-to-use food and a liquid, milk-baseddiet for the rehabilitation of severely malnourished children: arandomized trial. Am J Clin Nutr. 2003;78:302–7.

142. Boirie Y, Dangin M, Gachon P, Vasson MP, Maubois JL, Beaufrere B.Slow and fast dietary proteins differently modulate postprandialprotein accretion. Proc Natl Acad Sci USA. 1997;94:14930–5.

143. Hall WL, Millward DJ, Long SJ, Morgan LM. Casein and wheyexert different effects on plasma amino acid profiles, gastroin-testinal hormone secretion and appetite. Br J Nutr. 2003;89:239–48.

160S Supplement

at AR

LA F

OO

DS

on January 27, 2016jn.nutrition.org

Dow

nloaded from

144. Arnal MA, Mosoni L, Boirie Y, Houlier ML, Morin L, Verdier E, Ritz P,Antoine JM, Prugnaud J, et al. Protein pulse feeding improves proteinretention in elderly women. Am J Clin Nutr. 1999;69:1202–8.

145. Uauy R, Mize CE, Castillo-Duran C. Fat intake during childhood:metabolic responses and effects on growth. Am J Clin Nutr. 2000;72:1354S–60S.

146. Prentice AM, Paul AA. Fat and energy needs of children indeveloping countries. Am J Clin Nutr. 2000;72:1253S–65S.

147. Torun B, Solomons NW, Viteri FE. Lactose malabsorption andlactose intolerance: implications for general milk consumption. ArchLatinoam Nutr. 1979;29:445–94.

148. Waterlow JC, Golden MH. Serum inorganic phosphate in protein-energy malnutrition. Eur J Clin Nutr. 1994;48:503–6.

149. Stabler SP, Allen RH. Vitamin B12 deficiency as a worldwide prob-lem. Annu Rev Nutr. 2004;24:299–326.

150. World Food Programme. WFP: Food and Nutrition Handbook.Rome: World Food Programme; 2000.

151. Bucci LR, Unlu L. Protein and amino acid supplements in exerciseand sport. In: Driskell JA, Wolinsky I, editors. Energy-yielding mac-ronutrients and energy metabolism in sports nutrition. Boca Raton:CRC Press; 2000, 191-212.

152. U.S. Dairy Export Council. Reference manual for U.S. whey andlactose products. Arlington, VA: US Dairy Export Council; 2006.

153. USDA. USDA national nutrient database for standard reference.Washington, DC: USDA; 2006.

154. USAID. Commodity reference guide. Washington, DC: USAID;2006.

155. Shrimpton R, Victora CG, de Onis M, Lima RC, Blossner M,Clugston G. Worldwide timing of growth faltering: implications fornutritional interventions. Pediatrics. 2001;107:E75.

Milk proteins in fortified blended foods 161S

at AR

LA F

OO

DS

on January 27, 2016jn.nutrition.org

Dow

nloaded from