WO2015130678A1

WO2015130678A1 - Low fructose, low glycemic load ready-to-eat therapeutic formulations

Info

Publication number: WO2015130678A1
Application number: PCT/US2015/017314
Authority: WO
Inventors: Susan B. Roberts; Edward Saltzman
Original assignee: Tufts University
Priority date: 2014-02-25
Filing date: 2015-02-24
Publication date: 2015-09-03

Abstract

Provided are therapeutic formulations or supplements which are low in sucrose and fructose, have a low glycemic load that are read-to-eat. Also provided are methods of treating or preventing malnutrition in a human by administering these therapeutic formulations.

Description

[0001] The present disclosure is in the fields of nutrition and medicine. More particularly, this disclosure is directed to therapeutic supplements for treating or preventing malnutrition and for preventing later chronic disorders resulting therefrom,

BACKGROUND

[0002] There is now widespread recognition of children who are malnourished have increased risk of adult obesity with accompanying diabetes and cardiovascular disease (Uauy el al. (2002) J. Pub. Health Nutr. 5:223-229). In particular, early malnutrition is known to be associated years later with diminished ability to oxidize dietary fat, impaired regulation of food intake, low energy expenditure (Hoffman et al. (2000) Am. J. Clin. Nutr. 72:702-707; Hoffman, et al. (2000) J. Nutr. 130:2265-2270), and the development of excess visceral adipose tissue (VAT) (Hoffman et al. (2007) Nutr. 23:640-646). All of these factors that predispose to obesity and its health complications. The foods currently- fed to malnourished infants and children to promote recovery may also result in later-life impaired regulation of food intake, excess body weight, and excess V AT.

[0003] Currently, the prevention and treatment of malnutrition worldwide commonly involves the ingestion of ready-to-eat commercial therapeutic foods (RUTF) such as P lumpy 'nut (http://www.nutriset.fr/eu/prod

ready o-use-therapeutic-food-rutf.html), and ready-to-eat supplementary foods (RUSF) such as P lumpy 'sup (http://www. nutriset.fr/en/product-range/produit--par- produit/plumpy-sup.hrn i) and Plumpy'doz (h ://www .nurriset.fr/eri/product- range/produit-par-produit'plumpydoz.html). These foods contain ingredients that satisfy the general composition guidelines specified by the World Health Organization ("WHO") for treatment of severe acute malnutrition and or moderate acute malnutrition (e.g., http:/7w^\ v.who.mt/nutritiou^ublications/eu^/manage severe_malnutrition_eng.pdf), and facilitate recovery and catch-up growth of children suffering from malnutrition and prevention of malnutrition in at-risk children.

[0004] While these products facilitate short-term recovery from malnutrition, they may also facilitate long-term health problems due to their very high sugar content and high glycemic load. For example, the WHO recommends that RUTF contain 50 grams sugar per 1000 ml water, which is equivalent to 19% of energy from sugar, and that RUSF contain 70 grams sugar per 1000 ml water, which is equivalent to 26% to 27% of energy from sugar (http://www.who. mt/nutrition/publications/en/manage_severe_malnutrition__ eng.pdf).

[0005] High sugar content has two problems: the high glycemic load and the high fructose content (via sucrose). Both of these factors lead to increased risk of obesity, cardiovascular disease and the developing type 2 diabetes in adults and in animal models. One mechanism by which diseases develop as a result of high sucrose or fructose consumption is through increased visceral adipose tissue (VAT) accumulation.

[ 0006] Among carbohydrates, sucrose and fructose have been specifically linked to specific chronic health problems. In cross-sectional studies, individuals who consume more sugar-sweetened beverages have a greater percentage of VAT even after controlling for body mass index (BMI) or total fat mass in both adults and children (Pollock et al. (2012) J. Nutr. 142:251-257: Odegaard et al. (2012) Obesity 20:689-691). These findings have been supported by intervention studies in which individuals fed sucrose- containing or fructose-containing beverages over a six-month period had significantly higher VAT than individuals fed non-sucrose-, non-fructose-containing beverages (Maersk et al. (2012) Am. J. Clin. Nutr. 95:283-289; Stanhope et al. (2009) J. Clin.

Invest. 1 19: 1322-1334). Additional adverse effects of high fructose and high sucrose may include insulin resistance, which is a risk factor for the development of diabetes.

[0007] Thus, what is needed are improved therapeutic and supplementary foods for malnourished infants and children which do not cause the long-term health problems associated with high sugar content and glycemic load such as obesity, visceral obesity, and diabetes. SUMMARY

[00Θ8] Disclosed is a nutritional formulation comprising sources for the following: low sucrose, low fructose, low glycemic load energy, protein, fat (lipid, to include appropriate amounts of n-6 and n-3 fatty acids), vitamins, and minerals, the formulation containing no more than 0 to 5% sucrose or fructose,

[0009] Also disclosed is a method of treating a human suffering from malnutrition, comprising administering to the patient the nutritional formulation.

DESCRIPTION

[0010] Throughout this application, various patents, patent applications, and publications are referenced. The disclosures of these patents, patent applications, and publications in their entireties are hereby incorporated by reference into this application in order to more fully describe the state of the art as known to those skilled therein as of the date of the invention described and claimed herein. The instant disclosure wil l govern in the instance that there is any inconsistency between the patents, patent applications, and publications and this disclosure.

[0011] The present disclosure provides a therapeutic supplementary formulation that has a reduced sugar and fructose content relative to currently-available ready-to-use therapeutic supplements such as RUTF and RUSF. The low sugar and/or low glycemic load content of the present formulation has important metabolic advantages that help to prevent adverse metabolic programming leading to obesity, excess VAT, and related health issues in later childhood and adult life, including increased risk of cardiovascular disease, diabetes and premature death. As used herein, the terms "formulation,"

"product," and "supplement" are used interchangeably to describe the present invention.

[0012] With the exception of the sugar/carbohydrate energy source, the nutritional content of the present formulation satisfies the recommendations set and updated at intervals by WHO and includes proteins, fats, lipids, specific fatty acids, vitamins, minerals, and a low sucrose and low fructose source of carbohydrate. Sugar (sucrose) and fructose may be included but amounting to less than 5% energy intake. Other carbohydrate sources include lactose, starch, and starch derivatives such as maltodextrin, and low glycemic index carbohydrates (e.g., starches with relatively greater amyiose compared to amylopectin such as chickpea and low fat soy flour) as a further prevention against long-term obesity and chronic diseases including diabetes.

[0013] Table 1 provides a representative list of individual nutrients in the formulation of the present disclosure. The precise amounts of micronutrients will be current for WHO formulations.

Table 1

[0014] These nutrients can be derived from ingredients including soy, chick peas, other legumes, flax seed meal, corn, barley, rice, wheat, oil, peanuts, and/or milk. Water- containing foods such as meat, fish, leaves, fruits, and vegetables, can be used for preparing the formulation if measures are taken to ensure sterility of final product.

[0015] For example, the recipe in Table 2 is representative of a low sucrose and low giycemic load formulation for a RUTF.

Table 2

[0016] This mixture does not need to be cooked when packaged in a ready to use format consistent with safety regulation for sterility, because all ingredients are digestible in the raw state.

[0017] With the exception of the sugar component, the nutrient composition of this representative formulation is similar to F-100 (World Health Organization (1999)

Management of Severe Malnutrition: A Manual For Physicians and Other Senior Health Workers, Geneva, p. 13), the standard milk-based formula demonstrated to be effective in the treatment of severe childhood malnutrition.

[0018] An additional representative formulation for a RUSF according to the present disclosure is shown in Table 3.

Table 3

[0019] This formulation use most of the same ingredients as existing RUSF and meets the nutrient specifications for an F-75 formulation, with the exception of the sugar component, which has been replaced with a combination of rice flour, soy flour and/or maltodextrin.

[002Θ] Other representative formulations according to the present disclosure are shown in Table 4 and Table 5,

Table 4

mme ate y e ore use

Table 5

[0021] The formulations in Table 4 and Table 5 use different ingredients to achieve the desired nutrient composition. They can be presented in a mix that is ready to consume after water has been added or cooked prior to packaging.

[0022] For ail of these representative formulations, whol e or skim milk, or milk powder, or preparations of milk such as whey protein, produced by standard commercial techniques is can be used in their preparation.

[0023] The vegetable oil component, if used, can be any one of a mixture of vegetable oils made by standard commercial methods and including soy oil, cottonseed oil, rapeseed oil, and corn oil. Rapeseed oil and soybean oil are particularly useful as they provide a good balance of essential fatty acids. When flax seed meal or other high-fat flours are used, some or all of the oil is contained in the meal. For oils that do not provide the required n-3 and n-6 fatty acids, supplementation with these fatty acids is performed.

[0024] Commercial sources of non-fructose and non-sucrose carbohydrate sources can be used in the formulation. These include maltodextrin, dextrin, legume flours, rice flour, barley flour, wheat flour. Sucrose can be used in amounts to less than 5% energy content.

[0025] The micronutrient component of the formation can be formed from its constituent parts or can be a commercially available, premade mixture of vitamin, of minerals, or a combination of both, in any case, this micronutrient component provides the same amount of micronutrients to the malnourished child as F-100 or F-75

formulations. The content of a representative, powdered, 100 gram mixture from

Nutriset, Malauiiay, France is listed in Table 6.

Table 6

[0026] Where part of the formulation, peanuts and other legumes, are roasted and ground, without added oil, salt, or preservatives, peanut butter can be obtained from a commercial food processing company that makes peanut butter. [0027] To ensure safety, the formulation should comply with the Recommended International Code of Hygienic Practice for Foods for Infants and Children of the Codex Aiimentarius Standard CAC/RCP 21-1979 (http://www.codexalimentarius.net download/standards/297/CXP Q21e.pdf). The formulation does not contain any substance originating from microorganisms (e.g., yeast, molds, cofiform bacteria, Salmonella, Listeria, Staphylococci, Clostridium perfringens) or any poisonous or deleterious substances, including anti -nutritional factors, heavy metals, or pesticides in amounts that may represent a hazard to health.

[0028] The added minerals are water-soluble and do not form insoluble components when mixed together. The food supplement has a mineral composition that does not alter the acid-base metabolism of children with severe acute malnutrition. In particular, it has a moderate positive non-metabolizabie base sufficient to eliminate the risk of metabolic acidosis. The non-metabolizabie base can be approximated by the formula: estimated absorbed millimoies (sodium + potassium + calcium + magnesium) - (phosphorus + chloride). The mineral mix recommended for F-100 by WHO is an example of a mineral mix with a suitable positive non-metaboiizable base. All added mineral salts and vitamins should be on the Advisory List of Mineral Salts and Vitamin Compounds for Use in Foods for Infants and Children of the Codex .Alimentarius Standard CAC/GL 10- 1979 (available at http://www^r.codexalimentarius.net''dowTiioad/standards/300/CXG_ 010e.pdf) (de Pee et al. (2009) Food Nutr. Bull. Sep;30(3):S434- 63).

[0029] To increase mineral bioavailability, phytase may be added to the formulation during preparation at the last production step, or it can be used as a home fortificant. Phytase reduces phytate content, and serves to reduce micronutrient malabsorption. A range of phytases is available with different pH and temperature optimums. Thus, different phytases can be used for phytate degradation in different wet foods or in the iow-pH environment of the stomach (Rimbach et al. (2008) Curr. Topics Nutraceut. Res. 6: 131—44). However, phytase is not yet widely approved for human consumption but in some countries is considered as GRAS (Generally Regarded As Safe) status for persons aged 3 years and older, but not yet for younger.

[0030] The formulation can be in the form of a liquid, powder, paste, biscuit, cereal, and the like. If not in liquid or paste form, the formulation should be soft or crushabie and easy to eat for young children without preparation other than in some cases the addition of water. The formulation, like conventional RUTF and RUSF, is steri le and does not need to be prepared in any way prior to consumption except addition of water for some types of formulation (such as powder) and in some cases may be eaten straight from the package, making it practical for use where environmental contamination is widespread and/or cooking fuel and facilities are limiting constraints. This prevents food-bom contamination that could increase the risk of diarrhea and other infections and allows the formulation to be safely stored at ambient tropical conditions for three to four months.

[0031] In ail forms, the formulation is a homogenous mixture of lipid-rich and water- soluble foods. The lipids exist as a viscous liquid, and small particles of protein, carbohydrate, vitamins, and minerals are mixed throughout this liquid. In order to achieve a homogenous mixture, a specific mixing procedure may be followed. For example, the lipid elements of RUTF can first be stirred and heated; the powdered ingredients are then slowly added to the lipids during vigorous stirring. Once all the powdered ingredients are added, the entire mixture is stirred at higher speeds for several minutes. For mixtures containing amylose or amylopectin starches, the mixtures can be boiled prior to packaging to gelatinize the starch and ensure digestibility. As long as the powdered ingredients do not have a particle size that is larger than 200 microns, the mixture does not readily separate. When mixtures are made with larger particles, the formulation is stirred briefly (by hand just prior to consumption) to temporari ly suspend the large particles in the mixture. The use of oils that are liquids at ambient temperature facilitates the mixing process.

[0032] When the formulation is in the form of a paste or spread, it can be prepared from powdered ingredients embedded in a lipid-rich paste, resulting in an energy dense food that resists microbial contamination (e.g., Briend (2002) Nutr. Bull., 3 :239-243). In cases where the low water content of the paste is low, low water content makes it difficult for significant bacterial growth to occur in these foods (Briend (1997) Field Exch. 2: 15).

[0033] Additional procedures such as treatment with heat may be required for products of greater water content. Regardless of water content, pastes are produced and packaged to maintain sterility according to industry standards and Good Manufacturing Processes as per the electronic Code of Federal Regulations (eCFR) Part 1 10— Current Good Manufacturing Practice in Manufacturing, Packing, or Holding Human Food (http:// www.ecfr.gov/cgi-bin/text-ic c?c-ecfr&sid= cefdffi5373327b34dfa6f87642959825&rgn= <hv5&view=text&node=21 :2.0.1.1.10&idno=21#21 :2.0.1.1.10.2.1.2) or Codex regulations,

[0034] When the formulation is in the form of a biscuit or wafer the product is energy dense, and the low water content resists microbial contamination (e.g., Briend (2002) Nutr. Bull., 3 :239-243).

[0035] Reference will now be made to specific examples il lustrating the invention. It is to be understood that the examples are provided to illustrate embodiments and that no limitation to the scope of the invention is intended thereby.

EXAMPLES

EXAMPLE ί

Uncooked Peanut-Based Supplement

[0036] The composition contains protein 5-15% of energy; > 30% of protein from dairy source; fat 40~55%> of energy; carbohydrate making up the difference (30-40 of energy ); vitamin and mmeral mixtures to meet WHO specifications; low gl cemic load and low fructose (< 5% energy).

[0037] The composition includes 141 g protein, 186 g fat, and 418 g carbohydrate from the following ingredients:

206 g non-fat milk powder

367 g natural peanut butter

288 g maltodextrin

Vitamin/mineral mixtures to meet micronutrient targets

250 g water

[0038] The ingredients are mixed together in a sterile environment before use. EXAMPLE 2

Cooked Rice-Based Supplement

[0039] The composition contains protein 5-15% of energy; > 30% of protein from dairy source; fat 40-55% of energy; carbohydrate making up the difference (30-40 of energy); vitamin and mineral mixtures to meet WHO specifications; low glycemic load and low fructose (< 5% energy).

[0040] The composition includes 94 g protein, 229 g fat, and 360 g carbohydrate from the following ingredients:

140 g non-fat milk powder

117 g low fat soy flour

189 g maltodextrin

101 g white rice flour

215 g oil

Vitamin/mineral mixtures to meet micronutrient targets

660 g water

[0041] The ingredients are boiled for 1 min while stirring. For commercial purposes, cooking will also include sterilization using protocols known in the art.

EXAMPLE 3

Uncooked Flax-Based S u p 1 ement

[0042] The composition contains protein 5-15% of energy; > 30% of protein from dairy source; fat 40-55%) of energy; carbohydrate making up the difference (30-40 of energy); vitamin and mineral mixtures to meet WHO specifications; low glycemic load and low fructose (< 5% energy).

[0043] The composition includes 141 g protein, 208 g fat, and 328 g carbohydrate from the following ingredients:

205 g non-fat milk powder

400 g flax seed flour

132 g maltodextrin

69 g oil

Vitamin/mineral mixtures to meet micronutrient targets

250 g water [0044] All mgredients are mixed together in a sterile environment to make a smooth paste. An alternative paste version of this product can he made without water, in which case water is added at the time of consumption.

EQUIVALENTS

[0045] Those skilled in the art will recognize, or be able to ascertain, using no more than routine experimentation, numerous equivalents to the specific embodiments described specifically herein. Such equivalents are intended to be encompassed in the scope of the following claims.

Claims

1 , A nutritional formulation comprising a low sucrose, low fructose, low glycemic load energy source, a protein source, a fat (lipid) source, a source of n-6 and n-3 fatty acids, vitamins, and minerals, the formulation containing no more than 0 to 5% sucrose or fructose.

2. A method of treating a human suffering from malnutrition, comprising administering to the patient the nutritional formulation of claim 1.