Addressing Bioavailability & Digestibility

To provide health benefits, a nutrient in food must be digested and utilized by the body. In other words, the food must be digestible and the nutrient must be bioavailable. The December 2010 Food Safety & Quality column, “Simulating Digestion,” in Food Technology discussed the design and use of artificial human gastrointestinal tracts, and the January 2011 column, “Measuring Encapsulation Efficacy,” discussed encapsulation as a means of protecting or maintaining the bioavailability of compounds during digestion. This month’s column will add to the discussion of these topics by summarizing several relevant conferences and symposia.

Nutrient Bioavailability
The bioavailability of pharmaceuticals is specifically defined and rigidly regulated. The bioavailability of nutrients, in contrast, is less defined. Basically, it is the degree to which a nutrient is available to the target tissue after consumption or, as the European Food Information Council (www.eufic.org) puts it, the proportion of a nutrient that is absorbed from the diet and used for normal body functions.

In the human digestive system, food is broken down mechanically and chemically (enzymatically) to release and allow absorption of nutrients. The bioavailability of a nutrient in food is affected by numerous factors such as the food structure, the chemical form of the nutrient, how readily the nutrient is released from the food by chewing, effects of enzymes in the gastrointestinal tract, intestinal motility, health of the person consuming the food, and interactions with drugs and other foods or nutrients (e.g., vitamin C enhances iron absorption while phytic acid binds calcium, iron, and zinc, making them unavailable for absorption).

Knowledge of the bioavailability of nutrients is needed to translate physiological requirements into actual dietary requirements and recommendations, but determining the physiological requirements is difficult. The European Micronutrient Recommendations Aligned (EURRECA) Network of Excellence (www.eurreca.org) is making efforts to standardize assessment methodologies across Europe.

Designing for Digestibility
Although many studies have identified relationships between food structure and composition and the bulk properties, such as shelf life, texture, and flavor, fewer studies have addressed the changes that occur in foods upon ingestion, digestion, and absorption. Accordingly, a symposium titled “Rational design of food delivery systems: Physicochemical basis of Food component digestion, release, and absorption” was presented at the Institute of Food Technologists’ Annual Meeting & Food Expo in Chicago, Ill., in July 2010.

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Harjinder Singh of Massey University in New Zealand said that there is growing interest in understanding how food material properties can be manipulated under physiological conditions to control the uptake of lipids and lipid-soluble components. He described how the structure of emulsified lipids affects lipid digestion at various stages of physiology, with specific focus on the structure and interactions of milk protein-stabilized emulsions, using in vitro models.

Yael Vodovotz of Ohio State University said that gum disease and oral cancer have been associated with the development of systemic diseases such as diabetes, coronary heart disease, and stroke and that flavonoids in grapes and strawberries show promise in preventing oral diseases. However, much of the phytonutrients consumed from fruits shows little intrinsic activity because of poor absorption and biologic degradation. She described studies to improve biological uptake by localizing release of bioactives in the oral cavity at a desired rate. Starch confections were made with grape and strawberry with varying amounts of soy protein and water to produce products with different physicochemical and rheological characteristics. Sensory evaluation showed that despite individual differences in saliva production, differences in amorphous states of these confections resulted in differences in the duration of phytochemical deposition in the mouth.

Eyal Shimoni of Technion–Israel Institute of Technology said that since properties, digestion, and health-promoting effects of a food are affected by its three-dimensional structure, the design of this structure is at the heart of controlling all these properties. By understanding the driving forces behind these properties and their relation to food functionality, one can in principle design foods. For example, he said, using starch as a model component and structuring its crystalline polymorphism, structure, and interaction with low-molecular-weight compounds, one can tailor nutritional and physiological benefits.

Lingyun Chen of the University of Alberta in Canada said that many nutraceutical compounds have low bioavailability because of insufficient residency time, low permeability, and/or low solubility within the human gastrointestinal tract. For example, while beta-carotenoids can protect cells against oxidation to reduce the risk of cancer and other aging-related diseases, only a small proportion of the total amount found in fruits and vegetables is bioavailable. He said that nanoparticles may allow efficient delivery of nutraceuticals to the small intestine for improved absorption. He described the formation of plant protein-based nanoparticles and the impact of protein structure and particle size on their physicochemical and physiological properties.

Uri Lesmes of the University of Massachusetts described studies of food-grade emulsions as delivery systems for lipophilic ingredients, such as omega-3-rich oils, to improve their physical and chemical stability. He discussed the development of innovative delivery systems using interfacial biopolymer complexes. Lactoferrin-sodium caseinate complexes showed improved emulsion stability to pH, ionic strength, and lipid oxidation without affecting lipid digestibility by lipase, and beta-lactoglobulin-dextran complexes improved emulsion stability with slight impact on lipase digestibility.

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Designing for Bioavailability
The symposium “Nutrient Bioavailability by Design” was also presented at the 2010 IFT Annual Meeting & Food Expo. Fabiola Dionisi of the Nestlé Research Center in Switzerland said that food technology could play an important role in modifying foods to improve absorption of nutrients with low bioavailability and to decrease absorption of nutrients with high bioavailability (e.g., fats and carbohydrates) to reduce calorie intake or sustain release in the body. Different ways are available to design bioavailability for a targeted benefit, she said, such as modifying food structure and composition to influence gut microflora transformations and modifying transport through the gut.

Since fortifying foods with iron adversely affects color, taste, and shelf life, Nestlé has developed an inorganic iron source, ferrous ammonium phosphate, that is significantly more bioavailable than ferric pyrophosphate. The white, tasteless powder can be used in color- and flavor-sensitive foods. The company also has combined tomato oleoresin with whey protein to obtain a lycopene-rich ingredient with similar bioavailability to the lycopene from tomato paste and has enzymatically modified the citrus flavonoid hesperidin to produce hesperitin-7-glucoside, which significantly increases bioavailability and absorption.

Bruce German of the University of California, Davis, said that the nutritional value of food materials is related to their colloidal properties and the rate and extent to which they are disassembled, modified, and absorbed by humans. Colloidal science and nanoscience are being used to understand the relations between food structures and their health consequences. For example, mammalian milks—colloidal systems delivering all of the nourishment to young mammalians—are providing insights into design features of food structures for nutritional advantage.

Although complete absorption of most macronutrients in milk is clearly important, he said, some milk components appear to be structured to delay the rate of their absorption rather than to accelerate it. By coupling molecular dexterity of colloidal assembly of food materials with their metabolic, physiological, and immunological consequences, he said, it will be possible to design foods explicitly for a new generation of nutritional values, including metabolic regulation, intestinal protection, and immune regulation.

Thomas Wolever of the University of Toronto in Canada reviewed research on carbohydrates, including the effects of low-glycemic-index foods for diabetes and cardiovascular disease, which are presumably related by a reduced rate of absorption of carbohydrate, and the role of physicochemical properties of fiber on modifying the rates of absorption of nutrients and metabolic effects on blood glucose and lipids. Malabsorption of carbohydrates (i.e., colonic fermentation), he said, could have many effects, from modifying absorption of vitamins and minerals to systemic effects via colonic short-chain fatty acids related to obesity, diabetes, and coronary heart disease.

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Establishing Dietary Reference Values
A supplement to the May 2010 issue of the American Journal of Clinical Nutrition presented the proceedings of the workshop ‘‘Micronutrient Bioavailability: Priorities and Challenges for Setting Dietary Reference Values,’’ held in June 2009 by the International Life Sciences Institute and EURRECA in Barcelona, Spain.

Selenium. Susan J. Fairweather-Tait of the University of East Anglia in the United Kingdom said that obtaining information on selenium bioavailability is not straightforward because there are large variations in the selenium content of foods and its chemical forms are absorbed and metabolized differently. Efforts are needed, she said, to improve, standardize, and make more widely available techniques for species quantification. Similarly, reliable and sensitive functional biomarkers of selenium status are required, together with improvements in current biomarker methods, particularly because some functional biomarkers respond differently to the various selenium species.

Zinc. K. Michael Hambidge of the University of Colorado, Denver, said that several physiological factors determine the quantity of zinc absorbed and the efficiency of absorption, most notably the quantity of zinc ingested but also age and the time over which zinc is ingested. The principal dietary factor impairing zinc bioavailability is phytate.

Calcium. Steven A. Abrams of the Children’s Nutrition Research Center at the U.S. Dept. of Agriculture (USDA) Agricultural Research Service said that the determination of Dietary Reference Intakes (DRIs) for calcium, especially for children, has relied in significant part on the evaluation of the relation between the intake of calcium and its absorption and retention. Most of these studies are conducted using dual-tracer stable isotope, but mass balance and other isotope methods are still used occasionally. Other dietary factors, including vitamin D status and the presence of enhancers and inhibitors of calcium absorption, also have to be considered.

Vitamin A. Guangwen Tang of the Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University said that studies to assess the bioavailability and bioconversion of provitamin A carotenoids to vitamin A have advanced significantly in the past 10 years through the use of stable isotope methodology. Studies have been conducted on the effects of the food matrix, dietary fat, and genotype. She said that the vitamin A value of plant foods rich in provitamin A carotenoids may vary significantly and needs further investigation.

Iron. Richard Hurrell of the Swiss Federal Institute of Technology in Switzerland said that phytate, polyphenols, calcium, ascorbic acid, and muscle tissue have been shown to influence iron absorption in single-meal isotope studies whereas the effect of single components has been more modest in multi-meal studies with a varied diet and multiple inhibitors and enhancers. He said that the effect of fortification iron and food additives such as erythorbic acid on iron bioavailability from a mixed diet needs clarification as does the influence of vitamin A, carotenoids, and indigestible carbohydrates. The iron status of the individual and other host factors, such as obesity, play a key role in iron bioavailability, he said, generally with a greater effect than diet composition.

Folate. Marie A. Caudill of Cornell University said that bioavailability of folate is a function of absorptive and post-absorptive processes, which are influenced by diet, individuality, and complex diet-host interactions, so it is unlikely that a single bioavailability figure will accurately reflect food folate bioavailability from every diet for every person. Although there is broad agreement that naturally occurring food folate is not as bioavailable as folic acid, she said, questions remain as to the extent of these differences, particularly within the context of a whole diet.

Reference Values. Peter J. Aggett of Littlefield in the United Kingdom said that there is a need to establish physiologically based approaches to setting reference values for safe and adequate intakes, including considerations of excessive exposures. He said that a proposed biologically based approach to nutrient risk assessment has many features that could be extended to the creation of a similar approach to setting nutrient reference values.

Bioavailability Conference
Speakers at the “Bioavailability 2010” conference presented by the UC Davis Program in International & Community Nutrition in Pacific Grove, Calif., on September 26–30, 2010, discussed recent scientific research on micronutrient bioavailability.

The session “Advances in Knowledge about Mineral Metabolism Aiding Our Understanding of Bioavailability Issues” focused primarily on iron and zinc absorption and homeostasis. The session “Dietary Reference Values” also focused primarily on iron, zinc, and calcium and the factors needed for setting dietary reference values. And the session “Effects of Infection/Disease on Bioavailability” focused mainly on iron and zinc and the effects of malaria, anemia, infections, and parasites.

Three additional sessions under the general topic “Bioavailability – Applied studies and advances in methodology” were presented. “Food Factors” considered the effects of calcium on iron and zinc absorption. “Genetics/Individual factors” covered polymorphisms affecting trace element bioavailability, factors affecting bioavailability of vitamin B-12, vitamin E bioavailability, and zinc. And “Biofortification” covered provitamin A carotenoid bioavailability, zinc and iron biofortification, vitamin A, folate, and iron. Abstracts of the presentations are available at http://bioavailability2010.ucdavis.edu.

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Challenges Ahead
I asked Bruce German of UC Davis and Thomas Wolever of the University of Toronto for their views on challenges ahead in measurement of nutrient bioavailability. German responded by first reviewing some of the major advances that have occurred. There have been many interesting new discoveries, he said, such as the role of the intestine in metabolizing and excreting components from the diet; the role of the intestine in producing signaling molecules for regulation of whole-body processes, ranging from lipid metabolism to immune function, with bile acid metabolites providing a new communication language for the postprandial state; the importance of the microbiota in providing unique metabolites and in altering structure absorption and subsequent metabolism of dietary components; and the rediscovery of the postprandial state, whose measurement requires discrete models, statistics, and sampling techniques.

With regard to challenges ahead, German responded that a great deal of straightforward scientific standards is necessary to fully describe the postprandial state and the variations in humans in their ability to digest, absorb, and metabolize food components. Researchers and regulators should have been assembling consensus panels, regulatory guidelines, and standardized dietary mixtures long ago, he said. These will all have to be done now, discouragingly, in an economic climate where filling in the background studies isn’t easy to fund.

He added that researchers have very poor tools to describe the physical properties of complex food phases within the lumen of the intestine, from the nanometer length scale to the macroscopic. For example, it is still unknown what phases lipids are in as they are digested and absorbed. And the complex interplay among the chemistry, metabolism, and physiology of the gut remains a black box. Once the tools to measure the gut processes are in place, he said, the variation in the intestine’s functions will have to be overlaid onto variations in various health-related processes such as whole-body metabolism.

Wolever said that one of the challenges ahead is determining a valid measure of available carbohydrate (i.e., how much carbohydrate in foods is digested and absorbed in the small intestine). There is evidence, he said, that the current measures of resistant starch greatly overestimate the amount that actually escapes digestion in vivo. For more on resistant starch, see the April 2009 Food Safety & Quality column “Analyzing for Resistant Starch.”

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Forthcoming Conferences
Tracel 2011, 3rd International Symposium on Trace Elements & Health, Murcia, Spain, May 24–27, 2011. For information, visit www.tracel2011.com.

11th European Nutrition Conference, Federation of European Nutrition Societies, Madrid, Spain, October 26–29, 2011. For information, visit www.fensweb.eu.

Neil H. Mermelstein, a Fellow of IFT, is Editor Emeritus of Food Technology ([email protected])