Prevention of Vascular Calcification by Magnesium and Selected Polyphenols.

Arterial vascular calcification (VC) represents formation of calcium phosphate deposits on the interior of arteries, which could restrict blood flow leading to heart health problems, including morbidity and mortality. VC is a complex and tightly regulated process that involves transformation of vascular smooth muscle cells (VSMCs) to bone-like cells and subsequent deposition of calcium as hydroxyapatite. Natural bioactives, including quercetin (Q), curcumin (C), resveratrol (R), and magnesium (Mg), have been reported to inhibit VC. Thus, we conducted an in vitro study using rat vascular smooth muscle cells (rVSMCs) to evaluate the protective effect of natural bioactives found in OptiCel, that is, Mg combined with polyphenols (PPs), Q, C, and R. Calcification was induced by culturing rVSMCs in a high phosphate (HP) medium. The addition of Mg and Q + C + R separately decreased the HP-induced calcium deposition by 37.55% and 42.78%, respectively. In contrast, when Mg was combined with Q, C, and R, the inhibition of calcium deposition was decreased by 92.88%, which is greater than their calculated additive inhibition (80.33%). These results demonstrate that the combination of Mg with selected PPs (Q, C, and R) is more effective than when used separately. The findings also suggest the combination has a synergistic effect in inhibiting VC, which is a risk factor for cardiovascular disease. Thus, regular consumption of these natural bioactives could have a beneficial effect in reducing the development of heart diseases.

The role of iron and the factors affecting off-color development of polyphenols.

Iron deficiency affects over two billion people worldwide (Lotfi, M.; Venkatesh Mannar, M. G.; Merx, R. J.; Naber-van den Heuvel, P. Micronutrient Fortification of Foods: Current Practices, Research,and Opportunities; Micronutrient Initiative: Ottawa, Ontario, Canada, 1996). However, fortifying foods with highly bioavailable iron is technically challenging because of off-color and off-flavor development, catalytic degradation of vitamins, and oxidation of lipids. The role of highly bioavailable iron in the off-color development of foods and beverages is not well-understood. The goal of this research was to examine the interaction of iron with simple phenolics and polyphenols. Factors that may affect off-color development, such as pH, oxygen, temperature, and reducing and chelating agents, were evaluated as a model for food products. Our results demonstrated that the iron that reacts with the simple phenolic, catechol, to develop off-color must be in the oxidized state, and the iron is reduced in the presence of catechol. Because this is an oxidation/reduction reaction, the redox potential of all of the components is critical to the color development. Ferrous iron sources with low redox potentials and ferric iron sources with high redox potentials caused off-color development with catechol. Only polyphenols that contain ortho-hydroxyl groups cause off-color development with iron. All of the factors tested affect off-color development and redox potential of the system. Low pH, low oxygen, high temperature, and the presence of reducing and chelating agents inhibited off-color development. To confirm the model, foods that contained these polyphenols were evaluated for off-color development when iron was added. The foods tested reacted similarly to the models of polyphenols with iron. Off-color development was caused by oxidation-reduction interactions between ferric iron and polyphenols that contained ortho-dihydroxyl groups. Ferrous iron needed to be oxidized to participate in off-color development. In addition, methods identified in the models to prevent off-color development were effective in most of the food products examined. Using the ferrous form of iron and maintaining it in its reduced form by lowering pH, removing oxygen, and including reducing agents, it was possible to fortify foods with highly bioavailable iron.

Multiple-micronutrient fortification technology development and evaluation: from lab to market.

At the World Summit for Children (New York, 1990), a resolution was passed to eliminate vitamin A and iodine deficiencies and significantly reduce iron-deficiency anemia by the year 2000. In responding to this urgent call, we developed a unique multiple-micronutrient fortification delivery system called "GrowthPlus/CreciPlus." Using this technology, a fortified powder fruit drink has been formulated and extensively evaluated. One serving of the product delivers the following US recommended dietary allowances: 20-30% of iron; 10-35% of vitamin A; 25-35% of iodine; 100-120% of vitamin C; 25-35% of zinc; 15-35% of folate; and 10-50% of vitamins E, B2, B6, and B12. This was accomplished through (a) identifying and selecting the right fortificants, and (b) understanding their chemical and physical properties that contribute to multiple problems (product acceptability, stability, and bioavailability). Data from a home-use test showed fortification with the "Multiple-Fortification Technology" has no effect on the appearance and taste of the eventually consumed powder fruit drink. One-year stability studies demonstrated that iodine and the vitamins have adequate stability. Bioavailability evaluation by using double-isotope labeling technique showed that the iron from the fortified powder drink has excellent bioavailability (23.4% +/- 6.7). In conclusion, a powder fruit drink has been clinically demonstrated to deliver multiple micronutrients, which include adequate levels of bioavailable iron, vitamin A, iodine, zinc, vitamin C, and B vitamins, without compromising taste, appearance, and bioavailability. The critical limiting step in the micronutrient fortification program is the production and distribution of the multiple-micronutrient-fortified product. The fortified powder drink was marketed in Venezuela under the brand name NutriStar.

Efficacy trials of a micronutrient dietary supplement in schoolchildren and pregnant women in Tanzania.

Traditionally, the main strategies used to control micronutrient deficiencies have been food diversification, consumption of medicinal supplements, and food fortification. In Tanzania, we conducted efficacy trials using a dietary supplement as a fourth approach. These were randomized, double-blind, placebo-controlled efficacy trials conducted separately first in children and later in pregnant women. The dietary supplement was a powder used to prepare an orange-flavored beverage. In the school trial, children consumed 25 g per school day attended. In the pregnancy trial, women consumed the contents of two 25-g sachets per day with meals. This dietary supplement, unlike most medicinal supplements, provided 11 micronutrients, including iron and vitamin A, in physiologic amounts. In both trials we compared changes in subjects consuming either the fortified or the nonfortified supplement. Measures of iron and vitamin A status were similar in the groups at the baseline examination, but significantly different at follow-up, always in favor of the fortified groups. Children receiving the fortified supplement had significantly improved anthropometric measures when compared with controls. At four weeks postpartum, the breast milk of a supplemented group of women had significantly higher mean retinol content than did the milk of mothers consuming the nonfortified supplement. The advantages of using a fortified dietary supplement, compared with other approaches, include its ability to control several micronutrient deficiencies simultaneously; the use of physiologic amounts of nutrients, rather than megadoses that require medical supervision; and the likelihood of better compliance than with the use of pills because subjects liked the beverage used in these trials.

Effect of a multiple-micronutrient-fortified fruit powder beverage on the nutrition status, physical fitness, and cognitive performance of schoolchildren in the Philippines.

This study aimed to determine the effect of a multiple-micronutrient-fortified beverage on the micronutrient status, physical fitness, and cognitive performance of schoolchildren. The study was a randomized, double-blind, placebo-controlled trial of schoolchildren assigned to receive either the fortified or nonfortified beverage with or without anthelmintic therapy. Data on hemoglobin level, urinary iodine excretion (UIE) level, physical fitness, and cognitive performance were collected at baseline and at 16 weeks post-intervention. The fortified beverage significantly improved iron status among the subjects that had hemoglobin levels < 11 g/dl at baseline. The proportion of children who remained moderately to severely anemic was significantly lower among those given the fortified beverage. In the groups that received the fortified product, the median UIE level increased, whereas among those who received the placebo beverage, the median UIE level was reduced significantly. Iron- and/or iodine-deficient subjects who received the fortified beverage showed significant improvements in fitness (post-exercise reduction of heart rate) and cognitive performance (nonverbal mental ability score). The study showed that consumption of a multiple-micronutrient-fortified beverage for 16 weeks had significant effects on iron status, iodine status, physical fitness, and cognitive performance among iron- and/or iodine-deficient Filipino schoolchildren. Anthelmintic therapy improved iron status of anemic children and iodine status of the iron-adequate children at baseline but it had no effect on physical fitness and cognitive performance. The results from the clinical study showed that a multiple-micronutrient-fortified beverage could play an important role in preventing and controlling micronutrient deficiencies.

A multiple-micronutrient-fortified beverage affects hemoglobin, iron, and vitamin A status and growth in adolescent girls in rural Bangladesh.

Adolescent girls have high nutrient needs and are susceptible to micronutrient deficiencies. The objective of this study was to test the effect of a multiple-micronutrient-fortified beverage on hemoglobin (Hb) concentrations, micronutrient status, and growth among adolescent girls in rural Bangladesh. A total of 1125 girls (Hb > or = 70 g/L) enrolled in a randomized, double-blind, placebo-controlled trial and were allocated to either a fortified or nonfortified beverage of similar taste and appearance. The beverage was provided at schools 6 d/wk for 12 mo. Concentrations of Hb and serum ferritin (sFt), retinol, zinc, and C-reactive protein were measured in venous blood samples at baseline, 6 mo, and 12 mo. In addition, weight, height, and mid-upper arm circumference (MUAC) measurements were taken. The fortified beverage increased the Hb and sFt and retinol concentrations at 6 mo (P < 0.01). Adolescent girls in the nonfortified beverage group were more likely to suffer from anemia (Hb <120 g/L), iron deficiency (sFt <12 microg/L), and low serum retinol concentrations (serum retinol <0.70 micromol/L) (OR = 2.04, 5.38, and 5.47, respectively; P < 0.01). The fortified beverage group had greater increases in weight, MUAC, and BMI over 6 mo (P < 0.01). Consuming the beverage for an additional 6 mo did not further improve the Hb concentration, but the sFt level continued to increase (P = 0.01). The use of multiple-micronutrient-fortified beverage can contribute to the reduction of anemia and improvement of micronutrient status and growth in adolescent girls in rural Bangladesh.

Iron fortification technology development: new approaches.

The objective of our fortification technology development has been to deliver meaningful levels of bioavailable iron via commonly consumed foods and beverages without compromising taste, appearance, and stability. However, fortification of foods is accompanied with unsolved problems such as unacceptable taste, color, stability, and bioavailability. To solve these problems, we developed a fortification technology that prevents the iron-mediated undesirable taste and appearance of the final product while preserving stability and bioavailability. Iron was stabilized by applying principles of colloid chemistry (encapsulation), chelation, and electrochemical chemistry (redox modulation). Results from color and sensory evaluations showed that formulation of products using the new fortification technology known as "GrowthPlus" eliminated detrimental effects on taste, appearance, and product stability. Bioavailability evaluation using animal models and human subjects showed the GrowthPlus technology does not interfere with the bioavailability of iron from either ferrous bis-glycinate or ferrous fumarate. Multiple intervention trials showed that repeated consumption of the redox stabilized iron in the form of a powdered fruit beverage increased iron status indicators (hemoglobin and ferritin) and reduced iron deficiency anemia significantly in school children, adolescent girls, and pregnant women.

Eradication of iron deficiency anemia through food fortification: the role of the private sector.

Delivering iron fortified foods that provide meaningful levels of bioavailable iron without altering the accepted appearance and taste of the product presents multiple challenges. Issues relating to food technology, product formulation, acceptance and efficacy evaluation, marketing and quality control must all be addressed. Procter & Gamble Company has developed a unique technology that stabilizes iron in an aqueous system. Utilizing this technology, a fortified powder drink has been developed that is easy to distribute, store and use and that delivers 20-30% of the U. S. RDA for iron, as well as significant amounts of vitamin A, iodine, zinc and vitamin C in a single serving. Acceptance, bioavailability and effectiveness trials have all produced positive results. This type of fortified product can contribute to alleviating iron deficiency but requires scaling up, packaging, quality control and distribution through normal trade channels and public institutions to have a sustainable impact. To be effective, a well-planned communications campaign should also accompany any major iron fortification program. Eradication of iron deficiency anemia can be done but requires a holistic approach that addresses multiple barriers and leverages the untapped expertise and strength of the alliance between public and private sectors.

A micronutrient-fortified beverage prevents iron deficiency, reduces anemia and improves the hemoglobin concentration of pregnant Tanzanian women.

Maternal malnutrition continues to be a major contributor to adverse reproductive outcomes in developing countries, despite longstanding efforts to fortify foods or to distribute medicinal supplements to pregnant women. The objective of this study was to test the effect of a micronutrient-fortified beverage containing 11 micronutrients (iron, iodine, zinc, vitamin A, vitamin C, niacin, riboflavin, folate, vitamin B-12, vitamin B-6 and vitamin E) on the hemoglobin, iron and vitamin A status of pregnant women in Tanzania. A group of 259 pregnant women with gestational ages of 8 to 34 wk were enrolled in a randomized double-blind controlled trial in which study women received 8 wk of supplementation. Hemoglobin, ferritin and dried blood spot retinol were measured at baseline and at the end of the supplementation period. The supplement resulted in a 4.16 g/L increase in hemoglobin concentration and a 3 micro g/L increase in ferritin and reduced the risk of anemia and iron deficiency anemia by 51 and 56%, respectively. The risk of iron deficiency was reduced by 70% among those who had iron deficiency at baseline and by 92% among those who had adequate stores. The micronutrient-fortified beverage may be a useful and convenient preventative measure, one that could help improve the nutritional status of women both before and during pregnancy and thereby help avoid some of the potential maternal and fetal consequences of micronutrient deficiencies.

Micronutrient dietary supplements--a new fourth approach

Currently the three main widely used strategies to control micronutrient deficiencies are food diversification, fortification, and consumption of medicinal supplements. In Tanzania a fourth strategy has been evaluated in school children, and is to be studied in pregnant and lactating women. The dietary supplement comes in the form of a powder used to prepare a fruit flavored drink. Children consumed for six months 25 grams per school day attended, the powder being added to 200 ml of water. The dietary supplement provides between 40 and 100 percent of the RDA of 10 micronutrients, which includes iron, vitamin A and iodine. Unlike medicinal supplements it provides the multiple vitamins and minerals in physiologic, not megadoses. In a well conducted randomized double blind placebo controlled trial, a dietary supplement in the form of a fortified powder fruit drink produced statistically significant differences not only in vitamin A and iron status, but also in the growth of young school age children.