The Chilean flour folic acid fortification program reduces serum homocysteine levels and masks vitamin B-12 deficiency in elderly people

Hyperhomocysteinemia is considered a risk factor for cardiovascular disease and is prevalent in the elderly. Supplementation with folic acid, vitamin B-6 and B-12 lowers homocysteine levels. In January 2000, the Chilean government initiated a flour folic acid fortification program to decrease the occurrence of neural tube defects. The aim of this study was to evaluate the effect of this program on serum homocysteine and folate levels in elderly subjects after 6 mo. A total of 108 elderly people were studied. We measured serum folate, homocysteine and vitamin B-12 levels before the fortification started and 6 mo later. At baseline, folate deficiency (<6.8 nmol/L) was present in 1.8%, vitamin B-12 deficiency (<165 pmol/L) in 27.6% and hyperhomocysteinemia (>14 micromol/L) in 31% of the sample. Six months later, serum folate levels increased from 16.2 +/- 6.2 to 32.7 +/- 7.1 nmol/L (P < 0.001), homocysteine levels decreased from 12.95 +/- 3.7 to 11.43 +/- 3.6 micromol/L (P < 0.001) and vitamin B-12 levels were unchanged. Flour fortification with folic acid had a moderate lowering effect on homocysteine levels. Given that vitamin B-12 deficiency was more common than folate deficiency, it may be more appropriate to add vitamin B-12 to food, at least in foods for this age group.     

Development of a model for optimal food fortification: vitamin D among adults in Finland

Background Average vitamin D intake is low in Finland. Even though almost all retail milk and margarine are fortified with vitamin D, the vitamin D intake is inadequate for a significant proportion of the population. Consequently, expanded food fortification with vitamin D would be motivated. However, there is a risk of unacceptably high intakes due to the rather narrow range of the adequate and safe intake. Therefore, a safe and efficient food fortification practice should be found for vitamin D. Aim of the study To develop a model for optimal food fortification and apply it to vitamin D. Method The FINDIET 2002 Study (48-h recall and data on supplement use (n = 2007), and 3 + 3 days’ food records, n = 247) was used as the test data. The proportion of the population whose vitamin D intake is between the recommended intake (RI) and the upper tolerable intake level (UL) was plotted against the fortification level per energy for selected foods. The fortification level that maximized the proportion of the population falling between RI and UL was considered the optimal fortification level. Results If only milk, butter milk, yoghurt and margarine were fortified, it would be impossible to find a fortification level by which the intake of the whole population would lie within the RI-UL range. However, if all potentially fortifiable foods were fortified with vitamin D at level 1.2–1.5 μg/100 kcal, the intake of the whole adult population would be between the currently recommended intake of 7.5 μg/d and the current tolerable upper intake level of 50 μg/day (model 1). If the RI was set to 40 μg/day and UL to 250 μg/day, the optimal fortification level would be 9.2 μg/100 kcal in the scenario where all potentially fortifiable foods were fortified (model 2). Also in this model the whole population would fall between the RI-UL range. Conclusions Our model of adding a specific level of vitamin D/100 kcal to all potentially fortifiable foods (1.2–1.5 μg/100 kcal in model 1 and 9.2 μg/100 kcal in model 2) seems to be an efficient and safe food fortification practise.     

Folic acid: are current fortification levels adequate?

OBJECTIVE: Beginning on January 1, 1998, all cereal and grain products in the United States were fortified with folic acid to reduce the occurrence of the very common congenital malformations known as neural-tube defects. Three years have passed since the fortification program began, and it is time to evaluate whether the current fortification levels have met their intended objective. METHODS: We offer an overview of folate and its potential role in the etiology of neural-tube defects, review some of the highlights of the deliberations that led to the decision by the Food and Drug Administration to fortify the food supply, and offer a perspective on how to measure whether current fortification levels are adequate. RESULTS: There is no national system in the United States that monitors neural-tube and other birth defects over time, and no postmarketing surveillance was mandated to monitor the safety of the fortification program. Therefore, we must evaluate the program in other ways. Blood biomarkers of folate status such as the levels of folate in red blood cells and homocysteine in plasma provided the best evidence of the effectiveness of the folic-acid-fortification program because of their relatively high sensitivities in relation to their specificities as markers of folate status. In addition, these biomarkers might provide information about the risks of other diseases related to folate status such as vascular disease. CONCLUSION: Federal agencies should coordinate efforts to gather and evaluate markers of folate status at the population level. These measures can be used to evaluate the safety and efficacy of folic-acid fortification and whether changes are warranted in fortification levels.     

Calcium,magnesium, phosphorus and vitamin D fortification of complementary foods

Provision of the bone minerals and vitamin D as fortificants in food or as dietary supplements designed for older infants and toddlers in Latin America is likely to be beneficial and safe. Currently available data are inadequate to establish the precise amounts of these nutrients that would be required for such a supplement. These amounts would vary according to the local base diet. However, reasonable estimates can be made on the basis of current dietary recommendations as well as existing data on bioavailability and customary intake. The strongest case can be made for calcium and vitamin D supplementation. Because excessive dietary calcium can reduce zinc absorption as a result of interactive effects within the intestine, an appropriate ratio of calcium to zinc should be used, even if this means adding zinc as a fortificant or supplement. Magnesium supplementation may be appropriate in some circumstances but it cannot be routinely advocated at present. It is unlikely that phosphorus supplementation is needed for most population groups because of the relatively high usual dietary phosphorus intakes, primarily from phosphate salts added to carbonated beverages and as food preservatives.     

Perspectives on obesity and sweeteners, folic acid fortification and vitamin D requirements

This review summarizes three controversial areas of clinical practice that were discussed in many articles that appeared in the American Journal of Clinical Nutrition during the author's tenure as editor in chief. Controversy 1-obesity and high-fructose corn syrup. The increased frequency of obesity in the US is paralleled by increasing annual consumption of high-fructose corn syrup, an extracted sweetener that is routinely added to soft drinks and to many processed foods in the US diet. Metabolic studies implicate increased fructose consumption in increased body fat and obesity and with increased circulating triglyceride levels and hypercholesterolaemia in children. Controversy 2-folic acid fortification and supplements. Together with widespread use of supplemental multivitamins, fortification of the US diet with folic acid has resulted in high serum folate levels in much of the population, which may be associated with increased risk of cognitive decline in ageing people with low vitamin B12 status, decreased natural killer T-cell immune function and increased risk of recurrent advanced precancerous colorectal adenomas and breast cancer. Controversy 3-recommended intakes of vitamin D. Levels of serum 25(OH)D sufficient for fracture prevention are at least 75 nmol/l (30 ng/ml) but cannot be achieved by the current recommended dietary intakes in the US. A recent fracture risk prevention trial showed that the 4-year incidence of all cancers was reduced in US women who received high supplemental doses of both calcium and vitamin D.     

Food fortification and biofortification as potential strategies for prevention of vitamin D deficiency

Hypovitaminosis D (vitamin D deficiency) is widespread throughout the world. The cutaneous production of vitamin D through sunlight can be limited by several factors (e.g. skin pigmentation, sunscreen usage and, increasingly, indoor lifestyle). Thus, diet has become an important strategy to increase vitamin D intake and status {blood 25‐hydroxyvitamin D [25(OH)D]}. However, there are a limited number of foods that naturally contain vitamin D, and concentrations can vary significantly between and within species. The need for vitamin D‐fortified foods (including via direct fortification and biofortification) to support the adequacy of vitamin D status is a corollary of several limitations to synthesise vitamin D from sunlight. Ergocalciferol (vitamin D₂) and cholecalciferol (vitamin D₃) can be found in some mushrooms and animal‐derived foods, respectively. Evidence has shown vitamin D₃ is more effective than vitamin D₂ at raising 25(OH)D blood concentrations. The vitamin D metabolite, 25(OH)D_3, is present in animal‐derived foods (e.g. meat, eggs and fish), and several intervention trials have shown 25(OH)D₃ to be more effective at raising blood 25(OH)D concentrations than vitamin D₃. In addition, 25(OH)D₃ supplements may prove to be preferable to vitamin D₃ for patients with certain clinical conditions. However, there is limited evidence on the effects of 25(OH)D₃‐fortified foods on human vitamin D status and health, both in the general population and patients with certain conditions, and long‐term randomised controlled trials are needed in this area.     

Zinc and copper: proposed fortification levels and recommended zinc compounds

Micronutrient fortification of foods is now a highly relevant tool worldwide for overcoming micronutrient deficiency. Recent data show that subclinical zinc deficiency is widespread; in Mexico a national survey showed that 25% of children less than age 11 y had plasma zinc concentrations below 10.0 micromol/L (65 microg/dL). Copper deficiency in populations is unknown but copper supplementation is recommended to accompany zinc supplementation. Of the foods available for fortification, staple cereals are very good candidates for reducing micronutrient deficiencies. Because of its higher stability and lower cost, we recommend fortification of cereal flours with zinc oxide, which is absorbed as well as the less stable and more expensive forms of zinc. Depending on the amount of the food that is expected to be eaten, zinc fortification of staple foods could be 20-50 mg/kg of flour. For copper fortification the safer compound is copper gluconate. Copper sulfate is significantly less expensive, but an evaluation of potential physicochemical reactions that affect the final food product is recommended. The suggested amount of copper added to staple foods is 1.2-3.0 mg/kg of flour. For food supplements designed as part of supplementation programs to reduce micronutrient deficiency in children less than age 3 y, a dose of the final product (usually approximately 40-50 g) should contain approximately 4-5 mg of zinc and approximately 0.2-0.4 mg of copper depending on the habitual diet, magnitude of deficiencies and period of supplementation.     

Triple fortification of salt with microcapsules of iodine, iron, and vitamin A

BACKGROUND: In many developing countries, children are at high risk of goiter, vitamin A deficiency, and iron deficiency anemia. OBJECTIVE: We aimed to develop a stable, efficacious salt fortified with iodine, iron, and vitamin A. DESIGN: A novel spray-cooling technique was used with hydrogenated palm oil to package potassium iodate, micronized ferric pyrophosphate, and retinyl palmitate into microcapsules (mean particle size: 100 mum). We used the microcapsules to create triple-fortified salt (TFS) with 30 mug I, 2 mg Fe, and 60 mug vitamin A/g salt. After storage trials, we compared the efficacy of TFS with that of iodized salt in a 10-mo, randomized, double-blind trial in goitrous schoolchildren (n = 157) who had a high prevalence of vitamin A deficiency and iron deficiency anemia. RESULTS: After storage for 6 mo, losses of iodine and vitamin A from the TFS were approximately 12-15%, and color was stable. In the TFS group, mean hemoglobin increased by 15 g/L at 10 mo (P < 0.01), iron status indexes and body iron stores improved significantly (P < 0.05), and mean serum retinol, retinol-binding protein, and the ratio of retinol-binding protein to prealbumin increased significantly (P < 0.01). At 10 mo, prevalences of vitamin A deficiency and iron deficiency anemia were significantly lower in the TFS group than in the iodized salt group (P < 0.001). CONCLUSION: Newly developed microcapsules containing iodine, iron, and vitamin A are highly stable when added to local African salt. TFS was efficacious in reducing the prevalence of iron, iodine, and vitamin A deficiencies in school-age children.     

Strategies to improve vitamin D status in northern European children: exploring the merits of vitamin D fortification and supplementation

Adequacy of vitamin D in children in Europe has been the focus of a number of investigations. The results of measuring serum levels of 25-hydroxyvitamin D show high prevalence of vitamin D deficiency during the winter with lower prevalence during the summer. National policies on food fortification or individual supplementation with vitamin D have been recently revisited by the individual countries and the European Union as a whole. Optiford is a project managed by a coalition of scientists formed to optimize vitamin D fortification in the northern European Countries, was given the task to decide if food fortification with vitamin D is feasible and to provide a scientific basis for setting the vitamin D fortification level in Europe. This article presents the results of these investigations to date, with particular attention to potential corrective strategies to allow children and adolescents living in countries at high latitudes to maintain healthy circulating 25-hydroxyvitamin D levels year around, even in the absence of adequate sun exposure during a significant part of the year.     

An updated systematic review and meta-analysis of the efficacy of vitamin D food fortification

Food fortification is a potentially effective public health strategy to increase vitamin D intakes and circulating 25-hydroxyvitamin D [25(OH)D] concentrations. We updated a previous systematic review to evaluate current evidence from randomized controlled intervention studies in community-dwelling adults of the effect of fortified foods on 25(OH)D concentrations. Ovid MEDLINE, PubMed, CINAHL, Embase, and Cochrane Central Register of Controlled Trials were searched for randomized controlled intervention studies with vitamin D-fortified foods in free-living adults and data on circulating 25(OH)D. Two reviewers independently screened 441 papers for eligibility and extracted the relevant data. A meta-analysis of the absolute mean change in circulating 25(OH)D concentrations was conducted using a random effects model. Sixteen studies from 15 publications were included, of which 14 showed a significant effect of fortified foods on 25(OH)D concentrations. Heterogeneity was high (P = <0.0001, I(2) = 89%) and was partly explained by dose, latitude (range, 3-60°), and baseline 25(OH)D (range, 24.0-83.6 nmol/L). When combined in a random effects analysis (n = 1513; 767 treated, 746 controls), a mean individual intake of ~11 μg/d (440 IU/d) from fortified foods (range, 3-25 μg/d) increased 25(OH)D by 19.4 nmol/L (95% CI: 13.9, 24.9), corresponding to a 1.2 nmol/L (95% CI: 0.72, 1.68) increase in 25(OH)D for each 1 μg ingested. Vitamin D food fortification increases circulating 25(OH)D concentrations in community-dwelling adults. Safe and effective food-based strategies could increase 25(OH)D across the population distribution and prevent vitamin D deficiency with potential benefit for public health.     

Iron and ascorbic Acid: proposed fortification levels and recommended iron compounds

An adequate supply of dietary iron during the 1st 24 mo of life is essential for preventing iron deficiency with its attendant negative effects on mental, motor and emotional development as well as later cognitive performance. Iron reserves and the small amount of highly bioavailable iron in human milk are adequate to satisfy the iron requirements of breast-fed infants of adequate birth weight for the 1st 6 mo of life. Thereafter, complementary foods, iron supplements or both are needed to meet this requirement. Complementary foods should not displace the consumption of human milk. The quantities eaten, particularly by younger infants, may therefore be quite small. As a consequence it is essential that the iron be supplied in a highly bioavailable form. This can be achieved by fortifying complementary foods with ferrous sulfate and ascorbic acid provided that the ascorbic acid is not lost during storage or meal preparation. Suggested fortification levels for ferrous sulfate and ascorbic acid for some types of complementary foods are given. The use of ferrous fumarate or an elemental iron powder instead of ferrous sulfate has not been evaluated adequately. There is a need to develop alternative strategies for improving iron bioavailability in complementary foods because it may not be possible to preserve ascorbic acid activity in many of them.     

B vitamins: proposed fortification levels for complementary foods for young children

The B vitamins, except for folate, can be classified as group I nutrients during lactation. Nutrients in this category share the following characteristics: low maternal intake or stores during lactation reduce the concentration in human milk, and infants' stores are readily depleted. For some of these nutrients, the infants' stores at birth may be depleted by maternal deficiency during pregnancy. The prevalence of some B vitamin deficiencies, especially deficiencies of riboflavin and vitamin B-12, is probably much higher than is usually assumed. Taken together, these considerations emphasize the importance of supplying adequate amounts of B vitamins to infants and young children. Recommendations are made here on the amounts and densities of B vitamins that should be present in fortified complementary foods fed to children aged 6-24 mo. The values are based on the difference between recommended daily intakes and the amount that the child will receive from maternal milk using estimates reported in the literature. There are few concerns about the potential toxicity of any of these vitamins at the levels likely to be added to complementary foods. If there are losses during food preparation or concentrations of the vitamins are low in human milk, the estimates provided may need to be increased. The adequacy of these recommendations must be evaluated thoroughly.     

Effect of a voluntary food fortification policy on folate, related B vitamin status, and homocysteine in healthy adults

BACKGROUND: Mandatory folic acid fortification of food is effective in reducing neural tube defects and may even reduce stroke-related mortality, but it remains controversial because of concerns about potential adverse effects. Thus, it is virtually nonexistent in Europe, albeit many countries allow food fortification on a voluntary basis. OBJECTIVE: The objective of the study was to examine the effect of a voluntary but liberal food fortification policy on dietary intake and biomarker status of folate and other homocysteine-related B vitamins in a healthy population. DESIGN: The study was a cross-sectional study. From a convenience sample of 662 adults in Northern Ireland, those who provided a fasting blood sample and dietary intake data were examined (n = 441, aged 18-92 y). Intakes of both natural food folate and folic acid from fortified foods were estimated; we used the latter to categorize participants by fortified food intake. RESULTS: Fortified foods were associated with significantly higher dietary intakes and biomarker status of folate, vitamin B-12, vitamin B-6, and riboflavin than were unfortified foods. There was no difference in natural food folate intake (range: 179-197 microg/d) between the fortified food categories. Red blood cell folate concentrations were 387 nmol/L higher and plasma total homocysteine concentrations were 2 micromol/L lower in the group with the highest fortified food intake (median intake: 208 microg/d folic acid) than in the nonconsumers of fortified foods (0 microg/d folic acid). CONCLUSIONS: These results show that voluntary food fortification is associated with a substantial increase in dietary intake and biomarker status of folate and metabolically related B vitamins with potential beneficial effects on health. However, those who do not consume fortified foods regularly may have insufficient B vitamin status to achieve the known and potential health benefits.     

Planning, implementation, and evaluation of a fortification program. Control of vitamin A deficiency in the Philippines.

In a three-year pilot project in the Philippines, the magnitude of vitamin A deficiency and its clinical manifestation (xerophthalmia) was determined, and three alternate programs for eliminating and preventing it in various ecologic zones were designed and implemented concurrently in separate areas in each ecologic zone. Results were evaluated, and costs and benefits of each program were determined. The results of the fortification program are reported. Monosodium glutamate (MSG) was selected as the ideal carrier was fortified at a level which provided 15,000 I.U. retinol palmitate to the average family each day. Significant increases in serum A, especially for children with more deficient vitamin A status, resulted. The program's economic benefits significantly outweighted the costs, and the MSG fortification program has been expanded to several additional pilot provinces in the Philippines.     

Food patterns,flour fortification,and intakes of calcium and vitamin D: a longitudinal study of Danish adults

STUDY OBJECTIVE: Deficiencies in calcium and vitamin D intakes are involved in the aetiology of osteoporosis, and health authorities recommend that the population consume a diet providing sufficient calcium and vitamin D. However, in 1987 the Danish Government withdrew a mandatory fortification of flour with calcium. This study examines intakes of calcium and vitamin D over time, in relation to food patterns, recommendations, and legislation. DESIGN: Food and nutrient intakes were measured by a short food frequency questionnaire (FFQ) and a thorough diet history interview, in 1987/88, and again six years later. SETTING: Copenhagen County, Denmark. PARTICIPANTS: 329 men and women, aged 35-65 years at first examination in 1987/88. RESULTS: At both examinations the non-enriched median intakes of calcium in men as well as women were above the recommended 600 mg/day. However, apparently the fortification of flour supplied up to 30% of the total calcium intake, and without the mandatory fortification, the percentage of adults with intakes below this recommendation increased from 6% to 22%. This group of subjects consumed cheese, milk, and oatmeal less often than those who had calcium intakes over 600 mg/day. During the study period the median intakes of vitamin D, which were well below the recommended 5 micrograms/day, did not change significantly. Associations between foods and vitamin D intakes were, in general, weak and insignificant, except for a positive association with fish intake. CONCLUSIONS: Data on calcium intakes suggest that the decision to stop the mandatory fortification of flour with calcium may have been premature. The short FFQ may be used for a rough classification of people in relation to their calcium intake, while this method seems insufficient for ranking vitamin D intakes.       

Factors affecting iron absorption and the role of fortification in enhancing iron levels

Iron is an important micronutrient required for a number of biological processes including oxygen transport, cellular respiration, the synthesis of nucleic acids and the activity of key enzymes. The World Health Organization has recognised iron deficiency as the most common nutritional deficiency globally and as a major determinant of anaemia. Iron deficiency anaemia affects 40% of all children between the ages of 6 and 59 months, 37% of mothers who are pregnant and 30% of women between the ages of 15 and 49 years worldwide. Dietary iron exists in two main forms known as haem iron and non-haem iron. Haem iron is obtained from animal sources such as meat and shows higher bioavailability than non-haem iron, which can be obtained from both plant and animal sources. Different components in food can enhance or inhibit iron absorption from the diet. Components such as meat proteins and organic acids increase iron absorption, while phytate, calcium and polyphenols reduce iron absorption. Iron levels in the body are tightly regulated since both iron overload and iron deficiency can exert harmful effects on human health. Iron is stored mainly as haemoglobin and as iron bound to proteins such as ferritin and hemosiderin. Iron deficiency affects individuals at increased risk due to factors such as age, pregnancy, menstruation and various diseases. Different solutions for iron deficiency are applied at individual and community levels. Iron supplements and intravenous iron can be used to treat individuals with iron deficiency, while various types of iron-fortified foods and biofortified crops can be employed for larger communities. Foods such as rice, flour and biscuits have been used to prepare fortified iron products. However, it is important to ensure the fortification process does not exert significant negative effects on organoleptic properties and the shelf life of the food product.     

Lipid peroxidation in relation to vitamin C and vitamin E levels

Oxidative stress plays an important contributory role in the pathogenesis of age-related chronic diseases. Increased lipid peroxidation process is caused by an enhanced free radical formation together with a higher supply of substrates and by an insufficient defense by antioxidants as well. Levels of malondialdehyde to content of lipid peroxidation substrates (polyunsaturated fatty acids), promoters (homocysteine--hydroxyl radical producer) and inhibitors (essential vitamins C and E) were estimated in a group (n=92) of subjective healthy adults randomly selected from general population. The relationship of malondialdehyde levels to values of peroxidisability index of fatty acids as well as to levels of homocysteine is significantly positive linear A significant inverse linear correlation between malondialdehyde levels and natural antioxidant levels (vitamin C, vitamin E) was recorded. Lipid peroxidation products (conjugated dienes of fatty acids--initial, malondialdehyde--secondary) are significantly increased in groups of subjects with deficient levels of vitamin C (below the limit from antioxidative point of view), vitamin E and both vitamins, if compared to group with normal vitamin levels (over limit in accordance with antioxidative criterion). The results document that the deficiency in two key antioxidants for lipid peroxidation inhibition means the insufficient defense against free radicals and the increased lipid peroxidation.