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Unmetabolized folic acid in serum: acute studies in subjects consuming fortified food and supplements.

Periconceptual consumption of folic acid has been shown to decrease the incidence of neural tube defects. The strategy of universal fortification of staple foodstuffs with folic acid presents the possibility of life-long exposure to unmetabolized folic acid. Chief among the risks of exposure to folic acid in the circulation is that of masking the diagnosis of cobalamin deficiency in pernicious anemia and the progression of neurologic disease. Other effects are unknown. For instance, the effect of in vivo chronic exposure of adult and fetal cells to the synthetic form of the vitamin has never been investigated at the population level. This study examined the acute appearance of unmetabolized folic acid in serum in response to the consumption of some fortified foodstuffs by young and elderly volunteers. Subjects on a 5-d regimen of fortified ready-to-eat-cereal and bread in addition to their normal diet had a threshold intake of 266 micrograms folic acid per meal at which unaltered folic acid appeared in the serum. Subjects given folic acid in either isotonic saline, milk, or white bread also had a threshold > 200 micrograms. From patterns of food consumption in the United States, the implementation of flour fortification at 1.4 mg/kg is unlikely to lead to folic acid appearance in serum, assuming that consumption is spread throughout the day. Increasing this level of fortification, however, as has been advocated by some agencies, may result in the repeated appearance of folic acid in serum over many years, particularly in consumers in nontargeted populations of large amounts of fortified foods. The "safe level of intake" of 1 mg folate/d set by the US Food and Drug Administration may cause a serum folic acid effect. Furthermore, a repeated serum folic acid response is likely to be found in many women complying with the advice to take 400 micrograms folic acid/d to prevent the occurrence of neural tube defects.

Adolescent↗

Absorption of zinc from wheat products fortified with iron and either zinc sulfate or zinc oxide.

BACKGROUND: Several chemical forms of zinc have been proposed for food fortification, but information is needed on their absorption from common cereals having varied phytate content. OBJECTIVE: The goal was to measure zinc absorption from wheat products fortified with iron sulfate and either zinc sulfate or zinc oxide. DESIGN: Adult volunteers received either low-phytate bread (n = 11) or higher-phytate porridge (n = 11) once weekly on 2 or 3 occasions. The foods were fortified with 1 of the 2 zinc salts (60 mg elemental Zn/kg wheat flour) during week 1 and with the other during week 2, in random order. (65)Zn in the same chemical form as the fortificant was incorporated in each food to assess zinc absorption with the use of whole-body counting. The porridge group received an additional test meal fortified with zinc oxide during week 3, but the (65)Zn tracer was given as an oral solution of (65)ZnCl(2). RESULTS: Zinc absorption from bread (13.8%; 95% CI: 11.8%, 16.2%) was significantly (P < 0.001) greater than from porridge (6.4%; 5.5%, 7.6%), presumably because of the greater phytate content of the porridge. With control for food type, there were no significant differences in zinc absorption from meals fortified with zinc sulfate or zinc oxide (P = 0.24). When the porridge was fortified with zinc oxide and labeled with (65)ZnCl(2), absorption of the tracer (8.9%; 7.1%, 11.0%) was significantly (P = 0.007) greater than when (65)ZnO was incorporated in the porridge (5.6%; 4.5%, 6.9%). CONCLUSIONS: Either zinc oxide or zinc sulfate can be used to fortify wheat products consumed by presumably healthy persons. Isotopic tracers used to assess the absorption of mineral fortificants should have the same chemical form as the fortificant.

Adult↗

Laboratory investigation of a poisoning epidemic in Sierra Leone.

In June 1986, an epidemic of poisoning occurred in Sierra Leone, West Africa; it involved 49 persons--with 14 deaths. Our laboratory's approach and investigation of this incident is described. Using positive chemical ionization mass spectrometry and nuclear magnetic resonance spectroscopy, the toxicant was identified as parathion, a highly toxic organophosphorus pesticide. Analysis of various items supported the epidemiologic hypothesis that bread was made from contaminated flour and that the flour became contaminated with parathion during a truck shipment. Modern analytical instruments played a major role in this laboratory investigation and effected the identification of the unknown toxicant within hours of receiving the initial bread sample. Close cooperation and clear communication between the epidemiologic and laboratory teams were important in this investigation.

Bread↗

Products based on a high fiber barley genotype, but not on common barley or oats, lower postprandial glucose and insulin responses in healthy humans.

Postprandial blood glucose and insulin responses to cereal products made from common barley, oats or a barley genotype containing elevated levels of beta-glucans were evaluated in nine healthy subjects. Porridges were made from commercial Swedish whole-meal barley or oat flours, and a mixed whole-meal porridge using the high fiber barley genotype and commercial Swedish common barley (50:50). Also studied were two types of flour-based bread products composed of high fiber barley and common barley in ratios of 50:50 or 80:20, respectively. The common oat and barley porridges produced postprandial glucose and insulin responses similar to the white wheat bread reference, suggesting that the naturally occurring dietary fiber in these whole-meal flours has no impact on the glucose tolerance. In contrast, all high fiber barley products induced significantly lower responses than did the reference product, with the glycemic and insulin indices ranging from 57 to 72 or 42 to 72%, respectively. It is concluded that "lente" products of high sensory quality can be prepared from a barley genotype with an elevated content of soluble dietary fiber. The glycemic index of these products compares favorably with that of products made from common cereals, suggesting their use as a potential component of diets for patients with diabetes and hyperlipidemia, and for individuals predisposed to metabolic disease.

Adult↗

An examination of the possibility of lowering the glycemic index of oat and barley flakes by minimal processing.

Differences in glycemic responses to various starchy foods are related to differences in the rate of starch digestion and absorption. In this study, the importance of the degree of gelatinization and the product thickness for postprandial glycemic and insulinemic responses to rolled oats and barley were studied in healthy subjects (5 men and 5 women). Thick (1.0 mm) rolled oats were made from raw or preheated (roasted or steamed) kernels. In addition, thin (0.5 mm) rolled oats were made from roasted or roasted and steamed (processed under conditions simulating commercial production) oat kernels. Finally, steamed rolled barley kernels (0.5 or 1.0 mm) were prepared. All thin flakes elicited high glucose and insulin responses [glycemic index (GI), 88-118; insulinemic index (II), 84-102], not significantly different from white wheat bread (P: > 0.05). In contrast, all varieties of thick oat flakes gave significantly lower metabolic responses (GI, 70-78; II, 58-77) than the reference bread (P: < 0.05). Thick barley flakes, however, gave high glucose and insulin responses (GI, 94; II, 84), probably because the botanical structure underwent more destruction than the corresponding oat flakes. We conclude that minimal processing of oat and barley flakes had a relatively minor effect on GI features compared with the more extensive commercial processing. One exception was thick oat flakes, which in contrast to the corresponding barley flakes, had a low GI.

Adult↗

Gluten breakdown by lactobacilli and pediococci strains isolated from sourdough.

AIMS: To evaluate the growth and metabolic activity of lactobacilli and pediococci strains in a gluten base medium (GBM), formulated for a proper selection of proteolytic strains to be used in sourdough fermentation. METHODS AND RESULTS: Proteolytic activity by lactic acid bacteria (LAB) was evaluated by SDS-PAGE and by the amino acids released determined by reversed-phase high-performance liquid chromatography. Only 13 LAB (nine lactobacilli and four pediococci), among the 42 evaluated were able to utilize gluten as nitrogen source and to grow in GBM. Pediococcus pentosaceus CRL 797 showed a similar proteolytic activity to lactobacilli strains. In the majority of the cultures, basic amino acid group increased (c. 80% after 12 h incubation) mainly due to the release of ornithine, a flavour precursor of bread. Lysine, a limiting essential amino acid in wheat flour, increased by 150% in cultures of P. pentosaceus CRL 797. CONCLUSIONS: This study allows selecting P. pentosaceus CRL 797 and L. plantarum CRL 759 as potential starter culture for type III sourdough fermentation. It is shown for the first time that pediococci strains isolated from sourdough are proteolytically active on gluten. SIGNIFICANCE AND IMPACT OF THE STUDY: The physiological studies on gluten breakdown by LAB will contribute to the better selection of strains to produce breads with enhanced organoleptic characteristics.

Amino Acids↗

Purification and characterization of novel antifungal compounds from the sourdough Lactobacillus plantarum strain 21B.

Sourdough lactic acid bacteria were selected for antifungal activity by a conidial germination assay. The 10-fold-concentrated culture filtrate of Lactobacillus plantarum 21B grown in wheat flour hydrolysate almost completely inhibited Eurotium repens IBT18000, Eurotium rubrum FTDC3228, Penicillium corylophilum IBT6978, Penicillium roqueforti IBT18687, Penicillium expansum IDM/FS2, Endomyces fibuliger IBT605 and IDM3812, Aspergillus niger FTDC3227 and IDM1, Aspergillus flavus FTDC3226, Monilia sitophila IDM/FS5, and Fusarium graminearum IDM623. The nonconcentrated culture filtrate of L. plantarum 21B grown in whole wheat flour hydrolysate had similar inhibitory activity. The activity was fungicidal. Calcium propionate at 3 mg ml(-1) was not effective under the same assay conditions, while sodium benzoate caused inhibition similar to L. plantarum 21B. After extraction with ethyl acetate, preparative silica gel thin-layer chromatography, and chromatographic and spectroscopic analyses, novel antifungal compounds such as phenyllactic and 4-hydroxy-phenyllactic acids were identified in the culture filtrate of L. plantarum 21B. Phenyllactic acid was contained at the highest concentration in the bacterial culture filtrate and had the highest activity. It inhibited all the fungi tested at a concentration of 50 mg ml(-1) except for P. roqueforti IBT18687 and P. corylophilum IBT6978 (inhibitory concentration, 166 mg ml(-1)). L. plantarum 20B, which showed high antimold activity, was also selected. Preliminary studies showed that phenyllactic and 4-hydroxy-phenyllactic acids were also contained in the bacterial culture filtrate of strain 20B. Growth of A. niger FTDC3227 occurred after 2 days in breads started with Saccharomyces cerevisiae 141 alone or with S. cerevisiae and Lactobacillus brevis 1D, an unselected but acidifying lactic acid bacterium, while the onset of fungal growth was delayed for 7 days in bread started with S. cerevisiae and selected L. plantarum 21B.

Antifungal Agents↗

Antifungal activity of phenyllactic acid against molds isolated from bakery products.

Phenyllactic acid (PLA) has recently been found in cultures of Lactobacillus plantarum that show antifungal activity in sourdough breads. The fungicidal activity of PLA and growth inhibition by PLA were evaluated by using a microdilution test and 23 fungal strains belonging to 14 species of Aspergillus, Penicillium, and Fusarium that were isolated from bakery products, flours, or cereals. Less than 7.5 mg of PLA ml(-1) was required to obtain 90% growth inhibition for all strains, while fungicidal activity against 19 strains was shown by PLA at levels of < or = 10 mg ml(-1). Levels of growth inhibition of 50 to 92.4% were observed for all fungal strains after incubation for 3 days in the presence of 7.5 mg of PLA ml(-1) in buffered medium at pH 4, which is a condition more similar to those in real food systems. Under these experimental conditions PLA caused an unpredictable delaying effect that was more than 2 days long for 12 strains, including some mycotoxigenic strains of Penicillium verrucosum and Penicillium citrinum and a strain of Penicillium roqueforti (the most widespread contaminant of bakery products); a growth delay of about 2 days was observed for seven other strains. The effect of pH on the inhibitory activity of PLA and the combined effects of the major organic acids produced by lactic acid bacteria isolated from sourdough bread (PLA, lactic acid, and acetic acid) were also investigated. The ability of PLA to act as a fungicide and delay the growth of a variety of fungal contaminants provides new perspectives for possibly using this natural antimicrobial compound to control fungal contaminants and extend the shelf lives of foods and/or feedstuffs.

Antifungal Agents↗

In situ production of exopolysaccharides during Sourdough fermentation by cereal and intestinal isolates of lactic acid bacteria.

EPS formed by lactobacilli in situ during sourdough fermentation may replace hydrocolloids currently used as texturizing, antistaling, or prebiotic additives in bread production. In this study, a screening of >100 strains of cereal-associated and intestinal lactic acid bacteria was performed for the production of exopolysaccharides (EPS) from sucrose. Fifteen strains produced fructan, and four strains produced glucan. It was remarkable that formation of glucan and fructan was most frequently found in intestinal isolates and strains of the species Lactobacillus reuteri, Lactobacillus pontis, and Lactobacillus frumenti from type II sourdoughs. By the use of PCR primers derived from conserved amino acid sequences of bacterial levansucrase genes, it was shown that 6 of the 15 fructan-producing lactobacilli and none of 20 glucan producers or EPS-negative strains carried a levansucrase gene. In sourdough fermentations, it was determined whether those strains producing EPS in MRS medium modified as described by Stolz et al. (37) and containing 100 g of sucrose liter(-1) as the sole source of carbon also produce the same EPS from sucrose during sourdough fermentation in the presence of 12% sucrose. For all six EPS-producing strains evaluated in sourdough fermentations, in situ production of EPS at levels ranging from 0.5 to 2 g/kg of flour was demonstrated. Production of EPS from sucrose is a metabolic activity that is widespread among sourdough lactic acid bacteria. Thus, the use of these organisms in bread production may allow the replacement of additives.

Amino Acid Sequence↗

Thyrotoxicosis induced by iodine contamination of food--a common unrecognised condition?

The incidence of thyrotoxicosis in northern Tasmania rose significantly in 1964, two years before an epidemic of iodine-induced thyrotoxicosis was precipitated by the addition of iodate to bread to prevent goitre. Each time older patients accounted for most of the increase. The 1964 increase was probably iodine-induced as the use of iodophor disinfectants on dairy farms, which causes iodine residues in milk, began in 1963 and a fall in the prevalence of goitre in young children suggested an increase in dietary iodine at about that time. A further small increase in thyrotoxicosis in 1971 may also have been iodine-induced as it followed an extension of the use of iodophors. Dietary iodine is rising substantially in many places because of high iodine levels in milk and the use of iodine compounds in automated bread making, and this may be causing unsuspected iodine-induced thyrotoxicosis. Dietary iodine should be monitored regularly and clinicans alerted to any rise. Contamination of common foods with iodine should be more strictly controlled.

Adult↗

Dietary habits and mortality in 11,000 vegetarians and health conscious people: results of a 17 year follow up.

OBJECTIVE: To investigate the association of dietary habits with mortality in a cohort of vegetarians and other health conscious people. DESIGN: Observational study. SETTING: United Kingdom. SUBJECTS: 4336 men and 6435 women recruited through health food shops, vegetarian societies, and magazines. MAIN OUTCOME MEASURES: Mortality ratios for vegetarianism and for daily versus less than daily consumption of wholemeal bread, bran cereals, nuts or dried fruit, fresh fruit, and raw salad in relation to all cause mortality and mortality from ischaemic heart disease, cerebrovascular disease, all malignant neoplasms, lung cancer, colorectal cancer, and breast cancer. RESULTS: 2064 (19%) subjects smoked, 4627 (43%) were vegetarian, 6699 (62%) ate wholemeal bread daily, 2948 (27%) ate bran cereals daily, 4091 (38%) ate nuts or dried fruit daily, 8304 (77%) ate fresh fruit daily, and 4105 (38%) ate raw salad daily. After a mean of 16.8 years follow up there were 1343 deaths before age 80. Overall the cohort had a mortality about half that of the general population. Within the cohort, daily consumption of fresh fruit was associated with significantly reduced mortality from ischaemic heart disease (rate ratio adjusted for smoking 0.76 (95% confidence interval 0.60 to 0.97)), cerebrovascular disease (0.68 (0.47 to 0.98)), and for all causes combined (0.79 (0.70 to 0.90)). CONCLUSIONS: In this cohort of health conscious individuals, daily consumption of fresh fruit is associated with a reduced mortality from ischaemic heart disease, cerebrovascular disease, and all causes combined.

Adolescent↗

Clinical and epidemiological aspects of methylmercury poisoning.

An opportunity to study the effects of methylmercury poisoning in humans was provided by the large outbreak in Iraq in 1971-2. In adults, poisoning resulted from the ingestion of home-made bread prepared from methylmercury-treated seed grain and there was a highly significant correlation between the amount of bread ingested and blood mercury levels. Poisoning in infants resulted either from prior exposure in utero or from suckling or both. Blood mercury levels were higher in infants and children than in adults. There was no increased incidence of congenital defects. Symptoms and signs of poisoning and histopathological changes were mainly confined to the CNS. Symptoms developed, on average, 1-2 months after exposure. In children there was mental retardation with delayed onset of speech and impaired motor, sensory and autonomic function. Severely affected children were blind and deaf. In adults, the clinical picture could be classified as 1, mild (mainly of sensory symptoms) 2, moderate (sensory symptoms accompanied by cerebellar signs) and 3, severe (gross ataxia with marked visual and hearing loss which, in some cases, progressed to akinetic mutism followed by coma). Grades 1 and 2 carried a better prognosis thant grade 3. Interference with transmission at the myoneural junction was found in 14% of patients studied. There was no evidence of peripheral nerve involvement per se and sensory symptoms may be of central origin. The clinical differences between the Iraqi and Japanese outbreaks may be a result, in part at least, of the severe, prolonged and continuous exposure which occurred in the latter outbreak. Improvement was observed among the mild and moderate group. Treatment with chelating agents, thiol resin, haemodialysis and exchange transfusion lowered blood mercury concentrations but produced no convincing clinical benefit. To be effective, treatment may need to be instituted soon after exposure.

Adult↗

Human salivary sugar clearance after sugar rinses and intake of foodstuffs.

The aetiology of dental caries is in part related to the retention time of dietary carbohydrates in the oral cavity and their subsequent metabolism by the oral bacteria. Salivary clearance of fermentable carbohydrates from three different foodstuffs was examined in 5 subjects and analyses performed by high-performance anion-exchange chromatography with pulsed amperometric detection. The clearance of glucose, fructose, sucrose, maltose and sorbitol rinses was studied as well as that of chocolate bars, white bread and bananas. Of the sugar rinses studied, sucrose was removed from saliva most rapidly whilst appreciable levels of sorbitol remained even after 1 h. Clearance of residual carbohydrates from bananas and chocolate bars seemed marginally faster than in the case of bread, but sucrose levels still tended to fall more quickly than other carbohydrates studied. Surprisingly, carbohydrate residues from the three foods studied were still present in the mouth even 1 h after ingestion, which is longer than has hitherto been reported.

Bread↗

Toxicity and carcinogenicity of potassium bromate--a new renal carcinogen.

Potassium bromate (KBrO3) is an oxidizing agent that has been used as a food additive, mainly in the bread-making process. Although adverse effects are not evident in animals fed bread-based diets made from flour treated with KBrO3, the agent is carcinogenic in rats and nephrotoxic in both man and experimental animals when given orally. It has been demonstrated that KBrO3 induces renal cell tumors, mesotheliomas of the peritoneum, and follicular cell tumors of the thyroid. In addition, experiments aimed at elucidating the mode of carcinogenic action have revealed that KBrO3 is a complete carcinogen, possessing both initiating and promoting activities for rat renal tumorigenesis. However, the potential seems to be weak in mice and hamsters. In contrast to its weak mutagenic activity in microbial assays, KBrO3 showed relatively strong potential inducing chromosome aberrations both in vitro and in vivo. Glutathione and cysteine degrade KBrO3 in vitro; in turn, the KBrO3 has inhibitory effects on inducing lipid peroxidation in the rat kidney. Active oxygen radicals generated from KBrO3 were implicated in its toxic and carcinogenic effects, especially because KBrO3 produced 8-hydroxydeoxyguanosine in the rat kidney. A wide range of data from applications of various analytical methods are now available for risk assessment purposes.

Adenocarcinoma↗

Starchy foods and glycemic index.

Different starchy foods produce different glycemic responses when fed individually, and there is some evidence that this also applies in the context of the mixed meal. A major reason appears to relate to the rate at which the foods are digested and the factors influencing this. A similar ranking in terms of glycemic response to specific foods is seen independent of the carbohydrate tolerance status of the groups tested. Potentially clinically useful starchy foods producing relatively flat glycemic responses have been identified. Many of these are considered ethnic or traditional and include legumes; pasta; grains such as barley, parboiled rice, and bulgur (cracked wheat); and whole-grain breads such as pumpernickel. Specific incorporation of these foods into diets has been associated with reductions in low-density lipoprotein cholesterol and triglyceride levels in hyperlipidemia and with improved blood glucose control in insulin-dependent diabetic patients. To facilitate identification of such foods, it has been suggested that the glycemic response should be indexed to a standard (e.g., white bread) to allow comparisons to be made between the glycemic index of foods tested in different groups of subjects. The scope of application of this principle is subject to further investigation. It may be used to expand the range of possibly useful starchy foods for trial in the diets of diabetic patients.

Blood Glucose↗

Glycemic index of foods in individual subjects.

We studied 12 subjects with diabetes to determine how well the glycemic index (GI) predicted the ranking of glycemic responses of different foods in individuals. All subjects ate three mixed meals (bread, rice, or spaghetti with GIs of 100, 79, and 61, respectively) four times in a randomized complete block design. The mean glycemic response areas of the different meals ranked according to the predicted GI in every individual. The observed mean +/- SD GI values of the meals were significantly different from each other (bread 100 +/- 7, rice 75 +/- 9, spaghetti 54 +/- 9), with no significant difference in response between subjects. It is concluded that individuals share common mean GI values for different foods. Within confidence limits determined by the variability of glycemic responses, the number of repeated tests conducted, and the expected GI difference, the GI can be used to predict the ranking of the mean glycemic responses of mixed meals taken by individuals.

Adult↗

Glycemic response to wheat products: reduced response to pasta but no effect of fiber.

The blood glucose response to feeding 50-g carbohydrate portions of white and wholemeal bread and white spaghetti was studied in a group of nine diabetic subjects. Blood glucose rises after white and wholemeal bread were identical, but the response after spaghetti was markedly reduced. These results emphasize that food form rather than fiber may be important in determining the glycemic response and that pasta may be a useful source of carbohydrate in the diabetic diet.

Aged↗

Wernicke-Korsakoff syndrome in Sydney hospitals: before and after thiamine enrichment of flour.

OBJECTIVE: To estimate the incidence of Wernicke-Korsakoff syndrome (WKS) before and after the introduction of thiamine enrichment of bread flour in 1991. DESIGN: Retrospective survey of hospital records. Patient records with the diagnostic codes for Wernicke's encephalopathy (WE) or Korsakoff's psychosis (KP) were reviewed and details of acceptable cases were entered onto a data form. SETTING: All 17 major public general hospitals in the Sydney area (New South Wales), between 1978 and 1993. OUTCOME MEASURES: Numbers of confirmed or probable diagnoses of WE, KP or WKS and associated deaths, patient demographic and social characteristics and alcohol intake. RESULTS: 1,267 patients with WKS were found, with 1,012 acute cases. Although numbers of acute cases may have started to fall before 1991, numbers for the last two years were the lowest of all the 16 years (P = 0.004). Cases of KP outnumbered those of WE by about 3:1 and men outnumbered women 4:1. The peak age was 60-64 years (17%) and beer was the most commonly cited alcoholic drink (71%). The red-cell transketolase test was seldom used for diagnosis (3% of acute cases). CONCLUSIONS: The lower number of "acute" cases in 1992 and 1993 is consistent with a preventive effect of mandatory enrichment of bread with thiamine, but is not conclusive evidence. Longer follow-up of Sydney hospitals, results of postmortem examinations and follow-up in other areas of Australia are required.

Adult↗