Yukio Kadooka

Megmilk Snow Brand Group., Edo, Tōkyō, Japan

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Publications (17)39.44 Total impact

  • Ken Ukibe · Masaya Miyoshi · Yukio Kadooka
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    ABSTRACT: Administration of Lactobacillus gasseri SBT2055 (LG2055) has been shown to prevent body weight gain and it also down-regulates the expression of the Ccl2 gene in adipose tissue in diet-induced obese mice. The CC chemokine ligand 2 has a crucial role in macrophage infiltration into adipose tissue, which is known to exacerbate inflammation. However, it is not yet known how LG2055 affects the invasion of macrophages into adipose tissue. C57BL/6J male mice were fed a normal-fat diet (10 % energy fat), high-fat diet (HFD; 45 % energy fat), or HFD containing LG2055 for 12 weeks. After the feeding period, gene expression and macrophage population in adipose tissue were analysed by real-time PCR and flow cytometry, respectively. Body weight and abdominal fat weight were not altered by feeding LG2055. Flow cytometry analysis revealed that the population of macrophages in adipose tissue was significantly reduced by feeding LG2055 compared with HFD only. Furthermore, the ratio of classically activated inflammatory macrophages (M1 macrophages) to total macrophages was significantly decreased in the LG2055-fed group. The expressions of Ccl2, Ccr2 and Lep were down-regulated and that of Il6, Tnf and Nos2 tended to be down-regulated in adipose tissue by feeding LG2055. In addition, fasting glucose levels were significantly decreased in the LG2055-fed group. These data suggest that administration of LG2055 might attenuate inflammation, which is caused by the intake of an HFD, through the inhibition of macrophage invasion into adipose tissue.
    The British journal of nutrition 08/2015; DOI:10.1017/S0007114515002627 · 3.34 Impact Factor
  • Akihiro Ogawa · Yukio Kadooka · Ken Kato · Bungo Shirouchi · Masao Sato
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    Akihiro Ogawa · Yukio Kadooka · Ken Kato · Bungo Shirouchi · Masao Sato
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    Akihiro Ogawa · Yukio Kadooka · Ken Kato · Bungo Shirouchi · Masao Sato
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    ABSTRACT: Background Lactobacillus gasseri SBT2055 (LG2055) has been shown to prevent abdominal adiposity, and suppression of lipid absorption is considered a possible mechanism, detail of which, however, are poorly understood. In the present study, we evaluated the effects of LG2055 on fat hydrolysis by determining pancreatic lipase activity and fat emulsion properties in vitro. We also examined whether LG2055 influences fecal fat excretion in humans. Methods Pancreatic lipase activity was investigated in vitro using an artificially prepared fat emulsion and 4-methylumbelliferyl oleate (4-MUO) as substrates. The concentrations of free fatty acids and 4-methylumbelliferone were quantified. Fat emulsion droplet size was measured using a particle size analyzer. The clinical study was performed as a double-blind, randomized, placebo-controlled trial. Subjects consumed 100 g of fermented milk (FM)/d, either with or without LG2055 supplementation, for seven days. Fecal samples were collected during three-day pre-observational and FM intake periods and fecal fat levels were determined. Results LG2055 dose-dependently suppressed lipase activity in the fat emulsion assay but not in the 4-MUO assay. LG2055 dose-dependently increased fat emulsion droplet size. The effects of LG2055 on lipase activity and fat emulsion properties were increased compared with four other tested strains (Lactobacillus gasseri SBT0317, Lactobacillus gasseri JCM1131T, Lactobacillus. delbrueckii subsp. bulgaricus JCM1002T and Streptococcus thermophilus ATCC19258T). In our clinical study, fecal fat level after FM intake was significantly increased compared with that observed before FM intake in the LG2055-containing active FM group but not the control FM group lacking LG2055. Conclusions LG2055 increased fat emulsion droplet size, resulting in the suppression of lipase-mediated fat hydrolysis. The influence of LG2055 on the physicochemical properties of fat emulsion provides a mechanism for the probiotic-mediated suppression of lipid absorption and promotion of fecal fat excretion in humans. Trial registration UMIN000015772
    Lipids in Health and Disease 03/2015; 14(1). DOI:10.1186/s12944-015-0019-0 · 2.31 Impact Factor
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    ABSTRACT: Lactobacillus helveticus SBT2171 (LH2171) is a lactic acid bacterium with high protease activity and used in starter cultures in the manufacture of cheese. We recently reported that consumption of cheese manufactured using LH2171 alleviated symptoms of dextran sodium sulfate (DSS)-induced colitis in mice. In this study, we have examined whether LH2171 itself exerts an inhibitory effect on the excessive proliferation of lymphocytes. We found that LH2171 inhibited the proliferation of LPS-stimulated mouse T and B cells, and the human lymphoma cell lines, Jurkat and BJAB. Cell cycle analysis showed an accumulation of LH2171-treated BJAB cells in the G2/M phase. Further, phosphorylation of c-Jun N-terminal kinase (JNK) and c-Jun was reduced by LH2171 in BJAB cells. Subsequently, expression of cell division cycle 2 (CDC2), regulated by the JNK signaling pathway and essential for G2/M phase progression, was inhibited by LH2171. It was also demonstrated that intraperitoneal administration of LH2171 strongly alleviated symptoms of collagen-induced arthritis (CIA) in mice. These findings suggest that LH2171 inhibits the proliferation of lymphocytes through a suppression of the JNK signaling pathway and exerts an immunosuppressive effect in vivo.
    PLoS ONE 09/2014; 9(9):e108360. DOI:10.1371/journal.pone.0108360 · 3.23 Impact Factor
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    ABSTRACT: Probiotic bacteria provide benefits in enhancing host immune responses and protecting against infection. Induction of IgA production by oral administration of probiotic bacteria in the intestine has been considered to be one reason for this beneficial effect, but the mechanisms of the effect are poorly understood. Lactobacillus gasseri SBT2055 (LG2055) is a probiotic bacterium with properties such as bile tolerance, ability to improve the intestinal environment, and it has preventive effects related to abdominal adiposity. In this study, we have found that oral administration of LG2055 induced IgA production and increased the rate of IgA+ cell population in Peyer's patch and in the lamina propria of the mouse small intestine. The LG2055 markedly increased the amount of IgA in a co-culture of B cells and bone marrow derived dendritic cells (BMDC), and TLR2 signal is critical for it. In addition, it is demonstrated that LG2055 stimulates BMDC to promote the production of TGF-β, BAFF, IL-6, and IL-10, all critical for IgA production from B cells. Combined stimulation of B cells with BAFF and LG2055 enhanced the induction of IgA production. Further, TGF-β signal was shown to be critical for LG2055-induced IgA production in the B cell and BMDC co-culture system, but TGF-β did not induce IgA production in a culture of only B cells stimulated with LG2055. Furthermore, TGF-β was critical for the production of BAFF, IL-6, IL-10, and TGF-β itself from LG2055-stimulated BMDC. These results demonstrate that TGF-β was produced by BMDC stimulated with LG2055 and it has an autocrine/paracrine function essential for BMDC to induce the production of BAFF, IL-6, and IL-10.
    PLoS ONE 08/2014; 9(8):e105370. DOI:10.1371/journal.pone.0105370 · 3.23 Impact Factor
  • M Yamashita · K Ukibe · H Uenishi · T Hosoya · F Sakai · Y Kadooka
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    ABSTRACT: Consumption of a Lactobacillus helveticus SBT2171 (LH2171)-containing cheese has been reported to exhibit immunoregulatory actions, including an increase in regulatory T cell population and reduction in proinflammatory cytokine production in mice. We examined the in vitro effects of LH2171 cells per se on immune cell function, specifically proliferation and cytokine production, which are primary reactions of the immune response. Immune cell fractions were prepared by mechanical disruption of mesenteric lymph nodes (MLN), Peyer's patches (PP), and spleens (SP) of mice. The cell fractions were dispensed into a culture plate and stimulated with anti-CD3/CD28 antibody beads in place of antigen-presenting cells or lipopolysaccharide (LPS) in the presence or absence of heat-treated LH2171 cells and other bacterial strains for comparison. After incubation, proliferation, cytokine production, and cell viability of the immune cells were determined. The LH2171 significantly inhibited the proliferation of MLN immune cells stimulated with anti-CD3/CD28 compared with other bacterial strains. The antiproliferative potency of LH2171 was effective not only on MLN but also on PP and SP stimulated with anti-CD3/CD28 or LPS. The LH2171 also decreased LPS-stimulated IL-6 production from MLN, PP, and SP, and IL-1β production from SP, but LH2171 did not affect the viability of immune cells. The LH2171 inhibited immune cell proliferation and proinflammatory cytokine (IL-6 and IL-1β) production. The inhibitory actions were not due to cytotoxicity to immune cells, suggesting that LH2171 is a dairy Lactobacillus strain with beneficial immunoregulatory properties.
    Journal of Dairy Science 05/2014; 97(8). DOI:10.3168/jds.2014-8041 · 2.55 Impact Factor
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    ABSTRACT: The effect of dietary milk-derived sphingomyelin concentrate (SPC) on atopic-like dermatitis was investigated. Atopic-like dermatitis was induced by sensitization to and repeated challenges with picryl chloride in male NC/Nga mice. Mice were fed an SPC-containing diet for 12 weeks, beginning 2 weeks before sensitization. The effect of SPC was assessed by monitoring clinical scores, serum immunoglobulin E levels, scratching behaviours, and in vitro cytokine productivities by splenocytes and mesenteric lymph node cells. Skin lesions were histologically investigated. Scratching behaviours were improved in the SPC group compared with the control group. The clinical score was ameliorated, and interleukin-6 productivity by splenocytes was significantly reduced in the SPC group. The numbers of infiltrated and degranulated mast cells in skin lesions were significantly lower in the SPC group than in the control group. These results indicate that dietary SPC significantly ameliorates atopic-like dermatitis in NC/Nga mice by suppressing systemic and peripheral inflammation.
    Journal of Functional Foods 05/2014; 8:53–61. DOI:10.1016/j.jff.2014.03.001 · 4.48 Impact Factor
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    Akihiro Ogawa · Yukio Kadooka · Ken Kato · Bungo Shirouchi · Masao Sato
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    ABSTRACT: Lactobacillus gasseri SBT2055 (LG2055) inhibits dietary fat absorption in rats and exerts preventive effects on abdominal adiposity in rats and humans. The present study aimed to evaluate the effects of LG2055 on postprandial serum lipid responses in Japanese subjects with hypertriacylglycerolemia after the intake of oral fat-loading test (OFLT) meals. We conducted a single-blind, placebo-controlled, within-subject, repeated-measure intervention trial. Twenty subjects initially ingested the fermented milk (FM) without LG2055 for 4 weeks (control FM period), followed by a 4-week washout period, and then consumed FM containing LG2055 for 4 weeks (active FM period). The subjects were asked to consume FM at 200 g/day. At the end of each 4-week period, an 8-h OFLT was conducted. Blood samples were collected at fasting and every hour for 8 h after OFLT meal intake. Thereafter, postprandial serum non-esterified fatty acid (NEFA) and triacylglycerol (TAG) levels and fasting blood parameters were measured. The OFLT showed that the postprandial serum NEFA levels from 120 to 480 min and the postprandial serum TAG level at 120 min in the active FM period were significantly (P < 0.05) lower than those in the control FM period. The fasting serum NEFA level in the active FM period significantly (P < 0.001) decreased at week 4 from the initial period compared with the control FM period. The consumption of probiotic LG2055 reduced postprandial and fasting serum NEFA levels, suggesting its possible contribution to the reduction of the risk for obesity and type 2 diabetes mellitus. Trial registration: UMIN000011605.
    Lipids in Health and Disease 02/2014; 13(1):36. DOI:10.1186/1476-511X-13-36 · 2.31 Impact Factor
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    ABSTRACT: Probiotic Lactobacillus gasseri SBT2055 (LG2055) has an anti-obesity effect although it is unknown whether the effect influences inflammatory responses in adipose tissue and lipid metabolism in the liver, which are considered substantially relevant to adiposity. C57BL/6 mice were fed a 10 %-fat diet containing LG2055 cells for 24 weeks. We then studied body weight, fat tissue mass, liver fat content and inflammatory genes in the adipose tissue, and lipogenic and lipolytic genes in the liver. Consumption of LG2055 resulted in a significant reduction in body weight and fat tissue mass (epididymal and perirenal/retroperitoneal), with a lowered level of triglyceride content in the liver. DNA microarray analysis showed that LG2055 generally inhibited the up-regulation of pro-inflammatory genes, including CCL2 and CCR2, in the epididymal adipose tissue. In the liver, LG2055 tended to inhibit lipogenic gene up-regulation, including ACC1, FAS and SREBP1, but LG2055 did not markedly alter lipolytic genes. Real-time PCR analysis confirmed the DNA microarray results in part, showing a significant reduction in the mRNA expression of CCL2 in the epididymal adipose tissue, and a downward tendency in FAS mRNA expression in the liver, in the LG2055-fed group. LG2055 significantly prevented body weight gain, fat accumulation and pro-inflammatory gene expression in the adipose tissue. Relatively lower triglyceride levels and reduced expression of lipogenic genes were also observed in the liver. It is suggested that improvement in the inflammatory state of the adipose tissue might be a possible mechanism underlying the anti-obesity effect of LG2055.
    European Journal of Nutrition 08/2013; 53(2). DOI:10.1007/s00394-013-0568-9 · 3.84 Impact Factor
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    ABSTRACT: Consumption of fermented milk (FM) containing a probiotic, Lactobacillus gasseri SBT2055 (LG2055), previously showed a reduction in abdominal adiposity in a randomised controlled trial (RCT) using FM with 108 colony-forming units (cfu) of LG2055/g. However, whether the effectiveness is observed at lower concentrations, the recommended minimum or intermediate levels of probiotics (106 or 107cfu/g, respectively), remains to be examined. A multi-centre, double-blind, parallel-group RCT was conducted using 210 healthy Japanese adults with large visceral fat areas (80·2-187·8 cm2). They were balanced for their baseline characteristics and randomly assigned to three groups receiving FM containing 107, 106 or 0 (control) cfu LG2055/g of FM, and were asked to consume 200 g FM/d for 12 weeks. Abdominal visceral fat areas, which were determined by computed tomography, at week 12, changed from baseline by an average of - 8·5 % (95 % CI - 11·9, - 5·1; P< 0·01) in the 107 dose group, and by - 8·2 % (95 % CI - 10·8, - 5·7; P< 0·01) in the 106 dose group. Other measures including BMI, waist and hip circumferences, and body fat mass were also significantly decreased from baseline at week 12 in both groups; interestingly, the cessation of taking FM for 4 weeks attenuated these effects. In the control group, none of these parameters significantly decreased from baseline. These findings demonstrate that consumption of LG2055 at doses as low as the order of 108cfu/d exhibited a significant lowering effect on abdominal adiposity, and suggest that constant consumption might be needed to maintain the effect.
    The British journal of nutrition 04/2013; 110(09):1-8. DOI:10.1017/S0007114513001037 · 3.34 Impact Factor
  • T Hosoya · A Ogawa · F Sakai · Y Kadooka
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    ABSTRACT: Diet has a significant effect on immune and inflammatory responses. To date, no studies have described how consumption of a diet containing a relatively high amount of cheese affects immune responses and the inflammatory status of the body. We examined these responses in normal mice and mice with dextran sodium sulfate (DSS)-induced colitis associated with increased inflammatory responses, using a diet containing approximately 44% of a whole cheese powder and a diet containing casein, lard, and corn oil as the control. In normal mice, consumption of the cheese-containing diet induced regulatory T cells (T(reg)), which regulate immune and inflammatory responses, and suppressed the production of IL-17, IL-4, and IL-10 in Peyer's patch cells from the intestine. The T(reg) population and cytokine production were not altered in spleen cells. In mice with DSS-induced colitis, consumption of the cheese-containing diet alleviated the symptoms of colitis, as evidenced by prevention of body weight loss and colon length shortening, and inhibition of an increase in the disease activity index, which includes diarrhea and fecal bleeding. This relief of clinical symptoms was also associated with decreased production of proinflammatory cytokines (IL-17 and IL-6) and increased production of the antiinflammatory cytokine transforming growth factor-β1 in Peyer's patch cells. The T(reg) population was reduced by consumption of the cheese-containing diet in Peyer's patch cells and spleen cells, which might reflect the alleviated symptoms of colitis. Consumption of the cheese-containing diet compared with the control diet enhanced antiinflammatory and immune regulatory responses in normal mice and in a DSS-colitis mouse model.
    Journal of Dairy Science 06/2012; 95(6):2810-8. DOI:10.3168/jds.2011-4763 · 2.55 Impact Factor
  • Yukio Kadooka · Kazue Tominari · Fumihiko Sakai · Hisako Yasui
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    ABSTRACT: Rotavirus (RV)-induced diarrhea poses a major health problem, particularly to infants. An effective measure to prevent RV infection is to consume breast milk with higher levels of protective IgA. We therefore examined whether Lactobacillus gasseri SBT2055 (LG2055) could augment immunoglobulin (Ig) A levels and reduce the incidence of diarrhea in a mouse model of RV infection. Female BALB/c mouse dams were fed a diet containing 0.1% heat-treated LG2055 or a control, beginning 4 weeks before mating with male mice and continuing until the experiment ended. One week after mating, female dams were immunized orally with simian RV SA-11. Five days after birth, mouse pups were infected orally with RV and the incidence of diarrhea was determined 4 days later. RV-specific and total IgA were quantified by an enzyme-linked immunosorbent assay. LG2055-fed dams immunized with RV (LG2055/RV) secreted breast milk that significantly lowered the incidence of RV-induced diarrhea in their pups as compared with dams immunized with RV alone (C/RV). The LG2055/RV dams also produced a significantly greater amount of RV-specific IgA in breast milk obtained from the pups' stomach, but not in feces or Peyer's patch cell cultures. In addition, LG2055 stimulated total IgA production in splenocyte cultures from Toll-like receptor (TLR)-4-knockout mice, but not those from TLR-2-knockouts. LG2055-fed dams reduced RV infection in their pups and elevated RV-specific IgA levels in breast milk of stomach origin, the possible mechanism of which may be TLR-2 stimulation by LG2055.
    Journal of pediatric gastroenterology and nutrition 03/2012; 55(1):66-71. DOI:10.1097/MPG.0b013e3182533a2b · 2.87 Impact Factor
  • Yukio Kadooka · Akihiro Ogawa · Ken Ikuyama · Masao Sato
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    ABSTRACT: The probiotic Lactobacillus gasseri strain SBT2055 (LG2055) was tested for its anti-obesity and anti-inflammatory effects to determine health benefits of consuming this organism and to explore possible relationships between those effects. Visceral adipocyte size was used as a measure of obesity, and the level of soluble intercellular adhesion molecule-1 (sICAM-1) in the blood as an inflammatory marker that is elevated in obesity. Comparisons were made among rats fed a 10% fat diet based on non-fermented milk, those fed a diet containing yoghurt fermented with conventional yoghurt bacteria, and those fed a diet containing yoghurt together with the probiotic LG2055. These experiments demonstrated that the yoghurt containing LG2055, but not the control yoghurt, inhibited the enlargement of visceral adipocytes and prevented upregulation of sICAM-1. These findings indicate the utility of specific probiotics and suggest a correlation between the anti-obesity effect and the anti-inflammatory action of LG2055.
    International Dairy Journal 04/2011; DOI:10.1016/j.idairyj.2011.02.001 · 2.30 Impact Factor
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    ABSTRACT: In spite of the much evidence for the beneficial effects of probiotics, their anti-obesity effects have not been well examined. We evaluated the effects of the probiotic Lactobacillus gasseri SBT2055 (LG2055) on abdominal adiposity, body weight and other body measures in adults with obese tendencies. We conducted a multicenter, double-blind, randomized, placebo-controlled intervention trial. Subjects (n=87) with higher body mass index (BMI) (24.2-30.7 kg/m(2)) and abdominal visceral fat area (81.2-178.5 cm(2)) were randomly assigned to receive either fermented milk (FM) containing LG2055 (active FM; n=43) or FM without LG2055 (control FM; n=44), and were asked to consume 200 g/day of FM for 12 weeks. Abdominal fat area was determined by computed tomography. In the active FM group, abdominal visceral and subcutaneous fat areas significantly (P<0.01) decreased from baseline by an average of 4.6% (mean (confidence interval): -5.8 (-10.0, -1.7) cm(2)) and 3.3% (-7.4 (-11.6, -3.1) cm(2)), respectively. Body weight and other measures also decreased significantly (P<0.001) as follows: body weight, 1.4% (-1.1 (-1.5, -0.7) kg); BMI, 1.5% (-0.4 (-0.5, -0.2) kg/m(2)); waist, 1.8% (-1.7 (-2.1, -1.4) cm); hip, 1.5% (-1.5 (-1.8, -1.1) cm). In the control group, by contrast, none of these parameters decreased significantly. High-molecular weight adiponectin in serum increased significantly (P<0.01) in the active and control groups by 12.7% (0.17 (0.07, 0.26) microg/ml) and 13.6% (0.23 (0.07, 0.38) microg/ml), respectively. The probiotic LG2055 showed lowering effects on abdominal adiposity, body weight and other measures, suggesting its beneficial influence on metabolic disorders.
    European journal of clinical nutrition 03/2010; 64(6):636-43. DOI:10.1038/ejcn.2010.19 · 2.95 Impact Factor
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    ABSTRACT: We have demonstrated previously that a diet containing skimmed milk (SM) fermented by Lactobacillus gasseri SBT2055 (LGSP) reduces adipocyte size in Sprague-Dawley rats. Two experiments were conducted to extend these observations in order to elucidate the mechanism involved. In experiment 1, lean and obese Zucker rats were fed a diet containing SM or LGSP for 4 weeks. The LGSP diet, compared with the SM diet, resulted in lowering of the mesenteric adipose tissue weight (23 %; P < 0.05), adipocyte sizes (28 %; P < 0.001) and serum leptin concentration (36 %; P < 0.05) in lean rats. Obese Zucker rats did not display such dietary effects. Only the number of smaller adipocytes was increased (P < 0.05) by the LGSP diet in the subcutaneous adipose tissue of obese rats. The LGSP diet significantly reduced the serum and hepatic cholesterol in rats. In addition, the LGSP diet led to an increased excretion of faecal fatty acids and total neutral faecal sterols in both rat strains. In experiment 2, Sprague-Dawley rats with permanent cannulation of the thoracic duct were fed either the SM or LGSP diets and their lymph was collected. The LGSP diet lowered the maximum transport rate of TAG and phospholipids. These results indicate that fermented milk regulates adipose tissue growth through inhibition at the stage of dietary fat absorption in lean Zucker rats.
    The British journal of nutrition 09/2008; 101(5):716-24. DOI:10.1017/S0007114508043808 · 3.34 Impact Factor
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    ABSTRACT: Lactoferrin can solubilize over 200 molar equivalents of iron, and is expected as a natural iron solubilizer for food products and nutraceuticals from the viewpoints of bioavailability, safety, and productivity. To investigate the availability of iron solubilized by lactoferrin (FeLF) in humans, we recruited thirteen volunteers with serum hemoglobin values below 13 g/dl blood and/or ferritin levels below 45 ng/dl serum and served them a supplement containing FeLF (7.5 mg of iron) every day for twelve weeks. Significant increases in blood hemoglobin (Hb), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and serum ferritin concentrations were observed during the FeLf supplementation period. The hemoglobin level of three anemia subjects improved significantly during the period of FeLf supplementation, and, conversely, decreased after discontinuation of the supplementation. No side effects attributable to FeLf supplementation were observed either during or after the supplementation period. Thus, the results suggest that FeLf could be a useful food product for iron fortification to prevent anemia without the risk of toxicity often encountered with general iron supplementation.
    Nippon Shokuhin Kagaku Kogaku Kaishi 01/2007; 54(10):442-446. DOI:10.3136/nskkk.54.442 · 0.13 Impact Factor