Freeze-dried Lactobacillus plantarum 299v increases iron absorption in young females—Double isotope sequential single-blind studies in menstruating women



The probiotic strain Lactobacillus plantarum 299v has earlier been shown to increase iron absorption when added to foods. However, it is not known if the same probiotic strain in a freeze-dried format included in a capsule increases the iron absorption.


The aim of this study was to test the hypotheses that non-heme iron absorption from a light meal is promoted by a simultaneous intake of freeze-dried Lactobacillus plantarum 299v (Lp299v, DSM 9843).

Study design

With a single blinded placebo controlled sequential design, iron absorption from a light breakfast meal administered with or without capsules containing 1010 cfu freeze-dried Lp299v was studied in healthy female volunteers of fertile age. The methodology used was a double isotope technique (59Fe and 55Fe). Two studies were performed using the same protocol.


In study 1, the absorption of iron from a meal without Lp299v was found to be 17.4 ± 13.4%, and from an identical meal with Lp299v was found to be 22.4 ± 17.3% (mean ± SD). This difference was statistically significant (p = 0.040, n = 14).

In study 2, the absorption of iron from a meal without Lp299v was found to be 20.9 ± 13.1%, and from an identical meal with Lp299v found to be 24.5 ± 12.0% (mean ± SD, n = 28), which again was statistically significant (p = 0.003).


Freeze-dried Lp299v enhances the absorption of iron when administered together with a meal with a high iron bioavailability.

Trial registration Identifier: NCT02131870


Iron deficiency is the most common nutrient deficiency in the world, and is primarily present in women of reproductive age, who are at higher risk of developing iron deficiency because of iron losses during menstruation [1]. Other groups at risk of developing iron deficiency are infants, young children, adolescents, elderly with a poor nutrient intake, vegetarians, athletes and pregnant women [14]. Anemia affects an estimated two billion people, and causes approximately 0.8 million deaths a year worldwide [5]. Although iron deficiency is not the only cause of anemia, the WHO estimates that iron deficiency is responsible for approximately 50% of all anemia cases [6]. This approximates to 1 billion cases of iron-deficiency anemia worldwide. Consequences of iron deficiency, and primarily iron deficiency anemia, are diversified and range from fatigue [7,8] and decreased aerobic performance [912], to altered cognitive functions [13,14], immune system alterations [15] and increased risk of maternal and child mortality [1618].

In order to improve iron status by dietary means, iron deficient individuals are recommended to eat foods rich in iron or in combination with food components that increase the bioavailability of the dietary iron, where the latter has shown to be of major importance [19]. Ascorbic acid [20] and meat [21] are examples of dietary factors that have shown to enhance non-heme iron absorption, whereas calcium [22], polyphenols [23] and phytic acid [24] inhibit non-heme iron absorption. Another factor that may increase the absorption of iron is probiotics [25,26]. The definition of probiotics is, according to FAO/WHO, “live micro-organisms which, when administered in adequate amounts, confer a health benefit on the host” [27]. The human gastrointestinal (GI) tract hosts an astounding amazing >100 trillion (1014) microbes. In the human colon more than 1200 bacterial species have been identified, with each healthy individual harboring at least 160 shared species [28]. In iron deficient and anaemic women in southern India it was observed that the amount of faecal lactobacilli was significantly lower than in a control group but there was no difference between the two groups with respect to other investigated bacteria [29]. Earlier human meal studies have also shown that intake of lactic acid fermented vegetables and cereals give a significant increase in iron absorption [3032]. An intake of a lactobacilli may therefore increase the iron absorption and this has been investigated in earlier trials using the strain Lactobacillus plantarum 299v (Lp299v). Lp299v has been shown to possess the ability to survive the passage through the gastrointestinal tract [33], to colonize human intestinal mucosa [34,35], and also to increase the absorption of iron [25,26] when present live in fermented oat gruel and in fruit drinks.

The use of probiotics in food products poses some challenges when it comes to shelf-life, especially at room temperature. One potential alternative is to use freeze-dried lactobacilli in a capsule, with a shelf-life of 24 months. However, it is not known if freeze dried probiotics included in a capsule will increase the iron absorption similar to what has been shown for probiotics added directly into foods. The working hypothesis of the present study was that non-heme iron absorption from a meal is promoted by a simultaneous intake of freeze-dried Lactobacillus plantarum 299v (Lp299v).

Material and methods

General protocol / design

The study was executed by a nutritionist and a research engineer at the laboratory of the Department of Internal Medicine and Clinical Nutrition, Sahlgrenska Academy at the University of Gothenburg, Sweden. The study was designed as a single blinded placebo controlled sequential iron absorption trial in healthy, Swedish female volunteers of reproductive age. The subjects were students recruited at two Swedish universities, Sahlgrenska Academy at the University of Gothenburg, and Chalmers University of Technology. The methodology used was a double isotope technique [26,36,37], where iron absorption from two different meals (A and B) is determined by labeling the meals with either 55Fe or 59Fe. One of the benefits of this technique is that each subject becomes her own control. The double isotope technique can be considered the present golden standard in iron absorption methodology. With the double isotope technique iron absorption is assessed by calculating the difference between the administered radioactivity and the radioactivity measured either in blood (iron incorporation in erythrocytes) or in the total body (in a whole body counter). When using the whole body counting the iron absorption from the 59Fe (a γ-emitting isotope) labeled meal is calculated as the percentage of detected whole-body radioactivity, corrected for physical decay and background radioactivity. However, absorption from 55Fe, which is a β-emitting isotope, cannot be detected by whole-body counting. Thus, after WBC, a blood sample is drawn in which the relative absorption of each of the two isotopes is determined using a liquid scintillator. This relative absorption is then used to calculate the total body 55Fe absorption.

A light meal, consisting of two breakfast buns with table margarine and orange marmalade, and a glass of water, were served on four consecutive mornings to fasting subjects. During the first two mornings, together with the light meal, the fasting subjects were served capsules containing no lactobacilli (A), whereas capsules containing 1010 colony-forming units (cfu) Lp299v (B) were served on morning 3 and 4. The reason for chosing the order AABB was to avoid any remaining lactobacilli effect that may occur if Lp299v were administered before the placebo capsules [25]. Also, comparative studies have shown that iron absorption from two different meals labeled with either 55Fe or 59Fe does not differ between individuals regardless of administration order [37]. In order to reduce the day-to-day-variation in iron absorption [38] each meal (i.e. with and without Lp299v) was administered during two consecutive days from which the mean daily iron absorption was calculated. Two separate studies with the same protocol were performed. The number of subjects included in each of the two studies was 18 and 36, respectively. For study 1 participant were recruited during January–February 2014, and the study was executed during February–March 2014. For study 2 participants were recruited during April–May 2014, and the study was executed during May–June 2014. The study was registered at Clinical trials (NCT02131870). The authors confirm that all ongoing and related trials for this intervention are registered.

Meal content

Each meal consisted of two breakfast buns (made from a total of 80 grams of low extraction wheat flour, 56 grams of water, 5.2 grams of yeast, 2.6 g of sugar, and 0.8 g of NaCl) with Flora table margarine (15 grams), orange marmalade (20 grams) and a glass of water (200 mL). When baking the buns, they were fermented for 2 x 30 minutes, and then baked at 240°C for 10 min. After baking the buns were kept frozen at -20°C and thawed before serving. In addition the meal contained 0.6 mg iron, 21 mg Ca, and 2.6 mg ascorbic acid, the two latter being dietary factors known to influence iron absorption. The phytate content in the buns was negligible since a low extraction wheat flower was used and the dough was fermented twice [31]. The recipe for making the buns / wheat rolls has been used by our research group for almost 40 years and it was specially developed at our lab as to maximize the reduction of phytates [39]. It was also the basis from which the iron absorption algorithm by Hallberg and Hulthén was developed [24]. During the 35 years that the wheat rolls has been used by our research group the same individual in our staff has been involved in baking them. In our experience, there would not be any difference in phytate content in the meals between study 1 and 2.

Together with each meal a total of 3 capsules were administered. The capsules used, provided by Probi AB (Lund, Sweden), are vegetable capsules composed of hydroxypropylmethyl cellulose. The capsules are composed to have a medium dissolution profile and they will be dissolved in stomach after 20–25 minutes.

The capsules in meal A consisted of:

  • One capsule containing 30 μg of folic acid, 12 mg of ascorbic acid and 4.2 mg of iron.
  • Two capsules, each containing 50 μl 55FeCl3 in 0.1 M HCl and potato starch.

The capsules in meal B consisted of:

  • One capsule containing 30 μg of folic acid, 12 mg of ascorbic acid, and 4.2 mg iron + 1010 cfu lyophilised Lp299v.
  • Two capsules, each containing 50 μl 59FeCl3 in 0.1 M HCl and potato starch.

Measurement of iron absorption

The two capsules labeled with radioisotopes (as FeCl3 in HCl) were prepared right before serving. The lower half was filled with 320 mg of potato starch. The radioisotope was added by pippeting, whereupon the capsules upper part was mounted. The capsules were swallowed within 60 seconds from when they were prepared. To maximize isotope exchange [40] between the iron in the capsules and in the meal, the subjects were instructed to swallow all the capsules half way into the meal, that is, i.e., when one breakfast bun had been ingested, and one remained. No food or drink was allowed within three hours following the meals. Blinded administration was possible since the A and the B capsules were identical in appearance. Ten to 14 days after the meals were administered, blood samples were drawn and the radiation from the two Fe isotopes were determined. The total amount of blood taken from each subject for the analysis was 120 mL. Directly after drawing the blood sample a reference dose (3 mg 59Fe-labeled iron (II) + 30 mg of ascorbic acid dissolved in 10 mL of 0.01 M HCl) was orally administered together with 10 mL water on an empty stomach. The following morning yet another identical reference dose was served on an empty stomach. No food or drink was allowed within three hours following these reference doses. The daily mean absorption from the two reference doses was analysed in blood after a further 10–14 days (Fig 1). The total amount of blood drawn for the analysis of the reference dose absorption was 120 mL.


Fig 1. Study design.

The iron content in two different meals (A and B) was labeled with either 55Fe or 59Fe. Meal A contained no lactobacilli and was served on morning 1 and 2, whereas meal B, which contained 1010 cfu lyophilised Lp299v, was served on morning 3 and 4. Ten to 14 days after the meals were administered, blood samples were drawn and the radiation from the two Fe isotopes were determined. Directly after drawing the blood sample a reference dose (3 mg 59Fe-labeled iron (II) + 30 mg of ascorbic acid dissolved in 10 mL of 0.01 M HCl) was administered. The following morning yet another identical reference dose was served. After a further 10–14 days the daily mean absorption from the two reference doses was analysed in blood samples.

By relating the absorption from the capsule meals to the reference-dose-absorption, the variation depending on differences in iron absorption capacity, which primarily is dependent on iron status, was corrected. An informal agreement has been used to express absorption corresponding to a 40% reference dose absorption [41]. Thus, the iron absorption from each meal was normalized to the iron absorption that the subject would have if having a reference dose absorption of 40%. This is the percentage reference dose absorption seen in a subject with low iron stores, i.e. serum ferritin = 23 μg/l [24]. The recorded radioactivity for each subject in the different trials amounted to a total of 2 μCi from 55Fe and 2.0 μCi from 59Fe (2 x 0.5 μCi from reference-dose + 2 x 0.5 μCi from the capsule meals). The wet-chemical analysis of 55Fe and 59Fe was carried-out according to a modification of the analysis method described by Eakins and Brown [42]. Duplicates of whole-blood corresponding to 10 mg Fe were pre-treated and finally analyzed in liquid scintillator (Tri-Carb, Packard Instruments, Dallas) to determine the radiation from 55Fe and 59Fe. The absorption in percent was determined from the blood volume which was calculated from each individual’s height, weight and hemoglobin concentration [43].


The study was conducted according to the Ethical Principles for Medical Research Involving Human Subjects, adopted by the 18th World Medical Association General Assembly, in Helsinki, Finland, in June 1964 and amended by the 64th WMA General Assembly, in Fortaleza, Brazil, in October 2013. The study protocol was approved by the Regional Ethics Review Board in Gothenburg (Registration No. 178–13) and the Radiation Safety Committee at the Sahlgrenska University Hospital, Gothenburg, Sweden (Registration No: 13–12). The participating women gave informed written consent for participation in the study.

Inclusion / Exclusion criteria

The subjects had to be healthy menstruating women without medication (with the exception of oral contraceptives) or any gastrointestinal, malabsorptive or metabolic diseases. The subjects were not allowed to be pregnant, lactating or to have donated blood within two months prior to the study. Neither could they take any dietary supplements (including iron) or use any probiotic containing products during the study or within two weeks prior to the study. Exclusion criteria also included infection / inflammation since an activated acute-phase reaction can cause extensive changes in body iron metabolism, including reduced iron absorption [4446]. In the event of an activated acute-phase response, S-ferritin is falsely elevated [47]. A serum ferritin concentration of ≥120 μg/l [48,49] is above the 95th percentile of the WHO reference interval for women [50]. The reference interval is based on data from the National Health and Nutrition Examination Survey (NHANES) III-study [51], and from Custer et al [52]. A such high ferritin concentration of ≥120 μg/l is likely due to an inflammation [47]. Thus, in study 1 the exclusion criterion of S-ferritin ≥120 μg/L was chosen. However, in study 2 it was decided to be more stringent and the exclusion criteria of S-ferritin ≥60 μg/L was chosen. As an additional control of activated acute-phase response, blood was sampled for the analysis of C-reactive protein (CRP). The iron biomarkers were evaluated as a whole together with the CRP and the anamnesis in which the subjects were asked if they had experienced any signs of infection (such as fever, common cold etc.) in the previous weeks. To further increase the ability to detect any influence of activated acute-phase response during the study, blood samples destined for ferritin analysis were taken on three occasions; 1): At the first day of serving the meals. 2): Ten to fourteen days after ingesting the capsule meals and 3): After a further two weeks. By this it was possible to observe any discrepancy between occasions. A day-to-day variation (CV%) in S-ferritin >8% between these three occasions led to exclusion since this most likely was an expression of an activated acute-phase response [53].

Laboratory analysis

Blood samples were collected by venous puncture. Serum iron concentration (S-Fe), total iron binding capacity (TIBC), transferrin saturation (TSAT), S-ferritin, soluble transferrin receptor (sTfR), Hb and C-reactive protein (CRP) were analyzed at an accredited reference laboratory (Clinical Chemistry Laboratory, Sahlgrenska University Hospital, Gothenburg, Sweden), according to ISO/IEC 15189 Standard for Medical Laboratories.

Sample size

The primary hypothesis was that, in comparison with the control meal, there would be a significant increase in iron absorption after eating a meal together with freeze dried Lp299v. The sample size and power calculation was based on the fact that two different Fe isotopes were used in a sequential design, making each subject her own control, and by that, the paired student t-test can be used. When designing study 1 no previous study of this kind could be found, and by that no predictable absorption value to use in a sample size calculation existed. Consequently, Fe absorption from the control meal was predicted from the meal composition [24], and was expected to be approximately 21%. In order to, with a paired t-test and with a significance level of 0.05, have a 90% probability (i.e. a power of 90%) of observing a 10.0 ± 10.0 (SD) % difference in iron absorption [26], 13 subjects would have to be studied. Expected dropout- and exclusion frequency were estimated to be 30%, thus 18 subjects were recruited to the study.

However, although there was a significant difference in study 1 (p = 0.040), it was close to the margin of statistical significance. As such, there is a risk that we incorrectly reject the null hypothesis. Consequently, we decided to repeat the study and this time calculate the sample size based on the results in study 1. In order to, with a paired t-test and with a significance level of 0.05, have a 80% probability (i.e. a power of 80%) of observing a 5.0 ± 10.0 (SD) % difference in iron absorption [26], 31 subjects would have to be studied. Expected dropout- and exclusion frequency were estimated to be 15%, thus 36 subjects were recruited.

Sample size calculation was made using the StudySize 3.0 software (CREOSTAT HB, Västra Frölunda, Sweden).


Data were checked for normality of distribution using the Shapiro-Wilk test. Paired sample Student’s t-test, at a 95% confidence level, were used to analyze iron absorption differences. Student’s independent samples t-test, at a 95% confidence level, were used to analyze differences between study groups. The iron absorption variables were significantly skewed. Consequently, data were log-transformed before statistical analysis. For ease of interpretation, untransformed data is presented as mean and standard deviation (SD). All p-values were two-tailed and considered to be statistically significant if p<0.05. Statistical analyses were performed using IBM® SPSS® Statistics for Windows 22.0.0 (SPSS Inc., Chicago, IL, USA).

Protocol deviation

Due to unexpected technical problems at the whole body counter facilities at the Sahlgrenska University hospital, the intention to utilize the whole body counter in the study had to be abandoned (S1 and S2 Files).


All absorption values are normalized so that they corresponding to a 40% reference dose absorption [41].

Eighteen subjects were recruited for study 1 (Fig 2). None of the participants were consuming other products containing probiotics during the four days they were served the capsule meals, or during the two weeks before the test days. One subject was excluded in connection with the first test meal as it was discovered that she recently had had another isotope test that could influence the results. Another subject decided to stop the participation at the stage of blood sampling. One subject was excluded due to a high serum ferritin concentration (120 μg/L). An additional subject was excluded due to an increased CRP (> 5 mg/L). Thus, the data analysis is based on a total of 14 females with an age between 21–40 years, an Hb-value between 123–146 g/L and a serum ferritin concentration between 8–80 μg/L (Table 1).

Iron absorption from the capsule meals without Lp299v was found to be 17.4 ± 13.4% (mean ± SD). Iron absorption from capsule meals with1010 cfu freeze-dried Lp299v was found to be 22.4 ± 17.3% (mean ± SD). The mean difference in iron absorption between these two capsule meals was 5.0% (SD 11.0%) and statistically significant (p <0.040, n = 14) (Table 2, Fig 3A and S1 Data).


Fig 3. Iron absorption from a meal administered together with capsules with or without Lactobacillus plantarum 299v (Lp299v).

Fig 3A: Study 1 (n = 14). Fig 3B: Study 2 (n = 28). The bars illustrate mean iron absorption and the whiskers cover the standard deviation (SD), and the dots illustrate individual subject data. Paired two-sample Student’s t-test was used to analyze differences between meals with or without Lp299v. Data were log-transformed before statistical analysis. Abbreviations: cfu, colony forming units.

In study 2 a total of 36 subjects were recruited (Fig 2). One subject decided to drop out the day before start, and another subject dropped out after completing half the study. Three subjects were excluded due to high S-ferritin concentration (>60 μg/L), and another three subjects were excluded due to inflammation (CRP>5 mg/L). Accordingly, the data analysis of study 2 is based on a total of 28 females with an age between 19–51 years (the woman who was 51 years of age affirmed that she was menstruating), an Hb-value between 113–156 g/L and a serum ferritin concentration between 6–54 μg/L (Table 1).

In this study iron absorption from the capsule meals without Lp299v was found to be 20.9 ± 13.1% (mean ± SD). Iron absorption from the capsule meals with1010 cfu freeze-dried Lp299v was found to be 24.5 ± 12.0% (mean ± SD, n = 28). The mean difference in iron absorption between these two capsule meals was 3.6% (SD 8.6%) and statistically significant (p <0.003, n = 28) (Table 2, Fig 3B and S2 Data).

When comparing the data from both studies, there was no statistical difference between the iron absorption from the capsule meals with 1010 cfu Lp299v in study 1 and in study 2. Also when solely including subjects having S-ferritin <60 ug/L there was no statistical difference in iron absorption between the capsule meals with Lp299v in the two studies.


There seem to be a close relationship between diet, microbiota and health status [54], where dietary components are able to alter the gut microbiota [55,56]. However, survival and viability of externally added probiotic bacteria in gastric and pancreatic juice is often rather poor in in vitro trials [57]. Likewise, during refrigerated storage some probiotic strains exhibits loss in viability [58]. Freeze drying and microencapsulation, on the other hand, increases probiotic viability and stability [59,60], making these feasible methods for delivering the probiotic cultures in the right location of the gastrointestinal (GI) tract. Earlier studies have shown iron absorption enhancing properties of Lp299v when not lyophilized [25,26]. A previous study by Bering et al observed no effect on iron absorption from adding lyophilized Lp299v to oat gruel [61]. The explanation for lack of effect given in the publication was that the bacteria might not have been in a comparatively active state. However, the present study demonstrated that freeze-dried Lactobacillus plantarum 299v (Lp299v) is capable of increasing non-heme iron absorption from a concurrently administered meal. This is probably related to that the freeze-dried bacteria this time was included in a capsule and could be released in the stomach and thus had the possibility to reach the small intestine in an active state.

The increase in iron absorption was from a cereal meal already having a relatively high iron bioavailability since it contained a low content of phytates, the main contributor to low iron availability in cereals. Theoretically, when added to a meal with low iron bioavailability, the positive effect on iron absorption may be even more pronounced as has shown to be the case with ascorbic acid [39]. Consuming a meal of low iron bioavailability results in more iron residing in the GI lumen. By increasing the bioavailability of the iron in the diet by providing Lp299v, the dose of iron in the diet could be lower, reducing the amount of iron passing the GI tract without being absorbed. From an oxidative state of view, there are indications that redundant amounts of iron in the GI tract can result in an increased oxidative stress, with its negative aftermath [62].

By administering a fermented oatmeal drink with Lp299v to subjects for 4 weeks, Goossens et al significantly increased the number of lactobacilli in the fecal flora of the subjects within 1 week. However, this effect disappeared within 1 week after cessation of intake [34]. So, in order to detaining a steady colonization of Lp299v, and by that the positive effects, it seems to be necessary to keep supplying the lactobacilli.

The enhancing properties of Lp299v on iron absorption can probably be attributed to the persistency of Lp299v in the intestine. In order to reduce the day-to-day-variation in iron absorption in the present study mean absorption from two identical meals administered on two consecutive days was calculated. However, by using this methodology it is not possible to determine exactly how the Lp299v effect is mediated. Does it occur in the same way as other dietary factors influencing iron absorption, i.e., only in the common pool of the administered meal and thus having a transitory effect (i.e., same enhancing effect on day 1 as on day 2), or is it a more prolonged effect caused by intestine persistency? If the latter is the case, it could mean that the enhancing effect of administrating Lp299v differs between day 1 and day 2.

Interestingly, in vitro results recently showed that Lactobacillus fermentum has a ferric-reducing activity. This activity is proposed to be executed via an excreted molecule, p-hydroxyphenyllactic acid, which reduces ferric iron into the more bioavailable ferrous iron, and thereby boosts Fe(II) absorption through the DMT1 channels in the intestines [63]. If Lp299v also has a ferric-reducing activity is not known today.

The basis for including only women of reproductive age in the present study was the fact that this group is at higher risk of developing iron deficiency due to iron losses during menstruation. The presently used iron absorption methodology has been used extensively over the years and has been thoroughly discussed by Hallberg [36] and others. To the best of our knowledge there is nothing indicating that iron absorption would differ by mere gender. Thus, the present result is most likely applicable to other groups beside women of reproductive age.

Unfortunately, due to unexpected technical problems at the whole body counter facilities the intention to utilize the whole body counter for the present study had to be abandoned. Instead the iron absorption was solely assessed from radio iron incorporation into erythrocytes, which can be seen as a limitation of the study since it requires two important estimations. These are the percentage of absorbed iron that is incorporation in erythrocytes, and the actual blood volume of the subject. Estimates for blood volume are usually calculated from sex, weight, and height. In healthy subjects having normal iron status, approximately 80% of absorbed iron will be incorporated into erythrocytes. However, this figure can differ depending on e.g. iron status, or presence of inflammation or infection. Nevertheless, since each subject is her own control, this limitation has most likely only a potential effect on the accuracy, not the iron absorption ratio between meal A and meal B, which is the primary outcome of the present study.

In conclusion, the results brought forward in the present study further strengthen the evidence that Lp299v enhances iron absorption when concurrently added to a meal. Thus, Lp299v provide a valuable alternative for increasing iron bioavailability in the diet of vulnerable individuals who are in need of increasing their iron uptake due to high requirements. By increasing the bioavailability of iron in the diet by providing Lp299v it could be possible to lower the amount of iron added to a meal, and therefore reduce the amount of iron residing in the GI tract leading to negative health consequences.


We would like to acknowledge Elisabeth Gramatkovski at the University of Gothenburg for her valuable technical assistance in connection with all aspects in performing this study. We also would like to acknowledge Malin Björklund, Probi AB, for preparing the study products used in the study.


  1. 1.
    WHO/UNICEF/UNU (2001) Iron deficiency anaemia: Assessment, prevention, and control: a guide for programme managers. Geneva: WHO/NHD/01.3.
  2. 2.
    Umbreit J (2005) Iron deficiency: A concise review. Am J Hematol 78: 225–231. pmid:15726599
  3. 3.
    Landahl G, Adolfsson P, Borjesson M, Mannheimer C, Rodjer S (2005) Iron deficiency and anemia: a common problem in female elite soccer players. Int J Sport Nutr Exerc Metab 15: 689–694. pmid:16521852
  4. 4.
    Hercberg S, Preziosi P, Galan P (2001) Iron deficiency in Europe. Public Health Nutr 4: 537–545. pmid:11683548
  5. 5.
    WHO (2002) The World Health Report 2002—Reducing Risks, Promoting Healthy Life. Geneva: World Health Organization.
  6. 6.
    WHO (2011) Guideline: Intermittent iron and folic acid supplementation in menstruating women. Geneva, World Health Organization.
  7. 7.
    Verdon F, Burnand B, Stubi CL, Bonard C, Graff M, et al. (2003) Iron supplementation for unexplained fatigue in non-anaemic women: double blind randomised placebo controlled trial. Bmj 326: 1124. pmid:12763985
  8. 8.
    Patterson AJ, Brown WJ, Roberts DC (2001) Dietary and supplement treatment of iron deficiency results in improvements in general health and fatigue in Australian women of childbearing age. J Am Coll Nutr 20: 337–342. pmid:11506061
  9. 9.
    Brutsaert TD, Hernandez-Cordero S, Rivera J, Viola T, Hughes G, et al. (2003) Iron supplementation improves progressive fatigue resistance during dynamic knee extensor exercise in iron-depleted, nonanemic women. Am J Clin Nutr 77: 441–448. pmid:12540406
  10. 10.
    Friedmann B, Weller E, Mairbaurl H, Bartsch P (2001) Effects of iron repletion on blood volume and performance capacity in young athletes. Med Sci Sports Exerc 33: 741–746. pmid:11323542
  11. 11.
    Hinton PS, Giordano C, Brownlie T, Haas JD (2000) Iron supplementation improves endurance after training in iron-depleted, nonanemic women. J Appl Physiol 88: 1103–1111. pmid:10710409
  12. 12.
    Brownlie Tt, Utermohlen V, Hinton PS, Giordano C, Haas JD (2002) Marginal iron deficiency without anemia impairs aerobic adaptation among previously untrained women. Am J Clin Nutr 75: 734–742. pmid:11916761
  13. 13.
    Bruner AB, Joffe A, Duggan AK, Casella JF, Brandt J (1996) Randomised study of cognitive effects of iron supplementation in non-anaemic iron-deficient adolescent girls. Lancet 348: 992–996. pmid:8855856
  14. 14.
    WHO (2004) Food and health in Europe: a new basis for action.
  15. 15.
    Ahluwalia N, Sun J, Krause D, Mastro A, Handte G (2004) Immune function is impaired in iron-deficient, homebound, older women. Am J Clin Nutr 79: 516–521. pmid:14985230
  16. 16.
    Brabin BJ, Hakimi M, Pelletier D (2001) An analysis of anemia and pregnancy-related maternal mortality. J Nutr 131: 604S–614S; discussion 614S-615S. pmid:11160593
  17. 17.
    Brabin BJ, Premji Z, Verhoeff F (2001) An analysis of anemia and child mortality. J Nutr 131: 636S–645S; discussion 646S-648S. pmid:11160595
  18. 18.
    Stoltzfus RJ (2001) Iron-deficiency anemia: reexamining the nature and magnitude of the public health problem. Summary: implications for research and programs. J Nutr 131: 697S–700S; discussion 700S-701S. pmid:11160600
  19. 19.
    Hoppe M, Hulthén L, Hallberg L (2008) The importance of bioavailability of dietary iron in relation to the expected effect from iron fortification. Eur J Clin Nutr 62: 761–769. pmid:17538547
  20. 20.
    Hallberg L, Brune M, Rossander L (1986) Effect of ascorbic acid on iron absorption from different types of meals. Studies with ascorbic-acid-rich foods and synthetic ascorbic acid given in different amounts with different meals. Hum Nutr Appl Nutr 40: 97–113. pmid:3700141
  21. 21.
    Gibson S, Ashwell M (2003) The association between red and processed meat consumption and iron intakes and status among British adults. Public Health Nutr 6: 341–350. pmid:12795822
  22. 22.
    Hallberg L, Brune M, Erlandsson M, Sandberg AS, Rossander-Hulten L (1991) Calcium: effect of different amounts on nonheme- and heme-iron absorption in humans. Am J Clin Nutr 53: 112–119. pmid:1984335
  23. 23.
    Tuntawiroon M, Sritongkul N, Brune M, Rossander-Hulten L, Pleehachinda R, et al. (1991) Dose-dependent inhibitory effect of phenolic compounds in foods on nonheme-iron absorption in men. Am J Clin Nutr 53: 554–557. pmid:1989426
  24. 24.
    Hallberg L, Hulthen L (2000) Prediction of dietary iron absorption: an algorithm for calculating absorption and bioavailability of dietary iron. Am J Clin Nutr 71: 1147–1160. pmid:10799377
  25. 25.
    Bering S, Suchdev S, Sjoltov L, Berggren A, Tetens I, et al. (2006) A lactic acid-fermented oat gruel increases non-haem iron absorption from a phytate-rich meal in healthy women of childbearing age. Br J Nutr 96: 80–85. pmid:16869994
  26. 26.
    Hoppe M, Önning G, Berggren A, Hulthen L (2015) Probiotic strain Lactobacillus plantarum 299v increases iron absorption from an iron-supplemented fruit drink: a double-isotope cross-over single-blind study in women of reproductive age. British Journal of Nutrition 114: 1195–1202. pmid:26428277
  27. 27.
    WHO (2001) Report of a Joint FAO/WHO Expert Consultation on Evaluation of Health and Nutritional Properties of Probiotics in Food including Powder Milk with Live Lactic Acid Bacteria.
  28. 28.
    Lin CS, Chang CJ, Lu CC, Martel J, Ojcius DM, et al. (2014) Impact of the gut microbiota, prebiotics, and probiotics on human health and disease. Biomed J 37: 259–268. pmid:25179725
  29. 29.
    Balamurugan R, Mary RR, Chittaranjan S, Jancy H, Shobana Devi R, et al. (2010) Low levels of faecal lactobacilli in women with iron-deficiency anaemia in south India. Br J Nutr 104: 931–934. pmid:20447323
  30. 30.
    Gillooly M, Bothwell TH, Torrance JD, MacPhail AP, Derman DP, et al. (1983) The effects of organic acids, phytates and polyphenols on the absorption of iron from vegetables. Br J Nutr 49: 331–342. pmid:6860621
  31. 31.
    Brune M, Rossander-Hulten L, Hallberg L, Gleerup A, Sandberg AS (1992) Iron absorption from bread in humans: inhibiting effects of cereal fiber, phytate and inositol phosphates with different numbers of phosphate groups. J Nutr 122: 442–449. pmid:1311753
  32. 32.
    Scheers N, Rossander-Hulthen L, Torsdottir I, Sandberg AS (2015) Increased iron bioavailability from lactic-fermented vegetables is likely an effect of promoting the formation of ferric iron (Fe). Eur J Nutr 55: 373–382. pmid:25672527
  33. 33.
    Goossens D, Jonkers D, Russel M, Thijs A, van den Bogaard A, et al. (2005) Survival of the probiotic, L. plantarum 299v and its effects on the faecal bacterial flora, with and without gastric acid inhibition. Dig Liver Dis 37: 44–50. pmid:15702859
  34. 34.
    Goossens D, Jonkers D, Russel M, Stobberingh E, Van Den Bogaard A, et al. (2003) The effect of Lactobacillus plantarum 299v on the bacterial composition and metabolic activity in faeces of healthy volunteers: a placebo-controlled study on the onset and duration of effects. Aliment Pharmacol Ther 18: 495–505. pmid:12950422
  35. 35.
    Johansson ML, Molin G, Jeppsson B, Nobaek S, Ahrne S, et al. (1993) Administration of different Lactobacillus strains in fermented oatmeal soup: in vivo colonization of human intestinal mucosa and effect on the indigenous flora. Appl Environ Microbiol 59: 15–20. pmid:8439146
  36. 36.
    Hallberg L (1980) Food iron absorption. In: Cook JD, editor. Iron. New York: Churchill-Livingstone. pp. 116–133.
  37. 37.
    Brise H, Hallberg L (1962) A method for comparative studies on iron absorption in man using two radioiron isotopes. Acta Med Scand 171: 7–22.
  38. 38.
    Bjorn-Rasmussen E, Hallberg L, Magnusson B, Rossander L, Svanberg B, et al. (1976) Measurement of iron absorption from compositite meals. Am J Clin Nutr 29: 772–778. pmid:820179
  39. 39.
    Hallberg L, Brune M, Rossander L (1989) Iron absorption in man: ascorbic acid and dose-dependent inhibition by phytate. Am J Clin Nutr 49: 140–144. pmid:2911999
  40. 40.
    Hallberg L, Bjorn-Rasmussen E (1972) Determination of iron absorption from whole diet. A new two-pool model using two radioiron isotopes given as haem and non-haem iron. Scand J Haematol 9: 193–197. pmid:5055028
  41. 41.
    Magnusson B, Bjorn-Rassmussen E, Hallberg L, Rossander L (1981) Iron absorption in relation to iron status. Model proposed to express results to food iron absorption measurements. Scand J Haematol 27: 201–208. pmid:7313546
  42. 42.
    Eakins JD, Brown DA (1966) An improved method for the simultaneous determination of iron-55 and iron-59 in blood by liquid scintillation counting. Int J Appl Radiat Isot 17: 391–397. pmid:5967690
  43. 43.
    Hallberg L (1955) Blood volume, hemolysis and regeneration of blood in pernicious anemia; studies based on the endogenous formation of carbon monoxide and determinations of the total amount of hemoglobin. Scand J Clin Lab Invest 7 Suppl. 16: 1–127.
  44. 44.
    Cartwright GE (1966) The anemia of chronic disorders. Semin Hematol 3: 351–375. pmid:5341723
  45. 45.
    Jurado RL (1997) Iron, infections, and anemia of inflammation. Clin Infect Dis 25: 888–895. pmid:9356804
  46. 46.
    Hoppe M, Hulthen L (2007) Capturing the onset of the common cold and its effects on iron absorption. Eur J Clin Nutr 61: 1032–1034. pmid:17268421
  47. 47.
    Hulthen L, Lindstedt G, Lundberg PA, Hallberg L (1998) Effect of a mild infection on serum ferritin concentration—clinical and epidemiological implications. Eur J Clin Nutr 52: 376–379. pmid:9630391
  48. 48.
    Hallberg L, Hulten L, Gramatkovski E (1997) Iron absorption from the whole diet in men: how effective is the regulation of iron absorption? Am J Clin Nutr 66: 347–356. pmid:9250114
  49. 49.
    Pynaert I, De Bacquer D, Matthys C, Delanghe J, Temmerman M, et al. (2009) Determinants of ferritin and soluble transferrin receptors as iron status parameters in young adult women. Public Health Nutr 12: 1775–1782. pmid:19105865
  50. 50.
    WHO/CDC (2007) Assessing the iron status of populations: including literature review: report of a joint World Health Organization / Centers for Disease Control and Prevention technical consultation on the as sessment of iron status at the population level. Geneva, Switzerland.
  51. 51.
    Zacharski LR, Ornstein DL, Woloshin S, Schwartz LM (2000) Association of age, sex, and race with body iron stores in adults: analysis of NHANES III data. Am Heart J 140: 98–104. pmid:10874269
  52. 52.
    Custer EM, Finch CA, Sobel RE, Zettner A (1995) Population norms for serum ferritin. J Lab Clin Med 126: 88–94. pmid:7602240
  53. 53.
    Belza A, Ersboll AK, Henriksen M, Thilsted SH, Tetens I (2005) Day-to-day variation in iron-status measures in young iron-deplete women. Br J Nutr 94: 551–556. pmid:16197580
  54. 54.
    Claesson MJ, Jeffery IB, Conde S, Power SE, O’Connor EM, et al. (2012) Gut microbiota composition correlates with diet and health in the elderly. Nature 488: 178–184. pmid:22797518
  55. 55.
    Muegge BD, Kuczynski J, Knights D, Clemente JC, Gonzalez A, et al. (2011) Diet drives convergence in gut microbiome functions across mammalian phylogeny and within humans. Science 332: 970–974. pmid:21596990
  56. 56.
    Suez J, Korem T, Zeevi D, Zilberman-Schapira G, Thaiss CA, et al. (2014) Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Nature 514: 181–186. pmid:25231862
  57. 57.
    Del Piano M, Strozzi P, Barba M, Allesina S, Deidda F, et al. (2008) In vitro sensitivity of probiotics to human pancreatic juice. J Clin Gastroenterol 42 Suppl 3 Pt 2: S170–173.
  58. 58.
    Nighswonger BD, Brashears MM, Gilliland SE (1996) Viability of Lactobacillus acidophilus and Lactobacillus casei in fermented milk products during refrigerated storage. J Dairy Sci 79: 212–219. pmid:8708082
  59. 59.
    Ding WK, Shah NP (2009) An improved method of microencapsulation of probiotic bacteria for their stability in acidic and bile conditions during storage. J Food Sci 74: M53–61. pmid:19323758
  60. 60.
    Prakash S, Tomaro-Duchesneau C, Saha S, Rodes L, Kahouli I, et al. (2014) Probiotics for the prevention and treatment of allergies, with an emphasis on mode of delivery and mechanism of action. Curr Pharm Des 20: 1025–1037. pmid:23701572
  61. 61.
    Bering S, Sjoltov L, Wrisberg SS, Berggren A, Alenfall J, et al. (2007) Viable, lyophilized lactobacilli do not increase iron absorption from a lactic acid-fermented meal in healthy young women, and no iron absorption occurs in the distal intestine. Br J Nutr 98: 991–997. pmid:17764597
  62. 62.
    Troost FJ, Saris WH, Haenen GR, Bast A, Brummer RJ (2003) New method to study oxidative damage and antioxidants in the human small bowel: effects of iron application. Am J Physiol Gastrointest Liver Physiol 285: G354–359. pmid:12724133
  63. 63.
    González a A, Gálvez a N, J Mb, Reyes b F, Pérez-Victoria b I, et al. (2017) Identification of the key excreted molecule by Lactobacillus fermentum related to host iron absorption. Food Chemistry 228: 374–380. pmid:28317737
Rate this post