Iron and Its Lactic Strain

* Reference contributions
** Colony Forming Unit

Ingredients: Corn starch; Coating agent: hydroxypropyl methylcellulose (HPMC); Lactobacillus plantarum 299v® (DSM 9843); Iron-based preparation (ferrous fumarate, vegetable oil); Vitamin C complex (L-ascorbic acid, coating agent: ethylcellulose; MCT); Maltodextrin; Anti-caking agents: acacia gum, fatty acid; Quatrefolic® [5MTHF-glucosamine (folate)]. Quatrefolic® is a registered trademark of Gnosis. Lactobacillus plantarum 299v® is a strain of Probi.

Iron deficiency: biological aspects and figures

Iron is the chemical element (symbol Fe) with atomic number 26. It is the most abundant trace element, and therefore the most studied, in the human body. A trace element is a mineral (iron but also zinc, selenium, etc.) whose nutritional need is lower than the category of minerals (magnesium, calcium, etc.). Indeed, in addition to being relatively common, iron deficiency is associated with extremely complex absorption and regulatory mechanisms. However, an iron deficiency, if it turns into anemia, can have serious consequences for health.

Definition of iron deficiency [1,2]
The risk of potential deficiency appears mainly when the body's needs are increased (to compensate for greater losses, for example), and when the intakes are not adjusted accordingly. The early stages of a deficiency are not necessarily associated with anemia, although this is common. Iron deficiency without anemia (called iron deficiency) is characterized by a decrease in ferritin, the cellular iron storage protein in organs and present in lower quantities in the blood. Ferritin is the direct marker of the body's iron reserves and its blood test can detect a deficiency. The decrease in ferritin (non-anemic iron deficiency: <15–30 μg / l identifiable by blood test) is very early, it occurs even before the onset of anemia (and when anemia sets in, the ferritin collapses). Anemia is characterized by a decrease in hemoglobin (a protein in red blood cells that carries oxygen), and can be caused by iron deficiency or other factors. The hemoglobin blood test can be used to diagnose it.

• a deficiency in folate (vitamin B9),
• a deficiency in vitamin B12.

Note that iron deficiency without anemia is a latent condition of iron deficiency anemia.

Adapted from [2]

Health consequences
Iron deficiency anemia causes various symptoms such as fatigue, paleness of the complexion and more shortness of breath on exertion. The symptoms of iron deficiency alone (without anemia) are less well established, but this condition would also affect general well-being [2]. During pregnancy, the nutritional status of the mother is crucial and the pre, peri and postnatal periods are windows of programming for the health of the child. Adequate iron status during pregnancy will allow brain maturation and normal development of the newborn and then the child [3]. It therefore appears important to monitor the iron intake of pregnant women and, later, young children.

Prevalence data
A major analysis was carried out between 1993 and 2005 by the World Health Organization (WHO) on 192 countries to determine the prevalence of anemia. This work estimated the number of people affected by anemia at 1.62 billion, or 24.8% of the world's population. All countries are obviously not affected in the same way.

Looking at Europe, the prevalence of anemia among pregnant women was 25.1% compared to 19% for other women [4]. The prevalence in young children (0-5 years) was 21.7%.

The WHO has also assessed the percentage of anemia that may be affected by iron supplementation (with iron supplements in particular) (anemia which therefore originates from iron deficiency). In Europe, the organization gives the following figures:

• 54% of anemia in children (6 months to 5 years) could be corrected by iron supplementation,
• 55% of anemia in menstruating women or women of childbearing age (15-49 years),
• 62% of anemia in pregnant women (15-49 years).

All countries combined, research has established that 50% of anemia in women (menstruating, of childbearing age, pregnant) is the result of iron deficiency.

Data specific to the French population were published in 2001 [5]:

• In menstruating women, the prevalence of iron deficiency was between 8.1 and 23% with 1.3 to 4.4% associated with anemia,
• In pregnant women, the prevalence of iron deficiency was between 54 and 77% with 9 to 30% associated with anemia,
• In children under 2, the prevalence of iron deficiency was 29.2% with 4.2% associated with anemia,
• In children under 2 to 6 years of age, the prevalence of iron deficiency was 13.6% with 2% associated with anemia,
• In adult males and the elderly, the prevalence is low.

In summary, although anemia is not necessarily due to iron deficiency, the data suggests a high likelihood that iron deficiency is the cause. It therefore appears necessary to monitor the iron status of the population, particularly in France, with particular attention to people at risk of deficiency, and therefore also at risk of anemia (mainly pregnant women or women of childbearing age and those at risk of deficiency). young children).

The iron in our body and in our diet

The two forms of iron in the body [6]
Two forms of iron cations exist: ferrous iron Fe2 + and ferric iron Fe3 +. Most of the body's iron (70%) is in the so-called "heme" form (ferrous, Fe2 + contained in heme), the rest being in "non-heme" form (ferric, Fe3 +, a form of transport and Reserve) :

• Fe2 + (ferrous iron): It is present at several levels in the body and is part of the composition of: - Hemoglobin: 2.4 g or 60% of the total iron. Hemoglobin is the protein in red blood cells linked at its center by a co-factor called heme containing an iron atom. This structure is able to receive an oxygen molecule and transport it. By entering into the composition of hemoglobin, iron is therefore essential for the formation of red blood cells (= erythrocytes), a phenomenon of erythropoiesis, as well as for the transport of oxygen. - Several enzymes of cellular respiration (cytochromes, oxidases, peroxidase, catalases, Krebs cycle enzymes) and DNA synthesis: 0.01 g or 0.3% of total iron. Fe2 + is part of the composition of mitochondria (cytochrome C) and participates in cell renewal, in the synthesis of hormones and neurotransmitters.
• Fe3 + (ferric iron): Within the body, it is used for:
  - Iron reserves: 1.4 g or 35% of total iron is included in ferritin (mainly; iron storage protein),
  - Transport iron: 0.005 g is linked to transferrin (protein responsible for transporting iron in plasma).

Dietary iron
Fe2 + is the form found in animal tissues (such as meat and fish) while the Fe3 + form is found in grains, legumes (plants) and eggs. There are therefore two types of dietary iron intake, depending on the form, and the major categories of foods in which they are found (table below). Between these two forms the absorption by the body will also not be the same : 

• Fe2 + iron (heme, of animal origin) is the form best absorbed by the body (15 to 20%),
• Non-heme iron (mainly of plant origin) is the form the least well absorbed by the body, from 3 to 5%.

The nutritional composition of foods can be viewed on the ANSES website, the National Agency for Food, Environmental and Occupational Health Safety.

Iron metabolism

The general iron cycle in the body [7–9]
Within the body there is a well-established system around iron. If the absorption capacity at the enterocyte level (cells of the wall of the small intestine) is 1 to 2 mg per day, the losses are approximately of the same order, 1 to 2 mg per day, due to cell losses ( example: digestive cells, skin and integuments) and various secretions (sweat, urine, bile or breast milk). The only mechanism that regulates iron levels in the body is through absorption. In reality, intake and loss are two almost independent mechanisms, and it is possible to accumulate "too much iron" if the intake is too large for the losses. Iron is also subjected to a recycling system, a “recirculating” pool of 20 -25 mg per day, between the synthesis of red blood cells in the bone marrow and their normal destruction (phagocytosis) by the reticulo-endothelial system (set of immune cells involved in the purification of the body).

The absorption of dietary iron in the body [9,10]
In a physiological situation, intestinal absorption is the only route of entry for iron. After a solubilization step in the stomach, the level of absorption is highest at the very beginning of the small intestine (mature enterocyte cells).

• Fe2 + (the best absorbed form, 15-20% of the total present in the gut): When it is heme (in the haem), it is directly absorbed by the intestinal mucosa via a haem-specific transporter.
• Fe3 + (non-heme, the least well absorbed form 3-5%): Whatever the intake, via food or Nutra in the form of ferric salts, it must first be reduced by intestinal cytochrome B ( DCYTB) in Fe2 + which can then be taken over by the DMT1.

The absorption of nutraceutical iron in the body
It's not all about dietary iron. When deficits exist, one can go through nutraceutical salts.

• Fe2 +: When in the non-heme Fe2 + form, iron is absorbed directly via DMT1 and therefore exhibits less absorption compared to its heme form.
• Fe3 +: There is also some form of Fe3 + present in certain salts such as Ferric hydroxide polymaltose. Like dietary Fe3 +, its absorption is less good than heme Fe2 +.

Regulation of absorption in the body [11,12]
The regulation of iron stocks is hormonal and mainly takes place at the level of absorption. A small hormonal peptide synthesized by the liver plays a crucial role in controlling iron absorption: hepcidin. By binding ferroportin, the transporter of iron from inside enterocytes (intestinal cells) to the bloodstream, hepcidin breaks down. In summary, hepcidin works by decreasing the intestinal absorption of dietary iron as well as the recycling of iron from red blood cells by macrophages. The expression of hepcidin is regulated according to different stimuli:

• When the body needs it, hepcidin decreases and iron is completely taken up by enterocytes to reach the bloodstream quickly (as is iron from macrophages). In short, therefore, a low plasma concentration of hepcidin is associated with large movements of iron leading to an increase in the level of iron in the body.
• With high dietary iron intakes and inflammation (and / or infection), hepcidin is increased and iron remains in enterocytes and macrophages. In short, an increased concentration of hepcidin causes a blockage of iron movements resulting in limiting the rise in iron levels in the body.

For example, in the event of significant blood loss, hepcidin is reduced to allow maximum absorption of Iron, which activates erythropoiesis (synthesis of red blood cells).

Bioavailability of iron [13,14]

Iron in the haem is the form with the best bioavailability (15 to 20%) with Fe2 + in ionic form (absorption very variable depending on the formula or the source). Since plant iron is in the form of Fe3 +, it must be reduced in order to be absorbed. In addition, in plants, certain compounds complex iron (such as phytates) preventing it from being reduced and assimilated. In total, vegetable iron therefore displays a particularly low absorption of 3 to 5%. We know, for example, that the consumption of tea inhibits the absorption of iron due to the presence of polyphenols capable of complexing iron: tannins. Other polyphenols from vegetables and grains could be involved, but the data is not yet clear. Other compounds, on the other hand, facilitate the absorption of iron. Vitamin C (ascorbic acid) has been shown to be able to facilitate the reduction of ferric iron to ferrous iron as well as chelate iron (iron made soluble). Finally, some heavy metals could compete with iron absorption mechanisms. Lead is an example of a competitor for iron, but the prevalence remains low in young children, the most vulnerable population.

Iron intake and requirements

General aspects of requirements [15]
Iron responds to a balancing mechanism. The contributions must strictly compensate for the losses. As part of an imbalance, the risk of impairment (or even deficiency) or overload (possibly pathological) may arise. By adding the amount of iron contained in the body and for each compartment, we obtain a total of 4 g (a little less for women, closer to 3 g) of iron in total (see paragraph: the two forms of iron ). Food intake hovers around 10 to 15 mg per day but the intestinal absorption capacity is 1 to 2 mg per day. As iron is stored in the body, the dietary reference intakes have therefore been developed in such a way as to ensure reserves. In 2016, the recommendations were revised to 11 mg / day for:

• Man
• Women with weak or normal menstrual losses (80% of the premenopausal female population),
• The postmenopausal woman.

Specific physiological situations [15]
Dietary iron is used to compensate for losses but also to meet increased needs in certain physiological situations (adaptation of absorption). Among these situations subject to iron deficiencies due to increasing demand, we can distinguish (EFSA data for reference intakes):

• Women with high menstrual loss. The recommended intakes then drop from 11 mg / d to 16 mg / d.
• Pregnant and lactating women. The recommended intakes then drop from 11 mg / d to 16 mg / d.
• Infants 7-11 months old. The recommended intakes are already 11 mg / day.
• Adolescents and especially adolescent girls (12-17 years old). The recommended intakes are 13 mg / day.

Non-physiological situations of vigilance

All cases of change in need are not necessarily referenced by health authorities and bodies. In particular, we can identify lifestyles that are likely to induce greater needs.
- Diets low in meat and / or fish are low in iron and increase the risk of iron deficiency. These diets are represented in particular by non-heme iron intake, the sources of which themselves contain factors limiting the absorption of iron, including the famous phytates, which are very present in soybeans for example (see part: Bioavailability of iron) [16] .
- Vegetarian and vegan women, versus non-vegetarians, have a higher prevalence of risk of iron deficiency anemia [17]. Another case may be raised. As part of intense sports training, it is all the more important to check the iron status and intakes in women. Although not all data show an established relationship between intensive training and iron deficiency (or need for supplementation) [18], monitoring of iron status and intake is widely encouraged in order to optimize performance [19 ].

State of iron intake
In France, the INCA III study (National Individual Study of Food Consumption) assessed the iron intake of different age groups (0-10 years, 11-17 years and 18-79 years) [20]:

The results of this work show that most age groups and categories have intakes below nutritional recommendations.
In 2019, a European-wide review on the specific iron intakes of women of childbearing age showed that, in a very large majority of countries, iron intakes are below the recommended 11 mg / day [21].

Iron supplementation

The major target: pregnant women [2,22,23]
Iron supplementation is particularly aimed at pregnant women to prevent maternal anemia and direct complications related to fetal development. During pregnancy, iron requirements increase sharply in response to a 30% expansion of body mass in red blood cells.
Iron intake is a major public health concern, referenced by the World Health Organization (WHO). To meet these increased needs during pregnancy, the recommended iron intake is around 30 mg / day, a dose almost twice the basic needs and can cause digestive discomfort.
Slow-release dietary iron supplement formulas would prevent it, but they would not be as effective in actually meeting the needs.
Moreover, this dose would be justified only for iron deficiency observed before and during pregnancy. It would seem that for prevention and to ensure not to fall into deficiency, formulations with much lower doses and optimizing iron absorption are more suitable.

Forms of iron in nutraceuticals [24,25]
Outside of the food and body context, whether or not iron is linked to heme no longer makes sense. In the literature, several iron formulations are referenced based on ferrous iron (Fe2 +) or ferric iron (Fe3 +) (in the form of salts):

• Ferrous fumarate (Fe2 +),
• Ferrous gluconate (Fe2 +),
• Ferrous citrate (Fe2 +),
• Ferrous sulphate (Fe2 +),
• Ferrous fumarate (Fe2 +),
• Iron bisglycinate (Fe2 +),
• Iron protein succinylate (Fe3 +),
• Polymaltose ferric hydroxide (Fe3 +).

The forms of ferrous salts (Fe2 +) are better absorbed and therefore more bioavailable. In Nutraceuticals, certain salts (sulphate) are found less and less compared to more recent forms (bisglycinate). Depending on the form of salt, the content of elemental iron is not the same. Ferrous fumarate contains the most elemental iron: 33%, compared to 20% ferrous sulfate or 12% ferrous gluconate. Note that it is the solubility in an acidic medium (stomach) which causes the rapid release of Fe2 + ions at the start of the small intestine and which determines the quality of iron absorption.

Think about absorption first
In order to avoid high amounts of iron and their unwanted side effects, it is possible to focus specifically on optimizing iron absorption. The increased absorption of iron by vitamin C has been documented for over 40 years. Although the data do not always support each other, they do point to an interest of vitamin C in optimizing the absorption of non-heme iron [26].
On the one hand, this optimization would depend on the individual's iron status (plasma ferritin). The lower this status, the more effective vitamin C would be on iron absorption [27].
On the other hand, the vitamin C / iron ratio would be interesting. The richer the diet in iron absorption inhibitors (such as phytates), the more iron absorption would be optimized by an increased vitamin C / iron ratio [28]. While vitamin C is one of the best-known factors in improving iron absorption, more work is still needed to better understand its level of interest.
Also, competition with the absorption of zinc (Zn2 +) and calcium (Ca2 +) seems only valid under very high intake conditions. That is to say in a case of significant and simultaneous supplementation, for example, of these 3 minerals [29].
Finally, interestingly, a meta-analysis demonstrated the effect of lactic acid strains on improving non-heme iron absorption and iron status in several clinical studies [30]. By hypothesis, certain specific strains promote the absorption mechanisms of non-heme iron (by DCYTB (reduction of Fe3 + to Fe2 +) and DMT1 (entry into the cell)) by capturing iron at the duodenal level [31].

The Nutri & Co formula: Iron and its Lactic Strain

Much more than a simple dietary iron supplement, our Iron and its Lactic Strain brings together 4 elements:

• iron provided by ferrous fumarate, up to 4.4 mg, "in support" of food intake, and playing a role in the process of cell division,
• a lactic strain: Lactobacillus plantarum 299vⓇ,
• vitamin B9 provided in the form of reduced folate: 5-Methyltetrahydrofolate * (5-MTHF, QuatrefolicⓇ), contributing to the growth of maternal tissues,
• vitamin C (ascorbic acid) to increase iron absorption.

* The supplementation of 5-Methyltetrahydrofolate (5-MTHF), bioactive form, allows to obtain a high bioavailability of vitamin B9. This is because the 5-MTHF form undergoes less enzymatic transformation to become active compared to folic acid [32].

Three clinical studies were performed on the formula we selected. In women of childbearing age, the results show that iron absorption is significantly higher (difference of 47% and 23% respectively) in the groups receiving the strain, compared to those receiving the formula without Lactobacillus plantarum 299vⓇ [33.34]. Finally, in a study carried out on 356 pregnant women, the analyzes show that taking the formula with Lactobacillus plantarum 299vⓇ significantly limited the decrease (versus placebo) in the iron-related blood markers of these women (ferritin and hemoglobin during pregnancy; measurements at 25, 28 and 35 weeks of pregnancy). Ferritin decreased by 46.2 µg / L in the group that used the formula, while it fell by 52.7 µg / L in the placebo group at 35 weeks. Finally, the hemoglobin decreased more in the placebo group (-13.7g / L) compared to the group taking the formula with strain (-9.1g / L) [35]. In other words, even if the blood markers logically drop during pregnancy, our formula could significantly reduce this drop by:

• 13% for ferritin,
• 34% for hemoglobin.

Publications

1. HAS RAPPORT D’EVALUATION - CHOIX DES EXAMENS DU METABOLISME DU FER EN CAS DE SUSPICION DE CARENCE EN FER; 2011; p. 82;.
2. Pasricha, S.-R.; Tye-Din, J.; Muckenthaler, M.U.; Swinkels, D.W. Iron Deficiency. Seminar 2020, 1–16.
3. Black, M.M.; Quigg, A.M.; Hurley, K.M.; Pepper, M.R. Iron Deficiency and Iron-Deficiency Anemia in the First Two Years of Life: Strategies to Prevent Loss of Developmental Potential: Nutrition Reviews©, Vol. 66, No. S1. Nutr. Rev. 2011, 69, S64–S70, doi:10.1111/j.1753-4887.2011.00435.x.
4. De Benoist, B.; World Health Organization; Centers for Disease Control and Prevention (U.S.) Worldwide Prevalence of Anaemia 1993-2005 of: WHO Global Database of Anaemia; World Health Organization: Geneva, 2008; ISBN 978-92-4-159665-7.
5. Hercberg, S.; Preziosi, P.; Galan, P. Iron Deficiency in Europe. Public Health Nutr. 2001, 4, 537–545, doi:10.1079/PHN2001139.
6. Dassonneville, M. Métabolisme du fer et anémie par carence martiale, 2015.
7. Anderson, G.J.; Frazer, D.M.; McLaren, G.D. Iron Absorption and Metabolism. 2009, 7.
8. Winter, W.E.; Bazydlo, L.A.L.; Harris, N.S. The Molecular Biology of Human Iron Metabolism. 2014, 11.
9. Yiannikourides, A.; Latunde-Dada, G.O. A Short Review of Iron Metabolism and Pathophysiology of Iron Disorders. 2019, 15.
10. Silva, B.; Faustino, P. An Overview of Molecular Basis of Iron Metabolism Regulation and the Associated Pathologies. Biochim. Biophys. Acta BBA - Mol. Basis Dis. 2015, 1852, 1347–1359, doi:10.1016/j.bbadis.2015.03.011.
11. Nicolas, G. L’hepcidine, le chef d’orchestre de l’homéostasie du fer. Diabète Obésité 2009, 94–98.
12. Wallace, D.F. The Regulation of Iron Absorption and Homeostasis. 2016, 37, 12.
13. Hurrell, R.; Egli, I. Iron Bioavailability and Dietary Reference Values. Am. J. Clin. Nutr. 2010, 91, 1461S-1467S, doi:10.3945/ajcn.2010.28674F.
14. Abbaspour, N.; Hurrell, R.; Kelishadi, R. Review on Iron and Its Importance for Human Health. J. Res. Med. Sci. 2014, 12.
15. EFSA Scientific Opinion on Dietary Refrence Values for Iron; 2015; p. 115;.
16. Phillips, F. Vegetarian Nutrition. Nutr. Bull. 2005, 30, 132–167, doi:10.1111/j.1467-3010.2005.00467.x.
17. Pawlak, R.; Berger, J.; Hines, I. Iron Status of Vegetarian Adults: A Review of Literature. Am. J. Lifestyle Med. 2018, 12, 486–498, doi:10.1177/1559827616682933.
18. Houston, B.L.; Hurrie, D.; Graham, J.; Perija, B.; Rimmer, E.; Rabbani, R.; Bernstein, C.N.; Turgeon, A.F.; Fergusson, D.A.; Houston, D.S.; et al. Efficacy of Iron Supplementation on Fatigue and Physical Capacity in Non- Anaemic Iron-Deficient Adults: A Systematic Review of Randomised Controlled Trials. BMJ Open 2017, 9.
19. Alaunyte, I. Iron and the Female Athlete: A Review of Dietary Treatment Methods for Improving Iron Status and Exercise Performance. 2015, 7.
20. ANSES Etude Individuelle Nationale Des Consommations Alimentaires 3 (INCA 3). Avis de l’ANSES. Rapport d’expertise Collective; 2017; p. 566;.
21. Milman, N.T. Dietary Iron Intake in Women of Reproductive Age in Europe: A Review of 49 Studies from 29 Countries in the Period 1993–2015. J. Nutr. Metab. 2019, 13.
22. ANSES AVIS de l’Agence Française de Sécurité Sanitaire Des Aliments Relatif à l’évaluation Des Justificatifs Concernant Le Dépassement Des Doses Maximales Admises En Folates, Vitamine D et En Fer Dans Un Complément Alimentaire Destiné Aux Femmes En Période Périconceptionnelle et Aux Femmes Enceintes.; 2007; p. 4;.
23. Petry, N.; Olofin, I.; Hurrell, R.; Boy, E.; Wirth, J.; Moursi, M.; Donahue Angel, M.; Rohner, F. The Proportion of Anemia Associated with Iron Deficiency in Low, Medium, and High Human Development Index Countries: A Systematic Analysis of National Surveys. Nutrients 2016, 8, 693, doi:10.3390/nu8110693.
24. Santiago, P. Ferrous versus Ferric Oral Iron Formulations for the Treatment of Iron Deficiency: A Clinical Overview. Sci. World J. 2011, 5.
25. Manoguerra, A.S.; Erdman, A.R.; Booze, L.L.; Wax, P.M.; Scharman, E.J.; Woolf, A.D.; Chyka, A.; Keyes, D.C.; Olson, K.R.; Caravati, E.M. Iron Ingestion: An Evidence-Based Consensus Guideline for Out-of-Hospital Management. Clin. Toxicol. 2005, 43, 553–570.
26. Heffernan, A.; Evans, C.; Holmes, M.; Moore, J.B. The Regulation of Dietary Iron Bioavailability by Vitamin C: A Systematic Review and Meta-Analysis. Proc. Nutr. Soc. 2017, 76, E182, doi:10.1017/S0029665117003445.
27. Collings, R.; Harvey, L.J.; Hooper, L.; Hurst, R.; Brown, T.J.; Ansett, J.; King, M.; Fairweather-Tait, S.J. The Absorption of Iron from Whole Diets: A Systematic Review1–4. Am J Clin Nutr 2013, 98, 65–81.
28. Teucher; Olivares; Cori Enhancers of Iron Absorption: Ascorbic Acid and Other Organic Acids. Int. J. Vitam. Nutr. Res. 2004, 74, 403–419, doi:10.1024/0300-9831.74.6.403.
29. Scheers, N. Regulatory Effects of Cu, Zn, and Ca on Fe Absorption: The Intricate Play between Nutrient Transporters. nutrients 2013, 14.
30. Vonderheid, S.C.; Tussing-Humphreys, L.; Park, C.; Pauls, H.; OjiNjideka Hemphill, N.; LaBomascus, B.; McLeod, A.; Koenig, M.D. A Systematic Review and Meta-Analysis on the Effects of Probiotic Species on Iron Absorption and Iron Status. Nutrients 2019, 11, 2938, doi:10.3390/nu11122938.
31. Sandberg, A.-S.; Önning, G.; Engström, N.; Scheers, N. Iron Supplements Containing Lactobacillus Plantarum 299v Increase Ferric Iron and Up-Regulate the Ferric Reductase DCYTB in Human Caco-2/HT29 MTX Co-Cultures. Nutrients 2018, 10, 1949, doi:10.3390/nu10121949.
32. Pietrzik, K.; Bailey, L.; Shane, B. Folic Acid and L-5-Methyltetrahydrofolate: Comparison of Clinical Pharmacokinetics and Pharmacodynamics. Clin. Pharmacokinet. 2010, 49, 535–548, doi:10.2165/11532990-000000000-00000.
33. Hoppe, M.; Önning, G.; Berggren, A.; Hulthén, L. 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. Br. J. Nutr. 2015, 114, 1195–1202.
34. Hoppe, M. Freeze-Dried Lactobacillus Plantarum 299v Increases Iron Absorption in Young Females— Double Isotope Sequential Single-Blind Studies in Menstruating Women. PLoS ONE 2017, 12, 15.
35. Axling, U.; Önning, G.; Martinsson Niskanen, T.; Larsson, N.; Hansson, S.R.; Hulthén, L. The Effect of Lactiplantibacillus Plantarum 299v Together with a Low Dose of Iron on Iron Status in Healthy Pregnant Women: A Randomized Clinical Trial. Acta Obstet. Gynecol. Scand. 2021, aogs.14153, doi:10.1111/aogs.14153.