Lactoferrin-Enriched Whey for Iron-Deficiency Anemia

Overseen By Connor J kemp, BS

Age: 18 - 65

Sex: Female

Trial Phase: Academic

Sponsor: Utah State University

Must not be taking: NSAIDs, Corticosteroids, Anticoagulants, others

Disqualifiers: Pregnancy, Diabetes, Autoimmune diseases, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 2

Duration: 16 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines how a special drink mix can improve iron levels and reduce inflammation in active young women with iron-deficiency anemia. Participants will consume a drink enriched with lactoferrin (a protein found in milk), iron, and vitamin B12 twice daily for 16 weeks. The trial includes different groups testing variations with lactoferrin-enriched whey protein, rice protein, or maltodextrin. Women who exercise regularly and experience issues related to low iron might be suitable candidates. As an unphased trial, this study provides a unique opportunity to contribute to research that could benefit others with similar health concerns.

Do I have to stop taking my current medications?

You may need to stop taking certain medications or supplements that affect the study outcomes, like NSAIDs, corticosteroids, or iron supplements, if they can't be temporarily discontinued for the study.

Will I have to stop taking my current medications?

If you are taking medications or supplements that affect the study's outcome measures, like NSAIDs, corticosteroids, or iron supplements, you may need to stop them temporarily for this study.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that lactoferrin, when combined with iron and vitamin B12, is generally safe for people. Studies suggest that bovine lactoferrin (a protein from cow's milk) is safe to include in diets and is recognized as safe (GRAS) for consumption, meaning people can usually take it without worrying about serious side effects.

Other studies have found that treatments enriched with lactoferrin have very few side effects. This includes those mixed with proteins like whey or rice, as well as with maltodextrin (a carbohydrate used in foods). These combinations have been used to improve iron levels and appear safe based on current research.

Overall, evidence suggests that the treatments being studied, whether mixed with whey, rice, or maltodextrin, are well-tolerated and safe. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for iron-deficiency anemia, which typically involve oral or intravenous iron supplements, these investigational treatments incorporate lactoferrin paired with iron and B12 in different protein bases. Researchers are particularly excited about the potential of lactoferrin, a natural protein known for enhancing iron absorption and having anti-inflammatory properties. The use of different protein bases like whey, rice, and maltodextrin could offer tailored options for patients with specific dietary preferences or restrictions. This combination might lead to improved iron absorption, reduced side effects, and an overall more efficient treatment for iron-deficiency anemia.

What evidence suggests that this trial's treatments could be effective for iron-deficiency anemia?

Research has shown that combining lactoferrin with iron and vitamin B12 can greatly improve iron levels. Studies have found that these nutrients together increase hemoglobin (the protein in red blood cells that carries oxygen) and raise red blood cell counts in people with low iron. This combination also reduces inflammation, which helps the body absorb iron better. In this trial, participants will receive different formulations of lactoferrin, iron, and B12. Specifically, using lactoferrin in a whey protein drink, one of the study arms, improved iron levels more effectively than using non-milk proteins like rice, which is another arm in this trial. This suggests that the combination could be especially helpful for improving iron metabolism in young, active women. ^{1 3 4 6 7}

Are You a Good Fit for This Trial?

This trial is for active young women aged 18-30 with a BMI of 18-30 kg/m2 who are experiencing iron-deficiency anemia. Participants should exercise regularly, speak and understand English, and be able to give informed consent. It's not suitable for those outside these criteria.

Inclusion Criteria

I am female.

My Body Mass Index (BMI) is between 18 and 30.

For my safety and proper consent, I am...

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1 week

1 visit (in-person or virtual)

Treatment

Participants consume assigned supplements twice daily for 16 weeks

16 weeks

Weekly visits for supplement pickup and questionnaire completion

Mid-intervention Check-in

Participants complete a 7-day food log and other questionnaires

1 week

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Lactoferrin, Iron and B12 in Maltodextrin
• Lactoferrin, Iron and B12 in Rice Protein
• Lactoferrin, iron and B12 in Whey Protein

Trial Overview The study tests the effects of drinks enriched with lactoferrin (200 mg), iron (6 mg), and vitamin B12 (5.2 µg) on iron metabolism and inflammation in females when consumed twice daily over 16 weeks. The drinks are based on whey protein, rice protein, or maltodextrin.

How Is the Trial Designed?

Group I: Lactoferrin in Whey Protein Active Control 1 Intervention

Lactoferrin (200 mg), iron (6 mg), and B12 (5.2 ug) in a whey protein isolate drink (20 grams of protein) to be taken 2 times daily; once before the morning meal and once before the evening meal.

Group II: Lactoferrin in Rice Protein Active Control 1 Intervention

Lactoferrin (200 mg), iron (6 mg), and B12 (5.2 ug) in a rice protein drink (20 grams of protein) to be taken 2 times daily; once before the morning meal and once before the evening meal.

Group III: Lactoferrin Control Active Control 1 Intervention

Lactoferrin (200 mg), iron (6 mg), and B12 (5.2 ug) in a maltodextrin drink (0 grams of protein) to be taken 2 times daily; once before the morning meal and once before the evening meal.

Lactoferrin, Iron and B12 in Maltodextrin is already approved in United States, European Union for the following indications:

Approved in United States as Lactoferrin, Iron and Vitamin B12 Supplement for:

• Iron deficiency anemia
• Inflammation reduction

Approved in European Union as Lactoferrin, Iron and Vitamin B12 Supplement for:

• Iron deficiency anemia
• Inflammation reduction

Who Is Running the Clinical Trial?

Utah State University

Lead Sponsor

Trials

48

Recruited

5,200+

BUILD Dairy

Collaborator

Trials

2

Recruited

100+

Glanbia Nutritionals

Industry Sponsor

Trials

1

Recruited

80+

Published Research Related to This Trial

Lactoferrin, an important protein found in milk, has beneficial effects for both newborns and adults, leading to interest in its use as a nutritional supplement.

Human lactoferrin can be produced from various sources like yeast, transgenic cows, and rice, with the latter two being suitable for food applications, although they are still awaiting regulatory approval.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recombinant human lactoferrin: a valuable protein for pharmaceutical products and functional foods. Conesa, C., Calvo, M., Sánchez, L.[2022]

In a study involving SD rats with iron deficiency anemia, treatment with iron saturated recombinant human lactoferrin (Fe-rhLf) significantly improved hemoglobin levels and red blood cell counts compared to the control group, indicating its efficacy in treating this condition.

The high dose of Fe-rhLf not only enhanced hematological parameters but also altered liver hepcidin and ferroportin expression, suggesting a mechanism of action that may involve regulation of iron metabolism.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Efficacy of iron saturated recombinant human lactoferrin on alleviating iron deficiency anemia in rats]. Fang, YH., Feng, X., Xu, H., et al.[2019]

Lactoferrin supplementation significantly improved serum iron levels, ferritin, and hemoglobin concentration compared to ferrous sulfate, indicating its superior efficacy in managing iron-deficiency anemia.

The study suggests that lactoferrin's effectiveness may be linked to its anti-inflammatory properties rather than its influence on iron absorption, as it showed a reduction in fractional iron absorption compared to ferrous sulfate.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative Effects between Oral Lactoferrin and Ferrous Sulfate Supplementation on Iron-Deficiency Anemia: A Comprehensive Review and Meta-Analysis of Clinical Trials. Zhao, X., Zhang, X., Xu, T., et al.[2023]

In a study involving 100 pregnant women with iron deficiency anemia, both bovine lactoferrin and ferrous sulfate effectively increased hemoglobin and iron levels after 30 days of treatment, showing similar efficacy.

Bovine lactoferrin was associated with significantly fewer gastrointestinal side effects, such as abdominal pain and constipation, compared to ferrous sulfate, making it a potentially safer option for treating iron deficiency in pregnant women.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and tolerability of oral bovine lactoferrin compared to ferrous sulfate in pregnant women with iron deficiency anemia: a prospective controlled randomized study. Nappi, C., Tommaselli, GA., Morra, I., et al.[2014]

In a study involving lactating Wistar rats, the absorption and bioavailability of iron from 57Fe-Lf (apo-lactoferrin) and 57FeSO4 were compared, revealing that the type of iron and dosage significantly influenced iron distribution in the body.

The findings suggest that using iron salts in excess of lactoferrin is the most effective method for iron supplementation in formula milk, as it optimizes iron transport and storage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Iron bioavailability from supplemented formula milk: effect of lactoferrin addition. Fernández-Menéndez, S., Fernández-Sánchez, ML., González-Iglesias, H., et al.[2018]

Supplementation with bovine lactoferrin (bLf) in iron-fortified formulas significantly reduced the incidence of respiratory tract infections and diarrhea in weaned infants, as shown in a study of 260 infants over 3 months.

Infants receiving lactoferrin-fortified formula experienced fewer respiratory symptoms and diarrhea-related illnesses compared to those on non-fortified formula, suggesting that bLf may enhance immune function in this age group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of bovine lactoferrin from iron-fortified formulas on diarrhea and respiratory tract infections of weaned infants in a randomized controlled trial. Chen, K., Chai, L., Li, H., et al.[2016]

Supplementing iron bound to lactoferrin effectively prevents anemia in young mice, showing similar efficacy to traditional iron chloride supplementation, even after a 4-week diet low in iron.

Lactoferrin appears to be a safe and effective vehicle for iron supplementation, as it did not negatively impact the iron status of the mice, making it a promising option for addressing iron deficiency.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Supplementation of milk with iron bound to lactoferrin using weanling mice: L. Effects on hematology and tissue iron. Fransson, GB., Keen, CL., Lönnerdal, B.[2019]

In a study involving 100 weanling SD rats over 28 days, recombinant human lactoferrin (rhLF) showed no significant differences in food safety indicators compared to bovine lactoferrin (bLF), indicating that both are safe for consumption.

Both rhLF and bLF groups demonstrated improved serum iron levels and transferrin saturation compared to the control group, suggesting that these lactoferrins can enhance iron nutrition without adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Animal experiment of recombinant human lactoferrin based on the 28 days repeated oral toxicity]. Ma, B., Yuan, X., Wang, X., et al.[2019]

In a study involving 260 infants aged 4 to 6 months, those fed an iron-fortified formula with lactoferrin showed significantly improved hematologic indexes, including higher hemoglobin levels and total body iron content, compared to those on a standard iron-fortified formula without lactoferrin.

The lactoferrin-fortified group also had a lower prevalence of anemia and iron deficiency, indicating that lactoferrin enhances iron absorption and overall iron status in infants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Iron metabolism in infants: influence of bovine lactoferrin from iron-fortified formula. Ke, C., Lan, Z., Hua, L., et al.[2015]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10825996/

The effectiveness of oral bovine lactoferrin compared to ... Most of the studies report that LF showed a statistically significant increase in Hb concentration levels, compared to those in the iron group.

2. digitalcommons.usu.edu digitalcommons.usu.edu/cgi/viewcontent.cgi?article=2043&context=honors

The Impact of Lactoferrin and Iron-Enriched Whey on Iron ... The study aimed to determine whether lactoferrin-enriched whey protein would more effectively improve iron status compared to non-milk protein (rice) or ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8389615/

Lactoferrin for Prevention and Treatment of Anemia and ... The results of numerous studies indicate that diet supplementation with lactoferrin (LTF), an iron-binding protein, may be advantageous in prophylaxis and ...

4. journals.lww.com journals.lww.com/esnt/fulltext/2022/22040/role_of_oral_lactoferrin_as_a_source_of_iron.2.aspx

Role of oral lactoferrin as a source of iron supplementation ... Oral lactoferrin was found to be effective in treating iron-deficiency anemia regarding blood Hb, blood RBCs, serum iron, serum ferritin, and TIBC.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT04014855

Lactoferrin Versus Iron Supplement in Irondeficiency ... An unfavorable change in the health of a participant, including abnormal laboratory findings, that happens during a clinical study or within a certain amount of ...

6. withpower.com withpower.com/trial/phase-serum-ferritin-2-2024-14f0c

Lactoferrin-Enriched Whey for Iron-Deficiency Anemia The safety data for lactoferrin-enriched treatments, including those combined with iron and vitamin B12, suggest that lactoferrin is generally well-tolerated ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S0268005X23003181

Lactoferrin as a carrier of iron: Development and ... In this work, lactoferrin (LF) particles were developed by Nano Spray Dryer (NSD) and its capacity to be used as an iron carrier was evaluated.