Does Lactoferrin Make You Tired? Understanding the Surprising Link to Energy and Fatigue

December 25, 2025 •

4 min read

Lactoferrin, a multifunctional glycoprotein found in milk, is often hailed for its immune-boosting properties. Despite its many health benefits, anecdotal reports and a small number of studies have led some to wonder if this supplement could actually cause fatigue or tiredness. The reality is more complex, involving dosage, iron metabolism, and immune system response.

Quick Summary

Lactoferrin supplementation rarely causes fatigue at normal doses and is more likely to boost energy by improving iron levels and sleep. Minor tiredness is a reported side effect only at very high intakes.

Key Points

Rarely Causes Fatigue: Lactoferrin is more likely to boost energy and combat tiredness, not cause it.
High Doses Are Different: Only very high, excessive doses have been anecdotally associated with side effects like fatigue.
Improves Iron Status: It helps fight fatigue by improving iron absorption and metabolism, often more effectively and with fewer GI issues than traditional iron pills.
Supports Better Sleep: Studies have shown that lactoferrin supplementation can lead to improvements in sleep quality and reduced morning fatigue.
Fights Inflammation: Its anti-inflammatory properties can help reduce the systemic inflammation that often contributes to chronic fatigue.
Individual Responses Vary: Some research indicates a strong placebo effect for fatigue reduction, suggesting results can depend on the individual and their specific health condition.

The Lactoferrin-Fatigue Connection: A Complex Relationship

Lactoferrin's impact on energy levels is multifaceted, primarily linked to its roles in iron metabolism and immune regulation. Rather than causing fatigue, lactoferrin is more often associated with relieving it, particularly in individuals with underlying conditions like iron-deficiency anemia. Its ability to bind and transport iron is a key mechanism, ensuring the body has the necessary resources for producing red blood cells and maintaining cellular energy.

How Lactoferrin Improves Energy Levels

Lactoferrin's primary benefits for energy are indirect, stemming from its fundamental biological functions. By addressing common causes of fatigue, it helps the body function more efficiently.

Enhancing Iron Absorption: As an iron-binding protein, lactoferrin can improve the body's iron status more effectively and with fewer side effects than traditional ferrous sulfate supplements. Iron is critical for transporting oxygen via hemoglobin, and a deficiency leads directly to fatigue. By optimizing iron levels, lactoferrin can boost overall energy and vitality.
Modulating Inflammation: Chronic inflammation is a significant contributor to fatigue. Lactoferrin exhibits potent anti-inflammatory properties by regulating cytokine production. By helping to calm the immune system, it can reduce the systemic inflammation that drains energy and causes a feeling of malaise.
Supporting Sleep Quality: Several studies suggest that lactoferrin can improve sleep quality and reduce morning fatigue, especially in individuals with poor sleep patterns. One pilot study showed that tour conductors who took liposomal lactoferrin experienced significantly better subjective and objective sleep quality and less daytime tiredness despite shortened sleep duration. The mechanism may involve reducing neuroinflammation, which is linked to sleep disturbances.
Promoting Gut Health: Lactoferrin helps balance the gut microbiome by fostering the growth of beneficial bacteria like Bifidobacterium and Lactobacillus while inhibiting harmful pathogens. A healthy gut is strongly linked to overall energy levels and reduced systemic inflammation.

When Lactoferrin Might Cause Fatigue

While generally beneficial for energy, there are rare cases where lactoferrin might be associated with fatigue or tiredness. These instances are typically linked to extremely high doses, which can overwhelm the body's systems.

High-Dose Side Effects: One report indicates that at very high dosages, side effects such as fatigue, chills, diarrhea, and constipation have been noted. For most users taking standard supplemental doses, this is not an issue.
Individual Sensitivity: As with any supplement, individual body chemistry and sensitivity can play a role. Some people may be more sensitive to the initial effects of lactoferrin as their body adjusts, but this is uncommon.

A Deeper Look at Research and Effects

Research on lactoferrin's direct effect on fatigue has yielded mixed but generally positive results, with some notable exceptions. The benefits often depend on the context of the individual's health status.

Success in Iron Deficiency: A randomized controlled trial in pregnant women with iron-deficiency anemia found that lactoferrin supplementation improved iron status and significantly reduced fatigue. This highlights the protein's effectiveness in targeted populations where the root cause of fatigue is addressed.
Limited Effect in Long COVID: A randomized, double-blind, placebo-controlled trial on long-COVID patients, where fatigue is a common symptom, found no significant difference in fatigue reduction between the lactoferrin group and the placebo group. Both groups experienced an initial improvement in fatigue, suggesting a strong placebo effect or natural recovery, but lactoferrin did not offer a measurable additional benefit for this specific condition.

Lactoferrin vs. Traditional Iron Supplements

To understand lactoferrin's value, it helps to compare it with standard iron supplements, which are a common treatment for fatigue caused by iron deficiency.


Feature	Lactoferrin (Iron-Improving)	Ferrous Sulfate (Traditional Iron Supplement)
Primary Mechanism	Indirectly improves iron status via anti-inflammatory effects and better tolerance, rather than direct absorption of large iron quantities.	Directly supplements large amounts of elemental iron to boost iron levels quickly.
Iron Absorption	A meta-analysis found lactoferrin supplementation led to better iron parameters (serum iron, ferritin, hemoglobin) compared to ferrous sulfate, despite lower fractional iron absorption. The anti-inflammatory effect may be key.	High fractional iron absorption, but often with poor tolerance.
Gastrointestinal Side Effects	Generally well-tolerated at normal doses, with minor issues like diarrhea only at very high doses.	Higher incidence of unpleasant GI side effects, such as constipation, stomach pain, and nausea.
General Fatigue Effects	Often used to combat fatigue, particularly linked to anemia or sleep issues. Rarely, very high doses may cause fatigue.	Treats fatigue directly caused by iron deficiency but side effects can cause temporary discomfort.

Conclusion: The Final Verdict on Lactoferrin and Tiredness

For the vast majority of people, lactoferrin does not make you tired. In fact, its mechanism of action—improving iron metabolism, modulating the immune system, and promoting sleep—is designed to increase energy and reduce fatigue. Any reports of fatigue are exceptionally rare and typically associated with excessive, high dosages. The nuanced reality is that while not a universal cure for all types of fatigue (as seen in some long COVID studies), lactoferrin's role in addressing common underlying causes like poor iron status and inflammation makes it a promising tool for boosting vitality and overall wellness. As with any new supplement, it's always best to start with a standard dose and consult with a healthcare provider, especially if you have an existing health condition.

For more information on the comparison between lactoferrin and ferrous sulfate for improving iron status, you can review this meta-analysis: Comparative Effects between Oral Lactoferrin and Ferrous Sulfate Supplementation on Iron-Deficiency Anemia: A Comprehensive Review and Meta-Analysis of Clinical Trials.

Frequently Asked Questions

Lactoferrin rarely causes tiredness. It is generally well-tolerated, and any reported fatigue typically occurs only at very high dosages, along with other minor side effects like digestive upset.

Lactoferrin helps combat fatigue by improving the body's iron absorption, which is crucial for energy production. It also reduces inflammation and can support better sleep quality, all of which contribute to higher energy levels.

Yes, several studies suggest that lactoferrin may improve sleep quality. Research has shown that supplementation can lead to less 'sleepiness and fatigue on rising' and more restorative sleep, potentially by reducing neuroinflammation.

For fatigue caused by iron deficiency, some studies suggest lactoferrin can be a superior option. A meta-analysis found it improved iron status more effectively than ferrous sulfate, with significantly fewer gastrointestinal side effects.

Standard clinical studies have used doses ranging from 100 to 450 milligrams per day without significant issues. Adverse side effects like fatigue have only been reported at much higher, excessive doses.

People with iron-deficiency anemia, pregnant women experiencing fatigue, or individuals with poor sleep are among those who have shown the most benefit from lactoferrin supplementation in studies.

Yes, lactoferrin is not a cure-all for every type of fatigue. Fatigue can be caused by many factors, including other nutritional deficiencies, medical conditions, or lifestyle factors. It's important to consult a healthcare professional to identify the root cause.