What Is Lactoferrin: Benefits and Side Effects

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What Is Lactoferrin: Benefits and Side Effects

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What is Lactoferrin?

Lactoferrin is an iron-binding glycoprotein from the transferrin protein family. 

Lactoferrin can be found in many biological fluids including saliva, tears, reproductive fluids, and gastrointestinal fluids (1).

It is also present in polymorphonuclear(PMNs) leukocytes and plays an important role in immune defense (2).

High quantities of Lactoferrin are present in mammal colostrum (milk produced during or immediately after pregnancy). Lactoferrin and other bioactive compounds give immune protection to newborns (3).

Dietary lactoferrin supplement of human and bovine origin has been extensively used in research. Several health benefits of dietary lactoferrin have been discovered so far including antibacterial, antiviral, immune modulation, anti-inflammatory, and gut health. 

Lactoferrin is widely used in infant formula, beverages, milk products, and even cosmetics. It is also present in whey protein

The most relevant lactoferrin health benefits are described below.  

Milk in a glass
Milk contains lactoferrin

1) Lactoferrin can alleviate and even prevent anemia

Anemia has severe consequences for human health and disease. 

Anemia is defined as the condition in which “the hemoglobin levels are lower than a certain g/100ml of venous blood at sea level” (4). For example, in an adult non-pregnant female having lower than 11g of hemoglobin/100ml of blood is considered an anemic.

Approximately 50% of anemia cases are due to iron deficiency (5).

Human lactoferrin contains about 20% iron whereas bovine lactoferrin contains between 15-19 % iron (6).

Bovin lactoferrin milk formula was better at inducing iron absorption in infants compared to iron-fortified milk formulas (7).

In long-distance female runners, the use of lactoferrin was sufficient to prevent iron deficiency. Therefore, lactoferrin use can prevent anemia in female athletes (8).

A randomized control study found that lactoferrin is as effective as ferrous sulfate in increasing iron in pregnant women without any side effects (9).

In another study, iron deficiency anemia (IDA) pregnant women showed better iron recovery with lactoferrin compared to ferrous sulfate without any adverse effects (10).

Oral intake of 30% iron saturated bovine lactoferrin (100mg twice daily) significantly increased hemoglobin as well as iron in pregnant women. Ferrous sulfate treatment also improved hemoglobin and iron but with some side effects (11).

A meta-analysis of several studies found that lactoferrin is just as good a ferrous sulfate for IDA treatment with fewer gastrointestinal issues (12). Therefore, lactoferrin is the iron replacement agent of choice for the treatment of IDA in pregnancy.

Lactoferrin is a good choice in alleviating anemia. It is as good as ferrous sulfate and does not have adverse side effects. 

2)  Lactoferrin has a strong Antimicrobial effect

lactoferrin’s strong antimicrobial function is described by many studies. 

Several in vitro, animal, and human clinical trials describe the positive effects of oral lactoferrin intake.

Lactoferrin is broken down and converted into peptides in the stomach by digestive enzymes. These peptides have tremendous antimicrobial effects (13).

For example, lactoferricin peptide has a strong antimicrobial effect (14).

Another peptide called Lactoferrampin was effective against several microbial pathogens including E.coli, Bacillus subtilis, and Pseudomonas aeruginosa (15).

Lactoferrin is effective against Helicobacter pylori infection (16).

In humans, a double-blind randomized placebo control study showed that the use of bovine lactoferrin was effective in suppressing Helicobacter pylori (17).

Lactoferrin also showed antibacterial effects against Mycobacterium tuberculosis and Escherichia coli O157:H7 (18,19).

Lactoferrin has antiviral activity as well. 

Studies show that it can be effective against coronavirus (Covid-19) because of its broad-spectrum antiviral activity (20,21).

Another study found lactoferrin to be useful in hepatitis C treatment (22). It also inhibited the herpes simplex virus when used with or without standard therapy (23,24). Lactoferrin also shows antiviral activity against hepatitis B, human cytomegalovirus (CMV), and HIV (25,26,27,28).

Lactoferrin has a strong antibacterial and antiviral function. Lactoferrin-derived peptides are largely responsible for this antimicrobial function. 

3)  Lactoferrin boosts the immune system

The immunomodulatory effect of lactoferrin is proven by several research studies. 

Lactoferrin has a complex role in the immune response.

Lactoferrin from neutrophils is released at the site of infection and plays an important role in the immune defense. The concentration of lactoferrin increases many folds after an infection in the body (29,30).

Lactoferrin promotes specific immune cells such as T-lymphocytes and macrophages to enhance immune response (31,32).

Animal studies show an increase in immune cells such as NK cells and lymphocytes with lactoferrin intake (33,34).

Lactoferrin oral intake was associated with increased systemic immune response (35).

In humans, oral intake of up to 200mg bovine lactoferrin in healthy individuals significantly increased immune cells (helper T-cell and cytotoxic T-cells). Its use also provided an anti-oxidant effect (36).

Two other studies in humans confirmed that intake of oral bovine lactoferrin significantly boosted the immune system (37,38).

Lactoferrin has an immunomodulatory function. It improves immune defense against pathogens. 

4)  Lactoferrin has anti-inflammatory and pro-inflammatory effects

Lactoferrin has both pro-and anti-inflammation functions. High inflammation is damaging to the body whereas too little inflammation is ineffective for tissue repair after infection. By modulating the immune system it promotes a pro or anti-inflammatory response to maintain balance in the body (39).

Several in vitro and animals studies show the pro and anti-inflammatory function to inhibit infection. 

Lactoferrin exists in two forms apo-lactoferrin (non-iron bound) and holo-lactoferrin (iron-bound). 

Both forms are effective in reducing inflammatory responses of pathogens in immune cells (40).

In vitro use of lactoferrin shows its anti-inflammatory potential. It successfully inhibited the IL-8, IL-6, and TNFα  (41).

It also enhanced anti-inflammation by modulating immune responses to eradicate infection (42).

In animal disease models, it successfully induced a pro-inflammatory response for immune cell activation and protection from infection (43).

Other studies found similar pro-inflammatory functions (44).

In children, the use of curcumin and lactoferrin supplements successfully lowered the rate of recurrent respiratory infections by immune system modulation (45).

Similarly, in weaned infants, lactoferrin fortified milk formula was effective in lowering the incidences of respiratory illness and diarrhea (46).

Lactoferrin acts as a balancer by promoting both pro and anti-inflammation mostly via immune modulation in the body. This protects tissues from access damage while also protecting them from pathogens. 

4)  Lactoferrin can inhibit tumor cells growth

Lactoferrin may have the potential in inhibiting tumor cell growth because of its role in the immune system. 

Research shows that cancer incidences are increased when lactoferrin is produced in lower quantities due to dysfunction in its gene expression (47).

Therefore oral intake may be useful to supplement in individuals with low lactoferrin gene expression. 

Lactoferrin can selectively induce tumor cell death while leaving the healthy cells intact  (48).

In animal studies, lactoferrin and its peptides are effective in inhibiting tumor cell growth as well as metastasis (49).

Lactoferrin and its peptides were also beneficial in chemotherapy treatment. Their use reduced tumor growth in chemotherapy in the animal disease models (50,51,52).

In humans, the oral intake of 3g/day bovine lactoferrin significantly reduced the size of colorectal adenomatous polyp (53). 

Lactoferrin can selectively inhibit the growth of tumor cells because of its immune modulation effects. In humans, more clinical trials are required to fully understand lactoferrin’s efficacy.

5)  Lactoferrin can reduce symptoms of certain skin conditions

Since lactoferrin has anti-inflammatory, which may be effective against skin conditions that have inflammatory nature. 

A few studies show that the use of lactoferrin may be useful in acne control.

The use of chewable bovine lactoferrin tablets twice daily for 8 weeks reduced acne lesions in participants (54).

In a randomized control study, the use of fermented milk with 200 mg of lactoferrin for 12 weeks significantly reduced the acne symptoms including acne lesion count, acne grade, triacylglycerols, and free fatty acids (55).

A study found that the use of lactoferrin with vitamin C and Zinc significantly reduced acne lesions in people with mild to moderate acne vulgaris (56).

For psoriasis, a topical ointment containing lactoferrin may benefit in reducing the symptoms of psoriasis (57).

Use of 5g XP-828L twice daily for 56 days reduced psoriasis condition without any adverse effects (58).

In a placebo-controlled, double-blind study, patients suffering from athlete’s foot showed a significant improvement in symptoms after lactoferrin use (59).

Currently, only a handful of studies show lactoferrin benefits in skin conditions. But the research is promising for acne, psoriasis, and athlete’s foot.  

6)  Lactoferrin good for bone health

Lactoferrin can enhance cell growth and differentiation, therefore, can be useful in bone tissue regeneration (60).

Animal studies found that lactoferrin can improve osteoblast cell growth while minimizing cell death (61).

Tumor necrosis factor α (TNFα) and interleukin 1 beta (IL-1β) are cytokines that lead to bone cell loss. Lactoferrin decreases the secretion of these cytokines (62,63).

Lactoferrin promotes cell division by impacting different cellular pathways. It promotes bone formation and regeneration. 

Osteoclasts cause bone degradation. Lactoferrin inhibits osteoclasts (64).

In several in vitro and animal studies, lactoferrin promoted bone growth. However, there is a lack of robust human studies to confirm these results.

Other potential benefits

Lactoferrin promotes probiotics 

Lactoferrin in milk promotes friendly bacteria in the body. Several studies using bovine and human milk showed the growth of bifidobacterium probiotics (65,66,67). Thus, lactoferrin is beneficial in promoting probiotics which are good for maintaining a healthy body. 

Lactoferrin inhibits pathogenic bacteria but it also inhibits some probiotics as well (68).

Lactoferrin may have an anti-obesity effect

A few studies have investigated the use of lactoferrin in weight loss and obesity. 

In animals studies, the use of lactoferrin was beneficial in reducing fat and overall body weight (69,70).

In humans, the use of 300 mg/day enteric-coated lactoferrin for 8 weeks significantly reduced body fat (71).

More studies are required to confirm the role of lactoferrin in obesity.

Lactoferrin can be used as a bioindicator 

Lactoferrin can be a bioindicator for the detection of inflammatory bowel diseases (IBD). Both Crohn’s disease (CD) and ulcerative colitis (UC) are IBD. Increased concentration of lactoferrin is observed in IBD and thus, more lactoferrin is released in feces (72,73). This presents a non-invasive and safe detection method of IBD.

Lactoferrin levels are significantly reduced in the saliva of Alzheimer’s disease patients (74). This observation is specific to Alzheimer’s disease compared to other brain diseases, therefore, can be a useful tool for early detection and distinction of Alzheimer’s disease (75).

In dry eye disease, the concentration of lactoferrin is significantly reduced in tears. Therefore, lactoferrin levels present a way to detect dry eye disease in patients (76).

Lactoferrin side effects

To date, no study has noted any adverse effects of lactoferrin use. It is in the FDA’s GRAS (Generally Recognized As Safe) list. It is part of infant diet formulas worldwide (77).

It is also used in the production of yogurt, milk products, skim milk, pet food, supplements, and cosmetics (78).

The Gist

Since its discovery, many health benefits of lactoferrin have been discovered. 

Several animal studies have confirmed the role of lactoferrin in antimicrobial activity, immune systems, and inflammation. 

Current research in humans, although limited, is promising as several studies have confirmed the benefits but there are not many robust control trials to absolutely confirm those effects.

Future studies, in humans, will add to the existing benefits of lactoferrin.