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Showing posts with label FLA. Show all posts
Showing posts with label FLA. Show all posts

Friday, 12 December 2025

Lactoferrin - the "Liquid Gold" protein for babies, older people and some Autism

 


This post is rather long. You could summarise by "Trial lactoferrin, or camel milk."


For many families managing autism, the most challenging co-occurring issues are often chronic gastrointestinal (GI) problems and related behavioral challenges. The link between the gut, the immune system, and the brain—the Gut-Brain Axis—is a growing area of research, and one key protein is generating significant interest in Lactoferrin.

Lactoferrin is a multifunctional protein found naturally in milk, recognized for its anti-inflammatory, antimicrobial, and immune-modulating properties. But how exactly does this protein connect to the world of autism?

 

The "Good" Lactoferrin: Immune Support and Neuroprotection

When consumed as food or a supplement, lactoferrin acts as a protective agent. Its potential benefits for individuals with ASD are rooted in its ability to target two core issues: inflammation and microbial imbalance.

The Natural Power of First Milk

  • Human Colostrum & Research Status: Lactoferrin is abundant in colostrum (the "liquid gold" first milk). It acts as the newborn's first immune shield, helping to "seal" the gut, prevent infections, and establish a healthy microbiome. In the context of ASD, bovine colostrum products (BCP), often combined with probiotics, have been the subject of small-scale pilot studies. These initial trials suggest BCP may be well-tolerated and can help reduce GI inflammation and improve gut function, leading to associated improvements in certain behavioral symptoms. However, large-scale clinical trials are still required to validate colostrum as an effective core therapy for ASD.

  • Camel Milk's Unique Role: In regions like Saudi Arabia, camel milk has been traditionally used and studied as a complementary intervention for autism symptoms. Camel milk is naturally rich in lactoferrin—often higher than cow's milk—and possesses a unique protein profile.

    • High Bioavailability: Crucially, the lactoferrin in camel milk is considered more resistant to stomach acid and digestive enzymes than bovine (cow) lactoferrin, suggesting higher bioavailability (more of the intact, active protein reaches the lower intestine) in humans.
    • Immune Modulation & Allergy: Research suggests camel milk can modify the overall immune response. This is important because the benefits may not be limited to those with GI symptoms; its immune-rebalancing effect (immunomodulation) suggests it could benefit people with ASD who suffer from frequent allergies, eczema, or systemic immune dysregulation, even if they lack chronic GI distress.

 

How it Relates to Autism

Lactoferrin works by several different mechanisms:

Addressing Iron Dysregulation (The "Starvation" Mechanism)

  • Harmful gut bacteria and pathogens (which contribute to gut dysbiosis in ASD) thrive on free iron. When there is excess, unregulated iron in the gut, these pathogens proliferate, worsening the microbial imbalance and gut-related inflammation.
  • Lactoferrin is a powerful iron-binding protein that tightly sequesters two molecules of ferric iron (Fe3+) per molecule, even at the low pH often found in inflamed or infected tissues.
  • This process effectively starves the harmful bacteria of the iron they need to grow, limiting their colonization and virulence. This helps rebalance the gut microbiome, which is the first step in calming the Gut-Brain Axis.

Limiting Oxidative Stress (The "Antioxidant" Mechanism)

  • Free, unbound iron is highly reactive. It participates in the Fenton Reaction, leading to the creation of toxic Reactive Oxygen Species (ROS), which cause widespread oxidative stress. Oxidative stress is a well-documented biological abnormality in the brains and bodies of individuals with ASD, contributing to cellular damage and inflammation.
  • By binding nearly all free iron in the gut and circulation, Lactoferrin acts as an iron scavenger, preventing this iron from participating in the damaging Fenton reaction.
  • This significantly reduces overall oxidative stress and lipid peroxidation (damage to cell membranes), thus protecting brain cells from injury and supporting anti-neuroinflammatory mechanisms.

Optimizing Iron Delivery to the Brain (The "Transport" Mechanism)

  • Iron is an essential nutrient, critical for key neurodevelopmental processes like myelination (insulation of nerve fibers) and the synthesis of neurotransmitters (like Dopamine and Serotonin). Both iron deficiency and improperly delivered iron are linked to cognitive and behavioral deficits in ASD.
  • Lactoferrin is structurally related to transferrin (the main iron transporter in the blood) and has its own receptors that facilitate iron transport. LF can act as a more efficient, regulated iron supplier, particularly to cells that need it. Furthermore, it is believed to cross the Blood-Brain Barrier (BBB) and deliver iron to the central nervous system.
  • Ensures that the brain receives a regulated supply of iron for proper neuronal function and neurotransmitter balance, which is vital for attention, mood, and socio-communicative skills.

In summary, Lactoferrin's primary role regarding iron is to sequester free iron to kill pathogens and stop oxidative stress, while simultaneously regulating the delivery of iron to the cells that need it for brain development.


Mechanisms Mediated by the Gut-Brain Axis

Reducing Gastrointestinal Inflammation (Anti-Inflammatory Action):

o reduces chronic, low-grade inflammation in the gut by downregulating pro-inflammatory signaling molecules (cytokines like IL-6 and TNF alpha and promoting anti-inflammatory ones like IL-10.

o    Alleviates gastrointestinal distress, which is a common comorbidity that can worsen behavioral symptoms in ASD.

Healing the Intestinal Barrier ("Leaky Gut")

o     supports the structure and function of the intestinal lining by promoting the repair and maturation of the epithelial layer and reinforcing the tight junctions between cells.

o    Prevents the abnormal passage of inflammatory molecules and neurotoxic compounds from the gut into the bloodstream, thereby reducing peripheral inflammation that can compromise the brain.

  Rebalancing the Gut Microbiome (Antimicrobial Action):

o    Reegulates the availability of iron, which is essential for certain pathogenic bacteria (like some Clostridium species) often found in higher levels in the gut of some people with ASD. By binding to iron, limits their proliferation.

o    Corrects microbial imbalance (dysbiosis), leading to a healthier gut environment and more beneficial microbial metabolites.


The "Bad" Lactoferrin - Fecal Lactoferrin (FLA)

It is crucial to understand that not all lactoferrin is beneficial in all contexts.

While the lactoferrin you consume is protective, the lactoferrin measured in stool tells a different story:

Fecal Lactoferrin (FLA) is a diagnostic marker, not a nutrient. A high FLA score is "bad" because it signals that large numbers of neutrophils (white blood cells) are migrating into the intestines to fight active, destructive inflammation (like IBD or severe infection). A high FLA indicates a serious problem, whereas a normal or low FLA suggests that symptoms are likely due to a non-inflammatory functional disorder (like IBS).

High Fecal Lactoferrin (FLA) is observed in a distinct subgroup of children with autism and indicates active inflammation within their gastrointestinal tract. While the average FLA level across the entire ASD population is usually normal, studies consistently identify a minority (often around 20-30%) whose FLA is significantly elevated. This finding is crucial because FLA acts as a biomarker, signaling a high level of neutrophil infiltration—white blood cells rushing to the site of damage—which means their chronic GI symptoms (like pain, constipation, or diarrhea) are likely caused by an inflammatory disease (like undiagnosed Colitis or IBD) rather than a non-inflammatory functional disorder (like IBS).

The presence of high FLA in this subgroup is vital to the Gut-Brain Axis hypothesis in autism research. It suggests that in these children, the underlying GI inflammation releases chemical signals (cytokines) that may travel to the brain, contributing to neuroinflammation and potentially exacerbating core autistic symptoms and co-occurring behavioral issues. Therefore, detecting high FLA helps clinicians distinguish this subgroup and target their treatment, focusing on anti-inflammatory interventions to address the root physical cause of their distress and associated behavioral challenges.

Fecal Lactoferrin (FLA) is a very common and increasingly standard laboratory test in gastroenterology, particularly for diagnosing and monitoring inflammatory bowel conditions.


For those with access to a very good lab and are going to test FLA, consider also TGF-β – one of the most reliable biomarkers of immune dysfunction in autism

One of the most consistently abnormal immune markers in autism is Transforming Growth Factor-β1 (TGF-β1), a cytokine that plays a central role in immune tolerance, gut barrier integrity, and neurodevelopment.

Over the past 15 years, multiple research groups—particularly the MIND Institute at UC Davis—have shown that children with autism frequently have reduced blood levels of TGF-β1. What makes this finding stand out is the strong correlation with clinical features. The lowest levels of TGF-β1 are typically found in children who also have:

  • more severe social and communication impairments
  • increased irritability and repetitive behaviours
  • chronic gastrointestinal symptoms
  • food sensitivities and allergic tendencies
  • elevated pro-inflammatory cytokines (IL-6, TNF-α, IL-1β)
  • impaired regulatory T-cell function (Tregs)

TGF-β1 is required to generate and maintain Tregs, the immune cells responsible for shutting down unnecessary inflammation and maintaining tolerance to foods and gut microbes. When TGF-β1 is low, the immune system becomes biased toward inflammation and over-reactivity. This immune profile is exactly what many clinicians observe in the “GI + immune activation” subtype of autism.

The abnormalities are not limited to the peripheral blood. Smaller studies examining cerebrospinal fluid (CSF) have found altered TGF-β1 levels in some autistic individuals, with links to developmental regression and stereotypy. This suggests that dysregulation of TGF-β signalling is occurring both in the immune system and centrally in the brain.

Because TGF-β1 plays a major role in strengthening the intestinal barrier, promoting mucosal repair, and dampening inflammatory responses, low levels can help explain why so many autistic children experience gastrointestinal disturbances, eosinophilic inflammation, and reactions to specific foods. Several interventions commonly used in autism—such as lactoferrin, sodium butyrate, Bifidobacterium infantis, Lactobacillus reuteri, and vitamin A/retinoic acid—are known from the scientific literature to increase mucosal or systemic TGF-β activity, which may partly account for their benefits in responsive individuals.

Among the many immune abnormalities reported in autism, low TGF-β1 is one of the most reproducible and clinically meaningful findings. It provides a biologically plausible link between gut dysfunction, immune activation, and behavioural symptoms, and it highlights a subgroup of children who may benefit from treatments aimed at restoring immune tolerance and improving epithelial barrier function.


Back to Lactoferrin


Direct Neurodevelopmental and Neuroprotective Mechanism

Supporting Neurodevelopment via IGF-1Signaling:

o    Insulin-like Growth Factor-1, which is often found alongside lactoferrin  in sources like camel milk, is crucial for neuronal growth, differentiation, survival, and synaptic plasticity (the brain's ability to form and strengthen connections).

o    May directly counteract potential IGF- dysregulation linked to ASD etiology, promoting optimal brain maturation, connectivity, and cognitive function.

o    The IGF- in camel milk is theorized to be highly stable against gastric acid, allowing it to cross the blood-brain barrier (BBB) effectively.

 Reducing Neuroinflammation and Oxidative Stress:

o    Both lactoferrin and IGF-1 possess potent antioxidant and anti-inflammatory properties that help protect the brain. Lactoferrin has been shown in preclinical models to reduce inflammation in brain support cells (astrocytes) and shield the developing brain from injury.

o    Dampens the chronic neuroinflammation and high oxidative stress levels observed in the CNS of individuals with ASD, preventing neuronal damage.

 Enhancing Brain Trophic Factors:

o    Preclinical studies suggest lactoferrin can enhance the production of neurotrophins, such as Brain-Derived Neurotrophic Factor (BDN).

o    BDNF is vital for learning, memory, and the survival of neurons. Increasing its levels supports overall neurological health and development.

 

Beyond the Gut: Systemic Anabolic and Anti-Aging Signals

The benefits of lactoferrin extend far beyond the digestive tract, touching on areas of foundational health that are important across the lifespan. Research highlights its systemic anabolic (tissue-building) and regenerative potential:

 

1. Anabolic Signal to Bone

Lactoferrin is a known factor that promotes osteogenesis (bone creation) and bone health while inhibiting bone loss. It provides a crucial anabolic signal, making it a focus for research on improving bone density and fighting age-related bone decline.

2. Supporting IGF-1 Signaling

Lactoferrin has been shown to work through the Insulin-like Growth Factor 1 (IGF-1) signaling pathway. IGF-1 is a key hormone that:

  • Promotes cell growth and division (anabolism).
  • Is essential for neuroprotection and cognitive function.
  • Typically declines with age, with lower levels being linked to aging processes and poor metabolic health.

By supporting the IGF-1 pathway, lactoferrin may help maintain a critical regulatory signal for tissue regeneration, metabolism, and overall vitality, potentially counteracting some effects of aging and promoting optimal function.

  

Maximizing the Benefits: The Bioavailability Challenge

Lactoferrin is a protein, and like any protein, it is vulnerable to degradation by stomach acid and digestive enzymes. If the protein is broken down before it reaches the small intestine, its benefits are limited. This is the problem of bioavailability.

To maximize the therapeutic benefits of a lactoferrin supplement:

1.     Choose Liposomal Encapsulation: Look for liposomal lactoferrin. This technology encapsulates the lactoferrin molecule within a protective layer of fatty lipids (liposomes). This shield helps the protein survive the harsh acidic environment of the stomach intact, ensuring better delivery and absorption into the intestine.

2.     Timing is Key: For best absorption and targeted delivery, it is generally recommended to take lactoferrin on an empty stomach. Some suggest taking it before bed, as the digestive system is less active, allowing the protein longer contact time with the intestinal lining and minimizing competition with other food proteins for absorption.

 

Conclusion

Last year I did meet one of the Saudi authors of the research into camel milk, as an immunomodulatory treatment for autism.

If camel milk is impractical where you live, a little lyposomal lactoferrin might be an alternative. I do not think the benefits are limited to those with GI problems. It also looks interesting for older adults.

Camel milk not only contains ten times the level of lactoferrin than cow milk, but it appears to be more able to survive acid in the stomach. 

Camel milk also contains special protective proteins called immunoglobulins (which are essentially antibodies), but they are unique in the animal kingdom. Unlike the complex antibodies found in humans and cows, camel antibodies are missing half of their structure, making them incredibly small. These tiny, functional fragments are now known as nanobodies. Because they are so small, these nanobodies can reach tight spaces in the body that large antibodies cannot, helping them fight bacteria and viruses more effectively. Furthermore, they are very tough and stable, meaning they survive digestion even when consumed orally in the milk, which is why they are thought to help give camel milk its powerful health benefits. 


 



I think those people drinking camel milk in the Middle East are making a smart choice.