First, a shout out to Andra (@BioavailableNd) for bringing this superstar to our attention.
And we do mean superstar!
Everything's about timing and our introduction to lactoferrin so soon after a deep dive into blood donation and longevity/health speaks to this.
Both revolve around the powerful sway (both good and bad) of iron.
Lactoferrin's effects are so varied and powerful that it begs the question…is lactoferrin a key reason mammals are so successful?
We'll leave the philosophical questions for another day and instead, dive into the many different effects of lactoferrin across the body and brain:
- A quick intro to lactoferrin
- Lactoferrin and iron - the first role
- Lactoferrin and immune function
- Lactoferrin and cancer
- Lactoferrin and pain
- Lactoferrin and the gut
- Lactoferrin and the brain
- Lactoferrin and mitochondria
- Lactoferrin and longevity
- Lactoferrin safety and final notes
Let's get started!
A quick intro to lactoferrin
Lactoferrin is a protein that's constantly released from any mucous source with a strong influence on breast milk for mammals.
Tears, saliva, semen, vaginal fluid, lung/nasal fluid. All "wet" interactions between our inner body and the harsh outside world is going to get a handshake from lactoferrin.
There's a reason for this!
You can think of lactoferrin as a "consultant" of sorts for key systems of our body….with the immune system being front and center.
This explains why it's everywhere our body is vulnerable to outside microbes….bacteria, viruses, and the like which would love to gain entry.
We say "consultant" because its effects do not push in just one direction. This is so sooo important.
One of the reasons we love CBD isolate is that its effect can change depending on the state of the system. Bi or even tri-phasic. Cancer is a perfect example of this.
Lactoferrin doesn't just ramp up the immune system in response to attackers. It can also resolve the immune response!
Okay…you have our attention. This is a very special trick and we rarely find it in the world of supplements, medications, or even natural bodily substances.
Lactoferrin doesn't have a classic endocannabinoid pathway (tasked with balancing other systems) but nonetheless, it helps the body manage key pathways depending on the needs at the time.
Just fantastic in our books!
So…let's slowly build the case for this superstar. Starting at the start.
Lactoferrin and iron - the first role
The name literally means iron (ferro) and milk (lacto). It's not a source of iron but a "manager" of it.
Ridiculously powerful in fact:
Lactoferrin binds iron with an affinity constant of 1020, which is ∼260-times that of transferrin
https://www.jpeds.com/article/S0022-3476(16)00295-X/fulltext
Indeed, it's a major contributor to colostrum from mother's milk in mammals.
You can even get it from cow's milk (if you're wondering why you're craving it!!) with a pretty similar genetic recipe (689 versus 691 amino acids).
Lactoferrin is a complicated protein that has a very special gift around iron.
Iron is the second deal Nature made (after glucose) with the devil for life.
It's both the source of life on Earth (carries oxygen) and incredibly toxic (rust!!)
You're literally a controlled burn. It's amazing we exist at all and iron must be tightly managed.
- Too little? Anemia
- Too much? Destruction (Parkinson's, dementia, heart dysfunction….aging!!)
Lactoferrin's first "consulting" gig is around iron balance.
Here's the fascinating piece we touched on above…it can have different results depending on the state of the system!
Lactoferrin is a powerful iron chelator…meaning it "sequesters" or binds up excess iron:
Lf is able to reversibly chelate two Fe(III) ions per molecule with high affinity (Kd ~ 10 −20 M), as well as retain ferric iron until pH values as low as 3.0
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5618634/
The ph piece is interesting as it speaks to states of disease, infection, and inflammation.
Lactoferrin is incredibly powerful at sponging up free-floating (destructive) iron.
So…does that lead to anemia…too little iron?
Lactoferrin has been reported as an effective therapy in the treatment of anemia in both pediatrics and adults.
https://www.nature.com/articles/s41390-022-02136-2
A study compared giving lactoferrin versus iron itself and the results:
However, lactoferrin group had significantly higher mean Hb (P < 0.001), serum iron (P < 0.001), TS (P = 0.008), and serum ferritin (P = 0.006) compared to ferrous sulfate group after 3 months of treatment.
https://www.nature.com/articles/s41390-022-02136-2
Wait…what? Better iron profile for people with anemia than iron itself?
The key may be gut absorption where lactoferrin is a powerful manager and we'll touch on that below.
For now…know that lactoferrin's primary lever of choice is a tight and situational control of iron levels.
Iron just happens to be the "currency" of cellular activity (literally the burn of fuel) so the effects of this management…might be profound.
Let's then see how lactoferrin wields this weapon in its primary (and maybe first) role.
Lactoferrin and immune function
It turns out that viruses, bacteria, and other microbes need iron as well to flourish. They're actually pretty poor at sourcing it themselves (anaerobic) so they lean on our supply.
That's where lactoferrin comes in. In fact, this may be its original job description and speaks to why it's in breast milk and any other fluid where we meet the outside (hostile) world.
Its effect on bacteria/viruses is at first direct:
This effect of Lf is the result of its ability to sequester iron in biological fluids and destabilize the membranes of microorganisms
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4814036/
It "steals" iron from attackers. That's only the beginning.
It also coordinates (the consultant gig from above) our immune's response on the ground.
Summary level:
Lf is also considered a cell-secreted mediator that bridges the innate and adaptive immune responses.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4814036/
Oh goodness. "Mediator" for our immune response, both the original recipe (innate) and in response to new attackers (adaptive).
In fact, lactoferrin is released from immune players in response to infection to "ramp up" response.
But, and this is critical in times of cytokine storm and autoimmune, it also works the other way!
To resolve inflammation and immune response…as well as keep it from running amok (as dangerous as the bacteria/viruses themselves).
Consequently, bLf inhibits intracellular iron overload, an unsafe condition enhancing in vivo susceptibility to infections, as well as anemia of inflammation (AI), re-establishing IIH.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5618634/
IIH? Oh, that's just iron and inflammatory homeostasis. Homeostasis means "balance."
Again…it assists our immune system in delivering the right response:
Indeed, LTF serves as a critical control point in physiologic homeostasis, functioning as a sensor of immunological performance related to pathology
https://www.frontiersin.org/articles/10.3389/fimmu.2017.01438/full
We really thought it would be an endocannabinoid player but this is separate…special to mammals (and fish???).
Let's take this for a spin.
What about autoimmune?
This culminates in attenuation of pathological damage during inflammatory injury.
https://www.frontiersin.org/articles/10.3389/fimmu.2017.01438/full
So…calm the immune storm and "resolve" inflammation.
Please…get specific…
Oral administration of bovine lactoferrin suppresses the progression of rheumatoid arthritis in an SKG mouse model
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8836292/
Learn about autoimmune here.
So…that's just one example (of many) where the immune system is hyperactive and actually causing damage. Lactoferrin pushes back on this.
One note…our levels of lactoferrin go down with age (matching the increase of autoimmune) and there's a connection with female hormones (estradiol drives it) hence the gender difference with autoimmune (8:1).
So…a quick checklist:
- Lactoferrin ramps up an immune response to bacteria/viruses
- Lactoferrin helps resolve the immune response and "cap" it
- Lactoferrin protects from excessive immune response
Look…the immune gets complicated real quickly. Just one example of lactoferrin's multifarious effects:
it achieves this by regulating the function of Th1 and Th2 cells, promoting the Th1 response through the synthesis of IL-2 and IFN-γ and inhibiting the Th2 response, reducing the release of inflammatory mediators such as IL- 5 and IL-17 and causing the crosslinking of the T cell receptor, so that the activation of T cells is inhibited [29].
https://www.mdpi.com/1420-3049/26/1/205
Uncle?? We bring this up to mention the Th1 and Th2 equation. These are system-wide immune "settings".
- Th1 - pro-inflammation - Fight!
- Th2 - resolve inflammation - Stand down.
There's a delicate (and very complicated) dance between the two and lactoferrin definitely Tango's
As for the current virus-du-jour, we got in trouble last time we discussed it so we'll leave the NIH studies around lactoferrin for you to read:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8535893/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9676636/
Front page news, right?
Okay…selective immune response becomes really important for our next section.
Lactoferrin and cancer
Our immune system is tasked with detecting and killing cancer. In fact, it uses the same arsenal as any other wayward cell (including virally infected).
A massive dose of oxidative stress (just like chemo and radiation) but specific to the faulty cells only.
Cancerous cells are just like viruses/bacteria in that they need iron for growth.
Hello, lactoferrin:
Lf shows high bioavailability after oral administration, high selectivity toward cancer cells, and a wide range of molecular targets controlling tumor proliferation, survival, migration, invasion, and metastasization.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7175311/
Our favorite part (like CBD or Turkey Tail):
Of note, Lf is able to promote or inhibit cell proliferation and migration depending on whether it acts upon normal or cancerous cells, respectively.
Read that back over. It's so critical to everything we're discussing.
The effect depends on whether the cell is healthy…or faulty.
Remember how we said iron controlled the cellular "burn"?
Lactoferrin can fire-hose this burn at faulty cells to cause cell death (called apoptosis).
The anticancer effects of Lf have been extensively studied, and it has been observed that in the presence of Lf, different cancer cells suffer significant damage, such as cell cycle arrest, damage to the cytoskeleton, and induction of apoptosis, in addition to a decrease in cell migration
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7795860/
Lactoferrin literally has its finger on the trigger (or iron).
The beauty is that it can point directly at cancer cells:
Lf has high selective cytotoxicity, not all reported the selective cytotoxicity index (SCI), which gives the ability of a compound to kill cancer cells with minimal toxicity to non-cancer cells.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7795860/
This makes it an interesting "adjuvant" or add-on player for traditional cancer treatments (always work with your doctor).
In summary, bLf is a potent natural adjuvant and fortifying agent for augmenting cancer chemotherapy, but needs to be saturated with iron to be effective.
https://pubmed.ncbi.nlm.nih.gov/18268518/
We need to add it to our top tools to support cancer success.
Speaking of chemo, let's start to spread our wings a bit. To pain.
Lactoferrin and pain
Mother Nature likes to multi-task which speaks to all the side effects from common medications (gut and heart dysfunction from COX2 players like NSAIDs).
Not sure why this isn't front page news.
Lactoferrin has a powerful effect on system-wide pain sensitivity.
We're not talking about COX2 or even serotonin (which manages pain sensitivity) or even GABA (nerve and peripheral pain).
We mean the spinal cord. The layered network and pain relay can get "stuck" or even exhausted.
Where opioids operate (till they don't due to brutal tolerance).
Here's an animal pain sensitivity model (don't worry…we'll explain):
https://journals.physiology.org/doi/full/10.1152/ajpregu.00760.2002
It compared lactoferrin (cow) to morphine.
You see "analgesia" or reduced pain sensitivity improve with increasing dosage of lactoferrin. The highest level is just above morphine!
The most important part (for us anyway)...
In the tail-flick test, continuous spinal infusion of morphine via an osmotic minipump over 6 days resulted in the development of tolerance by day 4, but no tolerance of BLF was observed throughout the experiment.
No tolerance. The body didn't push back against the effect of lactoferrin by reducing natural pain pathways like it does with opioids!
Goodness.
They showed that oral lactoferrin increases NO levels in the spinal cord.
There's both an anti-inflammatory effect (think peripheral pain) and a systemic effect (think fibromyalgia, etc.)
The central effect appears to be around nitrous oxide in the spine which is known to increase our opioid system naturally.
We all know the opioid system for physical pain but keep in mind that it also manages psychological pain!
Come for the back injury, stay for the childhood trauma/neglect or shame.
Goodness…
These changes in parasympathetic (HF) and sympathetic (LF/HF) activities, however, were alleviated by lactoferrin compared with the placebo (P=0.007 and P=0.026, respectively). Collectively these results suggest that oral lactoferrin may mitigate psychological stress in humans.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5962838/
We're talking about our fight/flight (hello anxiety, PTSD, ADHD, etc.) system versus our rest/digest system.
And without tolerance.
Check out our review on CBD and pain to look at the players. CBD and lactoferrin could be interesting cohorts against pain.
We're big advocates of addressing the long term effects of early life trauma, infection, and stress.
Lactoferrin may figure into this:
In addition, GOS, PDX and LAC diet attenuated stress-evoked decreases in mRNA for the 5-HT1A autoreceptor in the DRN and increased basal BDNF mRNA within the prefrontal cortex.
https://pubmed.ncbi.nlm.nih.gov/27763700/
To translate (please!!), lactoferrin and two other milk-based products offset the downregulation of serotonin (5HT1A) and BDNF (our brain's fertilizer) caused by early life stress later in life. This is directly tied to EVERY mental health issue out there.
Learn more about early trauma and mental health. But we all have perfect childhoods (and 3rd trimesters), right?
Let's now go south…to the Gut!
Lactoferrin and the gut
This is so fascinating…we'll use the gut as an excuse to evaluate lactoferrin's effect on the entire metabolism complex.
People…this may be it for all things health.
So we don't get lost in the weeds, let's just highlight a few items:
- Lactoferrin and the gut barrier
- Lactoferrin and the microbiome
- Lactoferrin and gut inflammation
- Lactoferrin and metabolic profile
Speed round!
Lactoferrin and the gut barrier
This may be a key to autoimmune and many of the most brutal diseases you want to avoid. When bacteria and microbes escape across our gut barrier, only bad things can happen.
Lactoferrin is all over this defense:
bLF significantly increased the expression of three tight junction proteins—claudin-1, occludin, and ZO-1—at both the mRNA and protein levels, and consequently strengthened the barrier function
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6337092/
A study looked at the effects after a massive bowel surgery:
Compared with that in the SBS group, in the SBS-bLF group, bacterial translocation to regional organs was low and intestinal permeability was significantly reduced.
https://pubmed.ncbi.nlm.nih.gov/24830343/
Learn why this is so important at our gut barrier review.
Lactoferrin and the microbiome
Lactoferrin will attack hostile bacteria…but what about our friendly ones…the microbiome that practically functions as another organ?
Lactoferrin is able to target pathogenic or "bad" bacteria while supporting the good guys.
By using Lf as a component in pharmacological products, we may enable novel strategies that promote probiotic growth while conferring antimicrobial activity against multidrug-resistant microorganisms that cause life-threatening diseases, especially in neonates.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6801499/
In fact, a big reason lactoferrin is so present in breast milk is to "guide" the nascent bacteria zoo being established.
piglets fed 2.6 g rhLF/d were observed to have greater microbial diversity in the small intestine and lower microbial diversity in the colon than groups fed lower rhLF (1.3 g/d) or no rhLF.
https://www.jpeds.com/article/S0022-3476(16)00295-X/fulltext
And less of the bad:
More importantly, the high dose of rhLF reduced pathogen load (Salmonella and Escherichia coli) and promoted the growth of healthy microbes, including Bifidobacterium spp and Lactobacillus spp.94 The growth of Bifidobacterium spp supports the findings of the human intervention studies with bLF
What about a gut microbiome wrecked..say by antibiotics?
Conclusion: In a situation of intestinal dysbiosis induced by clindamycin, lactoferrin restores the normal levels of some anti-inflammatory bacteria and TLRs and, therefore, could be a good ingredient to be added to functional foods.
https://pubmed.ncbi.nlm.nih.gov/35545893/
This should affect gut inflammation states, right?
Lactoferrin and gut inflammation
Accumulating evidence indicate that LF has been reported to enhance intestinal epithelial cell proliferation, cytokines production, and immune cell functions in counteracting inflammatory processes and maintaining immune homeostasis
https://www.frontiersin.org/articles/10.3389/fnut.2021.759507/full
Accumulating indeed. That's a who's who of gut inflammation.
In fact, they're using lactoferrin levels in stool samples to determine IBD/IBS status.
Check out the review on gut inflammation.
Let's zoom out a bit.
Lactoferrin and metabolic profile
We could write a whole review on this but we'll hit the highlights.
- Lf and insulin
- Lf and glucose
- Lf and A1C
- Lf and cholesterol
- Lf and weight
- Lf and the liver
Lf and insulin
Lactoferrin improves hepatic insulin resistance and pancreatic dysfunction in high-fat diet and streptozotocin-induced diabetic mice
https://pubmed.ncbi.nlm.nih.gov/35477124/
Lf and glucose
These results suggest that Lf could suppress hyperglycemia, accompanied by elevated plasma levels of insulin via transiently accelerating GLP-1 secretion, and that Lf even enhances glucose absorption from the small intestine.
https://cdnsciencepub.com/doi/10.1139/bcb-2016-0082
Okay…so blunting glucose spikes and stimulating GLP-1, the pathway behind the blockbuster drug $30K Ozempic (which may push too hard…tolerance).
Lf and A1C
A measure of sugar damage to the blood.
The antidiabetic efficacy of lactoferrin was confirmed by significant improvement of the baseline levels of HbA1c, BMI and lipid profile of the obese pediatric cohort, which is evidenced by increased PPAR-γ and SIRT-1 expression.
https://www.researchgate.net/publication/329410858
Lf and cholesterol
Background: Lactoferrin (LF) is a multifunctional glycoprotein that can regulate lipid metabolism, lower cholesterol, reduce body weight, and prevent atherosclerosis.
https://pubs.rsc.org/en/content/articlelanding/2019/fo/c9fo01616c
Fine. What about homocysteine?
Lf and homocysteine
Conclusion: The findings indicated that bLF could improve the alteration of serum Hcy, leptin, apolipoproteins, and lipid changes in male rats fed with a high-cholesterol diet. So, bLF can counteract with HCD elicited hyper-homocysteinemia and hyper-leptinemia, suggesting it has useful therapeutic potential in patients with atherosclerosis and lipid disorder.
Lump in Apoe-B.
Does weight get affected?
Lf and weight
Measurement of the total fat area, VFA and subcutaneous fat area from computed tomography images revealed a significant reduction in VFA ( - 14.6 cm2) in the eLF group, as compared with the placebo controls ( - 1.8 cm2; P = 0.009 by ANCOVA). Decreases in body weight, BMI and hip circumference in the eLF group ( - 1.5 kg, - 0.6 kg/m2, - 2.6 cm) were also found to be significantly greater than with the placebo (+1.0 kg, +0.3 kg/m2, - 0.2 cm; P = 0.032, 0.013, 0.041, respectively).
https://pubmed.ncbi.nlm.nih.gov/20691130/
Mice study:
https://www.sciencedirect.com/science/article/pii/S1756464611000727
Most of this "operation" above is carried out in the liver. So…
Lf and liver function
Lactoferrin administration thus significantly lowered liver weight, resulting from a decrease in the triglyceride and cholesterol synthesis that activates hepatic steatosis.Taken together, these results suggest that lactoferrin protected against high-fructose corn syrup induced hepatic manifestations of the metabolic syndrome
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4016362/
Covered triglycerides there as well. It's a twofer.
The entire metabolic complex is affected. The big push right now is that metabolism is the root of all evil (or good). Check out "Brain Energy" by Chris Palmer as an example in terms of mental health.
Let's go north…to the brain
Lactoferrin and the brain
Again, we could write forever here but let's zero in on a few key players.
- Lf and BDNF
- Lf and microglia immune response
- Lf and brain barrier
- Lf and neurotransmitters
- Lf and mental health
Lf and BDNF
BDNF is our brain's fertilizer. It's literally holding the dam against:
- Trauma
- Stress
- Infection
- Injury
- Hyperactive immune response (and glutamate)
- Chemicals/Drugs
- Energy production waste
Top two triggers for drug relapse?
- Stress
- Reduced BDNF levels
It's THE player behind the curtain for all things mental health. Check out our BDNF review.
Is Lactoferrin in play here?
Damage from diabetes as an example:
In T2D rat, Lactoferrin corrected aberrant serum levels of SNE, BDNF and TNF-Alpha, in addition, Lactoferrin improves brain pathological changes might be through hypoglycemic, and/or anti-inflammatory actions and reduced DNA damage as compared to diabetic untreated rats.
https://link.springer.com/article/10.1007/s43994-023-00026-9
To whit:
Lf elevates the mRNA and protein levels of brain-derived neurotrophic factor (BDNF) and components of its signaling pathway
https://www.mdpi.com/2073-4409/10/7/1810
The biggest player for damage is the immune system when out-of-control (remember the bacteria escaping across the gut??)
Lf and microglia immune response
The major neurodegeneration diseases like Parkinson's and Dementia share something in common.
Excess iron. The immune system and its sentinels in the brain, microglia, may be part of the problem:
Further, pro-inflammatory factors released by activated microglia (e.g., IL-1β, IL-6, and TNF-α) contribute to the iron deposition by up-regulating the expression of IRP1 and iron transporters (e.g., DMT1) through production of ROS and RNS
https://www.frontiersin.org/articles/10.3389/fncel.2019.00514/full
We did a huge report on Iron Overload and health.
So…more inflammation and more excess iron which we know is toxic.
We should see a reduction of this iron…and a resulting improvement in brain areas?
Lactoferrin decreases iron deposits in the brains of aged mice. Metabolism alterations in the hippocampi of aged mice were partially reversed by lactoferrin intervention.
https://www.sciencedirect.com/science/article/pii/S1756464619306607
Most importantly..
Lactoferrin improves memory and learning ability of naturally aged C57/BL6J mice.
Does lactoferrin even get across the blood brain barrier?
Lf and brain barrier
Lactoferrin rapidly crosses the blood-brain barrier via receptor-mediated transcytosis and accumulates in the brain capillary endothelial cells. Lactoferrin receptors are additionally present on glioma cells, brain micro-vessels, and neurons.
https://pubmed.ncbi.nlm.nih.gov/33977807/
In fact, scientists are looking at lactoferrin to "ferry" other chemicals across the blood brain barrier.
So…how does this really translate?
Lf and mental health
We're just starting to get research.
BDNF is a huge player. When lactoferrin is withheld from diets in animal models, the result is the equivalent of depression or anxiety:
When exposed to external stimulation, adult lactoferrin feeding-deficient mice presented with worse depression-like symptoms; the mechanisms involved were activation of the LPS–TLR4 signaling pathway in the intestine and hippocampus, reduced BDNF signaling pathway in hippocampus, increased abundance of depression-related bacteria, and decreased abundance of beneficial bacteria.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5709556/
Immobility after stress for animals is a sign of…giving up. Look at the effect of lactoferrin!
Then, there's the excess iron issue:
As a regulator of neuro-redox, microglial lactoferrin is critical for protection/repair of neurons and healthy brain function. Iron imbalance and oxidative stress are common among patients with neurodegenerative disorders such as Parkinson's disease, Alzheimer's disease, dementia, depression, and multiple sclerosis.
https://pubmed.ncbi.nlm.nih.gov/33977807/
To translate…this is about Lf ability to balance the iron/energy system in the brain.
Check out oxidative stress to learn more.
This brings us to mitochondria, maybe the most important player in they body.
Lactoferrin and mitochondria
Everything we've discussed above revolves around energy production. After all, iron carries the "fire" (oxygen) and glucose is the energy that runs everything.
This all takes place…in mitochondria. We have a huge review on how to rescue mitochondrial function but lactoferrin must be at play here.
We'll avoid all the way the body uses iron to "kill" both hostile actors and faulty cells. What about mitochondrial function?
In fact, when bacteria do gain entry, it's a slippery slope towards scorched earth by our immune system (sepsis or autoimmune or cytokine storm).
Lactoferrin is the voice of reason:
Importantly, lactoferrin nearly abolished LPS-induced increases in mitochondrial ROS generation and the accumulation of oxidative damage in the DNA.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3030479/
If the cell is worth saving, lactoferrin helps to make the call.
Let's look at two energy hunger areas.
First the brain:
The Iron-Binding Protein Lactoferrin Protects Vulnerable Dopamine Neurons from Degeneration by Preserving Mitochondrial Calcium Homeostasis
https://molpharm.aspetjournals.org/content/molpharm/early/2013/09/27/mol.113.087965.full.pdf
That's Parkinson's folks. Our dopamine neurons are few and precious. Learn more at our dopamine rescue review.
And the heart?
Lactoferrin ameliorates pathological cardiac hypertrophy related to mitochondrial quality control in aged mice
https://pubs.rsc.org/en/content/articlelanding/2021/fo/d0fo03346d/unauth
As we age, our hearts literally grow to make up for lack of efficiency in keeping up with the workload. Check out our mitochondria rescue guide.
So…let's bring this all together!
Lactoferrin and longevity
Our review on blood donation pointed to a key point.
The removal of blood in itself may be a powerful longevity hack due to the removal of excess iron (and broken proteins).
Still early days but…
Moreover, LF has a pivotal role in modulating the major signaling pathways that influence the longevity of organisms. Thus, LF is expected to be able to attenuate the process of aging and greatly ameliorate its effects.
https://pubmed.ncbi.nlm.nih.gov/34928288/
Always starting with the poor worms:
A nutritional supplement containing lactoferrin stimulates the immune system, extends lifespan, and reduces amyloid β peptide toxicity in Caenorhabditis elegans
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5332254/
They found part of the effect was from better protein balance.
Let's hit some of the longevity highlights:
- Lf and mTOR
- Lf and SIRT
- Lf and AMPK
mTOR - the protein starvation sensor (rapamycin and fasting fame):
In addition, due to regulation of numerous genes expression (inhibition of NF-κB, mTORC1 and caspase via the Erk and Akt pathways), LF regulates cell growth, proliferation, apoptosis and inflammation.
https://www.mdpi.com/1420-3049/27/9/2941
SIRT - the cellular shock player (resveratrol, pterostilbene, CBD, etc)
The consumption of high concentrations of lactoferrin explains its hypoglycemic efficacy and counts for its insulin-sensitizing, anti-inflammatory and immunomodulatory effects via TLR4-NFκB-SIRT-1 signaling cascade.
https://pubmed.ncbi.nlm.nih.gov/30534206/
AMPK - metformin, berberine, and fasting
Lactoferrin promotes autophagy via AMP-activated protein kinase activation through low-density lipoprotein receptor-related protein 1
https://pubmed.ncbi.nlm.nih.gov/28867180/
Autophagy is the removal of faulty cells.
So…senescent cells or SASP?
Moreover, due to the induction of the targeted apoptosis of senescent cells or the disruption of the senescence-associated secretory phenotype (SASP), LF restores tissue homeostasis
https://www.mdpi.com/1420-3049/27/9/2941
Okay…we waive the white flag!
A few final notes!
Lactoferrin safety and 40,000-foot view
What about safety? A few elements that are essential for us:
First, the studies above that mention safety show no issue.
It is a safe raw material, which is confirmed by the documents issued by the European Parliament (EP) [132], European Food Safety Authority (EFSA) [133] and the Food and Drug Administration (FDA) in the United States [134].
https://www.mdpi.com/1420-3049/27/9/2941
We like seeing Europe's agency weigh in since the US can be…."flexible".
If you're allergic to cow's milk, then look for lactoferrin processed from rice. Lactose intolerance is generally not an issue since there's no lactose present.
As for dosage, there's a wide range:
It is widely used as a nutritional additive in infant formula, and clinical studies employed Lf doses ranging from 100 mg to 4.5 g a day for various indications without apparent toxicities.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7390755/
Standard doses available through supplements are around 250mg. This matches some of the studies above where different levels were given with increasing effect (at around the 250mg level).
Interestingly, higher levels are used for specific viral infections:
Hepatitis C. Some patients with hepatitis C seem to respond to lactoferrin taken from cows. Doses of 1.8 or 3.6 grams/day of lactoferrin are needed. Lower doses don't seem to work.
https://www.rxlist.com/lactoferrin/supplements.htm
Work with your doctor…this isn't medical advice or to be used in replacement of standard treatment. It just reflects a high level dose example.
That's 1800 to 3600mg. Again, 250mg over 8 weeks appears to be the best estimate from studies.
Now, there may be an initial window of GI adjustment. This is actually a good thing! Remodeling of the gut microbiome.
This speaks to pathogens, parasites, inflammation, fungi overload, and a general imbalance in the gut. We see this with any substance that shows positive effects in the gut (berberine, CBD isolate, etc.).
It should subside after 3-5 days max. Actually very positive.
What about steroids? We love rapamycin for longevity but not what it does to steroids.
We don't see research where lactoferrin supplementation affects steroidal hormone levels. We do see research where estrogen naturally boosts and manages lactoferrin expression!
Lactobacilli and lactoferrin are largely under the influence of female hormones and of paracrine production of various cytokines.
https://www.frontiersin.org/articles/10.3389/fimmu.2018.00376/full
You know our thoughts on the power of estradiol!
Beyond the scope of this review, there's interesting research on lactoferrin and pregnancy, fertility, cycle issues, etc.
Now…lactoferrin may cause just better processing of cholesterol and LDL cholesterol is the source of all hormones (via pregnenolone).
So…better processing, better steroidal hormone function:
Results of this study suggest that lactoferrin administration causes activation of androgen synthesis and lipid metabolism.
This is fascinating since steroidal hormone function goes down as we get older See reviews on why this matters across the body and brain:
You can get lactoferrin directly or colostrum. We reached out to one of the big colostrum providers to confirm levels of lactoferrin and they couldn't give a firm answer but estimated at .6%.
That's not much so we stick with straight lactoferrin like this one:
As for longer term use, we do not see signs of tolerance (the enemy!!) with longer term use up to a year from studies.
Remember, the powerful spinal cord opioid effect showed no tolerance whereas morphine nearly lost all effect within 4 days!
This may be the most important piece (along with PQQ, CBD isolate, magnesium, etc.).
Lactoferrin is a fascinating tool for almost every pathway we look at.
This speaks to a very foundational effect.
Our crazy thoughts?
Transferrin, the primary iron manager came on the scene around 580 million years ago
- Mammals appeared around 175 million years ago
- Lactoferrin appears around 125 million years ago
Lf clearly gave mammals an advantage in the age-old war with microbes and then its role expanded from there.
Ultimately, iron and glucose are the stuff of life and lactoferrin directly balances this controlled fire.
Very exciting to have such a hack available down here!