Introduction
The immune system and brain function work as one connected network, not as two separate departments. Most people picture immunity as defense against infection and nothing more. Your immune cells also help decide how neurons grow, connect, and survive. Two proteins sit near the center of that exchange, vascular endothelial growth factor (VEGF) and epidermal growth factor (EGF). This article explains what those growth factors do and what human research has actually measured. I will also explain why chasing a higher number is the wrong goal. My own clinical trials come last, including one result that argues against easy marketing.
The Immune System and Brain Function Share One Signaling Language
Medical training long treated the brain as a place immune cells did not enter. Scientists called that idea immune privilege. Two decades of research have retired the strong version of it.
Immune cells populate the tissues that surround and drain the brain. Filiano, Gadani, and Kipnis reviewed how T cells and their cytokines influence the healthy and the injured brain (Filiano et al., 2017). Most of the experimental work behind that review was conducted in mice. I therefore treat the mechanisms as hypotheses about people rather than as settled human fact.
Cytokines and growth factors supply the vocabulary of that conversation. Cytokines (i.e., short-lived messenger proteins released by immune cells) coordinate defense. Growth factors instruct cells to divide, migrate, mature, or stay alive.
One detail explains most of the confusion in this field. The same molecule can mean different things in different tissue, at different concentrations, in different people. Nothing about the immune system and brain function reduces to a single number on a lab report.
What VEGF and EGF Actually Do
Vascular endothelial growth factor, or VEGF, is best known for building blood vessels. Researchers call that process angiogenesis (i.e., the growth of new vessels from existing ones). Brain tissue depends heavily on that supply, because neurons cannot store fuel.
VEGF also acts directly on nerve cells. Fabel and colleagues blocked peripheral VEGF in adult mice and abolished the rise in hippocampal neurogenesis normally produced by running (Fabel et al., 2003). Baseline neurogenesis in the non-running mice was unaffected. Neurogenesis means the formation of new neurons, which continues in the adult hippocampus.
Epidermal growth factor, or EGF, carries a different assignment. EGF binds a receptor found on neural stem cells, astrocytes, and the precursor cells that produce myelin. Scalabrino reviewed that biology across rodent and cell culture work in an extensive translational overview (Scalabrino, 2022).
Both molecules are immune signals as much as brain signals. Immune cells produce them, and immune activity changes their levels. Growth factors and cognition therefore belong in the same discussion as inflammation and infection.
VEGF and Brain Health: What Large Human Studies Measured
Human evidence connecting the immune system and brain function to VEGF comes mostly from observational work. Association is not causation, and I refuse to blur that line. Reverse causation stays on the table in every study below.
The most cited analysis came from the Alzheimer’s Disease Neuroimaging Initiative. Hohman and colleagues examined cerebrospinal fluid VEGF in 279 older adults spanning normal cognition, mild cognitive impairment, and Alzheimer’s disease (Hohman et al., 2015). Higher cerebrospinal fluid VEGF was associated with larger hippocampal volume, better episodic memory, and better executive function in those older adults.
Two limits on that study deserve emphasis. Researchers measured VEGF in cerebrospinal fluid, which is not the blood test your physician can order. The cohort also included many adults already living with cognitive impairment, so the result does not describe a healthy population.
Exercise carries the most direct human evidence for moving this marker. Song and colleagues pooled 38 studies of healthy adults aged 50 and older and found modestly higher resting VEGF after exercise (Song et al., 2024). That increase was small, and it reached statistical significance only in the aerobic exercise subgroup. The authors also detected publication bias in that VEGF analysis, which you deserve to know.
I would not treat VEGF and brain health as a number you can chase. No clinician monitors it routinely in healthy people. No threshold defines a healthy value.
Epidermal Growth Factor, Myelin, and the Renewal of Brain Cells
Epidermal growth factor earns its place in this discussion through cell renewal. EGF drives the proliferation and differentiation of neural stem cells and oligodendrocyte precursors (i.e., the cells that mature into the cells making myelin). Most of that work was performed in rodents and in cell culture (Scalabrino, 2022).
Human data on EGF concentrate in one clinical population. Scalabrino reported that EGF levels run lower in the cerebrospinal fluid and spinal cord of patients with multiple sclerosis than in comparison subjects. Researchers study that deficit because myelin repair depends on the precursor cells EGF acts upon.
Nothing in that literature makes EGF a supplement target. No dietary ingredient has been shown to raise EGF in healthy adults in a randomized controlled trial. I want that stated plainly before I describe findings from my own work.
The renewal theme connects to ground I have covered separately. EGF signaling operates on the same stem and progenitor populations I describe in my article on how to increase stem cells naturally. Neuroimmune signaling and cell renewal are two descriptions of one process.
Why More Growth Factor Is the Wrong Goal
Growth factor marketing follows a predictable script. A molecule gets linked to something good, and a product promises to raise it. Biology rarely cooperates with that logic.
VEGF illustrates the problem well. VEGF exists to build new blood vessels and to make existing vessels more permeable. Apte, Chen, and Ferrara detail that biology in their review of VEGF signaling (Apte et al., 2019). Both actions serve repair. Neither is something you want running continuously in healthy tissue.
Chronic elevation is therefore not the goal for VEGF. A brief rise supports healing, while a sustained rise keeps vessel growth and leakage switched on past any useful purpose. If my own VEGF ran high year after year, I would want it to come down rather than climb.
EGF runs the opposite way. Scalabrino reported EGF levels below comparison values in the cerebrospinal fluid and spinal cord of patients with multiple sclerosis (Scalabrino, 2022). Where a signal is documented as deficient, higher is the direction that matches what the tissue requires. Direction depends on where a person starts, which is why the immune system and brain function respond to regulation rather than to maximization.
The same logic reaches past growth factors. Tumor necrosis factor-alpha, or TNF-α, is an inflammatory cytokine, and most people have learned to read it as purely harmful. Kalliolias and Ivashkiv describe TNF as pleiotropic, with roles in normal homeostasis as well as in disease (Kalliolias & Ivashkiv, 2016). TNF-α also participates in the response to bacterial and viral challenge, where activation is the assigned job. My own group noted that TNF-α is associated with both Th1 and Th2 cells (Lewis et al., 2024). Those are the two main arms of the T-helper response. A cytokine tied to both arms can move either way, and the direction alone tells you very little.
Ordinary inputs remain the honest levers here. Aerobic exercise, adequate sleep, and a whole-food, plant-based diet influence immune signaling across many measured markers. My article on how to increase BDNF naturally lays out that same case in more detail. Readers who are comparing products can also consult what I wrote about the best supplements for memory loss.
Immune-Cognitive Function in My Own Clinical Research
My own work on the immune system and brain function carries real constraints, and you should weigh them before the results. Both trials were open-label, meaning participants and investigators knew what was taken. Neither included a placebo group. Both samples were small, and both enrolled people living with a diagnosed neurological disease rather than healthy adults.
Here is what we measured in the first trial. We gave an aloe polymannose multinutrient complex to adults with moderate-to-severe Alzheimer’s disease for 12 months (Lewis et al., 2013). In those adults, VEGF decreased significantly, alongside significant decreases in TNF-α, interleukin-2, and interleukin-4. Cognitive scores on the ADAS-cog also improved clinically and statistically significantly at the 9-month and 12-month assessments.
A second analysis of that same group asked how BDNF tracked with immune markers. Among that same group living with moderate-to-severe Alzheimer’s dementia, BDNF correlated significantly with both VEGF and EGF at 12 months (Stillman et al., 2020). The correlation with EGF was the stronger of the two, at r = 0.74, against r = 0.55 for VEGF. I explain that molecule at greater length in my pillar article on brain-derived neurotrophic factor.
The multiple sclerosis trial pointed the other way on EGF. In adults with multiple sclerosis taking the same polysaccharide-based regimen for 12 months, EGF increased significantly (McDaniel et al., 2020). EGF did not change significantly in the Alzheimer’s sample over the same period.
Read those results together and the pattern makes biological sense. VEGF came down in a group where sustained elevation serves no repair purpose. EGF rose in a group with a documented deficit of it. In my reading, each marker moved toward what the tissue requires rather than simply up or down.
That pattern extends past the growth factors. TNF-α is an inflammatory signal. It decreased significantly in the adults who had Alzheimer’s disease (Lewis et al., 2013). It increased significantly in the adults who had multiple sclerosis (McDaniel et al., 2020). An increase in that setting is consistent with immune activation rather than with harm.
We described the regimen in the second paper as immunomodulatory, meaning it appeared to adjust immune signaling rather than drive it one way. Open-label trials without placebo groups cannot separate a balancing response from the natural course of each condition. None of it demonstrates that a supplement changes growth factors in a healthy person, and I will not suggest otherwise.
What this body of work does support is a standard for how a formula should be developed. We studied the complete formulation in people, not one isolated ingredient in a dish, and aloe polysaccharides anchored that formulation. Research of that kind is why my own name appears on the label of Daily Brain Care. My credentials in academic medicine and clinical research are listed on the about page.
Conclusion
The immune system and brain function communicate through molecules like VEGF and EGF, and that conversation shapes cognition over decades. Higher cerebrospinal fluid VEGF tracked with better memory in older adults, while EGF research centers on cell renewal and myelin. Neither one is a number to chase because what the tissue requires sets the direction. Exercise, sleep, and whole-food nutrition remain the foundation, and no formula replaces them. Put those habits in place first, and let any formula you add stand on published evidence. Give Daily Brain Care a place in your daily routine.
Frequently Asked Questions
How does the immune system affect brain function?
The immune system and brain function are linked through signaling. Immune cells populate the tissues surrounding the brain, and their molecules influence how neurons grow and survive. Cytokines and growth factors carry that signal. Much of the mechanistic detail comes from studies in mice.
What is VEGF?
VEGF stands for vascular endothelial growth factor. It promotes the growth of blood vessels and also acts on nerve cells. Higher cerebrospinal fluid VEGF was associated with larger hippocampal volume in 279 older adults (Hohman et al., 2015).
What is EGF?
EGF stands for epidermal growth factor. It stimulates neural stem cells, astrocytes, and myelin-producing precursor cells, mostly demonstrated in rodents and cell culture (Scalabrino, 2022). Researchers also study it in patients with multiple sclerosis.
Should I try to raise my VEGF or EGF levels?
Neither is a target you should chase. VEGF exists to build vessels and raise their permeability, so sustained elevation serves no repair purpose. EGF supports myelin-producing precursor cells, and researchers have documented low levels in patients with multiple sclerosis. What the tissue requires sets the direction, not a higher number.
What does immunomodulatory mean?
Immunomodulatory describes something that adjusts immune signaling rather than only raising or lowering it. Researchers used that word for the regimen studied in adults with multiple sclerosis (McDaniel et al., 2020). Open-label trials cannot confirm the mechanism behind it.
Can a dietary supplement change growth factor levels?
No supplement has been shown to raise VEGF or EGF in healthy adults in a randomized controlled trial. My own open-label trials measured changes in adults with a diagnosed disease. Those results do not transfer to healthy people.
References
Apte, R. S., Chen, D. S., & Ferrara, N. (2019). VEGF in signaling and disease: Beyond discovery and development. Cell, 176(6), 1248–1264. https://doi.org/10.1016/j.cell.2019.01.021
Fabel, K., Fabel, K., Tam, B., Kaufer, D., Baiker, A., Simmons, N., Kuo, C. J., & Palmer, T. D. (2003). VEGF is necessary for exercise-induced adult hippocampal neurogenesis. European Journal of Neuroscience, 18(10), 2803–2812. https://doi.org/10.1111/j.1460-9568.2003.03041.x
Filiano, A. J., Gadani, S. P., & Kipnis, J. (2017). How and why do T cells and their derived cytokines affect the injured and healthy brain? Nature Reviews Neuroscience, 18(6), 375–384. https://doi.org/10.1038/nrn.2017.39
Hohman, T. J., Bell, S. P., & Jefferson, A. L. (2015). The role of vascular endothelial growth factor in neurodegeneration and cognitive decline: Exploring interactions with biomarkers of Alzheimer disease. JAMA Neurology, 72(5), 520–529. https://doi.org/10.1001/jamaneurol.2014.4761
Kalliolias, G. D., & Ivashkiv, L. B. (2016). TNF biology, pathogenic mechanisms and emerging therapeutic strategies. Nature Reviews Rheumatology, 12(1), 49–62. https://doi.org/10.1038/nrrheum.2015.169
Lewis, J. E., McDaniel, H. R., Agronin, M. E., Loewenstein, D. A., Riveros, J., Mestre, R., Martinez, M., Colina, N., Abreu, D., Konefal, J., Woolger, J. M., & Ali, K. H. (2013). The effect of an aloe polymannose multinutrient complex on cognitive and immune functioning in Alzheimer’s disease. Journal of Alzheimer’s Disease, 33(2), 393–406. https://doi.org/10.3233/JAD-2012-121381
Lewis, J. E., McDaniel, H. R., Woolger, J. M., Anzola, E., & Kraft, G. (2024). The characterization of the Th1/Th2 ratio in multiple sclerosis patients and its response to a dietary supplement regimen. Journal of Dietary Supplements, 21(6), 771–790. https://doi.org/10.1080/19390211.2024.2386259
McDaniel, H. R., LaGanke, C., Bloom, L., Goldberg, S., Lages, L. C., Lantigua, L. A., Atlas, S. E., Woolger, J. M., & Lewis, J. E. (2020). The effect of a polysaccharide-based multinutrient dietary supplementation regimen on infections and immune functioning in multiple sclerosis. Journal of Dietary Supplements, 17(2), 184–199. https://doi.org/10.1080/19390211.2018.1495675
Scalabrino, G. (2022). Epidermal growth factor in the CNS: A beguiling journey from integrated cell biology to multiple sclerosis. An extensive translational overview. Cellular and Molecular Neurobiology, 42(4), 891–916. https://doi.org/10.1007/s10571-020-00989-x
Song, B. X., Azhar, L., Koo, G. K. Y., Marzolini, S., Gallagher, D., Swardfager, W., Chen, C., Ba, J., Herrmann, N., & Lanctôt, K. L. (2024). The effect of exercise on blood concentrations of angiogenesis markers in older adults: A systematic review and meta-analysis. Neurobiology of Aging, 135, 15–25. https://doi.org/10.1016/j.neurobiolaging.2023.12.004
Stillman, J., Martin, A., Miguez, M.-J., McDaniel, H. R., Konefal, J., Woolger, J. M., & Lewis, J. E. (2020). Relationship between brain-derived neurotrophic factor and immune function during dietary supplement treatment of elderly with Alzheimer’s dementia. Journal of Clinical and Translational Research, 5(2), 68–75. https://doi.org/10.18053/jctres.05.201902.005
