Get Your Personalized Supplement StackSupplement Stack Quiz

growth factors

Also known as: Growth factors, cytokines, mitogens, FGF-23, Fibroblast Growth Factor-23

Overview

Growth factors are a diverse class of naturally occurring proteins and peptides that play crucial roles in regulating cellular growth, proliferation, differentiation, and tissue repair. They act as signaling molecules, binding to specific cell surface receptors to activate intracellular pathways that govern cellular behavior. While many types exist, such as Epidermal Growth Factor (EGF) and Platelet-Derived Growth Factor (PDGF), Fibroblast Growth Factor-23 (FGF-23) is particularly relevant in the context of nutritional supplementation due to its involvement in mineral metabolism. Growth factors are found endogenously in the body and can be isolated or synthetically produced. They are primarily used in medical contexts for wound healing, skin regeneration, and anti-aging applications. The research maturity for specific growth factors in medical applications is moderate to advanced, but high-quality evidence for the efficacy of direct oral supplementation of intact growth factors in the general population is limited due to their susceptibility to degradation in the gastrointestinal tract. Instead, research often focuses on modulating endogenous growth factor levels through nutritional interventions, such as vitamin D supplementation.

Benefits

The primary benefit observed in the context of nutritional supplementation is the modulation of endogenous growth factors, particularly Fibroblast Growth Factor-23 (FGF-23), through vitamin D supplementation. Meta-analyses have shown that vitamin D supplementation can significantly increase serum levels of FGF-23, a hormone critical for phosphate metabolism and vitamin D regulation, which indirectly impacts bone health. While some studies show a non-significant weighted mean difference increase in serum FGF-23 concentrations with native vitamin D, other meta-analyses confirm a significant increase, suggesting a dose-dependent relationship. This modulation is mainly studied in populations with metabolic disorders, bone diseases, or vitamin D deficiency, where its clinical relevance is more pronounced. The increase in FGF-23 levels typically occurs over weeks to months of consistent vitamin D supplementation. Additionally, omega-3 fatty acid supplementation has been shown to influence the gene expression of other growth factors, such as FGF-21, which is involved in metabolic regulation, though this evidence is heterogeneous and requires further research.

How it works

Growth factors exert their effects by binding to specific cell surface receptors, such as tyrosine kinase receptors for FGFs. This binding initiates intracellular signaling cascades, including the MAPK, PI3K/Akt, and JAK/STAT pathways. These pathways ultimately regulate gene expression and cellular behavior, influencing processes like cell proliferation, differentiation, and metabolism in various tissues, including bone, skin, and vascular endothelium. For instance, FGF-23 primarily acts on the kidneys to regulate phosphate reabsorption and vitamin D activation. While direct oral supplementation of intact growth factors is generally limited by degradation in the gastrointestinal tract, their levels can be indirectly modulated. For example, vitamin D supplementation increases endogenous FGF-23 levels, thereby influencing mineral metabolism and bone health through these established signaling pathways.

Side effects

Direct supplementation of growth factors is not typically done orally due to degradation, and thus, side effects directly from growth factor supplementation are not well-documented in this context. When considering the modulation of growth factors like FGF-23 through vitamin D supplementation, the safety profile is generally favorable within recommended doses. Common side effects are not directly linked to growth factor modulation but rather to excessive vitamin D intake, which can lead to hypercalcemia. Uncommon and rare side effects are not well-documented for growth factor modulation itself. Drug interactions are primarily associated with vitamin D, which can interact with certain medications, but growth factors themselves have no known direct interactions when modulated endogenously. Contraindications for vitamin D supplementation include hypercalcemia or certain granulomatous diseases. Monitoring is recommended for individuals with kidney disease or disorders of mineral metabolism when modulating FGF-23 levels, as these conditions can affect its regulation and impact.

Dosage

Dosage guidelines for modulating growth factors like FGF-23 are primarily tied to vitamin D supplementation, as direct oral growth factor supplementation is not effective. For vitamin D to influence FGF-23 levels, studies have used a wide range of doses, typically between 800–4000 IU/day. There is no established optimal dosage specifically for growth factor modulation; instead, standard clinical guidelines for vitamin D supplementation are followed. The maximum safe dose for adults is generally considered to be up to 4000 IU/day. Effects on serum growth factors are typically observed after weeks to months of consistent supplementation. Native vitamin D3 (cholecalciferol) or active forms are used in studies. Absorption of vitamin D is enhanced when taken with dietary fat. While not strictly required, cofactors such as magnesium and vitamin K may support vitamin D metabolism and overall bone health.

FAQs

Can growth factors be effectively supplemented orally?

Direct oral supplementation of intact growth factors is generally ineffective due to their degradation in the gastrointestinal tract. However, endogenous growth factor levels, like FGF-23, can be modulated indirectly through nutritional interventions such as vitamin D supplementation.

Are there risks in increasing growth factor levels?

While excessive or dysregulated growth factor activity could theoretically promote unwanted cell proliferation, the changes in FGF-23 levels induced by vitamin D supplementation are typically within physiological ranges and are not associated with significant adverse events.

How soon can effects be expected?

Changes in serum growth factor levels, particularly FGF-23 in response to vitamin D supplementation, typically occur over a period of weeks to months of consistent intake.

Is supplementation effective for all populations?

The benefits of modulating growth factors through nutritional means are more evident and clinically significant in populations with specific deficiencies or diseases, such as vitamin D deficiency or metabolic disorders. Effects in healthy individuals are less clear.

Research Sources

https://pubmed.ncbi.nlm.nih.gov/34710560/ – This systematic review and meta-analysis of 27 RCTs investigated the effect of vitamin D supplementation on serum FGF-23 levels. It found a non-significant weighted mean difference for native vitamin D, indicating inconsistent effects across studies, highlighting heterogeneity and variable dosing as limitations.
https://pubmed.ncbi.nlm.nih.gov/31372708/ – This meta-analysis confirmed that oral vitamin D3 supplementation significantly increased serum intact FGF-23 concentrations. The findings suggest a dose-dependent relationship, supporting the biological plausibility of vitamin D's role in modulating growth factors involved in mineral metabolism.
https://www.frontiersin.org/journals/nutrition/articles/10.3389/fnut.2023.1202688/full – This systematic review and meta-analysis explored the impact of omega-3 fatty acids on the gene expression of growth factors, including FGF-21, in metabolic conditions. It noted significant heterogeneity and a limited number of studies, advising cautious interpretation of the results.