What is Procyanidin, and how does it encourage hair growth at the follicle level?

Procyanidins are a class of polyphenolic compounds belonging to the flavonoid family. Chemically, they are oligomers composed of smaller flavan-3-ol units such as catechin and epicatechin. The dimeric form known as Procyanidin B-2, primarily found in apple skins and grape seeds, has attracted scientific attention for its potential to stimulate hair growth. These compounds are known for their antioxidant and anti-inflammatory properties, which may influence biological pathways linked to hair follicle activity.

When we explore the molecular world of Procyanidin B-2, what stands out is its interaction with the cells that form and regulate the hair follicle. A follicle is not a simple pore; it is a mini-organ with its own growth cycles—anagen (growth), catagen (regression), and telogen (rest). Hair loss occurs when these cycles shorten or become disrupted, leading to miniaturized follicles that produce thinner and weaker strands. Understanding how Procyanidin interferes or supports these cycles is essential to assess whether its effects are scientifically justified.

How Procyanidin interacts with the hair follicle

At the cellular level, Procyanidin B-2 has shown the ability to promote the proliferation of epithelial cells within the follicle. A seminal study conducted in 1999 by Takahashi and colleagues at Tsukuba Research Laboratories investigated this effect using cultured mouse hair epithelial cells and C3H mice models. The in vitro component of the study demonstrated that Procyanidin B-2, at a concentration of 30 µM, increased cell proliferation by approximately 300% compared to controls after five days of culture.

The in vivo phase involved topical application of Procyanidin B-2 on the dorsal skin of mice in the telogen phase, resulting in a 69.6% ± 21.8% induction of hair growth compared to 41.7% ± 16.3% in the control group. While these results were statistically significant, they remain limited to animal and cell models, and extrapolating them to humans requires caution.

Mechanistically, Procyanidin B-2 may affect the activity of protein kinase C (PKC) isozymes, a family of enzymes that regulate numerous cellular processes. By suppressing specific PKC isozymes—such as PKC-α, PKC-βI, PKC-βII, and PKC-η—Procyanidin appears to lift an inhibitory mechanism that normally limits hair follicle cell growth. This action could partly explain the observed proliferation of epithelial cells. However, the mechanism remains hypothetical, as direct molecular pathways in human follicles have not yet been fully mapped.

Another notable mechanism involves the modulation of oxidative stress and inflammation, two processes that contribute to follicular miniaturization and premature entry into the resting phase. By acting as an antioxidant, Procyanidin may reduce cellular damage within the follicle’s microenvironment. This hypothesis aligns with findings that connect oxidative stress with androgenetic alopecia, although Procyanidin’s antioxidant role in the scalp has not been conclusively demonstrated in clinical trials.

Human studies: from laboratory promise to real-world application

The transition from animal research to human studies began with a double-blind, placebo-controlled clinical trial led by Kamimura et al. in 2000, conducted in 29 men aged 30 to 57 with androgenetic alopecia. Participants applied a 1% topical Procyanidin B-2 solution twice daily for four months. The researchers observed that 78.9% of participants experienced an increase in hair diameter, compared with 30% in the placebo group. The treated group also showed an average increase of 3.67 hairs per 0.25 cm², while the placebo group experienced a decrease of 2.54 hairs. These results indicated a statistically significant improvement, yet the small sample size and short duration of treatment limit the generalizability of these findings.

More than two decades later, Yeniay and Arca (2022) conducted another randomized, double-blind, placebo-controlled study with 40 male participants between 21 and 44 years old. The subjects applied a topical formula containing 1% Procyanidin B-2, biotin, and dexpanthenol twice daily for 16 weeks. **The evaluation used TrichoScan technology to measure hair density, growth phase ratio, and hair diameter, alongside photographic assessments. **

The Procyanidin group showed significant increases in total and anagen hair counts, while side effects were mild and limited to transient itching and redness. Nevertheless, the inclusion of biotin and dexpanthenol complicates interpretation, as the observed effects cannot be attributed exclusively to Procyanidin B-2.

A 2022 study by Lee and colleagues provided additional insights using C57BL/6 mice. In this model, daily oral administration of an Annurca apple extract rich in Procyanidin B-2 for 21 days led to increased hair length, thickness, and follicular density. Genetic analyses revealed upregulation of VEGFA and FGF-7, both associated with blood vessel formation and follicle cell proliferation, alongside suppression of type 1 5α-reductase, an enzyme responsible for converting testosterone to dihydrotestosterone (DHT). These findings suggest that Procyanidin may exert multi-level effects, influencing not only follicle growth but also the hormonal environment that regulates it.

A critical interpretation of the evidence

Although Procyanidin B-2 has repeatedly shown positive trends in laboratory and preliminary clinical research, several methodological limitations remain. Most studies have small sample sizes, short durations, and male-only populations. The concentration and formulation of Procyanidin vary among trials, making comparisons difficult. Additionally, studies that include other active ingredients introduce confounding variables that obscure Procyanidin’s specific contribution. The lack of large-scale, long-term, double-blind studies prevents definitive conclusions about its clinical efficacy.

Moreover, while the compound’s antioxidant and anti-inflammatory properties are well-documented in general physiology, their relevance in the complex pathology of hair loss remains uncertain. The precise molecular mechanisms through which Procyanidin acts on human follicles are not fully elucidated, and in vitro findings do not always replicate in vivo outcomes.

Despite these limitations, the compound appears to have a favorable safety profile, with no serious adverse effects reported in the studies reviewed.

From a practical standpoint, what we need to know as individuals interested in the biological foundation of hair health is that Procyanidin B-2 represents a promising but still exploratory avenue. Its mechanisms suggest real biological plausibility, yet the evidence base is not yet robust enough to consider it a proven therapy. Ongoing independent research, ideally involving larger, longer, and more diverse human trials, will determine whether its early promise can translate into meaningful clinical outcomes.

References

Kamimura, A., Takahashi, T., & Watanabe, Y. (2000). Investigation of topical application of procyanidin B-2 from apple to identify its potential use as a hair-growing agent. Phytomedicine, 7(6), 529–536. https://pubmed.ncbi.nlm.nih.gov/11194183/

Lee, Y. I., Ham, S., Lee, S. G., Jung, I., Suk, J., Yoo, J., Choi, S.-Y., & Lee, J. H. (2022). Annurca apple extract enriched in procyanidin B2 promotes hair growth in mice by modulating growth factor expression and 5α-reductase activity. Current Issues in Molecular Biology, 44(12), 428–439. https://pubmed.ncbi.nlm.nih.gov/36549226/

Takahashi, T., Kamiya, T., Hasegawa, A., Yokoo, Y., Honda, S., & Watanabe, Y. (1999). Procyanidin oligomers selectively and intensively promote proliferation of mouse hair epithelial cells in vitro and activate hair follicle growth in vivo. Journal of Investigative Dermatology, 112(3), 310–316. https://pubmed.ncbi.nlm.nih.gov/10084307/

Takahashi, T., Yokoo, Y., Inoue, T., & Ishii, A. (1999). Toxicological studies on procyanidin B-2 for external application as a hair-growing agent. Food and Chemical Toxicology, 37(5), 545–552. https://pubmed.ncbi.nlm.nih.gov/10456683/

Yeniay, Y., & Arca, E. (2022). Evaluation of the efficacy and safety of topical procyanidin B2 in male patients with androgenetic alopecia: A randomized double-blind, placebo-controlled study. Turkish Journal of Dermatology, 16(2), 108–115. https://turkjdermatol.com/pdf/337910e4-2271-4883-88bd-db7abaf5adda/articles/tjd.tjd_41_22/TDD-16-108-En.pdf