Mmmm, sweet honey. We're all familiar with this natural sweet nectar. Honey has a long history, not just in our food but in medicine. Honey is mentioned in nearly all ancient Egyptian medicines, often mixed with wine and milk (1). The Greeks, too, valued honey for its medicinal properties – Hippocrates, the father of modern medicine, frequently prescribed honey for a spectrum of ailments, from treating wounds to cold symptoms and certain nervous disorders (1). Modern science continues to explore honey's healing potential, and recent research has shed light on the remarkable properties of a particular type of honey: Manuka honey.
So, what is Manuka honey, and what makes it so unique? Manuka honey (MH) comes from the nectar of the Manuka tea tree, and what sets it apart from other types of honey is its high concentration of methylglyoxal - a compound known for its potent antibacterial and antioxidant properties. On top of that, MH is rich in flavonoids, phytochemicals, vitamins, amino acids, and minerals that all contribute to its diverse biological activities. Manuka honey was crucial in traditional medicine, but more recently, it has been catching the eye of modern scientists trying to quantify these "healing properties." According to a recent study, this honey's superpower may be its effectiveness in treating breast cancer.
Breast cancer remains a significant cause of death among women, and in many of these cases, a specific protein called estrogen receptor alpha (ERα) is involved. Some treatments target this protein effectively, but over time, some patients will become resistant to these therapies, which leaves chemotherapy as the only standard-of-care option. Preventing this resistance is vital for the fight against ER+ breast cancer.
A group from UCLA, led by Dr. Diana Marquez-Garban, explored MH's effects on both estrogen receptor-positive and negative breast cancer. (2). Using dehydrated MH powder in varying concentrations of 0.3-5.0%, the researchers showed that the growth of estrogen receptor-positive MCF-7 breast cancer cells was significantly inhibited. The honey worked in a dose-dependent manner, meaning the higher the concentration of honey, the more significant the reduction in cell growth. The effect of MH on triple-negative MDA-MB-231 cells was more limited compared to the significant reduction of proliferation seen in ER+ cells, implying that MH has an affinity for estrogen receptor-positive cells. The authors speculated this was due to "estrogen-like" compounds reported within MH, stating:
"Certain phenolic compounds that are constituents of honey are phytoestrogens with structural similarity to mammalian estrogens and can potentially bind to estrogen receptors. Hence, the occurrence of natural phytoestrogens as constituents of honey may be one explanation for these antitumor actions and suggests that endocrine-sensitive breast cancer cells may be a reasonable target to explore for MH or MH derivatives."
The UCLA group compared MH's effect on MCF-7 cells to Tamoxifen, a commonly used anti-estrogen therapy for ER-positive breast cancer. While their results alone were compelling, a synergistic effect was observed when the two were paired together.
"...we found that MCF-7 cell proliferation is markedly suppressed and was significantly less than that of either treatment administered alone."
Notably, the combination treatment had no toxic effect on non-cancerous human mammary cells, indicating that the treatment specifically targets the cancer cells.
In the second part of this study, the researchers wanted to investigate the potential of MH to induce apoptosis, or programmed cell death, in breast cancer cells. They compared MH against Mesquite honey and dextrose in varying concentrations, and what they found was illuminating. The findings revealed that MH induced a dose-dependent increase in apoptosis, particularly in MCF-7 cancer cells—MH was significantly more effective at this than Mesquite honey and dextrose—suggesting that MH's unique components, rather than its sugar content, are responsible for these results.
While these results are intriguing, how does the honey make this happen? One of the most salient and awe-inspiring features of cancer is immortalization, or resisting apoptosis, or natural "programmed cell death," a process that healthy cells undergo when damaged for the good of the whole organism. MH facilitates apoptosis through various mechanisms, allowing cancer cells to die in an orderly manner that does not provoke inflammation. Additionally, the study showed that MH reduces tumor progression and growth by targeting and inhibiting the critically important signaling pathways STAT3 and mTOR. Each of these targets is highly sought after by pharmaceutical companies that hope to develop drugs to target them individually; it is truly amazing that MH's diverse range of bioactive compounds can simultaneously target multiple critical cancer pathways.
There’s no denying that these results are fascinating, but not all in vitro models and mechanistic studies hold up in a living organism. In the pièce de résistance and the most exciting act of this study, mice were implanted with MCF-7 tumor cells to model breast cancer, and MH was given orally as the treatment. This showed that “MH administered by oral gavage significantly inhibited the growth and progression of established human breast tumor xenografts in nude mouse models by 84%.”(2).
Historically, the largest problem in cancer drug development has been the inexorably interwoven cellular pathways shared by cancer cells and healthy cells—in other words, finding targets present in cancer cells that are not present in healthy cells. This was the most significant problem in the 1940s when the first chemotherapy drugs were being developed, and it remains the most significant problem today. As such, the results shown above from a food as safe (and tasty) as honey are truly remarkable.
Never discount nature's intellectual property.
To be sure, the overwhelming problem with non-patentable, natural products like Manuka honey is that they rarely get the funding for a phase 3, randomized, controlled trial required to meet the FDA's burden of proof for approval and adoption.
Even so, given that Manuka honey presents no safety concerns, the risk/potential reward ratio is extremely low. The high fructose content of honey may worry those attempting to reduce blood sugar, but this is much less of a concern than other glucose-containing carbohydrates. Fructose has a lower glycemic index, does not spike blood glucose to the degree of different carbohydrates, and stimulates much lower insulin release. Some studies have shown that honey can improve insulin resistance (4).
As always, at Meakin Metabolic Care, we will continue to stay current with new research and attempt to break it down into understandable and actionable pieces.
Chuck Meakin MD
Disclaimer: This information is not meant as direct medical advice. Readers should always review options with their local medical team. This is the sole opinion of Dr. Meakin based on a literature review at the time of the blog and may change as new evidence evolves.
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References
Eteraf-Oskouei T, Najafi M. Traditional and modern uses of natural honey in human diseases: a review. Iran J Basic Med Sci. 2013 Jun;16(6):731-42. PMID: 23997898; PMCID: PMC3758027..
Márquez-Garbán DC, Yanes CD, Llarena G, Elashoff D, Hamilton N, Hardy M, Wadehra M, McCloskey SA, Pietras RJ. Manuka Honey Inhibits Human Breast Cancer Progression in Preclinical Models. Nutrients. 2024; 16(14):2369. https://doi.org/10.3390/nu16142369
PARP inhibitors. PARP Inhibitors | Targeted cancer drugs | Cancer Research UK. (2023, November 8). https://www.cancerresearchuk.org/about-cancer/treatment/targeted-cancer-drugs/types/PARP-inhibitors#:~:text=PARP%20is%20a%20protein%20(enzyme,cells%20and%20the%20cell%20dies.
Ramli NZ, Chin KY, Zarkasi KA, Ahmad F. A Review on the Protective Effects of Honey against Metabolic Syndrome. Nutrients. 2018 Aug 2;10(8):1009. doi: 10.3390/nu10081009. PMID: 30072671; PMCID: PMC6115915.
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