The safety of cyperus oil
How safe is this viral social media trend? Not as safe as you'd hope.
Cyperus oil went viral recently as a hair removal miracle. Is it safe and should you use it?
I previously covered the efficacy in this video – it is most likely ineffective.
As this oil has very limited safety data, I decided to conduct my own safety assessment. It will give us a very preliminary view of potential hazards and exposure risks.
Chemical risk assessments
When scientists evaluate the safety of a substance, like a skincare ingredient or essential oil, they follow a structured approach that consists of four main steps:
Hazard Assessment: This is all about identifying potential dangers. Scientists ask, “Could this substance cause harm, and if so, what kind?” They look at whether the chemical can cause health issues like skin irritation, organ damage, or even hormonal disruptions.
Dose-Response Relationship: This step is where scientists figure out how much of the substance is harmful. They study how different amounts of the chemical affect the body to determine the level at which it becomes dangerous – essentially, finding the line between a safe amount and a potentially harmful dose.
Exposure Assessment: The goal here is to understand how much of the substance people are likely to be exposed to. Scientists consider where and how often the substance is used, such as whether it’s applied to the skin, inhaled, or ingested.
Risk Management: Based on the information from the first three steps, this involves making recommendations to minimize any identified risks. This might mean setting safe use guidelines, adding warning labels, or even banning a substance if it is deemed too risky.
Cyperus oil risk assessment
As I am doing this risk assessment on cyperus oil with limited data and resources, I’ve used a simpler approach, focusing on just two of these steps: hazard assessment and exposure assessment. This type of computational or “in silico” approach is helpful as an early screening tool, but it is not a complete assessment.
To be more accurate, this is a first-tier assessment – an initial, streamlined risk assessment designed to quickly identify potential hazards and exposure risks without going into deep experimental or complex testing. It serves as a preliminary screening to flag substances that may require further, more detailed investigation.
What’s in cyperus oil?
The composition of cyperus oil can vary widely depending on where it’s sourced. I reviewed studies in South Africa, Nigeria, and Asia, where the oil showed different profiles based on the region.
I also came across a nice paper that did a fantastic job covering different variations of the oil and identifying the most frequent compounds in the 32 cyperus essential oils analyzed, from different geographical locations.
The most common compounds included:
Cyperene, identified 23 times in concentrations ranging from 19% to over 30%
β-Selinene (beta-selinene), identified 14 times in concentrations up to around 18%
These compounds stood out as primary components of the oil with known biological activities, so I selected them as the focus for my risk assessment.
Hazard assessment
Are cyperene and β-selinene dangerous?
As the oil is frequently described as having anti-androgenic properties, I decided to make the androgen receptor interaction my endpoint. In other words: are these chemicals able to interact with this receptor in any way?
I ran these compounds through a molecular docking software called SeamDock, an online tool for assessing chemical binding to biological targets. Molecular docking simulates how well these molecules could bind to a specific receptor – in this case, the androgen receptor, which plays a crucial role in regulating testosterone and cell cycle.
The goal of docking is to measure binding affinity, a measure of the strength of the interaction between the compound and the receptor. The binding affinity is calculated in kcal/mol, and a more negative value indicates a stronger interaction.
Hazard limitations
I want to highlight the first limitation here: binding doesn’t mean the compound will automatically trigger a biological effect. But it shows a potential for interaction, which is a useful preliminary indicator of risk.
To interpret these docking results, I included two control compounds:
Isopropylparaben, a compound banned in the EU for its endocrine-disrupting effects
Testosterone, the natural ligand for the androgen receptor
Calculated binding affinities (more negative indicates stronger interaction)
Cyperene: -7.3 kcal/mol
β-Selinene: -7.9 kcal/mol
Isopropylparaben: -6.8 kcal/mol
Testosterone: -9.2 kcal/mol
Testosterone had the strongest binding affinity. The values for cyperene and β-selinene, the main compounds from cyperus oil, are substantial enough to raise concerns. When compared to the result for isopropylparaben, they indicate that Cyperus oil components showed stronger binding than a compound already recognized as an endocrine disruptor.
Exposure Assessment
We now know that these compounds can interact with your androgen receptors with a relatively strong affinity. But if you apply them on your skin, are they able to penetrate the skin and reach systemic (whole-body) circulation? Are they able to travel to your receptors and interact with them?
To assess exposure, I used another computer model called IHSkinPerm, based on this publication if you want to read more.
As the oil is a complex mixture of active ingredients, modelling the complete oil would be very difficult for the model. The manual of this model suggested assessing every bioactive compound individually.
This publication specified that 0.25 mL is needed for application to the armpit area. Based on this, I calculated the millilitres needed for each square centimetre of skin.
Based on what I have seen online, people are applying it to the lower half of the face, armpits, legs, arms, and genitals. I used this publication to determine that the average skin surface area measured for these areas is 4114.5 cm2. Using these values, I calculated the volume applied to be 15.94 mL of oil.
The oil density was difficult to locate, but I found a value of 0.94. Following the dosage recommendation in the original study, I calculated 14,993 milligrams of oil to use for the computer model.
However, these active ingredients do not make up 100% of the oil.
The study reported an average of 18% β-selinene, giving an applied dosage of 2,698.8 mg per application. Cyperene was present at an average concentration of 30%, it is 4,498.1 mg.
I put these values into the IHSkinPerm software after adding all the physicohemical properties of those two compounds.
The results were not comforting.
Cyperene: After 2 hours and 17 minutes of application, 26.9% of the dose stays in the stratum corneum, the outer most layer and protective barrier of the skin. 73% (3,836 mg) is absorbed into the viable (living) epidermis, and is potentially available for systemic circulation.
β-Selinene: After 12 hours, only 3.4% is absorbed and potentially available for systemic circulation, a much better result.
To make the assessment as accurate as possible, I used the same computer model to estimate isopropylparaben absorption. Around 74% or 25.9 mg is absorbed and available for systemic circulation after application of the same dose.
Exposure Assessment Limitations
There are some limitations for using this model for exposure assessment.
Mixture vs single compound application: The oil is a mixture of actives, and the absorption of each can get complicated. This model examined one compound at time, which does not represent real life exposure, but it still gives us a decent estimate.
Essential oils can also play a role as penetration enhancers, allowing other compounds to pass more easily through the skin. So this assessment could be underestimating exposure to these compounds.
Metabolism: This exposure assessment did not look at any metabolism of these compounds as they pass through the skin. This could make my assessment a best or worst case scenario, depending on whether our skin transforms those compounds into something more or less active.
Risk of Cancer Induction
We now have preliminary information on the safety of this oil, and confirmed these compounds do have the potential to interact with your androgen receptors. They have the ability to penetrate through skin, and be absorbed in higher concentrations than what usually find in safely assessed cosmetics. This means the risk of inducing cancer is plausible.
Androgens in breast cancer
Androgens such as testosterone and its derivatives, and androgen receptors (AR), are present in both pre- and post-menopausal women. The role of androgens in breast cancer is complex, as they can either promote or inhibit cancer growth depending on the cancer subtype and the hormonal environment.
Androgen receptors in estrogen receptor (ER) positive breast cancer (ERPBC): Androgen receptor activation can inhibit cancer cell proliferation by modulating estrogen signaling. In these cases, blocking androgens could theoretically interfere with the anti-proliferative effect of androgen receptor, potentially allowing cancer cells to proliferate.
Androgen receptors (AR) in Triple-Negative Breast Cancer (TNBC): In ER-negative breast cancers, such as TNBC, AR are often expressed and can stimulate cell proliferation. In these cases, blocking AR (with anti-androgens) has been shown to inhibit tumour growth, making AR a therapeutic target for TNBC.
Risk considerations: The relationship between androgens and breast cancer risk is not straightforward. In post-menopausal women, higher levels of circulating androgens, particularly testosterone, have been associated with increased breast cancer risk. Blocking androgens could, in theory, reduce this risk in androgen-driven cancers, but the effect varies depending on whether the cancer is ER-positive or ER-negative.
Blocking androgen receptors might reduce cancer growth in AR-positive, ER-negative breast cancers like TNBC. However, blocking androgens in ER-positive breast cancers could reduce the anti-proliferative effects of androgens, potentially leading to an increased risk of cancer progression.
Conclusion
Is this oil safe for use on large surface areas, including high absorption areas such as the armpits and genital area?
My answer is probably not. Before doing this assessment, I recommended against using this oil. After investigating for 3 weeks, I am more confident that I really wouldn’t recommend it to anyone – if my family or loved ones asked, my answer would be an immediate “no”.
This also shows why critical thinking and listening to relevant experts is so important online. Dermatologist content creators are still recommending cyperus oil and insisting that it is safe, simply because it has been used for a long time. This is an example of how not every expert online can be trusted – dermatologists are not scientists, nor the ultimate experts on all topics related to cosmetics. Most dermatologists are deeply involved in clinical work, and not academia.
Risks that come from using a seemingly harmless looking oil can be far greater than risks from using a cosmetic product that follows regulations.
The recommendations around cyperus oil are based on nothing but fluff, glamorized by influencers including dermatologists, whose opinions seem to be largely based on the title of a publication. If the oil works, then it is strong enough to be a risk. If it doesn’t, then it is a waste of time, money, and still comes with minor risk. Neither situation is good.
References
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This article was originally published on BeautySciComm.