Squalene is a natural substance found most commonly in olive oil. It is praised for its anti-cancer and skin-protecting effects. However, squalene may also be beneficial in Parkinson’s disease, lower cholesterol levels, and act as an antioxidant. Learn more about it in this post.
What Is Squalene?
Squalene is a molecule produced by humans, animals, and plants. It is a precursor to cholesterol and all steroid hormones [1, 2].
It is structurally related to some of the beneficial compounds found in other plants, including ginseng, pumpkin, rosemary, and thyme (triterpenoids) [3].
Squalene is abundant in both olive oil and shark liver oil [2].
Squalene has some beneficial properties when consumed either from food or as a supplement. These include potential anticancer effects, protective and moisturizing role in the skin, antioxidant activity and it may even improve the immune response to vaccines.
Squalene vs. Squalane
It’s important not to confuse squalene with squalane.
Squalene is broken down into squalane in the body by certain enzymes (squalene epoxidase, also known as squalene monooxygenase) [4].
Squalane is also common in cosmetic products, but it differs from squalene in its health effects [4].
Natural Sources and Supplements
There are multiple natural sources of squalene and supplements of the following oils can be purchased:
- Olive oil: Olive oil is a common source of squalene. Olive oil contains about 3.9 to 9.6 grams of squalene per liter [5].
- Shark liver oil: Shark liver oil is the richest known source of squalene. Squalene levels are high in the fatty tissues of sharks.*
*Cancer researchers once thought that squalene was the reason that sharks seemingly did not get cancer. Although this has been shown to be false, as sharks do indeed get cancer, squalene still may play an important protective role.
- Other sources: Squalene is also found in palm oil, wheat-germ oil, amaranth oil, and rice bran oil [6].
- Squalene is also produced naturally within the body and is a precursor to cholesterol.
Mechanisms of Action
Squalene exerts its effects by [7, 8, 9, 10, 11, 12, 6]:
- Being a precursor to the synthesis of cholesterol and steroid hormones like testosterone and estrogen
- Inhibiting HMG-CoA reductase, which blocks ras pathways involved in cancer growth
- Increasing production of collagen (type 1 procollagen), reducing UV ray damage and wrinkles
- Supporting pro-hydration processes within the skin, acting as a natural moisturizer
- Reducing double-stranded breaks in DNA, lowering DNA damage
- Activating enzymes involved the Krebs cycle and oxidative phosphorylation, along with increases detoxing of the body (glutathione-dependant)
- Increasing fat metabolism by activating PPARα
- Protecting against oxidative damage in the striatum
- Possibly increasing healthy cholesterol levels (HDL)
Health Benefits of Squalene
Insufficient Evidence for:
1) Protecting the Skin
Squalene is found in the outer layer of the skin and plays a role in protecting against UV radiation [13].
Without sufficient squalene, UV rays can induce inflammation in the skin [14].
In 40 women over the age of 50, squalene supplementation given for 90 days reduced redness and improved collagen activity at low doses (13.5 grams per day). At higher doses (27 grams per day), it reduced wrinkles. Both doses were effective in reducing cell death caused by UV radiation [15].
In a clinical trial on 23 women, a combination of squalene and the antioxidant fullerene–C60 for 8 weeks reduced the appearance of wrinkles [16].
Squalene may be useful in the treatment of skin disorders like psoriasis, dermatitis, and acne [17, 18].
However, a pilot study of young men (aged 15 to 20) found two-fold higher squalene levels in those with acne, suggesting its potential to worsen this skin condition. Rather than squalene itself, its breakdown (oxidation) products have been suggested to lead to acne [19, 20].
Taken together, a few small clinical trials suggest that squalene may protect the skin from UV radiation and aging. However, the evidence to support this use is insufficient until larger, more robust clinical trials are conducted.
Although squalene is claimed to help with skin disorders, the only clinical trial suggests it may worsen acne. Because the evidence is insufficient, further clinical research is required.
2) Improving Response to Vaccines
In 13 volunteers, supplementation with shark liver oil, containing 3.6 grams of squalene, increased the number of white blood cells that fight bacteria [21].
Squalene is sometimes used as an additive in vaccines. In cell-based studies, it increased the immune response (activating antigen-presenting cells and T-cells) [22, 23].
Lack of Evidence
No evidence supports the use of squalene for any of the conditions listed in this section. While the clinical research investigating its effects on blood cholesterol levels produced contradicting results, the other potential benefits have only been tested in animals and cells. Therefore, the studies listed below should not be interpreted as supportive of any health benefit.
Cholesterol
Squalene is a precursor to cholesterol. Whether squalene increases good or bad cholesterol levels is still not understood.
Long-term squalene consumption in humans has not shown a consistent effect on cholesterol levels [24].
In a clinical trial on 120 elderly people, a combination of squalene and the statin drug pravastatin reduced total cholesterol, LDL, and triglyceride levels, while increasing HDL [25].
However, in 9 long-term hospital patients with heart dysfunction and high cholesterol, squalene given 3 times daily for 7 to 30 days had no effect on blood levels of triglycerides or total cholesterol [26].
Adding 1 mg of squalene per day for 9 weeks along with rapeseed oil reversed the beneficial effects of rapeseed oil on cholesterol levels, increasing levels of bad cholesterol (VLDL, IDL, LDL), in a small trial on 18 men [27].
Similarly, a single dose of squalene increased bad cholesterol levels (VLDL) within 9 to 12 hours following consumption and supplementation with shark liver oil, with a content of 3.6 g of squalene per day, increased the levels of total cholesterol and reduced the amount of good cholesterol (HDL) relative to total cholesterol in 2 small trials on 29 healthy people [24, 21].
The results were also mixed in animal studies.
In male mice, squalene increased HDL, the “good” cholesterol [11].
However, in rats, blocking squalene reduced bad cholesterol levels (VLDL and triglycerides) [28].
In hamsters, supplementation of both squalene and shark liver oil, which is a known source of squalene, significantly increased levels of total cholesterol in the blood. Squalene also increased triglycerides [29].
Squalene lowered high cholesterol in liver cells [30].
The effects of squalene on cholesterol levels may be different between humans, animals, and isolated cells. It also may depend on the duration of treatment. Therefore, more clinical research is needed before we can draw conclusions.
Antioxidant
In mice, combining squalene with astaxanthin, an antioxidant, lead to higher activation of antioxidant enzymes (SOD1, GPX1), compared to giving either substance alone. This suggests that combining squalene with other antioxidants may increase its antioxidant benefits [31].
In human skin cells, squalene scavenged free radicals and reduced damage caused by oxidative stress [32].
The combination of squalene and other antioxidants (astaxanthin and fucoxanthin/fucoxanthinol) reduced the damaging effect of fats in cells [33].
Mitochondrial Function
In both young and aged rats, squalene supplementation improved mitochondrial function in the liver by increasing the activities of several energy-producing pathways (Krebs cycle and oxidative phosphorylation) [9].
Squalene also supported detoxing processes in the body (glutathione-dependent) in rats [9].
Fatty Liver Disease
Squalene may help fatty liver disease by increasing fat metabolism (activates PPARα) [34].
Squalene synthase is the enzyme that produces squalene. Mice that do not synthesize squalene (deficient in squalene synthase) show signs of liver dysfunction and abnormal enlargement of the liver (due to increased farnesol production) [35].
However, higher levels of squalene synthesis in mice were linked to increased liver size and dysfunction, along with high cholesterol levels [36].
Therefore, a delicate balance between high and low squalene levels may be beneficial in treating liver dysfunction.
Parkinson’s
In mice with Parkinson’s disease, squalene, given for 7 days, maintained levels of dopamine in the brain (striatum). It reduced oxidative damage and prevented the toxicity of a chemical that destroys dopamine neurons (6-OHDA) [10].
In flies, both a plant extract (Bougainvillea glabra Choisy) containing squalene and a substance that causes Parkinson’s-like symptoms (paraquat) were given for 4 days. This improved mobility and prevented dopamine loss and cell death [37].
Anti-Cancer
Although squalene is sometimes used as an add-on to anticancer therapy, the research investigating this use is still in the animal and cell stage. The results are promising, but further clinical studies have yet to determine its effectiveness in cancer therapies.
Do not under any circumstances attempt to replace conventional cancer therapies with squalene or any other supplements. If you want to use it as a supportive measure, talk to your doctor to avoid any unexpected interactions.
Doxorubicin is a common chemotherapy drug. In mice, the combination of doxorubicin and squalene increased the anticancer activity of doxorubicin. Squalene increased the accumulation of doxorubicin inside the tumor, targeting the treatment of cancer cells only. It also prolonged the effects of doxorubicin in the body [38].
In mice with pancreatic cancer, squalene improved the accessibility of tumors to therapy. It did so by changing the network of blood vessels that supply the tumor [39].
The addition of squalene to the skin before exposure to cancerous molecules completely inhibited cancer growth in mice [40].
In cells, squalene combined with chemotherapy (cisplatin) was 10 times better at killing cancer cells than chemotherapy alone [41].
Squalene increased the anticancer properties of the chemotherapeutic drug doxorubicin in cells [38].
Reducing the Side Effects of Chemotherapy
Cisplatin is a chemotherapy drug that often causes side effects. In mice with intestinal tumors, a combination of squalene-cisplatin prevented the formation of tumors without any signs of toxic side effects [41].
In mice, squalene reduced the DNA damage caused by the chemotherapy drug doxorubicin, especially when squalene was given after doxorubicin. It increased tolerability to this drug 5-fold and prevented heart toxicity, a common side effect of doxorubicin treatment [42, 38].
Using Squalene Effectively
Dosage
Because squalene is not approved by the FDA for any conditions, there is no official dose. Users and supplement manufacturers have established unofficial doses based on trial and error.
The average intake of squalene is estimated to be around 30 mg per day [43].
However, when olive oil plays a more prominent role in the diet, like the Mediterranean diet, levels of squalene can reach anywhere from 200 to 400 mg per day.
Shark liver oil supplements commonly contain between 120 to 500 mg of squalene per dose.
Studies have indicated that squalene supplements are tolerable up to 27 grams with mild side effects [15].
Side Effects
Keep in mind that the safety profile of squalene is relatively unknown, given the lack of well-designed clinical trials. The list of side effects below is, therefore, not a definite one. You should consult your doctor about other potential side effects based on your health condition and possible drug or supplement interactions.
In 50 women taking squalene for 3 months, doses ranging from 13.5 to 27 grams per day caused loose stool. This side effect was minor and temporary [15].
Several cases of squalene-induced, chronic exogenous lipoid pneumonia have been identified. This may be due to the inhalation of squalene particles. This may be a good reason to avoid cooking with olive oil at high temperatures, which contains squalene [44, 45, 46].
One case of lipoid pneumonia has been linked with ingestion of squalene in the form of shark liver oil [47].
Oral consumption of squalene is relatively safe, considering that squalene is found naturally in food [48].
However, the use of squalene supplements in pregnant women is not recommended because safety has not been evaluated in that population. Pregnant women should stick to food doses.
Squalene added to vaccines may be linked to a number of side effects, including [49, 50, 51, 52]:
- Gulf War Syndrome – symptoms such as fatigue, pain, cognitive dysfunction, insomnia, and mood disturbances
- Pain at the site of injection
- Rash at site of injection
- Hardening of soft tissues
- Muscle pain
- A headache
- General discomfort
- Narcolepsy in children and adults
Therefore, it is possible that direct injection of squalene, even with the other potential benefits that it may play in vaccinations, could still lead to negative effects.
Limitations and Caveats
There are very few human studies that support the benefits of squalene use. Since many of the studies on squalene have been done in cell or animal models, there is no evidence that they will have comparable effects in humans.
Drugs Interactions
No known drug interactions have been claimed for squalene. Because squalene is a relatively uninvestigated substance, yet unknown interactions are possible. Talk to your doctor if you notice any adverse effects from combining squalene with any medications or supplements.
Genetic Variations That May Change Your Response to Squalene Supplementation
Certain genes may increase or decrease your response to squalene supplements.
- FDFT1: This gene codes for the squalene synthase enzyme, which is responsible for the internal synthesis of squalene. Variations in this gene may decrease or increase your natural levels of squalene, which would indicate how effective squalene supplementation will be for you [53].
- SQLE: This gene codes for squalene epoxidase enzyme, which is responsible for breaking down squalene. Variations in this gene may reduce the effectiveness of squalene or increase the amounts in your bloodstream. Higher levels of squalene epoxidase in patients are linked to breast, ovarian, and colorectal cancers [54].
User Reviews
The opinions expressed in this section are solely those of users, who may or may not have medical or scientific training. Their reviews do not represent the opinions of SelfHacked. SelfHacked does not endorse any specific product, service, or treatment.
Do not consider user experiences as medical advice. Never delay or disregard seeking professional medical advice from your doctor or other qualified healthcare providers because of something you have read on SelfHacked. We understand that reading individual, real-life experiences can be a helpful resource, but it is never a substitute for professional medical advice, diagnosis, or treatment from a qualified healthcare provider.
Pure squalene supplements are not commercially available. Therefore, people use shark liver oil supplements to exploit the benefit of squalene.
One user receiving chemotherapy began using shark liver oil. They claim that the supplement prolonged their lifespan by 3 years and improved quality of life.
This user also claimed the oil was easy to take and digest and caused no side effects.
Another user stated that taking shark liver oil helped resolve a sore throat within one day and caused no side effects.
Multiple users have stated they have had no negative side-effects from taking shark liver oil.
