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Unlocking the Potential of Squalene (Omega-2) for Pet Wellness
Introduction
Squalene (SQ) is a hydrophobic biomolecule classified under the triterpene group. Structurally, it consists of six isoprene units, forming a 30-carbon isoprenoid (C₃₀H₅₀) with six double bonds. This compound is a colorless, odorless, oily liquid. The term "squalene" was derived from its initial extraction by Tsujimoto from the liver oil of sharks, specifically from Squalus milsukurii and other squaloid species [1] [3]. Within eukaryotic cells, squalene functions as a key intermediate in the biosynthetic pathway of sterols [4]. In animals, it serves as a precursor to cholesterol, whereas in plants, it leads to the formation of phytosterols [3] [5].Squalene can be synthesized endogenously at the cellular level or obtained exogenously through dietary sources [6]. In humans, squalene biosynthesis occurs predominantly in the skin and liver, after which it is transported in the bloodstream via low-density and very-low-density lipoproteins (LDL and VLDL) [7] [8]. Research has indicated that in adipose tissue, squalene is primarily stored within adipocytes, with approximately 80% found in neutral lipid droplets and 20% associated with microsomal membranes [9] [6]. Of these, only the membrane-associated squalene is considered to be metabolically active, while nearly 90% of newly synthesized squalene is stored and around 10% is utilized for cholesterol production [10]. Among plant-derived sources, the richest concentrations of squalene are found in the oils extracted from amaranth, olive, rice bran, wheat germ, grape seed, peanuts, and soybeans [11].Within the plant kingdom, Amaranthus species yield the highest levels of squalene. This pseudocereal produces seeds and leaves with relatively high oil content compared to other cereal crops, and most of its lipids are located in the coat-embryo section, which comprises roughly 25% of the seed’s weight. A study revealed that amaranth oil contains a squalene content ranging from 7–11% (wt/wt), significantly exceeding that of olive oil, which contains only about 1% (wt/wt) [12]. Squalene provides a wide array of health benefits, including its role in supporting antioxidant defenses, promoting cardiovascular health, enhancing joint function, and improving cognitive performance. It also contributes to skin health, reduces stress, supports gut health, aids in detoxification, and may help in preventing certain types of cancer. The following sections will explore these benefits in detail, shedding light on their significance for overall health and their potential advantages for pets
Benefits of squalene
Antioxidant and Cellular Protective Effects
Squalene is recognized as a potent natural antioxidant, primarily due to the presence of multiple double bonds that enhance its free radical-scavenging capabilities. When compared to EPA and DHA, squalene possesses a higher molecular weight, which allows it to bind more effectively to receptor sites and penetrate cells more deeply and efficiently [11]. Both in vitro and in vivo studies have highlighted its antioxidant potential, attributing this activity to its molecular structure, which facilitates neutralization of reactive oxygen species [13]. Its flexible conformation enables smooth passage through cellular and subcellular membranes, ensuring widespread intracellular distribution [14]. Furthermore, squalene serves as a scavenger and quencher of specific free radicals, effectively disrupting lipid peroxidation chains during both the initiation and propagation stages [13]. As an omega-2 fatty acid, squalene exhibits redox activity that aids in the release of oxygen from water molecules, thereby enhancing the body’s overall oxygen availability. This property allows squalene to function as a natural oxygen generator, delivering a continuous supply of oxygen even to peripheral cells and contributing to improved metabolic function. Evidence suggests that co-administration of squalene with standard medications may improve therapeutic outcomes. Notably, infants and young children naturally possess the highest concentrations of squalene, which may contribute to their elevated energy levels and vibrant appearance. However, squalene levels begin to decline significantly after the age of 30, often correlating with a decrease in vitality and endurance. Supplementation with squalene may help replenish these levels, thereby restoring energy and enhancing physical performance [15]. Oxidative stress, which compromises cellular membranes, results from exposure to reactive molecules, with molecular oxygen (O₂) being the initial reactive oxygen species (ROS) involved in initiating lipid peroxidation. Squalene helps mitigate this damage by donating an electron to neutralize free radicals, thereby protecting cellular integrity [16]. SQ was also effective in alleviating oxidative stress caused by toxin exposure in chickens [17].
Cardiovascular Protection and Cholesterol Regulation
Cardiovascular disease (CVD) is an increasingly common issue not only in humans but also among pets, particularly as they grow older or become overweight. In both species, CVD is linked to several contributing factors such as elevated cholesterol levels (hyperlipidemia), high blood pressure (hypertension), obesity, and diabetes. Cholesterol levels serve as crucial biomarkers in assessing cardiovascular health, and effective regulation of these levels is fundamental to disease prevention. Research indicates that replacing saturated fats with unsaturated fats in the diet can offer protective effects for the heart. Amaranth grain, known for its rich content of tocotrienols and squalene, has been associated with improvements in cholesterol profiles. Squalene, alongside lanosterol and other methylated sterols, plays a key role in the biosynthesis of cholesterol [18] [19] [20]. In a study conducted [21], chickens that were supplemented with amaranth oil exhibited reduced cholesterol levels, a result that has been confirmed by additional research [22]. Moreover, earlier studies have demonstrated that amaranth oil enhances the fluidity of cellular membranes, a factor that becomes particularly relevant in hypertensive conditions. When membrane fluidity is compromised, the transport of essential ions such as sodium (Na) and potassium (K) can be disrupted, potentially leading to increased blood pressure. These physiological improvements suggest that oils abundant in squalene, like amaranth oil, may offer cardiovascular advantages by supporting lipid regulation and cellular function [23]. Supporting this idea, a separate experiment involving hamsters on a high-cholesterol diet revealed that the inclusion of 5% amaranth oil resulted in a 15% drop in total cholesterol and a 22% reduction in non-high-density lipoprotein (non-HDL) cholesterol compared to controls [24] . Amaranth oil has also been reported to influence the fatty acid profile of erythrocyte membranes [25], a finding later validated in human subjects who received 600 mg of squalene supplementation [26]. In a more extensive clinical trial involving 125 individuals, daily intake of 3 to 18 ml of amaranth oil over a period of three weeks produced a dose-dependent decrease in both systolic and diastolic blood pressure [23]. Animal studies further support squalene’s cardioprotective potential; in one experiment, rats given squalene orally on a continual basis exhibited reduced lipid peroxidation during myocardial injury, indicating antioxidant and protective benefits for cardiac tissue [27]. Squalene (SQ) contributes to cardiovascular stability by preventing abnormal increases in plasma and myocardial glycoprotein levels, preserving the function of glutathione peroxidase (GSH-Px), and maintaining structural integrity in cardiac tissue. Additionally, it has demonstrated beneficial effects on serum lipoprotein profiles, significantly lowering low-density lipoprotein (LDL) concentrations, elevating high-density lipoprotein (HDL) levels, and curbing lipid peroxidation reactions that occur between LDL particles and reactive oxygen species (ROS) [28]. These outcomes, though derived primarily from human and rodent models, suggest promising cardiovascular benefits of squalene that may extend to pets, particularly those at risk of heart disease due to aging or metabolic conditions.
Skin Health and Protection
The skin, being the largest organ in pets, serves as a protective barrier over the entire body and is frequently subjected to various environmental stressors, including ultraviolet (UV) radiation. In vivo studies have shown that administering high doses of squalene can lead to visible improvements in aging human skin by reducing wrinkle formation, enhancing the production of type I procollagen, and minimizing UV-induced DNA damage [29]. Furthermore, other research has highlighted the potential of squalene in protecting against skin cancers [30]. A study investigated the therapeutic effects of shark liver oil, which is rich in squalene and alkylglycerol. Their findings revealed significant antibacterial and antifungal protection, along with improvements in skin conditions such as xerosis and atopic dermatitis-related lesions. These therapeutic outcomes are thought to result primarily from the squalene content of the oil, although more in-depth studies are needed to confirm squalene’s independent antimicrobial activity [31]. In addition to its protective functions, squalene (SQ) has been shown to enhance immune responses by stimulating immune cells such as macrophages and T lymphocytes, thereby playing a role in maintaining the skin's immunological balance. This makes it a promising agent in managing inflammatory skin disorders like seborrheic dermatitis and other types of rashes [32]. A study by found that squalene helps counteract oxidative damage by neutralizing superoxide anions produced within keratinocytes under stress conditions. This action complements the skin's endogenous antioxidant defense, particularly the enzyme superoxide dismutase [33]. Further investigations [13] revealed that squalene is capable of neutralizing singlet oxygen molecules on the surface of the skin, which are highly reactive and can accelerate aging. By facilitating essential cellular activities and reducing oxidative deterioration, squalene contributes to smoother, healthier skin. It is also rich in unsaturated fatty acids, which are key in maintaining skin hydration. Notably, squalene constitutes about 10% of total surface lipids on human skin. In addition to its role in lipid metabolism, it enhances oxygen exchange in skin tissues. These collective properties lead to a range of dermatological benefits, including renewal of skin layers, enhanced metabolic activity in skin cells, improved hydration and elasticity, visibly softer texture, and some degree of UV protection. Moreover, it has demonstrated antifungal properties, being effective against infections such as candidiasis, mycosis, and athlete’s foot [11]. Although these effects have been primarily studied in humans, they indicate promising dermatological and immune support that could extend to pets suffering from similar skin conditions or immune-related issues.
Stress Relief
Animals respond to stress through various mechanisms, including behavioral changes, neural adaptations, and hormonal responses. Among these, behavioral changes are the most immediate and play a crucial role in avoiding harmful situations. Common stress-inducing factors such as weaning, transport, shifts in ambient temperature, vaccination, and forced molting can lead to an increase in free radical production within tissues. If not neutralized, these reactive oxygen species (ROS) can result in oxidative damage, potentially leading to cellular apoptosis. Squalene (SQ) has been shown to mitigate such stress effects by interacting with cysteine residues, thereby influencing the Keap1-Nrf2-ARE signaling cascade. This pathway is pivotal in cellular defense, as it activates the transcription of genes responsible for antioxidant enzymes like glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and catalase (CAT), contributing to reduced ROS and malondialdehyde (MDA) levels [32]. These findings suggest that squalene may offer promising stress-reducing and performance-enhancing benefits in pets subjected to similar environmental and physiological stressors.
Gut Health Support
Studies have demonstrated that squalene (SQ) enhances the activity of antioxidant enzymes in the intestinal lining, reduces inflammation markers, limits the infiltration of immune cells, and aids in the repair of damaged intestinal barriers by modulating key signaling pathways like NF-κB and Nrf2-Keap1 [34]. It was observed that [35] SQ helps improve nutrient absorption by increasing sugar transporter activity in the intestine and reduces structural damage caused by lipopolysaccharide (LPS) exposure. In piglets, which are typically weaned between 21 and 35 days of age but require up to 45 days to fully develop a healthy intestine, dietary supplementation with SQ during this period resulted in a marked reduction in diarrhea, lower mucosal permeability in the jejunum, and improved overall intestinal structure compared to the control group [36]. These effects contribute to a more balanced and healthy gut microbiome, promoting better intestinal health. However, due to the complexity of intestinal health, further research is needed to fully elucidate the mechanisms by which SQ provides these beneficial effects [32]. These findings in livestock suggest that squalene could also support gastrointestinal health and immune function in pets, particularly in managing stress or post-weaning digestive issues.
Toxin Elimination and Organ Protection
Evidence from research indicates that squalene (SQ) holds considerable promise as a natural detoxifier, particularly in eliminating lipophilic xenobiotics from the body, thereby enhancing the excretion of harmful substances and mitigating their toxic effects [37]. Experimental findings have shown that the administration of SQ can substantially lower the toxicity of certain chemicals, leading to the normalization of blood biochemical markers in treated animals [32]. Specifically, in rats exposed to a toxic drug, a daily dose of SQ significantly improved multi-organ function by decreasing levels of enzymes such as ALT, AST, and LDH, while simultaneously increasing the expression of glutathione (GSH), an important antioxidant [38]. The underlying detoxification mechanism of SQ is largely attributed to its potent antioxidant capacity and its ability to protect cellular membranes, both of which contribute to minimizing oxidative stress and subsequent tissue injury [21]. Furthermore, SQ plays a role in promoting the elimination of harmful metabolic byproducts and maintaining the homeostasis of antioxidant enzymes, providing added defense for vital organs and tissues [38]. It was also observed that SQ supplementation could counteract alcohol-induced toxicity, preserving both the lipid architecture and the optic nerve fibers in chicken embryo retinas [39]. In another instance, SQ was found to assist in the detoxification of hexachlorobiphenyl (HCB) by improving its excretion while simultaneously decreasing its absorption through the intestinal wall [40]. Beyond its effects on chemical toxins, squalene has demonstrated the capacity to attenuate the damage caused by heavy metals, lipopolysaccharides (LPS), harmful bacteria, and certain alkaloids [32]. Animal studies have emphasized that SQ boosts the fecal elimination of xenobiotics such as theophylline and strychnine. When stored xenobiotics accumulate in adipose tissue, squalene is released and enhances their clearance by stimulating bile secretion [6]. Collectively, these findings highlight the potential of SQ as a detoxifying agent that may assist animals in preserving physiological stability and withstanding the challenges posed by environmental pollutants and dietary toxins [32].
Anti-Inflammatory Activity
It highlighted the potent anti-inflammatory potential of squalene (SQ), attributing its effects to the regulation of immune cells such as neutrophils, monocytes, and macrophages. In a study using a mouse model of lipopolysaccharide (LPS)-induced inflammation, oral administration of SQ for 18 hours led to a notable reduction in inflammatory responses. This was indicated by the decreased expression of toll-like receptor 4 (TLR-4), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and pro-inflammatory cytokines like tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interferon-gamma (IFN-γ) [41]. These anti-inflammatory effects are believed to be primarily linked to the suppression of the nuclear factor-kappa B (NF-κB) signaling cascade [32]. Supporting this, it was [34] found that dietary SQ significantly mitigated colitis induced by dextran sulfate sodium (DSS) in weaned mice [32].
Joint Relief and Vascular Stability
Squalene has also been found to aid in alleviating pain and plays a supportive role in managing arthritic conditions. Additionally, it may contribute to the prevention of vein enlargement, such as varicose veins, and help inhibit bone decalcification [11]. These effects could potentially be beneficial for aging pets suffering from joint discomfort or vascular issues.
Chemoprotective and Antitumor Effects
Squalene (SQ) has demonstrated significant potential in inhibiting the development of various types of cancer [11]. The notably low cancer rates observed among Mediterranean populations are believed to be partially linked to their high intake of olive oil, which contains substantial amounts of SQ [6]. One study revealed that SQ, derived from olive oil, was able to reduce early markers of colon cancer in rats by more than 46%, all without altering cholesterol levels, suggesting its role in colorectal cancer prevention [43]. Additionally, research has shown SQ to offer protection against breast cancer while simultaneously helping lower serum cholesterol concentrations, underscoring its dual potential in cancer prevention and lipid regulation, particularly relevant to companion animal health [6]. Over the years, SQ has gained attention for its protective effects against a range of carcinogens, making its application as an adjunct therapy in certain cancers one of its most prominent nutraceutical roles. Though SQ alone has limited tumor-inhibitory capacity, its combined use with antineoplastic agents has shown promising results in halting or preventing tumor progression across multiple experimental models. Further studies have confirmed that administering SQ before or during anticancer treatments can enhance the suppression of chemically induced skin tumors and contribute to the shrinkage of existing tumors in animals. This indicates both chemoprotective and antitumor properties of SQ [3]. Dietary supplementation with 1% SQ has also proven effective in reducing aberrant crypt foci—precursors to colon cancer—in rodent models [42]. In support of these findings, additional animal research has demonstrated SQ’s preventive effects against tumor formation in organs such as the skin, colon, and lungs when administered before or during exposure to carcinogenic agents [43].
Support for Vision and Cognitive Function
Squalene (SQ) plays a vital role in maintaining eye health, particularly in supporting the function of light-sensitive retinal cells. It also contributes to cognitive health by promoting brain development, which in turn enhances memory and concentration—an effect that aligns with the fact that more than 80% of the brain consists of fatty acids [11]. In animal studies, SQ has shown significant involvement in the structure and function of the retina, especially in rod photoreceptor cells. It assists in the formation of rod outer segment (ROS) disk membranes, where much of the newly synthesized retinal squalene is directed, both in laboratory and living models. Its turnover rate mirrors that of the disk membranes themselves, indicating a tightly linked biological role [44]. Additional research has confirmed that SQ becomes integrated into ROS membranes and photoreceptor cells, highlighting its essential role in visual health [45]. These findings point to its potential as a protective agent for pets’ vision, particularly in mitigating age-associated retinal decline [6]. Squalene has also been associated with enhanced cognitive performance, including improvements in memory and focus. It may offer supportive benefits for individuals experiencing conditions like ADHD, hyperactivity, and dyslexia. [11]. These cognitive-supportive properties may also have implications for improving neurological health in pets, particularly in developmental stages or age-related cognitive decline.
Conclusion
In conclusion, squalene (Omega-2) stands out as a versatile and beneficial compound, offering a wide range of advantages for pet health, from supporting cardiovascular function and joint relief to enhancing cognitive performance and skin health. Its antioxidant, anti-inflammatory, and detoxifying properties make it a valuable addition to a pet's diet, especially as they age or face specific health challenges. At Ventura, we offer two specialized supplements—Omega+ and Omega+ Cat—designed for dogs and cats, respectively. These formulations contain Omega-2 fatty acids alongside other essential omega fatty acids, including Omega-3, 6, 7, and 9, ensuring comprehensive support for the pet's health.
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