Nixulin™ and Its Primary Lead Compound—Diethyl Azelate

Nixulin™ is the next-generation natural blood sugar support supplement, powered by revolutionary Insulin Sensitivity Technology. Its primary lead compound is Diethyl Azelate (DEA), an ester of azelaic acid, a medium-chain fatty acid. Azelaic acid, along with its esters—azelates—are naturally occurring compounds found in plants, animals, and humans.

Only recently, scientists have discovered a novel use for DEA to target impaired insulin insensitivity — the hallmark of metabolic issues that can increase the risk of uncontrolled blood sugar levels and health problems linked to dangerously high blood sugar levels [1]. Furthermore, research shows that impaired insulin sensitivity is associated with more serious complications such as organ damage or abnormal cell growth [2-7].

Impaired insulin sensitivity develops when the tissues of the body that are normally responsive to insulin (liver, muscles, etc.) become less sensitive to insulin.  — a hormone the pancreas releases to help maintain healthy levels of blood sugar (glucose) [8]. This subsequently causes sugar to quickly accumulate in the blood — an issue that can be detrimental to health.

Under healthy circumstances, insulin has several functions that include:

• Directing glucose in the blood to travel into fat, liver, and muscle cells where it can be used for energy or stored as an energy reserve.
• Ensuring that the pancreas produces less insulin in response to decreasing glucose levels in the bloodstream as it begins to enter cells.

For a number of reasons, fat, muscle, and liver cells may respond inappropriately to insulin or not at all. If this happens, the cells cannot take up glucose from the bloodstream or store it. Due to the cells’ impaired sensitivity to insulin, the pancreas continues to produce more of this hormone in an attempt to combat increased blood glucose (sugar) levels.

If the pancreas can produce sufficient amounts of insulin that overcome cells’ poor responses to insulin, blood sugar levels will remain in a healthy range. However, if the cells become increasingly resistant to insulin, blood sugar may rise to dangerous levels — a problem that can lead to metabolic difficulties.

Common Causative Factors

The combination of a Western diet and chronic mental stress with a sedentary lifestyle predisposes some individuals to impaired insulin sensitivity [8, 9]. In addition, research shows that a diet consisting of 50% or more carbohydrates with high fructose, sucrose, or glucose (sugar) levels can lead to impaired insulin sensitivity in healthy non-obese men in as little as 2-7 days [10]. The negative impact of high sugar levels is similar to that of alcohol [11].

More specifically, the excessive consumption of alcohol on a short- or long-term basis increases the risk of developing impaired insulin sensitivity [12-15]. Although there are a number of different causative factors, current treatments vary in terms of effectiveness and often depend on strict dietary and lifestyle changes as well as pharmaceuticals (e.g., prescription medication).

Traditional Interventions For Impaired Insulin Sensitivity

Traditional treatments do not effectively reduce the incidence of impaired insulin sensitivity, delay its progression, or offer a cure. In addition, many pharmaceutical interventions have major side effects that range from mild to life-threatening. Some adverse events associated with current treatments also warrant ‘Black Box’ warnings mandated by the Federal Drug Administration (FDA) in the United States.

In addition, certain types of medication for individuals with this health issue cause weight gain and low blood sugar, and often lose effectiveness over time [16]. Therefore, pharmaceutical approaches do not address the root cause or progressive nature of impaired insulin sensitivity.

In response to this ongoing issue, there is a need for novel, pre-pharmaceutical agents that demonstrate prolonged effectiveness, superior blood sugar-influencing potential, and better safety profiles. Furthermore, early intervention with supplements may help reinforce healthy blood sugar levels, glucose balance, and insulin sensitivity. The azelaic acid derivative, DEA, is showing promise as a useful supplement that promotes optimal blood sugar and insulin balance.

Diethyl Azelate (DEA): A Novel Approach

DEA and other azelates are naturally produced by the body where they support healthy immune responses [17, 18]. More specifically, azelates such as DEA, modulate the transfer of cellular signals that are responsible for key processes, including fat burning pathways, blood sugar balance, and insulin responses [19].

Azelates can also be found in grains and grain-derived products (e.g., liquors), along with fermented foods that undergo bacterial processing of fatty acids [20, 21]. For example, olives are converted to an edible form due to fermentation by bacteria called Lactobacilli [22, 23]. During this process, the Lactobacilli ferment a compound in olives called oleic acid into azelaic acid and azelates. Olive rinds also contain substantial amounts of azelaic acid, making them a natural source of beneficial nutriment [22].

Similarly, fermented products such as soybeans and douchi — a fermented black bean product — are well-known foods commercially produced for centuries that reinforce healthy blood sugar levels by targeting impaired insulin sensitivity and uncontrolled blood sugar levels [25, 26]. Notably, non-fermented soybean products have no influence on insulin response, suggesting that fermentation by-products (e.g., azelates) are responsible for the health benefits [25]. These properties make azelate derivatives, including DEA, particularly promising for individuals who struggle with dangerously high blood sugar levels [25].

Azelates are not currently used for pharmaceutical purposes but are used as food additives and lubricants. DEA is an approved flavoring additive in the European Union (EU) and a similar agent called diethylhexyl azelate is approved for food contact packaging in the U.S. [27, 28]. Another closely related ester, diethyl sebacate, that differs slightly from DEA, is on the list of Generally Regarded As Safe (GRAS) compounds and the Inactive Ingredients List designated by the FDA [29, 30]. This suggests that DEA has a good safety profile that makes it favorable for use as a supplement.

DEA Is Beneficial For People With Impaired Insulin Sensitivity

Cells in the body constantly detect and respond to environmental stimulation and communicate through special proteins on their surfaces called receptors. These proteins act as sensors that receive important information and activate specific processes that ensure normal, healthy function. Many receptor proteins are located on the protective outer layer of cells known as the plasma membrane, where they transfer signals between the outside to the inside of cells. Some receptor proteins detect foreign invaders and activate immune signaling pathways that help destroy them, while other receptor proteins can even sense abnormal cell growth.

In relation to insulin sensitivity, there are receptor proteins on the surface of specialized cells called beta cells that respond to blood glucose levels and release insulin. For people who have impaired insulin sensitivity, it is believed that the glucose detection system inappropriately responds to increases in blood sugar — causing glucose (sugar) to accumulate in the blood instead of entering cells to be used for energy or stored.

According to research, when cells are exposed to DEA, the compound temporarily alters the structure of cells’ outer layer — a process that allows DEA to influence the activity of receptor proteins [19]. In this case, DEA helps encourage proper responses to insulin and optimal blood sugar balance [19].

These benefits were demonstrated through a clinical study involving a group of individuals who were experiencing or at risk of impaired insulin sensitivity. More specifically, the study examined the impact of DEA on glucose (blood sugar) and insulin levels [19, 31]. The procedure involved measuring fasting insulin and fasting glucose levels, which are markers that indicate the body’s ability to regulate blood sugar levels on its own [32].

The American Diabetes Association (ADA) suggests that an A1c of 5.7%-6.4% indicates a mild to moderate problem with the body’s blood sugar regulation system that can lead to health problems if it is not addressed [33]. The ADA also explains that people who have an A1c just below 5.7% are at risk of developing impaired insulin sensitivity, which may occur before more serious problems with uncontrolled blood sugar begin to develop [33].

The findings from the clinical study showed that overweight and obese adults with impaired responses to insulin who took a supplement containing DEA for three weeks experienced healthier fasting insulin levels as well as fasting glucose levels [19]. Fasting glucose level is an indication of blood sugar regulation when an individual has not eaten overnight. Moderate to high fasting blood sugar levels (on an empty stomach) indicate that the body’s cells do not respond properly to insulin and that the person has an increased risk for uncontrolled blood sugar levels.

For the participants who took DEA for three weeks, fasting glucose levels lowered by 5.9% and fasting insulin levels lowered by 38%, demonstrating that DEA has a strong influence on impaired insulin sensitivity [19].

Based on these findings, the use of DEA as a dietary supplement shows great promise in supporting appropriate responses to insulin and healthy blood glucose (sugar) levels. By reinforcing vital metabolic processes, DEA also reinforces cardiovascular health and demonstrates a favorable safety profile that encourages long-term usage.

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