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This Is The Often Overlooked Cause Of Insulin Resistance (Nope, Not Sugar!)
When most people think about insulin resistance, sugar is usually the first thing that comes to mind. And while excessive sugar consumption can certainly play a role, emerging research—and experts like Cate Shanahan, M.D.—suggests that oxidative stress may be a major, and often overlooked, driver of insulin resistance.
On the mindbodygreen podcast, Shanahan shared her perspective on how oxidative stress, fueled in part by industrial seed oils, can disrupt metabolism and contribute to insulin resistance—a condition that affects one in three adults in the United States and significantly increases the risk of Type 2 diabetes and other chronic diseases.
Here's the science behind oxidative stress, how it impacts insulin signaling, and why cutting back on certain oils may be a smart step for your metabolic health.
What is oxidative stress & why does it matter?
Oxidative stress occurs when there's an imbalance between reactive oxygen species (ROS), which are unstable molecules produced during normal metabolism, and the body's ability to neutralize them with antioxidants. While small amounts of ROS are essential for cellular signaling, excessive levels can cause widespread damage to cells, tissues, and critical metabolic pathways.
Research has shown that oxidative stress plays a direct role in insulin resistance by interfering with the insulin receptor signaling pathway—the very process that allows your body to move glucose from the bloodstream into your cells.
According to Shanahan, one of the primary culprits driving oxidative stress is the modern diet, particularly the widespread use of refined vegetable oils like soybean, corn, and canola oil.
How oxidative stress disrupts insulin signaling
To understand how oxidative stress causes insulin resistance, it's helpful to break down the insulin receptor signaling pathway. This is the process that regulates glucose uptake in your body.
When you eat carbohydrates, your pancreas releases insulin, which binds to insulin receptors on the surface of muscle and fat cells. This triggers a cascade of signals that ultimately allows GLUT4, a glucose transporter protein, to move glucose from your blood into your cells, providing energy and maintaining healthy blood sugar levels.
But when oxidative stress is elevated, this system breaks down.
Research shows that reactive oxygen species (ROS) can disrupt this process in several ways:
- Inhibiting GLUT4 transporters: ROS reduce the expression of GLUT4, meaning glucose cannot effectively enter your cells, leading to elevated blood sugar levels.
- Mitochondrial dysfunction: Increased ROS production in mitochondria (your cells' energy factories) further amplifies oxidative stress, creating a vicious cycle that promotes insulin resistance.
- Inflammation activation: ROS triggers inflammatory pathways like NF-κB and JNK, which interfere with insulin receptor function and reduce insulin sensitivity.
This cascade ultimately leads to hyperinsulinemia—elevated insulin levels—as the pancreas works overtime to compensate for the body's reduced insulin sensitivity. Over time, this chronic overstimulation can exhaust the pancreas, increasing the risk of Type 2 diabetes.
The role of seed oils in oxidative stress
So, where do seed oils fit into this picture? According to Shanahan, the answer lies in their high polyunsaturated fat (PUFA) content, specifically omega-6 fatty acids like linoleic acid.
While omega-6 fats are essential in small amounts, excessive consumption, especially in their oxidized form, can significantly increase oxidative stress. Here's why:
- Highly unstable under heat: When exposed to high temperatures (such as during frying), the PUFAs in seed oils break down and generate harmful by-products called oxidized linoleic acid metabolites. These compounds promote inflammation and damage cellular structures.
- Stored in body fat: Unlike sugar, which is burned quickly for energy, PUFAs from seed oils are incorporated into your cell membranes and fat stores, where they can continue to promote oxidative damage over time.
- Mitochondrial stress: Research suggests that an increased PUFA load impairs mitochondrial function, leading to more ROS production, a key driver of insulin resistance.
In fact, research suggests that oxidized omega-6 fats may be a significant driver of coronary heart disease and other metabolic disorders.
Why obesity increases oxidative stress & insulin resistance
Excess body fat, particularly visceral fat, is a major contributor to oxidative stress. As fat cells grow, they release free fatty acids (FFAs) into the bloodstream. These FFAs not only promote inflammation but also increase ROS production by overloading the mitochondria with excess fuel.
Obesity also disrupts the balance of adipokines—hormones secreted by fat tissue. While beneficial adipokines like adiponectin protect against oxidative stress, their levels decrease as body fat increases. Meanwhile, pro-inflammatory adipokines stimulate immune responses that worsen inflammation and insulin resistance.
According to studies, mitochondrial dysfunction, triggered by both excess nutrients and ROS, has been directly linked to insulin resistance in skeletal muscle (the largest glucose-utilizing tissue in the body!).
How to reduce oxidative stress & improve insulin sensitivity
The good news? There are practical steps you can take to reduce oxidative stress and support healthy insulin function. Here's what Shanahan recommends:
1. Limit refined seed oils
Avoid oils high in omega-6 PUFAs, such as soybean, corn, canola, sunflower, and safflower oils. Instead, opt for stable, nutrient-rich fats like:
- Butter
- Extra-virgin olive oil
- Coconut oil
- Peanut oil
- Sesame oil
- Unrefined avocado oil
2. Eat whole, minimally processed foods
Whole foods naturally contain antioxidants that help neutralize ROS. Prioritize fresh vegetables, herbs, and antioxidant-rich foods like berries.
3. Support mitochondrial health
Incorporate lifestyle habits that promote mitochondrial function, including:
- Regular physical activity
- Quality sleep
- Stress management practices (like meditation)
4. Maintain a healthy weight
Reducing visceral fat through a balanced diet and regular exercise can lower free fatty acid levels and reduce inflammation.
The takeaway
While sugar often takes the blame for insulin resistance, emerging evidence suggests that oxidative stress, particularly from refined seed oils and excess body fat, may be a more significant driver of metabolic dysfunction.
By reducing your intake of unstable PUFAs, choosing nutrient-dense fats, and supporting mitochondrial health, you can take meaningful steps toward improving insulin sensitivity and long-term metabolic health.