Negative emotions such as anger, sadness, or fear stress the body, yet shame occupies a category of its own.

Shame devastates mental and physical health through self-blame, stress, and chronic inflammation—a phenomenon Dr. Will Cole, a leading functional medicine expert, calls “shameflammation.”

Cole sat down on EpochTV’s new talk show, “The Upgrade,“ where he explained why you ”can’t heal a body you hate.”

Shame Is Unlike Any Other Negative Emotion

Western medicine tends to separate mental health from physical health. Cole argues they are interconnected and bidirectional. Mental and emotional burdens are stored in our bodies just as much as environmental toxins.

Feelings of regulated shame can foster accountability and moral reasoning. However, unregulated or toxic forms of shame can lead to social withdrawal, negative self-identity, and mental illness.

Unlike feelings of guilt, which focus on behavior—“I did something bad”—shame strikes at identity—“I am bad.” Shame is the feeling of being exposed as fundamentally inadequate—not just failing—but being revealed as a failure.

A December editorial in The British Journal of Psychiatry describes shame as “a pervasive, multidimensional emotion influencing brain, body and social life.”

Why would shame trigger such powerful reactions?

Our bodies treat threats to how others perceive us as distinct from other forms of stress.

In a 2004 meta-analysis, UCLA researchers analyzed 208 stress studies to identify which conditions most activate the cortisol system. The answer wasn’t situations with extreme difficulty or effort. Cortisol spiked the most when people faced the threat of public negative judgment in situations they could not control and in which failure was unavoidable.

In one common protocol, participants delivered a speech and performed mental arithmetic aloud before stone-faced evaluators who offered no encouragement and demanded they restart whenever they made a mistake. Sounds stressful? Well, it is. Under these conditions, cortisol responses were nearly three times as large as in equally difficult tasks without social evaluation.

A follow-up study confirmed the mechanism. When participants faced evaluators, they reported significantly greater shame and lower social self-esteem. Shame correlated directly with cortisol reactivity; the threat of being seen as inadequate—not the challenge itself—drove the hormonal response.

Shame doesn’t just activate the stress system. It also causes substantial inflammation.

In a separate study, participants were asked to write about experiences that triggered self-blame. The researchers measured inflammatory markers before and after. Those in the self-blame condition showed significant elevations in TNF-α receptor activity, an inflammatory protein linked to autoimmune conditions and chronic disease. Notably, only shame predicted the inflammatory spikes. Guilt—although often a close cousin to shame—showed no correlation. Neither did general negative emotion.

How Shame Gets Under the Skin

The roots of shame often trace back to childhood. Cole explained that in his practice, every patient fills out an ACE questionnaire—Adverse Childhood Experiences—which evaluates exposure to abuse, neglect, and household dysfunction.

The mechanism is explained through chronic stress activation. ACE, such as abuse, neglect, and household dysfunction, often create shame because children survive by blaming themselves for what they cannot control, like a caregiver’s unpredictability or lack of care, leading to the belief that “something is wrong with me.”

When shame‑laden memories and unresolved trauma keep triggering the body’s stress response, cortisol eventually becomes less effective at shutting down inflammation, a phenomenon known as glucocorticoid resistance. As a result, the immune system is no longer properly regulated and instead stays on high alert, driving chronic inflammation even when there is no infection to fight.

“The higher your ACE score,” Cole said, “the more likely you are to have autoimmune problems, metabolic problems, fertility issues, and of course, mental health issues.”

Large-scale studies confirm the detrimental effect of ACEs. A study of more than 17,000 adults found that those with six or more ACEs died nearly 20 years earlier than those with none. Another study found that ACEs lead to increased depression, anxiety, and suicidality.

Cole used a metaphor: “Your genetics determine the size of your [health] bucket. Your environment determines what fills it. For many people today, the bucket is overflowing, there’s no wiggle room left.”

Once shame enters the picture, it creates a vicious negative cycle. Shame leads to poor choices, such as comfort eating and toxic relationships, which in turn generate more shame, which amplifies stress, feeding more inflammation.

The Wellness Trap

The shame barrier creates a paradox Cole sees constantly. People do everything “right”—they eat the most nutrient-dense foods under the sun, savor their kombucha, take all the right peptides and stem cells—but are still chronically ill.

“I see people stuck in that frenetic fight or flight,” he said.

The problem is that many people approach wellness as a form of self-punishment—an anxious, persistent doing that keeps the nervous system in a state of high alert. That’s not healing; the pursuit for wellness itself becomes another stressor.

Therefore, Cole observes his patient’s labwork and looks for “check engine lights”—high inflammation, hormonal imbalance, gut dysbiosis. He then links those biomarkers to the patient’s history. “Is it an environmental toxin? A virus?” he asks. “It could be. But we can’t ignore someone’s relationships, their work environment, and their past.”

The missing piece might not be another supplement or biohack. It might be the shame humming quietly in the background.

“What are we feeding our head and our heart on a daily basis?” he asks. “These things matter. They’re information for our biochemistry, just like anything else.”

Balancing Shame With Responsibility

Breaking out of the shameflammation cycle requires, as Cole described it, “balancing grace with truth.” While you shouldn’t stay stuck in patterns that harm you, beating yourself up doesn’t work either.

There is a fine line between self-blame and responsibility.

Self-blame is shame pointed inwards, and it paralyzes. Self-blame says: “I ate the cake because I have no willpower. I’m disgusting.” It conflates behavior with identity, triggering the same shame response the research describes: cortisol, inflammation, and the urge to withdraw. Because you’ve framed the problem as you, not something you did, there’s nothing actionable to fix—you just feel bad about who you are.

Responsibility rings a different tune: “I ate the cake. I was stressed and exhausted. What can I do differently next time?” The behavior is acknowledged, but it’s separate from your worth as a person. That separation is what allows you to actually change, rather than spiral into the shame that keeps you stuck.

“It’s really a conversation around discernment,” Cole said. “What are the things that love your body back, and what loves your soul back—and the things that don’t?”

Practically, you can start by developing self-compassion.

Remember the stress protocol where participants gave speeches before stone-faced evaluators, only to watch their cortisol spike? A 2014 study ran people through the exact same stress test but measured something else: whether self-compassion made a difference.

It certainly did. Participants who scored higher in self-compassion showed markedly lower inflammatory responses than their more self-critical peers. The effect held even after controlling for self-esteem, depressive symptoms, and how distressed participants felt during the task. How you view and relate to yourself under pressure significantly shapes how your body responds.

So what does self-compassion actually look like? Psychologist Kristin Neff, who developed the scale used in the study, identifies three core components:

1. Self-Kindness Over Self-Judgment

Instead of attacking yourself for a mistake, you might comfort yourself: “I’m going to be understanding and patient toward myself, even when I don’t like what I did.”

2. Common Humanity Over Isolation

Instead of feeling like you’re the only one who fails, you might say: “Struggling is part of being human. I’m not alone in this.”

3. Mindfulness Over Over-Identification.

Instead of spiraling into everything that’s wrong, you might ask: “This is painful, but I can take a balanced view of the situation?”

These are not just empty affirmations but rather a reframe that, according to research, changes how your body processes stress. The goal is not to let you off the hook, but rather to shift away from the self-criticism that breeds shame and illness.

You can’t heal a body you hate, but you can learn to stop hating it.