The Exercise Steroid Discovery That Psychiatry Is Missing
Dr. Sundeep Dugar, the pharmaceutical chemist who invented Zetia, made a confession at the IMMH2025 mental health conference in San Diego: after 38 years in pharma, Dugar cited published research indicating that a significant percentage of medications, including some SSRIs, show mitochondrial toxicity in studies, yet FDA doesn’t require mitochondrial toxicity testing in standard drug approval. Psychiatry prescribes drugs that harm what brains need most.
This revelation set the stage for what distinguishes Dugar’s presentation from typical mitochondrial health talks: he identified the actual biochemical mechanism exercise uses to create new mitochondria, then replicated it.
The Mechanism Nobody Understood
Scientists knew exercise creates new mitochondria but never understood how. Dugar discovered a novel steroid hormone that mitochondria produce during exercise, active at femtomolar levels (10 to the minus 15). Dr. Robert Lustig, the pediatric endocrinologist known for metabolic research, emphasized this potency matters: “Nothing works at femtomolar levels, but this does.”
What makes this steroid unique? Most steroidogenesis requires complex adrenal pathways. This steroid needs only two steps, both occurring in mitochondria. Any cell with mitochondria can produce it, creating systemic rebalancing without adrenal involvement.
From Chocolate to Pharma-grade Breakthrough
Dugar’s genius came from seeing molecular structures differently. He noticed epicatechin, found in dark chocolate and green tea, contains an unusual side chain appearing only in steroids. He synthesized a steroid based on this observation. While epicatechin increased mitochondrial biogenesis 300-fold, his synthetic steroid increased it 30,000-fold in laboratory studies
When someone asked why not just eat chocolate, Dugar explained the problem: chocolate and tea contain catechin, epicatechin’s stereoisomer, which blocks epicatechin from binding effectively. Green tea extracts show only mild benefits because competitive inhibitors come along during extraction. Purifying the active form was the pharma-grade purification achievement.
The mechanism involves ATP synthase, the molecular motor that rotates clockwise (making ATP) or counterclockwise (generating heat). This explains fever symptoms: mitochondria liberate energy as heat rather than capturing it, so you feel depleted. Epicatechin locks ATP synthase into clockwise rotation through a protein called IF-1, boosting chemical energy production.
The Mental Health Connection
Dugar connected this directly to psychiatric conditions beyond general “mitochondria matter” claims. In depression, mitochondrial failure prevents neuroplasticity and worsens neuroinflammation. Mitochondria control NFkappaB, the primary inflammatory regulator. In schizophrenia, altered glucose metabolism and reactive oxygen species damage neurons and synaptic junctions. For autism, postmortem analyses reveal substantial mitochondrial damage affecting calcium homeostasis.
Most provocatively, researchers suggest suicide attempts may represent physiological impulses to stop unbearable cellular stress responses, with energy production deficits in specific brain regions creating a mitochondrial signature.
The Measurement Challenge
When practitioners asked about testing, both speakers acknowledged frustrating limitations. Muscle biopsies are invasive and reveal only muscle status. Seahorse analysis works in dishes but fails in living patients.
Lustig offered a practical solution: fasting insulin levels. When mitochondria dysfunction, cells convert excess energy to fat, triggering insulin production. Fasting insulin serves as a proxy for liver mitochondrial dysfunction. He has argued for 15 years that everyone needs this measured with standard blood panels.
Their UCSF study demonstrated this: removing fructose from children’s diets dropped lactate levels 50%, a measurable marker of improved mitochondrial function.
The Systemic Priority System
What truly distinguished this research was observing how bodies prioritize. Muscular dystrophy patients show skeletal deficits first, then cardiac failure. But when treated with epicatechin, hearts responded first, then skeletal muscle. The body knows cardiac function matters more for survival than leg muscles.
This salutogenesis reflects internal healing intelligence. Clinical studies show not just reduced inflammatory cytokines but active rebalancing, with IL-6 decreasing while IL-10 increases, demonstrating how mitochondria sense and address system-wide dysfunction.
Why Psychiatry Fails
As Lustig argued, seventy-five years of genetic research has not solved a single chronic disease, suggesting our NIH may have banked on the wrong horse. The breakthroughs claimed as “polygenic” actually trace to mitochondrial dysfunction. Genetics cannot transcribe without mitochondria.
Peak mitochondrial capacity occurs at age 21, declining 10% per decade. Exercise remains the only proven natural replenishment method, but ultra-processed foods, particularly fructose, actively inhibit mitochondrial activity. You can supplement with ketoacids and CoQ10, but if fundamental mitochondrial levels are depleted, effects remain limited.
This presentation moved beyond “mitochondria are important” to “here is the biochemical mechanism, here is how we measured it, and here is how we replicate it for people who cannot exercise adequately.” Combined with the pharmaceutical insider’s perspective on what medical training ignores and what drug development deliberately avoids testing, this represents a fundamental challenge to psychiatry’s reductionist approach with a measurable pathway forward for addressing the energy crisis underlying mental health conditions.