Unregulated Peptide Side Effects Easy to Miss: Catherine Varney, DO

Unregulated peptides can cause harm that goes unrecognized until a patient is seriously hurt, because the symptoms are nonspecific and patients may not disclose their use or connect it to how they feel, according to Catherine Varney, DO, obesity medicine director at UVA Health.

Diffuse Symptoms Can Mask Serious Harm

Patients using gray-market peptides often present with fluid retention, muscle aches, and injection site reactions, Varney explained. Some compounds, notably MK-677, have been linked to serious cardiovascular events, including congestive heart failure. She believes both patients and clinicians need more education, since clinicians rarely encounter these products in daily practice.

"The interesting thing about peptides is that patients know more about these than I see clinicians knowing," she said.

Rising Demand Outpaces Oversight

Over the past 5 to 6 years, use has spread from athletes and bodybuilders to the broader population, driven largely by social media. The visible benefits of FDA-approved peptides have also fueled interest, and patients who cannot afford them often turn to lower-cost gray-market alternatives.

FDA-approved peptides undergo rigorous testing, and 503A and 503B compounding is legal for peptides on the FDA's permitted list, but gray-market research chemicals fall entirely outside oversight. Varney noted that distrust of regulators, which began during the COVID-19 pandemic and has been worsened by misinformation, leads some patients to see the FDA as an obstacle rather than a safeguard, when in reality demand has outrun enforcement capacity.

When patients ask about these products, Varney takes a thorough history, checks for adverse effects, and talks honestly about the lack of human safety data. She does not prescribe them but continues to support patients through evidence-based care. A weak adverse event reporting system makes the gaps harder to close.

"I think that in effect, clinicians are kind of managing downstream consequences of gap regulations that haven't closed," she said.