Benefits & Risks of Peptide Therapeutics for Physical & Mental Health

The source notes at the start that this transcript version is not final and will be updated. Andrew Huberman, a professor of neurobiology and ophthalmology at Stanford School of Medicine, opens by placing peptides in the news. Much of the current attention, he says, comes from excitement about GLP-1 (glucagon-like peptide) analogs or agonists, drugs used to treat type 2 diabetes and obesity. He then excludes them from this episode. He will focus instead on other peptides that are getting attention, specifically those for tissue healing and repair and those said to affect longevity and vitality.

He points out how broad the subject could be. Familiar molecules such as insulin, which regulates blood glucose, and oxytocin are peptides. Oxytocin is sometimes called the love hormone, a label he says is not the best description. He calls it a neuropeptide and hormone involved in everything from pair bonding to socialization, among other functions. These are two of the tens of thousands, possibly hundreds of thousands, of peptides in the brain and body. The episode narrows to peptides increasingly used for therapeutic purposes.

Huberman also acknowledges that the field is confusing, partly because of naming. Peptides are often known only by acronyms and numbers such as BPC-157 or MK-677. He promises a simple organizational framework that explains what these peptides are, why particular ones may suit particular purposes, and their potential risks and, in some cases, "outright dangers." He also says he will explain how they work alone and in combination toward physical and, in some cases, mental health goals.

Huberman sorts applied therapeutic peptides into three categories by how people get them. The first is FDA-approved peptides prescribed by physicians for specific purposes. The second is a gray market: peptides sold online whose safety and efficacy are "a bit questionable, in some cases, very questionable." The third is the black market. He states plainly that he does not suggest buying black-market peptides, because many are contaminated with substances that can cause problems in the short term and especially in the long term.

He returns to this framework later in more detail. In the prescription route, a board-certified medical doctor prescribes the peptide. Some peptides approved for one use can also be prescribed off-label. They are clinically tested, but often only within one area of medicine. His example is Sirmirelin (as transcribed), a peptide that promotes growth hormone release. It is FDA approved for short stature and is now often prescribed for other purposes when a physician and patient agree that augmenting the growth hormone pathway would be useful.

His main safety argument concerns purification. Prescription peptides come either from pharma companies or from compounding pharmacies, and in both cases they are cleaned of lipopolysaccharide (LPS), which can accumulate during manufacturing. LPS triggers an immune response. Huberman says a tiny amount might not cause a large response, but the accumulation of many exposures can become problematic. He notes that most peptides are injected subcutaneously or into muscle, while some can be taken orally or as a topical cream. Gray- and black-market products often contain the same peptide as the prescription version but frequently have not had the LPS removed. Black-market products in particular are often not what their labels claim.

If you are going to explore peptide therapeutics, I highly, highly recommend, indeed, I implore you to do so with a board certified physician and to acquire peptides through a reliable source where the LPS has been removed

He adds that a reliable source typically means a pharma company or a compounding pharmacy.

Before the substantive discussion, Huberman says the podcast is separate from his teaching and research roles at Stanford, and he reads sponsor messages. He promotes Mateina yerba mate and discloses that he is a partial owner of the company and personally helped develop its canned cold brew zero sugar product. He also promotes Levels, a program that pairs a continuous glucose monitor with feedback on how food, activity and sleep affect blood glucose. The third sponsor is Joovv (rendered variously as Juve, Juva and JOOV in the transcript), a maker of red and near-infrared light therapy devices. The health claims in these reads are advertising statements, not part of the peptide evidence discussed later.

Huberman defines a peptide as a small protein made of chains of amino acids. He separates this from dietary protein. The body contains many proteins that have nothing to do with the proteins we eat, although many of the amino acids that make up peptides and other proteins do come from food.

Strictly defined, a peptide is a chain of two to 50 amino acids. Chains of roughly 75 or 100 amino acids are often also called peptides. Combining peptides produces polypeptides, and many of the body's proteins are polypeptides. His mental image is beads on a string: two to 100 beads, each a different amino acid. The order of the amino acids along the string determines what the peptide is and what it does.

The central conceptual point of this section is that peptides multitask. Some are hormones, some are neuromodulators that adjust neuron activity, and Huberman says most have pleiotropic effects, meaning they affect many aspects of cells. He contrasts this with the podcast's usual discussions of dopamine or hormones such as testosterone and estrogen. A single therapeutic peptide may do many different things depending on cell type, the time of day or night it is present, and its downstream effects.

He explains downstream effects with a receptor analogy. A peptide binds a receptor, described as a parking spot on the cell surface, and starts a bucket brigade or conveyor belt of cellular processes. One pathway might drive cell growth, another cell migration, and another signaling to neighboring cells to stimulate blood vessel growth. He says a peptide typically does anywhere from four to perhaps a thousand different things, within cells, across cell types and across organ systems. Oxytocin is his example again: it is involved in milk letdown during lactation, in pair bonding in males and females, and in bonding between parent and child, and "maybe even parent and pet."

The practical consequence he draws is that targeted, specific effects are rare, if they occur at all. This matters for the effects a person can expect, for side effects, and for decisions about dosage, duration and whether to cycle a peptide. Someone may want to repair an injury, or increase growth hormone to get leaner, recover faster from exercise or feel more vitality. Peptides can act on those pathways, but they will always activate others as well.

There's simply no way to remove the pleiotropic feature of peptide therapeutics.