Inside your blood are messengers carrying instructions between organs and cells. One of them is IGF-1.
IGF-1 stands for Insulin-like Growth Factor 1. It is a growth signal. It tells muscles to rebuild. It tells neurons to survive. It is one way the body says, “you keep going.”
But IGF-1 is not free to act on its own. It has regulators. They decide when and where the signal can land.
The Blocker
Those regulators are IGF binding proteins (IGFBPs). They bind IGF-1 and modulate how much of it gets through. Think of them as gatekeepers.
One of them, IGFBP7, may overdo it. It holds IGF-1 back. It binds it too tightly. The growth message cannot reach the cell it’s meant for.
In the nervous system, that matters. Motor neurons depend on IGF-1 for repair, survival, resilience. If IGFBP7 is too active, the signal may never reach them.
The Reversals
Dr. Richard Bedlack at Duke University studies people who got worse with ALS diagnosis, and then got measurably better. These are called ALS reversals.
He runs the Study of ALS Reversals (ST.A.R.)
Among 62 confirmed reversal cases, about a third carry a genetic variant that lowers their IGFBP7 levels.
Less blocker. More growth signal. More neuron protection.
That insight became a hypothesis: maybe some people resist ALS progression because their biology lets IGF-1 work more freely.
You can hear Dr. Bedlack explain this at 25:15 in his talk. You can also read the related paper, Genetic Associations With an Amyotrophic Lateral Sclerosis Reversal Phenotype.
Beyond ALS
Dr. Bedlack’s hypothesis doesn’t exist in a vacuum. The same pattern shows up elsewhere.
In multiple sclerosis (MS), IGFBP7 levels are elevated in brain tissue compared to healthy controls.
In Alzheimer’s disease, researchers have seen the same thing. In one Alzheimer’s mouse model, scientists taught the mice a memory task, then injected IGFBP7 into the hippocampus. The mice forgot what they had learned. When they injected an antibody to block IGFBP7, the memories came back.
That’s a strong hint this protein isn’t just floating around, it has functional consequences inside the brain.
Dr. Bedlack has also confirmed through collaborations with ALS TDI, PrecisionLife, and databases from the New York Genome Center and Answer ALS that IGFBP7 levels are consistently higher in people with ALS than in healthy controls.
Together, these findings point toward IGFBP7 as a common thread in neurodegeneration, a potential bottleneck in how the brain repairs itself.
What We Don’t Know
Even Bedlack and colleagues admit: this is early. We don’t fully understand reversals.
Here are possibilities when someone improves after an ALS diagnosis:
- They may have an ALS mimicker.
- They may have an unusual form of ALS to start with.
- They may have innate compensatory mechanism that allows them to fight off the disease.
- They may be doing something that is helping them.
(Source: ST.A.R. Programme)
And even when IGFBP7 is high in ALS datasets, correlation is not proof. Blood levels might not mirror what’s happening in the spinal cord or brain.
Enter HMB
HMB (β-hydroxy-β-methylbutyrate) is a breakdown product of the amino acid leucine.
Athletes and older adults use HMB to support muscle, preserve lean mass, speed recovery. It has a good safety record.
In 2017, a paper titled “The effect of HMB ingestion on the IGF-I and IGF binding protein response to high intensity military training” examined HMB’s effect on IGF-I and IGF binding proteins.
That small study is often cited as evidence that HMB might influence IGFBPs (though not necessarily IGFBP7 in the brain). That’s the “clue” Bedlack leans on.
This is not a treatment. It is a hypothesis.
The Hypothesis
If lowering IGFBP7 increases IGF-1’s ability to signal, and that signal supports neuron survival, then reducing IGFBP7 could help in ALS.
HMB is a plausible, low-risk tool to test that. Bedlack is planning a pilot to see whether HMB can lower IGFBP7 in blood, perhaps even in CNS.
I want to be clear: I’ve added HMB to my own daily stack (2 grams per day), given its favorable risk profile and that possible upside. I’ll be watching that study closely. But I have no idea whether any effect will be perceptible.
This is not about a supplement cure. This is about testing a biological path.
The Safety Profile
HMB is one of the safest supplements studied.
- Typical dose: around 3 grams per day, split into 2 or 3 servings
- Form: calcium HMB powder or capsules
- Side effects: very rare; mild stomach upset in some
- Status: classified as Generally Recognized as Safe (GRAS) by FDA
That safety margin is precisely why it’s interesting to test — you can push the biology without undue harm.
From Blood to Brain
Here is how the mechanism is often illustrated:
- In blood, IGF-1 circulates, ready to deliver its repair message.
- IGFBP7 binds IGF-1, limiting its availability.
- In the neuron, IGF-1 normally binds its receptor and triggers survival and repair pathways.
- If IGFBP7 is too high, the message may not reach the receptor.
- If IGFBP7 is reduced, more IGF-1 can reach the receptor and do its work.
That is the core logic.
Diagram illustrating the IGF-1 / IGFBP7 interaction; it does not explicitly include HMB, but provides a visual reference for the signaling pathway being explored.
The Takeaway
This is not a cure. This is not medical advice.
It is not a recommendation from Dr. Bedlack or from me.
It is a hypothesis. A plausible, testable idea inspired by people who defied expectations.
Many supplements and drugs have shown promise in mouse models or small studies, only to fizzle in ALS clinical trials. This may be one of those. It’s also possible someone could take HMB powder and never know if it did anything.
Yet this theory comes from one of the neurologists leading the reversal movement. It deserves attention.
That is why tracking what we try, when we try it, and what changes over time matters, one reason I built StackDat.
If you want to explore what other supplements the ALSUntangled / Bedlack team considers worthy of more research, check this prior post: What Supplements Can Slow ALS Progression?
Science often advances by following small hints, not big guarantees.
Maybe the next clue is hidden in a supplement.
Maybe it’s not.
But the question is worth asking.
