In contrast to dietary supplements that do not claim medicinal properties, nutraceuticals are non-FDA-regulated, orally delivered products purported to have medicinal properties. This article discusses nutraceuticals with purported medicinal properties attributed to their protein ingredients and why orally delivered proteins cannot be absorbed into the bloodstream and thus can have no systemic activity.
All ingested proteins in the gut are broken down into their individual amino acid building blocks and are thus not absorbed intact into the bloodstream (Fig.1). The transfer of substances from the gut to the blood is known as systemic absorption. Intact proteins cannot be absorbed systemically. To be medicinally active a protein, must remain intact.
Figure 1. Digestion of proteins in the gut.
Let's do a quick reality check. FDA-regulated (prescription) drugs compete via their characteristics of safety, efficacy, and/or convenience (unfortunately, not by price). A major convenience factor is the route of delivery. Oral delivery is considered to be the most convenient, while delivery by injection is considered to be the least convenient. Yet, every prescription protein drug (think monoclonal antibodies) is delivered by injection because intact proteins are not systemically available via the oral route. Insulin, which is considered to be a peptide (a chain of amino acids with fewer amino acids than a protein), also cannot be delivered orally. All the people who have to self-inject or rely on pumps to deliver insulin would prefer to take it orally. Still, no matter how much they ingested, there would be no blood sugar regulation because there would be no intact circulating insulin.
In the improbable event that a whole foreign (nonhuman)protein did reach the bloodstream, there would be an additional and possibly life-threatening barrier to its efficacy. Foreign proteins are considered to be antigens that elicit an immune response. This response, at best, would neutralize the effectiveness of any foreign protein in the blood and, at worst, cause an anaphylactic shock response that could kill the patient.
Prevagen, a popular "memory" nutraceutical, lists apoaequorin, a protein found in bioluminescent jellyfish as its main ingredient. Apoequorin when ingested orally has no systemic immunogenicity or systemic medicinal activity because it is rapidly broken down to its amino acids by pepsin and acids in the gut. To be systemically active, apoequorin must be injected. However, as already stated, the human immune system would strongly respond to a jellyfish protein in the blood.
Another real barrier to apoequorin having a positive memory effect on the brain is the blood-brain barrier, which keeps foreign proteins and other molecules from crossing from the blood into the brain. Even if apoequorin did enter the bloodstream, it could not reach its purported activity site, the brain. There are no reports in the literature of anyone even attempting to inject apoequorin into a mammal, let alone a human. Taken together, the incontrovertible science discussed in the paragraph above caused New York State to successfully sue the manufacturer of Prevagen in 2024 and prohibit the manufacturer from making efficacy claims.
There are numerous other examples of medicinal claims for proteins in nutraceuticals. For instance, Immunoglobulin from bovine colostrum is purported to have numerous beneficial effects. Colostrum is secreted in mammals' milk and provides an immune boost to newborns. Newborns have a much more permeable gut than adult mammals, which is why colostrum can be systemically active in babies but not adults. While colostrum may have some effects in the adult gut, bovine immunoglobulin would not be absorbed intact into the bloodstream and thus could not provide systemic effects. To be fair, bovine colostrum has nonprotein nutrients. that can be absorbed. However, the scientific evidence that bovine colostrum has any beneficial effects in adults is, at best, equivocal. The following article is exemplary of this. Whereas the title is impressive, its conclusions are based on the word "may." This is not proof of activity.
TItle: The Effects of 12 Weeks Colostrum Milk Supplementation on the Expression Levels of Pro-Inflammatory Mediators and Metabolic Changes among Older Adults: Findings from the Biomarkers and Untargeted Metabolomic Analysis
Conclusion: In conclusion, consuming bovine colostrum milk may induce metabolic changes and reduce the expression of various pro-inflammatory mediators, thus improving the immune function in older adults. https://pubmed.ncbi.nlm.nih.gov/37513601/.
Hopefully, you got it now that you are not getting any systemic medicinal benefits from proteins in nutraceuticals.