What is Protein Toxicity?

The widespread promotion of protein shakes, powders, and bars would have us believe it is difficult to get enough protein in our diets. However, the amount of protein we actually need to consume may be greatly overestimated, and at certain amounts can be toxic. Also, most protein-forified products contain a vast array of other toxins in addition to the protein, which can cause far more harm than good, particularly if not consumed with enough fat. Protein poisoning (hyperproteinemia) occurs when protein intake exceeds the body's ability to process it. This condition leads to the bioaccumulation of protein waste products in the bloodstream, which can cause symptoms such as nausea, diarrhea, skin problems, cancer, neurodegeneration, and kidney damage.

The most common form of protein poisoning occurs though the misfolding of proteins, which causes the exposure of hydrophobic residues which in turn bind to other proteins, creating aggregates. These aggregated proteins like amyloid-beta fibrils and β-sheet plaques are associated with neurodegenerative diseases like Alzheimer’s and Huntington’s. Clearing these aggregates can be more difficult over time, depending on how many enzymes the body can produce. Because cells rely so heavily on proteins, and misfolded proteins present a significant challenge for any cell stressed by nutrient deficiency, mutagenic effects are common in high protein diets. 

In a recent study tumor cells were observed to have a higher ability to degrade misfolded proteins, enhancing their survivability (1). The authors suggest that this may explain why neurodegeneration and cancer are inversely correlated, such that patients with neurodegenerative conditions have a 50% reduced cancer rate (2).  

“I am convinced that cancer does not need a "specific" treatment. Cancer is a so-called degenerative disease, and all the degenerative diseases have to be treated so that the whole body at first is detoxified.” Dr. Max Gerson

One of the most critical areas needing protection from the damage of misfolded proteins is the nucleus of the cell, where DNA is transcribed. Recent discoveries have helped uncover some of the mystery surrounding how the nuclease is able to clear misfolded proteins. A 2023 study in Nature Cell Biology used particle tracking to examine protein clearance and found that the nucleus and cytoplasm were in communication to send misfolded proteins to a shared vacuole (5).   

How to Avoid Protein Toxicity

Avoiding protein toxicity is as simple as avoiding dense forms of protein. The worst are all forms of meat, and highly processed products like textured soy protein, which has additional downsides. Protein shakes, powders and bars, are all too high in protein, and often lack any good fat to hep the body deal with it. All meat, even grass-fed, contains too much protein for the human body to digest in anything other than small amounts. Green shakes can be just as filling, and contain far more bioavailable vitamins and antioxidants than protein shakes. Adding avocados or coconut oil adds an important compoentnt preventing protein toxicity and aiding nutrient absorbtion. 

According to many naturopaths and physicians who have high success rates for treating cancer patients, the human pancreas can only produce the enzymes to process about 6 ounces of protein a day. Any protein in excess leads to highly toxic metabolic waste products that also disrupt and change the microbiome towards pathogens like E. coli. Drinking green drinks, and beverages containing chlorophyll, help the body protect itself from and repair damage caused by damaged proteins.  

Limiting protein to 20-30 grams per day is another option recoomended by nutritionist and naturopaths, like Dr. Max Gerson and Dr Charlotte Gerson, whose clinics focused on removing high protein and salt from the diet, and supplementing with enzymes to degrade proteins and relase the burden on the pancreas, and potassium to flush out excess sodium. Studies have shown that the most protein we can digest is around 10 grams per hour, and no benefits are seen in consuming more than 30g per day (6) . 

Detoxifying Protein Aggregates

We could all use a protein detox, in which we give the body all it needs to clear misfolded and damaged proteins. Fibrinolytic and protylitic enzymes like Nattokinase, Serrapapetase and Bromelain help with degrading and clearing these cross-linked fibrins and other small peptides.

Nattokinase 

Nattokinase is a protease enzyme that has antiplatelet/anticoagulant liver-protecting, lipid-lowering, and neuroprotective effects. Nattokinase was shown to degrade amyloid-beta plaques, at normal body temperature and neutral pH, in a recent in vivo study (3). The authors explain that their, "findings demonstrated that NK entered the circulation when taken orally… and potentially cleared Aβ42/Aβ40 deposits in various parts of the body”. This study shows that Nattokinase taken orally is capable of decreasing amyloid plaque levels in the brain and blood.

Another study published in 2023 by Jesse Santiano, M.D. found in a case study that Nattokinase appeared to resolve the symptoms of prostrate and vascular issues that result from Parkinson’s.  Dr. Santiano points out that the meat industry uses protein-digesting enzymes to treat bone meal to prevent spreading any prion proteins to the cattle being fed, but that nattokinase did an even better job of degrading amyloid plaques and prions.

Bromelain

Bromelain is another fibrinolytic enzyme that reduces blood clotting by promoting the conversion of plasminogen to plasmin, and restricting the production of fibrin. Since excess protein in the diet causes increased fibrin, bromelain can be an effective anti-thrombotic, and anti-cancer therapy. Bromelain, “promotes monocytic cytotoxicity in women with breast cancer when administered orally [ 58]”, and stimulates autophagy. Studies using intraperitoneal injections of bromelain into tumor cell lines found that it demonstrated antitumor activity greater than the conventional drug, 5-FU ( 4).

Serrapeptase

Serrapeptase is a fibrinolytic enzyme that contains zinc, which itself has been found to mediate the degradation of amyloid plaques. Similar to nattokinase, it shows anti-biofilm, cardio-protective, and anti-inflammatory activity. A study comparing it to aspirin found it to be more effective, and another study found it was more effective than Ibuprofen for pain. The anti biofilm features of Serrapeptase show promise for a variety of medical applications, including antimicrobial-resistant infections. The reason is that biofilms secrete proteins that enhance their formation, but metalloproteases, like Serrapeptase containing zinc, have been found to have multiple anti-biofilm activities. Such enzymes work by changing the phenotype of the pathogenic bacteria, reducing even mature biofilms, and enhancing the effects of antibiotics.

Summary

Protein toxicity can be caused when people consume high-protein diets but fail to consume adequate levels of fat and carbs. Protein poisoning could also occur due to underlying medical conditions that impair protein metabolism, such as liver or kidney disease.

References

1. Chen, L., Brewer, M. D., Guo, L., Wang, R., Jiang, P., & Yang, X. (2017). Enhanced degradation of misfolded proteins promotes tumorigenesis. Cell reports, 18(13), 3143-3154.
2. Ji, J., Sundquist, K., & Sundquist, J. (2012). Cancer incidence in patients with polyglutamine diseases: a population-based study in Sweden. The lancet oncology, 13(6), 642-648.
3. Ni, A., Li, H., Wang, R., Sun, R., & Zhang, Y. (2023). Degradation of amyloid β-peptides catalyzed by nattokinase in vivo and in vitro. Food Science and Human Wellness, 12(5), 1905-1916.
4. Baez, R.; Lopes, M.T.; Salas, C.E.; Hernandez, M. In vivo antitumoral activity of stem pineapple (Ananas comosus) bromelain. Planta Med. 2007, 73, 1377–138
5. Sontag, E.M., Morales-Polanco, F., Chen, JH. et al. Nuclear and cytoplasmic spatial protein quality control is coordinated by nuclear–vacuolar junctions and perinuclear ESCRT. Nat Cell Biol 25, 699–713 (2023). https://doi.org/10.1038/s41556-023-01128-6
6. Symons TB, et al. A moderate serving of high-quality protein maximally stimulates skeletal muscle protein synthesis in young and elderly subjects. J Am Diet Assoc. 2009 Sep;109(9):1582-6.