Capsule Shells

Harmful Capsules? Cell Study Reveals Inflammatory Potential of Capsule Shells

A commissioned study reveals that generic HPMC and pullulan capsules are cytotoxic and can have inflammatory effects.

Purity Down to the Finest Detail

Sunday Natural stands for ultra pure supplements that are as natural as possible. That's why we completely abstain from all unnecessary additives and auxiliary materials in our products. We conduct extensive research to expose and exclude hidden impurities and non-disclosed additives. All the ingredients that we use must meet the highest standards of quality and purity. We pursue this principle of purity down to the finest detail.

The core of our product range is available in special PEG- and carrageenan-free capsules because they can be produced easily without the addition of any auxiliary materials. Tablets, by contrast, are much harder to press without using additives. Additionally, within capsules the nutrients are better protected against oxidation.

We commissioned this cell study to investigate the question of how different common capsule shell materials can affect cell health.

Many of our customers take capsules daily, meaning that the substance of the capsule shells aggregates to a relevant quantity of the ingredients. For this reason, capsule shells are not to be overlooked.

Capsule Shells - Many Hidden Ingredients

Generic capsule shells can contain a range of additives that are not legally required to be disclosed. In some cases, the producer may not even know what is in the capsule shells because suppliers may only provide this information upon specific request.

At Sunday Natural, we were one of the first to specialise in using ultra pure HPMC capsule shells from the very beginning: in contrast to generic capsule shells that may contain auxiliary substances such as carrageenans or PEG, our capsule shells are made without these additives. Though our capsule shells are more expensive as a result, we believe that this cost is necessary.

The Cell Study

To better understand the health risks associated with generic capsule shells, we commissioned a cell test from the independent institute, Dartsch Scientific, in 2020. Three in vitro tests were conducted to investigate the effects of generic HPMC capsule shells, pullulan capsule shells, as well as PEG- and carrageenan-free capsule shells.

The experiment was designed to investigate whether undesirable effects could be observed on organ-specific cell cultures (intestine epithelial cells, connective tissue fibroblasts, and functional neutrophils). There were 3 testing parameters: the effect on wound healing, toxic effects on the cells, and inflammatory parameters. Cell regeneration (wound healing) was tested via the repopulation of a cell-free space between the intestine epithelial cells. A potential cytotoxicity was investigated via cell activity measurements in connective tissue fibroblasts. Lastly, inflammatory effects were observed on neutrophil granulocytes, which are special immune cells in the blood.

For each series of tests, a stock solution made from 40 capsules in 100ml water was prepared. This corresponds to roughly 20 times the expected concentration in the intestines when taking 20 capsules a day.

The influence on cell regeneration and wound healing was tested with a diluted solution of 1:2.5. All other tests were conducted with solutions ranging from 1:1 to 1:100 in dilution, thus covering all concentrations that could be realistically expected in the human body.

Stock solution ~ 400 capsules

1:100 = 4 capsules
1:50 = 8 capsules
1:20 = 20 capsules
1:10= 40 capsules
1:5 = 80 capsules

Results: Toxic and Inflammatory Effects of Generic Capsule Shells

Wound Healing

The results were surprisingly straightforward. While the cell regeneration (wound healing) of intestinal epithelial cells exposed to the generic HPMC and pullulan capsule shell solutions was significantly impaired, the regeneration of cells exposed to the PEG- and carrageenan-free capsule shells was not negatively effected by even the highest concentrated solutions.

Fig. 1: Cell regeneration/wound healing of intestinal epithelial cells as measured via the repopulation of a synthetically produced cell-free space after treatment with different capsule shell solutions. Olympus IX-50 inverted microscope with 10x plan achromat lens in a transmitted light brightfield.

Cytotoxic Effects

In reference to cytotoxicity, the PEG- and carrageenan-free capsules also showed no significant difference to the control group (no exposure to a capsule solution). In the tests with generic HPMC and pullulan capsules, however, cell activity decreased by 12%. A reduction of cell activity was observed in all generic HPMC solutions and in the pullulan capsule solutions of 1:10 concentration and higher.

Fig. 2: Effect of the Various Tested Capsule Types on the Vitality of Connective Tissue Fibroblasts after 3-Day Exposure. The control group is set to 0. The mean ± standard deviation from 3 parallel tests is displayed.

Inflammatory Effects

In reference to inflammatory properties, the PEG- and carrageenan-free capsules also performed distinctly better than the others. A more than 75% increase in inflammation could be observed in the generic HPMC tests, increasing with dosage (statistically significant in all solutions) and about 70% in pullulan capsule tests (statistically significant starting from a concentration of 1:10). A statistically significant increase was not observed in higher concentrations of the PEG- and carrageenan-free capsule tests, and even at the high concentration of 1:5, an increase of only 20% was observed.

Fig. 3: Inflammatory Effect of Various Dilutions of Tested Capsule Types on Phorbol Ester Stimulated Functional Neutrophils. The control group is set to 0. The mean ± standard deviation from 3 parallel tests is displayed.

Conclusion

In all 3 tested areas (cell regeneration, cytotoxicity, inflammatory effects), the PEG- and carrageenan-free HPMC capsule shells performed demonstratively better than generic HPMC or pullulan capsule shells.

Commentary

Our avoidance of controversial additives such as PEG and carrageenans is justified by scientific experimentation. The results show that of the 3 tested capsule shells, the PEG- and carrageenan-free variety carries the fewest risks associated with cell regeneration, cytotoxicity, and inflammation.

Sunday Natural believes whole-heartedly in the highest standards of purity and transparency, which is why we will continue to work with independent laboratories. We have always had the majority of our product range independently tested for contaminants and impurities, and will continue to do so to guarantee our products' quality. With the goal of building a relationship of trust with our customers, we at Sunday prioritise the acquisition of the highest quality raw materials, regular laboratory testing, and absolute transparency about our processes and findings.