Polytetrafluoroethylene Ingestion as a Way to Increase Food Volume and Hence Satiety Without Increasing Calorie Content

Abstract

Since satiety is largely due to stretch of the stomach and people tend to eat a consistent weight of food, increasing food volume and mass increases satiety. This can be achieved without increasing the calories of food by mixing food with a material that cannot be metabolized. Such a material should be inert, safe, resistant to stomach acid, lack taste, available in powder form, smooth, resistant to heat, and cost effective. Polytetrafluoroethylene (PTFE) is an ideal substance for this purpose. It is a soft plastic that is widely considered to be the most inert material known and is extremely stable. Animal feeding trials showed that rats fed a diet of 25% PTFE for 90 days had no signs of toxicity and that the rats lost weight. This article publishes the data from these subchronic animal feeding trials, reviews the relevant available literature, and hypothesizes that increasing the volume of food by mixing the food with PTFE powder at a ratio of 3 parts food to 1 part PTFE by volume will substantially improve satiety and reduce caloric consumption in people.

Civilization has zero calorie drinks but we have not yet made the leap into the realm of zero calorie foods. The first step toward achieving this goal is the ability to increase the volume of food without adding calories. The industry of calorie free flavor agents such as artificial sweeteners like “Sweet’N Low” utilizes the idea of molecules which the body cannot metabolize or break down. Similar to this concept is the ability to substantially add satisfying volume and mass to food without adding calories, which can be achieved by mixing polytetrafluoroethylene (PTFE), an extremely inert plastic, into food. This article reviews the safety of this proposed innovation by examining existing knowledge relevant to PTFE ingestion and provides a thorough presentation of the available information.

Discussion

Though human satiety is complex, a significant contributing factor is the stretch of the stomach due to volume and mass of ingested material (i.e., gastric distention). Since people tend to eat a consistent amount of food, ¹ artificially increasing food volume and mass in the stomach can yield increased satiety. This can be achieved without increasing caloric content by using a nonmetabolized volume bulking agent. Fiber is sometimes supplemented to the diet for this purpose, but the use of fiber causes soft bulky stools and is commercially limited because it alters the taste and texture of food. Sugar based bulking agents that cannot be metabolized, such as xanthan gum, are limited by their hygroscopic properties which cause a toxicological effect of diarrhea at large volumes. ² PTFE is proposed as an inert nonmetabolized volume bulking agent that would avoid these problems.

PTFE, a plastic commonly known as Teflon®, can be used to supplement volume in the diet by mixing the raw material (virgin PTFE powder) into food. Because PTFE is heat resistant, its mixing into food can take place before or after cooking. PTFE is soft and contributes no flavor (evident by its use in tongue piercings) and hence does not detract from the eating experience. It is also resistant to the strongest acids (PTFE containers are used industrially for storing acids) and therefore will not be degraded by stomach acid. It is extremely inert^3,4 (widely considered to be the most inert material known) so it will not react within the body. It has a low coefficient of friction so that it will not scratch the lining of the gastrointestinal (GI) tract during transport. Because of its chemical and physical properties and long history of use and contact with humans, PTFE is widely considered a very safe material. It is extensively used in medical devices (for instance, a large portion of the artificial blood vessel grafts that have been successfully implanted into people for decades are made from pure PTFE). ⁵ For these reasons, PTFE is an ideal material for use as a nonmetabolized food volume bulking agent.

The authors hypothesize that increasing the volume of food by mixing the food with PTFE powder at a ratio of 3 part food to 1 part PTFE by volume will substantially improve satiety and reduce caloric consumption in people. This has applications for patients struggling with intentional weight loss. This hypothesis could be verified by a randomized clinical trial comparing ad libitum calorie consumption by subjects eating a PTFE containing food versus the same subjects eating the same food but without PTFE volumizing agent.

Review of Biological Safety of PTFE

A body of evidence supports the safety of PTFE ingestion. According to the Encyclopedia of Toxicology, “There is no apparent mechanism of toxicity for orally administered PTFE as no toxicologically significant effects were observed following oral administration to rats for up to 90 days. The lack of toxicity is most likely due to the following: 1) GI absorption of PTFE is negligible given its extremely high molecular weight (1,000,000-10,000,000 Da) for PTFE fine powder; 2) PTFE is chemically inert under physiological conditions; and 3) PTFE is not metabolized. . . . The oral toxicity of PTFE in rats is low. Following repeated dietary administration of up to 25% PTFE to rats for up to 90 days, no toxicologically significant effects were noted.” ⁶ The lack of toxicity of PTFE at 25% of the diet level in 90 day fed rats was validated by peer review of the Scientific Review Panel of the Hazardous Substances Data Bank (TOXNET), a high authority in toxicology.

Rat feeding trials supporting the above claims were performed by the Haskell Laboratory for Toxicology and Industrial Medicine of du Pont Company in the 1960s. These feeding trials were not done for nutritional or obesity treatment research purposes but rather to demonstrate that PTFE coating is safe to use as an antistick surface on cookware. These reports (Haskell Laboratory Reports 56-61 [1961] and 224-68 [1968])^7,8 were voluntarily filed by du Pont and are available on microfiche records at the US Environmental Protection Agency (EPA) library; they are included as supplemental documents to this publication for convenience. Du Pont fed rats a diet composed of 25% PTFE and observed that the animals lost weight. Subsequent trials were performed with only a 10% PTFE diet instead of 25% to avoid weight loss. The conclusion that the toxicological concern of PTFE feeding is low was further supported in a voluntary communication from Haskell Laboratory to the EPA Office of Toxic Substances in 1983 in a document signed by the chief pathologist of the lab along with a certificate of authenticity. This is also provided in full as an online supplement publication (Haskell Laboratory Medical Research Project 1080 [1982]). ⁹ The safety of feeding PTFE is corroborated by additional evidence compiled below.

PTFE is not considered genotoxic. ⁶ In fact, it is so inert that it has been used in the actual genotoxicity protocols or test methodologies, for example, PTFE used in the Salmonella typhimurium mutagenicity testing of the EPA Mobile Reaction Chamber. ¹⁰ Many other similar examples are available given that PTFE coated stirring rods are a common lab equipment.

Ingestion of large amounts of PTFE is reasonably certain to not cause reproductive harm. The du Pont MSDS report for PTFE notes “No toxicity to reproduction.” ¹¹ Reproductive safety is corroborated by a study that evaluated PTFE coating on bladder catheters and concluded that PTFE did not affect sperm motility or viability ¹² in contrast to other catheter materials that are toxic to sperm. ¹³ Furthermore, PTFE implants are used in gynecological surgeries to prevent formation of adhesions between the uterus and adjacent structures. A study of 68 women who underwent myomectomy (surgical removal of fibroids from the uterus) with subsequent PTFE implantation alongside the uterus and who later became pregnant, found that PTFE did not affect pregnancy outcomes; there were no documented cases of preterm labor, preterm premature rupture of membranes, or uterine rupture. ¹⁴

PTFE ingestion is reasonably certain to not cause developmental toxicity given its extreme inertness and its routine use in humans in vitro fertilization techniques. ¹⁵ For example, a study which transferred 194 human embryos and implanted them inside the uterus using different Teflon catheters ¹⁶ reported that it previously used nylon catheters for embryo transfer but replaced the practice with Teflon catheters based on experiments which showed that mouse embryos were unable to survive incubation for 1 hour within the nylon catheters but were unaffected by similar incubation within the Teflon catheters.

Dermal exposure to PTFE is considered safe. This is evident by the use of PTFE needles in intravenous access. ¹⁷ In fact, PTFE is used as a negative control material for ISO 10993-6, an international standard for biological evaluation of medical devices. ¹⁸ PTFE is also used in dermal cosmetic creams (due to its softness and smoothness) and PTFE strips can also be found in razors. ¹⁹ It is not a skin irritant or sensitizer in humans ⁶ and is widely used in dental floss.

PTFE is considered “non-antigenic” ²⁰ and safe in regards to immune toxicity. This is evident by the fact that it is generally well tolerated in situ in a wide range of surgical applications including ophthalmology. Carcinogenicity of a substance should be distinguished from an inflammatory response since any implanted foreign-body produces an inflammatory response; this is a general principle in the field of surgery and applies even to the most inert of compounds—PTFE. Extensive amount of studies (both animal and long-term human) involving some immune response to PTFE surgical implants exist, however, these studies do not provide meaningful information about the carcinogenicity of PTFE. PTFE is classified by the World Health Organization International Agency for Research on Cancer as Group 3 (i.e., the agent is not classifiable as to its carcinogenicity to humans). ⁶ Based on its chemical properties and extensive use, it can reasonably be concluded that PTFE is extremely unlikely to be carcinogenic. It is generally regarded as noncarcinogenic. It should be pointed out though that the monomer of PTFE, tetrafluoroethylene (TFE), is reasonably considered to be a human carcinogen. ²¹ However, TFE is a very different material than PTFE; TFE is an unstable explosive gas at room temperature. PTFE samples do not contain TFE residues, otherwise PTFE would not be the extremely stable compound that it is.

Regarding neurotoxicity safety, corroborating evidence can be found in a study which injected PTFE paste intravascularly in dogs either into a peripheral vein or into the carotid artery. ²² The study confirmed that PTFE paste injected into the carotid artery of dogs reaches the brain (as expected). In this study, the PTFE which was injected into the carotid artery did not cross the blood-brain barrier; it was found inside the small blood vessels of the brain. The study published histological images that clearly showed white PTFE deposition within the small blood vessels. Histological analysis showed that there was no evidence of demyelination in parenchyma around vessels containing the particles (by Luxol fast blue staining), no abnormality of nerve Purkinje fibers (by Cajal staining), and no reactive astrocytosis or loss of neurons (by GFAP immunohistochemical staining) in any of the animals who had intravenous or intra-arterial injection of PTFE paste. Similarly, another experimental study demonstrated that demyelination did not occur in the sheep’s brain after intra-arterial injection of PTFE paste. ²³

GI absorption is generally defined as passage of a material through the enterocytes and into the blood. Molecular weight (MW) is considered the main limiting factor in this process and the MW of PTFE, combined with its insolubility, makes its GI absorption unfeasible. Parenteral injections of radiolabeled polyvinylpyrrolidone in humans demonstrated that the permeability cut-off of the human small intestine is MW of 80 000 Da.^24,25 The GI permeability “cut-off” MW was also confirmed using polyethylene glycol (PEG)^26,27 and, even for patients with irritable bowel syndrome, it is below 80 000 Da^28,29 and therefore an order of magnitude below the MW of PTFE which is in the million Das.

In addition to toxicology of the material, to thoroughly analyze the risk of PTFE ingestion, bioaccumulation needs to be addressed. In addition to absorption, uptake of particles from the GI tract can occur by other mechanisms such as transcellular and paracellular transport or persorption. ³⁰ This makes particle size an additional important parameter for consideration.

Microparticle uptake (“absorption” is essentially only one way by which particle uptake into the body can occur) is of interest to drug delivery and has been studied extensively. It is widely accepted that GI uptake of microparticles is inversely correlated with particle size.^31,32 An extensive review of the topic concluded that “Particles of 20 µm diameter were rarely found in the tissue, and never beyond the epithelial layer; those 10 µm in diameter reached the submucosa but not deep vessels or the outer muscle layer, whereas 6 µm particles were found through to the serosa/adventitia and in mesenteric lymph nodes, as were the standard 2 µm particles.” ³⁰ As a reference point, the size of an enterocyte is ~1 µm in length and 0.1 µm in diameter. ³³

This conclusion, that the limit of GI particle uptake is in the range of 20 µm particle size,^34,35 is validated by a study that fed rats radiolabeled plastic beads of particle size 20-40 µm. In this study rats were fed poly(GMA-co-EGDMA) beads that were labeled with iodine-125 and then “sacrificed at 2.5 h (group 1), 8 h (group 2), or 24 h (group 3) after polymer administration. The selected time intervals were sufficient to observe the passage of polymer through the digestive tract. Immediately after sacrifice, the internal organs, including the digestive tract, were excised, and radioactivity was determined using an ionization chamber. . . . Almost the entire content was eliminated from the bodies of the rats. Radioactivity in the liver of this group [group 3] was not observed. In all animals, the radioactivity was also measured in the thyroid gland, spleen, heart, kidneys, and lungs. No radioactivity was detected in these organs. Thus, polymer was not absorbed; instead, it was eliminated with the feces. Only extremely low radioactivity (2.98% of the initial radioactivity) was detected in the lungs of 1 rat in group 3 (8HQB 24 h after administration). This animal likely aspired part of the radiolabeled polymer administered using a gastric probe. The polymer was not significantly absorbed from the gastrointestinal tract, as it is stable at model pH conditions. . . . This experiment clearly demonstrates that the polymer passed through the gastrointestinal tract and was not absorbed. . . . Because the macroporous polymeric beads are insoluble, it was expected that they would not be absorbed from the digestive tract. Therefore, we followed the absorption of radiolabeled 125I-8HQB after oral administration. We have shown that there was no measurable radioactivity in the internal organs except those of the digestive tract, through which the polymer passed. This result demonstrates that the polymer is nonresorbable (this is also clear in the PET/CT images).” ³⁶ Similarly, PTFE is an insoluble polymer and if used in particle size greater than 20 µm, is reasonably certain to not pass from the GI tract to the blood.

Further support to the understanding that the size limit of GI particles uptake is in the range of 20 µm is available from a study whereby “intestinal barrier function in mice was assessed after acute or chronic oral administration of 15.8- and 5.7-micron [µm] synthetic spherical particles. The results failed to confirm previous reports that ingested particles rapidly appear in blood. Furthermore, 15.8-micron particles did not accumulate in intestinal Peyer’s patches, mesenteric lymph nodes, or other organs of the reticuloendothelial system, even after the maximum dosage of 8 × 10⁶ particles per day for 60 d [days].” ³⁷ These data contrast with a few reports which claimed that the upper limit of GI uptake was 110-150 µm^38,39 based on observations of certain dietary ingredients which the human body cannot metabolize, such as some starches, in certain body tissues. Regardless, it is generally accepted that the body has mechanisms to excrete such substances after their uptake (presumably via the lymphatics, GI excretion, and urine) since, after all, people who eat diets rich in such starches do not suffer from embolisms of nonmetabolized starch. Pica (an eating disorder characterized by repeated eating of nonfood substances) is well studied and there is no evidence that such patients experience more embolisms. PTFE powder with particle sizes ≥20µm would essentially be restricted to the GI lumen, excreted in the feces, and would not bioaccumulate.

The feeding animal trials discussed above were performed using PTFE in the aqueous dispersion form. Aqueous dispersions of PTFE typically have an average particle size below a micron ⁴⁰ ; the most common PTFE aqueous dispersion has an average particle size of about 0.2 µm. ⁴¹ Despite the small particle size, large ingestion amount, and extensive exposure length in these feeding trials, the data indicates that the particles did not pass from the GI lumen to the blood. If the particles passed to the blood, via the portal circulation, they would be expected to accumulate in the liver. The data shows that there was no change in total liver weight and that liver biopsies showed no pathology or evidence of particle accumulation under direct mircoscopic observation. Because of this, it can reasonably be presumed that the PTFE was excreted in the feces and hence would not bioaccumulate. A possible explanation as to why such a small particle size did not pass to the blood is that PTFE is hydrophobic and clumps together in the hydrophilic environment of the GI lumen and essentially forms a larger effective particle size.

Specifications of Proposed Innovation

As in any engineered innovation, the exact specifications are important. We hereby propose the following specifications for PTFE ingestion: use of granular virgin PTFE resin powder (essentially pure or without significant residues or contaminants), not containing a dispersing agent (<1 ppm as based on the Haskell reports), manufactured without any perfluorooctanoic acid (PFOA), which is also known as C8, with a particle size distribution following a normal Gaussian function, a mean particle size ≥130 µm, and a standard deviation less than 15 µm.

The choice of particle size is based on several factors, including safety, environmental effects, user preference, and cost. Other factors equivalent, particle size for ingestion purposes should be small to avoid grainy feel within food. As noted in the above review of safety, particles with sizes ≥ 20 µm are expected to be excreted. We recommend and average particle size of 130 µm to ensure a large portion of particles to have size above 100 µm (97.5% of particles with the above Gaussian distribution). Particle sizes greater than 100 µm were chosen not as a mere arbitrary value above the 20 µm GI uptake limit, but rather to also address environmental factors and ensure no significant environmental impact occurs. PTFE waste with the above specifications would end-up predominantly in landfills as opposed to the oceans. This is because particles of size 100 µm or larger settle in the public wastewater treatment process thereby ending up in the sludge ⁴² as opposed to the secondary effluent which is discarded to the ocean. The hydrophobicity, density, and high MW of PTFE also ensure that it will gravitate toward the sludge and hence ultimately landfills. Extracting raw material plastic pellets from mixed landfill waste is economically viable and done by companies such as MBA Polymers, Inc. Recycled PTFE is already an existing industry. Given that PTFE is one of the more expensive plastics, recycling PTFE from landfills is a possible concept.

Conclusion

PTFE is proposed as a nonmetabolized food volume bulking agent for human ingestion as a therapeutic option for weight loss. The proposed mechanism is by increasing satiety via increased gastric distention and thus reduction of caloric input in PTFE-diluted foods. There is strong evidence supporting the biological safety of PTFE, including specifically for ingestion purposes. Large volume ingestion of PTFE, at levels of 25% of the diet, is generally recognized as safe based on extensive animal feeding trials and the extreme inertness of the material. Specifications are provided for a PTFE food volumization product that further addresses biological safety, environmental impact, ease of use, and manufacturability.