Fried foods, typically prepared with high-fat cooking methods, can delay gastric emptying and influence the enteric absorption of certain drugs, particularly those that are lipophilic. Traditional fried food is made by immersing it in hot oil at a typical temperature of 150–200°C. Worldwide fast-food companies supply fried foods, such as French fries, fried chicken, fried pork chops, fried sweet potatoes, fried banana chips, to count only a few. Fried foods are widely popular due to their unique taste and flavor, golden color, crisp texture and other for the consumers appealing attributes. However, some fried foods absorb a large amount of oil during the traditional frying process, and the final oil uptake can reach in extreme cases up to 50% of the total weight (6). In many fried foods, oil uptake is above 20% of the total weight. For instance, in case of potato chips, it is 34.6%, corn chips, 33.4%, tortilla chips, 26.2%, doughnuts, 22.9% of the total weight (7).

Reduction of oil uptake is possible by applying a plethora of processing techniques. The frying process, product characteristics and oil quality are key factors affecting oil absorption. At higher frying temperatures, oil absorption is usually reduced, as the process is shorter and the enhanced crust formation acts as a physical barrier for oil imbibition. For instance, potato crisps fried at 120°C have higher oil content compared with their counterparts fried at 180°C (7). Various innovative frying processes have been developed to reduce oil uptake, like vacuum frying (VF), microwave frying (MF), microwave-assisted vacuum frying (MVF), ultrasound combined microwave vacuum frying (UMVF), air frying, and radiant frying (8). Baking is also utilized and could reduce oil uptake significantly (9).

Notably, in addition to oil uptake, frying produces volatile/non-volatile compounds which darken the food’s color, generate aromas, and develop unique crust and textures (10, 11).

The high oil content of the fried foods could interact with the drug enteric coating. Some medications have enteric coatings to protect them from stomach acid and improve absorption in the intestines (e.g., erythromycin, pancrelipase, proton pump inhibitors, budesonide). Hence, different processing methods of the same food product, such as deep fat frying or baking may considerably and differently affect the dissolution of enteric coatings, by this way potentially altering the drug’s release profile.

To properly and comprehensively analyze the frequent interference of food frying with the enteric absorption of various medicines, one must take into account also that the high temperature of the oil may induce harmful chemicals, above all it enhances the oxidation of oil lipids, of course via non enzymatic pathways, and it also induces the formation of several other potentially harmful compounds, like acrylamide (due to a Maillard reaction), polycyclic aromatic hydrocarbons and heterocyclic amines. Several strategies to reduce acrylamide formation during food processing (e.g., frying, baking) were recently reviewed (12, 13).

Extensively studied since many decades is the oxidation of polyunsaturated fatty acids (PUFAs) at the level of the carbon–carbon double bond(s), a free radical chain reaction called lipid peroxidation, which is leading to alkoxy-, peroxy-, lipid radicals and lipid hydroperoxides; the latter molecules are highly unstable, so easily break down generating various still reactive but much more diffusible end-products, of which the most studied are aldehydes, since provided with different toxicological properties (14–16).

Of the several aldehydes stemming from PUFAs, the quantitatively and qualitatively more important are malonaldehyde, generated from both ω-3 and ω-6 PUFAs, 4-hydroxyhexenal (HHE) from ω-3 PUFAs and 4-hydroxynonenal (HNE) from ω-6 PUFAs (16). These carbonyl compounds, in particular HHE and HNE, readily form stable adducts with proteins and lipids by this way deranging their structure and function, for example at the level of the intestinal epithelial layer, and also exerting strong pro-inflammatory stimuli (16, 17).

Indeed, the generation of these toxic aldehydes by high fat frying has been shown for four different vegetable oils, all containing both ω-3 (linolenic acid) and ω-6 (linoleic acid) PUFAs namely soybean oil, sunflower oil, rapeseed oil and corn oil (18). In the food cooked with any of these four vegetable oils the production of relevant amounts of HNE was demonstrated (19). Previously, the same harmful aldehyde was consistently detected in relatively high concentration in French fried potatoes obtained from six different fast food restaurants (20). HNE is most likely the most toxic aldehyde produced during lipid peroxidation (16), a biochemical process which in the thermal processing of food is driven and sustained by the reactive oxygen species generated in high amount by heat (21).

As regards HNE, a very important observation was recently made that points to an additional mechanism of interference by this aldehyde with the pharmacological effect of orally taken drugs. In fact, in a screening study actually simulating a clinical worst case scenario, bags for endogenous saline infusion, catheters and disposable syringes, all made with plastic polymers, were shown to leach HNE in their medicinal contents (22). Based on the recognized readiness of this reactive and diffusible carbonyl to form protein and lipid adducts, a direct addition of HNE and maybe other reactive aldehydes to active pharmacological principles (API) appears a quite likely event.

Indeed, deep fat fried food by-products are at present considered as a significant dietary contributor to the most common chronic diseases especially affecting the elderly, including atherosclerosis, cancer and hypertension (23). Hence, a spectrum of alternative types of food processing should be taken into consideration (e.g., baking, air frying).

Methylglyoxal (MG) and glyoxal (G) are two alpha-ketoaldehydes (dicarbonyls) that may derive from autoxidation of polyunsaturated fatty acids and glucose, and are consistently present in foodstuff rich in these nutrients, in which they are mainly formed via the Maillard reaction. The two reactive dicarbonyls form adducts with proteins, by this way being potentially cytotoxic, in the case of food potentially enterotoxic, and, in addition, they readily lead to a quantitatively considerable formation of advanced glycation end products (AGEs), chemical species with strong pro-oxidant, pro-inflammatory and cytotoxic properties (24, 25). In fact, following the binding of AGEs to the membrane receptors for advanced glycation end products (RAGEs), a redox signaling is generated that activates the inflammatory reaction and induces an oxidative burst (25, 26).

An excessive production of MG and G, as it could occur especially at very high temperatures and long time exposures, would contribute to bring in the gut a mixture of reactive species, with likely derangement of enteric structure and function (24, 27). An indirect, while quite effective, mechanism of malabsorption not only of nutrients but also of medications. But, by far more important as regards food processing interaction with drug pharmacokinetics, is the demonstrated reaction of dicarbonyls and AGEs with membrane transporters like ABCA1 (ATP binding cassette sub-family A member 1), considerably expressed on the surface of the intestinal epithelial barrier. Indeed, in the gut, one of the largest groups of membrane transporters, namely the ABC family, allows the intracellular uptake of a great variety of molecules including many drugs, mainly lipophilic ones. Years ago, glyoxal, but not methylglyoxal, was shown to destabilize the activity of ABCA1, in cultured human skin fibroblasts and murine macrophages, even if the protein synthesis of the transporter was not affected (28). Much more recently, using murine macrophages, the same group demonstrated this time that the advanced glycation of human albumin (AGE-albumin) was able to markedly inhibit the synthesis of the membrane transporter ABCA1. Moreover, those authors elucidated the mechanisms of such an effect of AGE-albumin, namely a net enhancement of ABCA1 ubiquitination and consequent proteasome degradation (29). Thus, based on these findings, one should most likely expect a significant contribution also by a “dicarbonyl stress” to the potential interference of food thermal processing on the uptake of drugs.

The high temperatures that could be reached in the industrial food processing, and during frying, grilling or barbecuing of a large variety of foodstuffs, generate another wide class of potentially harmful compounds, namely stemming from the heat-dependent oxidation of sterols, quantitatively well represented in foods both of animal and vegetable origin. By far more investigated and characterized is the family of oxysterols, 27-carbon atoms compounds derived from the oxidation of cholesterol, while the oxyphytosterols, i.e., the oxidation products of phytosterols, still need further characterization as regards their possible detrimental effects on health.

The thermal processing of food of animal origin has clearly been demonstrated to induce the non-enzymatic formation of a large variety of oxysterols (30, 31) the most dangerous of which are certainly 7β-hydroxycholesterol (7βOHC) and 7-ketocholesterol (7KC), since provided with highly cytotoxic and pro-inflammatory properties (32–35). An indirect interference with the gut absorption of medicines is that affordable by a mixture of oxysterols like that present in the gut of people fed a Western type of diet, because it contributes to damage the intestinal epithelial layer, in particular by deranging both tight and adherens junctions (36, 37). The impairment of the intercellular adhesion molecules should then mainly affect the paracellular absorption of drugs, i.e., the main mechanism of intestinal uptake of hydrophilic drugs (38).

On the other hand, hydrophobic drugs are absorbed via a transcellular route, taken up by active transporters (38), hence the high oxysterols’ intake due to thermal processed food might represent an obstacle for the physiological action of the numerous multidrug protein transporters selectively expressed along the gastro-intestinal tract (39). In principle, oxysterols could readily oxidize these transporters through the up-regulation of reactive oxygen species production, and, in addition, two of them, namely 5α,6α-epoxycholesterol and 5β,6β-epoxycholesterol, were even shown to form protein adducts by reacting with the ε-amino group of lysine (protein sterylation) (40). However, the suggested addition reaction of defined oxysterols with drug protein transporters is at present just a speculation, since no specific literature is available yet. The same lack of specific literature (addition reaction with membrane transporters) applies for HNE and other aldehydes, any way shown to readily undergo addition reaction with proteins.

In the food of vegetable origin, steroids are largely represented and are named phytosterols, compounds having a structure similar to cholesterol (41), and like cholesterol being prone to autoxidation, leading to the generation of quite a number of oxyphytosterols. As in the case of oxysterols, the quantitatively more relevant oxyphytosterols are 7 K- and 7OH- derivatives of sitosterol and campesterol, but also the epoxy derivatives may reach elevated concentrations in the diet (41, 42).

A clear example of heat-induced oxidation of phytosterols, was provided by a careful and detailed analysis of the oxyphytosterol content of refined rapeseed oil, really one of the most used edible oils worldwide, before and after thermal treatment. Two different temperatures were considered, 60°C and 180°C, and various heating times. The total oxyphytosterol content detected in the rapeseed oil heated at 180°C for 15 min resulted to be four times as higher as that quantified in the 60°C heated oil (43). Even in this study, actually in line with a much earlier report (44), 7 K- and 7OH- and epoxide derivatives of sitosterol and campesterol represented the major oxyphytosterols detected (45).

While systematic analysis and characterization of these compounds are still missing, oxyphytosterols were already recognized to exert cytotoxicity when present in relatively high amounts in the diet (42, 45). Consequently, they in principle could affect the enteric absorption of those medicines that are taken up by the intestinal epithelial layer, if some cells of this layer are irreversibly damaged by phytosterol oxides. Further, one should expect that oxyphytosterol-epoxides, like oxysterol-epoxides could lead to stable sterylation of proteins, possibly including multidrug transporters. Indeed, protein sterylation by oxysterols and oxyphytosterols appears to be a very interesting emerging issue that deserves to be elucidated soon.

As regards the possible toxicity of oxysterols and oxyphytosterols stemming from thermal processing of food, the actual extent of it might be modulated by the adopted diet. For instance, many representative compounds of the Mediterranean diet, like tocopherols, fatty acids, polyphenols, argan and olive oils, different cytotoxic effects of 7βOHC and 7KC result to be quenched (46, 47).

Not only deep-fat frying, but also, while in a relatively less amount, air frying, barbecuing and grilling give rise to other harmful compounds, in particular acrylamide, polyciclic hydrocarbons, namely benzo[a]pyrene, benzo[a]anthracene, benzo[b]fluoranthene, chrysene, and heterocyclic amines (48, 49). Notably, all these compounds are metabolized by various hemoproteins of the cytochrome P450 (CYP) superfamily, and induce their own metabolism, as they are potent inducers of CYP enzymes (50, 51). Since several components of the CYP superfamily are involved in the metabolism and biotransformation of a great number of drugs, a possible interference by the aforementioned classes of side-products of thermal processing of food appears very likely, even if specific proofs are not available yet in the literature.

Figure 1 depicts the various mechanisms by which thermal processing of food may interact and affect the pharmaceutical action of several drugs, that is interfering with their intestinal uptake, both directly, by inhibition of or competition with the gut multidrug transporters and indirectly, by damaging the epithelial cells and the intercellular junction molecules of the intestinal barrier, and by affecting drug metabolism.

The heat-mediated oxidation of food may produce elevated amounts of electrophilic compounds, such as aldehydes and epoxides, ready to make irreversible adducts with nucleophilic, i.e., polar drugs, like some antibiotics and antiviral active compounds, by this way most likely altering their pharmacokinetics. On the other hand, the intestinal absorption of the numerous electrophilic drugs is mainly regulated by uptake transporters and export proteins expressed on the plasma membranes of the gut epithelial lining (52), susceptible to the attack by aldehydes and epoxides stemming from heat processed food. Not least of all, several harmful byproducts that could arise from heated food may quench the pharmacological effects of drugs metabolized by CYP enzymes.

A typical example of the effect of nonthermal minimally processed food is highlighted when comparing the in vitro bioavailability of isoflavones from soymilk-based beverages, high-pressure processing (HPP) (400–600 MPa, holding times from 1.5 to 6 min), pulsed electric field (PEF) (35 kV cm⁻¹) and typical regular thermal treatment (TT) (90°C for 1 min). The isoflavones concentration was found to be higher in HPP-treated samples (38.5%) whereas, in TT and PEF products, the range was significantly lower (25–26%) (69). These data highlight that processing plays a pivotal role in the bioavailability of isoflavones as well as many other active compounds.

It is known that flavonoids contained in grapefruit juice, such as naringinin and hesperidin, are responsible for the inhibition of transmembrane transporters, which play a role in the passage of several drugs from the intestinal lumen within the bloodstream (3). Thus, it clearly indicates that processing could have a significant potential interaction with drugs. As HPP orange and grapefruit juice are becoming quite popular currently, consumers are exposed to various levels of active compounds, such as relatively high concentrations of certain flavonoids. For instance, it was reported that the coadministration of drugs such as acebutolol, celiprolol or fexofenadine with grapefruit juice, or atenolol, ciprofloxacin, and fexofenadine with orange juice, decrease the oral bioavailability of antihypertensive, antibiotic and anti-histaminergic drugs (3, 70). In particular, the grapefruit juice can block the action of intestinal CYP3A4, the amount of which varies from person to person in the small intestine, so grapefruit juice may affect people differently even when they take the same drug. Besides the possible interference with drug metabolism, grapefruit juice can affect drug transporters proteins and the final result is that less drug enters the blood.

Besides grapefruit juice, Ginkgo biloba, an important herbal compound and a dietary supplement, has actually been proven to interfere with the effectiveness of some medications (71). Ginkgo biloba is used to improve brain performance and reduce fatigue (3). It is also commonly utilized by people experiencing cognitive decline; healthy adults seeking to improve performance or prevent a decline; and elite performers seeking to optimize their cognitive performance (72). The substances contained in the Ginkgo biloba that have pharmacological properties are flavonoids and triterpene lactones (gingkoloids and bilobalids). As a result, Gingko biloba is able to reduce platelet aggregation, and acts on the CPY2C9 and CYP3A4 isoenzymes, inhibiting the microsomal metabolism of warfarin (3). Therefore, herbal preparations containing Ginkgo biloba should be avoided in patients treated with antiplatelet or anticoagulant drugs (73). It should be also noted that products that are HPP-treated and contain ginkgo seed protein (GSP) showed markedly improved heat stability and emulsifying properties compared to the untreated GSP (74) and consequently may interfere with the effectiveness of some medications as aforementioned.

Another common nonthermal processing is high-pressure homogenization (HPH), that combines, in addition to high pressure action, some other physical effects (e.g., cavitation, shear stress, turbulence). Like HPH, microfluidization (MF) is a method used for production of micro and nanoscale size materials. It is commonly used both in pharmaceutical and food industry to make liposomal products, emulsion and to produce dairy products. Both processes could affect bioavailability of some active food compounds. For instance, HPH and MF processes were utilized in the emulsification of krill oil. Emulsions produced through MF exhibited several noteworthy advantages over those generated by HPH. Most prominently, MF-prepared emulsions featured smaller and more uniformly distributed particles, in stark contrast to the less uniform particles generated by HPH. Moreover, MF-based emulsions demonstrated significantly enhanced oxidative stability during storage. Astaxanthin degradation occurred at a substantially lower rate (38.1 and 89.4% for HPH and MF, respectively) (75). In in vitro simulated digestion, MF formulations exhibited superior stability and markedly higher bioaccessibility of food active components in comparison to their HPH counterparts. Significant increase in the release of free fatty acids was observed during the intestinal phase of digestion in MF emulsions, indicating an improved lipid digestion process (75). These findings highlight significant differences for ω-3 fatty acids, that can interact with blood thinning drugs and could have possible adverse effects, or determine therapeutic failure.

PEF deserves a closer look due to its unique capabilities as highlighted in the study of clinical applications and immunological aspects of electroporation-based therapies, food and medicine (76, 77). Consequently, PEF treatment is considered to be a promising technology that has in the last years received considerable attention in food and biotechnology related applications (78).

PEF impact causes membrane permeabilization, a process termed as electroporation (EP), and leads to an increased permeability of the membrane to ions and molecules (79). Depending on the intensity of the treatment applied (e.g., external electric field, single pulse duration, treatment time) and the cell characteristics (e.g., size, shape, orientation in the electric field), the viability of the electroporated cell can be preserved by recovering the membrane integrity (reversable permeability, REP). Conversely, EP can permanently lead to cell death (irreversible permeability, IRP). REP is a procedure commonly used in molecular biology and clinical biotechnological applications in vivo to gain access to the cell cytoplasm in order to introduce or deliver drugs (e.g., oligonucleotides, antibodies, plasmids) (78, 80). Most of food and biotechnology related applications of PEF are based on irreversible permeabilization of the cell membranes and mainly include “cold” pasteurization of liquid foods and disinfection of wastewater by means of microbial inactivation (78).

Typical applications of PEF technology in food processing include extended shelf life (81): 1. Apple juice; 2. Orange juice; 3. Milk; 4. Liquid egg processing (in combination with adopting a hurdle strategy); 5. Processing of green pea soup. Other applications include: Beer (inactivation and sublethal impairment of Lactobacillus plantarum a microorganism that can spoil beer). Most recent utilization of PEF includes (82): 1, Pineapple juice and coconut milk mixture; 2. Red wine; 3. Milk; and 4. Human milk (i.e., processing conditions were optimized to reduce bacterial counts in donor human milk, and to evaluate its effect on the bioactive proteins). Extraction of bioactive compounds in food using PEF processing is also a very common approach.

Nanosecond PEF (nsPEF) processed milk retaining over 60% of lysozyme, lactoperoxidase and lactoferrin, and 100% retention of xanthine oxidase and immunoglobulin A was reported. Additionally, the loss of milk proteins was smaller for samples treated with nsPEF (e.g., high voltage, high intensity pulses are used, with durations of 10–300 ns and electric fields of ~10 kV/cm to 300 kV/cm) in comparison with typical regular pasteurization process. These data indicated that nsPEF is a promising novel pasteurization method (83). However, the application of PEF to solid foods is much more difficult, mainly because microbial inactivation in this case is relatively unrealistic (82).

Despite many scientific studies on the principles and applications of PEF technology published to date, and the fact that PEF was introduced into the food industry many years ago, this technology is still considered as an emerging one. In the European Union there is no special legislation on food processed with PEF. In general, the use of this technique is coordinated by the Novel Food Regulation (EU) 2015/2283,¹ but implementation of PEF into production does not automatically mean that the food becomes “novel” (84). Novel food acknowledgement should be closely considered and evaluated when a new technology is to be implemented.

Although electroporation (EP) and electropermeabilization (EPP) are frequently used as synonyms, EP is related strictly to the aqueous pores formed in the lipid membranes of the cells, while EPP is related to all the events involved in the membrane permeabilization process, including modulation of membrane channels, cellular biophysical and biochemical changes (77). In medicine, EP is a platform technology for drug and gene delivery. When applied to cell in vitro or tissues in vivo, it leads to an increase in membrane permeability for molecules which otherwise cannot enter the cell (e.g., siRNA, plasmid DNA, and some chemotherapeutic drugs) (85). In oncology, reversible electropermeabilization (REPP) is applied for the intracellular transport of chemotherapeutic drugs as well as the delivery of genetic material in gene therapies and vaccinations. The physical changes of the membrane and the immunological aspects involved in electrochemotherapy and gene electrotransfer, were recently reviewed for two important EP-based cancer therapies in human and veterinary oncology (77). The two widely used chemotherapeutic drugs are bleomycin, a chemotherapy agent employed to treat various malignancies, including head and neck malignancy, lymphoma, and testicular tumors, among others,² and cisplatin, a chemotherapy drug used to treat testicular, ovarian, bladder, head and neck, lung and cervical cancer, among others.³

Delivery of therapeutics using synthetic polymers is challenging due to toxicity, immunogenicity and impaired bioavailability following administration of the latter compounds. However, natural polymers are being explored as safe for their use as a substitute for synthetic polymers. Derivatization of starches has the potential to achieve desired properties (e.g., improved solubility, stability, bioavailability) of an incorporated drug and lower-down induced toxicities. Starch structure and chemical modification methods integrating aspects of its use in developing drug delivery devices like tablets, hydrogel, and patches were described and may be applied as a reference for future chemically modified starch as excipient in drug carrier studies (107).

The consumption of specific carotenoids has been associated with reduced risks of contracting a number of chronic conditions. Extrinsic factors affecting carotenoid bioavailability include food-based factors, such as co-consumed lipid, food processing, and molecular structure, as well as environmental factors, such as interactions with prescription drugs, smoking, or alcohol consumption (108). Carotenoid bioavailability varies with different food cooking and processing procedures as well as with the amounts of dietary fat, fiber, and competing compounds present in the meal (109). Upon ingestion, carotenoids are released from the food matrix and are emulsified with fat and incorporated into lipid micelles in the small intestine for absorption by intestinal enterocytes. Once thought to be taken up strictly via passive diffusion, carotenoid absorption is facilitated via membrane proteins (109). Cooking, heating, or mechanical or enzymatic processing may also increase carotenoids accessibility by softening the tissue matrix (110). Another example is pasteurization shown to increase bioavailability of processed juice compared with its fresh counterpart (111).

Nanoparticles have unique biological properties which can be used for detection, prevention, and treatment of diseases, such as cancer, pulmonary diseases, etc. and for drug delivery and gene therapy as well (112–114). Nanomaterials can be created in one (nanoscale), two (nanowires and nanotubes), or three dimensions (nanoparticles) (115). Nanoparticles are a particular type of nanomaterial that can occur naturally, be created using unintentionally, or indeed be engineered on purpose (112). Numerous processing technique could be utilized to produce typical nanoparticles that could include liposomes polymer-drug conjugates, etc. To date, the utilization of food processing for the creation of nanoparticles faces some key issues and hurdles such as the need to use economical processing techniques to make edible delivery systems while also ensuring that they are safe and palatable for human consumption (116).

Whilst nanotechnology applications have been planned for a variety of benefits in the agri/food/feed chain, the use of materials that contain nanoscale particles has also raised concerns over their potential adverse effects on consumers’ health (117). Therefore, safety is of primary concern and should be carefully considered before nanoparticles could be used in foods.

A recent review focused the attention on the recent new interest in developing biomimetic plant foods (BPFs), considering the likely disassembly that plant food structures undergo during processing first, then during digestion in the human gastrointestinal tract (GI) (118). A deep insight into these modifications of the original plant food structure is needed in a way to properly design future nature-inspired food structures that could indeed safely contribute to health and well-being (118).

A recent and typical example of biomimetic is represented by the naringenin-loaded macrophage membrane-coated liposome-based nanoparticles. They are provided with distinct physicochemical compositions and biological attributes to improve the bioavailability of the carried drug specifically at the target site. The developed biomimetic nanoparticle (BNP) has shown good biocompatibility, stability, satisfactory particle size, pH-responsive drug (naringenin) release kinetics, and higher cellular uptake in vitro (119). Yet another study showed that oral supplementation of vegan collagen biomimetic has beneficial effects on human skin physiology (120). Biomimetics will most likely have a pivotal interaction with delivery of food components and drugs.

A reduced intake of sodium is often recommended for therapeutic reasons, especially in elderly, as mentioned before, but to deliver reduced-salt products through a process that would not affect their physicochemical and sensory and hedonic attributes, as it often happens with NaCl salt replacers, indeed represents a big challenge for food industry (121). In relation to this task, it is noteworthy to mention some successful results achieved through the adoption of defined procedures of non-thermal processing. For instance, the fruitful application of PEF in reducing NaCl content in the preparation of jerky beef has been very recently described. PEF treatment (0.52 kV/cm, 10 kV, 20 Hz, 20 μs) applied to jerky beef test samples allowed to diminish the product’s sodium content by 34% as to untreated identical meat samples, fully preserving the main characteristics and the overall acceptability of the controls (122).

At present, more reports are available as far as the HPP of food is concerned, experimentally shown to be both a direct salt reducing procedure and a technology able to enhance the safety of sodium reduced meat products. HPP (treatment at 150 MPa for 5 min) of pork meat before manufacturing breakfast sausages with a reduced salt concentration, was shown to allow salt lowering up to 1.5% without affecting the main quality features of the sausages themselves but actually minimizing the typical cooking loss of the non-HPP treated products (123). A marked prevention of cooking loss was observed in the production of ready-to-eat chicken breasts undergoing a partial substitution of NaCl with KCl, when HPP was applied for 5 min after tumbling (300 MPa) and for 3 min to the final product (600 MPa). Moreover, such a treatment allowed to maintain the physicochemical features and the sensory attributes of the food product and even improved its microbiological quality in comparison to identically processed but HPP untreated chicken breasts. Notably, while the affordable NaCl reduction with the standard non-HPP procedure was of about 25%, that achieved by HPP treatment was 50% (124).

A similar result was reported for a further type of food, namely cooked fish batter, in which a reduction by 25% of NaCl concentration was achieved through the application of HPP (300 MPa for 5 min at 25°C) (125). Just one more example that pointed out the possible adoption of this non-thermal processing to downsize sodium amount in meat, a food in which this chemical element is anyway essential to guarantee texture, microbiological safety and suitable shelf-life [see for a specific review (126)].

A clear example of food processing that in some way facilitates a clinically effective intake of drugs is represented by the iodization of salt as the best method of hypothyroidism prophylaxis. Iodine is necessary for thyroid hormone production and its deficiency causes mental retardation, short stature, goiter and an increased risk of death in childhood in developing countries (e.g., iodization of salt increased the survival and birthweight in some African countries). In developed countries iodine sufficiency is attained by iodization of salt and by the introduction of iodine in food processing (e.g., the use of iodine as a bread stabilizer). In regions where iodine deficiency is prevalent, iodine supplementation or iodized salt is often used to prevent hypothyroidism (127).

However, in areas with sufficient iodine in the diet, excessive iodine intake can also be a concern and may contribute to thyroid dysfunction. Patients who are taking drugs like levothyroxine to treat hypothyroidism, or propylthiouracil and methimazole to treat hyperthyroidism, or undertaking radioactive iodine therapy, must be warned of the potential drugs’ side effects due to the presence of iodine in foods.