In a broad terms there are three stages to the application of the NACCP process:
-
Stage 1 is the application of NACCP for quality principles.
-
Stage 2 is the application of NACCP for health principals.
-
Stage 3 is the implementation of NACCP process.
Each of these stages will be considered in the context of making NACCP really work in practice.
Stage 1- Application of NACCP for quality principles
To maintain nutritional quality it is necessary to act on all aspects of the food supply chain. The NACCP process, through the tracing of a nutritional biomarker, represents the conceptual and scientific evolution of the HACCP system, with nutritional quality of food in mind and the consumer’s health status as its main objective [17,18] (Figure 1).
Behind the NACCP process, there are four general principles in order to ensure: i) health maintenance; ii) nutritional quality assurance; iii) correct information for the consumers; iv) ethical profit (Figure 2).
Before food arrives on the table, it must follow a path along which it undergoes many transformations, which may lead to depletion of the nutrient content thus rendering it irrelevant at the health level. At present, therefore, the main objective is to be able to trace not only the food, but the nutrient of interest, which must be kept intact along the entire production chain to guarantee a real health benefit to the consumer (Figure 3).
On the other hand, it is important to guarantee the quality of those foods such as fruit, vegetables, fish and meat that have not undergone industrial transformation, in order to provide a health-giving product to the consumer without causing harm.
Stage 2- Application of NACCP for health principles
As highlighted in Figure 4, the actions of the NACCP process are envisaged to ensure high quality, nutritional food for the maintenance of good health through the prevention of CNCDs.
To make NACCP work in practice, the following actions must be adhered to: 1) identification of the nutritional marker (macronutrient, micronutrient, mineral salts, vitamins, antioxidants, dietary fiber), which must remain unchanged throughout the chain of production; 2) identification of critical control points of the food chain (area of production, technologies of cultivation and breeding, processing, heat treatment, transport, distribution and administration), which must be regulated in order to minimize the likelihood of a reduction in quality; 3) establishment, within the critical control points, of critical limits to maintain adequate levels of nutrient; 4) establishment, and implementation of effective monitoring procedures of critical control points; 5) establishment of the corrective actions to be taken when the monitoring indicates a non-conformity of a critical point; 6) identification of metabolic biomarkers; 7) evaluation of the effects of food intake, through the application of specific clinical trials; 8) establishment of procedures regarding consumer information; 9) implementation of the Health claim Regulation EU 1924/2006; 10) starting a training program.
The biological validity of the nutrient must be maintained throughout all the cited steps so that the food reaching the end consumer is both safe and physiologically significant. While the first five actions of the NACCP process have an ameliorative and preparatory function, for the nutritional quality maintenance of the food, the six and seven actions identify a biomarkers which allow future examination of the effect of a single nutrient on the consumer’s health, the last three actions aimed to educate and inform.
The NACCP process actions are described as follows:
Conformation with all steps of food supply chain should preserve the quality and amount of a selected nutrient. Nutrients, as well as ensuring the vitality of metabolic functions, affect the enzymes involved in physiological processes, effectively determining whether health is good or bad. According to Regulation CE 178/2002 a nutrient can be found into the following categories: i) nutrient: a food constituent in a form and at a level that helps support life; ii) dietary supplement: a product that contains one or more of the following dietary ingredients: vitamin, mineral, amino acid (protein) and also includes concentrates, constituents, extracts or metabolites of those compounds; iii) a nutraceutical: any nontoxic food component that has scientifically proven health benefits, including disease treatment and prevention.
Young defined a nutrient as “a fully characterized (physical, chemical, physiological) constituent of a diet, that serves as a significant energy yielding substrate, or a precursor for the synthesis of macromolecules or of other components needed for normal cell differentiation, growth, renewal, repair, defense and/or maintenance or a required signaling molecule, cofactor or determinant of normal molecular structure/function and/or promoter of cell and organ integrity” [19]. Therefore some functions of a nutrient can be those of signaling molecules [20] and substrate for macromolecules [21-23]. The nutrient can also modify molecular structures and promote assembly of mechanistic structures.
Food is more than metabolic fuel. There is good evidence that nutrients influence gene expression and there is an interdependence of morphologic expression of an organism with its genetic sequence and to its surrounding environment, including diet and life-style. Nevertheless, metabolism is dynamic and it changes in relation to the variations determined by environmental factors [24].
Selection of a nutritional biomarker with a potentially beneficial effect on the consumer’s health and the determination of its bioavailability appear to be of primary interest in the evaluation of the function and the effects arising from the consumption of a nutrient [25].
For the selection of a nutritional biomarker it is important to keep in mind:
-
1)
viability of identification, quantification and tracing of a selected nutritional biomarker. Moreover, the nutritional biomarker must remain intact throughout the entire food supply chain. Cellular events can modify response to bioactive food components (BFC), and on the other hand BFC can modify cellular events. This defines real nutritional homeostasis [26];
-
2)
execution of physical-chemical and qualitative (bromatological and microbiologcal) analysis to ensure that food contains the specific nutrient biomarker that interacts in a specific salutary way on the physiological functions of the organism;
-
3)
demonstration that the nutrient could determine a disease state, and may be toxic over an established threshold level [19,27]. Therefore, to prevent that nutrient becoming harmful to health awareness of its unique chemical structure and the dose to be administered is necessary. The analytical evaluations include: i) chemical characteristics: data relating to the chemical-nutritional food properties such as macro and micronutrients, minerals, fiber, vitamins, antioxidants during the processing stages; ii) physical characteristics: data relating to processes, such as any heat processing, pasteurization, killing organisms during thermal maturation and ripening; iii) microbiological characteristics: data on food symbiotic microorganisms, or probiotics that confer special properties (presence of particular strains of lactic acid-bacteria or molds and yeasts in dairy products).
Over the years, several scientific and technical recognitions have been instrumental in developing and forming principles and techniques to achieve acceptable food safety in certain conditions. According to Raspor [24], today the principal aim of food safety is to guarantee consumer’s health, through the absence of chemical, physical and biological contamination in food. For example, with regard to genetic toxicology, basic foodstuffs have generally been considered safe, but questions of safety, and particularly of the long-term effects of ingesting mutagenic/carcinogenic substances in food, have arisen with the development of food processing and the use of chemicals to improve the quality, palatability and shelf-life of food products. The intake of mutagens in the regular diet may exceed by far the amount taken in from industrial sources. The human population consumes about 10 tons (dry weight) of food by the age of 50 [28]. Food-related genotoxins are important because of the extent of the population exposed and because habit or custom leads to the frequent intake of certain foods. In vitro short-term mutagenicity assays have revealed that a number of naturally occurring constituents of foods and of compounds formed during processing are mutagenic [29]. Flavonoids, furans and some mycotoxins are among the naturally occurring constituents that have been shown to be mutagenic. Mutagens have also been found in certain classes of food and environmental contaminants (e.g. pesticides, packaging components, solvents) and additives (e.g. some colorings and flavorings) and among products formed during heating, irradiation, smoking, curing, solvent extraction, fumigation and storage. Ideally, testing for possible mutagenic effects requires in vivo studies, but at the present time, in vitro tests provide the only practical means of screening for mutagens in the large variety of food consumed and of studying factors that modify the mutagenic activity of food constituents. Such tests may also be used to assess how food processing methods may be modified to reduce the generation of mutagens.
Human’s food is obtained from a large number of sources and species and is characterized by its great variety. Before it is consumed it is subjected to various treatments. The toxicology of food is, thus, a complex problem. Society has recognized for generations that certain potential foodstuffs, such as some plants and fishes, are acutely toxic and social taboos prevent their consumption. However, acute toxic incidents cannot be relied upon to discourage the ingestion of food containing genetic toxins, since the latent period of the genetic effect may be prolonged, possibly stretching over several generations.
The HACCP system represents the most intelligible example of this development [30]. The application of all seven principles: i. Conduct to hazard analysis; ii. Identify critical control point; iii. Establish critical limits; iv. Monitor CCP; v. Establish corrective action; vi. Verification System; vii. Record keeping, is a prerequisite for the success of the NACCP process.
Each step of the food supply chain has its own HACCP system distinct from prior and subsequent steps. In order to tackle the existing barriers in implementing and maintaining food safety system [31,32], it is necessary to unify total quality management, through compliance with good manufacturing practice. A critical control point, is represented by each step of food chain and it should be considerate a point in which nutritional biomarker can be reduced. Moreover, for every single step or sub-process of the food chain, a hazard analysis has to be performed [33].
It is important to identify a measurable metabolic biomarker that is modulated in some way by the nutrient, and that reflects the nutritional effects of the “active” ingredient, or combination of food ingredients. Specific metabolic biomarkers, defined as molecules or groups of molecules whose simple presence is an indicator of a problem, state or condition, are required to understand the threshold value and eventually evaluate an excess (or deficit) of nutrient metabolism products. Since a single metabolic biomarker is often insufficient for assessment of metabolic disease, measurement of amounts of specific metabolic intermediates are frequently needed [27,34].
Since imbalances between the concentrations of metabolites, and not the appearance or disappearance of any single intermediate, forms the basis for metabolic disease, only quantitative and comprehensive metabolite measurements can identify metabolic imbalance [27].
An ideal metabolic biomarker: i) should respond sensitively, specifically and predictably to changes in the concentration and/or supply of the micronutrient; ii) should be amenable to objective and reproducible measurement both of form and quantity which should reliably reflect a change in the target tissue that has a direct effect on health; iii) should be in a measurable dose–response relationship [35].
The chief classes of metabolic biomarkers are: i) cholesterol, high-and low-density lipoproteins (HDL, LDL), oxidized LDL, triglycerides; ii) transaminases, glucose, and insulin; iii) homocysteine, fibrinogen, C-reactive protein, erythrocyte sedimentation rate, and proinflammatory cytokines; iv) albumin, prealbumin, and retinol binding protein.
Due to the innate complexity of human biology, compounded by a myriad of social and environmental factors that are crucial determinates of health, we propose experimental systemic approaches which permit integration of diverse data types to create an actionable model to verify the effects of foods. In fact, a modern approach to medicine and health requires that enormous amounts of information, such as social, medical, clinical, molecular, cellular, genetic, demographic, and environmental data, need be deciphered and integrated into a model that includes network interactions and integrations at many levels, relaying relevant biological and environmental information [36].
The analyses for investigating the effect of food must be conducted at various levels to identify the degree of interaction of the nutrient with the human body and its possible effects.
We define three levels of diagnostic investigation to verify any nutritional effects.
-
1)
Assessment of nutritional status by: a) family and individual history-taking; b) anthropometry (weight, height, circumferences, skinfolds); c) body composition analysis: determination of water compartments, such as Total Body Water (TBW), Extra Cellular Water (ECW), Intra Cellular Water (ICW), Body Cellular Mass (BCM), Body Cellular Mass Index (BCMI); Evaluation of lean body mass, fat and bone mineralization; d) Nutritional survey of dietary habits (Indali, Simplified Nutritional Appetite Questionnaire, i.e. SNAQ questionnaire); e) Functional evaluation: measurement of blood pressure and heart rate; assessment of physical activity (motor questionnaire, tests of strength and muscle power); assessment of quality of life (questionnaire of quality of life);
-
2)
Clinical and biochemical assessment: lipid profile, carbohydrate profile, liver profile, oxidative and inflammatory profile. Evaluation of inflammation and oxidative stress markers of DNA damage, oxidative stress marker, damage to lipids, inflammatory profile, etc. by using innovative analytical techniques (microarrays, real time PCR).
-
3)
Nutrigenetic and nutrigenomic assessment. As gene activation may be the result of various combinations of lifestyle and genetic factors, it is necessary to evaluate and manage both types of information. Moreover, given that significant evidence exists demonstrating the influence of genetic variation on dietary responses in human, an option in diseases prevention may be to use nutritional agents to modulate the biological results stemming from genetic variation [37]. In fact, many nutrients selectively alter gene expression through transcription factor systems that regulate the activation of specific sets of genes in different tissues and under different environmental conditions. Various nutrients bind to or in some way directly activate specific transcription factors and other nutrients alter the oxidation reduction status of the cell to indirectly influence transcription factor activity [38,39].
According to this evidence, practical application of nutrigenomics requires:
-
1.
identification of the genes and proteins expressed differentially in health and disease that are modifiable by nutrients;
-
2.
identification of genes, proteins, and metabolites that are influenced by specific nutrients known to be beneficial or harmful;
-
3.
identification of genetic variations that alter the nutrient– gene interactions in applications 1 and 2.
Subsequent nutritional interventions may help detect changes in gene expression related to intake of a particular food. Up-regulation or down-regulation of each gene in relation to baseline can then be determined, in relation to all administered interventions.
The three levels of diagnostic investigation can be grouped by macro-ranging biomedical analysis to analyze individual physiological aspects and analyzed together to formulate a grade of interaction (GI) of the nutrient.
We have defined the degree of interaction as “effective nutraceutical food”, evaluated through the different levels of biomedical analysis.
There is general consensus among scientists, consumers, authorities as well as industry that health claims on (functional) foods must be scientifically substantiated. This is in the interest of all stakeholders and contributes to fair trade. Several important developments have been made within the European Union; these cover scientific as well as regulatory aspects.
Food products that boast nutrition and health-promoting properties are becoming increasingly popular in the EU market. A nutrition claim states or implies that a food has beneficial nutritional properties such as “low fat”, “no added sugar” or “high in fiber”. Any statement given on the label, or used for advertising or commercial purposes, whereby the consumption of a particular food can be beneficial to health, is considered a health claim, such as claims that a food can help to strengthen the body’s natural defenses or improve learning ability [40].
Nutrient profiling is the classification of foods for specific purposes based on their nutrient composition. The establishment of nutrient profiles is essentially a way of classifying foods based on their nutrient content to determine the permissibility of a food to bear a claim. They are intended to prevent claims from masking the overall nutritional profile of a food and should be based on generally accepted scientific evidence relative to the relationship between diet and health. On request from the European Commission, who has the body responsible for their establishment, EFSA has provided scientific guidance on the setting of nutrient profiles within the context of the regulations taking into account the role of food groups within the diet [41]. The two key objectives of the claim are: i) to ensure that consumers are not misled with regard to claims made on or about food; ii) to facilitate cross-border trade within the EU. Nutrition claims impart information regarding the amounts of energy, nutrients and/or other substances.
In the same way as the evaluation of the effect of nutrition on the final consumer is the main goal of the whole system, so too is the proposal of a nutritional claim. The ability to verify the effect of the food and then the nutritional biomarker on human health, may allow the formulation of nutrition labeling as required by EC Regulation 1924/2006. As regards to the regulatory aspects, in December 2006 the EU adopted Regulation 1924/2006 on nutrition and health claims made on foods [Reg. EC 1924/2006]. The general objective of Regulation 1924/2006 is to harmonize the national rules on nutrition and health claims. Nutrition claims are claims that state, suggest or imply that a food has particular beneficial nutritional properties due to the energy it provides or the nutrients it contains [42]. The regulation lays down further restrictions on the use of nutrition and health claims through nutrient profiling. However, according to a recent publication, most proposed nutrition and health claims were negatively assessed by the European Food Safety Authority (EFSA), based on the quality of scientific substantiation, due to usage of scientific methods on which no consensus has been reached and the differences in expectations and requirements [43].
A nutrition claim states or implies that a food has beneficial nutritional properties. Foods with health claims may have an impact on dietary behavior; adoption of nutrient profiles might also stimulate the development of products with an improved nutritional composition by the food industry and as such food reformulation can contribute to public health [5].
One of the actions that are necessary for the success of the process is undoubtedly the organization of a trained team of experts capable of initiating and implementing NACCP. A successful NACCP team must have a clear understanding of the importance of identifying both the hazards and nutritional biomarkers, as well as the critical point that require monitoring. Therefore, the selection of a quality team member should be based on knowledge of raw material, products, processes, hazards, molecular biology, food chemistry, nutritional quality, clinical nutrition. The team must be prepared with in-depth training in the principles of NACCP and of the special skills and topics which underlie the application of these principles. It is necessary that the team has a complete knowledge of the NACCP vision, and has a precise understanding of the the initial actions to undertake as well as a clear perception of the end result.
Stage 3- Implementation of NACCP process
The production of each food can be controlled throughout the NACCP procedure, but not all foods have the same degree of interaction with the human body, which ensure beneficial effects on human health or prevent certain types of diseases.
Corresponding with this vision for nutritional safety, every step can be linked to create a unique good practice approach, called Good Nutritional Practices (GNP). In the NACCP system, the GNP are the critical control points, because the adherence to good practice at every single step of the food production process guarantees the presence of nutritional biomarkers and therefore total nutritional quality.
As described by Raspor [33], good practices concern: i) agriculture: as agronomic cultivars; the conditions for the growth and reproduction of the plant for the uptake of nutrients from the soil; the type of fertilizer needed for the development of plants; cultivation techniques (conventional, organic, biodynamic, homeodynamic); animal breeds and any mutations that can produce specific phenotypic characteristics; clinical and veterinary health status of animal; genetic and growth capacity; type of relaying; type of power supply. ii) environment: such as climatic and chemical conditions of the soil; iii) manufacturing-retail: the techniques of food processing represent important steps in the food production chain, since during processing, a large quantity of nutrients or other substances with potential beneficial effects on human health may be lost; iv) laboratory: such as qualitative systems governing organizational process, monitoring, recording and reporting; v) hygiene: such as practical procedures that return the processing environment to its original condition (disinfection or sanitation programs) and maintain food in optimal storage conditions; vi) storage, transport and distribution: these are of the utmost importance throughout the process, as all the nutritional characteristics derived from previous phases must be preserved and arrive intact to the consumer; vii) housekeeping: the selection of the principles and techniques of food storage and preparation at home directly carried out by the consumer.
The NACCP process evaluates the risk of loss of the nutritional biomarker as a result of nutritional practices at every step of the food supply chain. To understand in full the possibility of loss of a nutritional biomarker during a particular phase, it is necessary calculate the risk for the event. The criteria of analysis and evaluation are based on objective studies of the critical issues, identified by evaluating the actual likelihood of occurrence of an event directly attributable to the critical issues encountered. This probability is related to the gravity of the damage resulting from the occurrence event.
It is therefore necessary to verify any critical point in primary production, food practices and facilities, storage, retail, distribution and household activities.
If results from the monitoring of critical control points indicate that the process is out of control, corrective actions, tailored to the severity of the risk, have to be undertaken.
Corrective action is necessary when the parameter monitored has exceeded the specified critical point, and moreover demonstrates the likelihood that the quality of food is affected or even lost. Therefore, it is necessary to implement appropriate corrective actions to regain control of the condition and return within threshold values of parameters within which preservation of the nutritional quality of the food is guaranteed.
Corrective actions can be classified into two categories: i) preventive actions; ii) controls identifying finished products not meeting the terms of nutritional quality.
Only when all the critical points of the process will be under control it will be possible start to the assessment of the nutrient health effects through actions n. 6 and 7 described in the Stage 2.