Up today nutrition science, in Western countries, has been mainly experimented according to the reductionist paradigm. Reductionism is based on the assumption that since reality is too complex to be studied as such it needs to be fragmented into isolated entities that are studied according to the view that the whole is equal to the sum of the part (2 = 1+1) on the basis of a linear cause-effect relationship. As a result foods are considered as only sums of nutrients and calories ; and one nutrient is generally associated with one deregulated metabolism then one chronic disease (e.g., relationship between saturated fats, dyslipidemia and atherosclerosis whereas it is a reducing association). Reductionism can be considered as the main deep cause at the roots of diet-related chronic diseases that are encountered in populations consuming the most fractionated/recombined and refined ultra-processed foods, the ultimate consequence of reductionism. Indeed, if foods are only sums of nutrients why not cracking them in a multitude of nutrients and to recombine them. Nutritional supplements, functional foods and ultra-processed foods are therefore the consequences of our modern reductionist science. They are also based on the assumption that food health potential is based on its composition only. On the contrary, holism views whole foods as more than a sum of nutrients because of synergy of action of nutrients and food matrix effect. Holistic nutrition science defines food health potential as combination of both matrix and compositional effects. Food is more than the only sum of nutrients (2 > 1+1). Matrix effect is crucial because it impacts satiety potential and nutrient bioavailability, both playing a crucial role to maintain a good health. Therefore two foods of identical composition but with a different matrix have not the same health potential. Therefore to fight against the increasing prevalence of diet-related chronic diseases we need today to base more nutrition science on the holistic paradigm. Whereas recombined/refined ultra-processed foods are the fruit of reductionism whole and complex foods participate more of the holistic paradigm which should encourage technologists to less process foods to preserve their matrix, and public authorities to lay emphasis on minimally-processed foods as a basis of a healthy diet. In addition to food science and technology the holistic paradigm may find other important applications in the study of diets on human health. Randomized controlled studies are coming from reductionist and pharmacologist designs, very far from real life, and cannot yield long-term and effective applicable results. Nutrition science is not pharmacology and foods are not drugs: therefore application of holism should prompt nutritionists to carry out intervention studies in complex real life conditions (taking into account all aspects of dietary lifestyles), and not to control only one