Nutritional Deficiencies Associated with Obesity: Comparison
Please note this is a comparison between Version 2 by Beatrix Zheng and Version 1 by Carlos Esteban Guardiola Marquez.

Obesity is a critical medical condition worldwide that is increasingly involved with nutritional derangements associated with micronutrient deficiencies, including iron, zinc, calcium, magnesium, selenium, and vitamins A, C, D, and E. Nutritional deficiencies in obesity are mainly caused by poor-quality diets, higher nutrient requirements, alterations in micronutrient metabolism, and invasive obesity treatments. The current conventional agricultural system is designed for intensive food production, focusing on food quantity rather than food quality, consuming excessive agricultural inputs, and producing nutrient-deficient foods, thus generating severe health and environmental problems; agricultural food products may worsen obesity-related malnutrition. Therefore, modern agriculture is adopting new biofortification technologies to combat micronutrient deficiencies and improve agricultural productivity and sustainability.

  • agri-food systems
  • beneficial soil microorganisms
  • biofertilization
  • micronutrients
  • nanofertilization
  • obesity
  • malnutrition

1. Introduction

Obesity is a highly prevalent chronic medical condition characterized by the excessive or abnormal accumulation of body fat (adiposity) resulting from an imbalance between the energy consumed and the energy expended [1,2,3,4,5,6][1][2][3][4][5][6]. It is defined with a body mass index (BMI), estimated as weight/height2 (kg/m2), of 30 kg/m2 or above, and is associated with serious negative implications on human health and quality of life; in particular, excess body fat has been shown to negatively affect the metabolism of micronutrients in obese patients. In addition, obese individuals are susceptible to nutritional derangements because their diet is mainly based on inexpensive, energy-dense, and low-micronutrient quality foods [2,7,8][2][7][8]. Obese people are now facing a complex nutritional challenge characterized by the coexistence of under- and overnutrition. This concept has been recently defined as a “double burden of malnutrition”, involving an excessive consumption of calories associated with a shortage of certain microelements [5,9,10][5][9][10]. Several studies have reported a direct and clear link between obesity and various micronutrient deficiencies, including iron, zinc, magnesium, potassium, selenium, and vitamins A, C, E, and D [2,6,11,12,13][2][6][11][12][13]. These deficiencies can aggravate the obese phenotype and promote the development of comorbidities. For instance, vitamin A and C inadequacies correlate with leptin concentrations and elevated adipogenesis and fat deposition [2,13,14][2][13][14].
In addition to bad dietary choices and alterations in the metabolism of nutrients as causes of obesity-related micronutrient deficiencies, insufficient access to nutrient-rich foods, which is closely related to modern agricultural practices and the current agri-food system, also contributes significantly to the prevalence of these conditions in obese subjects [6,9,14][6][9][14]. However, modern agriculture faces critical challenges in solving health and environmental issues associated with macro and micronutrient deficiencies, food insecurity, low fertilizer-use efficiency, overfertilization, climate change, water scarcity, a reduction in agricultural lands, and soil degradation [15,16,17,18,19,20,21][15][16][17][18][19][20][21]. Long-term effects of modern intensive agronomic practices include significant losses in crop productivity and the nutritional value of agricultural products [17,20,21,22,23,24,25][17][20][21][22][23][24][25].
A sustainable food system provides sufficient, safe, nutritious, accessible, and affordable food to meet current dietary needs while preserving healthy environments and ecosystems that can supply future generations with a minimal negative environmental impact [26,27][26][27]. The agri-food system needs a significant transformation to be environmentally sustainable and productive [27,28][27][28]. Therefore, modern agriculture is adopting new biofortification technologies through fertilization to combat human micronutrient deficiencies and improve agricultural productivity and sustainability [19,29,30,31][19][29][30][31].
Firstly, the use of biofertilizers based on plant-growth-promoting microorganisms (PGPM) is a promising strategy for enhancing plant growth and food quality without environmental contamination; PGPM mobilizes soil nutrients, improves macro- and micronutrient bioavailability, produces plant growth regulators, protects crops from phytopathogens, and improves the soil structure [25]. Microorganism-mediated improvements in plant development are a relevant strategy for promoting the sustainability of the current agri-food system [15,17,20,32][15][17][20][32]. Research should focus on studying native microbial species as these have exhibited more significant benefits on plant growth promotion than non-native or commercial strains [33,34][33][34]. The other strategy is nanofertilization, which consists of applying nanosized minerals to facilitate the uptake and assimilation of nutrients by the crops, enhance plant nutrition, and reduce chemical fertilizer consumption and nutrient-related toxicity [35]. Both methods have been successfully applied to biofortify plants with mineral elements, vitamins, and other bioactive compounds [30].

2. Nutritional Deficiencies Associated with Overweight or Obese Patients

Obesity is a nutritional imbalance that negatively alters the micronutrient status of individuals; it has been recognized as a crucial risk factor for various nutrient deficiencies, being increasingly associated with an inadequate intake of minerals such as iron, calcium, magnesium, zinc, and copper, as well as vitamins (folate, vitamin A, D, and B12) [2,6,14,36][2][6][14][36]. Most micronutrients act as cofactors for the functioning of enzymes in living organisms and therefore regulate many vital metabolic processes in the body [6,23][6][23]. Deficiencies or a lack of homeostasis of micronutrients can cause severe implications for human health, such as congenital disabilities, stunted growth, learning disabilities, immune dysfunction, cancer, cardiovascular disease, defective antioxidant defense mechanisms, osteoporosis, neurodegenerative disorders, intestinal microbiota malfunction, deteriorates the functionality of most organs and systems, and contributes to the aggravation of many diseases. Since micronutrients are implicated in fat and carbohydrate metabolism, glucose metabolic pathways, the insulin-signaling cascade, and pancreatic β-cell function, their deficiency worsens the development of obesity [2,10,14,23,24][2][10][14][23][24].
A poor diet quality mainly causes the occurrence of nutritional deficiencies in obesity based on the overconsumption of processed foods that are calorie-dense and have a low nutrient density, which is generally accompanied by a decreased consumption of fruits and vegetables, being two of the primary sources of vitamins and minerals [2,9,37][2][9][37]. The NOVA food classification has established food processing as an important indicator of food quality. It divides foods into ultra-processed, processed, unprocessed, and culinary ingredients [38]. Ultra-processed foods (UPFs) account for more than 60% of the dietary energy intake and nearly 90% of added sugars in the diets of adults in the US [39]. UPFs are mainly ready-to-eat industrial formulations composed of processed ingredients refined from whole foods and usually have added fats, sugars, sodium, artificial flavors, colorings, and other food additives [40]. UPFs are nutrient-poor (low in dietary fiber, protein, micronutrients, and phytochemicals), energy-dense, and low-cost foods with important adverse health outcomes [39]. The obesity rate and its related nutritional deficiencies have been linked to an increased consumption of UPF, making children and adolescents their leading consumers [40,41][40][41]. In particular, sugar-sweetened beverages (SSBs) are strongly associated with weight gain and are recognized as a significant risk factor for type-2 diabetes, cardiovascular disease, and cancer. SSBs are one of the primary sources of added sugar in diets; a 355 mL serving of soda provides around 35–37 g of sugar and 140–150 calories [42]. Sweetened beverages are also recognized as nutrient-poor and linked to micronutrient deficiencies since their consumption is inversely correlated to the concentrations of vitamin D and calcium because of the lower intake of milk [2].
Another cause may be the higher nutrient requirements resulting from the pathophysiological and metabolic changes in individuals with obesity [2]. For example, obese patients present higher requirements of zinc, magnesium, chromium, manganese, and vanadium because they are involved in carbohydrate and fat metabolism. Thus, obese patients are at a greater risk of developing nutritional deficiencies related to these micronutrients [14].
Other studies have reported that increased adiposity and systemic obesity-related inflammation can disturb the absorption, distribution, metabolism, and elimination of micronutrients; obesity affects the protein binding, volume of distribution, hepatic metabolism, and renal clearance, mainly due to the elevated adiposity, blood composition and volume, cardiac output, lean body mass, and organ size (primarily liver and kidney) of obese patients [2,6,9][2][6][9]. For example, some minerals and lipophilic vitamins (vitamin D and A) can be sequestered in the adipose tissue, affecting their distribution, decreasing circulating concentrations, and reducing bioavailability for metabolically active tissues; obese people commonly have lower serum levels of vitamin D and A [6,11,14][6][11][14]. Obesity is also associated with deficiencies of water-soluble vitamins, including thiamine, folate, and ascorbic acid, partly because their excretion increases due to their high expenditure [14]. Elevated levels of triglycerides, cholesterol, and free fatty acids in the bloodstream of obese subjects may impact the distribution of protein-bound micronutrients. Likewise, minerals with chemical similarities to other compounds within the food matrix can compete for transport proteins or other absorption mechanisms, hindering their absorption and bioavailability [2,6][2][6].
Additionally, the treatment of morbid obesity involving bariatric surgery can increase the risk or aggravate micronutrient deficiencies by reducing their consumption or absorption [9,11][9][11]. Its effect and significance will depend on which part of the gastrointestinal tract is bypassed; for example, zinc, iron, manganese, selenium, chromium, calcium, and the vitamins A, C, E, K, folate, thiamine, biotin, riboflavin, niacin, pyridoxine, and pantothenate are absorbed in the duodenum and jejunum, whereas fat-soluble vitamins and vitamin C are absorbed in the ileum. In particular, vitamin B12 first binds to intrinsic factors in the stomach, and is then absorbed in the ileum [2,9][2][9]. Patients undergoing gastric bypass and related surgeries have a higher risk of presenting a malabsorption of micronutrients that are primarily metabolized and/or absorbed in the stomach and the first part of the ileum [2].
Several studies have been performed to study deficiencies in micronutrients in individuals with obesity (Figure 1), Guan et al. [43] evaluated nutritional deficiencies in Chinese patients undergoing Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG). They found several nutritional deficiencies in the bariatric candidates, identifying vitamin D deficiency as the most severe (78.8%), followed by vitamin B1 (39.2%), vitamin B6 (28.0%), folate (26.8%), vitamin C (18.0%), transferrin (11.6%), and phosphorus (11.5%). In a preoperative evaluation of 200 candidates for bariatric surgery, Pellegrini et al. [44] found that 85.5% of the patients presented at least one micronutrient deficiency: the most prevalent were vitamin D (74.5%), folate (33.5%), iron (32%), calcium (13%), vitamin B12 (10%), and albumin (5.5%). Similarly, Asghari et al. [45] studied the micronutrient status of morbidly obese candidates for bariatric surgery (mean age: 37.8 years, mean BMI: 44.8 kg/m2): deficiencies were identified for vitamin D (53.6%), vitamin B12 (34.4%), and serum iron (10.2%). In another study performed with 1732 patients with morbid obesity (age: 40 ± 12 years, mean BMI: 44 ± 9 kg/m2), data showed a high prevalence of micronutrient deficiencies: 63.2% of the patients presented deficiencies in folic acid (<5.3 ng/mL), 97.5% in vitamin D (<75 nmol/L), 9.6% in iron (ferritin < 15 μg/L), 6.2% in vitamin A (<1.05 μmol/L), and 5.1% in vitamin B12 (<188 pg/mL) [46]. McKay et al. [6] found associations between an increased BMI and low serum micronutrient levels in overweight and obese Australian adults (BMI: 25–40 Kg/m2, age:18–65 years) compared with the clinical micronutrient references. Significant associations were found for vitamin D (p = 0.044), folate (p = 0.025), magnesium (p = 0.010), and potassium (p = 0.023). Table 1 summarizes the most common micronutrient deficiencies observed in individuals with obesity.
Figure 1. Micronutrient deficiencies associated with obese patients. Ca: calcium, Cr: chromium, Fe: iron, I: iodine, Mg: magnesium, Mn: manganese, P: phosphorus, Se: selenium, Zn: zinc. Figure created with BioRender.com.
In addition to obesity-related micronutrient deficiencies, several studies have demonstrated that most of the global population currently suffers from micronutrient insufficiencies [2]. According to the World Health Organization, the most common micronutrient deficiencies include zinc, iron, iodine, and vitamins A, D, and B12 [79]. Micronutrient deficiencies affect more than two million people worldwide: 60% of people are iron (Fe)-deficient, 30% are zinc (Zn)- and iodine-deficient, and 15% are selenium-deficient [23,24][23][24]. In addition, the World Health Organization reported that a third of humans had been affected by zinc deficiencies. It is also estimated that 50% of children do not obtain the vitamins and minerals necessary for their development [19]. Therefore, it is critical to take global actions and develop strategies to counteract and cover the gaps in micronutrient intake in individuals across all weight categories, particularly in individuals with obesity, who represent a severe health and socio-economic problem worldwide.

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