Supplementation of Ocean-Based Advance Protein Powder (APP) for Restoration of Body Growth, Bone Development and Immune Functions in Protein Malnourished Mice: Implications for Preventing Child Malnutrition.

Child malnutrition is a global public health challenge. A protein malnutrition (PM) model in young mice was established in this study. The efficacy of an ocean-based protein (APP) extracted from by-catch fish as compared to casein and soy on restoring body weight, bone growth, and immunity of PM mice was evaluated. Results show that supplementation of APP increases body weight, lean muscle mass, bone area, mineral content and density. APP supplementation increases spleen, thymus weight, and interlukin-6 production. In conclusion, APP is an alternative source of protein to effectively restore body weight, bone growth and immune function of PM mice.

A Novel Concept of Amino Acid Supplementation to Improve the Growth of Young Malnourished Male Rats.

BACKGROUNDS/AIMS: This study was aimed at understanding the relationship between plasma amino acids and protein malnutrition and at determining whether amino acid supplementation associated with malnutrition and growth improves linear growth in growing rats. METHODS: Body length and plasma amino acids were measured in young male rats that were fed the following diet for 3 weeks, mimicking a low and imbalanced protein diets based on maize, a major staple consumed in developing countries: a 70% calorically restricted cornmeal-based diet (C), C + micronutrients (CM), CM + casein (CMC), CM + soy protein (CMS) or CMS + 0.3% lysine. RESULTS: A correlation analysis of linear growth and plasma amino acids indicated that lysine, tryptophan, branched-chain amino acids, methionine, and phenylalanine significantly correlated with body length. Supplementation with these 5 amino acids (AA1) significantly improved the body length in rats compared to CMC treatment whereas, nitrogen-balanced amino acid supplemented controls (AA2) did not (CM +1.2 ± 0.2, CMC +2.7 ± 0.3, CMS +2.1 ± 0.3, AA1 +2.8 ± 0.2, and AA2 +2.5 ± 0.3 cm). CONCLUSION: With securing proper amino acid balance, supplementing growth-related amino acids is more effective in improving linear growth in malnourished growing male rats. Analysis of the correlation between plasma amino acids and growth represents a powerful tool to determine candidate amino acids for supplementation to prevent malnutrition. This technology is adaptable to children in developing countries.

Leucine restores murine hepatic triglyceride accumulation induced by a low-protein diet by suppressing autophagy and excessive endoplasmic reticulum stress.

Although it is known that a low-protein diet induces hepatic triglyceride (TG) accumulation in both rodents and humans, little is known about the underlying mechanism. In the present study, we modeled hepatic TG accumulation by inducing dietary protein deficiency in mice and aimed to determine whether certain amino acids could prevent low-protein diet-induced TG accumulation in the mouse liver. Mice fed a diet consisting of 3 % casein (3C diet) for 7 days showed hepatic TG accumulation with up-regulation of TG synthesis for the Acc gene and down-regulation of TG-rich lipoprotein secretion from hepatocytes for Mttp genes. Supplementing the 3 % casein diet with essential amino acids, branched-chain amino acids, or the single amino acid leucine rescued hepatic TG accumulation. In the livers of mice fed the 3 % casein diet, we observed a decrease in the levels of the autophagy substrate p62, an increase in the expression levels of the autophagy marker LC3-II, and an increase in the splicing of the endoplasmic reticulum (ER) stress-dependent Xbp1 gene. Leucine supplementation to the 3 % casein diet did not affect genes related to lipid metabolism, but inhibited the decrease in p62, the increase in LC3-II, and the increase in Xbp1 splicing levels in the liver. Our results suggest that ER stress responses and activated autophagy play critical roles in low-protein diet-induced hepatic TG accumulation in mice, and that leucine suppresses these two major protein degradation systems. This study contributes to understanding the mechanisms of hepatic disorders of lipid metabolism.

Taurine supplementation restored the changes in pancreatic islet mitochondria in the fetal protein-malnourished rat.

Intra-uterine growth retardation has been linked to the development of type 2 diabetes in later life. Mitochondrial changes have been suggested as a link between fetal malnutrition and adult insulin resistance. Taurine has been implicated in this process. We investigated whether protein malnutrition in early life alters mitochondria of the pancreatic islets in adulthood, and whether taurine supplementation restores these changes. Male offspring of rats fed a control diet, a low-protein diet or a low-protein diet supplemented with taurine during pregnancy and lactation were weaned onto the control diet. In each group, at 20 weeks of age, intravenous glucose tolerance tests, euglycaemic-hyperinsulinaemic clamp studies, morphometric analysis of the pancreatic islets and ultra-structural analysis of the mitochondria of the ß-cells were performed. The expressions of cytochrome c oxidase (COX) I and mitochondrial respiratory chain complex II were also measured. Fetal protein-malnourished rats showed decreased pancreatic islet mass and reduced insulin-secretory responses to a glucose load. These rats also showed reduced mitochondrial DNA-encoded COX I gene expression in the islets. Electron microscopic examination showed abnormal mitochondrial shapes in the ß-cells of fetal protein-malnourished rats. Taurine supplementation to the low-protein diet restored all these changes. Our findings indicate that a maternal protein-restriction diet causes long-lasting mitochondrial changes that may contribute to the development of type 2 diabetes later in life. The lack of taurine may be a key causative factor for these dysfunctional mitochondrial changes.

Metabolic responses to acute physical exercise in young rats recovered from fetal protein malnutrition with a fructose-rich diet.

BACKGROUND: Malnutrition in utero can "program" the fetal tissues, making them more vulnerable to metabolic disturbances. Also there is association between excessive consumption of fructose and the development of metabolic syndrome. However, there is little information regarding the acute effect of physical exercise on subjects recovered from malnutrition and/or fed with a fructose-rich diet. The objective of this study was to evaluate the metabolic aspects and the response to acute physical exercise in rats recovered from fetal protein malnutrition with a fructose-rich diet. METHODS: Pregnant Wistar rats were fed with a balanced (B) diet or a low-protein (L) diet. After birth and until 60 days of age, the offspring were distributed into four groups according to the diet received: B: B diet during the whole experiment; balanced/fructose (BF): B diet until birth and fructose-rich (F) diet afterwards; low protein/balanced (LB): L diet until birth and B diet afterwards; low protein/fructose (LF): L diet until birth and F diet afterwards. RESULTS: The excess fructose intake reduced the body weight gain, especially in the BF group. Furthermore, the serum total cholesterol and the LDL cholesterol were elevated in this group. In the LF group, the serum total cholesterol and the muscle glycogen increased. Acute physical exercise increased the serum concentrations of glucose, triglycerides, HDL cholesterol and liver lipids and reduced the concentrations of muscle glycogen in all groups. CONCLUSION: An excess fructose intake induced some signs of metabolic syndrome. However, protein malnutrition appeared to protect against the short term effects of fructose. In other hand, most responses to acute physical exercise were not influenced by early malnutrition and/or by the fructose overload.

A low-protein diet supplemented with ketoacids plays a more protective role against oxidative stress of rat kidney tissue with 5/6 nephrectomy than a low-protein diet alone.

Dietary protein restriction is one major therapy in chronic kidney disease (CKD), and ketoacids have been evaluated in CKD patients during restricted-protein diets. The objective of the present study was to compare the efficacy of a low-protein diet supplemented with ketoacids (LPD+KA) and a low-protein diet alone (LPD) in halting the development of renal lesions in CKD. 5/6 Nephrectomy Sprague-Dawley rats were randomly divided into three groups, and fed with either 22 % protein (normal-protein diet; NPD), 6 % protein (LPD) or 5 % protein plus 1 % ketoacids (LPD+KA) for 24 weeks. Sham-operated rats were used as controls. Each 5/6 nephrectomy group included fifteen rats and the control group included twelve rats. Proteinuria, decreased renal function, glomerular sclerosis and tubulointerstitial fibrosis were found in the remnant kidneys of the NPD group. Protein restriction ameliorated these changes, and the effect was more obvious in the LPD+KA group after 5/6 nephrectomy. Lower body weight and serum albumin levels were found in the LPD group, indicating protein malnutrition. Lipid and protein oxidative products were significantly increased in the LPD group compared with the LPD+KA group. These findings indicate that a LPD supplemented with ketoacids is more effective than a LPD alone in protecting the function of remnant kidneys from progressive injury, which may be mediated by ketoacids ameliorating protein malnutrition and oxidative stress injury in remnant kidney tissue.

Influence of the timing of switching a protein-free to a protein-containing diet on the wound healing process in a rat all-layer skin defect.

We prepared full thickness skin defects in rats fed on a protein-free diet as a hypoproteinaemia model, then switched the animals to a diet containing a normal protein level 1, 6 or 12 days after wounding (inflammatory, granulation and rearrangement phases of the wound healing process) to examine whether improvement in the low-protein state promotes subsequent wound healing. The interval until wound healing in rats fed on a normal protein diet was significantly shorter, whereas that in rats continuously fed on a protein-free diet was significantly longer than those of other groups. Early correction tended to accelerate wound healing. Although wound contraction in groups receiving a protein-corrected or protein-free diet remained similar until 15 days after wounding, thereafter the duration of the rearrangement phase was significantly longer in the protein-free group than in the other groups. The collagen level per unit of granulation tissue area during wound healing was significantly lower in the protein-free group than in the other groups. These findings indicate that protein correction at any time after wounding accelerates wound healing, although early correction is more effective, and reduces the duration of the rearrangement phase more than those of the inflammatory and granulation phases because of the deposit of collagen.

Comparison of cricket diet with peanut-based and milk-based diets in the recovery from protein malnutrition in mice and the impact on growth, metabolism and immune function.

Some evidence suggests that edible insects could be used to treat malnutrition following protein deficiency. However, additional studies are needed to better assess the potential of edible insects as a therapeutic food supplement and their long-term impact on recovery from malnutrition. The goals of this study were to investigate the effectiveness of a cricket-based diet in recovery from protein-malnutrition in early life, and to compare cricket protein to more traditional sources used for food fortification and supplementation. Protein-malnutrition was induced by administration of an isocaloric hypoprotein diet (5% protein calories) in young male mice for two weeks during puberty, followed by a six-week recovery period using a cricket-, peanut- or milk-based diet. We examined the impact of protein-malnutrition and subsequent recovery on body weight, growth and select biomarkers of inflammation and metabolism. Protein-malnutrition resulted in growth retardation, downregulation of inflammatory markers in spleen tissue, decreased levels of serum triglycerides, and elevated serum levels of leptin and adiponectin. The cricket-based diet performed equally well as the peanut- and milk-based diets in body weight recovery, but there were differences in immune and metabolic markers among the different recovery diets. Results suggest edible crickets may provide an alternative nutrient-dense protein source with relatively low environmental demands for combating the effects of early-life malnutrition compared to more traditional supplementation and fortification sources. Additional investigations are needed to examine the short and long term impacts of different recovery diets on metabolism and immune function.

[The Influence of Protein on the Prevention of Fragility Fractures Among Senior Adults]. / Der Einfluss von Protein auf die Prävention von Fragilitätsfrakturen bei älteren Erwachsenen.

The Influence of Protein on the Prevention of Fragility Fractures Among Senior Adults Abstract. The aim of this review article is to discuss protein intake in senior adults at risk for fragility fractures as a modifiable factor for fracture prevention. Proteins are building blocks of the bone matrix and the muscles. This dual function fits in with the concept of prevention of fragility fractures in senior adults aimed at reducing both bone loss and falls. In older adults, a protein-rich diet could be another simple and effective way to promote bone and muscle health, in addition to the established recommendations for adequate vitamin D and calcium intake.

Stereology shows that damaged liver recovers after protein refeeding.

OBJECTIVE: The aim of the present study was to investigate the putative effects of a low-protein diet on the three-dimensional structure of hepatocytes and determine whether this scenario could be reversed by restoring the adequate levels of protein to the diet. METHODS: Using design-based stereology, the total number and volume of hepatocytes were estimated in the liver of mice in healthy and altered (by protein malnutrition) conditions and after protein renutrition. RESULTS: This study demonstrated a 65% decrease in the liver volume (3302 mm3 for the control for undernourished versus 1141 mm3 for the undernourished group) accompanied by a 46% reduction in the hepatocyte volume (8223 µm3 for the control for undernourished versus 4475 µm3 for the undernourished group) and a 90% increase in the total number of binucleate hepatocytes (1 549 393 for the control for undernourished versus 2 941 353 for the undernourished group). Reinstating a normoproteinic diet (12% casein) proved to be effective in restoring the size of hepatocytes, leading to an 85% increase in the total number of uninucleate hepatocytes (15 988 560 for the undernourished versus 29 600 520 for the renourished group), and partially reversed the liver atrophy. CONCLUSIONS: Awareness of these data will add to a better morphologic understanding of malnutrition-induced hepatopathies and will help clinicians improve the diagnosis and treatment of this condition in humans and in veterinary practice.

Biochemical and nutritional profile of patients with exclusive enteral nutrition during hospitalization / Perfil bioquímico y nutricional de pacientes con nutrición enteral exclusiva durante hospitalización

BACKGROUND: Enteral nutrition therapy (ENT) is intended to restore the nutritional status of patients. OBJECTIVE: The objective of this study was to evaluate the biochemical and nutritional profile of hospitalized patients with exclusive enteral nutrition. METHODS: It is a longitudinal study, with a sample of 42 hospitalized young and elder adults, with exclusive ENT, for at least seven days. The patients were submitted to nutritional, anthropometric (Body Mass Index, corrected arm muscle area and arm muscle circumference) and biochemical evaluation as albumin, hemoglobin, C-reactive protein, vitamin C, Iron, Zinc and Copper serum. Results and DISCUSSION: It was observed that anthropometric parameters such as weight, BMI, muscle area and circumference increased during hospitalization time only in the elderly (P= 0.016; P=0.018; P = 0.021; P = 0.020). The percentage of adequacy in energy, protein and micronutrients with vitamin C, iron, zinc and copper were adequate during hospitalization for both age groups, according to the estimated average needs. Serum levels of these micronutrients were within normal values for both age groups, with the exception of zinc, which decreased during hospitalization in the elderly. This may be associated with the greater need for this mineral in this age group or with a implicate in its absorption. CONCLUSION: The ENT influence the weight and muscle mass gain in hospitalized elderly patients and, although the appropriate administration of micronutrients, the absorption of zinc was affected. Therefore, monitoring of enteral nutrition is essential in order to avoid worsening nutritional status during hospitalization

INTRODUCCIÓN: La terapia de nutrición enteral (TNE) tiene la finalidad de recuperar el estado nutricional de los pacientes. Objectivo: Se evaluó el perfil bioquímico y nutricional de pacientes hospitalizados con nutrición enteral exclusiva. MÉTODOS: Estudio longitudinal, con muestra compuesta por 42 adultos y ancianos hospitalizados, con TNE exclusiva, por lo menos siete días. Los pacientes fueron sometidos a evaluación nutricional, antropométrica (Índice de Masa Corporal, área muscular del brazo corregida y circunferencia del brazo) y bioquímica como albúmina, proteína C-reactiva, vitamina C, hierro zinc y cobre sérico. Resultados y DISCUSIÓN: Se observó que los parámetros antropométricos como el peso, IMC, área y circunferencia muscular del brazo aumentaron durante el tiempo de internación solo en los ancianos (P= 0.016; P=0.018; P = 0.021; P = 0.020). El porcentaje de adecuación de energía, proteica y micronutrientes como vitamina C, hierro, zinc y cobre fueron adecuados durante el tiempo de internación para ambos grupos de edad, de acuerdo con las necesidades medias estimadas. Los niveles séricos de estos micronutrientes se mantuvieron dentro de los valores normales para ambos grupos de edad, a excepción del zinc, que disminuyó durante la hospitalización en ancianos. Esto puede asociarse a la mayor necesidad de este mineral en este grupo de edad o a un deterioro en su absorción. CONCLUSIÓN: La TNE influye en el aumento de peso y la masa muscular en ancianos y, apesar de la administración adecuada de micronutrientes, se observó un deterioro en la absorción de zinc. Por lo tanto, el monitoreo de la nutrición enteral es esencial para evitar el empeoramiento del estado nutricional durante la hospitalización

Nutritional assessment and support during infection.

Protein malnutrition is one of the principal factors relating to morbidity and mortality during infection. Nutritional assessment is required to determine the severity of depletion and degree of hypermetabolism affecting this patient population. Simple anthropometric and 24-hr urine collections together with routine biochemical analyses can readily allow clinical assessment to occur. Optimal utilization of dietary intake is dependent on the degree of protein catabolism and energy expenditure in excess of the basal energy requirement. Urinary nitrogen excretion in 24-hr on a protein-free diet is especially valuable in aiding this assessment. This analysis together with urinary creatinine which provide important estimates of lean body mass and serial measures will allow estimates of the progression of malnutrition. In infected adults optimal protein intake to produce positive nitrogen balance is 1.5 to 2.0 g of protein/kg per day. This would appear to reflect the fact that 16% of the caloric expenditure comes from protein sources during injury. Since this value is approximately twice that seen during nonstress, the reutilization of body protein would appear to be decreased. Careful appreciation of the metabolic response during infection is necessary prior to consideration of the nutritional support plan. Knowledge regarding the phase of infection, severity of nutritional depletion, and degree of hypermetabolism will influence the attainable goals of nutritional support.

Response of IGF-1 to nutritional support in malnourished hospital patients: a possible indicator of short-term changes in nutritional status.

IGF-1 is a circulating growth factor with hepatic release dependent on nutritional status. To determine if IGF-1 could be a useful nutritional index, 15 malnourished patients were assessed during nutritional support. Patients with protein or protein-calorie malnutrition had lower IGF-1 (39 +/- 7 micrograms/L) than did patients with calorie-only malnutrition (109 +/- 25 micrograms/L, p less than 0.005); transferrin concentrations did not differ between the two groups. Nutritional supplementation produced an increase in IGF-1 (123 +/- 32 micrograms/L, p less than 0.005); the relative increase in IGF-1 (264 +/- 62%, p less than 0.001) exceeded increases in albumin or transferrin (9 +/- 6% and 59 +/- 16%, NS and p less than 0.005, respectively). Reduction or termination of support was followed by a decrease in IGF-1 to 59 +/- 9% of peak values (p less than 0.001) but neither albumin nor transferrin decreased significantly. Changes in IGF-1 were correlated with nitrogen balance (r = 0.45, p less than 0.005). The strong relationship between IGF-1 and nutritional status suggests that IGF-1 determinations may be useful in guiding nutritional therapy in patients whose nitrogen balance is difficult to assess.

Enteropathy in adult protein malnutrition: light microscopic findings.

Light microscopy evaluation of the intestinal abnormalities seen in 35 severely malnourished adults revealed changes which are common to other well-documented enteropathies. These included shortening, widening and fusion of the villi, lost convolution of the nuclear line, and diminished epithelial cell height. With Masson's trichrome stain, dense material was seen to have accumulated in a subepthelial location in villi (as described in other enteropathies), in crypts, and perivascularly around the capillaries of the lamina propria. Two findings however appear to characterize the severely malnourished state: a consistent, significant reduction of intestinal mucosal thickness, and in many cases atrophy of the crypts. Statistical analysis of the total mucosal thickness data does not justify five but rather three histological categories. With protein repletion as the sole therapeutic modality, 17 patients in which adequate biopsy samples were available at its completion showed significant amelioration of the aforementioned histological abnormalities, as well as normalization of their previous absorptive defects. The mild enteropathy of severe protein malnutrition must be considered in the differential diagnosis of malabsorption in a tropical setting.

Protein metabolism in cystic fibrosis: responses to malnutrition and taurine supplementation.

Increased protein breakdown has been cited as an important cause of nutrient loss in cystic fibrosis (CF). Taurine deficiency, which is common in CF, may contribute to the increased breakdown. The occurrence of and the benefit of taurine supplementation to abnormal protein metabolism in apparently optimally treated CF were assessed using a 12-mo double-blind crossover technique in 14 well-nourished and seven mildly-moderately malnourished infection-free preadolescent CF children. Muscle protein breakdown (urinary 3-methylhistidine technique) was significantly decreased in well-nourished (1.35% degraded/24 h +/- 0.15, p less than 0.05) and malnourished (1.24 +/- 0.11, p less than 0.001) CF children compared with controls (1.50 +/- 0.17, n = 13). Whole-body protein flux, synthesis, and catabolism ([15N]-glycine technique) were similar in all groups. Net protein gain was greater in CF children, particularly those who were well-nourished (0.55 g/(kg X 10 h) +/- 0.35, p less than 0.01) compared with controls (0.16 +/- 0.26). Taurine supplementation did not significantly affect any of the indices. In the absence of infection, protein metabolism in CF children responds appropriately to malnutrition.

Enteropathy in adult protein malnutrition: a review of the Cali experience.

Since 1964, 41 patients with strictly defined, severe primary (dietetic) protein malnutrition have been studied under metabolic ward conditions during prolonged periods, initially on a low (20 g) and later on a high (100 g) protein diet. Clinical, nutritional, hematological, intestinal absorptive and histological studies were performed in the malnourished state, during and after protein repletion. Classical signs and symptoms of malnutrition, lasting for at least 4 months, were present in most patients. Mild diarrhea was frequent. All were normoblastically anemic, hypoproteinemic, and hypocholesterolemic; serum folate values were normal or low but serum B12 values were normal or high. Liver biopsy showed fatty liver in the cases where it was performed. Mild malabsorption was detected in over one-half of the patients, with moderate intestinal radiological abnormalities. Malabsorption was independent of concomitant folate deficiency. All the clinical, absorptive and histological abnormalities reversed with treatment consisting only of a high protein diet. In addition to protein lack, another factor has to be invoked in the pathogenesis of the intestinal abnormalities present in severely malnourished adults from rural areas in the tropics.

Cytogenetic studies in bone marrow cells from Wistar rats in protein malnutrition.

The effect of severe protein deficiency at weaning has been studied in bone marrow, which is a primary lymphoid organ. Our experimental model of secondary immunodeficiency in Wistar rats has shown: (1) a decreased number of viable bone marrow cells (P <.0001); (2) diminished percentage of mitosis (P <.01); and (3) severe alteration in the percentage of chromosome pairs 3, 11, and 12 bearing nucleolar organizer regions (NORs) (P <.05). This last finding indicates a poor ribosomal gene activity. These alterations were reverted after the oral administration of a 20% casein diet during 5 to 9 days. However, there were no karyotype variations between the experimental groups. We conclude from these results that severe protein deficiency at weaning alters several aspects of bone marrow cell proliferation and ribosomal gene activity as determined by the number of silver stained nucleolus organizer regions.

Lipid-based parenteral nutrition and the immunosuppression of protein malnutrition.

Protein malnutrition has been directly related to impaired immunocompetence. An experimental protocol was designed to determine the efficacy of a lipid-based system of total parenteral nutrition (TPN) in restoring immunocompetence in nutritionally depleted subjects. Thirty rats sensitized to PPD were made anergic by the oral administration of a protein-free diet. Nutritional repletion was instituted with either a complete oral diet or lipid-based TPN. The two groups of animals did not differ significantly in the time required to regain positive skin test reactivity or in the weight gained during the repletion period. The lipid-based system of TPN was comparable to the complete oral diet in reversing the anergy of protein malnutrition.

Developmental protein malnutrition in the rat: effects on single-unit activity in the frontal cortex.

This study evaluated the effects of developmental protein malnutrition on the spontaneous electrical activity of frontal cortex neurons in the anesthetized rat. Rats were raised prenatally and postnatally on either an 8% or 6% casein diet until adulthood. Compared to the 25% casein controls, both malnourished groups showed a 30-36% decrease in mean discharge rates and a 100-200% increase in the percentage of cells with very slow (less than 1/s) discharge rates. Most of the diet-related changes were confined to a zone 600-1200 micron below the brain surface, approximately cortical layers III, IV and V. A second set of studies in which diet reversals were introduced at birth or in adulthood found that: (a) restoration of a normal 25% casein diet at birth did not appreciably attenuate the effect of prenatal administration of an 8% casein diet; (b) introduction in adulthood of the 8% casein diet to a normally fed rat had no effect; (c) introduction of the 8% diet at birth, however, produced effects in adulthood comparable to those seen when the protein malnutrition was introduced in the prenatal period. Thus, the rat brain is sensitive to both prenatal and postnatal protein malnutrition (starting at birth). Most importantly, the effects of prenatal protein malnutrition on the activity of frontal cortex neurons do not appear to be reversible by restoration of a normal diet in adulthood or at birth.