ascorbic-acid and Starvation

Uric acid has historically been viewed as a purine metabolic waste product excreted by the kidney and gut that is relatively unimportant other than its penchant to crystallize in joints to cause the disease gout. In recent years, however, there has been the realization that uric acid is not biologically inert but may have a wide range of actions, including being both a pro- and anti-oxidant, a neurostimulant, and an inducer of inflammation and activator of the innate immune response. In this paper, we present the hypothesis that uric acid has a key role in the foraging response associated with starvation and fasting. We further suggest that there is a complex interplay between fructose, uric acid and vitamin C, with fructose and uric acid stimulating the foraging response and vitamin C countering this response. Finally, we suggest that the mutations in ascorbate synthesis and uricase that characterized early primate evolution were likely in response to the need to stimulate the foraging "survival" response and might have inadvertently had a role in accelerating the development of bipedal locomotion and intellectual development. Unfortunately, due to marked changes in the diet, resulting in dramatic increases in fructose- and purine-rich foods, these identical genotypic changes may be largely responsible for the epidemic of obesity, diabetes and cardiovascular disease in today's society.

Topics: Animals; Antioxidants; Ascorbic Acid; Blood Pressure; Evolution, Molecular; Fasting; Fructose; Gout; Humans; Inflammation Mediators; Insulin Resistance; Metabolic Syndrome; Models, Biological; Starvation; Urate Oxidase; Uric Acid; Weight Gain

Vitamin C deficiency is associated with defective connective tissue, particularly in wound healing. Ascorbate is required for hydroxylation of proline residues in procollagen and hydroxyproline stabilizes the collagen triple helical structure. Consequently, ascorbate stimulates procollagen secretion. However, collagen synthesis in ascorbate-deficient guinea pigs is decreased with only moderate effects on proline hydroxylation. Proteoglycan synthesis, which does not require ascorbate, also is decreased and both effects are correlated with the extent of weight loss during scurvy. Fasting, with ascorbate supplementation, produces similar effects. Both functions are inhibited in cells cultured in sera from either scorbutic or starved guinea pigs and inhibition is reversed with insulin-like growth factor (IGF)-I. The inhibitor appears to consist of two IGF-binding proteins induced during vitamin C deficiency and starving and may be responsible for in vivo inhibition of collagen and proteoglycan synthesis.

Topics: Animals; Ascorbic Acid; Carrier Proteins; Cartilage; Cells, Cultured; Collagen; Humans; Hydroxylation; Insulin-Like Growth Factor Binding Proteins; Insulin-Like Growth Factor I; Procollagen; Proteoglycans; Scurvy; Starvation

Topics: Ascorbic Acid; Bacteria; Biomass; Cell Cycle; Diabetes Mellitus; Diabetes Mellitus, Type 2; Erythrocytes; Glucose; Humans; Obesity; Polyhydroxyalkanoates; Sewage; Starvation; United Kingdom; Vitamin A; Vitamin A Deficiency

The view of scurvy being exclusively a nutritional disorder needs to be updated. Genetic polymorphisms of HFE and haptoglobin (Hp) may explain the geographic variability of mortality caused by the European famine of the mid-19th century. In this period, potatoes had fallen victim to the potato blight and Ireland was more severely hit than continental Europe. Hereditary hemochromatosis is a genetic disorder with mutations in the HFE gene, characterized by iron overload (with a reduced vitamin C stability) and with a predominance of affected men. The Irish have the world's highest frequency of the C282Y mutation and the particular iron metabolism of the Irish helps to understand the size of the catastrophe and the observed overrepresentation of male skeletons showing scurvy. Hp is a plasma α2-glycoprotein characterized by 3 common phenotypes (Hp 1-1, Hp 2-1 and Hp 2-2). When the antioxidant capacity of Hp is insufficient, its role is taken over by hemopexin and vitamin C. The relative number of scurvy victims corresponds with the Hp 2-2 frequency, which is associated with iron conservation and has an impact on vitamin C stability. As iron is more abundant in males, males are overrepresented in the group of skeletons showing scurvy signs.

Topics: Ascorbic Acid; Europe; Genotype; Haptoglobins; Hemochromatosis; Hemochromatosis Protein; Histocompatibility Antigens Class I; History, 19th Century; Humans; Iron; Iron Overload; Male; Membrane Proteins; Phenotype; Polymorphism, Genetic; Scurvy; Starvation; White People

Although fatty liver (FL) is considered an innocuous condition, the frequent incidence of graft failure when FL are transplanted has renewed interest in the intracellular disorders causative of or consequent to fatty degeneration. Oxidative stress and nutritional status modulate the tolerance to reperfusion injury in control livers (CL), but very little is known in the case of FL. This study was designed to compare the oxidative balance in CL and FL from fed and food-deprived rats. Serum and liver samples were collected from fed and starved (18 h) rats with CL or FL induced by a choline-deficient diet. Hepatic injury was assessed by transaminase activities and histology. The hepatic concentrations of glutathione (GSH), vitamin C, alpha-tocopherol, thiobarbituric acid-reactive substances (TBARS) and protein carbonyls (PC) were measured. Fed rats with FL had significantly greater TBARS and lower alpha-tocopherol and vitamin C levels than those with CL, whereas GSH and PC concentrations were not affected. Starvation impaired the oxidative balance in both groups. However, compared with the other groups, FL from food-deprived rats generally had the lowest hepatic concentrations of alpha-tocopherol, vitamin C and GSH. Unlike in CL, protein oxidation occurred in FL. These data indicate that fatty liver induced by consumption of a choline-deficient diet is associated with a lower level of antioxidants, which results in lipid peroxidation. Starvation further affects these alterations and extends the damage to proteins. In conclusion, steatosis and starvation may act synergistically on the depletion of antioxidants, predisposing fatty livers to a reduced tolerance to oxidative injury.

Topics: Animals; Antioxidants; Ascorbic Acid; Choline Deficiency; Diet; Fatty Liver; Glutathione; Lipid Metabolism; Lipid Peroxidation; Male; Oxidative Stress; Rats; Rats, Wistar; Starvation; Thiobarbituric Acid Reactive Substances; Transaminases

The aggravation of acid-induced gastric damage and its prevention by glucose, ascorbate or glutathione precursors was studied in fed and food-deprived rats. The stomachs of fed rats and those starved for 1, 3 or 5 d were vagotomized just before irrigating for 3 h with solutions containing 0-150 mmol HCI/L. Mucosal glutathione, mucus, lipid peroxides and acid back-diffusion were measured. Stomach ulcers were evaluated by morphological and histological examination. The preventive effects of glucose, ascorbate and a mixture of L-glutamine, L-glycine and L-cysteine were evaluated in the stomachs of rats that were starved for 5 d, vagotomized, then perfused for 3 h with 100 mmol HCI/L. Greater acid back-diffusion and ulcer formation, and lower glutathione and mucus levels in starved rats were dependent on the duration of starvation and luminal acidity. Increased acid back-diffusion and decreased glutathione and mucus production were negatively correlated (r < -0.80, P < 0.05) with ulcer formation. A significant enhancement in mucosal lipid peroxide concentration and serious damage of forestomach and corpus mucosal cells were observed in starved rats exposed to 100 mmol HCI/L. These ulcerogenic factors were effectively inhibited in acid-perfused stomachs of food-deprived rats by daily intraperitoneal injection of the amino acid mixture (150 mg/kg) or by an average daily consumption via drinking water of glucose (10 g) or ascorbate (1.2 g). Starvation aggravated acid-induced gastric damage and was associated with greater acid back-diffusion and oxygen radical generation, and lower mucosal glutathione and mucus production.

Topics: Amino Acids; Animals; Ascorbic Acid; Gastric Acid; Gastric Mucosa; Glucose; Glutathione; Hydrochloric Acid; Lipid Peroxides; Male; Rats; Rats, Sprague-Dawley; Starvation; Stomach Ulcer; Vagotomy

A 29-year-old man was admitted to hospital, unconscious and with extensive bleedings in skin and muscles. For many weeks he had been practically starving himself with suicidal intent. Physical examination revealed signs of anaemia and gingivitis with hypertrophy of the tooth borders and bleeding gums, as well as bright blood on rectal examination. There were extensive ecchymoses and petechiae, especially in the legs. Some of the body hair was corkscrew-curly. Haemoglobin level was 7.2 g/dl, mean corpuscular volume 93 fl, reticulocyte count 29/1000. The Rumpel-Leede test was abnormal (60 petechiae/4 cm2), as were the vitamin C level (0.026 mg/dl whole blood) and the ascorbic acid tolerance test. As these findings indicated scurvy, vitamin C was administered, 1 g daily intravenously for 5 days, followed by 500 mg daily by mouth. Remarkable improvement was apparent as early as 72 hours after onset of treatment. The endogenous depression, the underlying cause of the suicide attempt, was treated with clomipramine. When the patient was discharged after 13 days his physical and mental state was much improved.

Topics: Adult; Ascorbic Acid; Clomipramine; Depressive Disorder; Erythrocyte Count; Erythrocyte Indices; Hemoglobins; Humans; Male; Reticulocytes; Scurvy; Self-Injurious Behavior; Starvation; Suicide, Attempted

Both ascorbic acid content and SDH activity of kidney reached peak levels during sexual maturity and then declined. Starvation stress (21 days) induced low levels of ascorbic acid content and SDH activity of the kidney. Nocturnal levels of ascorbic acid content and SDH activity were significantly lower than the diurnal values.

Topics: Age Factors; Animals; Ascorbic Acid; Circadian Rhythm; Kidney; Lizards; Male; Starvation; Succinate Dehydrogenase

Topics: Animals; Ascorbic Acid; Cytochrome c Group; Glutathione; Guinea Pigs; Lung; Male; Oxidation-Reduction; Oxygen; Perfusion; Rats; Starvation

Effects of induced starvation on the morphology of the oocytic nucleus in Cyprinus carpio have been studied to assess the nature of structural aberrations caused and the adaptations induced in the oocytes during the period of stress on account of inanition. An attempt has also been made to study the fate of a number of metabolites during this period. It has also been observed that the nuclear membrane undergoes partial or complete degeneration and there is a proliferation in the number of nucleoli which tend to move into the cytoplasm. In addition, the degenerating oocytes tend to release most of the metabolites into the interstitial tissue surrounding the oocytes.

Topics: Animals; Ascorbic Acid; Carps; Cell Nucleus; Cyprinidae; Female; Glycogen; Lipid Metabolism; Nuclear Envelope; Nucleic Acids; Oocytes; Ovum; Starvation

Rats were orally administered ascorbic acid at a dose of 30 g/liter during either total starvation, partial starvation, the activity-stress ulcer procedure, or the restraint-cold procedure. In four experiments, ascorbic acid failed to exert significant protective action against stomach ulcer formation and, in fact, may have potentiated the ulcerogenic process.

Topics: Animals; Ascorbic Acid; Cold Temperature; Dose-Response Relationship, Drug; Male; Physical Exertion; Rats; Restraint, Physical; Starvation; Stomach; Stomach Ulcer; Stress, Physiological

The effect of 24 and 48 hours of food and water deprivation on ascorbic acid, liver, leukocyte counts and internal lymphoid organ weights of crossbred chicks was examined. Starvation caused an increase in plasma ascorbic acid level, a significant decrease in leucocyte count in peripheral blood, significant loss in body weight and a profound loss in liver, bursa of fabricius, spleen and thymus weights. Deprived chicks were I.V. injected with Escherichia coli dead bacteria and sheep red blood cells at different times before and after onset of deprivation. Blood samples were taken 3, 6, and 12 days thereafter. A lower antibody titer was found on the 6th day post vaccination in the groups where deprivation started on the day before or on the day of vaccination.

Topics: Animals; Antibodies, Bacterial; Antibody Formation; Ascorbic Acid; Chickens; Escherichia coli; Leukocyte Count; Male; Starvation

1. Male, adult guinea-pigs received a scorbutogenic diet and a daily supplement of 1-0 mg ascorbic acid/100 g body-weight. 2. Restriction of food intake for a period of 17 d resulted in a 25% loss in body-weight and a significant reduction in the retention of ascorbic acid by the spleen, liver and adrenal glands.

Topics: Animals; Ascorbic Acid; Guinea Pigs; Male; Metabolism; Organ Size; Starvation

The response of intact and bursectomized chicks to stressful stimuli has been examined. The stressors imposed were: a. fast-acting ACTH adminstration; b. immersion in cold water; c. starvation. In Bursa-intact chicks the results were as follows: 1. Plasma corticosterone was increased by all stimuli. 2. Adrenal corticosterone was decreased by ACTH treatment while it was increased by immersion in cold water and by starvation. 3. Plasma glucose was increased by ACTH administration and cold water immersion and decreased by starvation of the birds. 4. Adrenal ascorbic acid concentration was not influenced by all stimuli. 5. Adrenal weights were found to be increased by ACTH and starvation treatments only. 6. Bursa weights were increased by ACTH administration. 7. A very low concentration of corticosterone was found in the Bursa of Fabricius. Bursectomized chicks differed from the intact ones in the following: 1. Plasma and adrenal corticosterone concentrations were not increased by starvation. 2. Plasma glucose increased moderately with ACTH administration. 3. Adrenal ascorbic acid was depleted by all stimuli but was not related to the corticosterone level in the adrenals and blood plasma.

Topics: Adrenal Glands; Adrenocorticotropic Hormone; Animals; Ascorbic Acid; Blood Glucose; Body Weight; Bursa of Fabricius; Chickens; Cold Temperature; Corticosterone; Male; Poultry Diseases; Starvation; Stress, Physiological

Topics: Animals; Ascorbic Acid; Cholesterol; Cytochrome P-450 Enzyme System; Glucaric Acid; Glucuronates; Glucuronidase; Glucuronosyltransferase; Hydroxylation; Intestinal Mucosa; Liver; Male; Microsomes, Liver; NADPH-Ferrihemoprotein Reductase; Nitroanisole O-Demethylase; Phenobarbital; Phospholipids; Proteins; Rats; Rats, Inbred Strains; Starvation; Uridine Diphosphate Glucose Dehydrogenase

Topics: Adrenocorticotropic Hormone; Age Factors; Amino Acids; Animal Nutritional Physiological Phenomena; Animals; Animals, Newborn; Ascorbic Acid; Body Weight; Gluconeogenesis; Glucose; Liver; Organ Size; Starvation; Swine; Thirst; Time Factors

Topics: Administration, Oral; Animals; Ascorbic Acid; Body Weight; Female; Gastric Mucosa; Rats; Starvation; Stomach; Stomach Ulcer; Time Factors

Topics: Adrenal Glands; Aging; Animals; Animals, Newborn; Ascorbic Acid; Asphyxia; Brain; Brain Stem; Cerebellum; Female; Fetus; Guinea Pigs; Liver; Male; Nutrition Disorders; Pregnancy; Rats; Starvation

Topics: Aging; Animals; Ascorbic Acid; Carbon Tetrachloride Poisoning; Chemical and Drug Induced Liver Injury; Chlorobutanol; Gossypium; Granulation Tissue; Liver Diseases; Metabolism; Necrosis; Rats; Starvation

Topics: Animals; Ascorbic Acid; Colorimetry; Muscles; Scorpions; Starvation

1. The synthesis of ascorbic acid in rat-liver extracts is impaired during starvation, and more from glucuronolactone and glucuronate than from gulonate and gulonolactone. 2. The formation of xylulose from gulonate and from gulonolactone is greatly enhanced during starvation, whereas it is decreased from glucuronolactone and from glucuronate. 3. The activity of the enzymes of the glucuronic acid pathway during starvation has been determined in rat-liver preparations. Gulonolactone oxidase is decreased, NAD-linked gulonate dehydrogenase is enhanced, and uronolactonase, aldonolactonase and NADP-linked hexonate dehydrogenase are unchanged. 4. The impairment of ascorbic acid synthesis from gulonate observed during starvation can be accounted for by the depressed activity of gulonolactone oxidase. 5. The cause of the enhanced formation of xylulose has been located in the sedimentable fraction of liver homogenate. 6. The hypothesis is formulated of an increased utilization of the glucuronic acid pathway during starvation.

Topics: Alcohol Oxidoreductases; Ascorbic Acid; Carbohydrate Dehydrogenases; Carbohydrate Metabolism; Esterases; Glucuronates; Glucuronic Acid; Lactones; Liver; Liver Extracts; Metabolism; NADP; Oxidoreductases; Pentoses; Rats; Research; Starvation; Sugar Acids; Xylulose

1. The effect of starvation on the synthesis of ascorbic acid and of xylulose from glucuronolactone and from gulonate has been studied with liver extracts from cats, rabbits, hamsters, mice and guinea pigs. 2. The synthesis of ascorbic acid from glucuronolactone is decreased in all species except cats, and that from gulonate is decreased in hamsters and mice only. 3. The synthesis of xylulose from glucuronolactone was decreased in all species except cats and mice, whereas from gulonate it was enhanced in all the species examined.

Topics: Animals; Ascorbic Acid; Carbohydrate Metabolism; Cats; Cricetinae; Glucuronates; Guinea Pigs; Lactones; Liver; Liver Extracts; Metabolism; Mice; Pentoses; Rabbits; Research; Starvation; Sugar Acids; Xylulose

Topics: Absorption; Ascorbic Acid; Fluorides; Gastrointestinal Tract; Metabolism; Phosphates; Radioisotopes; Rats; Research; Starvation

Topics: Adrenal Glands; Adrenalectomy; Animals; Ascorbic Acid; Carbohydrate Metabolism; Flavins; Rats; Riboflavin; Starvation; Vitamin B Deficiency

Topics: Ascorbic Acid; Deficiency Diseases; Humans; Starvation