Cellular Health and Nutrition II PDF

BIOL 2006SEF CELLS IN HEALTH AND DISEASE TOPIC 5: CELLULAR HEALTH AND NUTRITION II Heidi Wong [email protected] Outline  Malnutrition: Marasmus, Kwashiorkor, Cachexia, Anorexia Nervosa and Bulimia, Vitamin A Deficiency, Iodine Deficiency Disorder (IDD), Scurvy  Functional Food ...

BIOL 2006SEF CELLS IN HEALTH AND DISEASE TOPIC 5: CELLULAR HEALTH AND NUTRITION II Heidi Wong [email protected] Outline  Malnutrition: Marasmus, Kwashiorkor, Cachexia, Anorexia Nervosa and Bulimia, Vitamin A Deficiency, Iodine Deficiency Disorder (IDD), Scurvy  Functional Food  Probiotics  Nicotinamide mononucleotide (NMN) Malnutrition According to World Health Organization (WHO) Malnutrition refers to deficiencies, excesses, or imbalances in a person’s intake of energy and/or nutrients. The term malnutrition addresses 3 broad groups of conditions: 1. undernutrition, which includes wasting (low weight-for-height), stunting (low height-for- age) and underweight (low weight-for-age); 2. micronutrient-related malnutrition, which includes micronutrient deficiencies (a lack of important vitamins and minerals) or micronutrient excess; and 3. overweight, obesity and diet-related noncommunicable diseases (such as heart disease, stroke, diabetes and some cancers). The WHO defines severe acute malnutrition (SAM) as a state characterized by a greatly reduced weight for height ratio that is below 3 standard deviation Marasmus (消瘦病) Marasmus develops when the diet is severely deficient both in protein and non-protein nutrients resulting from starvation A marasmic child suffers growth retardation and loss of muscle mass as a result of catabolism and depletion of the somatic protein compartment. The resultant reduction in muscle mass is reflected by reduced circumference of the midarm Lean and fat tissues have wasted away, burned off to provide energy to stay alive Concurrent infections are usually present Kwashiorkor (紅孩兒症/夸希奧科症) Kwashiorkor develops when the diet is more deficient in protein than in other nutrients Child displaced from breast-feeding by birth of second child This is the most common form of SAM seen in African children who have been weaned too early and subsequently fed, almost exclusively, a carbohydrate diet The visceral compartment is depleted more severely and the resultant hypoalbuminemia gives rise to generalized or dependent edema Cachexia (惡病體質) Develops in chronically ill, older, and bedridden patients, especially in patients with advanced cancer One of the most common causes of cancer death Characterized by anorexia, malnutrition, involuntary weight loss & tissue, inability to perform daily activities & metabolic alterations Pathophysiology is not completely understood:  accumulation of metabolites (e.g. lactate, ketones, oligonucleotides),  hypercatabolic state induced by “cachectic factors” (e.g. TNF- α) released by the tumor itself or by normal cells in response to tumor Anorexia Nervosa and Bulimia (厭食症,暴食症) Anorexia nervosa is a state of self-induced starvation resulting in marked weight loss Bulimia is a condition in which the patient binges on food and then induces vomiting. Bulimia is more common than anorexia nervosa and carries a better prognosis It is estimated to occur in 1% to 2% of women and 0.1% of men, with an average age at onset of 20 years Anorexia nervosa Effects on the endocrine system are prominent. Amenorrhea, resulting from decreased secretion of gonadotropin-releasing hormone Other common findings, related to decreased thyroid hormone release, include cold intolerance, bradycardia, constipation, and changes in the skin and hair. In addition, dehydration and electrolyte abnormalities are frequent findings. Body hair may be increased but usually is fine and pale (lanugo). Bone density is decreased, most likely because of low estrogen levels, which mimics the postmenopausal acceleration of osteoporosis. Bulimia Binge eating is the norm. Huge amounts of food, principally carbohydrates, are ingested, only to be followed by induced vomiting. Although menstrual irregularities are common, amenorrhea occurs in less than 50% of bulimic patients, probably because weight and gonadotropin levels are maintained near normal. The major medical complications are related to continual induced vomiting and chronic use of laxatives and diuretics. These include 1. electrolyte imbalances (hypokalemia), which predispose the patient to cardiac arrhythmias; 2. pulmonary aspiration of gastric contents; and 3. esophageal and stomach rupture. Nevertheless, there are no specific signs and symptoms for this syndrome, and the diagnosis must rely on a comprehensive psychologic assessment of the patient.  Vitamin A Deficiency Essential fat-soluble vitamin crucial for vision, immune function, and cell growth. Common in areas with limited access to diverse diets. Causes 1. Inadequate dietary intake of Vitamin A-rich foods. 2. Malabsorption issues affecting Vitamin A absorption. 3. Increased demand (e.g., during pregnancy or illness) without adequate intake. Clinical Presentation A. Ocular Manifestations 1. Night blindness: Difficulty seeing in dim light. 2. Conjunctival xerosis: Dryness of the conjunctiva. 3. Bitot's spots: Foamy patches on the conjunctiva. 4. Corneal xerosis: Dryness of the cornea. 5. Corneal ulceration and blindness in severe cases. B. Non-Ocular Manifestations 1. Impaired immune function leading to increased susceptibility to infections. 2. Skin changes: Dry, rough skin and increased vulnerability to dermatological issues. 3. Growth retardation, especially in children. 4. Increased mortality risk, particularly in vulnerable populations. Diagnosis and Evaluation - Clinical assessment of ocular and non-ocular symptoms. - Blood tests to measure serum retinol levels for confirmation. Management and Treatment A. Dietary Interventions 1. Encouraging consumption of Vitamin A-rich foods like liver, dairy products, and colorful fruits and vegetables. 2. Vitamin A supplementation programs in at-risk populations. B. Medical Interventions 1. Treatment of ocular complications with Vitamin A supplementation. 2. Addressing infections promptly to prevent complications. Iron Deficiency Anemia Most common form of anemia globally, caused by inadequate iron levels for red blood cell production. Prevalent in all age groups, particularly women of childbearing age and children. Causes 1. Inadequate dietary intake of iron-rich foods. 2. Blood loss from menstruation, gastrointestinal bleeding, or other sources. 3. Poor iron absorption due to medical conditions or dietary factors. Symptoms 1. Fatigue, weakness, and decreased exercise tolerance. 2. Pale skin and mucous membranes. 3. Shortness of breath and dizziness. 4. Cold hands and feet. 5. Headaches and lightheadedness. Physical Signs 1. Brittle nails and hair loss. 2. Angular stomatitis (cracks at the corners of the mouth). 3. Glossitis (inflammation of the tongue). 4. Pica (craving non-food substances like ice or dirt). Consequences A. Impact on Health 1. Impaired oxygen transport leading to fatigue and decreased physical performance. 2. Cognitive effects: Poor concentration, reduced work capacity. 3. Compromised immune function, leading to increased susceptibility to infections. 4. Adverse effects on pregnancy outcomes and child development. B. Long-Term Complications 1. Heart problems: Increased risk of heart failure and arrhythmias. 2. Developmental issues in children: Impaired growth and cognitive development. 3. Worsening of existing chronic conditions due to decreased tissue oxygenation. Diagnosis and Evaluation - Blood tests measuring hemoglobin, serum iron, ferritin, and transferrin levels. - Evaluation of red blood cell indices (MCV, MCH, MCHC) to assess anemia type. Management and Treatment A. Dietary Interventions 1. Iron-rich foods: Red meat, poultry, fish, legumes, dark leafy greens. 2. Vitamin C-rich foods to enhance iron absorption. B. Supplementation 1. Oral iron supplements for mild to moderate cases. 2. Intravenous iron therapy for severe or non-responsive cases. Iodine Deficiency Disorder (IDD) Result of inadequate iodine intake, crucial for thyroid hormone production. Global public health concern affecting all age groups, particularly pregnant women and infants. Causes 1. Insufficient dietary iodine intake due to low iodine levels in soil and water. 2. Lack of access to iodized salt, the primary source of dietary iodine. 3. Increased iodine requirements during pregnancy and lactation. II. Clinical Presentation A. Thyroid Manifestations 1. Goiter: Enlargement of the thyroid gland, visible as a swelling in the neck. 2. Hypothyroidism: Symptoms include fatigue, weight gain, cold intolerance. 3. Cretinism (severe hypothyroidism in infants): Intellectual disability, stunted growth, and physical deformities. Other Symptoms 1. Cognitive impairment: Reduced mental function, learning difficulties. 2. Developmental delays in children. 3. Increased susceptibility to infections. 4. Fertility issues and pregnancy complications. Consequences A. Impact on Health 1. Impaired thyroid function affecting metabolism and growth. 2. Neurological effects: Reduced IQ, attention deficits, and learning disabilities. 3. Growth retardation and physical deformities in severe cases. 4. Increased risk of miscarriage, stillbirth, and neonatal mortality. B. Endemic Goiter 1. Visible swelling in the neck due to thyroid enlargement. 2. Discomfort, difficulty swallowing, and breathing problems. 3. Psychosocial impact due to cosmetic concerns. Diagnosis and Evaluation - Assessment of thyroid function through blood tests measuring TSH and thyroid hormone levels. - Physical examination to detect signs of thyroid enlargement (goiter). Management and Treatment A. Iodine Supplementation 1. Universal salt iodization programs to ensure adequate iodine intake. 2. Iodine supplements for pregnant women and vulnerable populations. B. Education and Awareness 1. Promoting the use of iodized salt in cooking and food preparation. 2. Public health campaigns on the importance of iodine for health. Scurvy Scurvy is a condition caused by a severe deficiency of vitamin C (ascorbic acid). Historically associated with sailors on long sea voyages lacking fresh fruits and vegetables. Symptoms 1. Early Signs: - Fatigue and weakness. - Joint pain and muscle aches. - Easy bruising and petechiae (small red or purple spots on the skin). 2. Advanced Symptoms: - Swollen, bleeding gums. - Tooth loss and gum disease. - Slow wound healing and skin changes. Consequences A. Dental and Oral Health 1. Bleeding gums leading to tooth loss. 2. Gum infections and periodontal disease. B. Hematological Complications 1. Anemia due to impaired iron absorption. 2. Easy bruising and petechiae from weakened blood vessels. C. Musculoskeletal Effects 1. Joint pain and swelling. 2. Impaired bone formation and increased risk of fractures. Diagnosis and Evaluation - Clinical assessment based on symptoms and history of dietary deficiencies. - Blood tests to measure vitamin C levels for confirmation. Management and Treatment A. Vitamin C Supplementation 1. Immediate administration of vitamin C supplements. 2. Oral or intravenous vitamin C for severe cases. B. Dietary Changes 1. Encouragement of vitamin C-rich foods like citrus fruits, berries, and vegetables. 2. Education on the importance of a balanced diet for preventing scurvy. Functional Foods  A positive impact on health beyond basic nutrition  bioactive compounds that provide health benefits  contribute to the prevention of diseases or the promotion of health  In contrast to conventional foods, functional foods are specifically recognized for their role in health promotion Key Characteristics of Functional Foods 1. Nutritional Benefits: Functional foods are often enriched with vitamins, minerals, or other nutrients that add health benefits beyond basic nourishment. 2. Bioactive Compounds: These foods may contain phytochemicals (plant-derived compounds), antioxidants, fatty acids, or probiotics that can support various bodily functions and improve overall health. 3. Health Claims: Many functional foods can make specific health claims. For example, they may help improve cardiovascular health, enhance digestive health, or support immune function. Phytochemicals May play a role in reduction of risk of certain types of cancer and other diseases Prevent the formation of potential carcinogens Block the action of carcinogens on their target organs Act on cells to suppress cancer development No supports for claims that taking phytochemical supplements is as helpful as consuming the fruits, vegetables, beans, and grains from which they are taken Functional Foods Key Components Potential Health Benefits Soy Foods Soy protein Reduce risk of cancer and heart Isoflavones disease Reduce symptoms of menopause Green/Black Tea Catechins Reduce risk of certain cancer Whole Grains Fiber, Reduce risk of cancer and heart phytoestrogens disease Nuts Monounsaturated Reduce risk of heart disease Citrus Fruits ß-Carotene Improve cardiovascular health Garlic, Onion Organic sulfur Reduce risk of cancer and heart disease Functional Foods Key Components Potential Health Benefits Fatty Fish Omega-3 fatty acids Reduce risk of heart Probiotics disease Yogurt (Bifidobacteria Some dairy products Lactobacilli) Enhance body’s immune defense Probiotics (益生菌) Prebiotics and probiotics play a positive role in promoting human nutrition and health. Prebiotic was described as “a non-digestible food ingredient that beneficially affects the host by selectively stimulating the growth and/or activity of one or a limited number of bacteria in the colon, and thus improves host health”. E.g. whole grains, bananas, greens, onions, garlic, soybeans and artichokes Probiotics defined as microorganisms that have a beneficial effect on the host intestinal microbial balance E.g Lactobacilli (乳酸桿菌) and bifidobacteria (雙歧桿菌) are the most common types of microbes used as probiotics Prebiotics are compounds that cannot be digested by the host, but can be fermented by probiotics, so as to promote the reproduction and metabolism of intestinal probiotics for the health of body.  Major Mechanism of Action of Probiotics https://porcinehealthmanagement.biomedcentral.com/articles/10.1186/s40813-022-00295-6 https://www.researchgate.net/figure/Major-mechanisms-of-action-of-probiotics_fig1_272021145 The mechanism of action of probiotics, or how they exert their health benefits, can vary depending on the specific strains and the health condition being targeted. Here are some common mechanisms of action associated with probiotics: 1. Gut Microbiota Modulation:  influence the composition and diversity of the gut microbiota.  help restore or maintain a healthy balance of beneficial bacteria, which is important for overall gut health  compete with harmful or pathogenic bacteria for nutrients and adhesion sites in the gut, making it more difficult for the pathogens to establish and multiply 2. Production of Beneficial Substances:  produce short-chain fatty acids (SCFAs), such as butyrate, which are important for gut health and provide energy to the cells lining the intestinal wall  increase in SCFAs also leads to a decrease in the pH of the intestine and is beneficial to human health  a suitable pH value to maintain the adhesion ability of probiotics, promote their growth and colonization, and effectively inhibit the reproduction of harmful bacteria  produce antimicrobial substances that inhibit the growth of harmful bacteria in the gut 3. Enhancement of Intestinal Barrier Function:  strengthen the integrity of the intestinal barrier, which is a protective layer that prevents harmful substances from entering the bloodstream  help maintain the tight junctions between cells in the intestinal lining, reducing the permeability of the gut and potentially reducing the risk of harmful substances crossing into the bloodstream 4. Modulation of the Immune System:  interact with the immune system and help regulate immune responses  enhance the activity of immune cells and promote the production of anti- inflammatory substances, thereby modulating immune function and potentially reducing inflammation in the gut 5. Metabolism of Dietary Components:  Some strains of probiotics have the ability to metabolize certain dietary components that humans cannot digest on their own  For example, they can break down complex carbohydrates and fibers into simpler molecules that the body can absorb and utilize. 6. Reduction of Pathogenic Bacteria:  inhibit the growth of harmful or pathogenic bacteria through various mechanisms  outcompete the pathogens for nutrients or produce substances that directly inhibit their growth or kill them.  What is Nicotinamide mononucleotide (NMN)? Nicotinamide mononucleotide (NMN) is a naturally occurring molecule found in every living cell of all life forms. At the molecular level, it belongs to a class of molecules called nucleotides, the building blocks of RNA and DNA. Structurally, NMN is composed of three main chemical groups: a phosphate group, a ribose sugar, and a nicotinamide base. NMN is directly converted to nicotinamide adenine dinucleotide (NAD+), thereby elevating NAD+ levels, which is why NMN is sometimes referred to as an NAD+ booster. NAD+ Reduced NAD+ levels have been linked to all the hallmarks of aging. The declining NAD+ levels is associated with lower energy production, compromised genomic signaling, and DNA repair mechanism. NAD+ is an essential coenzyme found in the human body and is involved in several metabolic processes such as glycolysis, tricarboxylic acid cycle (TCA), mitochondrial respiration, and fatty acid beta-oxidation. In addition to being a coenzyme that catalyzes cellular redox reactions, NAD+ is found to be involved in DNA damage response, transcription, and translation. Environmental factors such as pollution, radiation, and inaccuracies in DNA replication can cause DNA damage in organisms as they age. The main cause of aging is associated with the accumulation of damaged DNA. Every cell contains the mechanism to repair this damaged DNA, and it utilizes the energy and NAD+ molecules. However, excessive DNA damage can deplete these important cellular resources.  NAD+ is required for the activation of one of the key DNA repair proteins referred to as Poly ADP-ribose polymerase (PARP). The amount of NAD+ in the body decreases as people age. As a result of the normal aging process, DNA damage accumulates, causing a rise in PARP, which causes a drop in NAD+ concentration. Any additional DNA damage in the mitochondria worsens this depletion. NAD+ is also required for sirtuins activation, which is associated with beneficial roles in anti-aging, longevity, and stress responses. NAD+ levels in mammals can be boosted through diet, intake of NAD+ precursors, caloric restriction (CR), fasting, and exercise. Precursors of NAD+ NAD+ is produced in human bodies naturally from smaller components known as precursors. Five precursors or intermediates for NAD+  tryptophan  nicotinamide  nicotinic acid (pyridine-3-carboxylic acid)  nicotinamide mononucleotide (NMN)  Nicotinamide riboside (NR) NMN is one of the last steps in the NAD+ synthesis Molecular Biology Reports (2022) 49:9737–9748 https://doi.org/10.1007/s11033-022-07459-1 NAD+ biosynthetic pathways (1) de novo pathway NAD+ is generated via tryptophan which is the amino acid found in the diet. Tryptophan from the diet is transported into the cell by transporters SLC7A5 and SLC36A4. Once tryptophan is inside the cell, it undergoes conversion to N-formylkynurenine via a rate- limiting enzyme indoleamine 2,3-dioxygenase 1 (IDO1) or tryptophan 2,3-dioxygenase 2 (TDO2). N-formylkynurenine is converted to L-kynurenine, and then to 3-hydroxykynurenine (3-HK), which further undergoes conversion to 3-hydroxyanthranilicm acid (3-HAA) and α-amino-β- carboxymuconate ε-semialdehyde (ACMS). ACMS is then auto condensed to quinolinic acid, which is converted to nicotinamide mononucleotide (NAMN) via the enzyme quinolinate phosphoribosyltransferase (QPRT), the point where it merges with the Preiss-Handler pathway. (2) Preiss-Handler pathway nicotinic acid (NA) is transported into the cell by either SLC5A8 or SLC22A13 transporter and then gets converted into NAD+ through three intermediate steps. Firstly, the enzyme nicotinic acid phosphoribosyltransferase (NAPRT) converts nicotinic acid to nicotinic acid mononucleotide (NAMN), and then enzymes nicotinamide mononucleotide adenylyltransferases (NMNAT1-3) converts NAMN to nicotinic acid adenine dinucleotide (NAAD) followed by NAAD to NAD+ conversion by NAD+ synthetase (NADS) (3) salvage pathway the most predominant in mammalian cells, which requires phosphorylation of NR to NMN by NR Kinase. In the salvage pathway, nicotinamide that is generated by nicotinamide adenine dinucleotide- consuming enzymes such as sirtuins (SIRTs), poly (ADP-ribose) polymerases (PARPs), and the signaling enzymes like CD38, CD157, and SARM1 is recycled. Sirtuins are considered key regulators in the process of aging and longevity.  Primarily, nicotinamide (NAM) is recycled to NMN via intracellular nicotinamide phosphoribosyltransferase (iNAMPT) and then to NAD+ via nicotimanide mononucleotide adenyltransferase (NMNAT). Alternatively, NMN is excreted via urine through methylation by the enzyme nicotinamide N- methyltransferase (NNMT). Extracellularly, NAM is converted to NMN by extracellular NAMPT (eNAMPT). The NMN then undergoes dephosphorylation, which is then converted to nicotinamide riboside (NR) and imported into the cell by an unknown transporter. Recent pre-clinical studies have shown that an NMN specific transported called SLC12A8 has the potential to transport NMN into the cell. Inside the cell, NR is converted to NMN by nicotinamide riboside kinase 1 (NRK1) which is then converted to NAD+ via NMNAT. Therapeutic potential of NMN age-related disorders in humans is closely correlated with an age-related reduction in NAD+ levels studies on human and animal models have demonstrated that age- related illnesses can be prevented by increasing NAD+ levels Research category:  Diabetes  Cardiovascular health  Brain health  Vascular health  Cancer  Retinal detachment  Infertility  Acute kidney injury Reference Sizer, F. S., & Whitney, E. N. (2020). Nutrition: concepts & controversies. 15th edition. Boston, MA, Cengage.