Vitamin B3 Niacin

Discovery Pellagra: In the early 1900s, primarily in the southern United States, cornbread was the staple food (the most severe deficiency disease in the history of the USA). Affected many individuals, causing severe skin lesions, diarrhea, and mental disturbances. In 1937, niacin was successfully isolated from brewers yeast and identified as the compound that cured pellagra. Niacin supplementation was shown to effectively treat and prevent the condition, healing skin lesions and other symptoms. B3 Niacin – Discovery Niacin Generic term for Nicotinic Acid and Nicotinamide. Both provide vitamin activity, but Nicotinic acid has a popular pharmacological role. Nicotinic acid = pyridine 3-carboxylic acid. Nicotinamide = nicotinic acid amide. B3 Niacin – Structure Food Sources Found abundantly in fish, meats and legumes. Fortified or enriched grains contribute significantly to niacin intake. Also produced by bacteria in the large intestine. Sources of Niacin Dietary Reference Intake: RDA Females: 14 mg/day Males: 16 mg/day What does cooking do to niacin? Niacin in foods is fairly stable (heat, light, oxidation, pH). B3 is generally heat resistant <250°C. Not depleted with normal cooking. Niacin will leach into boiling water. Therefore, avoid boiling in excessive water. OR consume the water that niacin is boiled in. B3 Niacin – Food Sources Supplements, niacin is provided as both Nicotinamide. Nicotinic acid. NAD Supplements? (big trend). Single-ingredient niacin: up to 500 mg. Nicotinamide is used to fortify foods. B3 Niacin – Food Sources Plant Sources of Niacin Niacin may be covalently bound to a carbohydrate or a protein in plants. Found primarily in corn, but also in wheat. Both forms cannot be digested/absorbed in the body. B3 Niacin – Food Sources In Mesoamerica, corn is subjected to alkaline treatment (limewater wash) before milling. The process is called nixtamalization. Promotes the elimination of the hull and the dissolution of hemicellulose. The alkali treatment releases niacin that is bound to the starches. Tortillas saved Mesoamerica from pellagra! B3 Niacin – Food Sources Animal Sources Niacin in animal products is found as: Niacin (B3) - Food Sources Niacin is also produced in the body Synthesized from tryptophan in the liver. An important contribution to the body's niacin needs. About 3% of ingested tryptophan is used to make niacin. B3 Niacin – Food Sources An important contribution to the niacin needs. Niacin Synthesis from Tryptophan B3 Niacin – Food Sources Digestion and Absorption Absorption of plant sources of niacin Niacin found as niacytin or niacinogen cannot be digested/absorbed. These forms of niacin are excreted from the body. B3 Niacin – Digestion and Absorption Absorption of animal sources of niacin Before absorption, NAD/NADP require conversion to free nicotinamide. Involves the enzymes Pyrophosphatase and Glycohydrolase. B3 Niacin – Digestion and Absorption B3 Niacin – Digestion and Absorption B3 Niacin – Digestion and Absorption B3 Niacin – Digestion and Absorption Metabolism and Coenzyme Role Coenzyme forms of niacin NAD = Nicotinamide Adenine Dinucleotide NADP = Nicotinamide Adenine Dinucleotide Phosphate Structure of NAD/NADP Structurally similar BUT differ at one site NAD has an H atom bound here NADP has P group bound here B3 Niacin – Coenzyme After being absorbed into tissues Nicotinamide is converted into NAD or NADP (active coenzyme form). Once converted, NAD and NADP are trapped within the cell. Must be degraded into free nicotinamide before they can leave cell. Most cells have higher amounts of NAD than NADP. B3 Niacin – Metabolism Key things to remember about niacin. When in transport: Niacin is generally in free form. When crossing membranes: Niacin in free form. When in cells/tissues: Niacin is converted to NAD or NADP. B3 Niacin – Metabolism Functions Energy Production: NADH fuels ATP synthesis in cellular metabolism. Biosynthesis: NADPH supports fat, cholesterol, and DNA synthesis. Antioxidant Defense: NADPH helps regenerate antioxidants like glutathione and vitamin C. DNA Repair & Gene Regulation: Through ADP-ribosylation (PARPs, Sirtuins, ARTs). Longevity & Aging: Sirtuins influence metabolism, DNA stability, and aging processes. B3 Niacin – Functions NAD and NADP Act as hydrogen donors or electron acceptors Required by 200 enzymes in the body (dehydrogenases) Oxidation/reduction of the nicotinamide moiety: B3 Niacin – Functions B3 Niacin – Functions Glycolysis NADH + H is generated during glycolysis in the step from glyceraldehyde 3-P to 1,3-diphosphoglycerate Reactions in which NAD participates: B3 Niacin – Functions Oxidative decarboxylation of pyruvate Oxidation of acetyl CoA in the Krebs Cycle Reactions in which NAD participates: B3 Niacin – Functions B3 Niacin – Functions The process of producing ATP from glucose involves a critical step known as the TCA cycle. The key outcome of the TCA cycle is the production of two important molecules: FADH2 and NADH. These molecules serve as high-energy electron carriers within the cell. FADH2 and NADH are analogous to the 'currency' of the cell because they carry high-energy electrons able to make a lot of “money” (ATP). These electrons play a pivotal role in the electron transport chain. FADH2 NADH In the electron transport chain, H+ ions move across the inner mitochondrial membrane from one side to the other. Both FADH2 and NADH contain hydrogen atoms (H) within their structures. These molecules transport these hydrogen atoms to the electron transport chain. The movement of these hydrogen atoms is crucial, as it fuels the generation of ATP. B3 Niacin – Functions Reactions in which NADPH participates: Remember: NADPH generated in the hexosemonophosphate shunt What vitamin is involved with the synthesis of NADPH? B3 Niacin – Functions NADPH as a Reducing Agent NADP is reduced to NADPH in the pentose phosphate pathway and provides reducing power for various biosynthetic reactions: Fatty Acid Synthesis: Required for creating cellular membranes and energy storage molecules. Cholesterol and Steroid Hormone Synthesis: Essential for producing hormones like cortisol, estrogen, and testosterone. Proline Synthesis: Supports collagen formation and connective tissue repair. Deoxyribonucleotide Synthesis: Supplies the precursors for DNA replication and repair. Folate Coenzyme Synthesis: Aids in producing forms of folate critical for nucleotide metabolism and amino acid interconversions. Biosynthetic processes occur in both the cytoplasm and mitochondria. B3 Niacin – Functions NADP Role in Antioxidant Defense NADPH provides the reducing power for antioxidant regeneration. Restores glutathione, the body’s primary antioxidant. Supports the regeneration of vitamin C and thioredoxin, crucial for cellular redox balance. NADPH is indispensable for maintaining the body’s antioxidant systems and protecting against oxidative stress. B3 Niacin – Functions NAD role in DNA Repair NAD is used by PARPs to detect and bind to DNA strand breaks, initiating the repair process. Essential for maintaining genomic integrity during cell replication. Regulates processes like DNA replication, differentiation, and apoptosis. Potential Role in Cancer Prevention: Proper DNA repair may prevent mutations that lead to cancer. Ongoing studies explore niacin’s link to reduced cancer risk. NAD fuels PARPs, ensuring efficient DNA repair and protecting against genomic instability. B3 Niacin – Functions Longevity and Aging Sirtuins, a class of NAD-dependent enzymes, regulate the deacetylation of proteins to modify gene expression and chromatin structure, enhancing genomic stability. Sirtuins are involved in cellular stress responses and DNA repair. They help delay aging-related processes by improving cell cycle regulation and preventing oxidative damage. Influence metabolic pathways linked to energy production and calorie restriction, associated with increased lifespan. May reduce age-related conditions by promoting genomic stability and stress resistance. NAD role in sirtuin activation contributes to improved genomic stability, energy regulation, and possibly delayed aging. B3 Niacin – Functions Requirements, Deficiency and Toxicity Nutrition labels only account for pre-formed niacin DRI niacin recommendation expressed as Niacin Equivalents 1 niacin equivalent (NE) = 1 mg of niacin = 60 mg tryptophan B3 Niacin – Requirements B3 Niacin – Requirements B3 Niacin – Requirements B3 Niacin – Requirements B3 Niacin – Requirements Deficiency disease: Pellagra Common in places where corn is a staple food. Rural South America. Also seen in Africa, Indonesia, and refugee populations. Deficiency symptoms (“Four Ds”) Dermatitis – at first, looks like a sunburn. Dementia – Apathy, memory loss, paralysis. Diarrhea – Also includes glossitis, vomiting. Death – If left untreated. B3 Niacin – Deficiency Who is at risk? Severe poverty and food insecurity Individuals with malabsorption disorders Alcoholism (decreased food/vitamin intake) Elderly (decreased absorption and intake) People taking anti TB medications Binds B6 – required for niacin synthesis B3 Niacin – Deficiency Side effects of consuming 1 g or more per day: Acute effects Vasodilation - Increased histamine release, flushing, itching Gastrointestinal – Heartburn, nausea, vomiting (>6 g/day) Chronic effects Gout – niacin competes with uric acid for excretion by kidney Liver injury B3 Niacin – Toxicity B3 Niacin – Toxicity NAD and NADP are first broken down to nicotinamide in the liver. This enzyme is also found in the small intestine. B3 Niacin – Excretion B3 Niacin – Excretion Clinical Uses High doses of niacin (nicotinic acid) are used to treat hypercholesterolemia Can correct different forms of dyslipidemia: High total cholesterol High LDL cholesterol High triglycerides Low HDL cholesterol Hypercholesterolemia treatment Niacin is the only treatment that affects all 4 lipid parameters! 6 g/day dose, divided over the day Supplements provide niacin as nicotinic acid. B3 Niacin – Clinical Uses B3 Niacin – Clinical Uses B3 Niacin – Clinical Uses B3 Niacin – Clinical Uses Nicotinamide, in large doses, does not reduce blood lipids. Used topically to reduce inflammation associated with acne vulgaris aka niacinamide Used orally to treat necrobiosis lipoidica (reddish-brown bruiselike markings, most often on the lower legs). Nicotinamide reduced the rates of new nonmelanoma skin cancers in individuals with at least two nonmelanoma skin cancers in the previous 5 years (500 mg doses given twice daily) B3 Niacin – Clinical Uses Identified as a cure for pellagra in 1937; critical in preventing deficiency-related diseases. Found in fish, meats, legumes, fortified grains, and synthesized from tryptophan in the liver. Nixtamalization enhances availability in corn-based diets. Animal sources: NAD/NADP converted to free nicotinamide before absorption. Plant sources: Bound forms of niacin (niacytin/niacinogen) are indigestible unless processed. Energy production: NADH fuels ATP synthesis. Biosynthesis: NADPH supports fatty acid, cholesterol, and DNA synthesis. Antioxidant defense: NADPH regenerates glutathione. DNA repair: NAD fuels PARPs to repair DNA damage. Longevity: Sirtuins, activated by NAD+, regulate aging-related processes. Deficiency leads to pellagra (Four Ds: dermatitis, diarrhea, dementia, and death). Excess intake (>1 g/day) can cause flushing, gout, and liver damage. Clinical Uses: High-dose nicotinic acid for managing hypercholesterolemia by improving lipid parameters. Nicotinamide reduces nonmelanoma skin cancer risk and treats acne.