Vitamins/Supplements Vitamins have the following defining characteristics: - They are organic compounds, required in minute amounts for growth and maintenance of health, and do not serve as a source of energy (in contrast to fats, carbohydrates, and proteins) but rather are essential for energy transformation and regulation of metabolic processes. Several vitamins are inactive in their native form and must be converted to active compounds in the body. RDA: is the average daily dietary intake sufficient to meet the nutrient requirements of nearly all (97% to 98%) healthy individuals. These figures are not absolutes. RDAs change as people grow older. AI: an estimate of the average daily intake required to meet nutritional needs. UL: the highest average daily intake that can be consumed without a significant risk for adverse AE - UL is not a recommended upper limit for intake. It is simply an index of safety. EAR: is the level of intake that will meet nutrition requirements for 50% of the healthy individuals in any life-stage or gender group. By definition, the EAR may be insufficient for the other 50%. AMDR: is a range for macronutrients (e.g., proteins, carbohydrates, and fats) associated with optimal health. - Intake of a nutrient below the established range for that nutrient i the risk for malnourishment. Intake of a nutrient above the established range for that nutrient the risk for chronic diseases. Fat-soluble Vitamins - Stored in massive amounts in body, this can the risk for deficiency but if taken excessively can risk for toxicity Vitamin A, D, E, K (Vitamin D covered already) Vitamin Vit. A (retinol) Functions Eye: role in adaptation to dim light Other: embryogenesis, spermatogenesis, immunity, growth, and maintaining the structural and functional integrity of the skin and mucous membranes Indication Prevention or correction of vitamin A deficiency Admin Night blindness 1st indc of deficiency High doses: can cause birth defects, liver injury, and bone-related disorders. To risk, UL: 3000 µg/day. Vitamin A is highly teratogenic (can cause malformation of the fetal heart, skull, and other structures of cranial–neural crest origin) Source Consumed in foods w/ preformed Vitamin A (meat, fish, oil, fish) provitamin A carotenoids (these are converted to retinol in intestines) in darkcolored carotene-rich fruits and veggies If pregnant: don’t exceed UL or RDA Vit. E No established role in human nutrition, has antioxidant properties High-dose: appears to risk for hemorrhagic stroke by inhibiting platelet aggregation. From vegetable oils (corn oil, olive oil, cottonseed oil, safflower oil, and canola oil). Also found in nuts, wheat germ, whole-grain products, and mustard greens. Required for synthesis of prothrombin and clotting factors VII, IX, and X. Vit. K Correction or prevention of hypoprothrombinemia and bleeding caused by vitamin K deficiency Control of hemorrhage caused by warfarin Vitamin K deficiency produces bleeding tendencies Severe deficiency: spontaneous hemorrhage may occur. The oral form of vitamin K1 is not toxic in adults. In newborns, intracranial hemorrhage is of particular concern. - Vitamin K toxicity can cause hyperbilirubinemia, hemolytic anemia, and jaundice in newborns. The vitamins are divided into two major groups: fat-soluble and water-soluble. In the fat-soluble group are vitamins A, D, E, and K. Water soluble Vitamins - Vitamin c, members of the vitamin B complex (thiamine, riboflavin, niacin, pyridoxine, pantothenic acid, biotin, folic acid, and cyanocobalamin). Except for vitamin B12, water-soluble vitamins undergo minimal storage in the body; hence frequent ingestion is needed to replenish supplies. Vitamins Vit. C Functions Indication Admin Source Synthesis of adrenal steroids, conversion of folic acid to folinic acid, and regulation of the respiratory cycle in mitochondria. Only indication is prevention and treatment of scurvy For severe, acute deficiency: parenteral administration is recommended. The main dietary sources of ascorbic acid are citrus fruits and juices, tomatoes, potatoes, strawberries, melons, spinach, and broccoli. At the tissue level, its required for production of collagen and other compounds that comprise the intercellular matrix, which binds cells together. Also, it facilitates absorption of dietary iron Niacin Role as both a vitamin and a medicine (nicotinic acid) Medicinal role: used to cholesterol levels Riboflavin Numerous enzymatic reactions must first be converted into one of two active forms: flavin adenine dinucleotide (FAD) or flavin mononucleotide (FMN). In the form of FAD or FMN, riboflavin acts as a coenzyme for multiple oxidative reactions. Deficiency can lead to scurvy, a disease rarely seen in the USA. Excessive doses can cause N/D, and abdominal cramps As a vitamin: only for the prevention or treatment of niacin deficiency The syndrome caused by niacin deficiency is called pellagra. off-label for the treatment of pellagra Large doses: can cause vasodilation, with resultant flushing, dizziness, and nausea Only for prevention and correction of riboflavin deficiency and migraines Riboflavin appears devoid of toxicity to humans. Has very low toxicity, and small doses are devoid of AE. Excess is rapidly excreted in the urine Orange juice and lemon juice are especially rich sources Particularly rich sources are liver, poultry, fish, potatoes, peanuts, cereal bran, and cereal germ Most dietary forms come from milk, yogurt, cheese, bread products, and fortified cereals. Organ meats are also rich sources. Thiamine (thiamine pyrophosphate Active form: essential coenzyme for carbohydrate metabolism Only indication for thiamine is treatment and prevention of thiamine deficiency. Severe thiamine deficiency produces wet beriberi and dry beriberi. Wet primary symptom is fluid accumulation in the legs leading to CV complications. Dry characterized by neurologic and motor deficits. Deficiency occurs most commonly among people with chronic alcohol consumption manifests as WernickeKorsakoff syndrome. - The principal dietary sources are enriched, fortified, or whole-grain products, especially breads and ready-to-eat cereals. The richest sources of the natural vitamin are fish (especially tuna, salmon, and anchovies) and liver. Chicken, pork, beef, and lamb are also good sources. nystagmus, diplopia, ataxia, and an inability to remember the recent past. Failure to correct the deficit may result in irreversible brain damage. Oral devoid of SE Pyridoxine (B6) Functions as a coenzyme in the metabolism of amino acids and proteins, must first be converted to its active form: pyridoxal phosphate. Prevention and treatment of all states of vitamin B6 deficiency. These include dietary deficiency, isoniazid-induced deficiency, and pyridoxine dependency syndrome Deficiency may result from poor diet, isoniazid therapy for TB, and inborn errors of metabolism. - Symptoms include seborrheic dermatitis, anemia, peripheral neuritis, convulsions, depression, and confusion. Dietary deficiency of vitamin B6 is rare except among people who abuse alcohol on a long-term basis. Principal dietary sources are fortified, ready-to-eat cereals; meat, fish, and poultry; white potatoes and other starchy vegetables; and noncitrus fruits. Especially rich sources are organ meats (beef liver) and highly fortified cereals or soy-based products. Low doses: pyridoxine is devoid of AE Extremely large doses: neurologic injury may result. - Ataxia and numbness of the feet and hands. To risk, >100 mg/day, the UL for this vitamin Interferes w/ levodopa Cyanocobalamin Involved in carb, fat, and protein synthesis and is a factor in the synthesis of DNA and (B12) in the formation of blood cells. For treatment of deficiency due to all causes. Has a low potential for toxicity Greatest sources are clams and liver. Functions as a coenzyme in the synthesis of nucleic acids (DNA and RNA). Folate It also has a role in the metabolism of amino acids. Also used to prevent deficiency in pts with vit B12 req (pregnancy or with hemorrhage or liver disease) Other sources are meat, fish, poultry, eggs, milk, and other animal products. It is also a component of fortified foods such as processed cereals. Prevent neural tube defects (NTDs) in the developing fetus. Beef liver is the highest source of folate. Other good sources include spinach, black-eyed peas, asparagus, and green leafy vegetables. They are also used to treat megaloblastic anemia. To folic acid in the American diet, the US Food and Drug Administration (FDA) requires that all enriched grain products (enriched bread, pasta, flour, breakfast cereal, grits, and rice) must be fortified with folic acid. Off-label to toxicity due to antifolate chemotherapy. Pantothenic acid An essential component of two biologic molecules: coenzyme A and acyl carrier protein. Coenzyme A is an essential factor in multiple biochemical processes, including gluconeogenesis, intermediary metabolism of carbohydrates, and biosynthesis of steroid hormones, porphyrins, and acetylcholine. The only known cause for pantothenic acid deficiency is pantothenate kinase– associated neurodegeneration 2 mutation, a rare genetic condition Present in virtually all foods. Deficiency is extremely rare. In a wide variety of foods, although the exact amount in most foods has not been determined. Acyl carrier protein is required for synthesis of fatty acids. Biotin Essential cofactor for several reactions involved in the metabolism of carbohydrates and fats treat hair loss and improve skin condition. Prescribed to treat biotinidase deficiency, a rare inherited disorder Biotin appears to be devoid of toxicity: subjects given large doses experienced no adverse effects In addition to being available in foods, biotin is synthesized by intestinal bacteria. Regulation of Dietary Supplements Dietary Supplement Health and Education Act (DSHEA) - The DSHEA categorizes botanical products, herbal supplements, vitamins and minerals as dietary food supplements rather than drugs. - By classifying these products as dietary supplements, this exempts them from undergoing FDA scrutiny and approval before marketing (can be manufactured and marketed without giving the FDA any proof they are safe or effective) If a product eventually proves to be harmful or makes false claims, then the FDA has the authority to intervene, but only after the product has already been released for marketing. All herbal products must be labeled as dietary supplements. Labels must not claim that the product can be used to diagnose, prevent, treat, or cure disease, its allowed to make claims about the body structure or function. The DSHEA does not address the issues of impurities, adulterants, or variability. As a result, dangerous products have been allowed to reach consumers. In June 2007, the FDA issued a set of standards to regulate the manufacturing and labeling of dietary supplements. These standards, referred to as CGMP, are designed to ensure that dietary supplements be devoid of adulterants, contaminants, and impurities and that package labels accurately reflect the identity, purity, quality, and strength of what is inside. - In addition, the label should indicate not only active ingredients but also inactive ingredients. The Dietary Supplement and Nonprescription Drug Consumer Protection Act, passed in 2006, mandates the reporting of serious adverse events for nonprescription drugs and dietary supplements. The following events should be reported: deaths, hospitalizations, life-threatening experiences, persistent or significant disabilities, and birth defects. Manufacturers and distributors must report these to the FDA within 15 days. Reports can be filed by telephone, by mail, or through the MEDWATCH program at http://www.fda.gov/Safety/MedWatch. Four private organizations: the US Pharmacopeia (USP), ConsumerLab, the Natural Products Association, and NSF International (formerly known as the National Sanitation Foundation) test dietary supplements for quality. - A “seal of approval” is given to products that meet their standards, which are very similar to the CGMP described previously. All four organizations require manufacturers to pay for the tests, and all four report on the following: purity, identity, potency; dissolution; and accuracy of labeling. 3-step process in which the manufacturer (1) prepares an extract of plant parts, (2) analyzes the extract for one or two known active ingredients, and (3) dilutes or concentrates the extract such that the final product contains a predetermined amount of the active ingredients. o The objective is to achieve therapeutic equivalence from batch to batch made by the same manufacturer and among batches made by different manufacturers. Herbal supplements Supplement MOA Indication Admin Black cohosh Used to treat symptoms of menopause including hot flashes, vaginal dryness, palpitations, depression irritability and sleep disturbance Unknown Insufficient evidence to support the management of menopausal symptoms Butterbur Taken for migraines, allergies, and asthma. Anti-inflammatory, antispasmodic, and vasodilatory effects. Long-term safety has not been established but appears to be safe for short-term use of less than 4 months at recommended doses. Drug interaction Adverse Effects Potentiate hypotensive effects of antihypertensive drugs, hypoglycemic effects of insulin and other diabetic drugs, and estrogen liver inflammation, rash, headache, and dizziness There is concern about liver injury because of pyrrolizidine alkaloids (PAs) Coenzyme Q-10 (ubiquinone, CoQ-10 Cranberry juice Echinacea One of the few botanicals recommended as a drug of 1st choice based on outcomes of trials The exact mechanism of action is unknown Antioxidant that serves a vital role in cellular energy production It participates in many metabolic pathways, most notably production of adenosine triphosphate (ATP). Used to treat heart failure, muscle injury caused by HMG-CoA reductase inhibitors (statins), and mitochondrial encephalomyopathies Preventing UTI and to urine odor in pts with urinary incontinence Some believe that butterbur works as a calcium channel blocker As we age, CoQ-10 levels Use during pregnancy and lactation is not established. This is structurally similar to Vit K2 and may antagonize effects of warfarin. Proanthocyanidins interfere with the bacterial adhesion to the urinary tract Oral: taken to stimulate immune function, suppress inflammation, and treat viral infections, including influenza and the common cold. May the INR of warfarin Daily intake helps prevent UTI in women in their teens or 20s and in elderly women, but not in middle aged adults or young girls. Used orally and topically More than 1L per day may cause kidney stones. Long term use should be avoided in those immunocompromised because long-term exposure can suppress immune function. Can oppose the effects of immunosuppressant drugs. Used primarily for the prophylaxis of migraine Hypersensitivity and altered immune responses, such as allergies, asthma, rheumatoid arthritis, and psoriasis Flaxseed Used to treat dyslipidemia and constipation May cause GI disturbances. Statins can the synthesis of CoQ-10. Topical: to treat wounds, burns, eczema, psoriasis, and herpes simplex infections. Feverfew Well tolerated It is a soluble plant fiber Seems to total cholesterol and LDL Similar to all fiber products but these effects occur primarily in postmenopausal women. Few AE have been reported. The most common complaint is unpleasant taste. Fever, N/V occur infrequently. This drug suppresses platelet aggregation shouldn’t be given if taking antiplatelets or anticoagulants. No serious AE. Should be taken one hour before or two hours after other medications because it could interfere with the absorption GI-related such as bloating and cramping It does not affect HDL cholesterol or Tg Garlic Tg and LDL, HDL Also has been used for antimicrobial and anticancer effects BP, platelet aggregation, arterial elasticity, and the formation of atherosclerotic plaque Ginger studies concluded that garlic does not appear to LDL but may BP To treat vertigo and to suppress N/V associated with motion sickness, morning sickness, seasickness, chemotherapy, and general anesthesia. Suppress platelet aggregation and it can lower blood sugar and may potentiate the hypoglycemic effects of insulin and other drugs for diabetes Improve memory, halt progression of dementia, and intermittent claudication. Green tea and green tea extracts Treat osteoarthritis Used to lose weight, improve mental clarity, and prevent and treat cancers of the stomach, skin, bladder, and breast. Excessive doses have the potential to cause CNS depression and cardiac dysrhythmias. Well tolerated May cause upset stomach, HA, dizziness, or vertigo Less common uses: erectile dysfunction and other conditions with perfusion Glucosamine and Chondroitin Garlic is generally well tolerated. Bad breath and body odor. In order to be effective, it has to be raw and not cooked (must have 1-2 cloves twice daily for the full effect) Has anti-inflammatory and analgesic properties that may help people with arthritis and other chronic conditions Ginkgo (Ginkgo biloba) Should be avoided in patients taking antiplatelets or anticoagulants. Some studies have demonstrated a modest improvement in joint structure but not pain Its produced from the exoskeletons of shellfish, caution w/ shellfish allergy. Most common: GI disturbances, such as N and heartburn. May the risk for bleeding (caution w antiplatelet drugs or anticoagulants) Glucosamine can also cause bronchospasm Caution w/ vasodilators, stimulants and other psychoactive medications, and medications w/ a known risk for liver damage. Contains a small amount of vit K, which may the anticoagulant effects of warfarin. Nadolol absorption Peppermint nausea, esophageal spasms (can esophageal sphincter pressure) Oils: for IBS, small intestinal bacterial overgrowth Peppermint water: nipple cracking and pain related to breastfeeding Help treat IBS, ulcerative colitis, C diff– associated diarrhea (CDAD), and, in children, rotavirus diarrhea containing S. boulardii are used for CDAD Resveratrol Antioxidant promoted for antiaging effects and protection against chronic diseases found in grapes, blueberries, cranberries, peanuts, and red wine Saw palmetto Relieve urinary symptoms associated with benign prostatic hyperplasia (BPH). It has also been promoted for treatment of androgenic alopecia Shouldn’t be taken with anticoagulants or antiplatelets. Soy protein and soy isoflavones Prevention of breast cancer and, treatment of vasomotor symptoms (hot flashes) and prevention of osteoporosis in postmenopausal women Soy should not be combined with tamoxifen and other drugs that can block estrogen receptors. well tolerated. St. John's wort Oral: mild to moderate depression, relieve pain and inflammation A CYP3A4 inducer: Pglycoprotein synthesis and can cause serotonin syndrome in patients taking SSRIs or SNRIs. well tolerated Probiotics Topically: manage local infection Lactobacillus species may reduce the duration of diarrhea in patients with rotavirus infection and other GI conditions Administer no sooner than 2 hours after dosing with antibacterial or antifungal drugs Well tolerated Has antiplatelet actions, which might intensify the effects of anticoagulants and antiplatelet drugs. well tolerated dangerous to a developing fetus. This medication must be given 3x daily Valerian root A sedative preparation used primarily to promote sleep, anxiety Can potentiate the actions of other drugs with CNSdepressant Daytime drowsiness, dizziness, depression, dyspepsia, and pruritus Harmful supplements: Comfrey - was removed from the market in 2001 because it can cause venoocclusive disease (VOD) and hepatic VOD. Kava - Can cause severe liver injury, FDA issued a public warning in March 2002; then, the CDC issued a report on kava-related hepatotoxicity. Kava is still on the market in US. Ma huang (ephedra) - contains ephedrine, can BP and stimulate the heart and CNS. High-dose ephedra has been associated with stroke, MI, and death. There is current a ban on Ma huang (ephedra) in the US but it does not apply to ephedra in traditional Asian medicines or herbal teas.
