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TABLE 1 Dietary Reference Intakes for Vitamin B6 by Life Stage Group DRI values (mg/day) EARa RDAb AIc ULd males females males females Life stage group NDe 0 through 6 mo 0.1 7 through 12 mo 0.3 ND 1 through 3 y 0.4 0.4 0.5 0.5 30 4 through 8 y 0.5 0.5 0.6 0.6 40 9 through 13 y 0.8 0.8 1.0 1.0 60 14 through 18 y 1.1 1.0 1.3 1.2 80 19 through 30 y 1.1 1.1 1.3 1.3 100 31 through 50 y 1.1 1.1 1.3 1.3 100 51 through 70 y 1.4 1.3 1.7 1.5 100 > 70 y 1.4 1.3 1.7 1.5 100 Pregnancy £ 18 y 1.6 1.9 80 19 through 50 y 1.6 1.9 100 Lactation £ 18 y 1.7 2.0 80 19 through 50 y 1.7 2.0 100 a EAR = Estimated Average Requirement. b RDA = Recommended Dietary Allowance. c AI = Adequate Intake. d UL = Tolerable Upper Intake Level. Unless otherwise specified, the UL represents total intake from food, water, and supplements. e ND = Not determinable. This value is not determinable due to the lack of data of adverse effects in this age group and concern regarding the lack of ability to handle excess amounts. Source of intake should only be from food to prevent high levels of intake.

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PART III: VITAMIN B6 183 VITAMIN B6 V itamin B6 (pyridoxine and related compounds) functions as a coenzyme in the metabolism of amino acids, glycogen, and sphingoid bases. Vita- min B6 comprises a group of six related compounds: pyridoxal (PL), pyridoxine (PN), pyridoxamine (PM), and their respective 5¢-phosphates (PLP, PNP, and PMP). The major forms found in animal tissue are PLP and PMP; plant-derived foods primarily contain PN and PNP, sometimes in the form of a glucoside. The primary criterion used to estimate the requirements for vitamin B6 is a plasma pyridoxal 5¢-phosphate value of at least 20 nmol/L. The Tolerable Up- per Intake Level (UL) is based on sensory neuropathy as the critical adverse effect. DRI values are listed by life stage group in Table 1. Rich food sources of vitamin B6 include highly fortified cereals, beef liver and other organ meats, and highly fortified, soy-based meat substitutes. The clinical signs and symptoms of vitamin B6 deficiency have only been observed during depletion with very low levels of the vitamin and have never been seen at intakes of 0.5 mg/day or more. No adverse effects have been associated with high intakes of the vitamin from food sources. Very large oral doses (2,000 mg/ day or more on a chronic basis) of supplemental pyridoxine have been associ- ated with the development of sensory neuropathy and dermatological lesions. VITAMIN B6 AND THE BODY Function Vitamin B6 functions as a coenzyme in the metabolism of amino acids, glyco- gen, and sphingoid bases. Vitamin B6 comprises a group of six related com- pounds: pyridoxal (PL), pyridoxine (PN), pyridoxamine (PM), and their re- spective 5¢-phosphates (PLP, PNP, and PMP). The major forms found in animal tissue are PLP and PMP; plant-derived foods primarily contain PN and PNP, sometimes in the form of a glucoside. Absorption, Metabolism, Storage, and Excretion Absorption of vitamin B6 in the gut occurs via phosphatase-mediated hydroly- sis followed by the transport of the nonphosphorylated form into the mucosal

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DRIs: THE ESSENTIAL GUIDE TO NUTRIENT REQUIREMENTS 184 cell. Transport occurs by nonsaturable passive diffusion. Even large doses of the nutrient are well absorbed. Most of the absorbed nonphosphorylated vitamin B6 goes to the liver, and certain forms of the vitamin (pyridoxal, pyridoxine, and pyridoxamine) are converted to their respective 5¢-phosphates by pyridoxal kinase. Vitamin B6 can be bound to proteins in tissues, which limits accumulation at very high intakes. When this capacity is exceeded, nonphosphorylated forms of vitamin B6 are released by the liver and other tissues into the circulation. At pharmacological doses of vitamin B6, high amounts accumulate in the muscle, plasma, and eryth- rocytes when other tissues are saturated. Most of the body’s vitamin B6 is found in the muscle; the muscle pool of the vitamin appears to very slowly turn over. Vitamin B6 is oxidized in the liver and then released and primarily excreted in the urine. DETERMINING DRIS Determining Requirements The primary criterion used to estimate the requirements for vitamin B6 is a plasma 5¢-pyridoxal phosphate value of at least 20 nmol/L. Criteria for Determining Vitamin B6 Requirements, by Life Stage Group Life stage group Criterion 0 through 6 mo Human milk content 7 through 12 mo Mean of extrapolation from younger infants and from adults 1 through 18 y Extrapolation from adults Plasma pyridoxal 5¢-phosphate level 19 through > 70 y Pregnancy £ 18 y through 50 y Plasma pyridoxal 5¢-phosphate level Lactation £ 18 y through 50 y Amount of vitamin B6 secreted in milk The UL The Tolerable Upper Intake Level (UL) is the highest level of daily nutrient intake that is likely to pose no risk of adverse effects for almost all people. Members of the general population should not routinely consume more than the UL. For adults, the UL for Vitamin B6 represents total intake from food,

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PART III: VITAMIN B6 185 water, and supplements and is based on sensory neuropathy as the critical ad- verse effect. The UL is not meant to apply to individuals who are receiving vitamin B6 under medical supervision. Based on data from the Third National Health and Nutrition Examination Survey (NHANES III, 1988–1994), 9 mg/day was the highest mean intake of vitamin B6 from food and supplements reported for any life stage and gender group. The highest reported intake at the 95th percentile was 21 mg/day in pregnant females aged 14 through 55 years, most of which was pyridoxine from supplements. The risk of adverse effects resulting from excess intake of vitamin B6 from food and supplements appears to be very low at these intake levels. DIETARY SOURCES Foods Data from the Continuing Survey of Food Intakes by Individuals (CSFII, 1994– 1996) indicated that the greatest contribution to the vitamin B6 intake of the U.S. adult population came from fortified, ready-to-eat cereals; mixed foods (including sandwiches) with meat, fish, or poultry as the main ingredient; white potatoes and other starchy vegetables; and noncitrus fruits. Especially rich sources of vitamin B6 include highly fortified cereals; beef liver and other organ meats; and highly fortified, soy-based meat substitutes. Dietary Supplements Approximately 26 percent of all adults reported taking a supplement contain- ing vitamin B6, according to the 1986 National Health Interview Survey (NHIS) in the United States. For adults over age 60 years who took supplements and participated in the Boston Nutritional Status Survey (1981–1984), the median supplemental vitamin B6 intake was 2.2 mg/day for both men and women. Bioavailability The bioavailability of vitamin B6 from a mixed diet is approximately 75 percent. Dietary Interactions This information was not provided at the time the DRI values for this nutrient were set.

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DRIs: THE ESSENTIAL GUIDE TO NUTRIENT REQUIREMENTS 186 INADEQUATE INTAKE AND DEFICIENCY In controlled studies, clinical signs and symptoms of vitamin B6 deficiency have only been observed during depletion with very low levels of the vitamin and have never been seen at intakes of 0.5 mg/day or more. The signs and symp- toms of vitamin B6 deficiency include the following: • Seborrheic dermatitis • Microcytic anemia (from decreased hemoglobin synthesis) • Epileptiform convulsions • Depression and confusion Special Considerations Medications: Drugs that can react with carbonyl groups have the potential to interact with a form of vitamin B6. For example, isoniazid, which is used in the treatment of tuberculosis, and L-DOPA, which is metabolized to dopamine, have been reported to reduce plasma concentrations of vitamin B6. Oral contraceptives: Studies have shown decreased vitamin B6 status in women who receive high-dose oral contraceptives. Plasma concentrations of the nutri- ent are lowered, but the decrease is quite small. (It should be noted that these studies were conducted when the level of estrogen in oral contraceptives was three to five times higher than current levels.) Alcohol: Chronic alcoholics tend to have low vitamin B6 status, which is dis- tinct from deficiency caused by liver disease or by poor diet. The extent to which this causes an increased vitamin B6 requirement is not known. Preeclampsia: Lowered vitamin B6 status is observed in preeclampsia and eclampsia, suggesting a potentially increased requirement for the vitamin in preeclampsia. EXCESS INTAKE No adverse effects have been associated with high intakes of vitamin B6 from food sources. Very large oral doses (2,000 mg/day or more) of supplemental pyridoxine, which are used to treat many conditions, including carpal tunnel syndrome, painful neuropathies, seizures, premenstrual syndrome, asthma, and sickle cell disease, have been associated with the development of sensory neu- ropathy and dermatological lesions.

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PART III: VITAMIN B6 187 KEY POINTS FOR VITAMIN B6 Vitamin B6 (pyridoxine and related compounds) functions as a 3 coenzyme in the metabolism of amino acids, glycogen, and sphingoid bases. The requirements for vitamin B6 are based on a plasma 3 pyridoxal 5¢-phosphate value of at least 20 nmol/L. The UL is based on sensory neuropathy as the critical adverse effect. Rich food sources of vitamin B6 include highly fortified cereals, 3 beef liver and other organ meats, and highly fortified, soy- based meat substitutes. Other contributors to vitamin B6 intake include mixed foods with meat, fish, or poultry as the main ingredient; white potatoes and other starchy vegetables; and noncitrus fruits. Clinical signs and symptoms of vitamin B6 deficiency have only 3 been observed during depletion with very low levels of the vitamin and have never been seen at intakes of 0.5 mg/day or more. The signs and symptoms of vitamin B6 deficiency are 3 seborrheic dermatitis, microcytic anemia, epileptiform convulsions, and depression and confusion. No adverse effects have been associated with high intakes of 3 vitamin B6 from food sources. Very large oral doses (2,000 mg/day or more) of supplemental 3 pyridoxine have been associated with the development of sensory neuropathy and dermatological legions.