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Suggested Citation:"Choline ." Institute of Medicine. 2006. Dietary Reference Intakes: The Essential Guide to Nutrient Requirements. Washington, DC: The National Academies Press. doi: 10.17226/11537.
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Suggested Citation:"Choline ." Institute of Medicine. 2006. Dietary Reference Intakes: The Essential Guide to Nutrient Requirements. Washington, DC: The National Academies Press. doi: 10.17226/11537.
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Page 219
Suggested Citation:"Choline ." Institute of Medicine. 2006. Dietary Reference Intakes: The Essential Guide to Nutrient Requirements. Washington, DC: The National Academies Press. doi: 10.17226/11537.
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Page 220
Suggested Citation:"Choline ." Institute of Medicine. 2006. Dietary Reference Intakes: The Essential Guide to Nutrient Requirements. Washington, DC: The National Academies Press. doi: 10.17226/11537.
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Page 221
Suggested Citation:"Choline ." Institute of Medicine. 2006. Dietary Reference Intakes: The Essential Guide to Nutrient Requirements. Washington, DC: The National Academies Press. doi: 10.17226/11537.
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Page 222
Suggested Citation:"Choline ." Institute of Medicine. 2006. Dietary Reference Intakes: The Essential Guide to Nutrient Requirements. Washington, DC: The National Academies Press. doi: 10.17226/11537.
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Page 223

Below is the uncorrected machine-read text of this chapter, intended to provide our own search engines and external engines with highly rich, chapter-representative searchable text of each book. Because it is UNCORRECTED material, please consider the following text as a useful but insufficient proxy for the authoritative book pages.

TABLE 1 Dietary Reference Intakes for Choline by Life Stage Group DRI values (mg/day) AIa,b ULc males females Life stage group NDd 0 through 6 mo 125 125 7 through 12 mo 150 150 ND 1 through 3 y 200 200 1,000 4 through 8 y 250 250 1,000 9 through 13 y 375 375 2,000 14 through 18 y 550 400 3,000 19 through 30 y 550 425 3,500 31 through 50 y 550 425 3,500 51 through 70 y 550 425 3,500 > 70 y 550 425 3,500 Pregnancy £ 18 y 450 3,000 19 through 50 y 450 3,500 Lactation £ 18 y 550 3,000 19 through 50 y 550 3,500 a AI = Adequate Intake. b Although AIs have been set for choline, there are few data to assess whether a dietary supply of choline is needed at all stages of the life cycle. It may be that the choline requirement can be met by endogenous synthesis at some of these stages. c UL = Tolerable Upper Intake Level. Unless otherwise specified, the UL represents total intake from food, water, and supplements. d 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.

PART III: CHOLINE 219 CHOLINE C holine is required for the structural integrity of cell membranes. It is also involved in methyl metabolism, cholinergic neurotransmission, transmembrane signaling, and lipid and cholesterol transport and metabolism. Choline in the diet is available as free choline or is bound as esters such as phosphocholine, glycerophosphocholine, sphingomyelin, or phosphatidylcholine. Since data were insufficient to set an Estimated Average Requirement (EAR) and thus calculate a Recommended Dietary Allowance (RDA) for choline, an Adequate Intake (AI) was instead developed. The AIs for choline are based on the intake required to maintain liver function, as assessed by measuring serum alanine aminotransferase levels. The Tolerable Upper Intake Level (UL) is based on hypotension as the critical effect, with fishy body odor as the secondary consideration. Although AIs have been set for choline, there are few data to assess whether a dietary supply of choline is needed at all stages of the life cycle. It may be that the choline requirement can be met by endogenous synthesis at some of these stages. DRI values are listed by life stage group in Table 1. Foods rich in choline include milk, liver, eggs, and peanuts. Lecithin, a food additive used as an emulsifying agent, also adds choline to the diet. Al- though choline is clearly essential to life, few data exist on the effects of inad- equate dietary intake in healthy people. The signs and symptoms associated with excess choline intake are fishy body odor, sweating, vomiting, salivation, hypotension, gastrointestinal effects, and liver toxicity. CHOLINE AND THE BODY Function Choline is required for the structural integrity of cell membranes. It is also involved in methyl metabolism, cholinergic neurotransmission, transmembrane signaling, and lipid and cholesterol transport and metabolism. For example, choline accelerates the synthesis and release of acetylcholine, an important neurotransmitter involved in memory and muscle control. It is also a precur- sor for the synthesis of phospholipids, including phosphatidylcholine (a mem- brane constituent important for the structure and function of membranes), for intracellular signaling and hepatic export of very low density lipoproteins. Lecithin, a substance commonly added to foods as an emulsifying agent, is

DRIs: THE ESSENTIAL GUIDE TO NUTRIENT REQUIREMENTS 220 rich in phosphatidylcholine. The term lecithin is often interchangeably used with phosphatidylcholine. Absorption, Metabolism, Storage, and Excretion Dietary choline is absorbed in the small intestine. Before it can be absorbed from the gut, some is metabolized by bacteria to form betaine, which may be absorbed and used as a methyl donor, and methylamines, which are not methyl donors. Choline is found in foods as free choline and as esterified forms such as phosphocholine, glycerophosphocholine, sphingomyelin, and phosphatidylcho- line. Pancreatic enzymes can liberate choline from some of the latter to form free choline. Free choline enters the portal circulation of the liver, whereas phos- phatidylcholine may enter the lymph in chylomicrons. All tissues, including the brain, liver, and kidneys, accumulate choline by diffusion and mediated transport. Some choline is excreted in the urine unchanged but most is oxi- dized in the kidneys to form betaine. DETERMINING DRIS Determining Requirements Since data were not sufficient for deriving an EAR, and thus calculating an RDA, an Adequate Intake (AI) was instead developed. The AIs for choline are based on the prevention of liver damage, as assessed by measuring serum ala- nine aminotransferase levels. The estimate is uncertain because it is based on a single published study and may need revision when data are available. This amount is influenced by the availability of methionine and folate in the diet (see “Dietary Interactions”). It may also be influenced by gender, pregnancy, lacta- tion, and stage of development. Although AIs are set for choline, it may be that the requirement can be met by endogenous synthesis at some of these life stages. Most major nutrition surveys in the United States and Canada do not re- port choline intake. The choline content of foods is also not included in major nutrient databases. Criteria for Determining Choline Requirements, by Life Stage Group Life stage group Criterion 0 through 6 mo Human milk content 7 through 12 mo Extrapolation from infants or from adults 1 through 3 y Extrapolation from adults 4 through >70 y Serum alanine aminotransferase levels

PART III: CHOLINE 221 Pregnancy £ 18 y through 50 y Age-specific + fetal and placental accumulation of choline Lactation £ 18 y through 50 y Age-specific + choline secreted in human 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. The UL for choline represents total intake from food, water, and supple- ments. Hypotension was selected as the critical effect in deriving a UL for cho- line, with fishy body odor selected as the secondary consideration. Because there is no information from national surveys on choline intakes or on supplement usage, the risk of adverse effects within the United States or Canada cannot be characterized. Special Considerations Individuals susceptible to adverse effects: People with fish odor syndrome (trimethylaminuria), renal disease, liver disease, depression, and Parkinson’s disease may have an increased susceptibility to the adverse effects of choline intakes at the UL. DIETARY SOURCES Foods Most choline in foods is in the form of phophatidylcholine in membranes. Foods that are especially rich in choline include milk, liver, eggs, and peanuts. It is possible for usual dietary intakes to provide as much as 1,000 mg/day of cho- line. Lecithin added during food processing may increase the average daily per- capita consumption of phosphatidylcholine by 1.5 mg/kg of body weight for adults. Dietary Supplements Choline is available as a dietary supplement as choline chloride or choline bi- tartrate and as lecithin, which usually contains approximately 25 percent phos- phatidylcholine or 3–4 percent choline by weight. There are no reliable esti- mates of the frequency of use or the amount of these supplements consumed by individuals in the United States and Canada.

DRIs: THE ESSENTIAL GUIDE TO NUTRIENT REQUIREMENTS 222 Bioavailability This information was not provided at the time the DRI values for this nutrient were set. Dietary Interactions Choline, methionine, and folate metabolism interact at the point that homocys- teine is converted into methionine. Disturbing the metabolism of one of these methyl donors can affect the metabolism of the others. INADEQUATE INTAKE AND DEFICIENCY Although choline is clearly essential to life, few data exist on the effects of inad- equate dietary intake in healthy people. Based on one study examining the effects of artificially induced choline deficiency in healthy men who consumed an otherwise adequate diet, liver damage occurred, resulting in elevated levels of alanine aminotransferase in the blood. Fatty infiltration of the liver has also been shown to occur in individuals fed with total parenteral nutrition (TPN) solutions devoid of choline. EXCESS INTAKE Choline doses that are in orders of magnitude greater than estimated intake from food have been associated with fishy body odor (trimethylaminuria), sweat- ing, salivation, hypotension, and hepatotoxicity in humans. There are no indi- cations in the literature that excess choline intake produces any additional ad- verse effects in humans. Fishy body odor results from the excretion of excessive amounts of trimethylamine, a choline metabolite, as the result of bacterial ac- tion. Lecithin does not present a risk of fishy body odor.

PART III: CHOLINE 223 KEY POINTS FOR CHOLINE Choline is required for the structural integrity of cell 3 membranes. It is also involved in methyl metabolism, cholinergic neurotransmission, transmembrane signaling, and lipid and cholesterol transport and metabolism. Since data were insufficient to set an EAR and thus calculate 3 an RDA for choline, an AI was instead developed. The AIs for choline are based on the prevention of liver 3 damage, as assessed by measuring serum alanine aminotransferase levels. Although AIs have been set for choline, there are few data to 3 assess whether a dietary supply of choline is needed at all stages of the life cycle. It may be that the requirement can be met by endogenous synthesis at some of these stages. The UL is based on hypotension as the critical effect, with fishy 3 body odor as the secondary consideration. People with fish odor syndrome (trimethylaminuria), renal 3 disease, liver disease, depression, and Parkinson’s disease may have an increased susceptibility to the adverse effects of choline intakes at the UL. Foods rich in choline include milk, liver, eggs, and peanuts. 3 Lecithin, a food additive used as an emulsifying agent, also adds choline to the diet. Although choline is clearly essential to life, few data exist on 3 the effects of inadequate dietary intake in healthy people. Based on one study examining the effects of induced inadequate dietary intake in healthy men who consumed an otherwise adequate diet, liver damage occurred. Choline doses that are in orders of magnitude greater than 3 estimated intake from food have been associated with fishy body odor (trimethylaminuria), sweating, salivation, hypotension, and hepatotoxicity in humans. There are no indications in the literature that excess choline intake produces any additional adverse effects in humans.

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Widely regarded as the classic reference work for the nutrition, dietetic, and allied health professions since its introduction in 1943, Recommended Dietary Allowances has been the accepted source in nutrient allowances for healthy people. Responding to the expansion of scientific knowledge about the roles of nutrients in human health, the Food and Nutrition Board of the Institute of Medicine, in partnership with Health Canada, has updated what used to be known as Recommended Dietary Allowances (RDAs) and renamed their new approach to these guidelines Dietary Reference Intakes (DRIs). Since 1998, the Institute of Medicine has issued eight exhaustive volumes of DRIs that offer quantitative estimates of nutrient intakes to be used for planning and assessing diets applicable to healthy individuals in the United States and Canada. Now, for the first time, all eight volumes are summarized in one easy-to-use reference volume, Dietary Reference Intakes: The Essential Reference for Dietary Planning and Assessment. Organized by nutrient for ready use, this popular reference volume reviews the function of each nutrient in the human body, food sources, usual dietary intakes, and effects of deficiencies and excessive intakes. For each nutrient of food component, information includes:

  • Estimated average requirement and its standard deviation by age and gender.
  • Recommended dietary allowance, based on the estimated average requirement and deviation.
  • Adequate intake level, where a recommended dietary allowance cannot be based on an estimated average requirement.
  • Tolerable upper intake levels above which risk of toxicity would increase. Along with dietary reference values for the intakes of nutrients by Americans and Canadians, this book presents recommendations for health maintenance and the reduction of chronic disease risk. Also included is a “Summary Table of Dietary Reference Intakes,” an updated practical summary of the recommendations. In addition, Dietary Reference Intakes: The Essential Reference for Dietary Planning and Assessment provides information about:
  • Guiding principles for nutrition labeling and fortification
  • Applications in dietary planning
  • Proposed definition of dietary fiber
  • A risk assessment model for establishing upper intake levels for nutrients
  • Proposed definition and plan for review of dietary antioxidants and related compounds

Dietitians, community nutritionists, nutrition educators, nutritionists working in government agencies, and nutrition students at the postsecondary level, as well as other health professionals, will find Dietary Reference Intakes: The Essential Reference for Dietary Planning and Assessment an invaluable resource.

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