What is the term for the maximum daily intake amounts of nutrients that are not likely to cause adverse health effects in almost all individuals in a life stage group?

Vitamin E Requirements

A recommended dietary allowance (RDA) for various food factors was first recognized in the USA with the publication of the first edition of the book on RDA requirements in 1946. A specific RDA for vitamin E was first recommended in the sixth edition (1964), in which the concept of the RDA was broadened and redefined from the 1946 idea – enough ‘to insure good nutrition’ – to an amount necessary ‘to permit full realization of … potential.’ Thus, in the 1964 edition, the concept was expressed that vitamins might have a pharmacological use beyond that necessary merely to prevent vitamin deficiency diseases. The 1997 edition sets the need for vitamin E as 10 α-TE per day for males and 8 mg for females, which is equal to 10 mg of the natural RRR-α-tocopherol (see Table 1).

The vitamin E requirement for humans increases as their diet includes more PUFAs because of the susceptibility of PUFAs to undergo autoxidation. A value of 0.4 for the ratio of the intake of RRR-α-tocopherol (in mg) to the intake of PUFA (in g) in the diet has been suggested to be adequate for adult humans. Thus, if a person eating a 2000-cal per day diet consumed 35% of their calories as fat, of which 40% was unsaturated (typical of today's American diet), they would require a daily intake of about 13 mg of α-tocopherol.

The intake of vitamin E for Americans on typical diets has been estimated to vary between 5 and 20 α-TE. The requirement of 10 α-TE for men and 8 α-TE for women (who are generally smaller) was established as the RDA because it is believed that very few Americans have overt vitamin E deficiency symptoms, and the amount ingested in a ‘normal’ diet must therefore be sufficient. This rather unsatisfactory, backward and ad hoc reasoning is thought to be the only approach possible for establishing an RDA for vitamin E, for which deficiency symptoms are only obvious in humans who have severe malabsorption. There is an increasing body of evidence, however, that vitamin E may provide benefits (such as protection from chemically induced cancers, cataracts, and ischemic heart disease) that require higher daily intakes; scientific studies of the usefulness of vitamin E in these contexts generally use amounts of vitamin E up to about 800 mg per day, which is generally agreed to be safe for humans. (See CANCER | Diet in Cancer Prevention.)

B Dietary Reference Intakes for Nutrient Adequacy

The RDA (or the AI if an RDA is not available) is the appropriate target for guidance to consumers on healthy nutrient intakes. Because an individual’s actual requirement is almost never known, the goal is to reduce to a very low level the risk that an intake is inadequate. By definition, usual intake at the level of the RDA or AI has a low risk of inadequacy (2 or 3% for the RDA). The appropriate target for vitamin D intake for a woman 31–50 years of age, for example, is the RDA of 600 IU (15 µg)/day [7]. Her target for potassium would be the AI of 4.7 g/day [6].

To reflect current information on bioavailability, the RDAs for two nutrients are expressed in forms that are unfamiliar to many consumers and clients: Folate is in micrograms of dietary folate equivalents (DFE) rather than total micrograms of folate, and vitamin E is in milligrams of α-tocopherol rather than in milligrams of α-tocopherol equivalents. The new DFE unit reflects the higher availability of fortification and supplemental forms of folate compared with naturally occurring folate in foods. Thus, the use of DFEs tends to increase estimates of an individual’s intakes of this nutrient. The newer vitamin E unit reflects the lower bioavailability of forms of tocopherol other than the RRR and 2R stereoisomeric forms of α-tocopherol. The less available forms include β-tocopherol and γ-tocopherol, which are not transported well from the liver. Furthermore, the all-racemic α-tocopherol form that is commonly used for fortification and in dietary supplements has a lower activity than does α-tocopherol. Therefore, intakes measured in the older units (α-tocopherol equivalents) will overestimate intakes of the active forms of the vitamin.

Recent changes in the DRIs for calcium and vitamin D merit special attention. In 1997, AIs had been set for calcium and vitamin D because the data were judged insufficient to set EARs and RDAs. The new reference values for these two nutrients are based on an exhaustive review of a much larger amount of information, including studies of higher quality than were available by 1997 [1]. The 2010 report [7] provides EARs and RDAs for both nutrients. Compared with the original DRI values, the RDAs for calcium are the same as the previous AIs for nearly all the age–gender groups. The exceptions apply to children ages 1–3 and 4–8 years, for whom the 2010 RDAs for calcium are 200 mg lower than the 1997 AIs. The changes in the DRIs for vitamin D are much more extensive. In particular, the 2010 RDAs for vitamin D are higher than the 1997 AIs for all the age–gender groups. They are 1.5 times higher for persons ages 1–70 years, 1.33 times higher for persons ages 71 or older, and 3 times higher for pregnant and lactating females. For infants ages 0–11 months, the 2010 AIs are twice as high as the 1997 AIs. For both the nutrients, the availability of EARs for all age groups above infants makes it possible to better assess the extent to which inadequate dietary intake may be a problem for groups of people.

Dietary Reference Intakes

The recommended dietary allowance (RDA) for males and nonpregnant and nonlactating females age 15 years and older is 400 μg DFE day−1 (Table 2). The RDA ranges from 65 to 300 μg DFE day−1 for ages 0–14 years. The RDAs for pregnant and lactating women are, respectively, 600 and 500 μg DFE day−1, which accounts for the increased demands for folate of the growing fetus and breast-feeding infant. There is no upper tolerable limit (UL) established for food folates. However, a UL for folic acid has been set at 1000 μg day−1. This is based not only on direct toxic effects of folic acid, but rather the possible masking of vitamin B12 deficiency by high dose folic acid, which can correct hematological abnormalities but not the neuropathological manifestations of B12 deficiency (see the Section Folic Acid Fortification Beyond NTDs).

Table 2. Recommended dietary allowances (RDA) for folate (US and Canada)

7.2.1 Vitamin A and provitaminic A carotenoids

Vitamin A is required for normal vision, gene expression, reproduction, embryonic development and immune function.

The recommended dietary allowance (RDA), or adequate intake (AI), ranges from 300 to 1300 μg/day. Vitamin A has two main origins. The first one is preformed vitamin A, mostly found as retinyl palmitate in liver, dairy products and fish. The second form comes from the provitaminic A carotenoids, present in numerous orange-coloured fruit (mangos, oranges, papaya, apricots), vegetables (carrots, pumpkin, corn, squash, green leafy vegetables) and red palm oil. Carotenoids are lipid-soluble plant pigments containing at least 40 carbons and an extensive conjugated double bond system. Carotenoids are either oxygenated (sub-class of xanthophylls) or non-oxygenated (sub-class of carotenes). Among carotenoids, beta-carotene, alpha-carotene and beta-cryptoxanthin display a provitaminic activity. Because xanthophylls are oxygenated carotenoids, they can be found in plant tissue as esters (conjugated with fatty acids), but also as free forms. Carrots, squash, sweet potato, and spinach are abundant in both beta- and alpha-carotene, and orange is rich in beta-cryptoxanthin.

5.2.1 The contribution of potato proteins to human diet

The Recommended Dietary Allowance of good-quality protein is 0.80 g/kg body weight/day, and the Acceptable Macronutrient Distribution Range for protein is 10–35% of energy for adults (Food and Nutrition Board, 2005). The best protein sources for humans are animal products. Potato tuber contains 20 g protein (range 6.9–46.3 g) per kg on a fresh-weight basis (OECD, 2002). The flesh of one boiled potato cooked in skin without salt has 2.54 g protein (1.87 g/100 g) (USDA, 2007). Potato consumption thus adds only a relatively small part to the total daily protein consumption. Even then, root-tuber crops such as potato and sweet potato represent a major non-cereal plant source of dietary protein worldwide (Davies, 1996). Potato protein is of high nutritional value because it contains high levels of the essential amino acids lysine, methionine, threonine, and tryptophan (OECD, 2002). The effect of storage of whole potatoes on protein content depends on the potato cultivar and the particular proteins being examined (Pots et al., 1999). Increased amounts and/or quality of protein in potato tubers by genetic modification have been reported in a few cases (Chakraborty et al., 2000; Ryan et al., 2005).

6.3 Supplementation

The RDA for selenium is 55 μg per day for adults. Selenium is found in a variety of foods, including both plant and animal sources, such as fish, shellfish, organ meats, red meat, chicken, eggs, and milk; the amount of selenium from plant sources depends on the amount of selenium in the soil in which the plant grew. Amounts in animal products also vary depending on the amount of selenium in the animal feed (Clark, 2007; NIH, 2009d). Although evidence indicates that selenium intake is marginal in some areas of the world, including parts of China, Northern Europe, New Zealand, and Russia, research suggests that most Americans obtain adequate amounts of selenium via their usual diets (Boosalis, 2008; Combs, 2001).

Individuals at risk for selenium deficiency include those with suboptimal dietary selenium intake, generally as a result of living in a geographic area with low soil selenium levels, and severe malabsorptive GI diseases (NIH, 2009d). Selenium deficiency has also been reported in individuals receiving long-term parenteral nutrition without selenium, and in patients with high-output chylous fistula losses (Clark, 2007; De Berranger et al., 2006). Selenium deficiency may lead to Keshan's disease, a form of cardiomyopathy, as well as oxidative injury and altered thyroid metabolism. Serum selenium is an indicator of short-term selenium status; depressed levels have been observed in the acute phase response so this should be taken into consideration when assessing selenium status. Erythrocyte selenium levels may also be measured to assess long-term selenium status (Clark, 2007).

Selenium can be supplemented in its organic form, selenomethionine, or in an inorganic form, such as sodium selenite or sodium selanate; however, because of improved absorption, selenomethionine is generally recognized as the preferred form. There are no specific guidelines regarding the ideal dose or duration of selenium supplementation; however, most commonly studied doses range from 50 to 200 μg d-1. Duration of supplementation should be determined on an individual basis, taking into account selenium intake from other sources and malabsorptive disorders (NIH, 2009d).

4.4.1.2 Calcium

The RDA values for Ca are high (1000 mg/day for adults (Institute of Medicine, 2011)), so a small enhancement in bioavailability would mean a reduction in the amount of Ca to be added. This could reduce the bulkiness of Ca fortificants and supplements, which may increase compliance. A range of studies has been done on particle size reduction of Ca compounds for nutrition, mostly with promising results. Nano-CaCO3 (agglomerate size 151 nm) and nano-Ca citrate (398 nm) significantly enhanced bone mineral density in OVX mice over micronsized CaCO3 (3.8 μm) and Ca citrate (1.8 μm), and showed no acute and chronic oral toxicity in mice (Huang et al., 2009). Feeding milk enriched with nano-Ca (not further characterized) to OVX rats resulted in a significant enhancement in bone mineral density and bone strength (Park et al., 2007), and also bone markers indicated an improved bone health (Park et al., 2008). Two sizes of CaCO3 (geometric mean diameter 18.5 vs. 13.0 μm) were compared in the OVX rat model, but there was no significant size effect on overall Ca balance and bone health. The authors concluded that the amount of Ca consumed was more relevant in maintaining skeletal strength rather than the particle size itself (Shahnazari et al., 2009). Similarly, Ca retention did not increase during a balance period of 3 weeks in adolescent girls for smaller CaCO3 (13.5 ± 10.4 μm vs. 18.0 ± 14.0 μm average particle diameter) (Elble et al., 2011). Nanosized (agglomerate size 470 nm) pearl powder showed a better Ca absorption and retention in healthy adults compared to micronized (172 μm) powder (Chen et al., 2008). Also feeding of rats with nanometer pearl powder (40–80 nm average diameter) resulted in an increased Ca absorption and retention, higher bone and serum Ca levels, and increased femur weight and length compared to micronsized pearl powder in a dose-dependent manner (Gao et al., 2008). Nano-CaCO3 (SSA 15.8 m2/g) was more rapidly absorbed than bulk CaCO3 (0.83 m2/g) in rats, but the absorption efficiency was not improved (Lee et al., 2015). Nanosizing also improved in vivo and ex vivo, but not in vitro gastric dissolution; under all conditions, the samples showed a partial transformation to CaHPO4·2H2O (Lee et al., 2015). Combined amorphous structuring and nanosizing of CaCO3 (40–100 nm from electron microscopy) significantly increased fractional calcium absorption in a rat model (Meiron et al., 2011) and in a clinical trial in postmenopausal women (Vaisman et al., 2014) compared to commercial CaCO3 (1–10 μm).

Calcium bioavailability and absorption as well as bone parameters were significantly improved in three rat groups (sham, OVX, and OVX-osteoporosis) after feeding Ca citrate nano-fortified milk powder (Erfanian et al., 2015). In a recent study, milk enriched with micron- and nanosized CaCO3 (average DLS size of 100 vs. 0.1 μm) and Ca citrate (average DLS size of 100 vs. 0.2 μm) was fed to OVX rats. Bioavailability and absorption of Ca was greater for nano-sized Ca carbonate than citrate. Feeding CaCO3-enriched milk resulted in better femur Ca content and mechanical properties, and absorption and bioavailability (Erfanian et al., 2017). Recently, we measured Ca absorption and retention in growing rats from five Ca compounds, namely three sizes of CaCO3 (SSA 3, 36, and 64 m2/g), a 50%–50% mixture of carbonate and hydroxyapatite (94 m2/g) and pure hydroxyapatite (100 m2/g). We did not find any differences in bone mineral density and femur Ca content, but there was a significant difference in Ca retention between the smallest CaCO3 and nanosized hydroxyapatite, suggesting that chemical composition could be a better predictor of Ca bioavailability than SSA. However, contribution of particle size could not be completely ruled out (Posavec et al., 2017). Also, when considering chemical composition, no differences in Ca bioavailability were seen between CaCO3 and hydroxyapatite in growing rats (particles were not characterized) (Kruger et al., 2003).

History

The DRIs replaced the RDA, a nutrient standard used in the United States from 1941 to 1989 and a similar Canadian standard. These newer values were developed because of changes in science, limitations of the existing RDA, and the need to consider the role of nutrients in preventing dietary deficiency diseases as well as their associations with diet-related chronic degenerative diseases and toxicities. Starting in 1994, expert committees examined the scientific data on requirements of nutrients for these functions. The Standing Committee on the Scientific Evaluation of DRIs coordinated the effort under the direction of the Food and Nutrition Board, Institute of Medicine (IOM) of the National Academy of Sciences, and Health Canada.

Recommended Dietary Allowance (RDA)

In the USA, the 1989 RDA for vitamin C is 60 mg per day for adults. At this level, saturation of tissue binding and maximal rates of metabolic and renal tubular absorption seem to be approached. The RDA of 100 mg per day for smokers is higher because the plasma concentration of vitamin C is lowered by the use of cigarettes. Plasma ascorbate levels of women decrease during pregnancy, and the RDA includes a 10 mg per day increment for pregnant women. A daily increment of 35 mg is recommended during the first 6 months of lactation and 30 mg thereafter. Assessments of human vitamin C status are based upon measurement of ascorbate concentrations in plasma and leukocytes.

15.3 Recommended dietary intakes

In the United States of America, recommended intakes of nutrients, including vitamins, are set by the Food and Nutrition Board (FNB) of the Institute of Medicine (IOM), National Academy of Sciences. Similar authorities exist in the United Kingdom, Canada and many other countries. As shown in Table 15.3, four reference values, namely the EAR, RDA, AI and UL, constitute the dietary reference intakes (DRIs) which have replaced the RDAs and the recommended nutrient intakes (RNIs) previously published in the USA and Canada, respectively (Mason, 2007; IOM, Dietary Reference Intakes: vitamins, 1997, 1998, 2000, 2001, www.nap.edu). The DRIs, unlike the RDA values, were established with decreased risk of chronic diseases as end points (Lupton, 2005) and cover 22 distinct life stages and sex groups (Kennedy and Meyers, 2005). The life stages include infants (birth to 6 m; 7–12 m), toddlers (1 to 3 years), early childhood (4 to 8 years), puberty (9 to 13 years), adolescence (14 to 18 years), young adulthood (19 to 30 years), middle ages (1 to 50 years), adulthood (51 to 70 years), older adults (70 years and above), pregnancy (≤18 years, 19–30 years, 31–50 years) and lactation (≤18 years, 19–30 years, 31–50 years). The DRIs specify appropriate body size, namely, body mass indices (BMI) of 24.4 and 22.8 for 19 to 30-year-old males and females, respectively. The latter specification may be irrelevant in the USA where the majority of adults have average BMI well above the reference body size (Kennedy and Meyers, 2005). This also applies to some urban communities in the developing world presently experiencing nutrition transition and increasing incidence of obesity (Popkin, 2006).

Table 15.3. Definitions of components of the dietary reference intakes (DRIs)*

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Recommended dietary allowance (RDA): This is the average daily dietary intake level sufficient to meet the nutrient requirement of nearly all (97–98%) healthy individuals in a life stage and gender group.

Estimated average requirement (EAR): This is the average daily nutrient intake value estimated to cover the requirement of one-half of the healthy people in a life stage and gender group. If requirement for the nutrient is normally distributed, the RDA is set at two standard deviations above the EAR.

Adequate intake (AI): A recommended intake value used when there is insufficient scientific data to calculate RDA. It is based on observed or experimentally deduced estimates of nutrient intake by a group (or groups) of healthy people that are assumed to be adequate. For example, AI for young infants is based on the estimated daily mean nutrient intake supplied by human milk for exclusively breast-fed, healthy full-term infants.

Tolerable upper intake level (UL): This is the highest level of average daily nutrient intake unlikely to pose risk of adverse health effects to almost all individuals in the general population. The potential risk of adverse effects increases with nutrient intake above the UL.

Where toxicity data exist, the DRIs include the UL which is not a desirable, recommended level of intake. As shown in Table 15.4, there are marked differences in the ULs proposed by various authorities and the key reasons for the variations are explained in a recent report (Mason, 2007). It should also be emphasized that UL values established for relatively healthy communities in the Western world do not necessarily apply to Third World countries where severe malnutrition and infectious diseases are endemic.

Table 15.4. Upper safety limits for vitamin intakes set by various authoritiesa

CRN/EHPM, upper safe level defined by the European Federation of Health Product Manufacturers Association and the UK Council for Responsible Nutrition as daily intakes from supplements that could be consumed on a long-term basis; EVM UK, values produced by the UK Expert Vitamin and Mineral Group; FNB USA, tolerable upper intake levels defined by the Food and Nutrition Board of the US National Academy of Sciences as the highest total level of a nutrient (diet plus supplements) that can be safely consumed on a daily basis that is unlikely to cause adverse health effects to almost all individuals in the general population; SCF EU, tolerable upper intake levels defined by effects on human subjects; AUS/NZ, upper levels of intake for vitamins in adult men and women (Australia, New Zealand).