Tolerable Upper Levels of Intake

3 Tolerable Upper Levels of Intake A number of the vitamins are known to be toxic in excess. For most, there is a considerable difference between reference intakes that are more than adequate to meet requirements and the intake at which there may he adverse effects, although for vitamins A (Section 2.5.1) and D (Section 3.6.1) there is only a relatively small margin of safety. 

The upper levels for over-the-counter supplements shown Table 1.10 are voluntary, but because the report (Shrimpton, 1997) was commissioned by the European Eederation of Health Product Manufacturers, it is likely that most manufacturers of nutritional supplements will abide by them. The problem is that in most countries nutritional supplements are covered by food 

European Union NOAEL, no adverse effect level, the highest level of intake at which no adverse effects are observed. 

Sources Shrimpton, 1997 Institute of Medicine, 1997, 1998, 2000, 2001 Scientific Committee for Food, 1993 where two figures are shown for vitamin A, the lower is for women and the higher is for men (Table 2.5). for niacin and nicotinic acid, the lower values are for sustained reiease preparations the EU upper level of 25 mg of vitamin Be was proposed by the Scientific Committee for Food Opinion, 2000 and the EU upper level of 200 xg of vitamin B12 was set because of the possible presence of inactive corrinoids in pharmaceutical preparations, not because of toxicity of the vitamin itself. 

Sources National Research Council, European Commission, 1990. 

Sources National Research Council, 1989 Scientific Committee for Food, 1993 European Commission, 1990. 

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Abnormal accumulation in tissues and overloading of normal metabolic pathways, leading to signs of toxicity and possibly irreversible lesions. Niacin (Section 8.7.1), and vitamins A (Section 2.5.1), D (Section 3.6.1), and Bg (Section 9.6.4) are all known to be toxic in excess (see Section 1.2.4.3 for a discussion of tolerable upper levels of intake). 

The U.S. /Canadian report (Instimte of Medicine, 1997) quotes a no adverse effect level of 60 /rg per day, leading to a tolerable upper level of intake of 50 /xg per day (and 25 /xg per day for infants). The toxic threshold for adults has not been established, but reports of hypercalcemia in adults have involved intakes in excess of 1,000 /xg per day. There is no evidence of adverse effects at plasma concentrations of calcidiol lower than 140 nmol per L, which requires an intake in excess of 250 /xg per day, suggesting that the currently accepted no adverse effect level is lower than necessary (Vieth, 1999). 

Regardless of whether or not high intakes of ascorbate have any beneficial effects, large numbers of people habitually take between 1 to 5 g per day of vitamin C supplements, and some take considerably more. The U.S. /Canadian tolerable upper level of intake is 2 g per day (Institute of Medicine, 2000). 

Tolerable Upper Intake Level (UL) UL is the highest average daily nutrient intake level that is likely to pose no risk of adverse health effects to almost all individuals in the general population. As intake increases above the UL, the potential risk of adverse effects may increase. The UL is not intended to be a recommended level of intake. ULs are useful because of the increased availability of fortified foods and the increased use of dietary supplements. The UL applies to chronic daily use. For some nutrients, there may be insufficient data on which to develop a UL. 

Figure 1.3. Derivation of reference intake [Recommended Dietary (or Daily) Amount (RDA)], and tolerable upper level (UL) for a nutrient. Curve shows the probability that a subject will show signs of deficiency (left) or toxicity (right) at any given level of intake.

The U.S./Canadian Dietary Reference intakes report (Institute of Medicine, 2000) departed from tradition by considering only the contribution of the 2R isomers to vitamin E intake, and proposed an equivalence of 0.45 iu per mg for synthetic all-rac-a-tocopherol, although in consideration of upper tolerable levels of intake (Section 4.6.1), they considered the contribution of aU isomers equally However, although the 2S isomers have a shorter half-life than -tocopherol in the circulation, and hence a lower apparent biological availability, they are active in animal biological assays (Hoppe and Krennrich, 2000). 

Derivation of reference intake (RDA) and tolerable upper level (UL)... 

There is little evidence that intakes of up 200 mg vitamin Bg per day for prolonged periods are associated with any adverse effects. The US Food and Nutrition Board set a tolerable upper level for adults of lOOmg/day the EU Scientific Committee on Food set 25 mg/day. 

Due to bleeding risk, individuals on anticoagulant therapy or individuals who are vitamin K-deficient should not take vitamin E supplementation without close medical supervision. Absent of that, vitamin E is a well-tolerated relatively non-toxic nutrient. A tolerable upper intake level of 1,000 mg daily of a-tocopherol of any form (equivalent to 1,500 IU of RRR a-tocopherol or 1,100 IU of all-rac-a-tocopherol) would be, according to the Food and Nutrition Board of the Institute of Medicine, the highest dose unlikely to result in haemorrhage in almost all adults. 

SCF (2000). Opinion of the Scientific Committee on Food on the Tolerable Upper Intake Level of Beta Carotene. Scientific Committee on Food, http //europa.eu.int/comm/ food/fs/sc/scf/index en.html. 

Vieth, R. (2006). Critique of the considerations for establishing the tolerable upper intake level for vitamin D Critical need for revision upwards. /. Nutr. 136,1117-1122. 

Opinion of the Scientific Panel on Dietetic Products, Nutrition and allergies on a request from the commission related to the tolerable upper intake level of fluoride, EFSA J. 192 (2005) 1-65 (Available at http //www.efsa.eu.int/science/nda/nda opinions/catindex en.html). 

Comparison of the components of the Dietary Reference Intakes. EAR = Estimated Average Requirement RDA = Recommended Dietary Allowance Al = Adequate Intake UL = Tolerable Upper Intake Level. 

ScientiE>c Committee on Food, Guidelines of the Scientil>c Committee on Food for the development of tolerable upper intake levels for vitamins and minerals SCF/CS/ NUT/UPPLEV/11 FINAL, 28 November 2000 http //ec.europa.eu/food/fs/sc/scf/ out80a en.pdf... 

Optimal dietary intake is difficult to determine. Dietary Reference Intakes (DRIs) in the US are reference values that are quantitative estimates of nutrient intakes to be used for planning and assessing diets for apparently healthy people. DRIs are composed of reference values including Estimated Average Requirements (EARs), Recoimnended Dietary Allowances (RDAs), Adequate Intakes (AIs) and Tolerable Upper Intake Levels (ULs). Most nations have established the eqnivalent ofthe US DRIs. These are consensus and statistical valnes obtained from retrospective public health dietary studies, controlled experiments on metabolic wards, epidemiological surveys, isotopic tracer investigations, and extrapolation from animal models. 

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