For these essential metals there is a range of intake over which their supply is adequate to the body (Fe 8-18 Mn/day, Mn 1.8-2.3 1.8-2.3 Cu 0.9 mg/day, Zn 8-11 mg/day, Ni 0.5 mg/day) [1, 2].
The midpoint was calculated for studies that only reported a range of intake by category.
However, even though intake was generally low, there was a range of intake for each of these nutrients.
A dataset of carcinogens based on the Gold Carcinogenic Potency Database was analyzed to find the proportion of chemicals in different structural groups that would yield an estimated lifetime risk >10−6 (one in a million) at a range of intake levels (Kroes et al., 2004).
Retrospective data suggest that, across a range of protein intakes that were below international recommendations, each 1 g.kg-1.d-1 increase in protein intake in the first week after birth in ELBW babies improves Mental Development Index scores by 8 points on a Bayley II assessment at 18 months [ 25].
Alterations in the reinforcing strength of cocaine were assessed after additional access to cocaine under a fixed-ratio (FR) schedule was provided in morning sessions and following various periods of abstinence (3, 7 and 14 days) from regimens of self-administration that resulted in a range of cocaine intakes.
In the only other study to examine a range of breakfast intakes, there was a gradient of BMI change in adolescents across categories of breakfast frequency, with never eaters experiencing the greatest increase and daily eaters experiencing the smallest increase (8).
Within a range of caloric intake above starvation for flies, greater calorie consumption leads to higher body weight, and a higher rate of reproduction but a shorter life span [ 42].
Crucially however, testing this hypothesis requires that lifespan be measured across a range of food intake levels (Figure 1).
In both cases, worms lacking either transcription factor showed the same lifespan across a range of dietary intake levels ranging from near starvation to ad libitum.
It is therefore paramount that DR is first 'optimized' for each genotype tested before epistasis analysis with a second genetic or pharmacological intervention is performed, i.e. the animals must be subjected to a range of food intake levels and that which causes maximum lifespan is set as the DR level for that genotype and used for epistasis studies.
