In this post we pursue yet another way of determining a nutrient requirement.
A feature common to most (if not all) nutrients is the effect plateau. If you start from a state of nutrient deficiency, increasing intake of the nutrient concerned produces a measurable, beneficial change in some function or outcome that expresses the nutrient’s activity. For example, if you have iron deficiency anemia and you start taking iron supplements, your hemoglobin and red blood cell count will increase. Your anemia will be treated and, in most cases, cured entirely. But there is a clear limit. Once your hemoglobin reaches normal values (about 14 g/100 mL of blood), no further increases can be produced by taking more iron – even if you double or triple or quadruple the dose. You have reached a plateau.
If you’re losing iron (as with heavy menstrual flow), you’ll need to take a maintenance dose of iron. A dose (actually, better: an iron intake) that is just sufficient to keep your hemoglobin up on its plateau is the intake that satisfies your body’s need for iron. It is your “iron requirement”. This behavior of hemoglobin in response to iron intake is depicted in the figure to the left, in which “intake” refers to iron status and “response” to blood hemoglobin concentration. The actual value of the requirement will vary from person to person and from time to time in an individual, depending on how much iron one’s body is losing every day.
Because iron is a building block of the hemoglobin molecule, if you don’t have enough iron you won’t have enough hemoglobin – i.e., you will be anemic. The same is true for calcium and bone. A newborn human baby’s body contains 25–30 grams of calcium. That mass will increase to 1000–1500 grams by the time the child reaches full adult status. All that additional calcium has to come in by mouth. If after weaning you rear experimental animals on diets with varying calcium contents, and measure how much bone they have when fully grown, you will get a curve that’s exactly the same as the one shown above. And like iron, once you’re on the plateau, extra calcium will produce no more bone.
This behavior is relatively intuitive for bulk nutrients such as iron and calcium. But it’s also true for nutrients that are not so much accumulated by the body as utilized in helping the body perform some key function. Vitamin D, for example, helps the body regulate intestinal absorption of calcium from the foods in our diets. When a person is vitamin D deficient, calcium absorption will be impaired – i.e., it will fall somewhere along the ascending limb of the curve in the figure. But once you’ve raised your vitamin D status and have absorbed as much calcium as your body needs, increasing vitamin D status has no further effect. You’ve reached the absorptive plateau.
[Actually, vitamin D doesn’t raise calcium absorption at all – as we once used to think. Instead, what it does is enable the body to increase calcium absorption when the body needs more calcium – but has no effect when the body has enough. That’s why, once you’re up on the absorptive plateau, no further absorption occurs. Knowledgeable readers will recall that there is a derivative of vitamin D, called calcitriol, which the body makes when it needs to augment calcium absorption and which does, indeed, increase calcium absorption directly (and essentially without limit). If you were to administer calcitriol – sometimes referred to as “active” or “activated” vitamin D – you would definitely increase calcium absorption, whether the body needed the calcium or not. But it’s not the native vitamin D that’s producing this effect. Dosing with calcitriol effectively bypasses the body’s regulatory controls. The reason why normally the body does not increase calcium absorption as vitamin D intakes rise is precisely because the body reduces its production of calcitriol once calcium absorption is adequate for the body’s needs.]
While, as noted at the outset, this plateau effect appears to be common to most or all nutrients, there are some for which there isn’t an easily measurable effect, and therefore no direct way to get at defining the effect plateau. Protein, for example, is necessary for growth and for increasing muscle mass during growth. Like other nutrients, once a person reaches the amount of muscle that’s just right for his or her hereditary constitution and physical activity, more protein will not make more muscle. But muscle mass is difficult and expensive to measure – unlike hemoglobin (for iron). However, there is a potentially very useful substitute measure – plasma insulin-like growth factor-1 [IGF-1] – a member of the class of compounds called “biomarkers”. IGF-1 concentration in blood does reflect protein intake and follows the rising limb of the curve above, just as does hemoglobin with iron. The IGF-1 plateau is not as well studied nor quite as precisely nailed down as some of the other relationships I’ve just reviewed. However the basic pattern – the plateau – seems to be the same as for other nutrients. More research is clearly needed. But available data indicate the IGF-1 concentrations begin to plateau at protein intakes in the range of 1.2–1.3 grams protein/kilogram/day, a figure that is about 50% higher than the current recommendation for protein intake.
For all nutrients for which we can define a plateau, the determination of the nutrient requirement – the “recommended” intake – follows directly from these behaviors. An intake sufficient to get 97.5% of a healthy population up onto the effect plateau is, manifestly, a defensible estimate of the requirement (specifically, it would be the RDA).
Interestingly, in its 2011 intake recommendations, the Institute of Medicine (IOM) used the plateau effect as a part of the basis for its recommendation for vitamin D. The IOM asserted that a 25(OH)D level of 20 ng/mL was sufficient to ensure that most individuals would be on the calcium absorptive plateau. Unfortunately, the IOM panel relied on absorption studies that did not use a nutritionally relevant calcium load. As a result they greatly underestimated the vitamin D status needed to guarantee optimal regulation of calcium absorption. This is seen immediately when we recall that absorption is a load phenomenon, i.e., how many ions of calcium can be carried across the intestinal mucosa during the short time during which the digested food is in contact with the absorptive mucosa. Vitamin D (actually calcitriol in this instance) causes the intestinal lining cells to manufacture calcium transporters. Clearly, if you have fewer calcium ions to transport, you can max out with fewer transporters. It’s just that straightforward. As a consequence, it follows that if you want to optimize absorptive regulation for nutritionally relevant calcium sources (e.g., a glass of milk), you’ve got to do your testing using nutritionally relevant calcium loads. And when you do that, the absorptive plateau begins at 25(OH)D concentrations of 32–35 ng/mL, not 20 as the IOM declared.