Low micronutrient intake may accelerate the degenerative diseases of aging through allocation of scarce micronutrients by triage
Contributed by Bruce N. Ames, October 6, 2006 (received for review September 20, 2006)
Inadequate dietary intakes of vitamins and minerals are widespread, most likely due to excessive consumption of energy-rich, micronutrient-poor, refined food. Inadequate intakes may result in chronic metabolic disruption, including mitochondrial decay. Deficiencies in many micronutrients cause DNA damage, such as chromosome breaks, in cultured human cells or in vivo. Some of these deficiencies also cause mitochondrial decay with oxidant leakage and cellular aging and are associated with late onset diseases such as cancer. I propose DNA damage and late onset disease are consequences of a triage allocation response to micronutrient scarcity. Episodic shortages of micronutrients were common during evolution. Natural selection favors short-term survival at the expense of long-term health. I hypothesize that short-term survival was achieved by allocating scarce micronutrients by triage, in part through an adjustment of the binding affinity of proteins for required micronutrients. If this hypothesis is correct, micronutrient deficiencies that trigger the triage response would accelerate cancer, aging, and neural decay but would leave critical metabolic functions, such as ATP production, intact. Evidence that micronutrient malnutrition increases late onset diseases, such as cancer, is discussed. A multivitamin-mineral supplement is one low-cost way to ensure intake of the Recommended Dietary Allowance of micronutrients throughout life.
Poor nutrition has been linked to an increased risk of many diseases, including cancer, heart disease, and diabetes. The human diet requires both macronutrients, which are the main source of calories, and micronutrients (≈40 essential minerals, vitamins, and other biochemicals), which are required for virtually all metabolic and developmental processes. The leading dietary sources of energy in the United States are abundant in carbohydrates and fats (1) but deficient in micronutrients (i.e., they are energy-dense and nutrient-poor) (2). Such foods are inexpensive and tasty and as a consequence are consumed excessively, particularly by the poor (3). Thus, even in the United States (4), inadequate intake of some vitamins and minerals is common (Table 1). Suboptimal consumption of micronutrients (4) often accompanies caloric excess (6, 88) and may be the norm among the obese and contribute to the pathologies associated with obesity.
Significant chronic metabolic disruption may occur when consumption of a micronutrient is below the current Recommended Dietary Allowance (RDA) (7–10) but above the level that causes acute symptoms. When one component of the metabolic network is inadequate, there may be a variety of repercussions in metabolism, including acceleration of degenerative diseases. The optimum intake of each micronutrient necessary to maximize a healthy lifespan remains to be determined and could even be higher than the current RDA, particularly for some populations (7, 10). For example, folic acid intakes above the RDA appear to be necessary to minimize chromosome breaks (10, 11).