Physiological Effects of Nutrients

Nutrients are required to drive the basic physiological activities that sustain life. Nutrients function in diverse roles as energy sources; coenzymes and cofactors in enzyme systems; structural components of cell membranes; hormone effectors; precursors of biologically active molecules that include eicosanoids, neurotransmitters and nucleic acids; initiators and modulators of metabolic activity; determinants of membrane electrochemical potential; regulators of differentiation of epithelial cells and osteocytes; and a broad spectrum of other cellular activities. Nutrients may also be involved in less well-defined roles such as in membrane receptor synthesis and activity and inflammatory responses, and as promoters and inhibitors of gene expression and cell replication.

If nutrient intakes are not sufficient to adequately support these basic physiological activities, adaptive mechanisms are triggered to conserve the available nutrient supply. Among these mechanisms are increased efficiency of intestinal absorption, enhanced renal reabsorption, adjustment of metabolic rate, and a compensatory shift to ancillary pathways that minimize nutrient demand. Although effective as temporary corrective measures, these adaptive responses will begin to lose effectiveness over time if inadequate intakes are not corrected.

Nutrient deficiencies may be classified as absolute or relative. Absolute deficiencies are caused by chronic inadequate consumption of nutrients that eventually results in depletion of reserves. Depleted nutrient reserves leave cells vulnerable to daily fluctuations in nutrient intakes or to sudden increases in demand that occur with unintended exposure to environmental stressors such as pathogens, chemical irritants, and oxygen free radicals, or to cellular injury from infection or trauma. Relative deficiencies can occur even if nutrients are consumed in adequate amounts to meet basic physiological requirements and maintain reserves, when these intakes are not sufficient to satisfy increases in metabolic demand.

Effects of Nutrients in Disease

The effects of nutrients in disease are the result of support for activities that impede or reverse the progression of cellular pathology and physiology. All innate cellular functions, defenses, and repair systems require a continuous supply of nutrients provided by nutrient reserves to make up the shortfall as dietary intakes fluctuate. Among the critical nutrient-dependent cellular defenses are free radical and cellular antioxidant enzymes, acute inflammatory responses, phagocytic and bactericidal activity, lymphocyte activation and proliferation, humoral and cell-mediated immunity, and the initiation and promotion of the coagulation cascade. Additional defensive roles supported by nutrients involve protein synthesis, reversal and repair of DNA and chromosomal damage, integrity of immune cell structure and function, and a whole host of other activities at the molecular level.

Nutrients function in disease by mechanisms that differ substantially from those of pharmacologic agents. Nutrients will modify nutrient fluxes and metabolic activities that are part of normal cellular processes whereas drugs will bind to membrane receptors and inhibit their activity to alter cell responsiveness. Nutrient requirements in the presence of disease are considerably higher than those that have been established to prevent the symptoms of the classic deficiency diseases. These requirements can increase incrementally by as much as 10 to more than 100 times the usual amounts. At these levels of intake, the roles for most nutrients are expanded to include functions that are not typically observed at physiological intakes. The higher requirements for nutrients in disease are needed to support the accelerated rate of metabolic activity that cellular systems demand in order to reduce the potential for permanent damage from the pathophysiological processes associated with the disease.

Metabolic Burden of Nutrient Imbalances

Nutrient imbalances may be linked to initiation and/or exacerbation of virtually all diseases. These imbalances can be caused by either deficiencies or excesses of one or more nutrients. Excesses can sometimes contribute to relative deficiencies by increasing demand for supporting nutrients to accommodate the increased rates of metabolism required for disposal of the nutrient surplus. Nutrient deficiencies most often involve inadequate intakes of vitamins, minerals and omega -3-fatty acids, and ingestion of low quality protein. Nutrient excesses most often involve overconsumption of energy, fat, saturated fat, omega-6 fatty acids, and cholesterol. Both types of nutrient imbalances can occur simultaneously from habitual consumption of diets high in energy and fat that provide low quality protein and are depleted of vitamins and minerals.

Nutrient imbalances impose a metabolic burden on all organ systems, with the greatest burden on those systems responsible for achieving and maintaining metabolic equilibrium. Long-term disruption of metabolic equilibrium will most often adversely impact the cardiovascular, pulmonary, renal, gastrointestinal, or musculoskeletal systems. In the absence of an adequate supply of nutrients to satisfy normal physiological requirements or adjust to increased metabolic demand, compensatory mechanisms involving one or more of these systems must be initiated to re-establish homeostasis. As with metabolic adjustments to address short-term nutrient deficiencies, these compensatory responses are important for correction of temporary imbalances, but if sustained over the long term, they may become maladaptive and contribute to the degenerative changes responsible for development or worsening of chronic diseases.

Compensatory Responses to Nutrient Imbalances

The primary objective of compensatory responses to nutrient imbalances is to re-establish physiological homeostasis. An example of a compensatory response to an excess intake is the increased secretion of insulin following ingestion of a meal high in rapidly digested and absorbed carbohydrate (high glycemic index foods). Over the short-term, this elevation in insulin is maintained until postprandial blood glucose is restored to fasting levels, usually within a few hours after the meal. When large amounts of high glycemic index foods are repeatedly consumed throughout the day, the postprandial insulin response is sustained for longer periods which will eventually promote the downregulation of insulin receptors that contributes to glucose intolerance. The compensatory response to consumption of large amounts of fat follows a similar path. Elevated postprandial triglyceride levels require secretion of large amounts of chylomicrons to transport the triglyceride load from the intestines to the liver where it is deposited, leaving behind a high concentration of chylomicron remnants. These particles are highly atherogenic with effects on arterial plaque formation similar to those of low density lipoproteins (LDL).

Other examples of compensatory responses to nutrient imbalances involve homeostatic adjustments to maintain body pools of nutrients such as what is observed when sodium intakes are excessive and when calcium intakes are inadequate. If the amount of sodium ingested exceeds renal capacity for elimination, plasma volume will expand until the excess amounts are excreted and sodium homeostasis is re-established. A temporary expansion of plasma volume triggers a compensatory increase in resistance of the peripheral microvasculature in order to maintain a steady rate of vascular perfusion through these tissues. A sustained expansion of plasma volume caused by continuous intakes of excess sodium that overwhelm renal elimination capacity may transform the compensatory increase in peripheral resistance to an increase in blood pressure and establishment of essential hypertension.

The compensatory response to imbalances in calcium homeostasis is initiated by intakes that are not sufficient to maintain plasma calcium levels. Since a critical level of calcium in plasma is an absolute requirement for normal neuromuscular activity, coagulation, and other calcium-dependent activities, short-term deficiencies in calcium intake will trigger the release of calcium from labile skeletal reserves. When these labile reserves are depleted by failure to adjust calcium consumption, bone mineral mass will be sacrificed to release structural calcium into circulation to prevent the plasma concentration from decreasing below critical levels.

Implications of Subclinical Nutrient Deficiencies

Clinical assessment of nutritional status has long been exclusively focused on detection of absolute nutrient deficiencies by relying on clinical evidence of signs and symptoms of classic deficiency states. Yet relative nutrient deficiencies due to disease are equally important, as is the detection of nutrient imbalances before clinical evidence of deficiency is present. At the point where altered cell function has evolved into clinical manifestations of nutrient deficiency, cellular activity will have been compromised for some time and the compensatory responses that might have allowed a temporary adjustment to the deficiency would no longer be effective. Detection of subclinical changes in cell processes early in the course of a nutrient deficiency when cell damage is minor and more readily reversible can have a considerable impact on prevention and treatment of disease. If subclinical deficiency is not corrected, then prolonged marginalization of cellular activity may not only increase vulnerability to disease, but also exacerbate progression of existing disease and interfere with effectiveness of treatment, since all drugs require some level of metabolic support to achieve their desired therapeutic effects.

Nutrient Requirements of Disease States

The involvement of nutrients in cellular defense and repair systems suggests that nutrient requirements must be modified by pathology. In disease, nutrient-dependent activities are expanded to include effects that enhance cellular responsiveness to treatment and accommodate accelerated rates of metabolic activity. Although specific nutrient requirements for different diseases have not been established, they may be imputed from current knowledge of the chemical, physical and biological properties of each nutrient, the nature of the disease, the tissues involved, the type of treatment indicated, and the cellular activities targeted by the treatment.

Neurotransmitters are a class of compounds derived from amino acid precursors that target specific cells to elicit a response to a particular effector molecule. These effector molecules may be a nutrient, a hormone, a nucleotide, an enzyme, a drug, an immunoreactive substance, an inflammatory mediator, or any other substance that has the ability to evoke a cellular response. The neurotransmitters that have been identified and characterized to date are serotonin, nitric oxide, brain histamine, gamma-amino butyric acid (GABA), acetylcholine, dopamine, and norepinephrine. These neurotransmitters are derived from tryptophan, arginine, histidine, glutamic acid, choline, and tyrosine (dopamine and norepinephrine), respectively. Each neurotransmitter will act on a specific target cells. In the presence of disease, the increased demand for neurotransmitters cannot be satisfied by consuming amounts of precursors from dietary sources alone. Supplementation may be needed to prevent relative deficiencies of these amino acid precursors that will ensure that sufficient amounts of neurotransmitters produced are to promote a robust response to treatment and support the processes of healing and recovery.