Less than 6% of the adult American public consumes below the Estimated Average Requirement (EAR) of phosphorus (580 mg/day) (Fulgoni et al., 2011). NHANES data (2003–2006) indicate the typical phosphorus intake among adult Americans is nearly 1,300 mg/day, whereas the Recommended Daily Allowance (RDA) for phosphorus among this population is approximately 700 mg/day (Institute of Medicine, 1997). Inorganic phosphorus in the food supply is quite small, whereas the majority of dietary phosphorus is in the form of phosphates, and to a lesser degree, phosphoproteins and phospholipids. The emerging questions focus on the potential impact of dietary phosphates, particularly among those with chronic kidney disease (CKD) which, based on declining glomerular filtration rates and chronic microalbuminuria, affects more than 13% of people in the United States. The apparent increase in CKD over the past two decades reflects the growing prevalence of diabetes and hypertension (Coresh et al., 2007).
Dietary phosphorus occurs naturally in a variety of foods derived from animal and plant sources. Plant-derived phosphates, such as phytates in grains, nuts, and legumes, present a low bioavailability (20–50%) (Schlemmer et al., 2009), whereas phosphates from food additives in products such as cheese and beverages, and those naturally occurring in protein-rich foods, such as eggs, milk, and poultry, are generally well absorbed (30–100%) (Noori et al., 2010). Epidemiological data suggest dietary phosphate intake is directly related to consumption of protein-rich foods (Boaz & Smetana, 1996) and the eating of foods with these functional ingredients (Ritz et al., 2012; Winger et al., 2012).
Phosphates in the form of food additives contributed to a 60% increase of total phosphorus intake, based on protein intake (Benini et al., 2011). Among a healthy population, protein and these sources of phosphates do not present health issues; however, published research over the past decade suggests they may be of clinical concern among those with chronic kidney disease (Uribarri and Calvo, 2003).
Section 182 of the Code of Federal Regulations provides a list of phosphate-containing ingredients that are Generally Recognized As Safe (GRAS). Examples of these ingredients (% PO4) include (tri)calcium phosphate (61.2%), (di)sodium phosphate (66.9%), (di)potassium phosphate (54.5%), and (tri)magnesium phosphate (72.3%). According to current regulations, their usage levels are safe when used in accordance with good manufacturing practice.
From a food science perspective, it is important to remember that these kinds of ingredients have many functional properties. Some of those functions include sequestering metal ions, buffering and adjusting pH, increasing water binding, anticaking, forming ionic “bridges,” microbial inhibition, and interacting with proteins in a variety of food products. Those products include carbonated beverages, cereals, baked goods, dairy, egg-based products, fruits and vegetables, gums and gels, and meats. For example, in dairy products, phosphates provide heat and age-gelation stability, improve emulsification, initiate chelation of iron and copper (butter), prevent churning (ice cream), and serve as whipping aids.
Basically, CKD reflects abnormal metabolism of calcium and phosphorus. It is believed that nephron/glomerular loss is associated with increased glomerular capillary pressure that in turn leads eventually to glomerular sclerosis of remaining nephrons. The clinical manifestations of this pathophysiology include hypertension, proteinuria, diabetes, hyperlipidemia, and hyperphosphatemia (or inadequate excretion of phosphorus) with attendant calcium-phosphate deposition in endothelium. The pathogenesis of vascular and soft tissue calcification has been associated with calcium-phosphate deposition that is implicated in vascular mortality of patients with CKD (Shanahan et al., 2011).
There appears to be a strong association between serum levels of phosphorus and Fibroblast Growth Factor-23 (FGF-23), which is believed to have a direct impact on renal function (Hasegawa et al., 2010). This factor is the principal hormone that regulates the biological effects of phosphorus, including 1,25(OH)2 vitamin D production in the kidney, and phosphorus excretion by the kidney (Fukumoto & Martin, 2009). It also appears that, independent of phosphorus metabolism, elevated FGF-23 contributes to an increased risk of cardiovascular disease and some forms of osteomalacia (Yamazaki et al., 2002). Recent evidence suggests vegan sources of phosphorus actually lead to a reduction in FGF-23 (Moe et al., 2011).
That about 50% of our daily phosphorus intake derives from widespread dietary sources and the balance from more bioavailable inorganic food additives has made it standard of care to restrict dietary phosphorous intake and limit GI absorption with phosphate binders (Kalantar-Zadeh et al., 2010; Sullivan et al., 2009). Despite these measures and even in conjunction with hemodialysis, it is a challenge to maintain homeostasis in phosphorus levels in a patient eating an average diet (Uribarri, 2001).
Dietary modification of phosphorus-rich foods in renal disease is not a simple matter. In addition to reducing phosphorus, the protein, sodium, potassium, and overall fluid balance must be carefully monitored and coordinated. CKD patients are exquisitely vulnerable to catastrophic weight loss and malnutrition.
It is for potential kidney health, especially among those with CKD that recent attention has focused on the plethora of food additives such as inorganic phosphate salts; in addition, organic phosphate-containing additives (with a wide range of legitimate technological functions) represent an emerging concern(Winger et al., 2012; Kemi et al., 2009).
The obvious target for effective and efficient intervention becomes this spectrum of food additives that contain significant concentrations of bioavailable phosphates. Importantly, from a public health perspective, higher dietary phosphorus intake is not necessarily associated with increased health risk, even among those with moderate CKD (Murtaugh et al., 2012).
More exhaustive, accurate, and quantitative reporting of phosphate additives is certainly essential. The development of foods with lower levels of phosphorus-containing additives is another obvious avenue for food science research as are methods of phosphorus extraction from various foods. Speculation on the health risk of dietary phosphorus for the general population with normal kidney function has been discussed, but available scientific and clinical data do not seem to offer evidence of a direct causal linkage between phosphates from any nutritional source and disease-producing mechanisms in healthy human subjects. As always, continued and diligent observation and investigation will further illuminate pathophysiology and all levels of intervention.
Roger Clemens, Dr.P.H.,
Chief Scientific Officer, Horn Company, La Mirada, Calif.
Peter Pressman, M.D.,
Medicine & Public Health Advisor, Daedalus Humanitarian Inc.