WHEN PHYSIOLOGY MEETS THE BUILT ENVIRONMENT: THE PHOSPHORUS STORY

ABSTRACT

Phosphorus metabolism disorders are independent risk factors for cardiovascular disease, kidney disease, and mortality. Given that excessive dietary phosphorus intake is prevalent in the general population and significantly contributes to disruptions in phosphorus balance, there is growing interest in limiting phosphorus intake as a potential strategy to enhance cardiovascular and kidney health. Socioeconomic status is a major determinant of phosphorus intake, as extensive epidemiological research indicates a direct correlation between income, education, and diet quality. Beyond individual socioeconomic indicators like income and education, built environment factors such as the availability of and access to healthy food outlets, as well as the density of fast-food restaurants in certain areas, greatly affect individuals’ ability to moderate phosphorus consumption. Given the strong link between the built environment and diet quality, any effective strategy to reduce excess phosphorus intake and improve health outcomes must address built environmental challenges in accessing healthy foods.

INTRODUCTION

Phosphorus is a crucial micronutrient involved in various essential biological processes. Disruptions in systemic phosphorus balance have been linked to cardiovascular disease events and mortality, especially in individuals with chronic kidney disease (CKD) (1–4). Although the reasons behind these associations are not fully understood, substantial evidence suggests that both local and systemic changes in phosphorus metabolism play a role in the development of adverse health outcomes (5–10).

Excessive dietary phosphorus intake is common in Western diets and can perturb phosphorus metabolism (11). As such, restricting dietary phosphorus may be a promising strategy for improving health outcomes. However, a number of barriers make reducing phosphorus consumption challenging in modern societies. Among them, socioeconomic status significantly impacts the quality of an individual’s diet. Research consistently shows that lower socioeconomic status is linked to higher consumption of foods that negatively affect metabolic and cardiovascular health, such as added fats, sugars, salt, and refined grains (12,13). Conversely, higher socioeconomic status is associated with greater intake of healthier foods like whole grains, fruits, and vegetables. While personal financial resources are crucial in determining the types of food that individuals can purchase and consume, other factors such as the neighborhood one resides in, the availability of stores selling health foods, access to transportation to and from these food sources, and the prevalence of fast-food restaurants, also play a significant role in the ability to obtain and consume nutritious foods (14,15). These built environment factors are particularly important and often overlooked in dietary management. For these reasons, the environment in which a person lives can greatly influence their ability to adhere to dietary recommendations to reduce phosphorus consumption, and associated risks of cardiovascular and kidney disease, in the modern era.

OVERVIEW OF PHOSPHORUS METABOLISM

Total body phosphorus balance is maintained through a complex interplay between dietary phosphorus absorption, urinary excretion, and exchanges with bone, soft tissues, and intracellular stores (16). The kidneys play a crucial role in this balance by adjusting urinary phosphorus excretion in response to dietary intake and tissue turnover. Typically, the majority of the phosphorus load (1,200–1,500 mg/day in a Western diet) comes from dietary sources, which the kidneys must excrete to maintain balance (17). Therefore, managing dietary phosphorus absorption is a key therapeutic strategy for preventing a positive phosphorus balance in individuals consuming a typical Westernized diet.

Phosphorus is absorbed across the intestinal tract through both passive (paracellular) and active transport (sodium-phosphorus co-transporters Npt2b and Pit1) pathways (18). In the kidneys, most circulating inorganic phosphorus is filtered by the glomeruli and reabsorbed in the proximal tubules via sodium-phosphorus co-transporters (Npt2a and Npt2c) (19). Typically, 80–90% of the filtered phosphorus is reabsorbed, with the remainder excreted in urine. Parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23) are key regulators of this process, reducing phosphorus reabsorption by downregulating these transporters, thus increasing urinary excretion (17,20). FGF23 also reduces dietary phosphorus absorption by lowering 1,25-dihydroyxvitmain D (1,25-OH-D) concentrations through inhibition of its synthesis and stimulation of its breakdown.

Increased dietary phosphorus intake triggers the secretion of PTH and FGF23, which help prevent hyperphosphatemia by enhancing urinary excretion and reducing dietary absorption (21,22). This mechanism is particularly important in CKD patients, where elevated levels of FGF23 and PTH are crucial for maintaining phosphorus balance despite high dietary intake—interventions that lower PTH or FGF23 concentrations can lead to increased serum phosphorus due to decreased urinary excretion, highlighting the importance of these hormones in phosphorus regulation (23). Additionally, restricting dietary phosphorus has been shown to lower FGF23 and PTH concentrations in CKD patients (24–34), supporting the role of dietary management in controlling phosphorus metabolism disorders in CKD.

Adverse Impacts of Excess Phosphorus on Cardiovascular and Kidney Disease

Excess phosphorus has been linked to adverse cardiovascular outcomes through various pathophysiologic mechanisms (6–9,35). Extensive research indicates that high phosphorus concentrations contribute to pathological calcification of vascular tissues and heart valves, induce cardiomyocyte hypertrophy, and impair vascular reactivity by inhibiting nitric oxide synthesis in both animals and humans. These findings provide strong mechanistic evidence that excess phosphorus can initiate or accelerate cardiovascular disease. Additionally, elevated serum phosphorus concentrations have been associated with increased inflammatory cytokines (36), and reducing gut phosphorus absorption has been shown to lower inflammation biomarkers in CKD patients (37–39). Collectively, these data suggest a link between high phosphorus intake and inflammation, a key factor in cardiovascular disease. Observational studies further support the clinical relevance of these experimental findings. Elevated serum phosphorus is associated with vascular calcification across different levels of kidney function. Higher serum phosphorus concentrations have also been linked to surrogate markers of vascular calcification, such as increased arterial stiffness, higher left ventricular mass index, and carotid artery disease (40–48). Phosphorus excess also can cause cardiovascular disease through stimulation of FGF23 secretion, which has been shown to induce left ventricular hypertrophy and associated heart failure, the likely mechanism underlying a robust association of FGF23 with adverse cardiovascular and survival outcomes (49–52). These associations highlight the potential impact of phosphorus excess on cardiovascular health.

Excess phosphorus has also been linked to the development of kidney disease through various mechanisms. In experiments from nearly nine decades ago, rats without kidney disease were fed diets that were designed to be high in inorganic phosphorus (2–6.5%) for about six weeks (53). These rats developed renal tubular necrosis, widespread renal calcification, inflammation, and interstitial fibrosis, and the effects were more pronounced in the presence of kidney disease. Ibels, et al published a study in 1978 that included two groups of rats that underwent subtotal nephrectomy to induce chronic uremia (54). They were then fed either a diet with normal amounts of phosphorus (0.5%) or a diet with a low amount of phosphorus (0.04%) plus aluminum hydroxide for six weeks. Both diets had similar protein content. Serum creatinine levels increased similarly in both groups after four weeks. However, creatinine levels continued to rise in rats on the standard phosphorus diet, while they stabilized in those on the low phosphorus diet. Additionally, all rats eating the standard diet died within six weeks, whereas only three of the 12 in the low phosphorus group died. Histological analysis showed higher calcium and phosphorus content and more interstitial fibrosis in the kidneys of rats on the standard diet, indicating a direct harmful effect of excess phosphorus.

While the impact of excessive phosphorus on the deterioration of kidney function in humans has not been extensively studied, existing evidence indicates that phosphorus overload may contribute to kidney function decline. Large observational studies have found that elevated serum phosphorus levels are linked to faster progression of kidney disease and a higher risk of developing end-stage kidney disease, independent of established risk factors such as lower baseline estimated glomerular filtration rate (eGFR) (55–59). Additionally, increased concentrations of FGF23 are a significant risk factor for CKD progression, potentially by predisposing kidney tubules to inflammation and interstitial fibrosis through the deposition of calcium-phosphorus crystals (60). Even in individuals with normal kidney function and serum phosphorus levels within the normal range, higher baseline phosphorus levels have been independently associated with an increased risk of developing CKD (57). This suggests that excess phosphorus can negatively affect kidney health across all stages of kidney function, supporting the goal of reducing a positive phosphorus balance by reducing phosphorus consumption.

Phosphorus Content in the Food Supply: Challenges for Mitigation

Effectively reducing dietary phosphorus intake in adults living independently is a complex task. This complexity arises from a variety of personal, cultural, and environmental factors that influence the amount and quality of dietary phosphorus consumed. Both individual and contextual socioeconomic factors play significant roles in determining food choices. Individual factors include a person’s financial ability to purchase nutritious foods, while contextual factors pertain to the characteristics of the built environment, such as the availability of grocery stores and the prevalence of fast-food outlets (14,61–67). These environmental aspects can greatly affect food purchasing decisions. Understanding these barriers is crucial, as they significantly impact systemic phosphorus balance by influencing daily phosphorus intake.

Socioeconomic status profoundly affects diet quality, which in turn influences patients’ ability to adhere to nutritional guidelines. Research consistently shows that individuals with lower socioeconomic status consume more foods associated with negative metabolic, cardiovascular, and kidney outcomes compared to those with higher socioeconomic status (68–72). This disparity complicates the management of chronic diseases, as numerous studies link poverty with increased risks of diabetes, obesity, coronary artery disease, and CKD (73,74). Both individual and contextual socioeconomic status factors contribute to these dietary disparities. Individual purchasing power determines the ability to buy healthier foods, such as fresh fruits and vegetables, which are often more expensive than processed and fast foods. Equally important are contextual factors related to the neighborhood environment, such as the availability of grocery stores and the density of fast-food restaurants. They also contribute to food insecurity, defined as the limited or uncertain ability to acquire nutritionally adequate and safe foods in socially acceptable ways (75).

Further complicating the task of reducing phosphorus consumption in individuals eating a Westernized diet is the widespread use of phosphorus-based additives in modern food production (76). The use of these additives surged in the latter half of the twentieth century, significantly increasing the phosphorus content of contemporary diets. Phosphorus additives are crucial in food manufacturing for functions such as pH stabilization, metal cation sequestration, emulsification, leavening, hydration, and bactericidal actions (76). While meat products with phosphorus additives have received significant attention, the baking industry uses even more phosphorus additives due to their essential role in dough leavening. Current estimates of how much phosphorus additives contribute to total phosphorus consumption in Westernized diets per day vary (Table 1) (11,77–82), but even at the low end of estimates (∼10%), the contribution is substantial.

Table 1.

Estimates of the Total Contribution of Food Additives to Phosphorus Consumption per Day

Author	Estimated Contribution
Bell, J Nutr, 1977	up to 1,000 mg/d
Feldheim, Milchwissenshaft, 1983	10% of total intake (~140 mg/d)
Greger and Krystofiak, Food Technol, 1982	20–30% of total intake per day (300–450 mg/d)
Zemel and Bidari, J Food Sci, 1983	250–1,000 mg/d
Oenning, J Am Diet Assoc, 1988	350 mg/d
Leon, J Renal Nutr, 2013	606 mg/d
Carrigan, J Renal Nutr, 2014	736 mg/d

Phosphorus is naturally abundant in the food supply, so most people in the United States easily meet or exceed the recommended daily allowance (RDA) of dietary phosphorus (76). The high levels of phosphorus additives in processed foods further increase phosphorus intake, with older studies estimating an additional 250 to 1,000 mg of phosphorus per day. Recent studies continue to show that phosphorus additives contribute significantly to total daily phosphorus intake in diets high in processed foods. For example, a study by León, et al analyzed the top five best-selling food products containing phosphorus additives across 15 food categories and compared them to similar products without additives (82). They found that additive-rich foods contributed an estimated 736 ± 91 mg of extra phosphorus per day compared to additive-free foods. Similarly, Carrigan, et al developed four-day menus for both low-additive and additive-enhanced diets (11). The low-additive diet adhered to U.S. Department of Agriculture (USDA) guidelines for energy and phosphorus intake and included minimally processed foods, while the additive-enhanced diet substituted highly processed foods. The study found that the additive-enhanced diet had an average of 606 ± 125 mg more phosphorus per day than the low-additive diet, representing a 60% increase in total phosphorus content. Additionally, the sodium content of the additive-enhanced diet was on average 1,329 ± 642 mg higher per day than the low-additive diet, highlighting the significant impact of sodium-based additives in processed foods. These findings underscore the challenges of managing phosphorus intake in individuals eating modern diets, particularly those from lower socioeconomic backgrounds who may rely more on processed and inexpensive foods.

One significant issue with phosphorus additives in processed and fast foods is that their quantities are often not disclosed on food labels, as manufacturers are not required to list them (76). This results in a largely “hidden” dietary phosphorus load in typical American diets. Moreover, these additives are absorbed more efficiently in the gut (over 90%) compared to organic phosphorus found in animal or vegetable proteins (about 50–60%), which can have significant implications (83). For instance, a study found that foods with higher phosphorus bioavailability significantly increased serum phosphorus and FGF23 concentrations in CKD patients, indicating that the high bioavailability of phosphorus additives may exacerbate their negative impact on phosphorus balance in CKD (30). The physiological implications of phosphorus additives on FGF23 secretion in individuals with normal kidney function have also been demonstrated by our group. We previously demonstrated that a diet enriched with phosphorus additives, providing approximately 1,700 mg of phosphorus and 700 mg of calcium per day, led to elevated circulating concentrations of circulating FGF23, osteopontin, and osteocalcin in healthy volunteers (84). In a subsequent study of healthy volunteers in which we more carefully controlled for the calcium to phosphorus ratio in the diet, fasting plasma FGF23 concentrations similarly increased relative to baseline values by about 11%, though the response to increased phosphorus consumption had no effect on osteopontin and osteocalcin (85). In the aggregate, these data not only demonstrate that phosphorus additives in the food supply are abundant, but that they also have meaningful impacts on hormones pathophysiologically linked to cardiovascular and kidney disease in individuals across the spectrum of kidney function.

The strong link between neighborhood characteristics and the consumption of processed and fast foods suggests that limited access to healthy food options likely contributes to excessive phosphorus intake by increasing reliance on highly processed foods. Although few studies have specifically examined the impact of access to food stores or fast-food restaurants on phosphorus intake, research on socioeconomic status and biochemical markers of phosphorus homeostasis offers some insights. Several studies have shown that lower annual family income is associated with higher serum phosphorus levels in participants of the National Health and Nutrition Examination Survey (86) and higher serum phosphorus and FGF23 levels in participants of the Chronic Renal Insufficiency Cohort Study (87). Conversely, a study using the Multi-Ethnic Study of Atherosclerosis (MESA) database found no association between annual family income and serum phosphorus levels when controlling for other factors, particularly female sex (88). Additionally, this study found no link between fast-food consumption and serum phosphorus levels.

Overall, these findings suggest that socioeconomic status partially influences biochemical measures of phosphorus homeostasis, though the strength and consistency of this association vary and are not clearly related to food access.

CONCLUSION

Phosphorus is abundant in the modern diet, making it challenging to restrict in order to avoid adverse health outcomes associated with excess phosphorus. To effectively accomplish this goal, it is essential to consider the types of foods being purchased and where they are sourced. This approach requires sensitivity to the availability of food establishments in each patient’s neighborhood and tailoring dietary advice to their specific circumstances. Research into new approaches to mitigate the abundance of phosphorus additives in the food supply due to entrenched built environment factors, especially in resource-limited communities, is necessary to address the impact of the build environment on cardiovascular and kidney disease related to excess phosphorus consumption, and developing sustainable methods to improve access to nutritious foods should be a top priority in public health research.

DISCUSSION

Arthur, Little Rock: Thanks for a great talk. When I talk with my patients, counsel them about diet, and send them to a dietician, I always think to myself that patients who are educated and well off will probably do what I say and patients who are not so well educated and not as well off will probably not do what I suggest. Are there other things that we could be putting in food besides phosphates that aren’t sodium or nitrates? You did a great job of presenting all the benefits of these additives, but are there other things that we could do?

Gutiérrez, Birmingham: A lot of work has been done to determine whether certain things might be better alternatives, though there are probably trade-offs. One of the practical things we can recommend to people across the social and economic gradient to at least decrease the effects of phosphorus is to increase the amount of calcium they consume. Much of the phosphorus already in food will then be bound and less will be absorbed, which could help to reduce some of these effects. In resource-poor areas, if people cannot afford heathier food, maybe they can at least increase their calcium intake.

Broch, Baltimore: Thank you very much for that great talk. I have one quick question about ultra-processed foods in the 1970s and 1980s. Some research now links that to the current obesity epidemic. Do you think there’s sort of a paradox—if you give a lot of phosphates, in the short term at least, you see some decrease in obesity and waist size differentials go down? Can you comment a little bit on that because I don’t completely understand how this all fits together?

Gutiérrez, Birmingham: That’s a great question. I think what you’re referring to is interesting data—largely animal data—but there’s some supporting human data as well that suggests if you consume a large amount of phosphorus, it reduces your weight, particularly the visceral adiposity. This seems to be related, in part, to changes in insulin sensitivity in these individuals. Certain individuals out there, such as Bob Heaney, have suggested we should be eating more phosphorus for our bone health and to reduce the obesity epidemic. The problem is when phosphorus is combined with all the other things in processed foods (which is probably a bad combination), these other “obesogenic” nutrients in processed foods will drive obesity. We believe the phosphorus in food will drive other factors that add to cardiovascular disease so the combination of those things ultimately is deleterious to overall health as opposed to phosphorus itself which may be beneficial for reducing weight per se.