Sugar sweetened beverage consumption is positively associated with Klotho levels at two years of age in LatinX youth | BMC Nutrition
Stress, income and Klotho
We foundÂ a significant positive association betweenÂ Î±-klotho levels at 2 years andÂ increased household incomeÂ possiblyÂ related to increased stress exposures in lower income households. In a previous study examining psychosocial factors in adults in relation to Î±-klotho levels, high-stress caregivers had lower serum Î±-klotho levels than low-stress ones . Lower Î±-klotho levels were also significantly associated with depressive symptoms, a common maladaptive brain response to stress . Other studies have shown that poverty increases stress responses not only in parents  but children  as well, affecting both physiological  and psychological  development even at very young ages. Efforts to alleviate poverty have been suggested to improve health outcomes in children . In our LEAD cohort, mothers who had higherÂ housheold incomes may have had children who experienced less chronic stress and therefore had higher Î±-klotho levels, than children in lower income households and higher exposures to stress.
Sugar sweetened beverages
We found a positive association between SSB intake and higher Î±-klotho levels supporting a potential association between secreted Î±-klotho levels and phosphate in young, low-income children [18, 19]. Children at 24âmonths of age who reported drinking any SSBs showed significantly higher Î±-klotho levels (2029.78âÂ±â999.45âpg/mL) than those who did not (1402.78âÂ±â496.28âpg/mL) even when controlling for weight Z score at birth, leptin levels at two years, insulin at birth, child sex, maternal education andÂ household income levels. Our findings suggest that dietary sources of phosphate as a food additive can influence this relationship . Phosphate is commonly used as an additive in sugary drinks marketed to children and especially colas , commonly consumed by young children, particularly inÂ higher risk low-income communities. Fifty-nine percent of our cohort was already consuming SSBs by 2âyears of age.
Phosphorous additives on food labels can be difficult to decipher Â and, the amount of phosphorous in sugar sweetened beverages can range from <â1âmg to 175âmg per serving . Even if parents in our study were avoiding giving their children carbonated sodas, the drinks they may have assumed were better alternatives containÂ high amounts of phosphorous per serving: Hawaiian Punch (175âmg), Fruit Works (63âmg-140), Aquafina Flavor (62âmgâ85âmg), Tropicana Fruit Punch (93âmg) . Even amounts of approximately 60âmg per serving serve as significant sources of dietary phosphates. TheÂ organic absorption rate of phosphates fromÂ meats, dairy, grains and beans is 40â60%  whileÂ the absorption rate Â from inorganic phosphates inÂ SSBs, processed meats and cheeses  can be as high as 100% .
TheÂ physiological regulation of phosphate is controlled by the FGF-23/Î±-klotho mechanism such that an increase in phosphate levels is associated with an increase in both FGF-23 24 and Î±-klotho levels [1, 6]. An increase in phosphate levels signals the FGF-23 complex to trigger a cascade which reduces the number of sodium-dependent phosphate (NaPi) cotransporters, type-2a (NaPi-2a), on the brush border membrane of proximal tubules, thereby promoting renal phosphate excretion . Î±-Klotho is required for FGF-23 to induce negative phosphate balance in this mechanism, demonstrated in previous studies where FGF-23 recombinant protein is unable to reduce serum phosphate levels in klotho deficient mice . While Î±-klotho is a necessary co-receptor of phosphate regulation , Î±-klotho also exhibits effects independent of FGF-23 and parathyroid hormone (PTH), which regulate calcium ion homeostasis in the kidneys . While previous evidence supports that high Î±-klotho levels have positive physiological effects  and benefits toÂ cognition , the elevation of Î±-klotho levels via activation of the FGF-23 phosphate regulation pathway raises concern of potential long term harm.
As significant sources of inorganic phosphates which are readily absorbed, SSBs create an artificial increase in FGF-23. Elevated FGF-23 is associated with negative health consequences including inflammation Â and is an early marker for chronic kidney disease . It is not clear whether theÂ positive effects of increased Î±-klotho levels would compensate for potential harm of chronicallyÂ elevated FGF-23 levels. Our previous study found that insulin at birth was inversely correlated with cord bloodÂ Î±-klothoÂ levels  .There may be a confounding relationship between Î±-klotho, SSBs and insulin. Controlling for insulin in our study strengthened the relationship between Î±-klotho and SSBs . Future studies should also assessÂ FGF-23 inÂ addition toÂ Î±-klotho levels.
Any consumption of SSBs in children,Â may be positively associated with Î±-klotho levels supporting previous studiesÂ that high phosphate diets and FGF-23/ Î±-klotho mechanisms are related [9, 18]. The initial increase in Î±-klotho may be an immediate response in the short term to control phosphate levels  but could have lasting negative effects. High FGF-23 concentrations are linked to cardiovascular damage and inflammation . Intake in early childhood could be particularly damaging as high dietary phosphates has been shown to be more detrimental at critical growth periods .
Dietary habits are known to be established early in life and previous evidence supports that diet quality tracks and declines from early childhood through adolesence . SSB consumption in early childhood could track through adolescence  especially with increased exposure to advertising  leading to a lifetime of increased consumption .
Future studies should include additional metabolic and micronutrient serum indicators. We did not assess serum phosphate, FGF-23 or vitamin D levels in our participants. These serum markers would have provided a more comprehensive understanding of the relationship between dietary phosphate intake, including inorganic phosphate from SSBs, Î±-klotho and metabolic profile including Vitamin D status . Further, future studies should account for all dietary sources of phosphate including those from other high phosphate foods (e.g. beans, lentils, pasta and rice) as well as intake of other source sources of inorganic phosphate fromÂ fast foods, other processed foods and canned foods.