IFAC Statement Regarding the Study “High-Phosphate Diet Induces Exercise Intolerance and Impairs Fatty Acid Metabolism in Mice”
In January 2019, an article titled “High-Phosphate Diet Induces Exercise Intolerance and Impairs Fatty Acid Metabolism in Mice” was published in the journal Circulation. The authors suggest dietary phosphorus is over consumed and found a link between higher phosphate consumption to exercise intolerance and less time spent exercising on a treadmill using mice models. As these findings were based on observational studies in mice and the researchers’ opinion of what “excess” means, they should be interpreted cautiously. Studies linking mice models to human health outcomes have many limitations, and multiple factors contribute to a person’s desire and ability to exercise, many of which should not be attributed to a slightly higher phosphate intake and the duration spent exercising.
The study was conducted to determine the association between inorganic phosphate, a food additive, with physical activity in humans. The authors suggest phosphate is “used in excess” as a preservative and flavor enhancer in foods, citing between 40 and 70 percent of common selling grocery items as containing phosphate additives. The researchers go on to report up to 25 percent of American adults have three or four times higher intakes of the recommended daily allowance of phosphorus.
In order to determine the “direct effects” of dietary phosphate on exercise capacity and other biochemical markers, a treadmill exercise test was conducted on mice fed either a normal phosphate diet (n=15-18; 0.6% of diet) or a high phosphate diet (n=4-7; 2.0% of diet) for 12 weeks. The researchers found that a high phosphate diet appeared to decrease time spent on a treadmill as compared to the normal phosphate diet. However, there was no effect on body weight and there were no significant differences in the biochemical markers of mice fed either diet. The researchers also studied phosphate levels in human blood/serum, and found higher phosphate levels appeared to “decrease physical activity independently of renal [kidney] function and body mass index.” As it relates to oxidation in skeletal muscle during exercise, the researchers made a determination on muscle strength in the human study after only one single bout of muscle contraction; daily physical activity ability was not determined. The researchers conclude the high phosphate diet in mice induces disruption in skeletal muscle metabolism and the study results may have a broader public health implication to the general population.
IFAC has numerous concerns with this study. First, it should be noted that many authoritative scientific and regulatory bodies have not provided tolerable upper intake levels for dietary phosphorus due to inadequate scientific evidence. The outcome of a 2017 research review indicated “available data were not sufficient to establish a Tolerable Upper Intake Level (UL) for phosphorus.” Therefore, in this study, the authors’ perception of “excess” intake should not be used to draw conclusions about excessive intake. IFAC believes another fault in the study includes a small sample size of mice which was only 4-7 mice in the high phosphate diet group and 15-18 mice in the normal phosphate diet group. The researchers attempt to correlate a higher phosphorus diet in only 4-7 mice with decreased time spent doing physical activity is not supported by strong evidence and, in this case, might simply be a matter of desire or interest of the mice participants. Regarding physical activity in humans, IFAC and the researchers can agree with findings from the Centers for Disease Control and Prevention that 80% of American adults do not meet the recommended “physical activity guidelines for aerobic and muscle strengthening.” However, IFAC believes multiple factors contribute to muscle strength, endurance, and overall exercise ability and no single dietary mineral can be attributed to physical stamina—especially if most people are not normally physically active and in the study “daily physical activity ability was not determined.”