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Journal of the American College of Nutrition, Vol. 20, No. 4, 271-278 (2001)
Published by the American College of Nutrition

Commentary

The Institute of Medicine’s "Dietary Reference Intake" for Phosphorus: A Critical Perspective

Leonard Sax, MD, PhD

Poolesville, Maryland E-mail: leonardsax{at}prodigy.net

Address reprint requests to: Leonard Sax, M.D., Ph.D., P.O. Box 108, Poolesville, MD, 20837. E-mail: leonardsax{at}prodigy.net

ABSTRACT

Two questions relevant to the safety of phosphate additives have been raised in the literature: 1) Is the dietary ratio of calcium to phosphorus clinically significant in humans? Specifically, can a high-phosphorus, low-calcium diet cause hypocalcemia and/or secondary hyperparathyroidism in humans? 2) Does the growing use of phosphate-containing food additives increase the risk of low bone density and/or fracture in humans?

In 1999, the Institute of Medicine published a monograph which addressed these two questions. This article critically reviews the findings and conclusions of the Institute of Medicine in the light of recent research.

Key words: dietary phosphorus, dietary calcium, parathyroid hormone, bone density

The Institute of Medicine (IOM) was established by the National Academy of Sciences in 1970. The Food and Nutrition Board of the IOM establishes dietary reference guidelines for the United States. In April 1996, the Food and Nutrition Board’s Dietary Reference Intake Standing Committee established a nine-member Panel on Calcium and Related Nutrients "to review the scientific literature and interpret the depth of current knowledge on calcium, phosphorus, magnesium, vitamin D, and fluoride metabolism in humans throughout the life span" [1]. The Panel met five times. The Panel’s preliminary report on Dietary Reference Intakes for Calcium, Phosphorus, Magnesium, Vitamin D, and Fluoride was released in 1997. The final report was released in 1999.

Prior to publication of the IOM report, two questions relevant to the safety of dietary phosphorus had been raised in the literature:

We will briefly survey the literature relevant to these two questions and then consider how these issues are addressed in the IOM report.

Is the Dietary Ratio of Calcium to Phosphorus Clinically Significant in Humans?

Specifically, can a high-phosphorus, low-calcium diet cause hypocalcemia and/or secondary hyperparathyroidism in humans?

Many investigators have found a significant and sustained rise in serum parathyroid hormone (PTH) in humans who ingest supplemental phosphates [2,3,4,5,6]. The mechanism of this rise in PTH after ingestion of phosphates is generally attributed to the formation of calcium phosphate complexes in the blood [6].

If dietary calcium is plentiful, then free ionized calcium lost to the formation of calcium phosphate can be replenished from the diet. But if calcium consumption does not keep pace with phosphate consumption, then the concentration of free ionized calcium in plasma may begin to decline [7]. A drop in calcium concentration will trigger release of PTH, promoting release of calcium from bone via bone resorption, normalizing the concentration of free ionized calcium at the expense of bone density.

Consumption of phosphorus per se would therefore be expected to be less important than the molar ratio of dietary calcium to dietary phosphorus. If there is rough parity in consumption of calcium and phosphorus, no effect on bone density would be expected. If consumption and absorption of phosphorus is substantially greater than consumption and absorption of calcium, then secondary hyperparathyroidism, and a decline in bone mineral content, may result.

Numerous animal studies have demonstrated that diets with low calcium-to-phosphorus ratios give rise to low bone densities (see [8] for review). The dietary calcium-to-phosphorus ratio has been shown to predict bone density, independent of the absolute intake of both elements, over a wide range of intakes in laboratory animals [9].

Two recent studies have demonstrated a similar finding in humans: namely, that while phosphorus consumption per se is not consistently predictive of bone density and calcium consumption per se is only slightly correlated with bone density, the dietary calcium-to-phosphorus ratio correlates significantly, and positively, with bone density. Metz, Anderson and Gallagher [10], studying 24-to-28-year-old Caucasian women, reported a slight negative association between phosphorus consumption and distal bone mineral content (p = 0.033), a modest positive association between calcium consumption and distal bone mineral content (p = 0.014), but a much more significant, positive correlation between the dietary calcium-to-phosphorus ratio and distal bone mineral content (p = 0.0068). A study of 510 perimenopausal women [11] reported similar findings: while there was no consistent correlation between phosphorus consumption alone and bone density, and an intermediate positive correlation (p < 0.01) between calcium consumption and bone density, the strongest predictor of bone density was the dietary calcium-to-phosphorus (Ca:P) ratio. "The Ca:P ratio proved to be a significant independent predictor of bone mineral content and bone mineral density in all regions (p < 0.0005)."

Do Phosphate Additives Increase the Risk of Hypocalcemia, Low Bone Density or Fracture, in Humans?

Phosphate additives are used as flavor stabilizers in all popular cola beverages sold in the United States. (Non-cola carbonated beverages use citric acid rather than phosphates for this purpose.) Several investigators have suggested that consumption of cola beverages, and the associated decline in milk consumption, may decrease bone density, particularly in children and young women. A recent study from the Harvard School of Public Health [12] reported that active teenage girls who drink cola beverages had a fracture risk 4.94 times higher than girls who denied drinking cola beverages, even if those other girls drank non-cola carbonated beverages (p = 0.002). This finding appeared to confirm and extend previous findings indicating that consumption of cola beverages predicted high fracture risk in teenage girls [13,14]. A similar finding, also specifically implicating cola beverages, was reported in Greek children [15]. On the other hand, a California study found that perimenopausal women who drank cola beverages were not at increased risk of low bone density, although it should be noted that only 3% of the women in this study admitted to drinking any cola beverages [16]. And, a more recent study of postmenopausal women found that women who drank one or more bottles per day of cola beverages had significantly higher serum PTH, and significantly lower serum calcium levels, than did women who drank no cola beverages [17].

A 1995 report described five children who consumed large amounts of soft drinks and developed hypocalcemic tetany [18]. In each of these five cases, all clinical and biochemical abnormalities disappeared after the children were no longer allowed access to soft drinks. The same group which reported this finding subsequently published a case-control study of 228 children [19], in which they found that children who drank at least 1.5 L/wk of soft drinks containing phosphates were significantly more likely to develop hypocalcemia (odds ratio 5.27, p < 0.001).

What Does the IOM Report Conclude about the Safety of Phosphate-Containing Food Additives?

The IOM monograph touches on the safety of phosphate-containing food additives only in two short passages. Because of the use to which these two passages have been put by the beverage industry, it is appropriate to quote them in full. We will begin with the passage which maintains that the dietary ratio of calcium to phosphorus has no clinical significance, and then proceed to the paragraph which concludes that even diets high in phosphorus are unlikely to have any adverse effect on bone health.

Is the Ratio of Calcium to Phosphorus in the Diet Clinically Significant in Humans?

The following paragraph begins on page 152 of the IOM report:

In the past, considerable emphasis was placed on the Ca:P ratio of the diet (for example, Chinn, 1981) [20], particularly in infant nutrition (for example, Fomon and Nelson, 1993) [21]. The concept has some utility under conditions of rapid growth (in which a large share of the ingested nutrients is converted into tissue mass), but it has no demonstrable relevance in adults. An optimal ratio ensures that, if intake of one nutrient is adequate for growth, the intake of the associated nutrient will also be adequate without a wasteful surplus of one or the other. However, the ratio by itself is of severely limited value.... If growth were the only consideration, the intake ratio would have to be substantially higher than 2:1 after infancy, because calcium absorption drops more sharply with age than does phosphorus absorption (Abrams et al., 1997b [22]; Fomon and Nelson, 1993 [21]). However, as larger fractions of ingested food are used for energy (and a correspondingly smaller proportion for growth), the notion of a dietary Ca:P molar ratio has little meaning or value, particularly since, on a mixed diet, there is likely to be a relative surplus of phosphorus. Under such circumstances it would be inappropriate to conclude, simply on the basis of a departure from some theoretical Ca:P ratio, either that calcium intake should be elevated or phosphorus intake reduced. In balance studies in human adults, Ca:P molar ratios ranging from 0.08:1 to 2.40:1 (a 30-fold range) had no effect on either calcium balance or calcium absorption (Heaney and Recker, 1982 [23]; Spencer et al., 1965, 1978a [24,25]). Thus, for the reasons cited, there is little or no evidence for relating the two nutrients, one to the other, during most of human life.

This passage repeatedly asserts that the dietary calcium-to-phosphorus ratio has little importance. However, there is no mention here of the numerous studies [e.g. 2,3,7,8,10,11,12,13,14,15,17] which suggest that the dietary calcium-to-phosphorus ratio is indeed important in calcium balance and bone turnover in humans. Instead, this paragraph cites three studies [23,24,25] which purportedly demonstrate that the dietary calcium-to-phosphorus ratio is not important in humans. Each of these three studies has shortcomings which severely constrain their relevance to the question of whether phosphate-containing food additives adversely affect bone density in humans.

Spencer, Menczel, Lewin and Samachson [24] studied seven inpatients at the Veterans Administration Hospital in Hines, Illinois. Four of the seven patients were women. One of the four women was 70 years old and had been diagnosed with osteoporosis and multiple myeloma; two others, ages 67 and 77, also had osteoporosis; the fourth, also age 70, had hypothyroidism. The mean age of these four women was thus 71 years. The study authors make no mention of whether any patients were taking prescription medication, antacids or other drugs. The IOM monograph makes no mention of the small size of this study or the advanced age and illnesses of the participants.

Spencer, Kramer, Osis and Norris [25] studied 19 male inpatients, again at the Veterans Administration Hospital in Hines, Illinois, who had an average age of 54 years (range, 38 to 65 years). No women were included. The only medical information provided about the participants in this study was the statement that they were "fully ambulatory, in good physical condition, and had normal kidney and gastrointestinal function" (p. 448). Given that these subjects were middle-aged veterans, one would like to know whether any of them were alcoholic. The prevalence of alcoholism among American military veterans, estimated at 21%, is more than double the prevalence of alcoholism among non-veterans [26,27]. Alcoholism can give rise to hypophosphatemia by a variety of mechanisms, including hypomagnesemia, metabolic acidosis and respiratory alkalosis (which is especially common in alcoholic smokers) [28]. Alcoholics are more likely to experience stomach upset and therefore more likely to use antacids. Some of the most commonly used antacids, such as aluminum hydroxide (found in Maalox® etc.) are avid binders of dietary phosphorus [29]. No information is provided regarding these men’s use of prescription medication, antacids or other drugs. The authors assert that "the patients had received this diet [with controlled levels of calcium and phosphorus] for several weeks or months prior to the start of the studies," but no information is provided regarding any measures taken to ensure that the patients did not obtain foods or beverages outside the prescribed diet.

Heaney and Recker [23] studied 168 Roman Catholic nuns in or near Omaha, Nebraska. The average age of the nuns was 42 years at entry to the study. While we are told that the nuns were allowed to continue their "usual medications" throughout the study (p. 47), we are not told what those medications were, whether antacids were allowed, etc. Again, no information is provided regarding the use of alcohol or the prevalence of smoking. The authors also provide no details regarding the diet of these nuns or the source of the minerals in question. For instance, we do not know whether the phosphorus in the diet came predominantly from soda beverages, food additives, meat, dairy products, etc. There is also no information regarding the mechanism whereby the authors compiled their information regarding what the nuns were eating: questionnaires, diet diaries, etc. There is likewise no evidence that the authors made any effort to verify that the nuns’ report of their dietary consumption was accurate.

Thus, the IOM monograph makes a broad generalization about the dietary calcium-to-phosphorus ratio based on just three studies. As already noted, the monograph does not mention the limitations of these studies which might constrain the extrapolation of the results to other populations, such as children and young women, which were not included in any of these three studies. The IOM monograph puts no constraints on its conclusion—that the dietary calcium-to-phosphorus ratio is not meaningful in humans—nor does it make any mention of the numerous studies which do not support that conclusion.

Can a High-Phosphorus, Low-Calcium Diet Cause Secondary Hyperparathyroidism?

The following sentence appears on page 182 in the report, opening a new paragraph:

Diets high in phosphorus and low in calcium produce a sustained rise in PTH (Calvo et al., 1988, 1990 [2,3]); but diets low in calcium without extra phosphorus produce the same change (Barger-Lux et al., 1995 [30]) and for that reason it is unlikely that the high phosphorus feature of the altered intake is the culprit in the first instance.

(This sentence contains an important error. The lead author of this chapter informed me [31] that the intended reference was not "Barger-Lux et al. 1995" [30]—which makes no mention of PTH as a function of dietary calcium—but rather Barger-Lux and Heaney 1993 [32], a citation which is not found in the monograph’s list of references.)

This sentence from the IOM monograph misstates the findings of Barger-Lux and Heaney 1993 [32]; but this misstatement can perhaps be partially excused on the grounds that Barger-Lux and Heaney themselves neglected to calculate the calcium-to-phosphorus ratio in the presentation of their findings. Fortunately, their presentation is sufficiently detailed to allow any reader to calculate the ratio from the data provided in the paper. In their study, they restricted women who had low dietary calcium intake at entry to the study to even lower calcium intakes, and they supplemented women with high calcium intake at entry to even higher calcium intakes. After that dietary modification, the mean serum iPTH was 34 ng/L in the low calcium group and 28 ng/L in the high calcium group (p < 0.05). But the dietary calcium-to-phosphorus ratio was not held constant. In the low-calcium group, the dietary calcium-to-phosphorus ratio was 0.47 at entry to the study (13.2/27.9); after the dietary modification, the calcium-to-phosphorus ratio decreased to 0.25 (5.1/20.7). In the high-calcium group, the dietary calcium ratio increased from 0.66 (28.5/43.2) to 1.85 (68.1/36.8). Thus, one can actually point to this study as evidence for the importance of the calcium-to-phosphorus ratio in influencing serum parathyroid hormone: lowering the calcium-to-phosphorus ratio in one group, while almost tripling it in the other, created a small but statistically significant difference in iPTH between the two groups in just two days.

This paragraph from the IOM monograph continues:

In addition, with respect to high phosphorus intakes, chronic administration of 2 g (65 mmol)/day phosphorus in men for at least 8 weeks produced no effect on calcium balance or calcium absorption relative to a diet containing only 806 mg (26 mmol) phosphorus (Spencer et al., 1965, 1978a [24,25]). Calcium intake (low, normal, or high) had no influence on this lack of effect, underscoring the lack of physiological relevance of the dietary Ca:P ratio in adults. Further, calcium kinetic studies performed in adult women in whom phosphorus intake was doubled from 1.1 to 2.3 g (35.5 to 74.2 mmol), showed no effect whatsoever on bone turnover processes after 4 months of treatment (Heaney and Recker, 1987 [33]). A similar conclusion was reached more recently by Bizik et al. (1996) [34] who doubled phosphorus intake (from 800 to 1,600 mg [26 to 52 mmol]/day) for 10 days in seven healthy young men (aged 22 to 31 years) and found no increase in urine deoxypyridinoline excretion. For all these reasons, it is doubtful whether phosphorus intakes, within the range currently thought to be experienced by the U.S. population and/or associated with serum phosphorus values in the normal range, adversely affect bone health.

This passage cites a total of four studies before stating its conclusion: that dietary phosphorus (including phosphate additives) does not adversely effect bone health. The shortcomings of two of these four studies [24,25] have already been discussed. In the third study, by Drs. Heaney and Recker [33], the study population consisted of just eight middle-aged women living in or near Omaha, Nebraska. These investigators measured the effect of giving each woman an additional phosphorus of 1144 mg per day, in the form of sodium phosphate and potassium phosphate, for four months. They found no effect of the additional phosphate on bone structure (trabecular bone volume and osteoid seam width, as measured directly on specimens obtained by trans-ilial biopsy), and no effect on calcium kinetics. However, Heaney and Recker specifically emphasized in their report that "the study was designed purely as a pilot project.... This sample size was recognized to be too small to detect small effects [page 434]...only very gross histomorphometric changes would have been detectable with samples this small" (page 437). One could also add that four months of supplementation might not be sufficient time to see any significant change in bone histomorphometry.

Finally, the IOM monograph cites Bizik, Ding, and Cerklewski [34]. These investigators used milk and cheddar cheese as the source of additional phosphorus in their study. The IOM monograph fails to note that these investigators, unlike the authors of this chapter in the IOM monograph, attached considerable significance to the dietary calcium-to-phosphorus ratio. Bizik, Ding and Cerklewski provided supplemental calcium carbonate to their subjects in the pre-test phase, in order to maintain a constant calcium-to-phosphorus ratio throughout the study—a critical fact which, as we have seen, is not mentioned in the IOM summary of their report. The authors of the IOM monograph, having explicitly chosen to neglect any possible role of the dietary calcium-to-phosphorus ratio, have misinterpreted this study’s findings. Bizik, Ding and Cerklewski reported that doubling dietary phosphorus consumption, while maintaining a constant calcium-to-phosphorus ratio, does not appear to affect bone turnover. This report thus provides evidence that the dietary calcium-to-phosphorus ratio is more important than the absolute amount of phosphorus ingested, with regard to bone turnover. The study does not provide evidence to support the assertion made in the IOM monograph that "it is doubtful that phosphorus intakes...adversely affect bone health," unless care has been taken to maintain a constant calcium-to-phosphorus ratio—a parameter which, according to the IOM monograph, is irrelevant.

Do Phosphate Additives Increase the Risk of Low Bone Density and Fracture?

We have already considered seven studies which suggest specifically that consumption of cola beverages may increase the risk of hypocalcemia, low bone density and/or fracture in humans, especially children and adolescents [12,13,14,15,17,18,19]. The phosphates added to cola beverages might conceivably be responsible for the increased risk of fracture. At the time that the IOM monograph was released in final form in 1999, two of these studies [12,17] had not yet been published. Of the five that had been published, only one [19] is mentioned in the IOM monograph. That study is mentioned and dismissed in a single sentence:

One report associates high intakes of phosphoric acid-containing cola beverages with slight reductions of serum calcium in Mexican children (Mazariegos-Ramos et al., 1995 [19]), but it is not clear to what extent the effect is due to the acid load of the colas, the associated low intake of calcium-rich beverages, or the phosphorus itself.

The phrase "slight reductions" may be misleading in this context. The study in question found that the odds ratio for hypocalcemia in the group with high cola consumption was 5.27 (p < 0.001). Additionally, this study found that children who had high intakes of cola beverages were significantly more likely to suffer from abdominal cramps (p < 0.001) and to experience seizures (p < 0.02) in the three months before the assessment.

Perhaps the most striking oversight of the IOM study is its failure to review the pediatric literature or to consider whether children and adolescents might have different dietary needs than adults do. As we have seen, most of the studies demonstrating a negative effect of dietary phosphorus in humans have been performed in children, adolescents or young adults. The five studies on which the IOM monograph relies in reaching its conclusion—that excessive dietary phosphorus is harmless—were all performed either in populations which were exclusively adult males [25,33] or which had an average age over 42 years [23,24,34].

This neglect of the pediatric literature is particularly troublesome in view of a recent study suggesting that the effects of cola beverages may be qualitatively different in the developing organism compared with the adult. In this study, immature and adult rats were randomly assigned either to receive Coca-Cola or tap water as their exclusive source of liquid [35]. After seven days, the arterial pH of the immature rats drinking Coca-Cola was significantly more acidic than that of the immature rats drinking tap water (7.33 ± 0.02 vs. 7.45 ± 0.04, p < 0.05). The immature rats drinking Coca-Cola also experienced a statistically significant drop in serum free calcium. Neither of these effects were replicated in the adult animals. However, the adult rats drinking Coca-Cola experienced a significant rise in PTH compared with adult controls drinking tap water; this effect was not seen in the immature animals.

The Consequences of the IOM Report

A recent study from the Harvard School of Public Health received considerable publicity in the lay media. As noted above, this study [12] reported that active teenage girls who drink cola beverages had a fracture risk 4.94 times higher than girls who denied drinking such beverages. In the words of the editorial published alongside the study, these "findings are alarming and warrant confirmation with well-designed prospective studies" [36].

Immediately after the study’s release, the National Soda Drink Association (NSDA)—the trade association representing Coca-Cola and Pepsi, among others—issued a press release attempting to rebut the findings of the Harvard study. The NSDA press release stated:

A National Academy of Sciences report on dietary intakes published last year said "It is doubtful whether phosphorus intakes, within the range currently thought to be experienced by the US population...adversely affect bone health."

(Ellipsis in original. The reader will recognize the quotation used in this press release as coming from the closing line of the final paragraph on page 183 of the IOM report, above.)

One NSDA spokesperson, Dr. Richard Adamson, branded the Harvard study as "nutritional nonsense." Dr. Adamson added that "in light of a conflicting body of scientific evidence, the author of the study, at a minimum, should insure [sic] her declarations are based on sound science and are not simply a recitation of discredited myths. In this instance, she failed that test" [37].

Without the IOM study, Dr. Adamson could not have made these harsh statements. The only source cited by Dr. Adamson which contradicts the Harvard findings is the IOM monograph. The scientific bias of that monograph has been the focus of this paper. Dr. Adamson refers to the "myth"—that phosphates may have an adverse effect on bone density—as "discredited," but the only source he cites in support of this contention is, once again, the IOM monograph.

The mainstream media—apparently impressed by the imprimatur of the National Academy of Sciences—have accepted the IOM monograph at face value and therefore continue to accept industry pronouncements, such as those by Dr. Adamson of the NSDA, without question. The Los Angeles Times, in reporting the Harvard study, noted that "in a report issued last year, the National Academy of Sciences concluded that there is no evidence that phosphorus levels in the U.S. diet are sufficient to adversely affect bone health" [38]. The NSDA’s rebuttal to the Harvard study was reported uncritically. "‘The whole business about soft drinks and bone fractures is nutritional nonsense and ill-serves consumers,’ said Richard Adamson"—so ran the story in the Boston Herald [39]. "‘The study is wrong and inconsistent with the findings of major governmental and academic research organizations,’ said [NSDA] spokesman Sean McBride"—for a report in the Chicago Sun-Times [40]. USA Today reported the Harvard findings briefly, then immediately added that "a spokesman for the National Soft Drink Association, Sean McBride, strongly questioned the study results. He said there is no scientific evidence that anything in cola causes fractures" [41].

The Washington Post recently published an extensive review of the risks of soft drinks. In considering the possible effect of soft drinks on bone density, the Post observed that "The National Academy of Sciences has set 3 grams per day as the tolerable upper limit of phosphorus for children ages 1 to 8 years, and 4 grams per day for those 9 years and older. To reach that amount would require drinking at least 100 cans of soda pop per day" [42]. The Post, following the lead of the Institute of Medicine monograph, thus implies that there is little risk in drinking soda beverages in the usual range of consumption.

The Coca-Cola Company, when queried about the risks of phosphates, responds as follows:

...The National Academy of Sciences has reviewed all the scientific literature about calcium [emphasis added]. They have concluded in the recently published "Dietary Reference Intakes for Calcium, Phosphorus, Magnesium, Vitamin D and Fluoride" that "diets high in phosphorus and low in calcium produce a sustained rise in PTH...but diets low in calcium without extra phosphorus produce the same change...and for that reason it is highly unlikely that the high phosphorus feature of the altered intake is the culprit in the first instance."

In addition, the National Academy of Sciences notes that studies showing negative effects of phosphorus have all been done in animals whose intake of phosphorus is much greater than that of humans. The effects shown in animals have not been replicated in humans...[43].

Public Health Implications

The incidence of obesity among American children has nearly doubled in the past three decades [44,45]. Obesity appears to increase bone density [46]. These findings might lead one to expect that today’s children would have a lower fracture risk than did children prior to 1970.

This expectation is not fulfilled. The risk of fractures in childhood and adolescence appears to have nearly doubled between the 1960’s and the 1990’s [47]. One recent study [48] reported that by a child’s 15th birthday almost two thirds (63.7%) of boys and more than one-third (39.1%) of girls now have sustained at least one broken bone. These investigators suggested that today’s children may have "a tendency towards fracturing bones at lower levels of trauma" than did children of past eras, but they did not explore possible mechanisms underlying this new tendency.

The increase in the risk of fractures in this context suggests that some change in children’s nutritional habits may be at least partly responsible for the increased fracture risk. Between 1970 and 1997, per capita consumption of carbonated soft drinks increased 118% while consumption of milk declined 23% [36]. The average teenager now drinks 65 gallons of carbonated beverages per year; this figure does not include juice or sports drinks [49]. Today, almost one-fourth of adolescents consume more than 26 ounces of carbonated beverages every day [50]. Roughly 70% of soda beverages consumed by college students contain phosphoric acid [51]; during exam period, consumption of cola beverages increases [52]. The rapid increase in the consumption of phosphates in the diet of American children, and the general decrease in the calcium-to-phosphorus ratio in the American diet, may be playing a role in the changing epidemiology of fractures in childhood and adolescence [53]. The IOM monograph, by denying any role for phosphate-containing food additives in the risk of fractures, prematurely discourages and undermines investigation into this possibility.

Conclusion

We began this paper by considering two questions:

  1. 1) Can a high-phosphorus, low-calcium diet cause hypocalcemia and/or secondary hyperparathyroidism in humans?
  2. 2) Does the growing use of phosphate-containing food additives increase the risk of low bone density and/or fracture in humans? We have considered studies which suggest that the correct answer to both these questions may be "yes." However, as we have seen, the IOM monograph answers both these questions with an unequivocal "no." The IOM monograph also does not address possible sex differences in the human response to diets with a low calcium-to-phosphorus ratio. On the contrary, the authors of the chapter freely extrapolate from studies done only in adult men when they make recommendations for the entire human population, including women and children. Although the chapter closes with a recommendation that "bone mineral mass as a function of dietary phosphorus intake should be investigated at all stages of the life cycle," the chapter otherwise neglects the pediatric literature. We might therefore add two additional questions as targets for future research:
  3. 3) Do diets with a low calcium-to-phosphorus ratio affect bone density in children and adolescents differently than in adults?
  4. 4) Do diets with a low calcium-to-phosphorus ratio affect bone density in human females differently than in males?

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