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epidemiological data
Type of information:
experimental study
Adequacy of study:
supporting study
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Quality case control epidemiological study. Measure of H3PO4 exposure may be inadequate.
Reason / purpose for cross-reference:
reference to same study

Data source

Reference Type:
Consumption of soft drinks with phosphoric acid as a risk factor for the development of hypocalcemia in children: A case-control study
Mazariegos-Ramos E, Guerrero-Romero F, Rodriguez-Moran M, Lazcano-Burciaga G, Paniagua R, Amato D
Bibliographic source:
J. Pediatr, 12

Materials and methods

Study type:
case control study (prospective)
Principles of method if other than guideline:
A comparison of 57 cases (in children with serum calcium concentration < 2.2 mmol/L) and 171 controls (in children with serum calcium level > or = 2.2 mmol/L) was carried out to assess whether the intake of at least 1.5 L/wk of soft drinks containing phosphoric acid is a risk factor for the development of hypocalcemia.
GLP compliance:

Test material

Constituent 1
Chemical structure
Reference substance name:
Orthophosphoric acid
EC Number:
EC Name:
Orthophosphoric acid
Cas Number:
Molecular formula:
phosphoric acid
Details on test material:
- Name of test material (as cited in study report): phosphoric acid in soft drinks


Details on study design:
HYPOTHESIS TESTED (if cohort or case control study): Assess the hypothesis that the intake of at least 1.5 L/week of soft drinks containing phosphoric acid is a risk factor for the development of hypocalcemia in children

- Type: Interview of children and their mothers / other: short history and physical examination including measurement of height and weight. The presence of seizures or cramps was also determined. Blood examination was also performed
- Details: The objective and hypothesis of the study were not told to the participating children or to their parents. In a masked and independent manner one of the researchers interviewed all the children and their mothers ot determine the number of bottles (1 bottle = 375 mL) of soft drink with phosphoric acid that they drank per week and to perform a directed short history and physical examination including measurement of height and weight. The presence of of seizures or cramps was also determined.


SETTING: case/control ratio of 1:3; cases were defined as a serum Ca level less than 2.2 mmol/L (8.8 mg/dl), and controls as serum Ca levels of at least 2.2 mmol/L. The study was planned to include 51 cases and 153 controls, a number 10% higher than that required to meet the criteria: alfa = 0.05; power, 80%; frequency of exposure in the cases, 43%

- Total population: 209 potential subjects of which only 119 fulfilled the matching criteria, the rest of control subjects were sought among children matched for age and sex to cases laking controls.
- Selection criteria: Children recruited from primary-care facilities were eligible only if they had been seen for healthy-child examinations, vaccination, minor trauma, or mild upper respiratory tract infections. Exclusion criteria: children with malnutrition, chronic diseases, or a history of having received drugs or other medical treatment within the past 3 months were exlcuded from the study; children with a serum Ca concentration of at least 3.0 mmol/L (12.0 mg/dL) were excluded
- Total number of subjects participating in study: 57 cases and 171 controls
- Sex/age/race: children of either sex, 18 months to 14 years of age, were recruited from primary care facilities of the Mexican Institute of Social Security and from elementary schools belonging to the government educational system in the urban area of Durango.
- Smoker/nonsmoker: not applicable
- Total number of subjects at end of study: 228
- Matching criteria: for age matching, children aged 3 months more or less than the corresponding case were considered
- Other: It was also possible to follow up 17 children (from oth case and control groups) who drank four or more bottoles of soft drink each week, who agreed to discontinue soft drink consumption and to have repeated measurements of serum Ca, Ps, and albumin 30 days later.

- Type: State registry / Regional registry / National registry / Control or reference group / Other comparison group:
- Details:

- Disease(s):
- ICD No.:
- Year of ICD revision:
- Diagnostic procedure:
- Other health effects:

Exposure assessment:
not specified

Results and discussion

Of the 57 children with serum Ca levels less than 2.2 mmol/L (8.8 mg/dL), 38 (66.7%) drank more than four bottles of soft drink per week, but only 48 (28%) of the 171 children with serum Calcium levels of at least 2.2 mmol/L did so (odds ratio = 5.27; 95% confidence interval, 3.17 to 8.75; p < 0.001). Four (7%) of the 57 sbujects in the case group and 1 (0.6%) of the 171 subjects in the control group had one or more episodes of seizures within the 3 months before the interview (p < 0.02). Cramps were present in 13 children (23%) in the case group and in eight (5%) of the control subjects (p < 0.001). For all 228 children, including case and control subjects in a single group, a significant negative correlation (r = -0.41; p < 0.01) between the serum Ca level and the number of bottles of soft drink consumed each week was found. In the 117 children that were followed up, basal serum Ca levels rose from 2.17 ± 0.25 mmol/L (8.7 ± 1.0 mg/dL) to 2.35 ± 0.15 mmol/L (9.4 ± 0.6 mg/dL; p < 0.003) and serum P levels dropped from 1.84 ± 0.42 mmol/L (5.7 ± 1.3 mg/dL) to 1.52 ± 1.9 mmol/L (4.7 ± 0.6 mg/dL; p< 0.002) 30 days after soft drink intake was discontinued.

Applicant's summary and conclusion

In this study the criteria supporting the hypothesis of a causal relationship between ingestion of soft drinks containing phosphoric acid and hypocalcemia - a strong relationship, a biologic gradient, a temporal reliationship, and a coherent explanation - seem to be present. However, this hypothesis requires further investigation and awaits confirmation from studies with different designs and other populations.