Vitamin D Intoxication in an Adolescent due to Over-Supplementation: A Case Report and Review of Literature

Abstract

Background/Objective

We describe a 17-year-old male who presented with symptomatic hypercalcemia due to prolonged, excessive ingestion of vitamin D through homemade milkshakes supplemented with vitamin D3.

Case Presentation

The patient presented with abdominal pain, knee pain, and anorexia in the setting of hypercalcemia (15.5 mg/dL [8.4-10.2 mg/dL]). History revealed an intake of homemade milk shake supplemented with vitamin D (vitamin D3 14 045 units/16 ounces): 16 ounces daily for about a year and 32 ounces daily for 10 days prior to his presentation. Further workup revealed: corrected calcium 13.2 mg/dL, phosphorus 2.9 mg/dL (2.5-4.5 mg/dL), 25-hydroxyvitamin D 594 ng/mL (30-100 ng/mL), 1,25 dihydroxyvitamin D 101 pg/mL (19-83 pg/mL), and parathyroid hormone 6.9 pg/mL (7.5-53.5 pg/mL), confirming a diagnosis of hypervitaminosis D. The patient was treated with intravenous fluids and a low calcium diet with improvement in symptoms in 2 days and resolution of hypercalcemia within 1 month and vitamin D level in 6 months.

Discussion

There have been few reports of vitamin D intoxication in adolescents. Our patient knowingly consumed vitamin D, but neither he nor his family knew the exact quantity he was taking or the risks of excess intake, a scenario consistent with other adolescent cases of vitamin D toxicity.

Conclusion

Health care providers should be aware of the dangerous practice of vitamin/supplement abuse by young individuals and should inquire about supplement use and educate them about the detrimental effects associated with inappropriate intake of certain supplements, such as vitamin D.

Highlights

• •Adolescents continue to be at an increased risk of excessive supplement intake
• •Supplements do not undergo the same level of regulatory oversight as medications
• •Hypervitaminosis D can occur in adolescents through over-supplementation
• •Health care providers should inquire about patients’ supplement use

Clinical Relevance

An increasing number of adolescents are taking dietary supplements, which are not subject to regulation. While vitamin D may be considered as harmless, excessive intake can lead to toxicity. This case represents one of the few reported cases of hypervitaminosis D in adolescent patients.

Introduction

Vitamin D plays a crucial role in maintaining healthy bones and mineral ion homeostasis. Vitamin D may lower the risk of infections such as tuberculosis, autoimmune diseases including type 1 diabetes, cancer, and metabolic syndrome.^1,2 Recommendations for vitamin D intake beyond the age of infancy vary ranging from supplementation only when there is suboptimal sun exposure or dietary intake to empiric supplementation with 400 to 600 IU/d.3, 4, 5 These recommendations primarily stem from studies that demonstrated significant increases in the incidence of vitamin D deficiency among children over the last decade, as well as the increased recognition of benefits of vitamin D supplementation in reducing the risk of the aforementioned disease states.^3,4,6,7 At the same time, an increase in cases of hypervitaminosis D has been reported with an increase in vitamin D treatments, majority of which resulted from inappropriate prescribing and use of high-dose over-the-counter (OTC) preparations, or unlicensed preparations.⁸

There have been few reports of hypervitaminosis D among adolescents. We report a 17-year-old male with symptomatic hypercalcemia due to hypervitaminosis D secondary to excessive use of supplements. We performed a literature review and identified 5 adolescents from 3 case reports with hypervitaminosis D.9, 10, 11

Case Presentation

An otherwise healthy 17-year-old male presented to our emergency department (ED) as a transfer from outside hospital where he presented with abdominal pain of 6 days, and bilateral intermittent knee pain, loss of appetite, nausea and emesis of 3 days duration. He was highly active and played basketball daily except for the last 6 days. He was not on any medications or supplements other than the homemade protein shakes, which he reported taking for the last 1 year. Family history was negative for fractures or kidney disease.

Examination revealed a tired-looking adolescent. He was afebrile with a blood pressure of 120/58 mmHg and pulse rate of 44 beats/min. His systemic examination was non-contributory.

Laboratory studies done at the outside hospital showed corrected calcium: 15.1 mg/dL (8.2-10.2 mg/dL), phosphorus: 3.3 mg/dL (2.5-4.5 mg/dL), and parathyroid hormone (PTH): 7.5 pg/mL (7.5-53.5 pg/mL). He received 1 bolus of normal saline (10 mL/kg) and 1 dose of furosemide prior to transfer to the ED. Further workup at the ED confirmed hypercalcemia and suppressed PTH (Table 1).

Table 1.

Workup for Hypercalcemia at Presentation

Laboratory parameter (units)	Day 1	Reference range
Corrected calcium (mg/dL)	13.2	8.4-10.2
Ionized calcium (mg/dL)	7.2	4.5-5.3
Phosphorus (mg/dL)	2.9	2.5-4.5
Blood urea nitrogen (mg/dL)	26	4-21
Creatinine (mg/dL)	2.6	0.70-1.50
Estimated GFR based on expanded Schwartz formula	33	≥90
PTH (pg/mL)	6.9	7.5-53.5
PTHrP (pg/mL)	12	11-20
FGF-23 (pg/mL)	891	<52
Calcitonin (pg/mL)	<2	≤6
24-h urine calcium (mg/24h)	614.2	100-300
25 (OH)D (ng/mL)	594	30-100
1,25 (OH)2D (pg/mL)	101	19-83
FT4 (ng/dL)	1.11	0.70-1.65
TSH (μIU/mL)	3.12	0.5-5.0

Abbreviations: FGF-23 = fibroblast growth factor-23; FT4 = free thyroxine; GFR = glomerular filtration rate; 1,25 (OH)₂ D = 1,25 dihydroxyvitamin D; 25 (OH)D = 25-hydroxyvitamin D; PTH = parathyroid hormone; PTHrP = PTH-related protein; TSH = thyroid stimulating hormone.

Given the laboratory findings, the inpatient team obtained a detailed description of the homemade protein shake, which was prepared by his grandmother by mixing 250 g bag of vitamin D3 powder (625 000 mcg of vitamin D3), 10 g bag of vitamin K2 powder (9990 mcg of menaquinone-7), and 1 kg bag of bulk supplements whey protein isolate (3894 mg of calcium). She added 2 ounces of this mixture (56.7 g that provided 28 090 units of vitamin D3) to a 32 oz milkshake of whole milk, ice cream, banana, and strawberries. The patient had been taking 16 oz of this preparation daily for the last 1 year. About 2 weeks prior to his presentation, both his mother and grandmother received a diagnosis of vitamin D deficiency and started weekly vitamin D dose of 50 000 units as prescribed by their primary care doctor. In turn, his grandmother advised him to increase his protein shakes to twice daily to prevent vitamin D deficiency. He had been taking protein shakes 16 oz in the morning and 16 oz in the evening for the last 10 days prior to presentation. His 25-hydroxyvitamin D [25(OH)D] level was 594 ng/mL (30-100 ng/mL). He had elevated 1,25 (OH)₂ vitamin D and normal PTH-related protein (PTHrP), TSH, and free T4. His electrocardiogram (ECG) showed short, corrected QT intervals (QTc) (294-379 ms) and renal ultrasound demonstrated mildly increased renal cortical echogenicity. He received a diagnosis of iatrogenic hypervitaminosis D.

His treatment consisted of low calcium diet, intravenous fluids at 2 times the maintenance rate (calculated using Holliday and Segar formula¹²) for 6 days and furosemide 20 mg IV every 6 h for 2 days. His symptoms resolved within a day with reduction in calcium concentration to around 12 mg/dL. His heart rate improved and ECG showed borderline short QTc (368 ms). Since he became asymptomatic and had only moderate hypercalcemia (12-14 mg/dL),¹³ we did not consider steroids, calcitonin or bisphosphonates. His discharge instructions on day 9 of hospitalization included low calcium diet and daily fluid intake goal of 4 L (about 2.2 L/m²/d). His calcium level at the time of discharge was 12.6 mg/dL.

He remained asymptomatic on follow-up. His calcium and vitamin D levels normalized by 1 month and 6 months, respectively (Figure). He was evaluated by cardiologist with Holter monitoring that demonstrated sinus rhythm with normal diurnal variation.

Fig.

25 (OH)D and calcium levels during the follow-up

Discussion

We describe an adolescent with symptomatic hypercalcemia due to hypervitaminosis D secondary to excess vitamin D supplementation. Through his protein shakes, he had been receiving approximately 14 000 IU of vitamin D daily for about 1 year, and double that amount for 10 days prior to his presentation.

Hypervitaminosis D leads to hypercalcemia, resulting in neuropsychiatric (confusion, restlessness, psychosis), cardiovascular (short QT interval, hypertension), gastrointestinal (abdominal pain, nausea, vomiting, constipation), and renal (acute kidney injury, dehydration, nephrocalcinosis) manifestations. These symptoms have been frequently reported in patients with serum vitamin D levels ranging from 150 to 1220 ng/mL. As per the American Academy of Pediatrics, hypervitaminosis D is defined by serum vitamin D levels above 100 ng/mL, and levels above 150 ng/mL are strongly associated with vitamin D intoxication.^3,11

Our patient presented with abdominal pain, nausea, emesis, acute renal failure, and ECG changes due to hypercalcemia. A detailed dietary history and laboratory parameters showing elevated 25(OH)D and 1,25(OH)₂D and suppressed PTH confirmed the diagnosis of hypervitaminosis D. His phosphorus level was low, an uncommon finding in cases of vitamin D toxicity. Similar finding has been reported by few other case reports14, 15, 16 Phosphate homeostasis is maintained by complex interactions between gut, kidney, and bone, involving multiple regulators such as vitamin D, PTH and phosphatonin, fibroblast growth factor (FGF)-23. Hypervitaminosis D may disrupt this intricate regulatory mechanism altering phosphate absorption and excretion.¹⁷ Phosphaturia induced by elevated FGF-23 level (Table 1) might have been higher than the hypervitaminosis D induced phosphate absorption resulting in hypophosphatemia in our patient.

Similar to prior case reports, his calcium and vitamin D levels were normalized by 1 and 6 months, respectively, after the discontinuation of supplements.^9,11

There have been few reports of hypervitaminosis D in adolescents. Our literature search identified 5 adolescents with hypervitaminosis D from 3 case reports (Table 2).9, 10, 11 All were males with an average age of 15.6 ± 2.91 years and hypervitaminosis D resulted from increased use of supplements containing high doses of vitamin D. Sources of hypervitaminosis D were creatine supplements used for athletic performance enhancement in 2 patients,⁹ OTC supplements that contained higher vitamin D content than the label reported in 2 patient,¹¹ and a veterinary compound with large quantities of vitamin D that was taken for silicone-like effect giving the impression of increased muscle mass in 1 patient.¹⁰ Symptomatic hypercalcemia led to the diagnosis of hypervitaminosis D in all but one. In 1 case, diagnosis of hypervitaminosis D in the sibling led to early diagnosis in the other sibling.¹¹ In contrast to our patient, all prior symptomatic patients received steroids, calcitonin, bisphosphonates or a combination of these for hypercalcemia in addition to low calcium diet and hydration. None of the patients were aware of the potential danger associated with excessive vitamin D supplementation, which was also the case with our patient.9, 10, 11

Table 2.

Reported Cases of Hypervitaminosis D in Adolescents

Reference, y country	Age, gender	Calcium (mg/dL) level at presentation	Symptoms	Complications	25 (OH)D (ng/mL)	1,25 (OH)2 D (pg/mL)	Estimated daily vitamin D intake (IU)	Estimated cumulative vitamin D intake (IU)	Source of vitamin D	Treatment
2011, Brazil10	19 y, M	13.6	Anorexia, nausea, vomiting	Acute kidney injury	150	26.8	40 000	15,000 000	parenteral veterinary compound containing 5 000 000 IU of vitamin D3/100 mL	Hydration, furosemide, zoledronic acid
2014, Italy11	12 y, M	15.70	Abdominal pain, constipation, vomiting	Acute kidney injury, hypertension, nephrolithiasis	542	—	254 400	7 632 000	Cod liver oil based supplement containing 42 400 IU vitamin D per pill	Hydration, diuretics, prednisone
	15 y, M	9.78	None	None	484	—	212 000	3 180 000		—
2023, Canada9	16 y, M	13.99	Abdominal pain, nausea, vomiting, anorexia, flank pain	Acute kidney injury, hypertension, ECG abnormalities (bradycardia, T wave inversions)	764	47.28	1 275 000	6 375 000	Creatine powder containing 425 000 IU vitamin D per serving	Low calcium diet, hydration, calcitonin, short course of steroids and pamidronate
	16 y, M	14.19	Nausea, vomiting, diarrhea, headaches, blurry vision	Acute kidney injury, hypertension	552	43.27	694 167	20,825 000		Low calcium diet, hydration, calcitonin, pamidronate
Our case	17 y, M	15.10	Abdominal pain, nausea, vomiting	Acute kidney injury, ECG abnormalities (bradycardia, shortened QT)	593	101	14 045 for 1 y and then 28 090 for 10 d	5 126 000	Vitamin D3 powder and whey protein isolates mixed with milk shake providing 14 045 units of vitamin D/16 ounces	Low calcium diet, hydration, furosemide

Abbreviations: ECG = electrocardiogram; 1,25 (OH)₂ D = 1,25 dihydroxyvitamin D; 25 (OH)D = 25-hydroxyvitamin D.

Increased use of dietary supplements has been well-established in youth, particularly in adolescent athletes, with studies documenting up to 98% of adolescent athletes between the ages of 11 to 25 years taking at least 1 dietary supplement, with younger athletes ages 11 to 17 years focusing more on vitamin and mineral supplements. Only about half of these adolescents reported meeting with a dietician to discuss the supplements.¹⁸ The United States considers supplements as food products and hence does not require regulated monitoring, unlike that for medications. Thus, there is significant variability in the quality and quantity of the ingredients, which is exacerbated by the large number of products and manufacturers and a lack of standardized methods to analyze the wide variety of ingredients found in supplements^.9,19

There is lack of knowledge amongst the general population regarding acceptable limits of vitamin D intake. For adolescents, the tolerable upper intake level for vitamin D is 4000 IU daily.²⁰ Primary care physicians may miss an opportunity to identify excessive supplement intake because many patients are unaware of the danger of excessive supplement consumption and often do not report supplements as they would for a medication. Excess intake of vitamin D for prolonged periods of time leads to hypervitaminosis D and secondary hypercalcemia as seen with our patient.

Conclusions

Our case highlights the importance of educating public regarding dangers of non-regulated supplements. Health care providers should be aware of the dangerous practice of vitamin/supplement abuse by young individuals and should inquire adolescents about supplement use and educate them about the detrimental effects associated with inappropriate intake of certain supplements such as vitamin D.

Conflicts of interest

None disclosed.