ABSTRACT
Title
Lack of standardization in a cod liver oil dietary supplement: three cases of hypervitaminosis D
Authors
A. Vannacci 1, E. Gallo 1, E. Giocaliere 1, A. Pugi 1, F. Menniti-Ippolito 2, D. Bettoni 3, F. Capurro 4, G. Pieraccini 1, G. Moneti 1, A. Mugelli 1, F. Firenzuoli 5
1 University of Florence, Department of Pharmacology, CIMMBA, Centre for Integrative Medicine, Florence 2 National Institute of Health, Rome 3 Spedali Civili, Brescia 4 Azienda Ospedaliera Universitaria Maggiore della Carità, Novara 5 Tuscan County, Reference Centre for Herbal Medicine, Florence
1 University of Florence, Department of Pharmacology, CIMMBA, Centre for Integrative Medicine, Florence 2 National Institute of Health, Rome 3 Spedali Civili, Brescia 4 Azienda Ospedaliera Universitaria Maggiore della Carità, Novara 5 Tuscan County, Reference Centre for Herbal Medicine, Florence
Abstract
Vitamin D is recognized for its importance in promoting bone and reducing the risk of chronic diseases such as autoimmune diseases, cancer and cardiovascular disease. It is generally well tolerated at the current recommended daily oral intake (200-800 International Units -IU- per day for adults) and to date cases of vitamin K over dosage are extremely rare. In the last year, three cases of hypercalcemia with acute renal failure caused by a cod liver oil based product, added with vitamin D and vitamin A, were reported to the Italian Surveillance System of Natural Health Products (National Institute of Health). Here we report the cases of three patients assuming a codfish-oil based multivitamin dietary supplement containing cholecalciferol as self-medication for a long period.
Case 1: A 34-year-old woman with celiac disease, osteoporosis and atopic dermatitis took 6 capsules for 11 months. She experienced severe hypervitaminosis, suppression of PTH, hypercalcemia, nephrocalcinosis and acute renal failure.
Case 2: A 40-year-old male assumed 7-9 capsules daily for 5 months. He was admitted to the hospital for hypervitaminosis, hypercalcemia and renal failure.
Case 3: A 57-year-old male assumed 3 capsules daily for 11 months as a supplement in a low calorie diet. He experienced a severe hypervitaminosis D, hypercalcemia and acute renal failure.
It was suspected that each capsule may contain higher dosage of Vitamin D3 than declared in the label (1.5 μg per capsule; 7.5 μg per 5 capsules). So it was conducted a HPLC-MS analysis which revealed that the real content of Vitamin D3 per 5 capsules was 6,6 mg: 880 times higher than stated.
In conclusion, the intake of Vitamine D of three orders of magnitudo higher than Recommended Daily Allowance (RDA) for several months, has proven to cause severe hypervitaminosis D, suppression of PTH, hypercalcemia, nephrocalcinosis and acute and subacute renal failure. Standardization is an important issue influencing the pharmaceutical quality of dietary supplements. The absence of standardization could lead to an increased concentration of bioactive molecules that means to increase the risk of toxicity.
Case 1: A 34-year-old woman with celiac disease, osteoporosis and atopic dermatitis took 6 capsules for 11 months. She experienced severe hypervitaminosis, suppression of PTH, hypercalcemia, nephrocalcinosis and acute renal failure.
Case 2: A 40-year-old male assumed 7-9 capsules daily for 5 months. He was admitted to the hospital for hypervitaminosis, hypercalcemia and renal failure.
Case 3: A 57-year-old male assumed 3 capsules daily for 11 months as a supplement in a low calorie diet. He experienced a severe hypervitaminosis D, hypercalcemia and acute renal failure.
It was suspected that each capsule may contain higher dosage of Vitamin D3 than declared in the label (1.5 μg per capsule; 7.5 μg per 5 capsules). So it was conducted a HPLC-MS analysis which revealed that the real content of Vitamin D3 per 5 capsules was 6,6 mg: 880 times higher than stated.
In conclusion, the intake of Vitamine D of three orders of magnitudo higher than Recommended Daily Allowance (RDA) for several months, has proven to cause severe hypervitaminosis D, suppression of PTH, hypercalcemia, nephrocalcinosis and acute and subacute renal failure. Standardization is an important issue influencing the pharmaceutical quality of dietary supplements. The absence of standardization could lead to an increased concentration of bioactive molecules that means to increase the risk of toxicity.