Vitamin D toxicity rare in people who take supplements
Over the last decade, numerous studies have shown that many Americans have low vitamin D levels and as a result, vitamin D supplement use has climbed in recent years. Vitamin D has been shown to boost bone health and it may play a role in preventing diabetes, cancer, cardiovascular disease and other illnesses. In light of the increased use of vitamin D supplements, Mayo Clinic researchers set out to learn more about the health of those with high vitamin D levels. They found that toxic levels are actually rare.
A vitamin D level greater than 50 nanograms per milliliter is considered high. Vitamin D levels are determined by a blood test called a serum 25-hydroxyvitamin D blood test. A normal level is 20-50 ng/mL, and deficiency is considered anything less than 20 ng/mL, according the Institute of Medicine (IOM).
The researchers analyzed data collected between 2002 and 2011 from patients in the Rochester Epidemiology Project, a National Institutes of Health-funded medical records pool that makes Olmsted County, Minn., the home of Mayo Clinic, one of the few places worldwide where scientists can study virtually an entire geographic population to identify health trends.
Of 20,308 measurements, 8 percent of the people who had their vitamin D measured had levels greater than 50 ng/mL, and less than 1 percent had levels over 100 ng/mL.
"We found that even in those with high levels of vitamin D over 50 ng/mL, there was not an increased risk of hypercalcemia, or elevated serum calcium, with increasing levels of vitamin D," says study co-author Thomas D. Thacher, M.D., a family medicine expert at Mayo Clinic.
Hypercalcemia, or high blood calcium, can occur when there are very high levels of vitamin D in the blood. Too much calcium in the blood can cause weakness, lead to kidney stones, and interfere with the heart and brain, and even be life threatening.
The Mayo researchers also found that women over age 65 were at the highest risk of having vitamin D levels above 50 ng/mL. The result was not surprising because that's a group that often takes vitamin D supplements, Dr. Thacher says.
Another notable outcome: The occurrence of high vitamin D levels over 50 ng/mL increased during the 10-year period of the study, from nine per 100,000 people at the start of the study up to 233 per 100,000 by the end.
"We were surprised by that degree of dramatic increase in vitamin D levels," Dr. Thacher says.
Only one case over the 10-year study period was identified as true acute vitamin D toxicity; the person's vitamin D level was 364 ng/mL. The individual had been taking 50,000 international units (IU) of vitamin D supplements every day for more than three months, as well as calcium supplements. The IOM-recommended upper limit of vitamin D supplementation for people with low or deficient levels is 4,000 IU a day.
It's important for doctors to ask their patients about the doses of vitamin D supplements that they are using, Dr. Thacher says, because even capsules containing as much as 50,000 IU of vitamin D are available without prescription. If taken on a daily basis, that amount could lead to toxicity.
Some natural sources of vitamin D include oily fish such as mackerel and salmon, fortified milk, and sunlight.
"Our bodies will naturally produce vitamin D when our skin is exposed to sunlight, however, we don't recommend excessive exposure to sun due to the risk of skin cancer," Dr. Thacher added.
In an accompanying editorial in Mayo Clinic Proceedings, Dr. Michael F. Hollick, Ph.D., M.D., describes vitamin D's dramatic medical history, the need for judicious dosing, but the importance of vitamin D supplementation in those with low or deficient levels.
"The evidence is clear that vitamin D toxicity is one of the rarest medical conditions and is typically due to intentional or inadvertent intake of extremely high doses," writes Hollick, a professor of medicine, physiology and biophysics at Boston University School of Medicine.
Low vitamin D levels associated with several risk factors in teenagers
• Low levels of vitamin D were associated with increased risk of high blood pressure, high blood sugar and metabolic syndrome in teenagers.
• The highest levels of vitamin D were found in whites, the lowest levels in blacks and intermediate levels in Mexican-Americans.
Low levels of vitamin D were associated with an increased risk of high blood pressure, high blood sugar and metabolic syndrome in teenagers, researchers reported at the American Heart Association’s 49th Annual Conference on Cardiovascular Disease Epidemiology and Prevention.
In the study, researchers analyzed 3,577 adolescents, 12 to 19 years old (51 percent boys), who participated in the nationally representative National Health and Nutrition Examination Survey (NHANES) conducted from 2001–2004.
After adjusting for age, sex, race/ethnicity, body mass index, socioeconomic status and physical activity, researchers found the adolescents with the lowest levels of vitamin D were:
• 2.36 times more likely to have high blood pressure;
• 2.54 times more likely to have high blood sugar; and
• 3.99 times more likely to have metabolic syndrome.
Metabolic syndrome is a cluster of cardiovascular disease and diabetes risk factors including elevated waist circumference, high blood pressure, elevated triglycerides, low levels of high-density lipoprotein (HDL or “good”) cholesterol and high fasting glucose levels. The presence of three or more of the factors increases a person’s risk of developing diabetes and cardiovascular disease.
“We showed strong associations between low levels of vitamin D and higher risk of high blood pressure, hyperglycemia and metabolic syndrome among adolescents, confirming the results of studies among adults,” said Jared P. Reis, Ph.D., the study’s lead author and post-doctoral research fellow at Johns Hopkins Bloomberg School of Public Health in Baltimore.
Researchers used a biomarker of vitamin D to measure levels in blood. The biomarker measures vitamin D obtained from food, vitamin supplementation and exposure to sunlight.
The ethnic breakdown was similar to the general U.S. population: 64.7 percent non-Hispanic whites; 13.5 percent non-Hispanic blacks; and 11 percent Mexican Americans.
The study highlights the association between high levels of vitamin D and lower risk of heart disease. The highest levels of vitamin D were found in whites, the lowest levels in blacks and intermediate levels in Mexican Americans. Whites had almost twice as high levels as blacks.
In whites, the average level of vitamin D was 28.0 nanograms per milliliter (ng/mL); in blacks, 15.5 ng/mL; and in Mexican Americans, 21.5 ng/mL.
“Although our study is important, we believe clinical trials designed to determine the effects of vitamin D supplementation on the risk of heart disease risk factors in adolescents should be conducted before recommendations can be made for vitamin D in the prevention of cardiovascular disease,” Reis said.
The Institute of Medicine recommends a daily intake of vitamin D of 200 International Units (IU) for those less than 50 years, which includes children and adolescents. More recent recommendations, however, from the American Academy of Pediatrics suggests a daily intake of 400 IU daily. While these intakes have been shown to be important in the prevention of skeletal conditions such as rickets in children and osteoporosis in adults, some specialists have suggested intakes of at least 1,000 IU daily may be needed for overall health.
Low levels of vitamin D are strongly associated with overweight and abdominal obesity. Since vitamin D is a fat-soluble vitamin, it may be sequestered within adipose tissue. This may explain why those who are obese are more likely to be vitamin D deficient, Reis said.
Vitamin D plays a useful role in general human health, particularly in bone health. Other roles are emerging, Reis said. “This is an exciting time; since we are just now beginning to understand the role that vitamin D may play in cardiovascular health.”
“These data on serum vitamin D levels in young people raise some concern about their food choices and even the amount of time they spend in the sunshine,” said Robert H. Eckel, M.D., American Heart Association past president. “The American Heart Association recommends an overall healthy diet and lifestyle, and that people get their nutrients primarily from food sources rather than supplements.”
Vitamin D deficiency associated with cardiovascular disease, diabetes, cancer, infections and neurodegenerative disease
From the European Menopause and Andropause Society January 2012:
Osteoporosis is a common condition in postmenopausal women leading to bone fractures. However, there is now evidence that vitamin D deficiency is also associated with other medical conditions important in older women. These include cardiovascular disease, diabetes, cancer, infections and neurodegenerative disease.
The major natural source of vitamin D is cutaneous synthesis through exposure to sunlight with a small amounts also coming from the diet in animal-based foods such as fatty fish, eggs and milk. Levels of vitamin D are lower in those with poor sun exposure and in the winter. Obesity, malabsorption syndromes and certain medications (e.g. anticonvulsants, antiretrovirals) can also lower vitamin D levels. Regular sunlight exposure (without sunscreens) for 15 minutes, 3-4 times a week, in the middle of the day in summer can generate healthy levels.
Supplements of vitamin D are recommended for those women who cannot obtain the required quantity through sun exposure and diet. The recommended daily allowance is 600 IU/day increasing to 800IU/day for those aged 71 years and older.
Not enough vitamin D in the diet could mean too much visceral fat, which has been associated with health risks such as heart disease, stroke, diabetes and hypertension.
Too little vitamin D could be bad for more than your bones; it may also lead to fatter adolescents, researchers say.
A Medical College of Georgia study of more than 650 teens age 14-19 has found that those who reported higher vitamin D intakes had lower overall body fat and lower amounts of the fat in the abdomen, a type of fat known as visceral fat, which has been associated with health risks such as heart disease, stroke, diabetes and hypertension.
The group with the lowest vitamin D intake, black females, had higher percentages of both body fat and visceral fat, while black males had the lowest percentages of body and visceral fat, even though their vitamin D intake was below the recommended levels. Only one group – white males – was getting the recommended minimum intake of vitamin D.
“This study was a cross-section so, while it cannot prove that higher intake of vitamin D caused the lower body fat, we know there is a relationship that needs to be explored further," says Dr. Yanbin Dong, a molecular geneticist and cardiologist at the MCG Gerogia Prevention Institute.
Dr. Dong, who also co-directs the MCG Diabetes & Obesity Discovery Institute, and Inger Stallman-Jorgensen, a research dietician at the GPI, present their findings this week at the American Heart Association’s Joint 49th Conference on Cardiovascular Disease Epidemiology and Prevention and Nutrition, Physical Activity and Metabolism in Palm Harbor, Fla.
The pair will next study whether it is feasible for teens to take a daily vitamin D supplement in pill form. Those results will help them design a larger study to explore the relationship between vitamin D intake and body fat levels in teens.
“We already know that encouraging teens to get an adequate amount of vitamin D in their diets will help promote a healthy body as they grow and develop,” Ms. Stallman-Jorgensen says. “Now we need to do intervention studies where we give teens vitamin D supplements to determine if there is a cause and effect relationship between vitamin D intake and fat.”
The American Academy of Pediatrics recommends adolescents get at least 400 units of vitamin D per day – either from milk or sun exposure. There are typically 100 units in one 8-ounce glass of whole milk. The recommended daily dose from the sun would require at least 30 minutes of adequate exposure to direct sunlight two or three times a week at peak hours, between noon and 3 p.m.
Ms. Stallman-Jorgensen said there are many reasons teens don't get enough vitamin D, which has been linked to the prevention of diabetes, cancer and cardiovascular disease.
“As humans, our largest source of vitamin D should be the sun. But we don’t spend enough time outdoors to get enough sun exposure and when we do, we’re often covered up and wearing sunscreen," she said. "We can get vitamin D from certain foods, like fatty fish and liver, but it’s not in a lot of foods that we commonly consume. In this country, our milk is fortified with vitamin D. Unfortunately, teens just don’t drink enough milk to get their daily requirements.”
She points out that low sunlight during the winter months reduces the amount of vitamin D the skin produces, and that darker-skinned people obtain less vitamin D from the sun because the extra melanin in their skin filters out more sunlight.
Some people can't tolerate milk because they lack the enzyme that processes lactose, the natural sugar in milk, though "most people can handle it in small amounts,” Ms. Stallman says.
Cultural issues may also be at play, Ms. Stallman-Jorgensen says.
“Most teens want to drink sodas and sugary drinks. It’s not cool to drink milk – they think of it as more of a food for babies,” she said.
Potential study participants had their weekday and weekend diets tracked by researchers seven times during a three-month period. Those who provided at least four diet reports were included in the final group of 659.
Body fat percentages were measured by dual energy X-ray absorptiometry scans, which can measure total body composition. Visceral fat was measured in a subset of 432 teens.
The role of vitamin D in critical illness of children
Vitamin D is increasingly being recognized as important for good health. Vitamin D is a hormone made in the skin following sun exposure or acquired from diet and supplement intake. Previous medical research has shown that low body levels of vitamin D make people more susceptible to problems such as bone fractures, poor mental health and infections like the common cold. Until recently, there had been little consideration given to the role of vitamin D in more severe diseases, which is why Dr. Dayre McNally's recent publication in the esteemed scientific journal Pediatrics is so compelling.
"This is the first study to report on vitamin D levels in a large group of critically ill children," said Dr. McNally, a clinical researcher and intensivist at the Children's Hospital of Eastern Ontario (CHEO) and assistant professor in the Department of Pediatrics at the University of Ottawa.
The study, led by Dr. McNally at the CHEO Research Institute, included over 300 children and teenagers at six hospitals in Ottawa, Toronto, Hamilton, Edmonton, Saskatoon and Vancouver. These children were admitted to an Intensive Care Unit (ICU) with severe infections, significant trauma or conditions requiring major surgery, such as congenital heart defects.
Their study found that in three of every four critically ill children, blood vitamin D levels were below the target considered safe by many experts and medical societies. Further, those with lower vitamin D levels were noted to be sicker, requiring more life-sustaining therapies (breathing tubes, medications to support heart function) and staying in the ICU for longer periods of time.
"Although these findings are of concern, we are very encouraged because we've discovered something that is modifiable," explained Dr. McNally. "There are simple ways to prevent this problem, and it may be possible to rapidly restore vitamin D levels at the time of severe illness."