Supplement Overdose Series, Part 3: How Does the Body Respond to Excessive Vitamin D?

In Parts 1 and 2 of the Supplement Overdose Series, I covered supplement basics and the effects of too much iodine in the body. In both blogs, I focus on the important question of, who has the expertise to recommend high-dose supplements? And, when does a supplement dose become a supplement overdose? In this third part of the series, I’ll explore how the body responds to excessive vitamin D.

Excessive vitamin D, or any of the fat-soluble vitamins A, D, E, or K, may be more detrimental than other vitamins in high doses.

Why?

These vitamins are stored in the liver and adipose tissue—they are fat-soluble (1). Water-soluble vitamins, however, are not stored and are excreted by the kidneys. Interestingly, the only exception is vitamin B12. It is also stored in the liver (2).

Vitamin D toxicity is rare. But, as with iodine, it is most commonly caused by excessive doses of supplements or prescription preparations. Reasonable supplementation may be helpful for:

  • people who live at or above 35-degrees latitude
  • the elderly or obese
  • people with dark skin
  • people who spend a lot of time indoors or with their skin covered
  • consumption of a low vitamin D diet
  • malabsorption issues such as Crohn’s or celiac disease
  • primary biliary cirrhosis
  • pancreatic insufficiency
  • SIBO
  • history of GI surgery
  • people who take vitamin D depleting drugs, including anticonvulsants or statins
  • infants who are exclusively breastfed (3).

The Recommended Daily Allowance (RDA) of vitamin D does not differ greatly across lifespan or gender. For instance, the RDA for infants ages zero to 12 months is 10 micrograms per day as cholecalciferol (vitamin D3). For children ages one to eight, and for adults under 70 years of age, the RDA is 15 micrograms per day. This RDA also includes pregnant and lactating women, though the amount is debated. The RDA increases to 20 micrograms per day in adults over 70 years of age.

The Tolerable Upper Intake Level of vitamin D3 increases gradually across the lifespan to 100 micrograms per day for adults. Both the Institute of Medicine and the National Endocrine Society agree that this UL is applicable to pregnant and lactating women (4).

For reference, one microgram of cholecalciferol equals 40 IU of vitamin D (56).

We can take cholecalciferol via supplementation or medication. We make it when our skin is exposed to UVB radiation from the sun. Through a series of chemical reactions occurring in the liver and kidneys, the body produces active vitamin D, 1α,25-dihydroxyvitamin D. Vitamin D plays a role in thousands of biochemical reactions affecting our immune, nervous, and cardiovascular systems, metabolism, and mineral balance via direct or indirect genetic influence (7).

The role of vitamin D in calcium and phosphorous balance is especially important. Close communication between the parathyroid glands, skeletal system, small intestine, kidney, and active vitamin D allows the maintenance of these bone-forming minerals.

A condition of excess calcium, called hypercalcemia, may result if this communication becomes disrupted. In fact, many symptoms of vitamin D toxicity are actually caused by this state of increased calcium! However, it’s important to note that the exact mechanisms of how excessive vitamin D creates toxicity are still unproven (8).

Symptoms of excessive vitamin D include stomach upset, such as changes in appetite, diarrhea, constipation, vomiting, or nausea.

Hypercalcemia can lead to excessive urination, excessive thirst, itchiness, and kidney stones, along with muscle and joint pain (18).

In my clinical practice, I’ve occasionally worked with clients who came to me while taking high doses of vitamin D, resulting in excessively high vitamin D levels. I first became concerned about the effects of excessive vitamin D during pregnancy while working with a client who had the highest vitamin D levels I’d ever seen.

Alice came to me in the summer of 2020, early in her first pregnancy. She was eating a nutrient-dense diet and was highly conscientious about her lifestyle and emotional health.

However, her vitamin D levels were 265 ng/mL. For reference, the lab range for 25(OH)D is 30-100 ng/mL.

Her midwife had recommended 5,000 IU per day of vitamin D in addition to the 2,000 IU/day in her prenatal. Alice was experiencing digestive distress and extreme fatigue and malaise, which she thought was run-of-the-mill morning sickness. I wondered if the high levels of vitamin D could be responsible for at least some of her symptoms.

She agreed to reduce her supplementation to just her prenatal. Two months later her blood levels had dropped to 112 ng/mL—still above the reference range, but certainly closer to the range than her previous test. Thankfully, her pregnancy progressed well. By the time her vitamin D levels stabilized, her GI issues and malaise were reduced. But the timing of vitamin D stabilization and transition into the second trimester coincided. So, we’ll never know how much the high vitamin D levels contributed to her symptoms, and how much came from first-trimester hormonal adjustments.

However, during a routine fetal scan, it was found that the femur length was below the 10th percentile. I still wonder whether the disruption in normal maternal and fetal vitamin D homeostasis may have caused issues with bone growth.

During pregnancy, the fetus is dependent on maternal levels of vitamin D, calcium, and phosphorus. Vitamin D regulates both maternal calcium balance and influences fetal bone development. Interestingly, only the inactive form of vitamin D, 25-hydroxyvitamin D (25(OH)D), can cross the placenta. It is then activated into 1α,25-dihydroxyvitamin D by the placenta or the fetus’ kidneys. Amazingly, both the placenta and fetus have multiple mechanisms to control levels of active vitamin D inside the placenta (4).

While many studies have examined the role of vitamin D deficiency in pregnancy, few have investigated the effects of excessive vitamin D. However, this is an important consideration. It’s reasonable to imagine that excessive vitamin D intake during pregnancy could lead to too much calcium in the blood of the fetus, i.e. fetal hypercalcemia.

A randomized controlled trial of 160 women in their third trimester found that four weeks of high-dose vitamin D (35,000 IU/week, 5,000 IU/day) slightly increased infants’ serum calcium, decreased parathyroid hormone, and influenced calcium balance from birth to day three of life. However, it was not associated with hypercalcemia. In fact, six infants from both the vitamin D and placebo groups experienced increased, but asymptomatic short-term calcium increases. Levels of calcium returned to normal one month after birth (9).

However, a 2017 case report described the chance finding of increased vitamin D levels and hypercalcemia in a newborn baby. Though the baby did not exhibit symptoms of excessive vitamin D, her blood levels of both D and calcium were high. Her medical team ruled out parathyroid dysfunction and found that her mother had taken supplemental vitamin D while pregnant—approximately 4,000 IU per day. The mother’s vitamin D levels were elevated at 127 nmol/L (50.8 ng/mL) (10).

The authors state, “There are limited data to suggest what dose is the safe upper limit for routine vitamin D supplementation in pregnancy.”

Additionally, in the 1950s, when milk and cereals in the United Kingdom were fortified with vitamin D, infant hypercalcemia increased. The incidences decreased by half when vitamin D fortification was reduced (4).

However, these examples are one case study of vitamin D supplementation leading to high blood levels of D and calcium and, though interesting and possibly important, an observed association. A thorough review also published in 2017 describes both randomized, controlled studies and observational studies in which hundreds of pregnant women were supplemented with up to 4,000 IU of vitamin D per day (1112).

No adverse events were attributed to vitamin D supplementation or circulating 25(OH)D levels in these well-designed studies.

The review also speaks to what they call “obstetrical paranoia” in regards to vitamin D supplementation during pregnancy. They attribute this to a “terrible, inaccurate association” between infantile hypercalcemia and hypervitaminosis D in Britain in the 1960s. This association occurred due to a then-unknown connection between abnormal vitamin D metabolism, hypercalcemia, and William’s Syndrome, a rare genetic disorder.

Ultimately, the authors suggest that 40 ng/mL of 25(OH)D is the level needed to achieve optimal active vitamin D status during pregnancy (11).

The take-home point of this discussion? Too little vitamin D and perhaps too much vitamin D may be problematic, especially for pregnant women and babies.

As previously stated, the mechanisms of vitamin D toxicity are still unknown. We have solid evidence that 4,000, or possibly even short-term doses of 5,000 IU/day of vitamin D are safe for pregnant women and babies. However, we still have to answer the critical question of who is qualified to safely make these, or higher, recommendations.

Want to learn more? I recommend these articles:
– “Maternal and newborn vitamin D status and its impact on food allergy development in the German LINA cohort study” (13)

References

  1. https://www.ncbi.nlm.nih.gov/books/NBK534869/
  2. https://www.merckmanuals.com/home/disorders-of-nutrition/vitamins/vitamin-b12-deficiency
  3. https://doctorgaby.com/
  4. https://www.karger.com/Article/FullText/487370#ref12
  5. https://www.ncbi.nlm.nih.gov/books/NBK56068/table/summarytables.t2/?report=objectonly
  6. https://www.ncbi.nlm.nih.gov/books/NBK56068/table/summarytables.t7/?report=objectonly
  7. https://lpi.oregonstate.edu/mic/vitamins/vitamin-D
  8. https://www.ncbi.nlm.nih.gov/books/NBK557876/
  9. https://www.nature.com/articles/pr201483
  10. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5534804/
  11. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3183324/
  12. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5573964/
  13. https://pubmed.ncbi.nlm.nih.gov/23253182/