VITAMIN D TOXICITY
Scientific ignorance of past findings often has dire consequences for the present.
In 1934, the Journal of the American Medical Association published a study on vitamin D overdose.24
The authors reported on 300 patients given high doses of vitamin D2 (ergocalciferol) for asthma and hay fever. The authors reported that each unit dose of vitamin D contained 900,000 IU. One patient received 3 cc per day for five days (total dose: 13.5 million IU) without clinical damage.
In their study summary, the researchers concluded:
- “There need be little apprehension about the administration of amounts ranging up to 150,000 international units daily for indefinite periods. Larger amounts had better be limited to periods of a few months at most, depending on the therapeutic effects desired.”
Also in 1934, researchers at the University of Illinois studied the effects of vitamin D on asthma and hay fever in 212 patients. The authors reported that 82% of the hay fever patients and 96% of the asthma patients experienced definitive significant relief. The authors concluded that the “optimum dose” of vitamin D was 60,000 to 300,000 IU per day.25
In 1935, researchers at the University of Illinois School of Medicine published their findings on 700 patients treated with “massive” doses of vitamin D for up to two years.26
The authors reported that vitamin D had remarkable treatment effects on both osteoarthritis as well as rheumatoid arthritis. Their report indicated that 67 arthritic patients treated with 200,000 IU of vitamin D (either D3 or D2) daily generated a remarkable 75% response rate.
The authors reported:
- “If there was no improvement and no evidence of sensitivity, the daily dose was increased by 50,000 units each week until there was some improvement or evidence of overdosage. In some stubborn cases, it was found necessary to increase to 600,000 or even 1,000,000 units for a few days and then reduce to 200,000 to 500,000 units. Most of our results have been obtained with daily doses of 300,000 to 500,000 units.”
The authors report that 63 of the 700 patients on this dosage became clinically toxic. Therefore, approximately 10% of the patients over a 2-year period taking massive doses of vitamin D daily (200,000 IU) became toxic.
In 1946, two case reports of fatal vitamin D toxicity in adults (the authors report five previous fatal cases in children) appeared in the medical literature.27,28 Another case report of a fatal dose of vitamin D in adults appeared in 1947. This death was associated with vitamin D2 at a dose of 150,000 IU daily for 18 months, with characteristic foot lesions associated with vitamin D toxicity.29
By 1948, a clinical case series documented symptomatic effects of vitamin D intoxication to include weight loss and fatigue, which occurred before anorexia (poor appetite) and vomiting.30 All of these patients suffered from kidney damage and anemia. Virtually all of the patients had a characteristic eye lesion associated with vitamin D toxicity (calcium deposition in the sclera and cornea, just beneath the conjunctival basement membrane). All patients had high blood calcium, ranging from 12.4 to 15.1 mg per 100 cc. Dosages of vitamin D ranged from the lowest at 150,000 IU/day for 4 months (serum calcium 13.9) to the highest at 500,000 IU/day for 18 months (serum calcium 14.3). The researchers reported on another patient who developed hypercalcemia after taking 300,000 IU of vitamin D2 for only 2 weeks; she also had eye lesions evident on ophthalmologic exam. No patients died but some suffered permanent renal damage from the massive doses of vitamin D. The treatment the authors used for vitamin D toxicity was discontinuation of vitamin D, 4,000 cc of fluid hydration daily, and a low-calcium diet. Improvement occurred within 2–8 weeks when symptoms resolved. Blood calcium decreased in all patients by one month but continued to be elevated for as long as a year in one patient.
Recent studies indicate that supplementation with doses of vitamin D far exceeding the IOM’s newly established DRI have not produced signs of toxicity.
In a study conducted in 40 breast cancer patients, 10,000 IU of vitamin D3 daily for four months was shown to be effective in reducing elevated parathyroid hormone levels and demonstrated no toxicity. The authors of this study concluded:
- “Daily doses of 10,000 IU vitamin D(3) for 4 months appear safe in patients without comorbid conditions causing hypersensitivity to vitamin D. Treatment reduced inappropriately elevated parathyroid hormone levels…”31
Another study monitored 59 patients who received 50,000 IU of vitamin D3 daily for 10 days. The investigators noted that thehigh-dose vitamin D effectively boosted patients’ 25-hydroxy vitamin D blood levels without elevated calcium levels or renal (kidney) toxicity:
- “No patient developed hypercalcaemia (corrected calcium > 2.6 mmol/L), vitamin D toxicity (25(OH)D > 200 nmol/L) or nephrolithiasis during the study.”32
In a separate study, researchers administered 4,000 IU vitamin D daily for three months to mothers one month postpartum. The authors of this study concluded:
- “High-dose vitamin D was effective in increasing 25(OH)D levels in fully breastfeeding mothers to optimal levels without evidence of toxicity. No mother or infant experienced vitamin D-related adverse events, and all laboratory parameters remained in the normal range.”33
A randomized, controlled trial assessed the effect of daily 1,800 IU of vitamin D in 73 elderly individuals over an 11-week period. The authors noted the safety of vitamin D in their conclusion: “The safety indicators, serum Ca, creatinine, and calcidiol, did not indicate any group or individual side effect.”34
Professor Reinhold Vieth of the University of Toronto is a world-renowned expert in vitamin D. His objective 1999 review paper on vitamin D toxicity revealed a fact either ignored or unknown to the authors of the current Institute of Medicine report:
- “Throughout my preparation of this review, I was amazed at the lack of evidence supporting statements about the toxicity of moderate doses of vitamin D.” He added: “If there is published evidence of toxicity in adults from an intake of 250 ug (10,000 IU) per day, and that is verified by the 25-hydroxy vitamin D concentration, I have yet to find it.”35
Professor Vieth reported that human toxicity probably begins to occur after chronic daily consumption of approximately 40,000 IU/day , more than ten-times the current threshold limit endorsed by the Institute of Medicine’ s current report.
John Cannell, MD, is executive director of the Vitamin D Council (http://www.vitamindcouncil.org/vitaminDToxicity.shtml), a not-for-profit educational organization. Dr. Cannell is an expert on vitamin D and has extensively reviewed past medical research on vitamin D with a keen eye towards dose range and toxicity.36
Dr. Cannell offers a critically important point concerning vitamin D dosing and evolutionary physiology:
- “The single most important fact anyone needs to know about vitamin D is how much nature supplies if we behave naturally, e.g., go into the sun. Humans make at least 10,000 units of vitamin D within 30 minutes of full body exposure to the sun, what is called a minimal erythemal dose.37 Vitamin D production in the skin occurs within minutes and is already maximized before your skin turns pink.
VITAMIN D HEALTH BENEFITS
Vitamin D has far-reaching implications that extend far beyond promoting bone health, which were either overlooked or ignored by the IOM committee.
Peer-reviewed scientific research clearly supports profound health benefits associated with vitamin D:
- Blood pressure: Individuals deficient in vitamin D are much more likely to have elevated blood pressure.38,39 Treatment with vitamin D and calcium significantly lowers systolic blood pressure.26 Vitamin D likely exerts this effect by suppressing the expression of the blood pressure hormone renin.40
- Inflammation: Vitamin D appears to have a potent effect on reducing inflammation through C-reactive protein (CRP).41
- Metabolic effects: Diabetes is more prevalent in individuals with low serum vitamin D levels.42 Vitamin D administration reduces blood sugar, increases sensitivity to insulin, and may decrease the risk of developing full-blown diabetes.43
- Chemoprevention: Vitamin D has demonstrated potent cancer-preventive effects in experimental and animal preparations and in humans.44 A recent study showed that supplementing with vitamin D and calcium reduced the incidence of all types of cancer in postmenopausal women.45
- Osteoporosis prevention: Women are routinely prescribed expensive prescription drugs costing hundreds of dollars per month yet are deficient in vitamin D, a crucial factor in bone health. Replacement to healthy vitamin D levels substantially increases bone density more effectively than calcium supplementation alone. Intestinal absorption of calcium is magnified considerably when sufficient vitamin D is present.46,47
- Prevention of stress fractures: Young men with an average age of 19 were shown to experience more stress fractures when blood levels of 25-hydroxyvitamin D were low.48
- Prevention of multiple sclerosis: Vitamin D deficiency has been linked to an increased likelihood of developing this debilitating neurological disorder in Caucasians; the correlation between poor vitamin D status and multiple sclerosis did not hold true in African American or Hispanic populations.49 Scientists believe that the active form of vitamin D helps avert multiple sclerosis — which is considered an autoimmune disease — by selectively regulating the immune system.
- Immune Enhancement: Noting that influenza epidemics are more common in the winter months, scientists have proposed that low levels of vitamin D may predispose individuals to succumbing to these potentially dangerous respiratory infections.50
Optimal 25-Hydroxy Vitamin D Blood Levels
When blood is tested to assess vitamin D status, the 25-hydroxyvitamin D form of the vitamin in the serum is measured.
Based on published studies, Life Extension’s optimal target range is 50–80 ng/mL of 25-hydroxy vitamin D. This level represents 25-hydroxy vitamin D concentrations seen in healthy young individuals getting plenty of direct sun exposure.51 One group of researchers assessed vitamin D status in healthy young adults aged 18–25 years. They found that in the summer months, vitamin D levels reached an average (mean) of 52.9 ng/mL and, accounting for statistical standard deviation (SD), as high as 86.6 ng/mL. The authors of this study went on to conclude:
- “Vitamin D sufficiency is a reality with a combination of young skin and optimal and effective sunshine exposure.”52
Moreover, experts in the field of vitamin D research including Bruce Hollis, Robert Heaney and Neil Binkley agree that an optimal range of 25-hydroxy vitamin D is 50–80 ng/mL.
John Cannell, MD, the executive director of the Vitamin D Council, a non-profit organization dedicated to the science of vitamin D, indicates:
- “In a recent study, Heaney, et al, expanded on Bruce Hollis’s seminal work by analyzing five studies in which both the parent compound (cholecalciferol) and 25(OH)D levels were measured. They found that the body does not reliably begin storing cholecalciferol in fat and muscle tissue until 25(OH)D levels get above 50 ng/ml. The average person starts to store cholecalciferol at 40 ng/ml, but at 50 ng/ml (125 nmol/L) virtually everyone begins to store it for future use. That is,at levels below 50 ng/ml, the body uses up vitamin D as fast as you can make it, or take it, indicating chronic substrate starvation — not a good thing. 25(OH)D levels should be between 50–80 ng/ml (125–200 nmol/L), year-round.”53
A startling 36% of the general population has 25-hydroxyvitamin D levels below 20 ng/mL, which may represent the world’sleading cause of unnecessary disease and death.54
HOW MUCH VITAMIN D DO YOU REALLY NEED TO TAKE?
Dr. Cannell has identified multiple peer-reviewed references55,56,57,58,59,60,61 42-48 in support of optimal vitamin D doses for adults between 4,600 and 10,000 IU, and further advises that the vast majority of adults (97.5%) need to take 5,000 IU a day of vitamin D to generate blood levels above the critical 50 ng/mL level.62
Fears of vitamin D toxicity have caused health-conscious people to limit their vitamin D3 intake to less than 800 IU a day. This amount is woefully inadequate and will not generate an optimal blood level of 25-hydroxy vitamin D.
It is important to monitor your blood level of 25-hydroxy vitamin D to ensure that you are getting adequate vitamin D to achieve blood levels of 50–80 ng/mL.
Those with a rare disorder called sarcoidosis, severe renal impairment, primary hyperparathyroidism, or any condition resulting in an elevated calcium level in the blood should consult with their physician before taking vitamin D supplements. A low-cost blood chemistry test easily rules out elevated blood calcium.
Conflict of Interest Among IOM Committee Members
IOM committee member Glenville Jones is a co-founder of a for-profit, publicly traded company called Cytochroma, which is in the process of developing a drug, currently identified as “CTAP101,” to treat vitamin D insufficiency.
IOM committee member Clifford Rosen has admitted to receiving financial support from pharmaceutical industry giants Eli Lilly and Novartis, and has served on the speaker’s bureau for Procter & Gamble. Procter & Gamble markets the controversial bisphosphonate osteoporosis drug Actonel®.63
IOM committee member J. Christopher Gallagher has disclosed financial relationships with GlaxoSmithKline, which recently received approval from the FDA for the drug Sorilux®, a patented vitamin D3 analog.
The recent Institute of Medicine’s recommendations for vitamin D intake are completely inadequate and ignore fundamental facts from the peer-reviewed literature on vitamin D safety and health benefits. The vast majority of health-conscious adults who do not routinely sunbathe require about 5,000 IU of vitamin D3 daily in order to achieve the low end of the target range (50–80 ng/mL) of 25-hydroxy vitamin D for optimal health.
To determine your individual requirements for vitamin D as well as your current 25-hydroxy vitamin D blood level, contact Life Extension’s Health Advisors toll-free (1-800-226-2370) and inquire about our inexpensive 25-hydroxy vitamin D blood test.
Copyright 2014. All rights reserved. Reprinted with exclusive permission of Life Extension Magazine.