September 29, 2019
Hello Dr. Ellis-I read your interesting article and noticed the patient had read a book on high dose vitamin d3- I am probably the author. I would like to explain to you what you were probably looking at. The elevated calcium on his test was certainly not the culprit as it was barely elevated compared to the reference range.
What you were witnessing was magnesium deficiency symptoms, as high dose Vitamin d3 will burn up a lot of magnesium, and most of us are magnesium deficient to begin with.
Amongst magnesium deficiency symptoms are included: confusion (long term symptom), constipation, fatigue. The blood tests for magnesium are highly unreliable as only 1% of the body’s magnesium is found in blood and it is tightly controlled. his magnesium should have been tested with the oral load test or a muscle biopsy.
So his not alarmingly low magnesium score actually hid a major magnesium deficiency in his tissues-exacerbated by 2 years of highi dose vitamin d3 use. He could have been quickly treated with a magnesium IV. and he would have been perfectly fine in an hour. And then you should have educated him on the requirement of co-supplementing with magnesium while taking high dose vitamin d3. I add an article at the and of this email that I am writing about the symptoms of and reasons for magnesium deficiency.
I would like you to forward this to your patient or give me his email address and I will have a little chat with him. Any thoughts?
Jeff T. Bowles
Clin Med (Lond). 2018 Aug; 18(4): 311–313.
doi: 10.7861/clinmedicine.18-4-311
PMCID: PMC6334045
PMID: 30072556
Risks of the ‘Sunshine pill’ – a case of hypervitaminosis D
Sebastien Ellis, acute medicine consultant,A Georgios Tsiopanis, CT1 anaesthetics,B and Tanuj Lad, acute medicine and critical care consultantC
Author information Copyright and License information Disclaimer
Address for correspondence: Dr Sebastien Ellis, Southampton General Hospital, Acute Medical Unit, Tremona Road, Southampton SO16 6YD, UK. Email: ku.shn.shu@sille.neitsabes
This article has been cited by other articles in PMC.
Case presentation
A 73-year-old man presented with a 4-week history of diarrhoea and 2-week history of confusion. He was a retired nuclear scientist who was previously fully independent with no history of cognitive impairment. There was no history of smoking, alcohol or substance abuse.
His wife reported cognitive disturbances including being unable to use a cassette player or turn on his electric razor and he had started urinating in the sink. He was visited by his GP who found him confused, drowsy and dehydrated. Observations were unremarkable but a rectal examination showed hard stool in the rectum. Presuming a urinary tract infection, laxatives and trimethoprim were prescribed and he was transferred to hospital for further investigations.
On admission there were no infective signs or symptoms. His cardiovascular, respiratory and abdominal examinations were unremarkable. He was extremely delirious requiring sedation and occasional reasonable physical restraint. He scored 3/10 on the Abbreviated Mental Test Score (AMTS) but had no other neurological signs. His electrocardiogram (ECG), chest X-ray (CXR) and computed tomography (CT) brain were all normal. Admission blood test results are shown in Table Table11.
Table 1.
Patient’s blood test results on admission
| Parameter | Results | Units | Normal values |
| Haemoglobin | 123 | g/L | 130–180 |
| WBC count | 4.4 | 109/L | 4–11 |
| Platelet count | 168 | 109/L | 150–500 |
| RBC count | 4.15 | 1012/L | 4.5–6.5 |
| Haematocrit | 0.375 | L/L | 0.38–0.54 |
| MCV | 90.2 | Fl | 76–103 |
| Neutrophils | 3.43 | 109/L | 1.5–8 |
| Sodium | 141 | mmol/L | 133–146 |
| Potassium | 4.2 | mmol/L | 3.5–5.3 |
| Urea | 9 | mmol/L | 2.5–7.8 |
| Creatinine | 202 | umol/L | 59–104 |
| eGFR | 25 | mL/min/1.73m2 | 60–99 |
| Bilirubin | 5 | umol/L | 0–21 |
| ALT | 12 | U/L | 0–60 |
| ALP | 78 | U/L | 46–116 |
| Albumin | 35 | g/L | 34–50 |
| CRP | <2 | mg/dL | <3 |
| Procalcitonin | 0.12 | ng/mL | <0.25 |
| Calcium | 3.06 | mmol/L | 2.15–2.6 |
| Corrected calcium | 3.15 | mmol/L | 2.2–2.62 |
| Phosphate | 1.04 | mmol/L | 0.8–1.5 |
| Magnesium | 0.94 | mmol/L | 0.7–1 |
| TSH | 1.76 | mu/L | 0.55–4.78 |
| B12 | 560 | ng/L | 211–911 |
| Folate | 14.76 | ug/L | 3.38–23.9 |
| Ferritin | 18 | ug/L | 22–322 |
ALP = alkaline phosphatase; ALT = alanine aminotransferase; CRP = C-reactive protein; MCV = mean corpuscular volume; RBC = red blood cell count; TSH = thyroid stimulating hormone; WBC = white blood cell count
Diagnosis
Investigations for his hypercalcaemia revealed low parathyroid hormone 0.6 pmol/L and a toxic 25-hydroxyvitamin D (25[OH]D) concentration 881 nmol/L (normal range 25–100 nmol/L), suggesting a diagnosis of hypervitaminosis D. Other causes of hypercalcaemia such as malignancy, thyroid disease and sarcoidosis were excluded. On further questioning his daughter reported he had been taking 60,000 IU vitamin D capsules per day for the last 2 years having read a book advocating its health benefits.
Initial management
According to www.toxbase.org guidelines, he was treated with intravenous fluids followed by a single dose of 60 mg pamidronate. Steroids were considered but not used in this case following discussion with endocrinology department colleagues.
Case progression and outcome
After 1 week of supportive treatment the patient showed signs of improvement with calcium concentrations and renal function now normal. His repeat AMTS was 6/10 as cognitively he started to recover. Two weeks after admission he was back to baseline and discharged home. Weekly blood tests were arranged over the next month to ensure no rebound hypercalcaemia and all vitamin D supplements were discontinued.
Discussion
Vitamin D is a fat-soluble vitamin essential for calcium homeostasis and bone health. Vitamin D2 (ergocalciferol) and D3 (cholecalciferol) can be obtained naturally from dietary sources (eg wild mushrooms and oily fish). Vitamin D3 is also formed by UV-B mediated conversion of 7-Dehydrocholesterol in the skin.1 Due to a wide therapeutic index hypervitaminosis D is extremely rare; however, there are a small number of global case studies showing it can occur at excessively high doses of supplementation.2–5 The reported non-musculoskeletal health benefits of vitamin D supplementation,6,7 including links to sepsis severity,8 acute respiratory distress syndrome (ARDS)9 and respiratory tract infections (RTIs)10 have seen its use increase significantly. There are also widespread claims in non-medical publications and the media that vitamin D supplementation is a ‘miracle cure’.11
The right amount of vitamin D
The Scientific Advisory Committee on Nutrition (SACN) and the National Institute for Health and Care Excellence (NICE) state that a 25(OH)D concentration below 30 nmol/L qualifies as vitamin D deficient and there are clear links with poor musculoskeletal health.12,13 Apart from the possible prevention of RTIs,10 robust evidence linking vitamin D deficiency to non-musculoskeletal diseases such as cancer, cardiovascular disease and obesity is still lacking.6,7 Autier et al suggest that low 25(OH)D concentrations may simply be a marker of ill health rather than primarily causing disease.14
Conversely, vitamin D toxicity with hypercalcaemia can cause bone demineralisation and both renal and cardiovascular toxicity.12 The third National Health and Nutrition Examination Survey (NHANES III) also suggested that vitamin D concentrations higher than 75 nmol/L could be associated with adverse effects, including increased mortality and incidence of cardiovascular disease.15
Based on the robust evidence for musculoskeletal outcomes alone, SACN and NICE currently recommend a vitamin D reference nutrient intake (RNI) of 400 IU daily alongside sensible sun exposure for all healthy adults in the UK to prevent vitamin D deficiency. Although there is currently no evidence for an optimal vitamin D status, NICE states that serum 25(OH)D concentrations >50 nmol/L are ‘adequate’. For vitamin D deficient adults the maximum dose for supplementation recommended by SACN should not exceed 4,000 IU/day. There are fixed loading regimes recommended by NICE, for example 50,000 IU once a week for 6 weeks (300,000 IU in total), and although these are not expected to cause adverse effects, may cause hypercalcaemia in some individuals.12,13 50,000 IU vitamin D capsules are easily purchased on the internet and one has to question whether such high doses should be available to the public without prescription.
Pharmacokinetics and clinical course of hypervitaminosis D
To appreciate the clinical course of hypervitaminosis D, it is important to understand the pharmacokinetics. The lipophilic nature of vitamin D explains its adipose tissue distribution. It has a slow turnover in the body with a half-life of approximately 2 months. Its main transport metabolite, 25(OH)D, has a half-life of 15 days while the more active metabolite, Calcitriol or 1,25(OH)2D, has a half-life of 15 hours.16–18 Therefore, depending on the level of toxicity, it can be expected that patients with hypervitaminosis D may exhibit symptoms for several weeks before showing signs of improvement.
Hypervitaminosis D treatment
The majority of symptoms are due to hypercalcaemia; therefore, the mainstay of successful treatment in case reports has included initial rehydration with intravenous fluids followed by bisphosphonate therapy. Some cases were managed using diuretics, calcitonin or glucocorticoids as second line treatment.2,3,19 We consulted Toxbase and local endocrinology expertise to guide treatment. Due to the risk of rebound hypercalcaemia and arrhythmias, we monitored biochemical parameters and ECGs regularly. Given the fact that hypervitaminosis D is so rare it is important to also consider and exclude other causes of hypercalcaemia during treatment.
Key learning points
- Hypervitaminosis D is a rare condition and can be life-threatening
- Given the increasing self-supplementation and medical prescriptions of vitamin D, consider hypervitaminosis D as a differential diagnosis in patients presenting with hypercalcaemia
- Refer to the SACN and NICE guidelines for vitamin D intake and supplementation in adults to prevent and treat vitamin D deficiency
- Important for clinicians to understand the pharmacokinetics of vitamin D to help predict the clinical course of patients with hypervitaminosis D
- The mainstay of hypervitaminosis D treatment involves the correction of hypercalcaemia with rehydration and bisphosphonate therapy.
Magnesium deficiency
I estimate that magnesium deficiency causes up to about 20% of all human disease, from heart and blood pressure disturbances to neurological problems and much more. (See the list of symptoms of magnesium deficiency at the end of this chapter.)
Estimates of how many people are magnesium deficient in industrialized countries range as high as 88%!
Why don’t doctors know this or test for this? Because the adult human body contains about 25 grams of magnesium, 60% in the bones and about 40% in the soft tissues. Only 1% is found in the blood and it is tightly regulated. Anytime you need more blood magnesium it is taken from the bones or soft tissues and the blood level remains relatively constant. If the blood magnesium gets out of whack just a little bit you will immediately know it due to fainting, dizziness, falls, panic attacks, abnormal heart rhythms, heart palpitations, large blood pressure changes, cramps, and many more-see below
Because blood magnesium is tightly controlled, there is no good or easy blood test for magnesium deficiency. So almost no doctor knows the level of magnesium in your body. There are more difficult tests like “inject and collect” which means you get a large injection of magnesium solution and then you have to collect your urine for 24 hours and see how much comes out. If nothing comes out in your urine, you are very magnesium deficient! I bet almost anyone reading this has never had this test. That is why 80%+ of us can be magnesium deficient and the doctors have no clue!
So the most practical way to determine if you are magnesium deficient is to look at the long list of symptoms and if you have one some or many of them it points towards magnesium deficiency. And many people taking a daily magnesium supplement may still be magnesium deficient as it is a very difficult deficiency to correct!
How did we all become so magnesium deficient? Through “modern” farming practices that are designed to grow big healthy looking fruits and vegetables quickly without regard to their nutritional content.
According to nutrition experts, the magnesium content of foods has been declining dramatically since preindustrial times and continues at an accelerated rate. In 2004, the Journal of the American College of Nutrition released a study which compared nutrient content of crops at that time with 1950 levels. Declines were found as high as 40%.
So, the final conclusion we can take away from all this is-
YOU CANNOT GET ENOUGH MAGENSIUM FROM
A MODERN DIET ALONE!
EVERYONE MUST SUPPLEMENT WITH MAGNESIUM EVERYDAY!
So what happens when you are magnesium deficient?
(the following is adapted and modified from an article by GreenMedInfo LLC)
Magnesium Deficiency Symptoms and Diseases
A magnesium deficiency can affect virtually every system of the body.
Early signs-
-leg cramps, foot pain, or muscle ‘twitches’
-constipation
-fatigue, and weakness
-insomnia
-numbness, tingling,
-personality changes (Mag deficient people seem “uptight”)
-abnormal heart rhythms
-panic attacks
-palpitations,
-heart arrhythmias
-fainting, dizziness, & falls (vertigo)
-high blood pressure / large blood pressure changes
-angina due to spasms of the coronary arteries,
-coronary spasms
Longer Term Symptoms of Magnesium Deficiency
-Type II (adult onset) diabetes
-muscle tension, muscle soreness, back aches, neck pain, tension headaches
-migraine headaches
-TMJ (jaw or joint dysfunction)
-chest tightness
-loss of appetite, nausea, vomiting,
-breathing difficulties -feeling you can’t take a deep breath.
-sighing a great deal
-hypertension
-depressed immune response
-urinary spasms;
-menstrual cramps;
-difficulty swallowing
-lump in the throat-especially provoked by eating sugar
-abnormal sensations, buzzes, nerve zaps and vibrations
-salt craving
-swelling of legs and ankles after sitting long periods
-carbohydrate craving and carbohydrate intolerance,
especially chocolate,
-poor digestion,
-breast tenderness
-Tinnitus (ringing in the ears).
-calcifications
-cataracts
-Hearing loss
-Heart failure
-Myocardial infarction
-Sudden cardiac death
-Stroke
Mental Issues Caused By Magnesium Deficeincy
-photophobia (hard to adjust to oncoming bright lights)
-loud noise sensitivity
-anxiety
-insomnia
-panic attacks
-personality changes (Mag deficient people seem “uptight”)
-hyperactivity and restlessness with constant movement
-irritability
-agoraphobia
-premenstrual irritability.
-hyper-excitable,
-apprehensive
-belligerent.
-clouded thinking,
-psychotic behavior
-confusion,
-disorientation
-depression
-terrifying hallucinations of delirium tremens
-tantrums (consider increasing magnesium deficiency as a possible cause of mental changes that lead to mass shootings?)
Long Term Skeletal Consequences of Magnesium Deficiency
-Calcification of organs
-tooth decay,
-poor bone development,
-osteoporosis
-slow healing of broken bones and fractures
Extreme Consequences of Magnesium Deficiency
-seizures,
-mitral valve prolapse.
-cachexia (more on this shortly)
Note that not all of the symptoms need to be present to be diagnosed with a magnesium deficiency; but many often occur together. For example, people with mitral valve prolapse frequently have palpitations, arrythmias, anxiety, panic attacks and premenstrual symptoms. People with magnesium deficiency often seem to be “uptight”.
And When Blood Levels Get Too Low
(these will be important later when we examine High Dose Vitamin D3 induced magnesium deficiency symptoms!)
-Fainting, Dizziness, & Falls!
-abnormal heart rhythm
-insomnia
-panic attacks
-palpitations,
-heart arrhythmias
Magnesium is needed by every cell in the body including those of the brain. It is one of the most important minerals when considering supplementation because of its vital role in hundreds of enzyme systems and functions related to reactions in cell metabolism, as well as being essential for the synthesis of proteins, for the utilization of fats and carbohydrates. Magnesium is needed not only for the production of specific detoxification enzymes but is also important for energy production related to cell detoxification. A magnesium deficiency can affect virtually every system of the body.
One of the principle reasons doctors write millions of prescriptions for tranquilizers each year is the nervousness, irritability, and jitters largely brought on by inadequate diets lacking magnesium
If the deficiency is more severe or prolonged, they may develop twitching, tremors, irregular pulse, insomnia, muscle weakness, jerkiness and leg and foot cramps.
If magnesium is severely deficient, the brain is particularly affected. Clouded thinking, confusion, disorientation, anxiety, belligerence, irritability, depression, panic attacks, tantrums, and even the terrifying hallucinations of delirium tremens are largely brought on by a lack of this nutrient and remedied when magnesium is given. (Could the increasing scourge of mass shootings plaguing the US be related to increasing rates of magnesium deficiency amongst the population? I think a great study would be to determine the magnesium content of tissue samples from mass shooters).