In a paper critical of higher levels of vitamin D for allegedly increasing a marker of inflammation, c-reactive protein (CRP), Drs. Muhammad Amer and Rehan Qayyum of the Johns Hopkins School of Medicine, began their paper by saying:

“The cardiovascular protection offered by vitamin D and its analogues is probably mediated by modulation of inflammatory cytokines.”

Amer M, Qayyum R. Relation Between Serum 25-Hydroxyvitamin D and C-Reactive Protein in Asymptomatic Adults (From the Continuous National Health and Nutrition Examination Survey 2001 to 2006). Am J Cardiol. 2011 Oct 12.

If you will notice, both physicians know that vitamin D offers “cardiovascular protection.” However, they are concerned 25(OH)D levels higher than 20 ng/ml will increase inflammation as measured by CRP and thus worsen cardiovascular protection. CRP is a protein in the blood which tends to rise in response to inflammation or injury. Its physiologic role is to take part in the “complement system.”

The authors arrived at this conclusion by adjusting their data for up to 9 variables and finding that a 25(OH)D of 20 ng/ml is associated with a CRP (range 0-5) of approximately 1.7 while a 25(OH)D of 50 ng/ml is associated with a CRP of 1.9. Their raw findings contradict their adjusted data in that the raw data showed what we have known for some time and that is that in the lower ranges of 25(OH)D, vitamin D reduces CRP. As with most biomarkers of vitamin D, the big improvement is in people who get their 25(OH)D up  from 5 ng/ml up to 20 ng/ml. We know that in most cases, the biggest bang for the buck is in treating severe deficiency in people with such low levels.

So if you have natural levels of vitamin D, say a 25(OH)D of 50 ng/ml, and you want to decrease your CRP by 0.2, then stop your vitamin D and stay out of the sun, get your levels to 20 ng/ml, and see if all the corrections and adjustments the doctors performed were correct. I certainly am not going to do such a silly thing.

Dozens of studies now exist showing supplemental vitamin D3 reduces mortality rates, in part due to its cardiovascular protection. The majority of these studies show that improvement in mortality continues through 30 ng/ml and even up to 40 ng/ml. Not enough people have levels of 50 ng/ml for scientists to see if such levels offer further protection. However, cardiovascular disease is rare in native peoples around the equator where vitamin D levels of 50 ng/ml are not uncommon.

The takeaway message from this paper is that scientists will need to recalculate lots of different “normals,” using vitamin D sufficient subjects. It’s not just that normal CRP may be a bit higher in vitamin D sufficient people, their red blood count and the protein albumin may be a bit lower, for example. The point is that pathologists and epidemiologists will need to redo much of their work. We don’t know the normal range of CRP in 65-year-old men; we know the range of CRP in 65-year-old vitamin D deficient men. Likewise, we don’t know the incidence of heart disease in 65-year-old men; we know the incidence of heart disease in vitamin D deficient 65 year-old men. We have lots of work to do.

Source: Vitamin D Council Newsletter

http://www.foodmanufacture.co.uk/Ingredients/Criminals-drop-drugs-for-food-fraud

When we talk about T scores, osteopenia and osteoporosis, we assume we are talking about older people, especially post-menopausal women. However, a group of obstetricians and pediatricians from the University of Sienna, led by Dr. Franco Bagnoli, reported that 42% of infants have osteopenia.

Bagnoli F, Casucci M, Rossetti A, Nappini S, Cecchi S, Toti S, Franci MB. Vitamin D as a drug. J Matern Fetal Neonatal Med. 2011 Oct;24 Suppl 1:7-11

What I like was that the authors said, “To be safe, vitamin D administration should be increased to 2,000 IU/day for neonates, 5,000 IU/day for children and 10,000 IU/day for all adults.” Obstetricians are generally regarded as the one group of physicians that seldom change their mind. My hat is off to these seven obstetricians.

So many infants have craniotabes, or softening of the fontanels, it is considered normal although such infants show signs of vitamin D deficiency. That is, about a third of our infants show evidence of having low vitamin D during their development in the womb.

Yorifuji J, Yorifuji T, Tachibana K, Nagai S, Kawai M, Momoi T, Nagasaka H, Hatayama H, Nakahata T. Craniotabes in normal newborns: the earliest sign of subclinical vitamin D deficiency. J Clin Endocrinol Metab. 2008 May;93(5):1784-8.

Finally, if you look at the incidence of rickets inside the womb by ultrasound, about a third of infants have signs of intrauterine rickets (splaying or widening of the femur) during their pregnancy.

Mahon P, Harvey N, Crozier S, Inskip H, Robinson S, Arden N, Swaminathan R, Cooper C, Godfrey K; SWS Study Group. Low maternal vitamin D status and fetal bone development: cohort study.J Bone Miner Res. 2010 Jan;25(1):14-9.

Then there is the evidence that vitamin D deficiency during pregnancy is associated infection, toxemia and caesarean section, not to mention a host of diseases as the child ages, including diabetes, asthma, and infections. If you know any pregnant or breastfeeding woman, make sure she is taking at least 6,000 IU/day (10,000 IU/day is fine) and then make sure the child takes 2,000 IU/day of vitamin D when he is weaned and progressively more as he ages, until he is on 5,000 IU/day as a teenager.

However, you and I both know many people will not take supplements or give them to their children, which is why Professor Walter Willett of Harvard believes this is a public health problem that will only be solved through adequate food fortification. Also, prenatal vitamin makers could easily increase the vitamin D in their products up to 4,000 IU/day and stay within the safety guidelines of the Food and Nutrition Board. Many more foods need to be fortified, and these foods need to be foods that all subgroups of people eat in similar amounts, such as cheese and cereals. These foods need to have 400 IU per serving, not 100 IU per serving. I wish I could tell you that I think I will live to see it.

Dr John Cannell

In September, 2011, two papers with three case reports of vitamin D toxicity were published. Two cases were manufacturing errors and one was a pharmacist’s mistake. Vitamin D levels associated with clear toxicity ranged from 194 to 1220 ng/ml. To my knowledge, toxicity occurring at 194 ng/ml is the lowest vitamin D level causing clear toxicity known in the medical literature.

In the first case, a pharmacist’s dispensing error occurred when the doctor wrote a prescription for 1,000 IU/day of D3. Since it was not a prescription item, the pharmacist thought the doctor meant prescription Drisdol, which is 50,000 IU. So the patient, a 70-year old woman with mild dementia, began taking 50,000 IU/day of D2. She was also taking, for reasons unknown, 3100 mg of calcium per day.

Jacobsen RB, Hronek BW, Schmidt GA, Schilling ML Hypervitaminosis D Associated with a Vitamin D Dispensing Error (October). Ann Pharmacother. 2011 Sep 13.

Three months later she developed confusion, slurred speech, unstable gait, and increased fatigue. Probably due to her dementia, she did not complain of the most common symptoms of toxicity: lack of appetite, excessive thirst, nausea, abdominal pain and increased urination. Her vitamin D level was 194 ng/ml, her calcium (CA) was 14.6 (8.5-10.5 is normal); her kidney function was impaired with a creatinine of 5.3 (CR); her activated vitamin D level was normal, her urine CA/CR ratio was elevated, but she had no anemia. All vitamin D and calcium was withheld and her doctors treated her with IV fluids. Four days later her symptoms disappeared and her calcium returned to normal and her creatinine improved to 3.0. Five months later her vitamin D level was 40, her calcium was 9.2, and her creatinine was back at baseline, 1.8.

To my knowledge, this is the first modern case report of toxicity at 50,000 IU/day (and this was D2), although this case also included 3100 mg/day of calcium. Unfortunately, I have heard that a few physicians use 50,000 IU/day routinely. It is too much, way too much. However, this lady completely recovered with no damage to her kidneys.

Secondly, why would anyone take 3100 mg/day of calcium? In this case she was demented. However, many people believe that the government recommendation of 1200 mg/day of calcium for females over the age of 50 means they should literally take 1200 mg/day as a supplement. It does not mean that at all. It means total dietary and supplement intake should be 1200 mg/day and everyone gets some calcium in their diet. Most people need no more than 500 mg/day of calcium as a supplement and many people who eat dairy three times a day need none.

The other two cases were equally interesting, but involved manufacturing errors. It is one of the reasons I recommend you get your vitamin D from one of our sponsors, Stop Aging Now or Bio-Tech-Pharmacal (links on the right). Both companies are experienced and careful in their vitamin D manufacturing process.

In case two, an otherwise healthy man developed fatigue, excessive thirst, frequent urination and confusion. Three weeks later he was admitted to hospital in a coma with a vitamin D level of 1220 ng/ml (24 times that of a healthy level), calcium of 15, activated vitamin D of 106, massive calcium loss in the urine, mild anemia, and elevated urine CA/CR ratio. He had been taking “Formula F,” labeled to contain 1600 IU of vitamin D but it really contained 186,400 IU per capsule. In addition, “Formula F’s” label recommended 10 capsules per day, not one, so the patient had been taking 1,864,000 IU daily for two months! After treatment, calcium returned to normal in three weeks; the vitamin D level and the creatinine returned to normal in a year. That is, he completely recovered.

Araki T, Holick MF, Alfonso BD, Charlap E, Romero CM, Rizk D, Newman LG. Vitamin D Intoxication with Severe Hypercalcemia due to Manufacturing and Labeling Errors of Two Dietary Supplements Made in the United States. J Clin Endocrinol Metab. 2011 Sep 14.

Case three (in the above paper) was a 40-year old man who presented with excessive thirst, frequent urination, muscle aches, nausea, vomiting, elevated calcium (13.2), elevated creatinine (1.78), vitamin D level of 645 ng/ml, elevated activated vitamin D of 99, mild anemia, and an elevated urine Ca/Cr ratio. He reported taking “Gary Null’s Ultimate Power Meal” for a month, which mistakenly contained 970,000 IU of vitamin D per serving. Calcium returned to normal in several days, kidney function returned to normal in 4 weeks, vitamin D level normalized in 10 months but activated vitamin D took a year to normalize. No permanent injuries occurred, much to the chagrin of the trial lawyers.

The takeaway from these three papers is that if you take more than 10,000 IU/day, you must check your 25(OH)D regularly. I am concerned that people with levels greater than 150 ng/ml may be urinating out more calcium than they should; that is urinating out their bones. A 1988 paper suggested exactly that and I have clinic experience that shows in at least one person, a 24 hour urine calcium was elevated before the urine Ca/Cr ratio was abnormal. To be safe, keep your 25(OH)D vitamin D levels below 100 ng/ml.

First, what is the vitamin D level of our closest simian relatives, such as chimpanzees living wild in Africa? Professor Reinhold Vieth reports the answer is between 40 and 60 ng/ml. This, by itself, does not prove we need such levels, but it certainly raises that question.

Second, what is the vitamin D level of humans who work in the sun without clothes, such as lifeguards, and without supplementing? We lived in the sun for 2 million years, so certainly lifeguards have more natural vitamin D levels than do people who work indoors. Again, the answer is between 40-60 ng/ml. Here, we have stronger naturalistic evidence unless one assumes the vitamin D levels of indoor workers are natural.

Third, what vitamin D levels do women have to achieve to convert from having little to having lots of vitamin D in their breast milk? Professors Bruce Hollis and Carole Wagner recently answered that question, again 40-60 ng/ml, enough to sustain the infant’s vitamin D levels. One could claim breast milk is not supposed to have vitamin D in it, and that primitive man was supposed to expose newborns to sunlight. But then you would be arguing that primitive man was supposed to expose their infants to predators, which I find unlikely. Besides, we know from the second reason that any woman receiving consistent full body sun exposure would have vitamin D in her breast milk.

Finally, what is the vitamin D level of people who show no evidence of substrate starvation? That is, at what level do people begin to store the parent compound (cholecalciferol) in their fat and muscles? Professor Robert Heaney answered that question: around 40 ng/ml. I remember seeing several patients in the hospital who had vitamin D levels of 40-50 ng/ml in February. Both had worked as roofers the summer before and both had worked with their shirts off. The mechanism for humans who migrated away from the equator must have been the same, to store the parent compound in muscle and fat during the summer for use in the winter. The body stores it well before it turns on the enzymatic machinery to get rid of excess vitamin D.

So we have the above four questions, questions from four very different sources. Chimps, outdoor workers, lactating women, and clinical subjects all lead to the same answer: 40 ng/ml is the lower limit of a natural level. Taking into account errors in laboratory testing and variations in human techniques, we must accept what the Endocrine Society recently recommended, that healthy vitamin D levels are somewhere around 50 ng/ml, levels the Vitamin D Council has advocated for the last 8 years.

From the Vitamin D Council Newsletter 19 September 2011