QUICK TAKE ON VITAMIN D DOSING [more complete information on dose is near the bottom]  Robert D. McMullen, MD   

            The  dose of vitamin D3 is based on weight.   A 100 lb person needs 4000 I.U./day.  One can easily extrapolate all other doses from that.  At 10-pound bay would need 1/10 of 4000 = 400 I.U.    50 lbs need 2000 I.U./d, 200 lbs need 8000 I.U. /day.   The half-life of 6 weeks allows once a month dosing — convenient, easier to remember, and costs ~$10 per years.   In the elderly [e.g., over 75, check their level as they metabolize slowly].  The 100-pound person needs 4000 I.U./day for 30 days = 120,000 I.U. So, she could take 2 pills of 50K I.U. once a month.  If you forget to take it, or cannot remember if you took,  take it later in the month.  The 10 lb baby be given ~2800 I.U. once a week, or 12,000 I.U. once a month [3 drops if each drop has 4000 I.U.

An ideal dose for many adults is a 50,000 I.U. pill of D3 (not D2) per week—or 4 pills once a month—since the ideal dose for someone ~175 lbs is 7000 I.U./day, and 7 days x 7000 = ~50,000 I.U.  An athletic in-law of mine recently underwent delicate surgery by David Altchek, MD, orthopedist and Medical Director for the NY METS.  He was astonished that he had been taking 50,000 I.U. per week of D3 for 10 years.  He rarely meets anyone who is taking the appropriate dose for their weight–and never met anyone on the correct dose so long.   He wondered who the “genius” was that suggested it.

The optimal blood level of vitamin D level is ~70 ng/ml. [Levels of vitamin D 25-OH from 100 ng/ml to 200 ng/ml are safe in the short run, though excessive. Long periods with levels > 150 ng/ml are unhealthy, increasing cardiovascular risk. This increased risk is probably similar to taking high dose calcium for years.]  People who work outside all day with very little clothes—such as hunter-gatherers—have a level of ~ 80 ng/ml.  Except for the last 10-12K years, our level for about 2.5 million years was ~80 ng/ml.

A  loading dose is advisable—up to 600,000 I.U. in an adult (12 pills of 50K in one dose; I have done it dozens of times–see reference below). At minimum I would suggest giving double the daily dose for the first month.   Otherwise reaching a steady state can take 6 months, a long time to wait. I remember a study where the benefit in reducing new cancers began only after one year on D.  Early cancers were probably present prior to the D.   In addition, many early cancers were probably not annihilated because the D level was so low in the early months.

A Chassidic Rabbi, Herschel Meisels, told me years ago that the daily dose of D3 for children should be 1000 I.U. for every 25 lbs.  After a lot of reading, I found he was  right. The same rule holds for adults.  Remember that a 100 lb person needs 4000 I.U./day and every other dose is easy to calculate: a 10 lb baby would need 1/10= 400 I.U./day. A 200 lb person would need 8000 I.U./day.

Toxicity occurs if one takes ≥ 10 X  the appropriate dose.  People over 75 y.o. sometimes only need 1000-2000 I.U./day, because of slow metabolism.  Check the level.

If you double the dose, the level may only increase ~20%.  D induces its own metabolism.

 

A FEW OF THE MOST IMPORTANT REASONS D IS NECESSARY:

  • Osteoporosis: Lack of calcium in the diet is not why one sees so many elderly with osteoporosis – – stooped over and having lost inches in height. The osteoporosis is because of decades of low vitamin D. The first thing D does is facilitate the absorption of calcium from food.   Optimal benefit is only at a level of 30 ng/mL or more.  Calcium is a priority, so body will not use D for the immune system, etc. until the levels climb above 40 and 50 and optimal is 70 ng/ml.
  • Glutathione is the main antioxidant in the body. D has the specific property of stimulating the formation of glutathione in the brain. This has a number of implications, including a benefit for depression. I think one of the main reasons its anti-depressant effect has not been well established is it 6-week half-life.  If you start on the correct dose –e.g., 4000 I.U. /day in a 100-lb person (less if elderly)—it may take 30 weeks to read a steady state with a level around 70 ng/ml.   Studies last 6 weeks, not 6 months.  To see the benefit, one would have to give a loading dose.  A researcher told me that give a loading dose of 600,000 I.U. would not pass the ethics committee—though there was one study on its safety—see page 4.

EXAMPLES OF IMPORTANCE TO THE IMMUNE SYSTEM:

  • Cold viruses and influenza are more common in the winter because vitamin D levels of the population is lower.
  • Surgical morbidity and mortality are higher if D levels are low.
  • D helps screen out early cancers by three different methods. At least 20 cancers are highly associated with low vitamin D. Around the world, colon cancer and breast cancer become approximately twice as common north of the latitude of Atlanta (the reverse in the southern hemisphere).   Latitude is a proxy for vitamin D level in the population –assuming a similar lifestyle.  Colon cancer is 11 times as common in the U.S. as the parts of Africa where most people still work outside.  S. blacks have 50% more colon cancer than whites.  I believe that means U.S. blacks have 17 times as much colon cancer as blacks in Africa!   These are people with the same genetics. If not low vitamin D level (much lower than whites), what is the alternative cause?
  • Autoimmune disorders become more common the farther one is from the equator. The highest rates of MS, autism, rheumatoid arthritis, type I diabetes, Crohn’s disease, et al, are in Europe  and North America [with Canada being a little higher]—where few people work outside- and much less common in undeveloped areas, especially near the equator.    Intermediate rates are found in South Africa and Australia.    Despite living in very sunny countries, many are at high risk of autoimmune disorders if they rarely leave air-conditioning and work indoors.

 

  • GENETICALLY WE ARE HUNTER GATHERERS.

Humans emerged  2.5 million years ago when they suddenly developed a large brain.  Farming started 10-12,000 years ago.  In other words, humans have existed around 40 hours, and have been farmers for 1 second.   We were an upright  bare-skinned primate continually exposed to sunlight.   The human uses vitamin D for many purposes—different purposes in different cell types.  We were adapted to having significant amounts of vitamin D—and using.   The remaining hunger gatherers are found largely near the equator.  They wear virtually no closing.   At most they made an apron of leather or a sling of leather to carry a baby or toddler.

We evolved to use and need the very high level of D we manufactured.     The concentration of calcidiol (Vitamin D 25-OH)–which  is stored on VDB (vitamin D binding protein)—is optimally about 70 ng/mL (70,000 pcg/ml).  The concentration of the active form – calcitriol (Vitamin D 1,25,dihydroxy)—might be about 70 pcg/ml. The calcidiol concentration is1000 times as much as calcitriol.  Each cell type takes in calcidiol and converts it to calcitriol in the amount it needs.  But the cells will not take in the D until the levels are far about that which is needed to maintain good bone.   Each cell type uses D for different purposes.  It serves to optimize immune cell activity.  Muscle cells use to influence greater growth.

When humans moved out of Africa and into Europe, the purpose of a large amount of melanin in their skin was to prevent in skin cancers.  In  Europe, the melanin prevented the manufacture of the necessary amount of vitamin D.  Evolution to skin with less melanin was no doubt rapid.  In addition, they had to store D for the winter.

The differences amount of melanin in your skin indicates how far your ancestors were from the equator.    Swedes are paler than Italians because they must make D more easily and rapidly.  When the sun is at its apex only 1% of UVB  penetrates the atmosphere.  A decline from the apex increases the amount of atmosphere to pass through.  At 45 degrees none penetrates. Northern peoples contend with a short summer and a sun that is never very high.

Early Europeans probably wore fur in the winter.  What did they wear in the summer?  The choices were:   leather, fur, or something woven from plants.  None sound comfortable.   Like all the surviving hunter-gatherers, they probably wore at most a leather garment, not something covering most of the body.     On any part of the skin, “white” people can only make vitamin D for about one hour.  Only the next day can more be produced.  Darker-skinned people may need as much as 3 hours to manufacture the same amount.  There is plenty of sunlight where dark-skinned people come from to make D year-round. Dark skin prevents skin cancers.

If a large amount of skin exposed when the sun is high, we can easily make 10,000 I.U./day.  It is possible to make 15K I.U.

If we can make 10K I.U. per day, it seems logical that we might require something in the range of 5K to 10K per day as repletion of this hormone we are grossly deficient in.  Many of us believe that a 125 lb person needs about 5K per day. The 400 I.U. that the FDA recommended in the past is grossly adequate.  Though humans and dogs have different in D requirements, one would assume a 150 lb human would need more than a 10 lb dog—especially when you consider that animals have lower levels of D.  The level of D in a dog is ~14 ng/ml.  We should be ~70 ng/ml.  Animals have little skin exposure and have less efficient methods of obtaining it.  A goat has 15 ng/ml; a sheep 11; a cow 40; red deer 5, a pig 20.  Reptiles make D by sunning themselves. Even insects make it.  Only two animals lack D (the Ethiopian fruit bat and the African mole-rat– which never comes above ground.  This is an indication of how important it is.

Calcitriol attaches to the nucleus via vitamin D receptor (VDR),  a member of the nuclear receptor family of transcription factors. Animals have the same receptor.  Since animals have lower levels of D, they have evolved to be more sensitive to the D they possess.

 

MORE INFORMATION ON THIS STEROID HORMONE—In about 1919-20, Mellanby in England cured rickets in beagle puppies with a teaspoon per day of cod liver oil.   He assumed the agent was the vitamin A in cod liver oil. Elmer McCollum at Columbia discovered the antirickettsial  substance in cod-liver oil was not vitamin A.  When cod liver oil was denatured of vitamin A, it still cured rickets.   It was some other substance.  It seemed obvious at the time that this was the 4th vitamin, after A, B, and C– so he called it “vitamin” D.   Since they could not isolate it,  each teaspoon of cod liver oil was said to contain 400 I.U. of D. It was later discovered a teaspoon contains only a tiny amount–10mcg–of D.  Since 10mcg = 400 I.U., 1mg = 40,000 I.U.   All these zeros have inhibited doctors and laymen from using an optimal dose.

Like us, fish need  D3 to absorb calcium and make bone.  A little is found in fish liver, but most is stored in their skin–which is why Eskimos have sufficient D despite virtually no UVB light—they eat fish skins.  Vitamin D arose as part of the process of making the skeleton in the first animals that made bones—i.e., fish.   Subsequently, all vertebrates except 2 need D.  Fish obtain D2 from plants and convert it to D3.

Years later scientists realized it was a hormone—too late to change the name.   Such a label forever condemned “vitamin” D to not be taken seriously.   Even among people who understand its importance will unconsciously discount the importance because of the name and will start forgetting to take it.

Take heed:  Avoid vitamin D2, which is by prescription only– 50,000 I.U. gel caps are intended to be taken once a week. D2 is from plants, is less potent and has a shorter ½ life. It was grandfathered in as a prescription. There was no other good source of D  80+ years ago. All non-prescription vitamin D is D3—our own vitamin D.

Obtaining and selling D3 is a big industry.   D3 is obtained from the lanolin of sheep. When the oil/lanolin reaches the end of the wool, UVB light converts half  of pre-D3 (7-dehydrocholesterol) into D3. It cannot convert more than ½ because it is an isomer that is converted both  ways by UVB light.

When a sheep licks the wool of his/her significant other, he/she obtains the necessary D dose. When Australians press out ~ 330 mL of lanolin from each sheep, it is sold  to factories: two in China and one in Germany. In a complicated process, pre-D3 is extracted and all of it is converted to D3.  Large quantities are sold to  companies which provide animal feed.  Food animals, most raised in indoor factories now,  become ill if  not given vitamin D.  If their health is impaired without abundant sunlight, what about us and our millions of years of sun exposure?    
NOTE:   Prominently published in the New England Journal of Medicine, a large five-year Boston study [Manson, NEJM, 1/3/19]  set back the cause of vitamin D for years.   The research was to find whether  vitamin D prevented cardiovascular disease and cancer.   In 2012 I was appalled when I read the plan of the study.  A negative outcome was predictable, if not inevitable.   A daily dose of Vitamin D3 2000 I.U.’s [50 mcg / 0.050 mg] is appropriate for a 50-pound child, not an adult.   The vitamin D 25-OH levels at the end of the study were 40 ng/ml  in the study group and 30 ng/ml in the controls, not a large difference.  One needs 30 ng/ml for maximum calcium absorption and good bones.  In my experience most patients on 2000 I.U. barely reach 30 ng/ml, if they reach it at all.  Patients in the study must have been taking extra vitamin D or were in the sun a lot.  The benefits for cancer, diabetes, et al, seem to occur at much higher doses, say ≥  50ng/ml.  My internist pointed out that, uncharacteristically, the NEJM did not subsequently publish a single letter about this misguided study. There must have been dozens.

  • Many studies indicate higher levels are better. A study in Finland used 2000 I.U.’s  per day during the entire first year of life!—5 times the requirement of a 10 lb baby, and the proper amount for a 50-lb child.   The incidence of type I diabetes plummeted 78%.   Many recognized that 2000 I.U.’s per day in newborns had been excessive, but no apparent harm resulted.
  • Toxicity only occurs when taking ≥ 10 times the optimal dose for a few months.   All reported toxicity [usually industrial accidents] was at  ≥ 50K I.U. /day, and usually did occur for several months.  There are no reported cases of toxicity taking ≤ 40K per day.  It is well established that levels up to 200 ng/ml are perfectly safe in the short run. Levels above  125-150 ng/ml are unhealthy over the long run.  There is no reason to have a level over 100 ng/ml.

REGARDING USE of D3 50,000 I.U. PILLS

  • Someone weighing 100 to 150 lbs can take just 3 pills once a month. With 10 years of experience, I have found people are much more likely to stay on it if it is monthly.   If someone has several children, it is vastly easier to distribute their doses once a month than daily (G-d forbid) or weekly.
  • Someone > 150 lbs can take 4 pills per month.
  • For a person weighing 50 to 100 lbs, the dose is 2 pills once a month.
  • SOMEONE over 75 y.o. may be metabolizing it slowly and need 1000 to 3000 I.U. /daye., 1- 2 pills per month of 50,000 I.U. pills.  Check your level.    If you change the dose, check the level 3 to 6 months later.
  • Because the half-life is about 6 weeks, #1: one can take a dose once a month and the level will remain steady,  and #2:  it builds up slowly.   If you start at 5000 I.U. /day [or 3 pills of 50,000 once a month],  you  may not reach a steady state for 5 x 6 weeks = 30 weeks, about 6 months.   If your level is low, it advisable to take a loading dose. At minimum, double the dose for the first month.    I
  • LOADING DOSE: In a study young adults who with an  average level of 16 ng/ml  were given a  single dose of 600,000 I.U.  [12 pills of 50K I.U.]—enough for 3 months in the average adult.  A few days later their D level was about 77 ng/ml.]  Effect of a Single Oral Dose of 600,000 IU of Cholecalciferol [D3] on Serum Calciotropic Hormones in Young Subjects with Vitamin D Deficiency: A Prospective Intervention Study   Cipriani et al, J Clin Endocrinol Metab 95: 4771–4777, 2010
  • In Canada and India there is available a syringe pre-filled with 600K I.U. so the PMD can give the patient a 3 months’ supply without having to worry about compliance.
  • CHILDREN CAN TAKE LIQUID D ONCE A MONTH. The doses below are assuming  there is 4000 i.e. in each tiny drop.   With a different concentration, the # of drops must be adjusted.  [I use Zahler’s, because the vitamin D is an olive oil, so young children do not know it is medicine and it can be put on their food.  The dose of D3  correlates with weight, just as it does with thyroid hormone (thyroxine).  The daily requirement of both  steroid hormones is ~100-200mcg].  Adults and children need about 1000 I.U./day for every 25 lbs.   [A recent paper indicates that infants in their first year may be better off on more, but for now I am staying at a conservative 1000 I.U. per 25 lbs = 400 I.U. for every 10 lbs.]
    • Since a drop of olive oil [not a dropper full!] contains 4000 I.U. of D3, and the dose is 1000 I.U./day for every 25 lbs, then a 100 lb person needs 4000 I.U. /day = one drop per day= 30 drops once a month. You can extrapolate from that all weights. A 50 lb  child therefor needs ½ of 30 = 15 drops once a month.  A 10 lb baby needs 1/10 of 30 drops = 3 drops once a month.   You don’t have to be exact.  If  ½ dropper full is about 15 drops, then you can give a 50 lb child approximately ½ dropper full once a month.  A 10 lbs baby needs 3 drops once a month          15 lbs: needs 4 drops/ once a month     20 lbs: 6 drops/ mo   25 lbs: 8 drops/ mo          50 lbs:15 drops/ mo  75 lbs:  23 drops/ mo        100 lbs:30 drops/mo

 

THE ABSTRACT OF THE 1999 REVIEW THAT FIRST ALERTED US TO THE GROSS INADEQUACY OF OUR VITAMIN D DOSING. This was not new research. This is a review based on the existing body of literature.    

American Journal of Clinical Nutrition, Vol. 69, No. 5, 842-856, May 1999     © 1999 American Society for Clinical Nutrition    

NOTE: vitamin D:  0.4 nmol/L =  ng/ml

 

Vitamin D supplementation, 25-hydroxyvitamin D concentrations, and safety1,2

Reinhold Vieth      1 From the Department of Laboratory Medicine and Pathobiology, University of Toronto, and Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto.

2 Address reprint requests to R Vieth, Pathology and Laboratory Medicine, Mount Sinai Hospital, 600 University Avenue, Toronto, Ontario M5G 1X5 Canada. E-mail: rvieth@mtsinai.on.ca.

 

Abstract:    For adults, the 5-µg (200 IU) vitamin D recommended dietary allowance may prevent osteomalacia in the absence of sunlight, but more is needed to help prevent osteoporosis and secondary hyperparathyroidism. Other benefits of vitamin D supplementation are implicated epidemiologically: prevention of some cancers, osteoarthritis progression, multiple sclerosis, and hypertension. Total-body sun exposure easily provides the equivalent of 250 µg (10000 IU) vitamin D/d, suggesting that this is a physiologic limit. Sailors in US submarines are deprived of environmentally acquired vitamin D equivalent to 20–50 µg (800–2000 IU)/d. The assembled data from many vitamin D supplementation studies reveal a curve for vitamin D dose versus serum 25-hydroxyvitamin D [25(OH)D] response that is surprisingly flat up to 250 µg (10000 IU) vitamin D/d. To ensure that serum 25(OH)D concentrations exceed 100 nmol/L [40 ng/ml] , a total vitamin D supply of 100 µg (4000 IU)/d is required. Except in those with conditions causing hypersensitivity, there is no evidence of adverse effects with serum 25(OH)D concentrations <140 nmol/L [56 ng/ml], which require a total vitamin D supply of 250 µg (10000 IU)/d to attain. Published cases of vitamin D toxicity with hypercalcemia, for which the 25(OH)D concentration and vitamin D dose are known, all involve intake of 1000 µg (40000 IU)/d. Because vitamin D is potentially toxic, intake of >25 µg (1000 IU)/d has been avoided even though the weight of evidence shows that the currently accepted, no observed adverse effect limit of 50 µg (2000 IU)/d is too low by at least 5-fold.