Genetics, as well as dose, determine response to vitamin D supplements.
Vitamin D council newsletter March 13 2010
Your vitamin D blood level depends entirely on how much you take or how often you sunbathe, right? Wrong. Prior studies of identical twins show that about 25 -50% of the variation of Vitamin D levels depends on genetics. In July, researchers at the University of Toronto discovered the heritability of 25(OH)D is probably mediated through the Vitamin D binding protein (VDBP).
[http://list.netatlantic.com/t/51077657/93991066/126139/0/|Fu L, Yun F, Oczak M, Wong BY, Vieth R, Cole DE. Common genetic variants of the vitamin D binding protein (DBP) predict differences in response of serum 25-hydroxyvitamin D 25(OH)D to vitamin D supplementation. Clin Biochem. 2009 Jul;42(10-11):1174-7.]
One of the common emails I get (and I’m sorry I can’t answer individual emails) is “I am taking 5,000 IU per day but my blood level is only 35 ng/ml.” What should I do? This study helps answer such questions. You probably inherited a tendency to not respond to higher doses of Vitamin D. Simply take a little more and get your blood tested again in 3-4 months.
Also, don’t forget your weight. Does it make sense that if you weigh 300 pounds, you need more vitamin D than a 3 pound baby? If that makes sense to you, congratulations, it has not made sense to any of the five Food and Nutrition Boards (FNB) that have convened and issued recommendations to Americans over the last 60 years; they have all recommended the same 200 IU/day dose for infants and young adults, no matter how much the adults weigh.
More researchers actually recommend that people take Vitamin D and not just give more money to scientists.
Researchers from Austria concluded their review paper on vitamin D and high blood pressure by stating: “In view of the multiple health benefits of vitamin D and the high prevalence of vitamin D deficiency, as well as the easy, safe, and inexpensive ways in which vitamin D can be supplemented, we believe that the implementation of public health strategies for maintaining a sufficient vitamin D status of the general population is warranted.”
Good for Austria! By the way, while vitamin D may improve hypertension, it is not the be all and end all of hypertensive disease. If your doctor can stop your high blood pressure medication after you start taking vitamin D, great, but I doubt that will happen. Most people will have to continue taking their antihypertensive medication even after adequate vitamin D supplementation, albeit sometimes at a lower dose.
While I am on the subject, remember, that vitamin D will not prevent all cancer or heart disease or respiratory infections. True, evidence is accumulating that it will help, but you can still develop cancer, heart disease and respiratory infections with adequate blood levels of vitamin D. That’s why I believe in complimentary, not alternative, medicine.
Professor Michael Holick keeps increasing the amount of vitamin D he recommends.
As readers know, Professor Holick is one of the world’s foremost authorities on vitamin D. However, after being on the 1997 Food and Nutrition Board (FNB), he stuck with the FNB’s 200 IU/day recommendation well into the next century. Then he slowly went to 400 IU, then 800 IU, then 1,000 IU and now he is at 2,000 IU/day. Professor Holick is going in the right direction and is almost there.
Professor Robert Heaney of Creighton University just discovered that if you take 2,200 IUof vitamin D every day, you only have about 12 days supply of vitamin D in your body
I love Robert Heaney’s papers. In a previous paper, Dr. Heaney discovered that at blood levels of 35 ng/ml, 50% of people are using up their vitamin D as quickly as they take it, that is, they are not storing any for future use and suffer from chronic substrate starvation. Obviously, one wants to take enough so the body has all it can use, which is why I recommend 25(OH)D levels of at least 50 ng/ml. At that level, no one should have chronic substrate starvation.
In the paper below, Dr. Heaney collaborated with two other Creighton scientists, Dr. Diane Cullen and Dr. Laura Armas, as well as one of the premier experts in measuring vitamin D in the world, Dr. Ron Horst of Heartland Assays. Ron runs tens of thousands of vitamin D samples a year as Heartland Assays performs vitamin D testing for most of the big studies and Dr. Horst is one of the few people in the world who can accurately measure cholecalciferol, and not just 25(OH)D.
Anyway, in his latest paper, Dr. Heaney found that if you regularly take 2,200 IU per day, you have about 12 days supply of vitamin D in your body. He explained, “What this indicates is that fat reserves of the vitamin are essentially running on empty and that . . . additional vitamin D inputs are converted to 25(OH)D almost immediately.” . . “The currently recommended intake of vitamin D needs to be revised upward by at least an order of magnitude.”
What is not known, at least by me, is what happens when cholecalciferol intake far exceeds the body’s requirement. We know it is stored in the body, mainly in fat and muscle, but what does the body do to control excess cholecalciferol from building up in the body? Professor Reinhold Vieth has written that much of it will simply be excreted unchanged in the bile, but how does that system work exactly, to get rid of excess cholecalciferol? We know it works because the few patients with vitamin D toxicity reported in the literature – almost always due to industrial errors – reduce their vitamin D levels rather quickly by simply stopping the vitamin D and staying out of the sun.
Zocor has no effect on vitamin D levels.
I know several studies have found statins raise vitamin D levels but different scientists report different findings. This paper found Zocor had no effect of vitamin D levels while a previous paper found Crestor almost tripled vitamin D levels. What’s the truth? I don’t know. The above study did find that higher vitamin D levels were strongly associated with better triglycerides and weakly associated with higher HDL (the good cholesterol) levels.
Rejnmark L, Vestergaard P, Heickendorff L, Mosekilde L. Simvastatin does not affect vitamin d status, but low vitamin d levels are associated with dyslipidemia: results from a randomised, controlled trial. Int J Endocrinol. 2010;2010:957174.
Vitamin D lowers statin blood levels
This study makes the point that things are often more complex than they first appear. Almost nothing is known of vitamin D’s drug-drug interactions. That is, how does vitamin D affect the blood level of other drugs? The below study measured the effects of vitamin D on Lipitor levels and cholesterol levels hours after Lipitor was given to patients taking vitamin D. The authors were looking for drug-drug interactions and found them.
The above study found vitamin D not only lowered Lipitor levels, but vitamin D lowered bad cholesterol levels as well. That is, the lowest bad cholesterol levels were found in patients on vitamin D with the lowest Lipitor levels, just the opposite of what one would think. I mean, wouldn’t higher Lipitor levels result in lower cholesterol levels? Not when vitamin D was taken into account. If you think my explanation of this study is confusing, you should read the study.
Intensive treatment with vitamin D, statins, and omega-3 fish oil reverses coronary calcium scores.
The below open study by Dr. William Davis and colleagues studied 45 adults with evidence of calcified coronary arteries, treating them with high dose statins, niacin, fish oil (not cod liver oil) capsules, and enough vitamin D (average of about 4,000 IU/day) to obtain 25(OH)D levels of 50 ng/ml. They found that regimen reduced coronary calcium scores in 20 patients and slowed progression in 22 additional patients. That is, it reversed the coronary calcification process in about half of patients and slowed its progression in most of the rest.
Davis W, Rockway S, Kwasny M. Effect of a combined therapeutic approach of intensive lipid management, omega-3 fatty acid supplementation, and increased serum 25 (OH) vitamin D on coronary calcium scores in asymptomatic adults. Am J Ther. 2009 Jul-Aug;16(4):326-32.
Most studies have shown high dose statins on their own do not reverse coronary arthrosclerosis, so we know it was not the statins alone. What would vitamin D levels of 70 ng/ml do? So, if you have coronary artery disease: ask your cardiologist about statins and niacin, take 5-10 fish oil capsules per day, and at least 5,000 IU of vitamin D3 per day.
A word about fish oil is in order. Fish oil means fish body oil, not fish liver oil. And, four or five capsules of omega-3 fish oil a day will do very little if you do not limit your intake of omega-6 oils. Your ratio of omega-6 to omega-3 is the crucial number, your want that ratio at 2 or below, which means no chips, no French fries and no processed foods, a difficult diet. Omega-6 oils are vegetable oils such as corn oil, safflower oil, soybean oil, sunflower oil and cottonseed oil. Read the packages to see what is in them and if they contain the above oils do not eat them. In additions to taking fish oil capsules, try to eat wild-caught salmon three times a week.
Our group’s second paper on influenza is now the most accessed paper in the history of Virology Journal.
I was asked to write the paper by the editor of another journal, who then refused it! I almost decided to scrap the paper but, in the end, submitted it to Virology Journal. I’m glad I did.
I was glad to see that six other experts recently recommended that the diagnosis and treatment of vitamin D deficiency be part of our national preparedness for the H1N1 pandemic.
In addition, I hear through the grapevine that the CDC has discovered that, of the 329 American children who have died so far from H1N1, vitamin D levels in the dead children were lower than in children who survived the swine flu. Maybe something can be done to save our children by next winter? Not to mention the 16,000 adult Americans the CDC thinks died from H1N1.
Reuters. Up to 80-million Americans have been infected with H1N1. 1/15/2010
Low vitamin D levels mean higher death rates in patients with kidney disease.
The below study is the first of its kind; Dr. Rajnish Mehrota and his eight colleagues studied 3,000 of the 28 million U.S. adults who have chronic kidney disease, finding those with vitamin D levels below 15 ng/ml had a 50% increased risk of death compared to those with levels above 30 ng/ml over the nine years of the study. These researchers from UCLA, Harvard, the Los Angeles Biomedical Research Institute, and other institutions concluded: “The broad public health implications of our findings cannot be overemphasized given the high prevalence of vitamin D deficiency among individuals with chronic kidney disease, and the ease, safety, and low cost of maintaining replete vitamin D levels.”
Mehrotra R Mehrotra R, Kermah DA, Salusky IB, Wolf MS, Thadhani RI, Chiu YW, Martins D, Adler SG, Norris KC.. Chronic kidney disease, hypovitaminosis D, and mortality in the United States. Kidney Int. 2009 Nov;76(9):977-83.
These words are music to my ears; these words are strong words, urgent words, and, better yet, they are not my words. This is the first large study looking at a representative group of Americans with kidney disease, before dialysis, finding about 1/3 of them died over the 9 years of the study. Those with low vitamin D levels were more likely to die; in fact, they were more likely to have about every chronic disease you can think of before they died. The average age of those with kidney disease was only 55. This is a very important study, well written and well-conducted.
However, there is a scandal in medicine, a scandal not openly discussed in scientific papers, one not yet reported by the mainstream press. The scandal is this: if you are on dialysis, the chances are very high that your kidney doctor thinks he is giving you vitamin D when he is doing no such thing and some drug companies encourage such ignorance.
Drug companies market very lucrative activated vitamin D drugs to nephrologists as “vitamin D.” The kidney doctors, in turn, think they are giving vitamin D to their dialysis patients when they are doing no such thing. If anything, the activated vitamin D analogs nephrologists use in kidney disease will lower 25(OH)D levels by turning on the enzyme that gets rid of vitamin D.
The ugly secret is that plain old dirt-cheap vitamin D would lower the amount of activated vitamin D analogs needed to treat kidney disease. We used to think it was all or none, the kidneys would either make activated vitamin D to maintain blood calcium or the kidneys would not, as in renal failure. However, it is not all or none; the more vitamin D building blocks available to the diseased kidneys, the more activated vitamin D diseased kidneys can make. And, tissues other than the kidney, such as the skin, pancreas, adrenal medulla, and certain white blood cells, can contribute to serum activated vitamin D levels, and probably would if they had enough of the building block (plain old, dirt-cheap old, regular old, vitamin D).
Just out: Vitamin D administration (plain old vitamin D) to renal dialysis patients reduces the need for expensive vitamin D analogues, reduces inflammation, reduces the need for medication that increases red blood count, and improves cardiac function.
As I was about to finish this tirade about vitamin D and kidney failure, the below open study was published on March 4, 2010 and I ordered it. (By the way, the Council has to pay $11.00 for every paper I get and only one paper in ten is worth reporting on). The study below confirms what the above authors predicted; plain old cheap vitamin D helps patients with kidney disease.
Matias PJ, Jorge C, Ferreira C, Borges M, Aires I, Amaral T, Gil C, Cortez J, Ferreira A. Cholecalciferol Supplementation in Hemodialysis Patients: Effects on Mineral Metabolism, Inflammation, and Cardiac Dimension Parameters. Clin J Am Soc Nephrol. 2010 Mar 4.
Dr. Patricia Matias and colleagues in Portugal gave vitamin D3 to 158 patients on renal dialysis, using a sliding scale of vitamin D3 administration dependent on baseline 25(OH)D levels. Some patients got 50,000 IU per week, some got 10,000 IU per week, etc. Their dosing regimen increased 25(OH)D levels from a mean of 22 ng/ml at the beginning of the study to a mean of 42 ng/ml during treatment, indicating half of patients still had levels lower than 42 ng/ml after treatment. Interestingly, most of the patients who did not increase their 25(OH)D very much had diabetes, suggesting the metabolic clearance (how quickly it is used up) of vitamin D is increased in diabetes. By the way, we know the patients took the vitamin D; the doctors gave it to them when they came in for dialysis.
The results of this study were amazing. After vitamin D administration, parathyroid hormone, albumin, CRP (a measure of inflammation), brain natriuretic peptide (a measure of heart failure), and left ventricular mass index (a measure of heart function) all improved significantly. The dose of activated vitamin D (Zemplar in this case) was reduced, and some patients were able to stop it all together. Also, the dose of two other drugs used in kidney failure, one to bind phosphorus and the other to raise hemoglobin, was reduced.
It is a tragedy that drug companies sell more expensive vitamin D analogs by having their drug salesman assure kidney doctors that the expensive vitamin D analogues are vitamin D, even if it kills their clients. But, with the brand new knowledge that kidney failure patients live much longer on vitamin D, the drug companies might want to do some simple math. They might make even more money if they kept their patients alive longer. True, they will need less vitamin D analogues and other expensive kidney drugs every day, but the patients may live many more days.
John Cannell, MD