In April, we chatted with John J. Cannell, M.D., about the function of vitamin D and the recent developments that affect our need to increase our dietary intake of vitamin D. This month, we will discuss optimizing our vitamin D intake.

Dr. Cannell graduated with a degree in zoology from the University of Maryland, where he was a member of Phi Beta Kappa. He received his M.D. from the medical school at the University of North Carolina. After a year-long surgery internship at the University of Utah and four years of practicing itinerant emergency medicine, he began as a general practitioner in the coalfields of Appalachia.

Later, Dr. Cannell left general practice and went back to school to study psychiatry. He moved to Atascadero, CA, in the late 1990s and began working as a psychiatrist at Atascadero State Hospital, the largest hospital in America for the criminally insane. There, his long-held interest in clinical nutrition was re-awakened. The further he studied nutrition, the more and more vitamin D3 (cholecalciferol) caught his attention.

As Dr. Cannell began to study the effects of vitamin D, he immediately realized that the recommendations of the Food and Nutrition Board (FNB) of the IOM were placing many Americans at risk. He found that vitamin D insufficiency was common in older adults, even using conservative cutoff points for vitamin D blood levels. Dr. Cannell was left wondering whom he should believe, Nature or the FNB? In 2003, he recruited professional colleagues, scientists and friends for a board of directors and took the steps necessary to incorporate The Vitamin D Council as a tax exempt, nonprofit, 501(c)(e) corporation.

In September 2006, Dr. Cannell’s seminal article, “Epidemic Influenza and Vitamin D” was published in the Journal of Epidemiology and Infection. The article presented a revolutionary new theory on vitamin D’s link to influenza and was co-written with some of the world’s top vitamin D experts.

Passwater: Dr. Cannell, how do we know how much vitamin D is required for our optimal health?

Cannell: We have learned a lot about this question by studying the amount of a compound called 25-hydroxy vitamin D (or 25-(OH)D). After vitamin D is formed in the skin or put in your mouth, it goes to the liver where it is hydroxylated by two enzymes to form 25-hydroxy vitamin D, which can be measured in the blood. This is used to determine vitamin D adequacy.

For years and years, the range in all major reference labs was about 20–100 ng/ml. It was found people having levels of 10 ng/ml or less often had rickets or osteomalacia, the adult form of rickets. So, 20 ng/ml is high enough not to get rickets, but 20 ng/ml is still on the low end.

On the other hand, we have lifeguards in Miami Beach in August who have levels near 100 ng/ml. This is high on the normal range of 20–100 ng/ml. As more and more research came out, the lower range moved from 20 to 25 to 30 ng/ml. Now, most labs list 30 ng/ml as the lower limit of normal.

So, the question is not what is the best vitamin D intake, but what is the ideal 25-hydroxy vitamin D level in the blood.

There are several ways to think about this. One is regarding public health for the entire population, understanding that the more melanin you have in your skin, the lower your vitamin D levels will be. Some people have so little melanin and are very efficient at making vitamin D that a short walk to the mailbox will generate quite a bit.

But the more melanin you have in your skin, the lower the level of 25-hydroxy vitamin D you will have. So, when you think about a public health situation, you have to think about all these people who have very low levels such as African Americans. That’s one of the reasons that we recommend 5,000 international units (IU)/day because 95% of the people who take 5,000 IU of vitamin D/day will get the full health benefits of vitamin D and no one will get toxic effects.

Intake of 5,000 IU of vitamin D/day will generally lead to a 25-hydroxy vitamin D level of about 50–70 ng/ml, although that amount varies considerably from person to person. There’s a large genetic factor in the determination of your vitamin D level, and this surprises a lot of people. You inherit your vitamin D machinery and this affects how high or low your actual vitamin D level is in the blood. If you think about it in terms of public health involvement, it’s a Gaussian distribution where you want to shift the curve to the right so that nobody’s levels are down around 15 or 20 ng/ml; at the same time, nobody has levels of 150 ng/ml.

Levels of 50 ng/ml are ideal for one other reason. Think of vitamin D as being like a lake on top of a mountain. There are many streams that flow down the mountain from the lake. As you go down the mountain, there are hundreds of pools that are being fed by this lake at the top. When the lake gets low, the pools dry up. This is much like the way vitamin D synthesis works. Vitamin D in the form of 25-hydroxy vitamin D is the lake on top of the mountain. This lake is involved with calcium function, so the lake determines your blood calcium levels. This is a life or death situation as blood calcium must not fall too low or you die.

The primary function—and by primary, I mean the minute-to-minute life-sustaining function—of vitamin D is to maintain your serum calcium levels. Serum calcium is a cation that must be regulated precisely. If it goes up too high, you start calcifying your internal organs and you get cardiac arrhythmias; if it gets too low, you also get cardiac arrhythmias and all kinds of other problems. You can die from either too high or too low calcium levels in your blood.

If your body only has a little vitamin D, the lake won’t be dry, but it will be low with nothing left over for the streams and pools below. The pools lower down are those that we have been discovering over the last 10 years: the pools of autism, breast cancer, hypertension, congestive heart disease, diabetes, dental caries, macular degeneration, influenza and more. All these pools are underneath the primary lake of vitamin D. To get the full benefit of vitamin D, the lower pools as well as the lake above must be full. We don’t yet know exactly how high each pool must be, and we don’t know which pool is filled first, second or last.

Passwater: There is a similar hierarchy for selenium. The first priority for selenoproteins is for various general antioxidant defenses, the second hierarchy is for brain functions and the third priority—if there is any selenium still available—is for anti-cancer functions via apoptosis.

Cannell: We do know that there are 38 organs in the body that use vitamin D. Its need is certainly widespread. But, if you think about it that way, if you realize that we don’t have to know the details, and that all we need to know is that when all those pools are full, what happens? If all those pools are full, the body would start saving some of the vitamin D itself, not the 25-hydroxy vitamin D, for future use. This vitamin D is stored in muscles and fat.

Most people’s vitamin D level (not the 25-hydroxy vitamin D) in their blood is almost zero! The levels are so low that they are undetectable. This implies that none of the 25-hydroxy vitamin D is getting all the way down the mountain. It is all being used up on the way down the mountain, so none of the vitamin D is being saved for the future.

Now, if you found someone who had a vitamin D level of 50 ng/ml, as well as a 25-hydroxy vitamin D level of 50 ng/ml, you could then say that this person definitely has enough vitamin D. He no longer suffers from what is called chronic substrate starvation. If your vitamin D level is zero—not the 25-hydroxy vitamin D level, but the vitamin D itself, which is something no one ever measures because it is very difficult to do—you are suffering from chronic substrate starvation by definition. None of the 25-hydroxy vitamin D got all the way down the mountain, so no vitamin D is being stored for the future.

Passwater: Chronic substrate starvation! Exactly what does the term mean? Vitamin D insufficiency?

Cannell: It means the substrate—in this case, vitamin D the building block, for the prohormone (25-hydroxy vitamin D) and active steroid (1,25-hydroxy vitamin D)—is in short supply and the body is starved for vitamin D.

There was an elegant study done by a researcher that I admire, Professor Robert Heaney, M.D., of Creighton University. He wanted to find out what level of 25-hydroxy vitamin D was needed to get vitamin D to be measurable in that person. He found that if your 25-hydroxy vitamin D level was 30 ng/ml, your vitamin D level was zero. That means if your 25-hydroxy vitamin D level is 30 ng/ml, not all the pools are full and you have chronic substrate starvation.

Passwater: But, don’t the new guidelines from the Institute of Medicine (IOM) recommend 20 ng/ml of 25-hydroxy vitamin D as being adequate? This recommendation would still result in chronic substrate starvation!

Cannell: Yes, it would. It is simply nonsense, and dangerous nonsense.

At around 30 ng/ml of 25-hydroxy vitamin D, about 25% of people started having detectable vitamin D levels in their blood. At 35 ng/ml 25-hydroxy vitamin D, half of the population will also have detectable amounts of vitamin D in their blood. If you get up to 50 ng/ml of 25-hydroxy vitamin D in your blood, then everyone has some detectable vitamin D in their blood as well, with more stored in their muscles and fat.

That means that if your blood level of 25-hydroxy vitamin D is 50 ng/ml or more, you will not have chronic substrate starvation. If your level is 35 ng/ml, you have a 50% chance of having chronic substrate deficiency. If it is 30 ng/ml, you have a 75% chance of having chronic substrate deficiency.

Passwater: Please remind our readers once again what is the practical health consequence of having chronic substrate starvation.

Cannell: It means the body does not have enough of one of the building blocks it needs—in this case, enough vitamin D—to meet the body’s needs.

Passwater: And, the IOM recommendation for blood level of 25-hydroxy vitamin D is what again?

Cannell: 20 ng/ml.

Passwater: There seems to be a disconnect between the facts and the IOM recommendations. Is the IOM committee unaware of Dr. Heaney’s findings?

Cannell: They are aware, but they were a political committee. For example, if they said 30 ng/ml, they would also have had to address food fortification, which they did not want to do. And, if they said 30 ng/ml, they would have had to make recommendations based on skin color, another politically impossible thing for them to do. (Very few Blacks have levels of 30 ng/ml, but about 50% of Whites do. So, by saying 20 ng/ml, they hoped to avoid the skin color issue.)

Passwater: You recommend between 50 and 70 ng/ml.

Cannell: Yes, about what people who work outdoors have in the summer.

You also have to ask the question, what group are we talking about. Is the person someone who is in apparent perfect health other than chronic substrate deficiency? If so, 50 ng/ml may be fine. Or, are we talking about a child with autism? In the case of autism, we want the level that helps the child.

Passwater: What I find interesting is that virtually all of the vitamin D researchers that I speak with all recommend 5,000 IU of supplemental vitamin D per day, the same as The Vitamin D Council.

Cannell:  Yes. There’s an interesting article by Martin Mittelstaedt, who writes for the Toronto Globe and Mail, in which he polled vitamin D researchers. He asked them, “You have been doing vitamin D research. How much vitamin D do you take?” Do you know what the average was for the vitamin D researchers? 5,000 units a day.

Passwater: Well, that’s what I found, and recently several physician columnists who commented about the new IOM recommendations said they were taking 5,000 IU  and were recommending between 2,000 and 5,000 IU for their patients.

Cannell: Yes. I find the same thing; even those who are recommending only 2,000 IU to their patients are taking 5,000 IU themselves.

Passwater: I’ve seen the same phenomenon over the years for other nutrients, especially the antioxidant nutrients. The thinking is something like, “Well, there isn’t enough absolutely conclusive evidence that this much is needed. But, I am very familiar with the vitamin D research and from what I am seeing, I want to take 5,000 IU for myself.” They are afraid that they will be criticized by anti-supplement forces that speak out against doctors who recommend supplements. So, they take the safe course and recommend what they can justify by conclusive evidence and then take what the leading edge of research suggests is right for themselves.

Most of our readers may be unaware that the FDA tried to limit the amount of vitamin D in dietary supplements to 400 IU and were pushing to even lower it further. On December 19, 1972, FDA Commissioner Alexander M. Schmidt proposed, by publishing in the Federal Register, a regulation of the FDA that preparations of vitamin D in excess of 400 IU per dosage unit be restricted to prescription sale and that such dietary supplements be labeled accordingly.

Now how many people would that have harmed? If the body of scientific evidence shows that supplements of 5,000 IU are required to optimize blood levels of vitamin D, how many people would have been sentenced to cancer and various other diseases by this stupid and arbitrary action of the FDA?

Solgar submitted voluminous factual material and expert opinions opposing the proposed regulations to the FDA, but the FDA Commissioner ignored them and the regulation was promulgated on July 25, 1973 to become effective October 1, 1973 (38 Fed. Reg. 20723, 20725 [1973]). We took Secretary of Health Casper Weinberger and FDA Commissioner Alexander M. Schmidt to court to have this action stopped.

At first, we (Solgar joined by the then National Nutritional Foods Association) were not successful in the court and we had to appeal to United States Court of Appeals, second Circuit. Attorneys Milton Bass and Robert Ullman argued the appeal on October 19, 1973 and the court decided in our favor on December 11, 1973. Our industry was able to continue to provide products based on science to improve the health of people.

Another part of the story in learning about widespread vitamin D deficiency is that one of the most frequently used reference analytical laboratories that determine how much vitamin D is in patients’ blood was giving the wrong results. You uncovered this problem and led to having it corrected. Please tell our readers a little bit about this problem.

Cannell: I was the first to report that Quest Laboratories, the largest reference laboratory doing vitamin D analysis in the United States, was reporting incorrect results that made it appear the patients had more vitamin D than they actually did. Levels of 25-hydroxy vitamin D may have actually have been 20 ng/ml, but Quest was sometimes reporting it as twice that.

I reported this on-going error in my newsletter in July 2009. It was first picked up by Dr. Joseph Mercola, D.O., and then a trade journal for reference laboratories reported on it. Then, The New York Times reported it in December 2009. Quest then announced that they fixed the problem.

One of the things that The Vitamin D Council does is to check on laboratory results. We are doing a study in which we have asked our readers to have their blood analyzed for 25-hydroxy vitamin D by two different laboratories on the same day. We asked our readers to have their blood drawn and sent to Quest and then have it drawn again the same day and sent to LabCorp. LabCorp uses a technique that is the standard in the field. So, we are seeing whether or not Quest has solved its analytical problem.

Passwater: What was the nature of the problem? Was it an extraction problem?

Cannell: Yes. As you know, you have to prepare your sample specimen extremely carefully. This technique requires a highly skilled operator, who often holds a Ph.D. When vitamin D tests became the single most-requested lab test in the country, which happened about a year-and-a-half ago, the number of requests that Quest was getting for vitamin D increased 100-fold. You can’t rush the test with the procedure that Quest was using. Basically, it is a research method used to identify substances in blood. In contrast, the technique used by other reference labs is a simplified, fool-proof method. The standard technique is mechanized, more like most laboratory tests, and it doesn’t require an especially skilled operator. It can be done by most technicians.

Once that huge upswing in demand for vitamin D testing occurred, you can imagine the effect it had on the operators of this highly specialized instrument Quest uses. There were thousands of blood samples waiting for the analyst to run. You can guess what happens then. They’re human beings and they may rush the procedure to get everyone’s tests done. They don’t want to face a big backlog every day. When the procedure is rushed, the extraction is incomplete and not representative of the amount in the sample.

Passwater: How did you uncover the testing problem?

Cannell: I used to work in a state forensic hospital, where patients would come out of solitary confinement from prisons and would be checked out by us because they often became psychotic. We knew that they were not getting any sun. Even the hour that they were sent outside to exercise in a shaded area was not enough to give them adequate vitamin D, especially the darker skinned inmates. The Quest results said that their 25-hydroxy vitamin D levels were fine and I knew they were not. I knew the Quest results were impossible.

There is a need to have vitamin D tests done so that doctors can learn how small of a dose 5,000 IU is. The only way that doctors can learn that lesson is to have a vitamin D test, give 1,000 IU/day and then be surprised that nothing much happens. Next, give 2,000 IU/day; the blood level may go up a little bit in the spring, but in the fall or winter, the level may actually go down. That is because of the overpowering effect that the sun has on vitamin D levels. The decrease in UVB radiation during the autumn overpowered the effect of the 2,000 IU per day.
Passwater: Didn’t this huge demand for vitamin D testing result in a move by the insurance companies to discourage them?

Cannell: There have been attempts by two different Medicare Regional Districts to stop paying for vitamin D tests. The Vitamin D Council was involved in fighting back through letter-writing campaigns. So far, we have been successful in fighting back those attempts, as far as I know.

Passwater: Many doctors practice defensive medicine and hesitate to recommend supplements unless they have laboratory evidence of deficiency.

Cannell: That’s a big part of the problem. However, the fact is that vitamin D blood tests really aren’t needed. All you have to do is to take 5,000 IU daily. I say they are not needed because if the doctors and patients are really knowledgeable about vitamin D, about the physiology and pharmacology, they know 5,000 IU/day is not very much. The problem is that the patients seem to think that 5,000 IU is a lot.

Passwater: Is this because they think 5,000 is a large number?

Cannell: Yes, but it is not a large amount by weight. The trouble is that 5,000 IU is only an eighth of a milligram of cholecalciferol; that’s only 125 micrograms. Micrograms, not milligrams! There are 1,000 micrograms in a milligram. When I explain to them how 5,000 IU actually is 125 mcg, they say, “Well, I’ll take that.”

Passwater: Yes, the average person can find the conventional systems for expressing quantities of nutrients to be confusing—USP Units, International Units, enzyme units, grams, milligrams, micrograms, etc.

The system of using standardized units was developed to measure biochemical activity long before the structure of the nutrient was determined. Not all International Units correspond to the same weight of a given nutrient. As an example, 1 IU of vitamin E can be 0.671 mg of natural (RRR-alpha-tocopherol or d-alpha-tocopherol) vitamin E, or Y mg of synthetic (all-racemic- alpha tocopherol or dl- alpha-tocopherol) vitamin E, or 0.735 mg of d-alpha-tocopheryl acetate, or Z mg of gamma-tocopherol. International Units for the various vitamins are not the same weight units and they are not directly interchangeable. They must be converted to weight measurements for meaningful comparisons.

The international unit for vitamin D activity dates back before 1931 and was based on the antirachitic activity for the rat.

One thousand IU of vitamin D is only 25 mcg of cholecalciferol and the same 25 mcg for the other form of vitamin D, the irradiated analog whose patent has expired, ergocalciferol (also called vitamin D2).

After a doctor becomes familiar with the pharmacology of vitamin D, all that has to be done when a patient comes in is to look at his/her skin type, look at the amount of melanin in the skin, ask about his sun behavior, what kind of job he has, does he have a covered garage, does he get up in the morning and put on his sun block, drive his car to work, etc. If the patient works inside, wears sunblock, and doesn’t take any vitamin D, he has a 100% chance of being vitamin D deficient. He doesn’t need a blood test.

So, 5,000 IU isn’t a lot of vitamin D and a lot of physicians and vitamin D researchers agree with your recommendation. Next month, we can chat a little bit about the safety/toxicity facts and how the U.S. Food Administration was pushing to lower the allowed amount of vitamin D in supplements to 200 IU in the 1980s. Then, we can discuss your findings, Dr. Cannell. WF

Dr. Richard Passwater is the author of more than 40 books and 500 articles on nutrition. He is the vice president of research and development for Solgar Vitamin and Herb. Dr. Passwater has been WholeFoods Magazine’s science editor and author of this column since 1984. More information is available on his Web site,

Published in WholeFoods Magazine, June 2011