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Is Vitamin D Supplementation Helpful or Hazardous?

Posted By Cameron On May 21, 2009 @ 1:37 am In Health & Nutrition | 10 Comments

(This article was updated on May 22, 2009, to add more on the growing mainstream consensus to reduce widespread vitamin D deficiency [around 40% to 60% of US population!] via dietary supplements and on the Marshall Protocol and related research which disputes this position.)

The last year has seen the release of numerous studies and articles about the wonders of vitamin D ^[1]. The reports are quite convincing and consistent that most people don’t get enough vitamin D and that low levels of it increase the risk of health problems of a wide range of diseases ranging from common cardiovascular disease, cancer, and depression to less common multiple sclerosis and autism.

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Public Health Call for Raising Vitamin D Levels

Already calls to action are being made. For example, top researchers from the medical schools and biological sciences departments of the University of California are banding together to call for widespread use of vitamin D3 supplements at intakes around 2000 IU per day for adults:

(from The Vitamin D Deficiency Epidemic: A Call to D*action ^[4])

There are newly appreciated associations between vitamin D insufficiency and many other diseases, including tuberculosis, psoriasis, multiple sclerosis, inflammatory bowel disease, type-1 diabetes, high blood pressure, increased heart failure, muscle myopathy, breast and other cancers which are believed to be linked to the non-calcemic actions of the parent vitamin D and its daughter steroid hormone. However a causal link has yet to be proven by appropriate vitamin D intervention studies.

It is projected that the incidence of many of these diseases could be reduced by 20%-50% or more, if the occurrence of vitamin D deficiency and insufficiency were eradicated by increasing vitamin D intakes. The appropriate intake of vitamin D required to effect a significant disease reduction depends on the individual’s age, race, lifestyle, and latitude of residence. New evidence indicates that the intake should be in the range of 2000 IU per day for adults. Intake of 2000 IU/day is the current upper limit of the National Academy of Sciences, Institute of Medicine, Food and Nutrition Board.

It is well documented that the darker the skin, the greater the probability of a vitamin D deficiency. Even in southern Arizona, 55% of African Americans and 22% of Caucasians are deficient.

The COST to our society of vitamin D deficiency is $100-$200 billion dollars a year.

A Scientists’ Call to Action has been issued to alert the public to the importance to have vitamin D serum levels between 40 and 60 nanograms/milliliter to prevent these diseases. Implementing this level is safe and inexpensive.

Vitamin D Levels and Reductions in Diseases Risks

Vast numbers of studies say that vitamin D3 helps health in many ways. Other research and common sense indicates that our lifestyle today is likely to result in lower vitamin D levels and increased health problems related to them because of reduced sun exposure from spending a lot more time indoors than our ancestors did. As you may know, some people call vitamin D “the sunshine vitamin” because the human body manufactures it when exposed to sunlight.

One of our readers provided a link to a very interesting chart that attempts to correlate research on vitamin D levels with reductions in the rates of various diseases. You can take a look at it here ^[5] on the website of GrassrootsHealth. GrassrootsHealth is backing a major campaign to encourage vitamin D supplementation to achieve blood serum levels of 25D (the inactive form of vitamin D) between 40 to 60 ng/ml to reduce disease rates and mortality.

Interview with Dr. Cedric Garland on Vitamin D and Cancer Mortality

Vitamin D Deficiency

Nutrient deficiency diseases include anemia and neural tube defects (often caused by insufficient folic acid), scurvy (caused by insufficient vitamin C), and several others. Older definitions of vitamin D deficiency are based upon the level required to avoid the development of rickets. This presently is defined as 32 ng/mL (nanograms per milliliter) or higher. Dr. Heaney in the video below explains how this level was set based upon short-term deficiency, but that long-term deficiency was not considered.

Presentation by Dr. Heaney on Vitamin D Deficiency

As Dr. Heaney mentions, recent vitamin D research suggests that a better target for vitamin D serum levels is between 40 to 60 ng/mL and this may be achieved for nearly 100% of the population with around 2600 IU per day of vitamin D3 supplements plus normal diet and sun exposure with nearly zero risk of toxicity. He also points out that dosing elderly patients in nursing homes and hospitals with 100,000 IU of vitamin D3 once every two months may be a way to very inexpensively and drastically reduce fractures, bone loss, and other complications of deficient vitamin D.

Current mainstream research suggests that getting too much vitamin D is not a likely risk. Evidence of toxicity from vitamin D is claimed to start with only very high vitamin D intakes that lead to blood serum 25D levels of 100 ng/mL or higher. It is claimed that all known cases of vitamin D toxicity involved intakes of over 40,000 IU per day for extended periods of time:

(from Wikipedia: Vitamin D ^[6])

The exact long-term safe dose of vitamin D is not known. In 1997 the U.S. Dietary Reference Intake Tolerable Upper Intake Level (UL) of vitamin D for children and adults was set at 50 micrograms/day (2,000 IU), but this is viewed as outdated and overly restrictive. A 2007 risk assessment suggested that 250 micrograms/day (10,000 IU) in healthy adults should be adopted as the tolerable upper limit.[38] In adults, sustained intake of 2500 micrograms/day (100,000 IU) can produce toxicity within a few months.[2] For infants (birth to 12 months) the tolerable UL is set at 25 micrograms/day (1000 IU), and vitamin D concentrations of 1000 micrograms/day (40,000 IU) in infants has been shown to produce toxicity within 1 to 4 months. Other sources indicate that the threshold for vitamin D toxicity in humans is 500 to 600 micrograms per kilogram body weight per day.”[39] In rats an oral LD50 of 619 mg/kg is noted.[40] All known cases of vitamin D toxicity with hypercalcemia have involved intake of or over 1,000 micrograms/day (40,000 IU)[41].

Vitamin D3 Supplementation

Much of the new vitamin D research makes it appear that vitamin D3 supplementation could solve a lot of problems and help ensure long-term health. It’s cheap, widely available, and so many studies are saying it is good for health. Many of them are advocating as much as 5000 IU per day of vitamin D, especially for people like me who don’t get out in the sun much.

Taking 2000 IU of vitamin D3 supplements twice per day was one of my methods to improve health. Can I say it worked? I could, but I’d be irresponsible to say it did because I really don’t know if it did or didn’t. I felt fine, but not much different than before taking so much vitamin D3.

Health effects are so complicated, it is difficult to determine what works and what doesn’t without lots of testing and experimentation and many research subjects and sometimes several years of therapy or supplementation to observe long-term effects. Unfortunately, there’s just one of me, I don’t have a fortune to spend on getting frequent extensive lab tests, and I haven’t yet acquired a time machine to find out what my health future will be in 10 or 20 years.

Increasing Caution Regarding Vitamin D3 Supplements

However, I’ve recently cut back on my vitamin D supplementation as I’ve run across a compelling set of arguments that says vitamin D may not be so good for my health after all. I’m still skeptical, but recall reading about how for decades nobody believed the arguments of a small group of scientists who argued that many human stomach ulcers ^[7] were due to bacterial infections. In fact they were ridiculed. But they were right, as was eventually acknowledged by growing research that proved that about 80% of ulcers are caused by Helicobacter pylori ^[8] bacterial infection. In 2005, two of the key researchers in this discovery, Dr. Barry Marshall and Dr. Robin Warren, were award the Nobel Prize in Physiology or Medicine for their research.

Common sense can be wrong, and so can the consensus of the medical community. When it is, it can be very difficult to figure out the truth of the matter. I’m at this point somewhat confused about the vitamin D debate and think that for some people, vitamin D supplementation may not be a good idea. Let me explain why.

Vitamin D Isn’t Vitamin — It Is a Steroidal Hormone!

Vitamin D is not really a vitamin but a steroidal hormone. More precisely, it is a secosteroid ^[9]. This is a common misunderstanding, but a very important one.

There is a school of thought on the action of vitamin D in the body that says rather than always helping the immune system, it sometimes acts as an immunosuppressant like many other steroids do. Microbiology researcher Trevor Marshall, Ph.D. ^[10], is one of the main advocates of a theory that contends the seemingly beneficial effects of vitamin D supplementation are really the result of short-term reduction in inflammation by compromising the ability of the immune system to fight long-term slow-growing bacterial infections that result in large releases of toxins and inflammatory cytokines ^[11] as bacteria are destroyed. Stop destroying the bacteria, and the inflammation goes down. But the infection spreads, causing other hard-to-treat health problem such as fibromyalgia ^[12], chronic fatigue syndrome ^[13], Crohn’s disease ^[14], rheumatoid arthritis ^[15], and other diseases believed to have origins in autoimmune disorders or unknown causes.

Trevor Marshall apparently suffered from a disease known as sarcoidosis ^[16] for much of his life. Researchers discovered that part of what occurs in this disease is that excessive levels of the activated form of vitamin D (1,25D) are generated by malfunctioning human white blood cells. Marshall had noticed that his symptoms flared up with sun exposure, and speculated that vitamin D might be involved in the illness. Marshall has come up with an experimental therapeutic technique to treat chronic diseases that function somewhat like sarcoidosis. His first patient was himself. More of the story of its development can be found in History of the Marshall Protocol ^[17].

Unsurprisingly given the egocentricity of many humans, the treatment protocol has been called the Marshall Protocol ^[18]. It involves long-term treatment with pulsed and varied cycles of multiple antibiotics (minocycline ^[19] is one of them) that inflict damage on the bacteria involved. The drug olmesartan (Benicar) ^[20] is used to kick the inactive form of vitamin D and L-form bacterial proteins out of the vitamin D receptors and to properly activate them to get the intracellular immune system working properly. Patients are taught how to lower their vitamin D intake levels as far as they can. This can be extreme including steps such as blacking out your windows, not going outside during daylight, and avoiding all vitamin D rich foods such as fish, milk with vitamin D fortification, and eggs.

Some people who have tried the Marshall Protocol for diseases believed to have an autoimmune component such as fibromyalgia and chronic fatigue syndrome claim that it has saved their lives, others claim it has just made them more miserable than before. It appears there is not enough evidence to know if it really works. Further, it seems that advocates of the Marshall Protocol want to try to apply its reasoning to many poorly understood chronic diseases yet don’t really know who it may help and who it may hurt.

Marshall and some other researchers believe that many chronic inflammatory diseases which are believed to have unknown causes or may be autoimmune disorders could be caused by slow-growth bacterial infections that interfere with the operation of the vitamin D receptor in human cells. Such diseases include chronic fatigue syndrome, fibromyalgia, chronic Lyme disease, sarcoidosis, and likely many others. Writer Bryan Rosner in his book The Top 10 Lyme Disease Treatments: Defeat Lyme Disease with the Best of Conventional and Alternative Medicine ^[21] discusses his own use of the Marshall Protocol to treat chronic Lyme disease. He believes it has been effective for him. In this way, he’s a bit like Trevor Marshall himself — a man motivated to fix his own health problems who has tried lots of ideas and stumbled across something that seems to work and therefore wants to share it with others.

L-Form Bacteria

Marshall and others pointing to chronic diseases having bacterial origin point out that there is an unusual form of bacteria known as the “L-form” that seems to explain why these bacteria are not easily killed off by the human immune system and regular antibiotics. What is really unusual about the bacteria is that they infect the body inside human cells. This is quite different from how normal bacterial infections occur.

L-form bacteria ^[22] bacteria are bacteria that exist without normal cell walls. They are also called “cell wall deficient” bacteria. This enables them to get inside of human cells and hide there, safe from many of the normal human immune system defenses. Inside human cells, they can continue to reproduce and slowly spread the infection. Additionally, some of them may possess the ability to create biofilms ^[23] that help further protect bacteria from attack by the human immune system and antibiotics.

L-form bacteria are not a recent discovery. They were documented in 1935 and possibly discovered even earlier. What today is a major controversy about them is whether they cause human infections and if so what are the results of those infections. The infectious L-form bacteria are called Th1 pathogens in much of the literature related to this theory as this refers to their capability of infecting “T helper cells type 1” that are part of the human immune system.

It is believed that there are at least several dozen species of bacteria that can transform from “wild form” with cell walls into “L-form” without cell walls. This might explain why observations of L-form bacteria inside human cells from patients suffering a particular chronic inflammatory disease include a variety of bacteria.

Moreover, it is very possible that modern antibiotics are increasing the number of L-form bacterial infections in humans and animals:

(from Understanding L-form Bacteria ^[24])

Multiple studies have also shown that when one of the Beta-lactam antibiotics (a class of antibiotics that includes penicillin) are applied to wild-type bacteria in a Petri dish, small colonies of L-form bacteria form on the edges of the plate. “Treatment with penicillin does not merely select for L-forms (which are penicillin resistant) but actually induces L-form growth,” states researcher Josep Casadesus in a paper about L-form bacteria published last month in the medical journal BioEssays.[3]

Why Studies Showing Vitamin D Health Benefits Are Flawed

One of the best explanations for the view that vitamin D supplementation can cause health problems that I’ve run across is an article The Truth About Vitamin D: Fourteen Reasons Why Misunderstanding Endures ^[25]. It’s really long, but makes some very good points and is extensively footnoted. If you’re at all interested in your health, I’d suggest you read it for yourself. Set aside at least half an hour to do so — it’s quite long and thought-provoking and is likely to get you interested in looking at some of the linked content, too.

One of the points is that lowered vitamin D serum levels as measured by 25(OH)D tests are a symptom of an illness, not a cause. Determining cause and effect in medicine can be really difficult as there are so many interrelated factors and unknown variables. The articles also points out that many studies done regarding vitamin D health effects never measured the blood 1,25(OH)D level, only the 25(OH)D level. This is claimed to be significant because the researchers backing this theory claim that a lot of the people who have low levels of the inactive form 25(OH)D also have very high levels of 1,25(OH)D which is the activated form of vitamin D. Thus, as this argument goes, these people don’t really have low vitamin D levels at all. The claim is that their problem is that the activated vitamin D in their bodies doesn’t work right because of L-form bacterial infections that block vitamin D receptors in cells.

As mentioned, the L-form bacteria are unusual in that they grow inside of human cells and are therefore harder for the human immune system to destroy. Trevor Marshall claims they produce proteins that block vitamin D receptors, meaning that even very high levels of activated vitamin D (which would be shown by the 1,25(OH)D test) don’t trigger the results that they should.

Such L-form bacterial infections could be more widespread for some reason than they were in the past. For example, our current practice of medicine, widespread usage of antibiotics, food additives, or longer lifespans may allow these bacteria to have more time to spread within individuals and increase success of spreading between people, too.

Some molecular biologists are claiming that both the proteins from L-form bacteria and vitamin D in the unactivated form 25(OH)D (also called 25D) block the vitamin D receptor, all of this without activating the transcription of some immune system genes that the 1,25(OH)D activated form (also called 1,25D) of vitamin D would trigger. Consequently, for people who are already infected with L-form bacteria, adding vitamin D3 supplements could make their long-term health worse.

Many Commonly Held Beliefs About Vitamin D May Be Wrong

Even the commonly held belief that rickets is caused by vitamin D deficiency may not be accurate ^[26]. There is evidence that it is really caused by phosphorous deficiency that is a secondary result of calcium deficiency but that these are not intrinsically related to vitamin D deficiency because experiments that knock out vitamin D receptors in mice didn’t result in the mice getting rickets.

However, Marshall’s theories are widely controversial. With a little digging I found people who claim to have tried the Marshall Protocol to treat chronic diseases for which they could get little if any conventional medical help. They have mixed opinions on the effectiveness of the treatment. Some of them point to the Marshall Protocol’s guidance to lower vitamin D intake as low as possible was something that they achieved as indicated by blood tests showing levels less than 10 ng/mL, far below normal medical recommendations. But some of those people claim they had significantly accelerated bone density loss. The counterargument coming from Marshall and his advocates is that this loss of bone density could have been caused by prednisone or other steroidal treatments that were used prior to the Marshall Protocol.

Who’s right? I’m not sure. There need to be more comprehensive tests and monitoring done on patients using Marshall Protocol and they need to be done by groups other than those controlled by Trevor Marshall. Marshall needs to start sharing his molecular biology models that show how his theory of vitamin D receptor activation and blockage works so that they can be studied by other molecular biologists.

Furthermore, it’s not just the Marshall group that needs to make some changes. The pro-vitamin D crowd led by Dr. John Cannell ^[27] of the Vitamin D Council ^[28] needs to read and comprehend Marshall’s work before trashing it in a fashion that shows they didn’t understand it. Vitamin D studies also should be monitoring both 25D and 1,25D forms of vitamin D in the body to understand if perhaps some patients do respond to certain forms of vitamin D negatively as Marshall is claiming.

Both sides have possible motives to distort the vitamin D debate. The Vitamin D Council ^[28] is aligned with many of the researchers and supplement manufacturers, meaning that besides the obvious human nature of “wanting to be right” there could also be financial incentives that might influence some study outcomes. As for Trevor Marshall, he’s filed patents on the Marshall Protocol (click here ^[29] to see one of them) and could benefit financially if he’s right. To be clear, having financial motives do not mean that people are automatically greedy liars. But it is possible they could subtly influence even well-meaning people to reach conclusions that aren’t represented quite accurately.

“Human Element” May Obscure That Both Sides Are Partially Correct

It could be that both sides are more right than wrong, but their egos and agendas get in the way of finding the truth. I have done some reading in the area of the politics and sociology of science. Science is driven by people, and these people often have ego-driven competitiveness just like people in many other fields. Just the name “Marshall Protocol” all on its own points to some level of egotism. One of the books I recall reading that did a great job on portraying the problems caused by ego, competition, and the human element in scientific research is James Watson’s book The Double Helix: A Personal Account of the Discovery of the Structure of DNA ^[30]. If you think that all scientists are objective, analytical, and dispassionate, this book will help you see that’s not really the case.

If I were forced to select one possibility most likely to be the truth given the material I’ve reviewed, it would be that vitamin D supplementation is beneficial to most but not all people. It does appear there is evidence that it could be harmful to some people with L-form bacterial infections and certain chronic diseases including chronic fatigue syndrome, sarcoidosis, and Lyme disease. However, figuring out what group you are in may not be so easy to do as it seems current medical science cannot readily discriminate between these groups, in part because of inadequate understanding of L-form bacterial infections and how to detect them.

Misunderstanding of Vitamin D Could Lead to Tragedy

It’s really hard to know what the truth is about this matter, but I’m worried about the truth being discovered only after widespread actions are taken that may turn out to be dangerous to some people. Vitamin D supplementation is becoming extremely common and it is being added into more and more foods. Doctors are recommending increasingly high dosages of it for patients. At some hospitals, it is standard procedure to give cardiac patients 50,000 IU or even 100,000 IU of vitamin D3 on admission and to recommend between 2000 IU to 5000 IU per day thereafter.

If it turns out that massive vitamin D3 supplementation is really only masking the symptoms of L-form bacterial infections while helping them spread further, it could be this advice is going to harm a lot of people. It is really important to figure out what the truth is quickly, before tens or hundreds of millions of people’s lives could be shortened due to misinformation and resultant mistakes.

However, it appears that questioning vitamin D today is a politically incorrect thing to do, just as questioning the assertion that ulcers were not the result of infections was once politically incorrect. If the vitamin D fans are wrong, it may be decades and thousands or millions of premature deaths later by the time it is proven to be the case. Conversely, if the researchers blaming L-form bacterial infections for many health problems are wrong and vitamin D supplementation could have helped many that avoid it because of L-form bacteria concerns, that would also be a tragedy.

So Should I Use Vitamin D Supplements Or Not?

I’m not coming down on either side of this debate, at least not yet. That’s because both sides have arguments that on the surface look plausible. The common sense factor about vitamin D deficiency and correlations with diseases and reduced sun exposure does sway me, but I’m also alarmed by some of the really obscene “scientific politics” examples over the years that have prevented unorthodox theories like those of Trevor Marshall from being accepted until decades longer than it should have taken.

I’m hoping that some good solid objective research will provide the answers in the next couple of years and the controversy will be resolved. But there’s no guarantee of this. This controversy could turn into another Helicobacter pylori ^[31] ulcer debacle or even into something as bad as the female hormone replacement therapy mess that unwittingly raised heart attack, stroke, and breast cancer risks for millions of women for many years before the side effects were discovered.

Until there are well-proven answers to the questions surrounding vitamin D and chronic inflammatory diseases claimed to be treatable with the Marshall Protocol, I’d suggest you be particularly careful if you think you suffer from an autoimmune disorder before you take vitamin D supplements. I suspect that someday it may be shown that the human body becomes more susceptible to L-form bacterial infection due in part to low vitamin D levels and overusage of antibiotics, but that once these infections set in then Marshall may be on the market with his concerns.

I myself plan to supplement with vitamin D at about 2800 IU per day via 400 IU from a multivitamin, 400 IU from calcium plus vitamin D, and 2000 IU from a vitamin D tablet. On the balance, it appears the benefits outweigh the risks given that I have not been diagnosed with any of the diseases that the Marshall Protocol is claimed to treat. You will ultimately have to make the decision of what is appropriate for yourself and your family.

You should consult with your physician. You can print this article and ask your physician to review it and request vitamin D blood serum 25D and 1,25D tests to see if you might have low 25D along with highly elevated 1,25D levels that may indicate the types of diseases the Marshall Protocol is designed to treat. Then set your vitamin D intake based upon those test results and the guidelines discussed earlier in the article.