Naked at Noon, Understanding Sunlight and Vitamin D- Excerpts with References

Print Friendly and PDF Copyright Krispin Sullivan, MS CN 2003

Excerpt from Naked at Noon, Understanding Sunlight and Vitamin D, Krispin Sullivan, CN- All materials are copyrighted and may not be copied, quoted, reproduced or used in any form without permission from the author.

How Humans Store D And Why This Is Really Important

The fat-soluble vitamins A and D store in the human body. The upside of storage? Mechanisms and capacity for storage imply we have the ability to hold onto a reserve available for use when environmental or dietary sources are low. The downside? This capacity for storage can be dangerous. Hypervitaminosis is the term used to indicate the presence of excess A or D and the metabolic consequences, which in the case of too much D can be very serious indeed.

In 1972 a team from the University Department of Medicine, The Royal Infirmary, Manchester, England set out to determine if and where vitamin D is stored in the human body. Vitamin D metabolites, including the three we are focusing on, are very very very small. Vitamin D in blood and tissue is measured in nanogram or nanomole amounts. To give you an idea of just how small, a nanogram is one billionth of a gram and if you haven't got around to metrics yet it takes 28,349,520,000,000 nanograms to make one ounce. As our bodies contain 'nano' amounts of any of the D metabolites, tissue storage studies need comparatively large amounts of tissue to analyze.

The Royal Infirmary study design used radioactively labeled vitamin D3. As the study explains "Because of the small dose of radioactivity used in these studies, large samples were required" adequate material could be obtained only at autopsy or from an amputated limb.' The authors explain further that this is an 'opportunistic study' which I will define as meaning, 'under these conditions, dying or having a limb amputated to be able to complete the study, you take whatever you can get'. 60 patients volunteered and received the radioactively labeled vitamin D injection. Of these 60 an unfortunate 6 supplied the samples for the study. Two other patients, who did not receive the D3 injection, but had been treated with oral ergocalciferol (D2) up until time of their deaths, also provided tissue samples.

With one exception all tissue donors were patients suffering from illness or injury serious enough to cause death or amputation. Four died from chronic renal (kidney) failure, one from cancer, one from post-operative complications, and one from biliary disease. In addition to the problem of serious illness possibly clouding the outcome, one of the subjects had been treated with large amounts of ergocalciferol (D2) before receiving the injection of radioactive vitamin D3. The remaining volunteers receiving the injection were low or deficient in vitamin D. A few of the limitations of the storage study include small sample size, time elapsed between the injection and analysis of samples, possible complications due to kidney failure as the kidney plays a major role in D metabolism and prior treatment with vitamin D. Even considering the limitations the study does offer us an approximation of D storage.

The researchers analyzed tissue samples of liver, spleen, kidney, heart, lung, thyroid, pancreas, adrenal, intestine, skin, bone, marrow; muscle, tendon, and fat to see where the radioactive vitamin D ended up and how much ended up in each part. They looked for just two of our Ds, cholecalciferol, and 25(OH)D.

And the results: Every tissue studied demonstrated vitamin D activity. This is interesting because at the time very little was known about the actions of D in tissues other than bone. Later researchers would locate receptors for vitamin D in all parts of our bodies as you have learned.(1)

After the injection the cholecalciferol cleared rapidly from the blood. Quick review: Whether from skin production, oral intake or an injection vitamin D travels first to the liver where the cholecalciferol begins its metabolic journey by conversion to metabolite 25(OH)D and other less well known metabolites. In this study some of the injected cholecalciferol was excreted in bile, either unchanged or as one of several metabolites of D, some was converted to 25(OH)D circulating in the bloodstream, and some, both cholecalciferol and 25(OH)D, was removed from circulation by being partitioned off into fat cells or bound to tissue proteins. Our livers play an important role in handling all of the fats and fat-soluble substances we ingest or produce in our bodies.

Your body has metabolic pathways designed to break down and get rid of excesses thereby maintaining the normal balance, homeostasis, necessary for functioning. The liver breaks down fat-soluble toxins and other fat-soluble elements such as estrogen and excretes them in bile. Fat-soluble toxins, drug residues from antibiotics or chemicals such as DDT or pCBs that overload the system are unable to be metabolized and excreted in bile. Excesses can be kept out of the bloodstream by being stored in fat tissues as a protection from toxicity. In this study the path of vitamin D excess appears to be similar. When serum levels were elevated by the injection the body responded by storing excess in fat cells.

perhaps this occurred because the dose given was much greater than a physiological dose, like a toxin needing to be trapped outside of circulation to prevent damage. Circulating in the bloodstream high levels of vitamin D can be dangerous causing damage to arteries and promoting calcification of soft tissues.(2;3) At a minimum, excessively elevated serum D may disrupt normal feedback mechanisms necessary to regulate the D endocrine system. perhaps this occurred as a natural process to keep blood levels of vitamin D within normal ranges and store any extra for later use.

Back to the study-The tissues containing the highest amounts of vitamin D, totals that include both cholecalciferol and 25(OH)D, were fat and bone marrow (high in fat content). Total D activity recovered from voluntary muscle nearly equaled that found in fatty tissue because while concentrations of D were lower, total body mass was greater; the body contains more muscle than fat. As discussed before vitamin D goes through many changes over time becoming any one of a number of metabolites. The time between the initial injection and the analysis of tissue ranged from 4 days to 90 days. At any time point the blood and skin samples contained primarily 25(OH)D with one exception. In the samples from patients on prior vitamin D therapy the blood and skin contained higher levels of unmetabolized D, cholecalciferol. The liver, kidney and lung tissues had a significantly higher percentage of 25(OH)D than cholecalciferol. As the interval of time increased, D in muscle shifted from cholecalciferol to the metabolite 25(OH)D. In bone marrow and fat there was a mix of cholecalciferol and 25(OH)D with the unmetabolized cholecalciferol predominating in most samples.

Gp overview: An injection of D moderately raises levels of serum 25(OH)D over a number of days. Excess (my word, not the study's) is stored in tissues, in fatty tissues as the unmetabolized D, cholecalciferol, and in muscle initially as unmetabolized D but shifting to 25(OH)D over time. The skin contains vitamin D primarily as the metabolite 25(OH)D.

Vitamin D's fate is to be finally broken down and excreted in bile, as is the fate of all fat-soluble substances in our bodies. D is also removed as our bodies shed the cells of our mucous linings and skin, both of which contain all 3 metabolites of vitamin D. Traveling from initial intake, by mouth or skin, to active metabolites to degradation and elimination takes a significant period of time.

When vitamin D supplies are diminished or absent vitamin D stored in tissues and organs is rapidly released while fat stores of D release very slowly.(2) In patients who had previously been on extended D therapy large amounts of vitamin D activity were detectible in tissues even after 15-20 months.

What this study doesn't tell us: It does not offer any insight into optimal levels of vitamin D, in blood or in tissues. It doesn't tell us if storage in fat offers a useful reserve of vitamin D when serum levels decline. Holmes and Kummerow found vitamin D in fat (also from excess doses of D) loath to leave, dispersing extremely slowly.(4)

This storage study doesn't tell us what normal humans, getting their D from sunlight and diet, actually do with vitamin D. Do they have D stored in their fat? If so in what form and how much is where?

In a study published in 2002 Barger-Lux and Heaney checked the 25(OH)D levels of men spending the summer out of doors participating in activities including landscaping, construction, farming and recreation. The average value of D reached at summer's end was 48.8 ng/ml. Approximately 5 months later the average of the 26 participants dropped to 29.6 ng/ml. Three of the men had values less than 20 ng/ml and 15 had less than 30 ng/ml.(19) Gp, the reality of storage looks quite different from the premise doesn't it?

Studies evaluating the system overload of an injection, with or without prior D therapy, or single or chronic high dose D as used in animal storage studies, may offer clues to D metabolism. The doses of D used in these studies may also completely imbalance the system so that the primary question answered is 'What happens to vitamin D in the human or animal body when an overload is given?' (4)

At no time, ever, from any source, could the human or animal body have gotten the massive doses of vitamin D being used today in research, in medicine and as additives in feed in animal husbandry.

This storage study helps to show some of the difficulties encountered in understanding the relationship between our bodies and vitamin D. As there is general acceptance within and outside of the medical community that vitamin D stores in the body as a natural process clinicians have developed the protocol of giving high dose vitamin D. The idea is very user friendly. An injection once every three months or a pill once a week or other prescription allows the physician to treat the condition and not have to be concerned about compliance.

Many of the studies using D for osteoporosis or other D related disorders used tens of thousands and even hundreds of thousands of International Units of vitamin D. The current prescription vitamin D supplement Calciferol, contains 50,000 IU of vitamin D2. protocols for various conditions continue to suggest 50,000 IU to as much as 700,000 IU daily or intermittently (weekly, monthly or once every 3 or 6 months) to treat hyperparathyroidism, vitamin D resistant rickets, osteoporosis, osteomalacia, vitamin D myopathies or just to build or maintain levels of 25(OH)D.(20-23)

When these doses are given they must be given by prescription and monitored by the physician. At the doses used there is always a possibility of toxicity(24) and if the patient inadvertently combines the treatment with sun exposure(25) or with supplements that contain vitamin D the possibility for toxicity increases exponentially. What is unclear to me is why these doses were ever used. physiological doses of D and sunlight are effective.

Continuing excerpts-

Too Much Vitamin D?

A review from the section on testing: Normal values of 25(OH)D range from 20 ng/ml - 57 ng/ml Optimal levels are probably 35-60 ng/ml or the range may turn out to be as broad as 30-70 ng/ml. In Vieth's review of vitamin D he was unable to find studies showing toxicity at levels of 25(OH)D below 56 ng/ml.(26) As mentioned earlier chronically sun-exposed individuals in the tropics or subtropics reach higher values. Some researchers have made comments that these naturally derived elevations of D, such as found in one farmer in puerto Rico, 90 ng/ml, are from sun and therefore normal and without danger. past and recent research suggests the safety of elevated levels of D from sun is less clear.

When I first began exploring vitamin D in 2000 I spoke with Barbara Boucher, M.D. from the Department of Diabetes and Metabolic Medicine, Medical and Dental School, Queen Mary, University of London, Royal London Hospital, Whitechapel, London, U.K. Dr. Boucher is one of the world's top researchers regarding vitamin D and Syndrome X, that is the complex comprised of insulin resistance, obesity, hypertension and adult onset non-insulin dependent diabetes. At the time of our conversation I had mentioned Reinhold Vieth's idea of higher doses of D being safe and perhaps even necessary. Dr. Boucher was unaware of Vieth's work but strongly disagreed with any suggestion that D in high doses for extended periods of time would be safe and suggested that I review this problem carefully. Her tone was so very intense and serious the caution stuck with me over the three years of book preparation.

Studies, however scientific, don't prove as much as the researchers, health promotion agencies, media and advertising would like us to think. Journals are filled with researchers comments arguing among themselves on why results often differ. Methods, testing procedures, number of participants, kind of participants and contrary results ruffle feathers frequently. Studies don't give us truth they give us approximations. While there may not be sufficient evidence to say levels of 25(OH)D above 70 ng/ml are absolutely harmful there is equally no sufficient evidence to support values above 70 ng/ml as natural, necessary, optimal, or safe.

Hypervitaminosis D indicates excess intake of vitamin D leading to elevated levels of 25(OH)D though D2 or D3, the vitamin you take or make, can also be elevated in hypervitaminosis Vitamin D toxicity, intoxication, or poisoning are terms reserved for very high levels of D accompanied by elevated serum calcium and potential or actual calcification of soft tissues. As usual the research community continues to discuss these terms among themselves and define what they might 'really mean'.

For our purposes I use the term hypervitaminosis D to expressly mean chronically elevated, >70 ng/ml, levels of 25(OH)D, caused by supplementation and/or UV-B light exposure whether from sunlight or UV-B lamps.

In August 1997 a letter was published in the Annals of Internal Medicine. The title,- Gains in Bone Mineral Density with Resolution of Vitamin D Intoxication, should give us pause. The authors, Dr. John S. Adams and Gene Lee found 4 patients they determined to have hypervitaminosis D. These patients were discovered during a 1992-93 admittance screening at the Cedar-Sinai Bone Center in Los Angeles, CA. The purpose of the screening was to determine if a policy of giving a standard testing profile including fasting blood levels of parathyroid hormone, TSH (thyroid stimulating hormone), calcium and 25(OH)D and fasting urine levels of calcium and creatinine would help evaluate patients for osteoporosis or low bone mineral density. (27)

The four women had high levels of calcium in fasting urine, three times greater than normal values, demonstrated bone loss, and a 25(OH)D >50 ng/ml. There were no other abnormalities in the blood with the exception of a lower level of parathyroid hormone. TSH, 1,25(OH)2D and serum calcium were all within normal ranges. All four patients had experienced demonstrable bone loss.

Two of the four women had unknowingly been taking supplements containing high levels of vitamin D. All of the women had been taking a minimum of 1,000 mg of calcium prior to and at the time of their diagnosis. This is important to note because the extra calcium did not protect them from the loss of bone attributed to excess 25(OH)D. In a manner as yet undetermined the elevated level of 25-hydroxyvitamin D caused or contributed to loss of calcium in the urine and increased bone loss.

While there are some arguments among experts about whether these women actually had hypervitaminosis D and whether it was the cause of their bone loss all four patients regained bone mass when elevated 25(OH)D and urinary calcium decreased to more normal values. The drop in D and decrease in urinary calcium took several months. Bone mass increased by an average of 2% a year following the resolution of hypervitaminosis D, very good news.

In the two women with the highest levels of 25(OH)D, 89 ng/ml and 80 ng/ml, the vitamin D causing the elevation was being taken without their knowledge. The high amounts of vitamin D were found to be an unlisted ingredient in preparations purchased from health food stores. None of the patients KNOWINGLY took more than 1,200 IU of vitamin D daily. One of the supplements tested contained 3,600 IU of D, not listed on the label.

According to the vitamin D endocrine system model 1,25(OH)2D (calcitriol) is the active D, the hormone. All of the women with hypervitaminosis D had normal levels of 1,25(OH)2D. Only 25(OH)D was elevated. Adams doesn't know why bone loss occurred but he suggests that the high levels of 25(OH)D may have displaced 1,25(OH)2D in cell function, potentially stopping or slowing the formation of new bone or otherwise altering production of elements necessary for bone maintenance.

Adams, Holmes, Kummerow, and the next study from India have documented damage to bones or arteries when 25(OH)D is elevated. In some of the studies done by them or reviewed by them damage occurred when the only abnormalities were elevated 25(OH)D and excess calcium in the urine.(3;4;27-29) Some very experienced vitamin D researchers believe there isn't a known upper limit on 25(OH)D if serum calcium remains normal. They accept hypercalcemia (too much calcium in the blood) as the indicator of excess D. This may be a mistake.

Researchers from the Department of Cardiology and Achutha Menon Centre for Health Science Studies, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Trivandrum, India considered that high levels of D are used to cause heart disease in experimental animals.(30;31) They wondered if high levels of 25(OH)D generated from exposure to tropical sun would also contribute to heart disease. In comparing 25(OH)D3 levels between a control group of 70 men without heart disease and 143 men with known heart disease, either recent heart attack or coronary artery blockage, levels equal to or greater than 89 ng/ml were present in 22.1% of the controls and 59.4% of the heart disease patients. The numbers indicate a strong association yet to be understood.(32) As low and high levels of D may contribute to heart disease I asked one of the studies authors the percentage of those with heart disease in the range I believe is optimal, 40-60 ng/ml. Fifteen percent had 25(OH)D within this range, 85% had levels higher or lower.

The researchers in India knew these elevated levels were from sunlight, not supplements, because the test was specifically for 25(OH)D3. D3 is only produced on the skin or taken in vitamin D3 supplements such as cod liver oil. Vitamin D3 supplements are not generally available in many parts of the world including India. The test used commonly in the U.S. tests total 25(OH)D, which includes 25(OH)D2 and 25(OH)D3. Both D2 and D3 supplements are available here and both will raise 'total' 25(OH)D. This is important because the Indian research suggests the possibility of too much D from sun, generally thought not to be possible. (That old assumption trap.)

In December of 2001 a client being medically treated for psoriasis with a special narrowband UV-B light prescribed by his dermatologist tested 25(OH)D at 97 ng/ml. The light treatment was immediately stopped by the choice of the client, not the dermatologist. The client then left for his yearly trip to Hawaii staying three months from Jan-March of 2002. He did not intentionally avoid the sun, believing, as I did at the time, hypervitaminosis D from natural sunlight was impossible. He ate local Hawaiian foods, including eggs and fish. On his return to northern California his 25(OH)D had risen to 127 ng/ml.

This man used no supplements containing D. His calcium supplementation was between 1,000-1,200 mg daily in addition to food sources. His D dropped slowly, just 6 ng/ml each month with complete avoidance of sunlight and any foods that might contain a significant amount of D. After 8 months of sun avoidance and avoidance of fish and eggs his D dropped to 78 ng/ml.
His dermatologist refused to request the initial test for vitamin D. After being presented with the results the dermatologist stated he had no information on elevations of vitamin D from UV-B light treatment nor did he know if this was good, bad, or insignificant. After several attempts to get medical advice the client was referred to an endocrinologist who also didn't know anything about elevated D and UV-B light treatment. He was willing to order testing, one time. The clients last test reported a 25(OH)D of 57 ng/ml. after 12 months of complete sun avoidance and no fish, eggs, or supplements containing vitamin D.

His elevated 25(OH)D was caused by prescription psoriasis treatment with narrowband UV-B light made worse by exposure to tropical sun. This is iatrogenic (induced by a physician's treatment) hypervitaminosis D. When he first reported the elevation of vitamin D to his dermatologist a partner in the practice admitted they had seen excessively elevated levels of 25(OH)D before in persons treated with narrowband UV-B before. They did not know what it meant, or whether or not it might be a problem, nor was it their policy to monitor D. They demonstrated no interest in testing serum calcium, pTH, or fasting urinary calcium and refused a request to do so. Narrowband UV-B light can raise 25(OH)D to hypervitaminosis D levels.

A woman with severe osteoporosis, demonstrating a lumbar SD -4.6 and low 25(OH)D began taking D3, cholecalciferol, 3,000 IU a day. Her serum 25(OH)D rose from below 20 ng/ml to 42 ng/ml within 4 months and a follow up bone scan after 8 months of D supplementation showed some not significant (very slight) bone gain had occurred. The client did not want the expense of testing, it was not supported by her physician or HMO, so did not test D again. She continued to take the original 3,000 IU of D about five days a week. This dose is slightly lower than the dose of 4,000 IU sometimes suggested or used by some D researchers and clinicians. She also took between 1,000-1,500 mg calcium in addition to food sources and did not avoid foods containing D. The next bone scan, about 1 year after the scan showing a slight gain and 2 years after starting vitamin D, showed normal pTH (43 ng/ml); 25(OH)D 95 ng/ml; and lumbar SD -4.8 in addition to more loss in the femur for SD -2.2 to -2.5. Overall she experienced a 6% loss of bone density.

Her blood and urine tests confirmed her bone loss to be a case of hypervitaminosis D. She had the requisite elevated calcium in the urine with all other tests normal, serum calcitriol, pTH and serum calcium, just as Dr. Adams had found in his screenings.
When the clients second scan showed bone loss her doctor, an osteoporosis specialist, did not want to test her D. Her physician believed the problem was hormonal and insisted on tests for TSH and pTH, both normal, and other similar studies. The only reason the patient got her D tested is because she stood her ground and demanded it, forcing her doctor to order the test.

Had the vitamin D test not been done her physician would have determined 'bone loss with unknown cause'. The physician had immediately prescribed Fosamax and estrogen for treatment. These treatments would have been ineffective in treating the problem, excess supplementation of vitamin D, though they do help correct bone loss from hypervitaminosis D.''' What she needed to do was to stop taking the D.

The test showing 95 ng/ml was done in July. All supplements were stopped and foods with vitamin D, fish, eggs and fortified dairy were avoided. Summer sunlight was neither avoided nor sought out. In November 25(OH)D reached 110 ng/ml. Vitamin D levels dropped slowly over the next six months, about 8 ng/ml per month. At last testing her D was 61 ng/ml.

For about six months prior to the July test showing 95 ng/ml she had been experiencing 'bone ache', fatigue and depression. Within several weeks of stopping vitamin D the pain resolved and energy and mood returned to normal, interesting because her 25(OH)D continued to climb during this time. Her serum calcium remained normal at all times.

Message: Don't take vitamin D in amounts beyond the 400-800 IU range without testing and when you begin to take D test every three or four months the first year and every six months the second and third year to make sure you have the right dose.

Retest if you move to a different latitude or increase or decrease your exposure to UV-B (summer or tropical sun). Find a healthcare provider that will support you in this process. Studies using high doses of D, in excess of 2,000 IU, to my knowledge have never lasted longer than 6 months. In many cases elevated D doesn't appear until the second or third year of supplementation.

If you suffer from any autoimmune disease and/or chronic fatigue syndrome, have both your 25(OH)D and 1,25(OH)2D tested. If either number is elevated seek help from a health care professional experienced in vitamin D abnormalities.

Lessons To Be Re-learned

There are several important points to consider in these real stories.

You have to make a choice. Because you have enough D, from supplements or food, you do not stop producing D in your skin. Levels just increase. You may take D and avoid the sun or figure out your winter D dose and stop in the summer or combine some D and some sun. To do any of these safely you must test, test, and retest.

Am I sounding like someone's mother? I worry. I remember Dr. Barbara Boucher's voice from the U.K. She had seen the problems with too much D given in infant formulas and fortified foods. There the problem stemmed from well-intentioned but unwise supplementation. The U.K. far north, across the ocean from Canada, with often overcast skies. Getting excess D from sunlight at any season would be extremely difficult. Here in the U.S. the situation is much more complex. We have a higher UV-B range at any season and in some areas subtropical sun. I firmly believe that we all need vitamin D and having too little contributes to both chronic and acute conditions that could be corrected if we got enough.

I also firmly believe getting too much vitamin D from supplements or light or a combination can create a serious and potentially dangerous situation. There are rarely obvious symptoms of D marginal deficiency or overabundance. Conditions associated with too much or too little vitamin D involve inappropriate mineralizaton or demineralization of bone, or joints or calcification of tissues and organs that include arteries, bone, kidneys, brain, or muscles.

I have seen an advertisement on TV for a calcium supplement that seems to suggest very high levels of vitamin D and calcium are safe and will cure any number of things. I have also visited websites produced by well-meaning persons suggesting massive doses of D, cod liver oil or a 'natural' source, is safe in any amount and providing 'references' to prove this. The references are without merit and the statements are completely and dangerously false.

You can take too much of anything but the consequences of too much D are extreme and many of these consequences are not reversible. In seeking light we must use moderation. We need a little sunlight and D, more perhaps than we get right now but not ever levels higher than reasonably available from food or natural sunlight.

The moral of all of these stories is simple. America is a BIG melting pot with latitudes tropical, subtropical, temperate, and arctic and skins from very light to very dark. We are all different. We get different light. We respond to light and supplements differently. We live in different places. We have different skin colors and varied ability to produce and store D. We can all avoid damage by testing and responding sensibly to the results.

Below I quote Dr. Adams in his reply to criticism regarding his observations as published in the Annals of Internal Medicine Letter, March 1998:
"The most crucial point raised is the importance of detecting the opposite condition, vitamin D deficiency. We agree with the recommendation to increase the current recommended daily allowance for oral vitamin D consumption by 50% to 100% (from 400 to 600 or 800 IU daily), particularly in elderly persons who have limited sunlight exposure and cutaneous vitamin D synthetic capacity. This intake level is safe and will not cause hypercalciuria. What is not always safe and reliable is the label of a food supplement not regulated by the U.S. Food and Drug Administration. In our patients, the vitamin D content of the supplement was at least one order of magnitude greater than that advertised on the label. It is fortunate that the serum 25(OH)D level is the best screen for both hypervitaminosis D and hypovitaminosis D. physicians should take better advantage of this versatile screening tool." (Underlining and bold added by me.)

A complicating addition to Dr. Adams' comments: Remember the two women with optimal D, the lucky ones who got to spend winters in the tropics? Both women were postmenopausal and candidates for a blanket prescription. of calcium and D. ANY supplementation would have elevated D to unnecessary levels. Even Dr. Adams' moderate dose of 800 IU is inappropriate if 25(OH) D is adequate. Testing really is critical.

The Causes- A Review

In our examples the elevated vitamin D came from supplements or sunlight or a combination of both. Remember the complex systems model and my warning about the devil being in skipping the details? Not getting enough vitamin D is clearly an issue in many parts of the world and so is getting too much. With all the voices, research, opinion, sales, media, the only safe path is working out your own need and your response and knowing that it works, safely, because you have tested.

The following list concerns low level hypervitaminosis D as that seen with Adam's cases of bone loss or the calcification of arteries in the southern Indians NOT clinical intoxication with elevated serum calcium.

The Complications Of Too Much D

Our few examples showed bone loss and calcification of soft tissue, in this case the arteries. In research extremely high levels of vitamin D are given to lab animals, rats in most cases, to cause a condition similar to heart disease with calcifications in arteries. While the doses of vitamin D used to cause artery damage in rats are extreme after considering the Indian study, with a strong association between heart disease and elevated 25(OH)D, there should be a concerned response and more research in this area. It certainly appears that both low and elevated levels of vitamin D may contribute to heart disease.

Holmes and Kummerow found elevations of 25(OH)D, independent of serum calcium, caused damage to tissues. Excess 25(OH)D was found primarily in the kidney, liver, lung, aorta, and heart. places known to develop calcifications with D intoxication. As in our cadaver storage study Holmes found unconverted D primarily in fat and 25(OH)D in blood. Remember DBp prefers 25(OH)D. Research suggests DBp entry into cells may be a normal process. Usually only 1% of DBp contains vitamin D, any of its metabolites. Holmes suggests elevations of vitamin D may increase DBp binding of D to as much as 40%.

The question of what constitutes hypervitaminosis D revolves around whether deposits of calcium in soft tissues are a result of excess calcium in the blood or excess 25(OH)D. Holmes and others have found calcium deposits related most to elevations of 25(OH)D. The pathologic changes he found in tissues, calcium infiltration of cells, occurred at levels lower than those causing elevated serum calcium. His theory as to why this happens suggests D-binding protein excess 25(OH)D may alter cell membrane permeability allowing entry of calcium.(4;37) Increased calcium influx in a cell leads to calcium deposits, cell damage or death.(38;39)

Most researchers have noticed excess calcium in the urine as 25(OH)D levels increase and this has been attributed to improved absorption of calcium. Dr. Adams did not find that to be true and even if you aren't concerned about arteries or bone loss consider this- Excess calcium in the urine combined with elevated 25(OH)D has been associated with kidney stones.(40)

Vitamin D moves calcium around our bodies; into and out of bone, muscle, hair, arteries, and cells. Both low and high levels of vitamin D appear to contribute to misbehaving calcium. Goldilocks Rule: Not too much, not too little, just right.

In vitamin D poisoning calcification of the kidney and kidney failure are listed as cause of death. These unfortunate conditions have occurred in rare instances when children or adults have unknowingly been exposed to hundreds of thousands of units in a very short period of time or a somewhat lower dose of vitamin D over weeks or months. It is unlikely that any of you will find yourself suffering from poisoning in any of these ways. My concern is that in trying to be as healthy as you can be you may, in your enthusiasm, raise levels of 25(OH)D above the upper limit of safety, which to my mind is lower than some experts seem to believe.

Reference List

(1) Holick MF. Vitamin D: A millenium perspective. J Cell Biochem 2003;88(2):296-307.
(2) Holmes Rp, Kummerow FA. The vitamin D status of elderly Americans. Am J Clin Nutr 1983 Aug;38(2):335-9.
(3) Toda T, Ito M, Toda Y, Smith T, Kummerow F. Angiotoxicity in swine of a moderate excess of dietary vitamin D3. Food Chem Toxicol 1985 Jun;23(6):585-92.
(4) Holmes Rp, Kummerow FA. The relationship of adequate and excessive intake of vitamin D to health and disease. J Am Coll Nutr 1983;2(2):173-99.
(5) Vieth R, Cole DE, Hawker GA, Trang HM, Rubin LA. Wintertime vitamin D insufficiency is common in young Canadian women, and their vitamin D intake does not prevent it. Eur J Clin Nutr 2001 Dec;55(12):1091-7.
(6) Guillemant J, Le HT, Maria A, Allemandou A, peres G, Guillemant S. Wintertime vitamin D deficiency in male adolescents: effect on parathyroid function and response to vitamin D3 supplements. Osteoporos Int 2001;12(10):875-9.
(7) Chapuy MC, Schott AM, Garnero p, Hans D, Delmas pD, Meunier pJ. Healthy elderly French women living at home have secondary hyperparathyroidism and high bone turnover in winter. EpIDOS Study Group. J Clin Endocrinol Metab 1996 Mar;81(3):1129-33.
(8) Oliveri MB, Ladizesky M, Somoza J, Martinez L, Mautalen C. [Winter serum levels of 25-hydroxy-vitamin D in Ushuaia and Buenos Aires]. Medicina (B Aires) 1990;50(4):310-4.
(9) Heaney Rp, Davies KM, Chen TC, Holick MF, Barger-Lux MJ. Human serum 25-hydroxycholecalciferol response to extended oral dosing with cholecalciferol. Am J Clin Nutr 2003 Jan;77(1):204-10.
(10) Aguado p, del Campo MT, Garces MV et al. Low vitamin D levels in outpatient postmenopausal women from a rheumatology clinic in Madrid, Spain: their relationship with bone mineral density. Osteoporos Int 2000;11(9):739-44.
(11) Aguirre C, Depix MS, pumarino H. [Determination of 25-hydroxyvitamin D serum levels and its seasonal variations in healthy young people]. Rev Med Chil 1996 Jun;124(6):675-9.
(12) Arnaud SB, Matthusen M, Gilkinson JB, Goldsmith RS. Components of 25-hydroxyvitamin D in serum of young children in upper midwestern United States. Am J Clin Nutr 1977 Jul;30(7):1082-6.
(13) Barth J, Gerlach B, Knuschke p, Lehmann B. Serum 25(OH)D3 and ultraviolet exposure of residents in an old people's home in Germany. photodermatol photoimmunol photomed 1992;9(5):229-31.
(14) Brot C, Vestergaard p, Kolthoff N, Gram J, Hermann Ap, Sorensen OH. Vitamin D status and its adequacy in healthy Danish perimenopausal women: relationships to dietary intake, sun exposure and serum parathyroid hormone. Br J Nutr 2001 Aug;86 Suppl 1:S97-103.
(15) Chapuy MC, preziosi p, Maamer M et al. prevalence of vitamin D insufficiency in an adult normal population. Osteoporos Int 1997;7(5):439-43.
(16) Davies pS, Bates CJ, Cole TJ, prentice A, Clarke pC. Vitamin D: seasonal and regional differences in preschool children in Great Britain [published erratum appears in Eur J Clin Nutr 1999 Jul;53(7):584]. Eur J Clin Nutr 1999 Mar;53(3):195-8.
(17) El Hajj FG, Nabulsi M, Choucair M et al. Hypovitaminosis D in healthy schoolchildren. pediatrics 2001 Apr;107(4):E53.
(18) Webb AR, Kline L, Holick MF. Influence of season and latitude on the cutaneous synthesis of vitamin D3: exposure to winter sunlight in Boston and Edmonton will not promote vitamin D3 synthesis in human skin. J Clin Endocrinol Metab 1988 Aug;67(2):373-8.
(19) Barger-Lux MJ, Heaney Rp. Effects of above average summer sun exposure on serum 25-hydroxyvitamin D and calcium absorption. J Clin Endocrinol Metab 2002 Nov;87(11):4952-6.
(20) [Vitamin D supplementation in pregnancy: a necessity. Committee for Nutrition]. Arch pediatr 1995 Apr;2(4):373-6.
(21) Byrne pM, Freaney R, McKenna MJ. Vitamin D supplementation in the elderly: review of safety and effectiveness of different regimes. Calcif Tissue Int 1995 Jun;56(6):518-20.
(22) Mallet E, Gugi B, Brunelle p, Henocq A, Basuyau Jp, Lemeur H. Vitamin D supplementation in pregnancy: a controlled trial of two methods. Obstet Gynecol 1986 Sep;68(3):300-4.
(23) Zeghoud F, Ben Mekhbi H, Djeghri N, Garabedian M. Vitamin D prophylaxis during infancy: comparison of the long-term effects of three intermittent doses (15, 5, or 2.5 mg) on 25- hydroxyvitamin D concentrations. Am J Clin Nutr 1994 Sep;60(3):393-6.
(24) Davies M. High-dose vitamin D therapy: indications, benefits and hazards. Int J Vitam Nutr Res Suppl 1989;30:81-6.
(25) Matsuoka LY, Wortsman J, Haddad JG, Hollis BW. Elevation of blood vitamin D2 levels does not impede the release of vitamin D3 from the skin. Metabolism 1992 Nov;41(11):1257-60.
(26) Vieth R. Vitamin D supplementation, 25-hydroxyvitamin D concentrations, and safety [see comments]. Am J Clin Nutr 1999 May;69(5):842-56.
(27) Adams JS, Lee G. Gains in bone mineral density with resolution of vitamin D intoxication. Ann Intern Med 1997 Aug 1;127(3):203-6.
(28) Kummerow FA, Cho BH, Huang WY et al. Additive risk factors in atherosclerosis. Am J Clin Nutr 1976 May;29(5):579-84.
(29) Kummerow FA. Nutrition imbalance and angiotoxins as dietary risk factors in coronary heart disease. Am J Clin Nutr 1979 Jan;32(1):58-83.
(30) Kieffer p, Robert A, Capdeville-Atkinson C, Atkinson J, Lartaud-Idjouadiene I. Age-related arterial calcification in rats. Life Sci 2000 May 5;66(24):2371-81.
(31) Taura S, Taura M, Imai H, Kummerow FA, Tokuyasu K, Cho SB. Ultrastructure of cardiovascular lesions induced by hypervitaminosis D and its withdrawal. paroi Arterielle 1978 Oct;4(4):245-59.
(32) Rajasree S, Rajpal K, Kartha CC et al. Serum 25-hydroxyvitamin D3 levels are elevated in South Indian patients with ischemic heart disease. Eur J Epidemiol 2001;17(6):567-71.
(33) Feingold KR, Williams ML, pillai S et al. The effect of vitamin D status on cutaneous sterologenesis in vivo and in vitro. Biochim Biophys Acta 1987 Sep 14;930(2):193-200.
(34) Adams JS, Kantorovich V, Wu C, Javanbakht M, Hollis BW. Resolution of vitamin D insufficiency in osteopenic patients results in rapid recovery of bone mineral density. J Clin Endocrinol Metab 1999 Aug;84(8):2729-30.
(35) Ballmer pE. [Vitamins and metals: possible hazards for humans (published erratum appears in Schweiz Med Wochenschr 1996 Jun 8;126(23):1042)]. Schweiz Med Wochenschr 1996 Apr 13;126(15):607-11.
(36) Schwartzman MS, Franck WA. Vitamin D toxicity complicating the treatment of senile, postmenopausal, and glucocorticoid-induced osteoporosis. Four case reports and a critical commentary on the use of vitamin D in these disorders. Am J Med 1987 Feb;82(2):224-30.
(37) Holmes Rp, Yoss NL. 25-Hydroxysterols increase the permeability of liposomes to Ca2+ and other cations. Biochim Biophys Acta 1984 Feb 29;770(1):15-21.
(38) Trump BF, Berezesky IK. The role of altered [Ca2+]i regulation in apoptosis, oncosis, and necrosis. Biochim Biophys Acta 1996 Oct 11;1313(3):173-8.
(39) Trump BF, Berezesky IK. The mechanisms of calcium-mediated cell injury and cell death [correcgted]. New Horiz 1996 Feb;4(1):139-50.
(40) Berlin T, Bjorkhem I. Effect of calcium intake on serum levels of 25-hydroxyvitamin D3. Eur J Clin Invest 1988 Feb;18(1):52-5.

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