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Vitamin D3
Essential for Good Health
and
How to Determine if You are Getting Enough and Using It
Charlie Skeen, C.N.C

Vitamin D3’s Actions
Vitamin D3 is well known for its role for the growth and health of the bone as it helps to regulate the absorption of calcium, phosphorus, and magnesium. A deficiency will result in soft, malformed bones unable to repair themselves, resulting in diseases called rickets in children and osteomalacia in adults. However, research for the last 10 years has shown that receptors for vitamin D are present in a wide variety of cells, and has biologic effects which extend far beyond control of mineral metabolism. Besides its involvement in at least twenty other cell types, vitamin D3 has the potential to reduce the risk of other diseases such as breast, colon and prostate cancers, multiple sclerosis, chronic fatigue, autism, diabetes, high blood pressure, heart attacks and strokes, asthma, Alzheimer's disease and other forms of dementia, muscle weakness due to aging, joint, low back and muscle pain, osteo and rheumatoid arthritis, inflammation, and regulation of neuromuscular and immune function. It is interesting to note that people who live closer to the equator and who get regular sufficient exposure to sunlight suffer less from these diseases.

What is Vitamin D3?
D3 is considered a vitamin since it is found in foods and can be taken as a supplement. But, it also is what is called a prehormone as it has no biological activity until the body converts it into an active hormone. In this case, into 25-hydroxycholecalciferol by the liver.

Process of Hormonal Production
When sunlight hits the skin it absorbs ultraviolet (UVB) radiation converting liver cholesterol molecules (ergosterol) under the skin into 7-dehydrocholesterol, then into previtamin D3 and continues until it becomes provitamin D3, or cholecalciferol. It has been found in studies that when people with fair skin are exposed to the summer sun for about 15 to 30 minutes wearing just a bathing suit, the skin can manufacture anywhere between 10,000 to 50,000 units of cholecalciferol. Vitamin D researcher Michael Holick, Phd. of Boston University School of Medicine looked at the studies and determined the average amount produced is around 20,000 units. This is far above the 200 I.U. recommended by the Institute of Medicine of the National Academy of Sciences. However, as a person's skin becomes more tan, wears sun block, or has naturally darker skin, the skin produces less.

Note: While 20,000 I.U. is cited here other people have been known to manufacture even higher amounts and maintain that level based on their exposure to the sun. This would indicate that the mechanisms invloved will of course vary due to the individual. What one's body may produce and consider a safe level will naturally be different for others.

Vitamin D3 in Supplements
Besides the production of vitamin D3 by the body we can also take it in oral form as a supplement. The natural supplement form of D3 is made from the wool of sheep which does not hurt the animal.

The Skin Prevents Toxicity
In order to prevent toxic levels of cholecalciferol from building up in the body the skin has the ability to degrade, or eliminate it, when it reaches about 20,000 units, or whatever the individual's body considers a safe level. This is accomplished with the same ultraviolet light from the sun hitting the skin so that as you make it above the saturation point you maintain a steady state safe for that person, in this case around 20,000 units. Due to this mechanism there has never been a reported case of vitamin D toxicity due to exposure from the sun.

Toxicity Can Occur When Taking Supplements of D
When taking supplements of vitamin D3 orally there is a risk of reaching a level of toxicity. However, the amount needed to become toxic would have to an extremely high amount over a period of time. One of the scientists involved in vitamin D3 research, Dr. Reinhold Vieth of the University of Tornoto in Canada, indirectly asked the medical community in 1999 to provide any evidence that 10,000 I.U. of D3 a day would be toxic. He found that there was a lack of evidence that would support statements about even moderate doses of vitamin D becoming toxic. Dr. Vieth stated, "If there is published evidence of toxicity in adults from an intake of 250 ug (10,000 IU) per day, and that is verified by the 25(OH)D concentration, I have yet to find it." In the Journal of Clinical Nutrition Dr. Vieth asserts that toxic levels of D would occur after taking around 40,000 I.U. per day. That is the equivalent of 100 capsules of 400 I.U. of vitamin D. When a person also combines heavy sun exposure with excessive D supplementation there is increased risk of toxicity, but Dr. Vieth is not aware of any cases being reported. Vieth R. Vitamin D supplementation, 25-hydroxyvitamin D concentration, and safety. Am J Clin Nutr. 1999;69:842–56.

Case of Overdose
I did find one case of a vitamin D overdose in a letter written to Dr. Cannell, another research scientist on D, in April 2010. In this letter the indivdual reported that he was taking 60,000 I.U. a day of D3 in a liquid, and occasionally took 180,000 I.U. for about eight months to try and help him get over a sinus infection, and to prevent the cold and flu. This was in 2009. Then he goes on to write that in November 2009 he started to have symptoms of irregular heartbeats, nervousness, insomnia, weight loss, difficulty concentrating, and muscle weakness. After having blood work done by a physician he discovered his D3 level was 406 nanograms per milliliter, about 4 times higher than what is recommended, and his calcium level was excessvely above the healthy range for his blood chemistry. After he stopped taking vitamin D3 he says the physician didn't recommend anything else except to recheck his blood levels of D3 and calcium in a few months. He says he is 46 and has been in excellent health all of his life with no serioius medical issues.

Dr. Cannell's reply to him was that he did overdose on vitamin D3 reaching toxic levels, and he recommended that he stay out of the sun until his calcidiol level was normal (50 to 80 nanograms per milliliter), drink at least 8 eight-ounce glasses of water daily to flush his kidneys and system, have a chemistry panel periodically to make sure the kidneys were functionaing normally, and to check the calcium level, although Dr. Cannell felt that his calcium was no longer elevated. He also told him that there probably was no permanent damage to any of his internal organs because there were others who had higher levels of calcidiol and they did not have any permanent damage to their internal organs or kidneys.

Note: I included this case because I wanted to empahsize that you really have to take a lot of vitamin D3 over a period of time for it to become toxic, and to point out the unfounded fear of taking it in doses of anywhere between 2,000 to 10,000 I.U. a day.

Hypersensitivity Mistaken for Toxicity
When some people react adversly to vitamin D it is sometimes mistaken as toxicity when in actuality it is hypersensitivity syndromes due to excess calcium in the blood. This hypersensivity can be due to several things such as hyperparathyroidism which is excessive production of parathyroid hormone (PTH), parathormone, by the parathyroid glands, and granulomatous diseases such as sarcoidosis. Sarcoidosis is a disease of unknown cause that leads to inflammation and can affect various organs in the body. Normally, your immune system defends your body against foreign or harmful substances. For example, it sends special cells to protect organs that are in danger. These cells release chemicals that recruit other cells to isolate and destroy the harmful substance. Inflammation occurs during this process. Once the harmful substance is destroyed, the cells and the inflammation go away. In people who have sarcoidosis, the inflammation doesn't go away. Instead, some of the immune system cells cluster to form lumps called granulomas in various organs in your body.

Other things that can contribute to this hypersensitivity is abnormal tissue in the kidneys causing them to over-produce calcitriol which raises the blood calcium level too high, and cancers, such as oat cell carcinoma of the lung, and non-Hodgkin's lymphoma. Other health problems can contrbute as well. When people have these health problems they should not take vitamin D without the help of a knowledgeable physician and periodic testing of their 25-hydroxycholecalcifero (calcidiol) and calcium levels, as well as their PTH and 1,25-hydroxycholecalcifero (calcitriol).

Natural D3 Versus Plant Based and Synthetic D2
While D3 (cholecalciferol) is produced by the body and made from sheep’s wool, D2 (ergocalciferol) comes from plants and is made by the drug industry synthetically by irradiating yeast. Synthetic D2 is often added to foods such as milk and can found in supplements as well. While plants contain very little D2 and found to be harmless, the synthetic form of D2 can accumulate in the body and has been known to produce severe health problems such as malformed bone development, kidney damage and calcification of tissues in the body such as hardening of the arteries. Research over the years has demonstrated that it provides no benefits in preventing or overcoming osteoporosis. The main form of D used by the body is cholecalciferol, or D3. If you are presently using supplements of D2, or foods fortified with it, it would be wise to stop and obtain the natural form of D3.

The Rest of the Story
Thus far we have learned that D3 can be obtained from sunlight hitting the skin and taken as a supplement. However, this is just the beginning as the body has to convert D3 (cholecalciferol) into the biologically useful forms, calcidiol and calcitriol, before it can be used.

Metabolism of D3 into the Bioactive Forms
1st. Step - The Liver Produces Calcidiol from Cholecalcifero (D3)
As D3 (cholecalciferol) enters the bloodstream, either produced by the body from sunlight or as a supplement, it travels to the liver where the enzyme D-25-hydroxylase (25-OHase) converts it into 25-hydroxycholecalciferol, also known as calcidiol. It then goes into the blood stream to be circulated throughout the body. This hormonal form of vitamin D is five times more potent than cholecalciferol. It's important that that we produce adequate amounts of calcidiol as we shall see under the 2nd and 3rd Step below.

2nd. Step - The Kidneys Produce Calcitriol from Calcidiol
When calcium levels in the blood drop below a certain level, around 9-11 mg per 100 milliliter of blood, this is picked up by the parathyroid glands located on the posterior aspect, or back, of the thyroid gland located in the neck. This causes them to release a hormone called Parathyoid Hormone (PTH), or parathormone, which tells the body to produce and secrete immune system cells called cytokines which tell other cells called osteoclasts to digest some of the bony matrix in the skeleton and release ionic calcium and phosphate into the blood. This also causes the kidneys to hold onto the calcium and decrease retention of phosphate when forming urine. PTH also acts on the kidneys to convert calcidiol by the enzyme 25-hydroxyvitamin D3-1a-hydroxylase (1-OHase) into 1,25-hydroxycholecalciferol [1,25-(OH)2D], also known as calcitriol. This hormonal form is ten times more potent than cholecalciferol and is the most potent form of vitamin D in the body. Calcitriol also enhances the absorption of calcium from the food and supplements and increases the ability of PTH to break down bone. When calcium level becomes too high this is picked up by the cells in the thyroid called parafollicular cells. These cells release a hormone called calcitonin which decreases the activity of the osteoclasts and activates other immune system cells, or cytokines, to tell the osteoblasts to deposit calcium forming new bone tissue. Calcitonin also increases the excretion of calcium through the kidneys.

It is vital that the homeostasis, or balance, of calcium be maintained in the blood and extra cellular fluid that surround all of the cells at all times. That's because calcium is required for numerous physiological processes such as transmission of nerve impulses and release of neurotransmitters, contraction of muscles, coagulation of blood, gland secretions and cell division. Even just very small changes in the level of calcium in the blood away from the homeostatic range can produce severe neuromuscular problems ranging from hyper excitability to the inability to function. Also, if the calcium level became too high for long periods that could lead to the buildup of calcium in the blood vessels, kidneys, and other soft organs, interfering with their ability to function.

Vitamin D3 Essential to Maintaining Healthy Bones and Blood Homeostasis of Calcium
While the body takes calcium from the bones to maintain blood homeostasis it also uses calcium from the food and supplements we ingest. This process of breaking down and building bone is an ongoing dynamic process throughout our lives, and when suffcient calcium is ingested along with a healthy lifestyle and diet which includes appropriate amounts of D3, calcidiol and calcitriol, the bones will remain strong and healthy. However, if there is an insufficent amount of calcium, or none is available, the body will take it from the existing bone tissue to maintain the homeostasis of the blood because without it the cells throughout our body, such as the heart muscle and muscles of respiration, or breathing, could not function and we would die. If this process of contantly taking calcium from the bone to support blood homeostasis occurs long enough it can result in osteopenia, and if left unchecked into osteoporosis. The body will also be more susceptible to illness and disease.

Conversion by Other Tissue Cells
3rd. Step - Other Tissue Cells Convert Calcidiol into Calcitriol for Other Health Benefits
At one time it was thought that only the kidneys were involved in converting calcidiol into calcitriol. However, scientists have discovered that other tissue cells can make the conversion as well. In fact, this has been the focus of much research for the last ten years. While it has been understood for some time that D3 being converted into calcidiol by the liver then into calcitriol by the kidneys is important to maintain healthy calcium status in the blood and for strong healthy bones, they have discovered other far reaching implications of its postive effects on other cells of the body such as cancer protection. In order for this to take place though there must be an adequate amount of calcidiol produced each day. If the body only produces enough calcidiol for the kidneys to produce calcitriol to maintain the calcium status in the blood and for healthy bones you will not have enough left over for the other tissue cells in the body to produce it. This will put your body at higher risks for various cancers such as breast, prostate and colon, and a whole host of other diseases such as osteoarthritis, muscle, joint and low back pain, heart disease, Type 1 diabetes, and auto immune diseases such as lupus, multiple sclerosis and rheumatoid arthritis.

Many People Are Deficient in Vitamin D
Based on studies by William B. Grant, Ph.D, one of the top vitamin D researchers in the world, 80% to 90% of Americans are deficient in vitamin D3. Another expert on vitamin D3, Dr. Michael Holick of Boston University, states in his book, “The Vitamin D Solution” (Hudson Street Press, 2010), that everyone should be above 30 nanograms per milliliter of 25-hydroxycholecalcifero (calcidiol) which is the best indicator of a healthy level. In the third National Health and Nutrition Examination Survey it was discovered that in the United States Caucasians average only 18 to 22 nanograms per milliliter, and African-Americans average 13 to 15 nanograms per milliliter. Also, African-American women are 10 times as likely to have levels at, or below, 15 nanograms per milliliter as Causcasian women.

Less Sun Exposure Increases Health Risks
Dr. Holick believes such low levels of 25-hydroxycholecalcifero (calcidiol) could contribute to the high occurrences of several of the chronic diseases in the United States. He points out that in the Northeast United States the sun exposure is reduced resulting in lower amounts of vitamin D being manufacturered by the body. When compared to the South United States, where there is greater sun exposure, cancer rates are lower. Dr. Holick also points out that among dark-skinned Americans the amount of prostate cancer, heart disease and high blood pressure are higher than among whites.

Rise of Type 1 Diabetes
Type 1 diabetes has been on the rise some time. Based on Dr. Holick's observations this may be due in part to the fact parents are protecting their children from exposure to the sun. He sights a study done in Finland where 2,000 I.U's of vitamin D3 a day were given to the infants. The results demonstrated an 88 percent reduction in Type 1 diabetes.

The Recommended Levels are Too Low, So How Much Vitamin D Do We Need?
The current Recommended Dietary allowance for vitamin D3 as established by the Institute of Medicine of the National Academy of Sciences is:
0-50 year: 200 IU per day (including pregnant women)
50-70 years: 400 IU per day
> 70 years: 600 IU per day

These dosages listed above are being challenged because extensive research for the last 10 years reveals the fact that the levels of D3 listed are not sufficient to bring the bioactive form of calcidiol up to the healthy level, which is over 30 nanograms per milliliter in the blood. Reserachers such as Dr. Holick, are recommending a dosage of vitamin D3 daily of 1,000 to 2,000 I.U. for people who do not receive suffcicent sun-light, women who are pregnant and those who are are breast feeding, and people over 50 years of age. As for infants who are being breast-fed the American Academy of Pediatrics recommends they receive a daily supplement of 400 units until they are weaned and are able to consume a diet that includes at least 400 I.U. of vitamin D from food sources.

Higher Dose Recommeded

While Dr. Holick recommends a level of clacidiol of over 30 nanograms per milliliter other scientists recommend a higher amount with a optimal low and high range. The low range would be around 50 nanograms per milliliter, or 125 nanomoles per liter, and the high would be 80 nanograms per milliliter, or 200 nanomoles per liter. These are just conservative figures that are considered safe. Each person will have determine how much vitamin D3 they will require daily to produce these levels of calcidiol due to different body sizes, metabolism, health, nutrient precursers, and body fat. Since vitamin D3 is fat soluble the more body fat you carry the more you will require because it will become stored in the fat. Also, the extra blood vessels to the fat will decrease, or water down, the vitamin D3.

Besides making sure you are getting enough vitamin D daily you also want to avoid taking too much to prevent toxicity. A toxic level can cause such things as muscle cramps, artery and tissue hardening, calcified bone, irritabilty and kidney and heart damage. But I have to admit in all my years of dealing with people I haven't found anyone who was getting too much vitamin D3. It has always been the opposite, they were getting too little. As you read earlier toxic levels wouldn't occur until you took around 40,000 I.U. daily for several years.

Test for Proper Levels of D and Calcidiol
In order to really know if your body is receiving the correct amount of D3 each day and is being converted into the bioavailable form, calcidiol, you need to take a simple blood test. You can go to your physician and request it, or you can click on the link Vitamin D, 25-Hydroxy (Calcidiol) and order it over the internet without seeing a physician. When you go to take the test you will find that it is done by a well known professional lab called LabCorp Patient Service Center that has thousands of locations throughout the United States and usually near your home. I have checked around and found that their cost is very reasonable.

Test for Calcitriol
Normally you would only have to test for calcidiol. However, if you have, or had, kidney problems and you wish to make sure you are producing adequate amounts of calcitriol click on the link Vitamin D, 1,25 Dihydroxy(Calcitriol) to take this test.

Ranges to Check
When vitamin D3 levels are measured by a lab there are given as either nanograms per milliliter, and nanomoles per liter.
The safe healthy ranges you are looking for are:
Low End: 50 nanograms per milliliter, or 125 nanomoles per liter
High End: 80 nanograms per milliliter, or 200 nanomoles per liter
You want your low end to be at least over 50 nanograms per milliliter, or 125 nanomoles per liter to receive the benefits of vitamin D3.

The lab test from LabCorp Patient Service Center on the internet will be given as nanograms per millilter. I gave both measurements in case you go to a physician to have your test done and the lab used gives the readings as nanomoles per litre. Also, make sure that if you go to a physician to order your test that you tell him to order the one for Vitamin D, 25-Hydroxy (Calcidiol), and not Vitamin D, 1,25 Dihydroxy(Calcitriol).

Testing Will Assist in You in Finding the Proper Amount of Vitamin D3 to Use
If you have been taking vitamin D3 and take the blood test and find your calcidiol level is too low then you need increase it. Conversely, if it is too high then you need to reduce it. Although, many more people will find that they are too low. Then test again to make sure you are in the healthy range. Many people take vitamin D3 in the range of 1,000 and to 2,000 I.U. daily but when tested had to increase it even more as they were not producing enough calcidiol. Some individuals had to increase their daily intake to 5,000 and 10,000 I.U. You will not know if you have to increase your intake or not until you have your blood tested. Once you achieve a healthy blood level of calcidiol you should check it once a year. Also, if you check it in the winter time and you live in a part of the United States where you don't recieve much sun, you need to check it again when you are exposed to more sunlight in the spring and summer. Remember, as you expose yourself to more sunlight you will require less as a supplement. You will have to probably be taking higher amounts as a supplement during the winter, such as 2,000 to 10,000 I.U., and less in the months you are exposed to the sun, such as 1,000 to 2,000 I.U. And, for those who try to avoid the sun, once you find your level of intake of vitamin D3 daily you will more than likely have to maintain that dosage all year around, even if you live in a sunny climate.

Sources of Vitamin D3
Sunlight - ultraviolet (UVB) radiation
Food sources of vitamin D3: cold water fish such as mackerel, salmon, sardines, herring, butter, egg yolks, sweet potato, sunflower seeds, spinach, dandelion greens
Herbs: alfalfa, nettle parsley, eyebright, fenugreek
Supplements: D3 in cod liver oil, fish oil softgels, and tablets and capsules of varying strengths made from the wool of sheep.


Things That Interfere with Vitamin D
3, Its Conversion, and Use In the Body
Liver and kidney disease
Weak liver and kidney function due to stress and poor diet
Excess Body Fat
Excessive alcohol consumption
Excessively Low fat diet
Excessively High fat diet
Processed fats and oils
Insufficient sunlight
Air Pollution
Chlorine in the drinking water and bathing in it.
Alumium Fluoride in the drinking water and toothpaste
Flourescent lights
Sunscreens
Dark Skin

Aging
Smoking
Processed and refined foods such as white flour and rice, sugars, processed fats and oils)
Fried Foods
Nutrient Deficiencies
Pharmaceutical over-the-counter (OTC) and Prescription Drugs
Steroids
Laxatives such as Mineral Oil
“Bile acid sequestrants” like Questran
Sleeping Pills
Barbiturates like phenobarbital
Prednisone
Corstisone
Dilantin
Anticonvulsants
Bisphosphonates such as Fosamax

Nutrients Required to Convert Vitamin D3 into the Bioactive Forms
As can been seen from the list above there are many things that interfere or prevent your body from absorbing, converting, and using vitamin D3. However, its use and conversion is very complex and depends upon other nutrients for its use. Some of the major nutrients involved are magnesium, boron, zinc and vitamin K2, which most people are deficient in as well. When deficiencies occur it is very difficult for the body to convert D3 into the useful biologically active forms no matter how much D3 we ingest. So when you test for calcidiol levels and find that you are not producing what you should, even though you may be taking high amounts of D3, you need to examine not only the things listed above that could prevent the conversion, but also look at any possible companion nutrient deficiencies and if found, correct them.

I hope this information has helped you to have a better understanding of the importance of getting enough natural vitamin D3 daily, and of how to assist the body in using it for improved health and protection against disease for a better quality of life.


References
Laurlee Sherwood, Fundamentals of Physiology 2nd Edition, West Publishing Company, 1995
Marieb, Elaine N., R.N., Ph.D., Human Anatomy and Physiology, 1992
Joseph B. Marion, Anti-Aging Manual - The Encyclopedia of Natural Health, 1996
Michael T. Murray, N.D., Encyclopedia of Nutritional Supplements, 1996
Elson M. Hass, M.D., Staying Healthy with Nutrition - The Complete Guide to Diet and Nutritional Medicine, 1992
Holick MF. “Vitamin D Deficiency,” New England Journal of Medicine (July 19, 2007), Vol. 357, No. 3, pp. 266–80.

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